Direct aromatic carbon-oxygen and carbon-hydrogen bond functionalization via organic photoredox catalysis

Abstract

The present invention relates generally to methods of preparing substituted arenes via direct C-H, C-O, C-S, or C-N bond transformations and methods of synthesizing isotopically labeled substituted arenes via direct carbon-halogen bond transformations. The present invention also relates to anaerobic catalyst systems comprising an azinium photocatalyst and a nucleophile selected from halides, cyanides, and isotopically labeled amines. This abstract is intended as a scanning tool for purposes of searching in particular fields of art and is not intended to be limiting of the present invention.

Description

[0001] Cross-references to related applications

[0002] This application claims the benefit of U.S. Application No. 62 / 812,179, filed on February 28, 2019, the contents of which are hereby incorporated by reference in their entirety.

[0003] Statement on Federally Funded Research

[0004] This invention was completed with government support under grant numbers GM120186 and EB014354 granted by the National Institutes of Health in the United States. The government holds certain rights to this invention. Background Technology

[0005] Aromatic fluorination has attracted widespread attention in pharmaceutical and agrochemical development, leading to an urgent need for simple fluorination methods. Although several methods for forming fluorination compounds from aryl halides, trifluoromethanesulfonates, boric acid, and tinane have recently been developed... 19 Cross-coupling methods for F]CF bonds have been reported (Lee et al. (2011) Science 334:639-642; Lee et al. (2012) Journal of the American Chemical Society 134:17456-17458; Mossine et al. (2014) Organic Chemistry Letters 17:5780-5783; Makaravage et al. (2016) Organic Chemistry Letters 18:5440-5443), but only a limited number of examples of direct ortho-CH fluorination in aromatic compounds have been reported. However, such ortho-CH fluorination methods rely on non-removable template groups to guide the reaction and require electrophilic fluorination sources (Wang et al. (2009) J. Am. Chem. Soc. 131(22):7520-7521; Yamamoto et al. (2018) Nature 554(7693):511-514). Recently, the development of one of the first CH fluorination reactions of aromatic compounds has been reported; however, it requires electrophilic fluorinating agents (i.e., Selectfluor or NFSI) (Lee et al. (2011) Science 334(6056):639-642).

[0006] 18The generation of F-labeled drug compounds is of particular interest. These compounds can be quantitatively measured via positron emission tomography (PET) to determine site-specific chemical reactions, including their spatial distribution and metabolic perturbations, as well as subsequent in vivo biological processes. Despite the remarkable promise of PET imaging, the availability of PET reagents is limited in many cases due to the lack of efficient and simple labeling methods for modifying bioactive molecules. 18 F-fluorides are the most widely used PET isotopes in clinical practice; however, effectively introducing fluorine into inactivated aromatic molecules remains a significant challenge, limiting the development of novel tracers. Several aromatic precursors, such as triarylsulfonium and trimethylaniline-onium trifluoromethanesulfonates, diaryl sulfoxides, diaryl selenium sulfones, and spirocyclic iodoonium inner salts, have been identified through S... N Ar reaction has been successfully applied to aromatics. 18 F fluorination (Preshlock et al., (2016) Chem. Rev. 116:719-766). Recently, fluorination via ureon intermediates through synergistic S... N Ar reaction and phenol via nucleophilic aromatic substitution through N-aryl syringone intermediate 18 F-deoxyfluorination, and it serves as a practical tool for late-stage labeling (Neumann et al., (2016) Nature 534:369-373). More rarely [ 18 F] Aromatic fluorination reactions. In fact, current methods in the art require pre-formed palladium or nickel aromatic complexes derived from the essential aromatic halide or the corresponding arylboronic acid (Lee et al. (2011) Science 334:639-642; Lee et al. (2012) Journal of the American Chemical Society 134:17456-17458). Unfortunately, these methods are highly impractical for clinical technicians, either because they require specialized O2-free techniques for handling aryl palladium and nickel complexes, or because boronic esters or other relevant precursors are not readily available. Furthermore, the involvement of metal catalysts can complicate quality control processes when the reagents are used in humans. Further analysis is needed to demonstrate that residual metals are within acceptable conversion ranges.

[0007] In summary, despite the increasing importance of fluorinated reagents in drug discovery, developing simple direct conversion processes to obtain CF bonds remains challenging. Therefore, there is still a need for direct aryl fluorination methods that occur under mild conditions and are tolerant of a wide range of substrates. Furthermore, the value of such methods would be significantly enhanced if they were also applicable to conversions using other nucleophiles. This invention addresses these and other needs. Summary of the Invention

[0008] According to the purposes of the invention, as embodied and broadly described herein, the invention relates in one aspect to methods for synthesizing substituted aromatics via direct CH, CO, CS, or CN bond conversion and methods for synthesizing isotopically labeled substituted aromatics via direct carbon-halogen bond conversion.

[0009] Therefore, a method for preparing compounds having a structure represented by the following formula is disclosed:

[0010] Ar 1 -Z,

[0011] Z is selected from halogens, -CN, -NH2, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino, provided that when Z is -NH2, C1-C4 alkylamino, or (C1-C4)(C1-C4)dialkylamino, Z contains a radioactive isotope; where Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 15b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 30 and R 32 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 31a and R 31b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Ar... 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar1 The structure is represented by the following formula:

[0012]

[0013] The method includes making aromatic hydrocarbons having a structure represented by the following formula:

[0014] Ar 1 -E,

[0015] The electron-donating group E is selected from the following electron-donating groups: -OR 20 -SO3R 20 -SR 20 -NR 21a R 21b -OC(=O)R 20 -OC(=O)OR 20 -OC(=O)SR 20 and -OC(=O)NHR 20 ;where R 20 R 21a and R 21b When present, it is independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkenyl, and Ar. 3 ; and among them Ar 3 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino.

[0016] The compound is formed by reacting a nucleophile selected from halides, cyanides, and amines in the presence of a catalytically effective amount of acridine-onium photocatalyst under anaerobic conditions.

[0017] Also disclosed is a catalyst system comprising an acridine-onium photocatalyst and a nucleophile selected from halides, cyanides and isotopically labeled amines, wherein the catalyst system is anaerobic.

[0018] A method for preparing compounds having a structure represented by the following formula is also disclosed:

[0019] Ar 1 -Z,

[0020] Z is selected from halogens, -CN, -NH2, C1-C4 alkylamino and (C1-C4)(C1-C4) dialkylamino, and Z contains a radioactive isotope; Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Ar... 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0021]

[0022] The method includes making aromatic hydrocarbons having a structure represented by the following formula:

[0023] Ar 1 -E,

[0024] Where E is hydrogen or an electron-donating group selected from the following: -OR 20 -SO3R 20 -SR 20 -NR 21a R 21b -OC(=O)R 20-OC(=O)OR 20 -OC(=O)SR 20 and -OC(=O)NHR 20 ;where R 20 R 21a and R 21b When present, it is independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkenyl, and Ar. 3 ; and among them Ar 3 The compound is formed by reacting a nucleophile selected from aryl and heteroaryl groups in the presence of 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino in the presence of a catalytically effective amount of acridineonium photocatalyst with a halogen, cyanide and amine.

[0025] A method for preparing compounds having a structure represented by the following formula is also disclosed:

[0026] Ar 1 -Z,

[0027] Z is selected from halogens, -CN, -NH2, C1-C4 alkylamino and (C1-C4)(C1-C4) dialkylamino, and Z contains a radioactive isotope; Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; wherein R 16 When present, it is a hydroxyl protecting group; and Ar is present in it. 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0028]

[0029] The method includes making aromatic hydrocarbons having a structure represented by the following formula:

[0030] Ar 1 -E,

[0031] Where E is hydrogen or an electron-donating group selected from the following: -OR 20 -SO3R 20 -SR 20 -NR 21a R 21b -OC(=O)R 20 -OC(=O)OR 20 -OC(=O)SR 20 -OC(=O)NHR 20 ;where R 20 R 21a and R 21b When present, it is independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkenyl, and Ar. 3 ; and among them Ar 3 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino.

[0032] The compound is formed by reacting a nucleophile selected from halides, cyanides, and amines in the presence of a catalytically effective amount of acridine-onium photocatalyst.

[0033] A method for preparing compounds having a structure represented by the following formula is also disclosed:

[0034] Ar 1 -Z,

[0035] Where Z is a halogen, and Z contains a radioactive isotope; where Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; wherein R 16 When present, it is a hydroxyl protecting group; and Ar is present in it. 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0036]

[0037] The method includes making aromatic hydrocarbons having a structure represented by the following formula:

[0038] Ar 1 -H,

[0039] The steps of reacting halides with an LED having a wavelength of approximately 425 nm, a TBPA, and a catalytically effective amount of an acridine-onium photocatalyst having the following structure:

[0040]

[0041] This forms the compound.

[0042] A method for preparing compounds having a structure represented by the following formula is also disclosed:

[0043] Ar 1 -X,

[0044] Where X is a halogen and X contains a radioactive isotope; where Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Ar... 2When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0045]

[0046] The method includes making aromatic hydrocarbons having a structure represented by the following formula:

[0047] Ar 1 -X',

[0048] Where X' is a halogen and X' does not contain a radioactive isotope.

[0049] The compound is formed by reacting a nucleophile selected from halides, cyanides, and amines in the presence of a catalytically effective amount of acridine-onium photocatalyst.

[0050] Also disclosed is a catalyst system comprising an acridine-onium photocatalyst and a nucleophile selected from halides, cyanides and isotopically labeled amines, wherein the catalyst system is anaerobic.

[0051] A catalyst system comprising an acridine-onium photocatalyst, an isotope-labeled halide, and an oxidant was also disclosed.

[0052] While various aspects of the invention may be described and claimed in specific legal categories (such as the systems category), this is merely for convenience, and those skilled in the art will understand that each aspect of the invention can be described and claimed in any legal category. Unless expressly stated otherwise, it is never intended to interpret any method or aspect set forth herein as requiring its steps to be performed in a particular order. Therefore, where a method claim does not specifically state in the claims or specification that the steps will be limited to a particular order, it is never meant to imply an inference of order in any aspect. This applies to any possible non-express basis for interpretation, including logical questions regarding the arrangement of steps or operational flows, explicit meanings derived from grammatical organization or punctuation, or the number or type of aspects described in the specification. Attached Figure Description

[0053] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several aspects and, together with the specification, serve to explain the principles of the invention.

[0054] Figure 1 This diagram illustrates a representative example of the direct conversion of phenolic derivatives into aromatic fluorides for use in PET imaging.

[0055] Figure 2A -C indicates the characteristics of phenolic derivatives. 18 A representative schematic diagram of fluorination (F) Figure 2A ) and substrate ( Figure 2B and Figure 2C ).

[0056] Figure 3 The structure of a representative organic photo-oxidation-reduction catalyst is shown.

[0057] Figure 4A Representative schematic diagrams are shown, and Figure 4B The instructions are shown directly to S. N Representative substrates for the preliminary reaction range of Ar cyanidation reaction.

[0058] Figure 5 A representative schematic diagram of the proposed mechanism is shown.

[0059] Figure 6 A representative schematic diagram of the proposed aromatic CH fluorination mechanism is shown.

[0060] Figure 7 A representative schematic diagram of direct CF fluorination of aromatics is shown.

[0061] Figure 8 The typical catalyst structure is shown.

[0062] Figure 9 A representative schematic diagram illustrating direct CH radioactive fluorination via LED illumination photocatalysis is shown.

[0063] Figure 10 The representative structure of the catalyst explored in this paper is shown.

[0064] Figure 11 A representative schematic diagram illustrating a proposed mechanism for the oxidation of CH[18F] fluorination of aromatic compounds is shown.

[0065] Figure 12 The data shown represent the range of radioactive fluorination of aromatic hydrocarbons (CH).

[0066] Figure 13 This demonstrates the preparation via direct CH fluorination. 18 A representative schematic workflow of F-labeled reagents and its application 18 Applications of F-DOPA in synthesis.

[0067] Figure 14The image shows a representative image illustrating LED illumination of a hot reaction mixture in a quartz U-tube.

[0068] Further advantages of the invention will be set forth in part in the description which follows, and in part will be apparent from the description, or may be learned by practice of the invention. The advantages of the invention will be realized and obtained by means of the elements and combinations particularly pointed out in the appended claims. It should be understood that the foregoing general description and the following detailed description are merely exemplary and illustrative, and not intended to limit the invention as claimed. Detailed Implementation

[0069] The invention can be more readily understood by referring to the following detailed description of the invention and the examples included therein.

[0070] Before disclosing and describing the compounds, compositions, articles, systems, devices, and / or methods of the present invention, it should be understood that, unless otherwise stated, they are not limited to specific synthetic methods, or, unless otherwise stated, they are not limited to specific reagents, and therefore they can certainly vary. It should also be understood that the terminology used herein is for descriptive purposes only and is not intended to be limiting. Although any methods and materials similar to or equivalent to those described and used herein may be used in the practice or testing of the invention, exemplary methods and materials are now described.

[0071] While various aspects of the invention may be described and claimed in specific legal categories (such as the systems category), this is merely for convenience, and those skilled in the art will understand that each aspect of the invention can be described and claimed in any legal category. Unless expressly stated otherwise, it is never intended to interpret any method or aspect set forth herein as requiring its steps to be performed in a particular order. Therefore, where a method claim does not specifically state in the claims or specification that the steps will be limited to a particular order, it is never meant to imply an inference of order in any aspect. This applies to any possible non-express basis for interpretation, including logical questions regarding the arrangement of steps or operational flows, explicit meanings derived from grammatical organization or punctuation, or the number or type of aspects described in the specification.

[0072] Throughout this application, various publications have been cited. The full disclosures of these publications are incorporated herein by reference in order to more fully describe the current state of the art to which this application pertains. Disclosed references are also individually and specifically incorporated herein by reference for the material contained therein discussed in sentences relying on those references. Nothing herein should be construed as an admission that the invention is not entitled to any prior invention by virtue of such disclosure. Furthermore, the publication date provided herein may differ from the actual publication date, which may require independent verification.

[0073] A. Definition

[0074] As used herein, the naming of compounds, including organic compounds, may be given using common names, IUPAC, IUBMB, or CAS nomenclature recommendations. When one or more stereochemical features are present, the Cahn-Ingold-Prelog rule of stereochemistry, E / Z norms, etc., can be used to specify stereochemical priority. If a name is given, those skilled in the art can easily use naming conventions to systematically reconstruct the compound structure or use commercially available software such as CHEMDRAW. TM Cambridgesoft Corporation (USA) determined the structure of the compound.

[0075] As used in the specification and appended claims, the singular forms “an,” “a,” and “the” include plural referents unless the context clearly indicates otherwise. Thus, for example, references to “functional group,” “alkyl,” or “residue” include mixtures of two or more such functional groups, alkyl groups, or residues.

[0076] A range may be expressed herein as “about” to a particular value and / or “about” to another particular value. When expressing such a range, a further aspect includes from one particular value and / or to another particular value. Similarly, when a value is expressed as an approximation using the antecedent “about”, it will be understood that a particular value forms a further aspect. It will be further understood that each endpoint of a range is significant relative to and independent of the other endpoint. It should also be understood that there are multiple values ​​disclosed herein, and each value is also disclosed herein as “about” to that particular value, in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. It should also be understood that each unit between two particular units is also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0077] References to parts by weight of a particular element or component in the composition in this specification and concluding claims indicate a weight relationship between that element or component and any other element or component in the composition or article expressed in parts by weight. Thus, in a compound containing 2 parts by weight of component X and 5 parts by weight of component Y, X and Y are present in a weight ratio of 2:5, and in such a ratio, regardless of whether the compound contains other components.

[0078] Unless otherwise specified, the weight percentage (wt%) of a component is based on the total weight of the formulation or composition in which the component is contained.

[0079] As used herein, the terms “optional” or “optionally” mean that an event or situation described below may or may not occur, and the description includes both cases in which the event or situation occurs and cases in which the event or situation does not occur.

[0080] As used herein, the term “catalytically effective” refers to an amount of catalyst sufficient to promote reactions as disclosed herein (e.g., CH and / or CO functionalization).

[0081] As used herein, the term "derivative" refers to a compound having a structure derived from a parent compound (such as those disclosed herein) and whose structure is sufficiently similar to those disclosed herein, and based on this similarity, those skilled in the art would expect it to exhibit the same or similar activity and utility as the claimed compound, or to induce the same or similar activity and utility as the claimed compound as a precursor. Exemplary derivatives comprise salts, esters, amides, salts of esters or amides, and N-oxides of parent compounds.

[0082] As used in the specification and concluding claims, a residue of a chemical substance refers to a portion of the product obtained as a result of the chemical substance in a particular reaction scheme or subsequent formulation or chemical product, regardless of whether that portion is actually obtained from the chemical substance. Thus, for example, an ethylene glycol residue in a polyester refers to one or more -OCH2CH2O- units in the polyester, regardless of whether ethylene glycol is used to prepare the polyester. Similarly, a sebacic acid residue in a polyester refers to one or more -CO(CH2)8CO- portions in the polyester, regardless of whether that residue is obtained by reacting sebacic acid or its ester to obtain the polyester.

[0083] As used herein, the term “substituted” is intended to encompass all permissible substituents of an organic compound. In a broad sense, permissible substituents encompass acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, and aromatic and non-aromatic substituents of an organic compound. Illustrative substituents include, for example, those described below. For a suitable organic compound, permissible substituents may be one or more and may be the same or different. For the purposes of this disclosure, heteroatoms such as nitrogen may have hydrogen substituents and / or any permissible substituents of the organic compound described herein that satisfy the valence of the heteroatom. This disclosure is not intended to be limited in any way by the permissible substituents of an organic compound. Furthermore, the terms “substituted” or “replaced” include the implicit condition that such substitution is consistent with the permissible valence state of the substituted atom and the substituent, and that such substitution results in a stable compound, such as a compound that does not spontaneously undergo transformations such as those by rearrangement, cyclization, elimination, etc. It is also contemplated that, in some respects, unless explicitly stated otherwise, a single substituent may be further optionally substituted (i.e., further substituted or unsubstituted).

[0084] When defining various terms, "A" 1 “A” 2 “A” 3 "and "A 4 "These symbols are used in this document as general symbols to denote various specific substituents. These symbols can be any substituents, not limited to those disclosed herein, and while they are defined as certain substituents in one case, they can be defined as some other substituents in another case."

[0085] As used herein, the term "aliphatic" or "aliphatic group" refers to a hydrocarbon moiety that can be straight-chain (i.e., unbranched), branched, or cyclic (including fused, bridged, and spirofused polycyclic rings), and can be fully saturated or contain one or more unsaturated units, but is not aromatic. Unless otherwise stated, an aliphatic group contains 1-20 carbon atoms. Aliphatic groups include, but are not limited to, straight-chain or branched alkyl, alkenyl, and alkynyl groups, and their hybrids, such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl, or (cycloalkyl)alkenyl.

[0086] As used herein, the term "alkyl" is a branched or unbranched saturated hydrocarbon group having 1 to 24 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl, tetradecyl, hexadecyl, eicosyl, tetradecyl, etc. Alkyl groups can be cyclic or acyclic. Alkyl groups can be branched or unbranched. Alkyl groups can also be substituted or unsubstituted. For example, an alkyl group can be substituted by one or more groups, including but not limited to alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxyl, nitro, silyl, sulfo-oxo, or thiol, as described herein. A "lower alkyl" group is an alkyl group containing one to six (e.g., one to four) carbon atoms.

[0087] Throughout this specification, "alkyl" is generally used to refer to both unsubstituted and substituted alkyl groups; however, substituted alkyl groups are also specifically referred to herein by identifying the specific substituents on the alkyl group. For example, the terms "halogenated alkyl" or "halogenated alkyl" specifically refer to an alkyl group substituted with one or more halides such as fluorine, chlorine, bromine, or iodine. The term "alkoxyalkyl" specifically refers to an alkyl group substituted with one or more alkoxy groups, as described below. The term "alkylamino" specifically refers to an alkyl group substituted with one or more amino groups, as described below, and so on. When "alkyl" is used in one context and a specific term such as "alkyl alcohol" is used in another, this does not mean that the term "alkyl" does not refer to a specific term such as "alkyl alcohol," etc.

[0088] This practice is also applied to other groups described herein. That is, while terms such as “cycloalkyl” refer to both unsubstituted and substituted cycloalkyl moieties, substituted moieties may be specifically identified separately herein; for example, a specifically substituted cycloalkyl group may be referred to as, for example, “alkylcycloalkyl.” Similarly, a substituted alkoxy group may be specifically referred to as, for example, “haloalkoxy,” and a specifically substituted alkenyl group may be, for example, “alkenyl alcohol,” etc. Likewise, the practice of using general terms such as “cycloalkyl” and specific terms such as “alkylcycloalkyl” does not imply that the general terms do not include the specific terms.

[0089] As used herein, the term "cycloalkyl" refers to a non-aromatic carbonyl ring consisting of at least three carbon atoms. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl, etc. The term "heterocyclic alkyl" is a class of cycloalkyl groups as defined above and is included within the meaning of the term "cycloalkyl," wherein at least one carbon atom of the ring is replaced by a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. Cycloalkyl and heterocyclic alkyl groups can be substituted or unsubstituted. Cycloalkyl and heterocyclic alkyl groups can be substituted by one or more groups, including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxyl, nitro, silyl, sulfo-oxo, or thiol groups as described herein.

[0090] As used herein, the term "polyalkylene group" is a group having two or more CH2 groups linked together. Polyalkylene groups can be represented by the formula -(CH2). a - indicates that "a" is an integer from 2 to 500.

[0091] As used herein, the terms "alkoxy" and "alkoxyl" refer to alkyl or cycloalkyl groups bonded by ether bonds; that is, the "alkoxy" group can be defined as -OA. 1 A 1Alkyl or cycloalkyl groups as defined above. "Alkyl" also includes polymers of alkoxy groups just described; that is, alkoxy groups can be polyethers, such as -OA. 1 -OA 2 or -OA 1 -(OA 2 ) a -OA 3 Where "a" is an integer from 1 to 200 and A 1 A 2 and A 3 It is an alkyl and / or cycloalkyl group.

[0092] As used herein, the term "alkenyl" refers to a hydrocarbon group having 2 to 24 carbon atoms in a structural formula containing at least one carbon-carbon double bond. Asymmetric structures, such as (A... 1 A 2 C = C(A) 3 A 4 The designation aims to include E and Z isomers. This can be inferred from the structural formula herein containing an asymmetric olefin, or explicitly indicated by the bond symbol C=C. The alkenyl group may be substituted with one or more groups, including but not limited to alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxyl, ketone, azide, nitro, silyl, sulfonyl-oxo, or thiol as described herein.

[0093] As used herein, the term "cycloalkenyl" refers to a non-aromatic carbonyl ring consisting of at least three carbon atoms and containing at least one carbon-carbon double bond, i.e., C=C. Examples of cycloalkenyl groups include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, cyclohexadienyl, norbornyl, etc. The term "heterocyclic alkenyl" is a class of cycloalkenyl groups as defined above and is included within the meaning of the term "cycloalkenyl," wherein at least one carbon atom of the ring is replaced by a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. Cycloalkenyl and heterocyclic alkenyl groups can be substituted or unsubstituted. Cycloalkenyl and heterocyclic alkenyl groups can be substituted by one or more groups, including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxyl, ketone, azide, nitro, silyl, sulfonyl-oxo, or thiol.

[0094] As used herein, the term "alkynyl" is a hydrocarbon group having a structural formula containing at least one carbon-carbon triple bond of 2 to 24 carbon atoms. The alkynyl group may be unsubstituted or substituted with one or more groups, including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxyl, ketone, azide, nitro, silyl, sulfo-oxo, or thiol.

[0095] As used herein, the term "cycloalkynyl" refers to a non-aromatic carbonyl ring consisting of at least seven carbon atoms and containing at least one carbon-carbon triple bond. Examples of cycloalkynyl groups include, but are not limited to, cycloheptynyl, cyclooctyynyl, cyclononynyl, etc. The term "heterocyclic alkynyl" is a class of cycloalkenyl groups as defined above and is included within the meaning of the term "cycloalkynyl," wherein at least one carbon atom of the ring is replaced by a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. Cycloalkynyl and heterocyclic alkynyl groups can be substituted or unsubstituted. Cycloalkynyl and heterocyclic alkynyl groups can be substituted by one or more groups, including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxyl, ketone, azide, nitro, silyl, sulfonyl-oxo, or thiol.

[0096] As used herein, the term "aromatic group" refers to a ring structure having a ring cloud of delocalized π electrons above and below the plane of the molecule, wherein the π cloud contains (4n+2)π electrons. Further discussion of aromaticity can be found in Morrison and Boyd's *Organic Chemistry* (5th edition, 1987), Chapter 13, entitled "Aromaticity," pp. 477–497, which is incorporated herein by reference. The term "aromatic group" includes aryl and heteroaryl groups.

[0097] As used herein, the term "aryl" is a group containing any carbonyl aromatic group, including but not limited to benzene, naphthalene, phenyl, biphenyl, phenoxybenzene, etc. The term "aryl" also includes "heteroaryl," which is defined as a group containing an aromatic group having at least one heteroatom incorporated into a ring of that aromatic group. Examples of heteroatoms include, but are not limited to, nitrogen, oxygen, sulfur, and phosphorus. Similarly, the term "non-heteroaryl" (which is also included in the term "aryl") defines a group containing an aromatic group that does not contain a heteroatom. Aryl groups can be substituted or unsubstituted. Aryl groups can be substituted by one or more groups, including but not limited to alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, -NH2, carboxylic acid, ester, ether, halide, hydroxyl, ketone, azide, nitro, silyl, sulfonyl-oxo, or thiol. The term "biaryl" is a specific type of aryl group and is included in the definition of "aryl". Biaryl refers to two aryl groups that are linked together by a fused ring structure (such as naphthalene) or by one or more carbon-carbon bonds (such as biphenyl).

[0098] As used herein, the term "aldehyde" is represented by the formula -C(O)H. In this specification, "C(O)" is the simplified symbol for the carbonyl group, i.e., C=O.

[0099] As used herein, the term "amine" or "amino" is derived from the formula -NA. 1 A 2 It means that A 1 and A 2 It can be hydrogen independently or alkyl, cycloalkyl, alkenyl, cycloalkenyl, ynyl, cycloynyl, aryl or heteroaryl as described herein.

[0100] As used herein, the term "alkylamino" is represented by the formula -NH(-alkyl), where alkyl is the alkyl group described herein. Representative examples include, but are not limited to, methylamino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, (sec-butyl)amino, (tert-butyl)amino, pentylamino, isopentylamino, (tert-pentyl)amino, hexylamino, etc.

[0101] As used herein, the term "dialkylamino" is represented by the formula -N(-alkyl)2, wherein the alkyl group is as described herein. Representative examples include, but are not limited to, dimethylamino, diethylamino, dipropylamino, diisopropylamino, dibutylamino, diisobutylamino, di(sec-butyl)amino, di(tert-butyl)amino, dipentylamino, diisopentylamino, di(tert-pentyl)amino, dihexylamino, N-ethyl-N-methylamino, N-methyl-N-propylamino, N-ethyl-N-propylamino, etc.

[0102] The term "carboxylic acid" as used in this article is represented by the formula -C(O)OH.

[0103] As used herein, the term "ester" is derived from the formula -OC(O)A 1 or -C(O)OA 1 It means that A 1 It may be alkyl, cycloalkyl, alkenyl, cycloalkenyl, ynyl, cycloynyl, aryl, or heteroaryl as described herein. As used herein, the term "polyester" is derived from formula -(A 1 O(O)CA 2 -C(O)O) a -or-(A 1 O(O)CA 2 -OC(O)) a - indicates that A 1 and A 2 It can be independently an alkyl, cycloalkyl, alkenyl, cycloalkenyl, ynyl, cycloynyl, aryl, or heteroaryl group as described herein, and "a" is an integer from 1 to 500. "Polyester" is a term used to describe a group produced by the reaction between a compound having at least two carboxylic acid groups and a compound having at least two hydroxyl groups.

[0104] As used herein, the term "ether" is derived from formula A. 1 OA 2 It means that A 1 and A 2 It may independently be alkyl, cycloalkyl, alkenyl, cycloalkenyl, ynyl, cycloynyl, aryl, or heteroaryl as described herein. As used herein, the term "polyether" is derived from the formula -(A 1 OA 2 O) a - indicates that A 1 and A 2 It can be independently alkyl, cycloalkyl, alkenyl, cycloalkenyl, ynyl, cycloynyl, aryl, or heteroaryl as described herein, and "a" is an integer from 1 to 500. Examples of polyether groups include polyethylene oxide, polypropylene oxide, and polybutane.

[0105] As used herein, the terms “halogenated,” “halogen,” or “halide” are used interchangeably and refer to F, Cl, Br, I, or At.

[0106] As used herein, the terms “pseudohalide,” “pseudohalogen,” or “pseudohalogenated” are used interchangeably and refer to functional groups that behave substantially like halides. For example, such functional groups include cyano, thiocyanate, azide, trifluoromethyl, trifluoromethoxy, perfluoroalkyl, and perfluoroalkoxy groups.

[0107] As used herein, the term "heteroalkyl" refers to an alkyl group containing at least one heteroatom. Suitable heteroatoms include, but are not limited to, O, N, Si, P, and S, wherein nitrogen, phosphorus, and sulfur atoms are optionally oxidized, and the nitrogen heteroatom is optionally quaternized. Heteroalkyl groups may be substituted as defined above.

[0108] As used herein, the term "heteroaryl" refers to an aromatic group having at least one heteroatom bonded within the ring of an aromatic group. Examples of heteroatoms include, but are not limited to, nitrogen, oxygen, sulfur, and phosphorus, wherein N-oxides, sulfur oxides, and dioxides are permitted heteroatom substitutions. Heteroaryl groups can be substituted or unsubstituted. Heteroaryl groups can be substituted by one or more groups, including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxyl, nitro, silyl, sulfo-oxo, or thiol groups as described herein. Heteroaryl groups can be monocyclic or alternatively fused-ring systems. The heteroaryl group includes, but is not limited to, furanyl, imidazolyl, pyrimidinyl, tetrazolyl, thiophene, pyridinyl, pyrroleyl, N-methylpyrroleyl, quinolinyl, isoquinolinyl, pyrazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, pyrazinyl, benzofuranyl, benzodioxazolyl, benzothiophene, indolyl, inazolyl, benzimidazolyl, imidazopyridyl, pyrazolopyridyl, and pyrazolopyrimidinyl. Further non-limiting examples of heteroaryl groups include, but are not limited to, pyridinyl, pyrimidinyl, pyrazinyl, thiopheneyl, pyrazolyl, imidazolyl, benzo[d]oxazolyl, benzo[d]thiazolyl, quinolinyl, quinazolinyl, indazole, imidazo[1,2-b]pyridinyl, imidazo[1,2-a]pyrazinyl, benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]oxadiazolyl, and pyrido[2,3-b]pyrazinyl.

[0109] As used herein, the term "heterocyclic" refers to monocyclic and polycyclic aromatic or non-aromatic ring systems in which at least one ring member is not carbon. Heterocyclic compounds include pyridine, pyrimidine, furan, thiophene, pyrrole, isoxazole, isothiazole, pyrazole, oxazole, thiazole, imidazole, oxazole (including 1,2,3-oxadiazole, 1,2,5-oxadiazole and 1,3,4-oxadiazole), thiadiazole (including 1,2,3-thiadiazole, 1,2,5-thiadiazole and 1,3,4-thiadiazole), triazole (including 1,2,3-triazole, 1,3,4-triazole), tetrazolium (including 1,2,3,4-tetrazolium and 1,2,4,5-tetrazolium), pyridine, pyridazine, pyrimidine, pyrazine, triazine (including 1,2,4-triazine and 1,3,5-triazine), tetraazine (including 1,2,4,5-tetrazine), pyrrolidine, piperidine, piperazine, morpholine, azacyclobutane, tetrahydropyran, tetrahydrofuran, dioxane, etc.

[0110] As used herein, the term "bicyclic heterocycle" or "bicyclic heterocyclic group" refers to a ring system in which at least one ring member is not carbon. A bicyclic heterocyclic group includes a ring system in which an aromatic ring is fused to another aromatic ring or in which an aromatic ring is fused to a non-aromatic ring. A bicyclic heterocyclic group includes a ring system in which a benzene ring is fused to a 5- or 6-membered ring containing 1, 2, or 3 heteroatoms or in which a pyridine ring is fused to a 5- or 6-membered ring containing 1, 2, or 3 heteroatoms. Bicyclic heterocyclic groups include, but are not limited to, indole, indazole, pyrazolo[1,5-a]pyridinyl, benzofuranyl, quinolinyl, quinoxalinyl, 1,3-benzodioxacyclopentenyl, 2,3-dihydro-1,4-benzodioxacyclohexenyl, 3,4-dihydro-2H-chromenyl, 1H-pyrazolo[4,3-c]pyridin-3-yl; 1H-pyrrolo[3,2-b]pyridin-3-yl; and 1H-pyrazolo[3,2-b]pyridin-3-yl.

[0111] As used herein, the term "heterocyclic alkyl" refers to an aliphatic, partially unsaturated, or fully saturated 3- to 14-membered ring system, comprising monocyclic, bicyclic, and tricyclic ring systems with 3 to 8 atoms. The heterocyclic alkyl ring system comprises one to four heteroatoms independently selected from oxygen, nitrogen, and sulfur, wherein the nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen heteroatom may optionally be substituted. Representative heterocyclic alkyl groups include, but are not limited to, pyrrolidinyl, pyrazolinyl, pyrazolyl, imidazolinyl, imidazolinyl, piperidinyl, piperazinyl, oxazolyl, isoxazolyl, morpholinyl, thiazolinyl, isothiazolyl, and tetrahydrofuranyl.

[0112] As used herein, the term "hydroxyl" or "hydroxyl" is represented by the formula -OH.

[0113] As used in this article, the term "ketone" is derived from formula A. 1 C(O)A2 It means that A 1 and A 2 It can be independently alkyl, cycloalkyl, alkenyl, cycloalkenyl, ynyl, cycloynyl, aryl or heteroaryl as described herein.

[0114] As used herein, the term "azide" or "azide group" is represented by the formula -N3.

[0115] As used in this article, the term "nitro" is represented by the formula -NO2.

[0116] As used herein, the terms “nitrile” or “cyano” are represented by the formula -CN.

[0117] As used herein, the term "silyl" is derived from the formula -SiA 1 A 2 A 3 It means that A 1 A 2 and A 3 It can be hydrogen independently or alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl or heteroaryl as described herein.

[0118] As used herein, the term "sulfonyl-oxo" is derived from the formula -S(O)A 1 -S(O)2A 1 -OS(O)2A 1 or -OS(O)2OA 1 It means that A 1 It can be hydrogen or alkyl, cycloalkyl, alkenyl, cycloalkenyl, ynyl, cycloynyl, aryl, or heteroaryl as described herein. Throughout this specification, “S(O)” is the simplified symbol for S=O. The term “sulfonyl” is used herein to refer to the compound of formula -S(O)₂A. 1 The sulfonyl-oxo group represents A. 1 It can be hydrogen or alkyl, cycloalkyl, alkenyl, cycloalkenyl, ynyl, cycloynyl, aryl, or heteroaryl as described herein. As used herein, the term "sulfone" is derived from formula A. 1 S(O)2A 2 It means that A 1 and A 2 It can be independently alkyl, cycloalkyl, alkenyl, cycloalkenyl, ynyl, cycloynyl, aryl, or heteroaryl as described herein. As used herein, the term "sulfone" is derived from formula A. 1 S(O)A 2 It means that A 1 and A 2 It can be independently alkyl, cycloalkyl, alkenyl, cycloalkenyl, ynyl, cycloynyl, aryl or heteroaryl as described herein.

[0119] As used in this article, the term "thiol" is represented by the formula -SH.

[0120] As used in this article, “R” 1 “R” 2 “R” 3 “R” n ", where n is an integer and can independently have one or more of the listed groups. For example, if R 1 If the alkyl group is a straight-chain alkyl group, one of the hydrogen atoms in the alkyl group may optionally be replaced by a hydroxyl group, an alkoxy group, an alkyl group, a halide, etc. Depending on the selected group, the first group may be incorporated into the second group, or alternatively, the first group may be side-attached (i.e., connected) to the second group. For example, in the phrase "alkyl group including an amino group," the amino group may be incorporated into the backbone of the alkyl group. Alternatively, the amino group may be attached to the backbone of the alkyl group. The nature of the selected group will determine whether the first group is inserted into or attached to the second group.

[0121] As described herein, the compounds of the present invention may contain an "optionally substituted" portion. Generally, the term "substituted," regardless of whether it is preceded by the term "optionally," refers to the substitution of one or more hydrogens of the specified portion by suitable substituents. Unless otherwise stated, the "optionally substituted" group may have suitable substituents at each substituted position of the group, and when more than one position in any given structure may be substituted by more than one substituent selected from the specified group, the substituents may be the same or different at each position. The combinations of substituents contemplated in the present invention are preferably those that result in the formation of stable or chemically viable compounds. It is also contemplated in some aspects that, unless explicitly stated otherwise, individual substituents may be further optionally substituted (i.e., further substituted or unsubstituted).

[0122] As used herein, the term “stable” means a compound that remains substantially unchanged when subjected to conditions that permit its production, detection, and in some respects its recovery, purification, and use for one or more purposes disclosed herein.

[0123] A suitable monovalent substituent on the substituted carbon atom of an "optionally substituted" group is independently a halogen; -(CH2) 0-4 R o ;-(CH2) 0-4 OR o ;-O(CH2) 0-4 R o -O-(CH2) 0-4 C(O)OR o ;-(CH2) 0-4 CH(ORo )2;-(CH2) 0-4 SR o ; can be R o Substituted -(CH2) 0-4 Ph; can be R o Substituted -(CH2) 0-4 O(CH2) 0-1 Ph; can be R o The substituted -CH=CHPh can be replaced by R o Substituted -(CH2) 0-4 O(CH2) 0-1 -pyridyl; -NO2; -CN; -N3; ​​-(CH2) 0-4 N(R o )2;-(CH2) 0-4 N(R o )C(O)R o ;-N(R o )C(S)R o ;-(CH2) 0-4 N(R o )C(O)NR o 2; -N(R) o )C(S)NR o 2;-(CH2) 0-4 N(R o )C(O)OR o ;-N(R o )N(R o )C(O)R o ;-N(R o )N(R o )C(O)NR o 2; -N(R) o )N(R o )C(O)OR o ;-(CH2) 0-4 C(O)R o ;-C(S)R o ;-(CH2) 0- 4C(O)OR o ;-(CH2) 0-4 C(O)SR o ;-(CH2) 0-4 C(O)OSiR o 3; -(CH2) 0-4 OC(O)R o ;-OC(O)(CH2) 0-4 SR-、SC(S)SR o ;-(CH2) 0-4 SC(O)Ro ;-(CH2) 0-4 C(O)NR o 2; -C(S)NR o 2;-C(S)SR o ;-SC(S)SR o -(CH2) 0-4 OC(O)NR o 2; -C(O)N(OR) o )R o ;-C(O)C(O)R o ;-C(O)CH2C(O)R o ;-C(NOR) o )R o ;-(CH2) 0-4 SSR o ;-(CH2) 0- 4S(O)2R o ;-(CH2) 0-4 S(O)2OR o ;-(CH2) 0-4 OS(O)2R o ;-S(O)2NR o 2;-(CH2) 0-4 S(O)R o ;-N(R o )S(O)2NR o 2; -N(R) o )S(O)2R o ;-N(OR) o )R o ;-C(NH)NR o 2; -P(O)2R o ;-P(O)R o 2; -OP(O)R o 2; -OP(O)(OR o )2; SiR o 3; -(C 1-4 (linear or branched alkylene)ON(R) o )2; or -(C 1-4 (straight-chain or branched alkylene)C(O)ON(R) o )2, where each R o It can be substituted and independently defined as hydrogen, C. 1-6 Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph, -CH2- (5-6 membered heteroaryl ring) or a 5-6 membered saturated, partially unsaturated or aryl ring having 0-4 independent heteroatoms selected from nitrogen, oxygen, or sulfur, or, despite the above definition, two independently occurring Ro Together with the atoms in between, they form 3-12 saturated, partially unsaturated, or aryl monocyclic or bicyclic rings with 0-4 independent heteroatoms selected from nitrogen, oxygen, or sulfur, which can be substituted according to the following definition.

[0124] R o (or two independently occurring R) o The appropriate monovalent substituents on the ring formed together with the atoms in between are halogens, -(CH2). 0-2 R · 、-(haloR · -(CH2) 0-2 OH, -(CH2) 0-2 OR · -(CH2) 0-2 CH(OR · )2;-O(haloR · -CN, -N3, -(CH2) 0-2 C(O)R · -(CH2) 0-2 C(O)OH, -(CH2) 0-2 C(O)OR · -(CH2) 0-2 SR · -(CH2) 0-2 SH, -(CH2) 0-2 NH2、-(CH2) 0-2 NHR · -(CH2) 0-2 NR · 2, -NO2, -SiR · 3. -OSiR · 3. -C(O)SR · -(C 1-4 (straight-chain or branched alkylene)C(O)OR · or -SSR · , where each R · It is not replaced, or if preceded by "halogenated", it is replaced by one or more halogens and is independently selected from C. 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph or a 5-6 member saturated, partially unsaturated, or aryl ring having 0-4 independent heteroatoms selected from nitrogen, oxygen, or sulfur. R o Suitable divalent substituents on saturated carbon atoms include =O and =S.

[0125] Suitable divalent substituents on the saturated carbon atom of the "optionally substituted" group include the following: =O, =S, =NNR. *2、=NNHC(O)R * =NNHC(O)OR * =NNHS(O)2R * =NR * =NOR * -O(C(R) * 2)) 2-3 O- or -S(C(R) * 2)) 2-3 S-, where each independently occurring R * Selected from hydrogen, C can be substituted according to the following definition 1-6 Aliphatic, or having 0-4 unsubstituted 5-6 membered saturated, partially unsaturated, or aryl rings independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents attached to the ortho-substituted carbon of the "optionally substituted" group include: -O(CR * 2) 2-3 O-, where each independently occurring R * Selected from hydrogen, the substituted C can be defined as follows: 1-6 Aliphatic, or having 0-4 unsubstituted 5-6 saturated, partially unsaturated or aryl rings independently selected from nitrogen, oxygen or sulfur.

[0126] R * Suitable substituents on aliphatic groups include halogens, -R · -(halogenated R) · -OH, -OR · -O (halogenated R) · -CN, -C(O)OH, -C(O)OR · -NH2, -NHR · -NR · 2 or -NO2, where each R · When not substituted or preceded by "halogenated", it is substituted by one or more halogens and is independently C. 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph or a 5-6 member saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0127] Suitable substituents on the substituted nitrogen of the "optionally substituted" group include or Each of them Independently, hydrogen can be substituted C as follows: 1-6Aliphatic, unsubstituted -OPh or having 0-4 independently selected heteroatoms of nitrogen, oxygen or sulfur, unsubstituted 5-6 membered saturated, partially unsaturated or aryl rings, or, despite the above definition, two independently occurring... Together with the atoms in between, they form unsubstituted 3-12 saturated, partially unsaturated, or aryl monocyclic or bicyclic rings with 0-4 independent heteroatoms selected from nitrogen, oxygen, or sulfur.

[0128] Suitable substituents on the aliphatic group can be halogens or -R. · -(halogenated R) · -OH, -OR · -O (halogenated R) · -CN, -C(O)OH, -C(O)OR · -NH2, -NHR · -NR · 2 or -NO2, where each R · When not substituted or preceded by "halogenated", it is substituted by one or more halogens and is independently C. 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph or a 5-6 member saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0129] The term "leaving group" refers to an atom (or group of atoms) with electron-withdrawing ability that can be replaced along with bonding electrons as a stable substance. Examples of suitable leaving groups include halides and sulfonates, including but not limited to trifluoromethanesulfonates, methanesulfonates, toluenesulfonates, p-bromobenzenesulfonates, and halides.

[0130] The terms “hydrolyzable group” and “hydrolyzable moiety” refer to functional groups that are capable of undergoing hydrolysis under, for example, basic or acidic conditions. Examples of hydrolyzable residues include, but are not limited to, acyl halides, activated carboxylic acids, and various protecting groups known in the art (see, for example, “Protective Groups in Organic Synthesis”, TW Greene, PGM Uts, Wiley-Interscience, 1999).

[0131] The term "organic residue" is defined as a carbon-containing residue, that is, a residue comprising at least one carbon atom, and including, but not limited to, carbon-containing groups, residues, or free radicals as defined above. Organic residues may contain various heteroatoms, or may be linked to another molecule via heteroatoms (including oxygen, nitrogen, sulfur, phosphorus, etc.). Examples of organic residues include, but are not limited to, alkyl or substituted alkyl groups, alkoxy or substituted alkoxy groups, mono- or di-substituted amino groups, amide groups, etc. Organic residues preferably comprise 1 to 18 carbon atoms, 1 to 15 carbon atoms, 1 to 12 carbon atoms, 1 to 8 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms. In a further aspect, organic residues may comprise 2 to 18 carbon atoms, 2 to 15 carbon atoms, 2 to 12 carbon atoms, 2 to 8 carbon atoms, 2 to 4 carbon atoms, or 2 to 4 carbon atoms.

[0132] A very close synonym for the term "residue" is the term "free radical," which, when used in the specification and concluding claims, refers to a fragment, group, or substructure of the molecule described herein, regardless of how the molecule is prepared. For example, the 2,4-thiazolidinedione free radical in a particular compound has the following structure:

[0133]

[0134] Regardless of whether a thiazolidinedione is used to prepare the compound. In some embodiments, the radical (e.g., an alkyl group) may be further modified (i.e., substituted alkyl groups) by having one or more "substituent radicals" bonded to it. The number of atoms in a given radical is not critical to the present invention unless otherwise stated elsewhere herein.

[0135] As defined and used herein, the term "organic radical" contains one or more carbon atoms. Organic radicals may have, for example, 1-26 carbon atoms, 1-18 carbon atoms, 1-12 carbon atoms, 1-8 carbon atoms, 1-6 carbon atoms, or 1-4 carbon atoms. In a further aspect, organic radicals may have 2-26 carbon atoms, 2-18 carbon atoms, 2-12 carbon atoms, 2-8 carbon atoms, 2-6 carbon atoms, or 2-4 carbon atoms. Organic radicals typically have hydrogen atoms bonded to at least some of their carbon atoms. An example of an organic radical that does not contain inorganic atoms is the 5,6,7,8-tetrahydro-2-naphthyl radical. In some embodiments, the organic radical may contain 1-10 inorganic heteroatoms bonded thereto or bonded thereto, including halogens, oxygen, sulfur, nitrogen, phosphorus, etc. Examples of organic free radicals include, but are not limited to, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, monosubstituted amino, disubstituted amino, acyloxy, cyano, carboxyl, alkoxycarbonyl, alkylcarboxamide, substituted alkylcarboxamide, dialkylcarboxamide, substituted dialkylcarboxamide, alkylsulfonyl, alkylsulfinyl, thioalkyl, thiohaloalkyl, alkoxy, substituted alkoxy, haloalkyl, haloalkoxy, aryl, substituted aryl, heteroaryl, heterocyclic or substituted heterocyclic free radicals, wherein the terms are defined elsewhere herein. Some non-limiting examples of organic free radicals containing heteroatoms include alkoxy radicals, trifluoromethoxy radicals, acetoxy radicals, dimethylamino radicals, etc.

[0136] As defined and used herein, the term "inorganic radical" contains no carbon atom and therefore includes only atoms other than carbon. Inorganic radicals comprise bonded combinations of atoms selected from hydrogen, nitrogen, oxygen, silicon, phosphorus, sulfur, selenium, and halogens such as fluorine, chlorine, bromine, and iodine, which may exist individually or bonded together in chemically stable combinations. Inorganic radicals have 10 or fewer, or preferably one to six or one to four inorganic atoms bonded together as listed above. Examples of inorganic radicals include, but are not limited to, known inorganic radicals such as amino, hydroxyl, halogen, nitro, thiol, sulfate, and phosphate. Inorganic radicals do not contain periodic table metal elements (such as alkali metals, alkaline earth metals, transition metals, lanthanides, or actinides), although these metal ions can sometimes serve as pharmaceutically acceptable cations for anionic inorganic radicals such as sulfate, phosphate, or similar anionic inorganic radicals. Inorganic free radicals do not include metalloid elements such as boron, aluminum, gallium, germanium, arsenic, tin, lead or tellurium, or noble gas elements, unless otherwise specified elsewhere in this document.

[0137] The compounds described herein may contain one or more double bonds, and therefore may produce cis / trans (E / Z) isomers and other conformational isomers. Unless otherwise stated, the invention encompasses all such possible isomers and mixtures of such isomers.

[0138] Unless otherwise stated, formulas having chemical bonds represented only by solid lines rather than wedges or dashed lines consider every possible isomer, such as each enantiomer and diastereomer, and mixtures of isomers, such as racemic or non-racemic mixtures. The compounds described herein may contain one or more asymmetric centers and thus may produce diastereomers and optical isomers. Unless otherwise stated, the invention encompasses all such possible diastereomers and their racemic mixtures, their substantially pure resolved enantiomers, all possible geometric isomers, and their pharmaceutically acceptable salts. Stereoisomers and mixtures of separated specific stereoisomers are also included. In synthetic procedures used to prepare such compounds, or in the use of racemicization or epimerization procedures known to those skilled in the art, the products of such procedures may be mixtures of stereoisomers.

[0139] Many organic compounds exist in optically active forms, possessing the ability to rotate the plane of plane-polarized light. In describing optically active compounds, the prefixes D and L or R and S are used to indicate the absolute configuration of the molecule with respect to its chiral center. The prefixes d and l or (+) and (-) are used to indicate the rotational sign of the compound with respect to plane-polarized light, where (-) indicates that the compound is levorotatory. Compounds with the prefix (+) or d are dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are non-superimposed mirror images of each other. Specific stereoisomers can also be called enantiomers, and mixtures of such isomers are generally referred to as enantiomeric mixtures. A 50:50 mixture of enantiomers is called a racemic mixture. Many of the compounds described herein may have one or more chiral centers and therefore may exist in different enantiomeric forms. If desired, the chiral carbon can be indicated by an asterisk (*). When the bonds with chiral carbon are depicted as straight lines in the disclosed formulas, it should be understood that both the (R) and (S) configurations of the chiral carbon, and therefore the two enantiomers and mixtures thereof, are included in the formulas. As used in the art, when it is desired to specify an absolute configuration with respect to chiral carbon, one of the bonds with chiral carbon can be depicted as a wedge (bond with atoms above the plane), while the other can be depicted as a series or wedge of short parallel lines (bond with atoms below the plane). The Cahn-Ingold-Prelog system can be used to assign (R) or (S) configurations to chiral carbons.

[0140] The compounds described herein include atoms with both natural and non-natural isotopic abundances. The disclosed compounds may be isotopically labeled or isotopically substituted compounds, but in fact, one or more atoms are replaced by atoms with atomic masses or mass numbers different from those commonly found in nature. Examples of isotopes that may be incorporated into the compounds of this invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, for example... 2 H, 3 H, 13 C 14 C 15 N、 18 O、 17 O、 35 S, 18 F and 36 Cl. The compound further comprises its prodrug, and a pharmaceutically acceptable salt of the compound or the prodrug containing the aforementioned isotopes and / or other atoms is within the scope of this invention. Certain isotope-labeled compounds of this invention, such as those doped with radioactive isotopes such as 3 H and 14 Compounds containing C can be used for drug and / or substrate tissue distribution assays. Tritized isotopes (i.e., 3 H) and carbon-14 isotopes (i.e. 14 C) are particularly preferred because they are easy to prepare and detect. Furthermore, heavier isotopes such as deuterium (i.e., 2 H) substitution can provide certain therapeutic advantages stemming from greater metabolic stability, such as increased in vivo half-life or reduced dose requirements, and may therefore be preferred in certain situations. The isotopically labeled compounds and their prodrugs of the present invention can generally be prepared by performing a procedure in which readily available isotopically labeled reagents are substituted for non-isotopically labeled reagents.

[0141] The compounds described in this invention can exist as solvates. In some cases, the solvent used to prepare the solvate is an aqueous solution, and thus the solvate is generally referred to as a hydrate. The compound can exist as a hydrate, for example, a hydrate can be obtained by crystallization from a solvent or from an aqueous solution. In this respect, one, two, three, or any number of solvates or water molecules can be combined with the compound according to the invention to form a solvate and a hydrate. Unless otherwise stated, the invention encompasses all such possible solvates.

[0142] The term "cocrystal" refers to the physical association of two or more molecules due to their stability through non-covalent interactions. One or more components of this molecular complex provide a stable framework in a crystal lattice. In some cases, guest molecules are incorporated into the lattice as an anhydrous or solvant; see, for example, "Crystal Engineering of the Composition of Pharmaceutical Phases. Do Pharmaceutical Co-crystals Represent a New Path to Improved Medicines?" Almarasson, O. et al., The Royal Society of Chemistry, 1889–1896, 2004. Examples of cocrystals include p-toluenesulfonic acid and benzenesulfonic acid.

[0143] It should also be understood that some of the compounds described herein can exist as a balance of tautomers. For example, ketones having α-hydrogen can exist in a balance of ketone and enol forms.

[0144]

[0145] Similarly, amides with N-hydrogen can exist in a balance between amide and imine forms. As another example, pyrazoles can exist in two tautomeric forms, N... 1 - Unreplaced 3-A 3 and N 1 - Unreplaced 5-A 3 As shown below.

[0146]

[0147] Unless otherwise stated, this invention encompasses all such possible tautomers.

[0148] Chemical substances are known to form solids in different ordered states, known as polymorphs or modifications. Different modifications to polymorphic substances can vary considerably in their physical properties. Compounds according to the invention can exist in different polymorphic forms, where specific modifications may be metastable. Unless otherwise stated, the invention encompasses all such possible polymorphic forms.

[0149] In some respects, the structure of a compound can be represented by the following formula:

[0150]

[0151] It is understood to be equivalent to the following formula:

[0152]

[0153] Where n is usually an integer. That is, R n It is understood to represent five independent substituents R n(a) R n(b) R n(c) R n(d) R n (e) "Independent substituents" means that each R substituent can be defined independently. For example, if in one case R n(a) If it is a halogen, then in this case R n(b) It doesn't have to be halogen.

[0154] Some of the materials, compounds, compositions, and components disclosed herein are commercially available or can be readily synthesized using techniques generally known to those skilled in the art. For example, the starting materials and reagents used to prepare the disclosed compounds and compositions are available from commercial suppliers such as Aldrich Chemical Co. (Milwaukee, Wisconsin), Acros Organics (Morrison Plains, New Jersey), Fisher Scientific (Pittsburgh, Pennsylvania), or Sigma (St. Louis, Missouri), or by methods known to those skilled in the art, according to references such as Fieser and Fieser's Reagents for Organic Synthesis, Volume 1–17 (John Wiley and Sons, 1991); Rodd's Chemistry of Carbon Compounds, Volume 1–5 and Supplements (Elsevier Science Publishers, 1989); Organic Reactions, Volume 1–40 (John Wiley and Sons, 1991); March's Advanced Organic Chemistry, (John Wiley and Sons, 1991). The procedures described in Wiley and Sons (4th edition) and Larock's Comprehensive Organic Transformations (VCH Publishers Inc., 1989) are as follows.

[0155] Unless otherwise expressly stated, no method described herein shall be construed as requiring its steps to be performed in a particular order. Therefore, no inference is made in any respect of the order in which the method claims do not actually describe the order of their steps, or where the claims or description do not otherwise specifically state that these steps are to be limited to a particular order. This applies to any possible non-express basis for interpretation, including logical questions concerning the arrangement of steps or operational flows, explicit meanings derived from grammatical organization or punctuation, or the number or type of embodiments described in the specification.

[0156] The components used to prepare the compositions of the present invention and the compositions themselves used in the methods disclosed herein are disclosed. These and other materials are disclosed herein, and it should be understood that when combinations, subsets, interactions, groupings, etc., of these materials are disclosed, although specific references to every individual and collective combination and arrangement of these compounds are not explicitly disclosed, each is specifically considered and described herein. For example, if a particular compound is disclosed and discussed, and many modifications that can be made to a number of molecules comprising said compound are discussed, then every combination and arrangement of said compounds and possible modifications are specifically considered, unless the opposite is specifically indicated. Thus, if an example of a class of molecules A, B, and C, and a class of molecules D, E, and F and examples of combined molecules is disclosed, then AD is disclosed; and AE, AF, BD, BE, BF, CD, CE, and CF are considered disclosed even though each is not individually enumerated, but the meaning of each combination is considered individually and collectively. Similarly, any subsets or combinations of these are also disclosed. Thus, for example, subgroups of AE, BF, and CE would be considered disclosed. This concept applies to all aspects of this application, including but not limited to the steps in methods of preparing and using the compositions of the present invention. Therefore, if there are various additional steps that can be performed, it should be understood that each of these additional steps can be performed together with any specific embodiment or combination of embodiments of the method of the present invention.

[0157] It should be understood that the compositions disclosed herein have certain functions. This document discloses certain structural requirements for performing the disclosed functions, and it should be understood that various structures exist that can perform the same functions associated with the disclosed structures, and these structures will generally achieve the same results.

[0158] B. Compounds

[0159] On the one hand, compounds that can be prepared by the disclosed methods are disclosed (e.g., compounds prepared by converting carbon-hydrogen, carbon-oxygen, carbon-sulfur, or carbon-nitrogen bonds to carbon-carbon, carbon-halogen, or isotopically labeled carbon-nitrogen bonds, and compounds prepared by converting carbon-halogen bonds to isotopically labeled carbon-halogen bonds). Each disclosed derivative is contemplated to be optionally further substituted. It is also contemplated that any one or more derivatives may be optionally omitted from the invention. It should be understood that the disclosed compounds can be provided by the disclosed methods.

[0160] 1. Structure

[0161] In one aspect, compounds having a structure represented by the following formula are disclosed:

[0162] Ar 1 -Z,

[0163] Z is selected from halogens, -CN, -NH2, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino, provided that when Z is -NH2, C1-C4 alkylamino, or (C1-C4)(C1-C4)dialkylamino, Z contains a radioactive isotope; where Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Ar... 2When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0164]

[0165] In one aspect, compounds having a structure represented by the following formula are disclosed:

[0166] Ar 1 -Z,

[0167] Z is selected from halogens, -CN, -NH2, C1-C4 alkylamino and (C1-C4)(C1-C4) dialkylamino, and Z contains a radioactive isotope; Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Ar... 2When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0168]

[0169] In one aspect, compounds having a structure represented by the following formula are disclosed:

[0170] Ar 1 -Z,

[0171] Z is selected from halogens, -CN, -NH2, C1-C4 alkylamino and (C1-C4)(C1-C4) dialkylamino, and Z contains a radioactive isotope; Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; wherein R 16 When present, it is a hydroxyl protecting group; and Ar is present in it. 2When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0172]

[0173] In one aspect, compounds having a structure represented by the following formula are disclosed:

[0174] Ar 1 -Z,

[0175] Where Z is a halogen, and Z contains a radioactive isotope; where Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; wherein R 16 When present, it is a hydroxyl protecting group; and Ar is present in it. 2When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0176]

[0177] In one aspect, compounds having a structure represented by the following formula are disclosed:

[0178] Ar 1 -X,

[0179] Where X is a halogen and X contains a radioactive isotope; where Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Ar... 2When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0180]

[0181] In a further aspect, the compound has a structure represented by the following formula:

[0182]

[0183] Where R 30a R 30b R 30c R 30d and R 30e Each of these elements is independently selected from hydrogen, halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 , or R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered ring or heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0, 1, 2, or 3 groups independently selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

[0184] In a further aspect, the compound has a structure represented by a formula selected from the following:

[0185]

[0186] In a further aspect, the compound has a structure represented by the following formula:

[0187]

[0188] In a further aspect, the compound has a structure represented by the following formula:

[0189]

[0190] Z is selected from -CN and halogens.

[0191] In a further aspect, the compound has a structure represented by the following formula:

[0192] In a further aspect, the compound has a structure represented by the following formula:

[0193] Z represents halogen.

[0194] In a further aspect, the compound has a structure represented by a formula selected from the following:

[0195]

[0196] In a further aspect, the compound has a structure represented by the following formula:

[0197] In a further aspect, the compound has a structure represented by the following formula:

[0198]

[0199] Z is selected from -NH2, C1-C4 alkylamino and (C1-C4)(C1-C4) dialkylamino.

[0200] In a further aspect, the compound has a structure represented by a formula selected from the following:

[0201]

[0202] Where R 30a R 30b R 30c R 30d and R 30eEach of these elements, when present, is independently selected from hydrogen, halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 , or R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered ring or heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0, 1, 2, or 3 groups independently selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

[0203] In a further aspect, the compound has a structure represented by a formula selected from the following:

[0204]

[0205] In a further aspect, the compound has a structure represented by the following formula:

[0206]

[0207] In a further aspect, the compound has a structure represented by the following formula:

[0208]

[0209] Z is selected from -CN and halogens.

[0210] In a further aspect, the compound has a structure represented by the following formula:

[0211]

[0212] In a further aspect, the compound has a structure represented by the following formula:

[0213]

[0214] Z represents halogen.

[0215] In a further aspect, the compound has a structure represented by a formula selected from the following:

[0216]

[0217]

[0218] In a further aspect, the compound has a structure represented by the following formula:

[0219]

[0220] In a further aspect, the compound has a structure represented by the following formula:

[0221]

[0222] Z is selected from -NH2, C1-C4 alkylamino and (C1-C4)(C1-C4) dialkylamino.

[0223] In a further aspect, the compound has a structure selected from the following:

[0224]

[0225] In a further aspect, fluorine is 18 F.

[0226] In a further aspect, the compound has a structure selected from the following:

[0227]

[0228]

[0229] In a further aspect, cyanide is 11 CN.

[0230] In a further aspect, the compound is selected from:

[0231]

[0232]

[0233] In a further aspect, Z is a halogen and the nucleophile is a halide. In yet another further aspect, Z is... 18 F, and the nucleophile is...18 F-TBAF.

[0234] aZ group

[0235] In one aspect, Z is selected from halogens, -CN, -NH2, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino, provided that when Z is -NH2, C1-C4 alkylamino or (C1-C4)(C1-C4)dialkylamino, Z contains a radioactive isotope.

[0236] In one aspect, Z is selected from halogens, -CN, -NH2, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino, and wherein Z contains a radioactive isotope.

[0237] In a further aspect, Z contains a radioactive isotope, such as a radioactive isotope that can be used for imaging and therapy. Examples of radioactive isotopes include, but are not limited to, those mentioned above. 18 F, 11 C 34 Cl、 76 Br、 123 I, 124 I, 131 I, 125 I and 211 At, although other radioisotopes for imaging and treatment are also envisioned. In a further aspect, the radioisotopes are selected from... 18 F, 11 C 34 Cl、 76 Br、 123 I, 124 I, 131 I, 125 I and 211 At. In a further aspect, the radioactive isotopes are selected from... 18 F and 11 C. In a further aspect, radioactive isotopes are 18 F. In a further aspect, radioactive isotopes are 11 C.

[0238] In a further aspect, Z is selected from halogens and -CN. In an even further aspect, Z is selected from fluorine, chlorine, iodine, astatine, and -CN. In an even further aspect, Z is selected from fluorine, chlorine, astatine, and -CN. In an even further aspect, Z is selected from fluorine, chlorine, and -CN. In an even further aspect, Z is selected from fluorine and -CN.

[0239] In a further aspect, Z is selected from fluorine, chlorine, -CN, -NH2, -NHCH3, -NHCH2CH3, -NHCH2CH2CH3, -NHCH(CH3)2, -N(CH3)2, -N(CH3)(CH2CH3), -N(CH3)(CH2CH2CH3), -N(CH3)(CH(CH3)2), -N(CH2CH3)2, -N(CH2CH3)(CH2CH2CH3), -N(CH2CH3)(CH(CH3)2), -N(CH2CH2CH3)2, -N(CH2CH2CH3)(CH(CH3)2), and -N(CH(CH3)2)2. In an even further aspect, Z is selected from fluorine, chlorine, -CN, -NH2, -OH, -NHCH3, -NHCH2CH3, -N(CH3)2, and -N(CH3)(CH2CH3). In a further aspect, Z is selected from fluorine, chlorine, -CN, -NH2, -NHCH3 and -N(CH3)2.

[0240] In a further aspect, Z is selected from C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino. In a still further aspect, Z is selected from -NHCH3, -NHCH2CH3, -NHCH2CH2CH3, -NHCH(CH3)2, -N(CH3)2, -N(CH3)(CH2CH3), -N(CH3)(CH2CH2CH3), -N(CH3)(CH(CH3)2), -N(CH2CH3)2, -N(CH2CH3)(CH2CH2CH3), -N(CH2CH3)(CH(CH3)2), -N(CH2CH2CH3)2, -N(CH2CH2CH3)(CH(CH3)2) and -N(CH(CH3)2)2. In an even further aspect, Z is selected from -NHCH3, -NHCH2CH3, -N(CH3)2 and -N(CH3)(CH2CH3). In a further aspect, Z is selected from -NHCH3 and -N(CH3)2.

[0241] In a further aspect, Z is selected from -NH2, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino. In an even further aspect, Z is selected from -NH2, -NHCH3, -NHCH2CH3, -NHCH2CH2CH3, -NHCH(CH3)2, -N(CH3)2, -N(CH3)(CH2CH3), -N(CH3)(CH2CH2CH3), -N(CH3)(CH(CH3)2), -N(CH2CH3)2, -N(CH2CH3)(CH2CH2CH3), -N(CH2CH2CH3)2, -N(CH2CH2CH3)2, -N(CH2CH2CH3)(CH(CH3)2) and -N(CH(CH3)2)2. In a further aspect, Z is selected from -NH2, -NHCH3, -NHCH2CH3, -N(CH3)2, and -N(CH3)(CH2CH3). In an even further aspect, Z is selected from -NH2, -NHCH3, and -N(CH3)2.

[0242] In a further aspect, Z is selected from halogens, -CN, and -NH2. In an even further aspect, Z is selected from fluorine, chlorine, -CN, and -NH2.

[0243] In a further aspect, Z is selected from -CN and -NH2. In an even further aspect, Z is -CN. In an even further aspect, Z is -NH2.

[0244] In a further aspect, Z is a halogen. In an even further aspect, Z is selected from fluorine, chlorine, iodine, and astatine. In an even further aspect, Z is selected from fluorine, chlorine, and astatine. In an even further aspect, Z is selected from fluorine and chlorine. In an even further aspect, Z is chlorine. In an even further aspect, Z is fluorine. In an even further aspect, Z is astatine.

[0245] bR 10 R 11 R 12A R 12B R 13 and R 15 Group

[0246] In one aspect, R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups. In a further aspect, R... 10 R 11 R 12a R 12b R13 and R 15 Each of these, when present, is independently selected from hydrogen, methyl, ethyl, n-propyl, and isopropyl. In a further aspect, R... 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen, methyl, and ethyl. In a further aspect, R... 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and ethyl. In a further aspect, R... 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and methyl. In a further aspect, R... 10 R 11 R 12a R 12b R 13 and R 15 Each of them is hydrogen when it exists.

[0247] In a further aspect, R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from C1-C4 alkyl groups. In a further aspect, R... 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from methyl, ethyl, n-propyl, and isopropyl. In a further aspect, R... 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from methyl and ethyl. In a further aspect, R... 10 R 11 R 12a R 12b R 13and R 15 Each of these is an ethyl group when it exists. In a further aspect, R... 10 R 11 R 12a R 12b R 13 and R 15 Each of them is a methyl group when it is present.

[0248] In a further aspect, R 11a It is hydrogen and R 11b It is a C1-C4 alkyl group. In a further aspect, R... 11a It is hydrogen and R 11b Selected from methyl, ethyl, n-propyl, and isopropyl. In a further aspect, R... 11a It is hydrogen and R 11b Selected from methyl and ethyl. In a further aspect, R 11a It is hydrogen and R 11b It is ethyl. In a further aspect, R 11a It is hydrogen and R 11b It is a methyl group.

[0249] cR 14A and R 14B Group

[0250] In one aspect, R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups. Examples of amine protecting groups include, but are not limited to, benzyloxycarbonyl, p-methoxybenzylcarbonyl, tert-butoxycarbonyl, 9-fluorenylmethyloxycarbonyl, acetyl, benzoyl, benzyl, carbamate, p-methoxybenzyl, 3,4-dimethoxybenzyl, p-methoxyphenyl, toluenesulfonyl, and 4-nitrobenzenesulfonyl. Therefore, in a further aspect, R 14a and R 14b Each of these, when present, is independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, benzyloxycarbonyl, p-methoxybenzylcarbonyl, tert-butoxycarbonyl, 9-fluorenylmethyloxycarbonyl, acetyl, benzoyl, benzyl, carbamate, p-methoxybenzyl, 3,4-dimethoxybenzyl, p-methoxyphenyl, toluenesulfonyl, and 4-nitrobenzenesulfonyl. In a further aspect, R 14a and R 14b Each of these, when present, is independently selected from hydrogen, methyl, ethyl, and tert-butoxycarbonyl. In a further aspect, R... 14a and R 14b Each of them, when present, is independently selected from hydrogen and tert-butoxycarbonyl.

[0251] In a further aspect, R14a and R 14b Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups. In a further aspect, R... 14a and R 14b Each of these, when present, is independently selected from hydrogen, methyl, ethyl, n-propyl, and isopropyl. In a further aspect, R... 14a and R 14b Each of these, when present, is independently selected from hydrogen, methyl, and ethyl. In a further aspect, R... 14a and R 14b Each of these, when present, is independently selected from hydrogen and ethyl. In a further aspect, R... 14a and R 14b Each of these, when present, is independently selected from hydrogen and methyl. In a further aspect, R... 14a and R 14b Each of them is hydrogen when it exists.

[0252] In a further aspect, R 14a and R 14b Each of these, when present, is independently selected from C1-C4 alkyl groups. In a further aspect, R... 14a and R 14b Each of these, when present, is independently selected from methyl, ethyl, n-propyl, and isopropyl. In a further aspect, R... 14a and R 14b Each of these, when present, is independently selected from methyl and ethyl. In a further aspect, R... 14a and R 14b Each of these is an ethyl group when it exists. In a further aspect, R... 14a and R 14b Each of them is a methyl group when it is present.

[0253] In a further aspect, R 14a It is hydrogen and R 14b It is a C1-C4 alkyl group. In a further aspect, R... 14a It is hydrogen and R 14b Selected from methyl, ethyl, n-propyl, and isopropyl. In a further aspect, R... 14a It is hydrogen and R 14b Selected from methyl and ethyl. In a further aspect, R 14a It is hydrogen and R 14b It is ethyl. In a further aspect, R 14a It is hydrogen and R 14b It is a methyl group.

[0254] dR 16 Group

[0255] In one aspect, R 16 When present, it is a hydroxyl protecting group. Examples of hydroxyl protecting groups include, but are not limited to, acetyl, benzoyl, benzyl, β-methoxyethoxymethyl ether, dimethoxytriphenylmethyl, methoxymethyl ether, methoxytriphenylmethyl, p-methoxybenzyl ether, methyl thiomethyl ether, neopentanoyl, tetrahydropyranyl, tetrahydrofuran, triphenylmethyl, silyl ether, methyl ether, and trifluoromethanesulfonate. Therefore, in various aspects, R 16 It exists as a trifluoromethanesulfonate.

[0256] eR 30A R 30B R 30C R 30D and R 30E Group

[0257] In one aspect, R 30a R 30b R 30c R 30d and R 30e Each of these elements, when present, is independently selected from hydrogen, halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 , or R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered ring or heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0, 1, 2, or 3 groups independently selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

[0258] In a further aspect, R30a R 30b R 30c R 30d and R 30e Each of these elements, when present, is independently selected from hydrogen, halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Each of these elements, when present, is independently selected from hydrogen, halogen, -CN, -NO2, C1-C4 alkyl, C1-C4 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Each of these elements, when present, is independently selected from hydrogen, halogen, -CN, -NO2, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30eEach of these elements, when present, is independently selected from hydrogen, halogen, -CN, -NO2, methyl, ethyl, methoxy, ethoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Each of these elements, when present, is independently selected from hydrogen, halogen, -CN, -NO2, methyl, methoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Each of them is hydrogen when it exists.

[0259] In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered ring or heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0, 1, 2, or 3 groups independently selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R30c R 30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered ring or heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0, 1, or 2 groups independently selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered ring or heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0 or 1 group selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered ring or heterocycle having 0, 1, or 2 heteroatoms and being monosubstituted by a group selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered ring or heterocycle with 0, 1, or 2 heteroatoms that are not substituted.

[0260] In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered ring substituted independently with 0, 1, 2, or 3 groups selected from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered ring substituted independently with 0, 1, or 2 groups selected from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered ring substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10-C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered ring monosubstituted with a group selected from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered unsubstituted ring.

[0261] In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 5-membered ring substituted independently with 0, 1, 2, or 3 groups selected from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 5-membered ring substituted by 0, 1, or 2 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 5-membered ring substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 5-membered ring monosubstituted with a group selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30eAny two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 5-membered unsubstituted ring.

[0262] In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 6-membered ring substituted by 0, 1, 2 or 3 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 6-membered ring substituted by 0, 1, or 2 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 6-membered ring substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 6-membered ring monosubstituted with a group selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 6-membered unsubstituted ring.

[0263] In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0, 1, 2, or 3 groups independently selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30eAny two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0, 1, or 2 groups independently selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0 or 1 group selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered heterocycle having 0, 1, or 2 heteroatoms and monosubstituted with a group selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered heterocycle with 0, 1, or 2 heteroatoms and are not substituted.

[0264] In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5-membered heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0, 1, 2, or 3 groups independently selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5-membered heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0, 1, or 2 groups independently selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 5-membered heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0 or 1 group selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 5-membered heterocycle having 0, 1, or 2 heteroatoms and being monosubstituted by a group selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 5-membered heterocycle with 0, 1 or 2 heteroatoms that are not substituted.

[0265] In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 6-membered heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0, 1, 2, or 3 groups independently selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 6-membered heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0, 1, or 2 groups independently selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 6-membered heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0 or 1 group selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R 30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 6-membered heterocycle having 0, 1, or 2 heteroatoms and being substituted by a single group selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, R30a R 30b R 30c R 30d and R 30e Any two adjacent atoms in the ring are optionally covalently bonded and together with the intermediate atom form a 6-membered heterocycle with 0, 1 or 2 heteroatoms that are not substituted.

[0266] f.AR 1 Group

[0267] In one aspect, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ; or Ar 1 The structure is represented by the following formula:

[0268]

[0269] Examples of aryl and heteroaryl groups include, but are not limited to, phenyl, naphthyl, furanyl, pyridyl, pyrazinyl, pyrroleyl, imidazolyl, pyrazolyl, oxazolyl, thiophene, benzimidazolyl, purine, indolyl, quinolinyl, isoquinolinyl, phthalazinyl, and quinazolinyl. Other examples of aryl and heteroaryl groups are disclosed elsewhere herein. In a further aspect, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ; or Ar 1 The structure is represented by the following formula:

[0270]

[0271] In one aspect, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C4 alkyl, C1-C4 alkoxy, -O-(C1-C4 alkyl)-CO2-(C1-C4 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, -OCH2CO2CH3, -OCH2CH2CO2CH2CH3, -OCH2CO2CH(CH3)2, -OCH2CO2CH2CH2CH3, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR16 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, methyl, ethyl, methoxy, ethoxy, -OCH2CO2CH3, -OCH2CH2CO2CH2CH3, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, methyl, methoxy, -OCH2CO2CH3, -OCH2CH2CO2CH2CH3, -OCH2CO2CH(CH3)2, -OCH2CO2CH2CH2CH3, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

[0272] In a further aspect, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0, 1, or 2 independently selected groups from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0 or 1 group selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 Selected from aryl and heteroaryl groups, and monosubstituted by a group selected from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 Selected from aryl and heteroaryl groups and not substituted.

[0273] In various aspects, Ar 1Selected from aryl and heteroaryl groups, and substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C4 alkyl, C1-C4 alkoxy, -O-(C1-C4 alkyl)-CO2-(C1-C4 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, -OCH2CO2CH3, -OCH2CH2CO2CH2CH3, -OCH2CO2CH(CH3)2, -OCH2CO2CH2CH2CH3, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R14b CO2R 15 In a further aspect, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, methyl, ethyl, methoxy, ethoxy, -OCH2CO2CH3, -OCH2CH2CO2CH2CH3, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, methyl, methoxy, -OCH2CO2CH3, -OCH2CH2CO2CH2CH3, -OCH2CO2CH(CH3)2, -OCH2CO2CH2CH2CH3, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

[0274] In a further aspect, Ar 1 It is an aryl group substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14bCO2R 15 In a further aspect, Ar 1 It is an aryl group substituted by 0, 1, or 2 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is an aryl group substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is an aryl group substituted with a single group selected from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is an unreplaced aryl group.

[0275] In a further aspect, Ar 1 It is an aryl group substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is an aryl group substituted by 0, 1, or 2 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is an aryl group substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is an aryl group that is monosubstituted by one of the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2-OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

[0276] In a further aspect, Ar 1 It is a phenyl group substituted with 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is a phenyl group substituted with 0, 1, or 2 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is a phenyl group substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1It is a phenyl group monosubstituted with one of the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 Unsubstituted phenyl group.

[0277] In a further aspect, Ar 1 It is a phenyl group substituted with 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is a phenyl group substituted with 0, 1, or 2 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1It is a phenyl group substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is a phenyl group monosubstituted with one of the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

[0278] In a further aspect, Ar 1 It is a naphthyl group that is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1It is a naphthyl group substituted with 0, 1, or 2 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is a naphthyl group substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is a naphthyl group that is monosubstituted with one of the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is an unsubstituted naphthyl group.

[0279] In a further aspect, Ar 1 It is a heteroaryl group substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is a heteroaryl group substituted with 0, 1, or 2 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is a heteroaryl group substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is a heteroaryl group monosubstituted with one of the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is an unsubstituted heteroaryl group.

[0280] In a further aspect, Ar 1It is a pyridyl group substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is a pyridyl group substituted with 0, 1, or 2 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is a pyridyl group substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is a pyridyl group monosubstituted with one of the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR14a R 14b CO2R 15 In a further aspect, Ar 1 It is an unsubstituted pyridinyl group.

[0281] In a further aspect, Ar 1 Selected from 5-aryl, 6-aryl, 5-heteroaryl, and 6-heteroaryl, and substituted by 0, 1, 2, or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 Selected from 5-aryl, 6-aryl, 5-heteroaryl, and 6-heteroaryl, and substituted by 0, 1, or 2 independently selected groups from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 Selected from 5-aryl, 6-aryl, 5-heteroaryl, and 6-heteroaryl, and substituted by 0 or 1 group selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar1 Selected from 5-aryl, 6-aryl, 5-heteroaryl, and 6-heteroaryl, and monosubstituted by a group selected from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 In a further aspect, Ar 1 It is selected from 5-aryl, 6-aryl, 5-heteroaryl and 6-heteroaryl, and is not substituted.

[0282] In a further aspect, Ar 1 The structure is represented by the following formula:

[0283]

[0284] g.AR 2 Group

[0285] In one aspect, Ar 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2, or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, or 2 independently selected groups from: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 2When present, it is selected from aryl and heteroaryl groups and is substituted by 0 or 1 group selected from: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 2 When present, it is selected from aryl and heteroaryl groups, and is monosubstituted by a group selected from: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 2 It is selected from aryl and heteroaryl groups when present and is not substituted.

[0286] In one aspect, Ar 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2, or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, or 2 independently selected groups from: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 2When present, it is selected from aryl and heteroaryl groups and is substituted by 0 or 1 group selected from: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 2 When present, it is selected from aryl and heteroaryl groups and is monosubstituted by a group selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino.

[0287] In a further aspect, Ar 2 When present, it is an aryl group substituted by 0, 1, 2, or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 2 When present, it is an aryl group substituted by 0, 1, or 2 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 2 When present, it is an aryl group substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 2When present, it is an aryl group monosubstituted with a group selected from the following: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 2 It is an unsubstituted aryl group when it exists.

[0288] In a further aspect, Ar 2 When present, it is a phenyl group substituted with 0, 1, 2, or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 2 When present, it is a phenyl group substituted with 0, 1, or 2 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 2 When present, it is a phenyl group substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 2 When present, it is a phenyl group monosubstituted with a group selected from the following: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 2 It is an unsubstituted phenyl group when it is present.

[0289] In a further aspect, Ar 2 When present, it is a naphthyl group independently substituted with 0, 1, 2, or 3 groups selected from the following: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 2 When present, it is a naphthyl group substituted with 0, 1, or 2 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 2 When present, it is a naphthyl group substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 2 When present, it is a naphthyl group monosubstituted with a group selected from the following: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 2 It exists as an unsubstituted naphthyl group.

[0290] In a further aspect, Ar 2 When present, it is a pyridyl group independently substituted with 0, 1, 2, or 3 groups selected from the following: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 2When present, it is a pyridyl group substituted with 0, 1, or 2 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 2 When present, it is a pyridyl group substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 2 When present, it is a pyridyl group monosubstituted with a group selected from the following: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 2 It is an unsubstituted pyridinyl group when it is present.

[0291] In a further aspect, Ar 2 When present, it is selected from 5-aryl, 6-aryl, 5-heteroaryl, and 6-heteroaryl groups, and is substituted by 0, 1, 2, or 3 groups independently selected from: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 2When present, it is selected from 5-aryl, 6-aryl, 5-heteroaryl, and 6-heteroaryl groups, and is substituted by 0, 1, or 2 independently selected groups from: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 2 When present, it is selected from 5-aryl, 6-aryl, 5-heteroaryl, and 6-heteroaryl, and is substituted by 0 or 1 group selected from: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 2 When present, it is selected from 5-aryl, 6-aryl, 5-heteroaryl, and 6-heteroaryl groups, and is monosubstituted by a group selected from: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 2 When present, it is selected from 5-aryl, 6-aryl, 5-heteroaryl, and 6-heteroaryl, and is not substituted.

[0292] 2. Exemplary Structure

[0293] In one respect, the compound can exist in the following form:

[0294]

[0295] In one respect, the compound can exist in the following form:

[0296]

[0297] In one respect, the compound can exist in the following form:

[0298]

[0299] In one respect, the compound can exist in the following form:

[0300]

[0301] In one respect, the compound can exist in the following form:

[0302]

[0303] In one respect, the compound can exist in the following form:

[0304]

[0305] In one respect, the compound can exist in the following form:

[0306]

[0307] In one respect, the compound can exist in the following form:

[0308]

[0309]

[0310] 3. Prediction Example

[0311] The following compound examples are predictive and can be prepared using the synthetic methods described above and other generalized methods known to those skilled in the art. Thus, in one aspect, the compound can be: ,

[0313] and.

[0314] In one aspect, the compound can be: , , , ... , ...

[0321]

[0322] In one aspect, the compound can be:

[0323]

[0324]

[0325] In one aspect, the compound can be:

[0326]

[0327] In one aspect, the compound can be:

[0328]

[0329] In one aspect, the compound can be:

[0330]

[0331]

[0332] C. Aromatic compounds

[0333] In one aspect, aromatic hydrocarbons that can be used in the disclosed methods are disclosed. Each disclosed derivative is contemplated to be optionally further substituted. It is also contemplated that any one or more derivatives may be optionally omitted from the invention. It should be understood that the disclosed compounds can be provided by the disclosed methods.

[0334] 1. Structure

[0335] In one aspect, aromatic hydrocarbons having a structure represented by the following formula are disclosed:

[0336] Ar 1 -E,

[0337] Among them, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Ar... 2When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0338] as well as

[0339] Where E is selected from the following electron-donating groups: -OR 20 -SO3R 20 -SR 20 -NR 21a R 21b -OC(=O)R 20 -OC(=O)OR 20 -OC(=O)SR 20 and -OC(=O)NHR 20 ;where R 20 R 21a and R 21b When present, it is independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkenyl, and Ar. 3 ; and among them Ar 3 When present, it is selected from aryl and heteroaryl groups and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino.

[0340] In one aspect, aromatic hydrocarbons having a structure represented by the following formula are disclosed:

[0341] Ar 1 -E,

[0342] Among them, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11-C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Ar... 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0343] as well as

[0344] Where E is hydrogen or an electron-donating group selected from the following: -OR 20 -SO3R 20 -SR 20 -NR 21a R 21b -OC(=O)R 20 -OC(=O)OR 20 -OC(=O)SR 20 and -OC(=O)NHR 20 ;where R 20 R 21a and R 21b When present, it is independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkenyl, and Ar. 3 ; and among them Ar 3When present, it is selected from aryl and heteroaryl groups and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino.

[0345] In one aspect, aromatic hydrocarbons having a structure represented by the following formula are disclosed:

[0346] Ar 1 -E,

[0347] Among them, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; wherein R 16 When present, it is a hydroxyl protecting group; and Ar is present in it. 2When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0348]

[0349] Where E is hydrogen or an electron-donating group selected from the following: -OR 20 -SO3R 20 -SR 20 -NR 21a R 21b -OC(=O)R 20 -OC(=O)OR 20 -OC(=O)SR 20 -OC(=O)NHR 20 ;where R 20 R 21a and R 21b When present, it is independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkenyl, and Ar. 3 ; and among them Ar 3 When present, it is selected from aryl and heteroaryl groups and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino.

[0350] Aromatic hydrocarbons having a structure represented by the following formula were also disclosed:

[0351] Ar 1 -H,

[0352] Among them, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10-C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; wherein R 16 When present, it is a hydroxyl protecting group; and Ar is present in it. 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0353]

[0354] In one aspect, aromatic hydrocarbons having a structure represented by the following formula are disclosed:

[0355] Ar 1 -X',

[0356] Where X' is a halogen and X' does not contain a radioactive isotope; and Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Ar... 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0357]

[0358] In a further aspect, the aromatic hydrocarbon has a structure represented by the following formula:

[0359]

[0360] Where R 30a R 30b R 30c R 30d and R 30e Each of these elements is independently selected from hydrogen, halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 , or R 30a R 30b R 30c R30d and R 30e Any two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered ring or heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0, 1, 2, or 3 groups independently selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

[0361] In a further aspect, the aromatic hydrocarbon has a structure represented by a formula selected from the following:

[0362]

[0363] In a further aspect, the aromatic hydrocarbon has a structure represented by the following formula:

[0364]

[0365] In a further aspect, the aromatic hydrocarbon has a structure represented by a formula selected from the following:

[0366]

[0367] Where R 30a R 30b R 30c R 30d and R 30e Each of these elements, when present, is independently selected from hydrogen, halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 , or R 30a R 30b R 30c R 30d and R 30eAny two adjacent atoms are optionally covalently bonded and together with the intermediate atom form a 5- to 6-membered ring or heterocycle having 0, 1, or 2 heteroatoms and being substituted by 0, 1, 2, or 3 groups independently selected from: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

[0368] In a further aspect, the aromatic hydrocarbon has a structure represented by a formula selected from the following:

[0369]

[0370] In a further aspect, the aromatic hydrocarbon has a structure represented by a formula selected from the following:

[0371]

[0372] In a further aspect, the aromatic hydrocarbon has a structure represented by the following formula:

[0373]

[0374] In a further aspect, the aromatic hydrocarbon has a structure represented by the following formula:

[0375]

[0376] In a further aspect, the aromatic hydrocarbon has a structure represented by the following formula:

[0377]

[0378] aE group

[0379] In one aspect, E is an electron-donating group. Exemplary electron-donating groups are well known to those skilled in the art and include, but are not limited to, alkyl, alcohol, thiol, alkoxy, thioalkoxy, silyloxy, amine, ester, amide, and aryl groups. Thus, in one aspect, E is an electron-donating group selected from: -OR 20 -SO3R 20 -SR 20 -NR 21a R 21b -OC(=O)R 20 -OC(=O)OR 20-OC(=O)SR 20 and -OC(=O)NHR 20 .

[0380] In one aspect, E is hydrogen or an electron-donating group selected from: -OR 20 -SO3R 20 -SR 20 -NR 21a R 21b -OC(=O)R 20 -OC(=O)OR 20 -OC(=O)SR 20 -OC(=O)NHR 20 In a further aspect, E is hydrogen.

[0381] In a further aspect, the electron-donating group is selected from -OR 20 -OC(=O)R 20 and -OC(=O)OR 20 In a further aspect, the electron-donating group is selected from -OR 20 and -OC(=O)R 20 In a further aspect, the electron-donating group is selected from -OR 20 and -OC(=O)OR 20 In a further aspect, the electron-donating group is selected from -OC(=O)R 20 and -OC(=O)OR 20 In a further aspect, the electron-donating group is -OR 20 In a further aspect, the electron-donating group is -OC(=O)R. 20 In a further aspect, the electron-donating group is -OC (=O)OR 20 .

[0382] In a further aspect, the electron-donating group is selected from -SO3R. 20 -SR 20 and -OC(=O)SR 20 In a further aspect, the electron-donating group is selected from -SO3R. 20 and -SR 20 In a further aspect, the electron-donating group is selected from -SO3R. 20 and -OC(=O)SR 20 In a further aspect, the electron-donating group is selected from -SR. 20 and -OC(=O)SR 20 In a further aspect, the electron-donating group is -SO3R. 20 In a further aspect, the electron-donating group is -SR.20 In a further aspect, the electron-donating group is -OC (=O)SR. 20 .

[0383] In a further aspect, the electron-donating group is selected from -NR. 21a R 21b and -OC(=O)NHR 20 In a further aspect, the electron-donating group is -NR. 21a R 21b In a further aspect, the electron-donating group is -OC(=O)NHR 20 .

[0384] In a further aspect, the electron-donating group is selected from -OH, -SH, -NH2, C1-C8 alkyl, C1-C8 alkoxy, C1-C8 thioalkoxy, C1-C8 silyloxy, C1-C8 alkylamino, (C1-C8)(C1-C8)dialkylamino, -OC(=O)R 6 -NHC(=O)R 7 -OAr 2 and Ar 2 In a further aspect, the electron-donating group is selected from -OH, -SH, -NH2, C1-C8 alkyl, C1-C8 alkoxy, C1-C4 thioalkoxy, C1-C4 silyloxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino, -OC(=O)R 6 -NHC(=O)R 7 -OAr 2 and Ar 2 .

[0385] In a further aspect, the electron-donating group is selected from -OH, -SH, -NH2, C1-C8 alkyl, C1-C8 alkoxy, C1-C8 thioalkoxy, C1-C8 alkylamino, (C1-C8)(C1-C8)dialkylamino, -OC(=O)R 6 -NHC(=O)R 7 and Ar 2 In a further aspect, the electron-donating group is selected from -OH, -SH, -NH2, C1-C8 alkyl, C1-C8 alkoxy, C1-C4 thioalkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino, -OC(=O)R 6 -NHC(=O)R 7 and Ar 2 .

[0386] In a further aspect, the electron-donating group is selected from -OH, -SH, -NH2, C1-C8 alkyl, C1-C8 alkoxy, C1-C8 thioalkoxy, C1-C8 alkylamino, (C1-C8)(C1-C8)dialkylamino, -OC(=O)R 6 and -NHC(=O)R 7 In a further aspect, the electron-donating group is selected from -OH, -SH, -NH2, C1-C8 alkyl, C1-C4 alkoxy, C1-C4 thioalkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino, -OC(=O)R 6 and -NHC(=O)R 7 In a further aspect, the electron-donating group is selected from -OH, -SH, -NH2, methyl, ethyl, n-propyl, isopropyl, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH(CH3)2, -SCH3, -SCH2CH3, -SCH2CH2CH3, -SCH(CH3)2, -NHCH3, -NHCH2CH3, -NHCH2CH2CH3, -NHCH(CH3)2, -N(CH3)2 , -N(CH3)(CH2CH3), -N(CH3)(CH2CH2CH3), -N(CH3)(CH(CH3)2), -N(CH2CH3)2, -N(CH2CH3)(CH2CH2CH 3), -N(CH2CH3)(CH(CH3)2), -N(CH2CH2CH3)2, -N(CH2CH2CH3)(CH(CH3)2), -N(CH(CH3)2)2, -OC(=O)R 6 and -NHC(=O)R 7 In a further aspect, the electron-donating group is selected from -OH, -SH, -NH2, methyl, ethyl, -OCH3, -OCH2CH3, -SCH3, -SCH2CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -N(CH3)(CH2CH3), -N(CH2CH3)2, -OC(=O)R 6 and -NHC(=O)R 7 In a further aspect, the electron-donating group is selected from -OH, -SH, -NH2, methyl, -OCH3, -SCH3, -NHCH3, -N(CH3)2, -OC(=O)R 6 and -NHC(=O)R 7 .

[0387] In a further aspect, the electron-donating group is a C1-C8 silanoxy group. In yet another further aspect, the electron-donating group is selected from trimethylsilanoxy, triisopropylsilanoxy, and tert-butyldimethylsilanoxy. In still another further aspect, the electron-donating group is selected from trimethylsilanoxy and triisopropylsilanoxy. In an even further further aspect, the electron-donating group is tert-butyldimethylsilanoxy. In yet another further aspect, the electron-donating group is triisopropylsilanoxy. In yet another further aspect, the electron-donating group is trimethylsilanoxy.

[0388] In a further aspect, the electron-donating group is selected from -OH, -SH, -NH2, C1-C8 alkyl, C1-C8 alkoxy, C1-C8 thioalkoxy, C1-C8 alkylamino, and (C1-C8)(C1-C8)dialkylamino. In yet another further aspect, the electron-donating group is selected from -OH, -SH, -NH2, C1-C8 alkyl, C1-C4 alkoxy, C1-C4 thioalkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, the electron-donating group is selected from -OH, -SH, -NH2, methyl, ethyl, n-propyl, isopropyl, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH(CH3)2, -SCH3, -SCH2CH3, -SCH2CH2CH3, -SCH(CH3)2, -NHCH3, -NHCH2CH3, -NHCH2CH2CH3, -NHCH(CH3)2, -N(C H3)2, -N(CH3)(CH2CH3), -N(CH3)(CH2CH2CH3), -N(CH3)(CH(CH3)2), -N(CH2CH3)2, -N(CH2CH3)(CH2CH2CH3), -N(CH2CH3)(CH(CH3)2), -N(CH2CH2CH3)2, -N(CH2CH2CH3)(CH(CH3)2) and -N(CH(CH3)2)2. In a further aspect, the electron-donating group is selected from -OH, -SH, -NH2, methyl, ethyl, -OCH3, -OCH2CH3, -SCH3, -SCH2CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -N(CH3)(CH2CH3) and -N(CH2CH3)2. In a further aspect, the electron-donating group is selected from -OH, -SH, -NH2, methyl, -OCH3, -SCH3, -NHCH3 and -N(CH3)2.

[0389] In a further aspect, the electron-donating group is selected from -OH, -SH, -NH2, -OC(=O)R 6 -NHC(=O)R 7-OAr 2 and Ar 2 In a further aspect, the electron-donating group is selected from -OC (=O)R. 6 -NHC(=O)R 7 -OAr 2 and Ar 2 In a further aspect, the electron-donating group is -OAr. 2 .

[0390] In a further aspect, the electron-donating group is selected from -OH, -SH, -NH2, -OC(=O)R 6 -NHC(=O)R 7 and Ar 2 In a further aspect, the electron-donating group is selected from -OC (=O)R. 6 -NHC(=O)R 7 and Ar 2 In a further aspect, the electron-donating group is selected from -OC (=O)R. 6 and -NHC(=O)R 7 In a further aspect, the electron-donating group is -OC(=O)R. 6 In a further aspect, the electron-donating group is -NHC(=O)R 7 In a further aspect, the electron-donating group is Ar. 2 .

[0391] In a further aspect, the electron-donating group is selected from C1-C8 alkyl, C1-C8 alkoxy, C1-C8 thioalkoxy, C1-C8 alkylamino, and (C1-C8)(C1-C8)dialkylamino. In yet another further aspect, the electron-donating group is selected from C1-C8 alkyl, C1-C4 alkoxy, C1-C4 thioalkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, the electron-donating group is selected from methyl, ethyl, n-propyl, isopropyl, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH(CH3)2, -SCH3, -SCH2CH3, -SCH2CH2CH3, -SCH(CH3)2, -NHCH3, -NHCH2CH3, -NHCH2CH2CH3, -NHCH(CH3)2, -N(CH3)2, -N(CH3)(CH2CH3), -N(CH3)(CH2CH2CH3), -N(CH3)(CH(CH3)2), -N(CH2CH3)2, -N(CH2CH3)(CH2CH2CH3), -N(CH2CH3)(CH(CH3)2), -N(CH2CH2CH3)2, -N(CH2CH2CH3)(CH(CH3)2) and -N(CH(CH3)2)2. In a further aspect, the electron-donating group is selected from methyl, ethyl, -OCH3, -OCH2CH3, -SCH3, -SCH2CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -N(CH3)(CH2CH3), and -N(CH2CH3)2. In yet another aspect, the electron-donating group is selected from methyl, -OCH3, -SCH3, -NHCH3, and -N(CH3)2.

[0392] In a further aspect, the electron-donating group is selected from -OH, -SH, and -NH2. In yet another further aspect, the electron-donating group is selected from -OH and -SH. In still a further aspect, the electron-donating group is selected from -OH and -NH2. In an even further further aspect, the electron-donating group is selected from -SH and -NH2. In yet another further aspect, the electron-donating group is -OH. In yet another further aspect, the electron-donating group is -SH. In an even further further aspect, the electron-donating group is NH2.

[0393] In a further aspect, the electron-donating group is -OR 20 .

[0394] In a further aspect, the electron-donating group is -OCH3.

[0395] In a further aspect, E stands for hydrogen.

[0396] bR 20R 21A and R 21B Group

[0397] In one aspect, R 20 R 21a and R 21b Each of these elements, when present, is independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkenyl, and Ar. 3 In a further aspect, R 20 R 21a and R 21b Each of these elements, when present, is independently selected from hydrogen, C1-C4 alkyl, C1-C4 alkenyl, and Ar. 3 In a further aspect, R 20 R 21a and R 21b Each of them is hydrogen when it exists.

[0398] In a further aspect, R 20 R 21a and R 21b Each of these, when present, is independently selected from hydrogen, C1-C8 alkyl, and C1-C8 alkenyl. In a further aspect, R... 20 R 21a and R 21b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and C1-C4 alkenyl. In a further aspect, R... 20 R 21a and R 21b Each of these, when present, is independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, vinyl, n-propenyl, and isopropenyl. In a further aspect, R... 20 R 21a and R 21b Each of these, when present, is independently selected from hydrogen, methyl, ethyl, and vinyl. In a further aspect, R... 20 R 21a and R 21b Each of them is independently selected from hydrogen and methyl when present.

[0399] In a further aspect, R 20 R 21a and R 21b Each of these, when present, is independently selected from C1-C8 alkyl and C1-C8 alkenyl groups. In a further aspect, R... 20 R 21a and R 21b Each of these, when present, is independently selected from C1-C4 alkyl and C1-C4 alkenyl groups. In a further aspect, R... 20 R21a and R 21b Each of these, when present, is independently selected from methyl, ethyl, n-propyl, isopropyl, vinyl, n-propenyl, and isopropenyl. In a further aspect, R... 20 R 21a and R 21b Each of these, when present, is independently selected from methyl, ethyl, and vinyl. In a further aspect, R... 20 R 21a and R 21b Each of them is a methyl group when it is present.

[0400] In a further aspect, R 20 R 21a and R 21b Each of them, when present, is independently selected from hydrogen and Ar. 3 In a further aspect, R 20 R 21a and R 21b Each of them is r when it exists. 3 .

[0401] c.AR 3 Group

[0402] In one aspect, Ar 3 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2, or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 3 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, or 2 independently selected groups from: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 3When present, it is selected from aryl and heteroaryl groups and is substituted by 0 or 1 group selected from: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 3 When present, it is selected from aryl and heteroaryl groups, and is monosubstituted by a group selected from: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 3 It is selected from aryl and heteroaryl groups when present and is not substituted.

[0403] In a further aspect, Ar 3 When present, it is an aryl group substituted by 0, 1, 2, or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 3 When present, it is an aryl group substituted by 0, 1, or 2 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 3 When present, it is an aryl group substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar...3 When present, it is an aryl group monosubstituted with a group selected from the following: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 3 It is an unsubstituted aryl group when it exists.

[0404] In a further aspect, Ar 3 When present, it is a phenyl group substituted with 0, 1, 2, or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 3 When present, it is a phenyl group substituted with 0, 1, or 2 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 3 When present, it is a phenyl group substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 3 When present, it is a phenyl group substituted with a single group selected from the following: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 3It is an unsubstituted phenyl group when it is present.

[0405] In a further aspect, Ar 3 When present, it is a naphthyl group independently substituted with 0, 1, 2, or 3 of the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 3 When present, it is a naphthyl group substituted by 0, 1, or 2 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 3 When present, it is a naphthyl group substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 3 When present, it is a naphthyl group monosubstituted with a group selected from the following: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 3 It exists as an unsubstituted naphthyl group.

[0406] In a further aspect, Ar 3When present, it is a pyridyl group independently substituted with 0, 1, 2, or 3 groups selected from the following: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 3 When present, it is a pyridyl group substituted with 0, 1, or 2 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 3 When present, it is a pyridyl group substituted with 0 or 1 of the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 3 When present, it is a pyridyl group monosubstituted with a group selected from the following: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar... 3 It is an unsubstituted pyridinyl group when it is present.

[0407] In a further aspect, Ar 3When present, it is selected from 5-aryl, 6-aryl, 5-heteroaryl, and 6-heteroaryl groups, and is substituted by 0, 1, 2, or 3 groups independently selected from: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 3 When present, it is selected from 5-aryl, 6-aryl, 5-heteroaryl, and 6-heteroaryl groups, and is substituted by 0, 1, or 2 independently selected groups from: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 3 When present, it is selected from 5-aryl, 6-aryl, 5-heteroaryl, and 6-heteroaryl, and is substituted by 0 or 1 group selected from: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 3 When present, it is selected from 5-aryl, 6-aryl, 5-heteroaryl, and 6-heteroaryl groups, and is monosubstituted by a group selected from: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, Ar 3 When present, it is selected from 5-aryl, 6-aryl, 5-heteroaryl, and 6-heteroaryl, and is not substituted.

[0408] 2. Exemplary Aromatic Hydrocarbon Structure

[0409] In one aspect, aromatic hydrocarbons can exist in the following forms:

[0410]

[0411] In one aspect, aromatic hydrocarbons can exist in the following forms:

[0412]

[0413] In one aspect, aromatic hydrocarbons can exist in the following forms:

[0414]

[0415]

[0416] In one aspect, aromatic hydrocarbons can exist in the following forms:

[0417]

[0418] In one respect, the compound can exist in the following form:

[0419]

[0420] In one respect, the compound can exist in the following form:

[0421]

[0422] In one respect, the compound can exist in the following form:

[0423]

[0424] In one aspect, aromatic hydrocarbons can exist in the following forms:

[0425]

[0426] D. Acridine-onium photocatalyst

[0427] In one aspect, acridine-onium photocatalysts that can be used in the disclosed methods are disclosed. It is contemplated that each disclosed derivative may optionally be further substituted. It is also contemplated that any one or more derivatives may optionally be omitted from the invention. It should be understood that the disclosed compounds can be provided by the disclosed methods.

[0428] 1. Structure

[0429] In one aspect, an acridine-ium photocatalyst having a structure represented by the following formula is disclosed:

[0430]

[0431] Q is selected from O and NR. 9 ;where R 9Selected from C1-C4 alkyl, aryl, and heteroaryl groups, and substituted by 0, 1, 2, or 3 independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino; wherein X is selected from BF4, TfO, PF6, and ClO4; wherein R 7 The phenyl group is selected from C1-C4 alkyl groups and substituted with 0, 1, 2 or 3 groups independently selected from the group consisting of halogens and C1-C4 alkyl groups; and wherein R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the groups in ' is independently selected from hydrogen, halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, C1-C4 dialkylamino and phenyl groups substituted with 0, 1, 2 or 3 groups independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino.

[0432] In one aspect, an acridine-ium photocatalyst having a structure represented by the following formula is disclosed:

[0433]

[0434] Where X is selected from BF4, TfO, PF6, and ClO4; where R 7 The phenyl group is selected from C1-C4 alkyl groups and phenyl groups substituted by 0, 1, 2 or 3 groups independently selected from the following groups: halogen and C1-C4 alkyl; wherein R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the groups in ' is independently selected from hydrogen, halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, C1-C4 dialkylamino and phenyl groups substituted with 0, 1, 2 or 3 groups independently selected from: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino; and wherein R 9It is selected from C1-C4 alkyl, aryl and heteroaryl groups and is substituted by 0, 1, 2 or 3 groups independently selected from the following: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino.

[0435] In one aspect, an acridine-onium photocatalyst having the following structure is disclosed:

[0436]

[0437] In a further aspect, the acridine-onium photocatalyst has a structure selected from the following:

[0438]

[0439]

[0440] In a further aspect, the acridine-onium photocatalyst has the following structure:

[0441]

[0442] In a further aspect, the acridine-onium photocatalyst has the following structure:

[0443]

[0444] In various aspects, the acridine-ium photocatalyst is present in amounts of about 0.1 mol% to about 10 mol%, about 0.1 mol% to about 8 mol%, about 0.1 mol% to about 6 mol%, about 0.1 mol% to about 5 mol%, about 0.1 mol% to about 4 mol%, about 0.1 mol% to about 2 mol%, about 2 mol% to about 10 mol%, about 4 mol% to about 10 mol%, about 5 mol% to about 10 mol%, about 6 mol% to about 10 mol%, about 8 mol% to about 10 mol%, about 2 mol% to about 8 mol%, or about 4 mol% to about 6 mol%.

[0445] In various aspects, the acridine nitrogen photocatalyst is present in amounts of about 0.1 mol%, about 2 mol%, about 4 mol%, about 5 mol%, about 6 mol%, about 8 mol%, or about 10 mol%. In further aspects, the acridine nitrogen photocatalyst is present in amounts of about 5 mol%.

[0446] aQ group

[0447] In one aspect, Q is selected from O and NR. 9 In a further aspect, Q is O. In an even further aspect, Q is NR. 9 .

[0448] bX group

[0449] In one aspect, X is selected from BF4, TfO, PF6, and ClO4. In a further aspect, X is selected from BF4, TfO, and PF6. In an even further aspect, X is selected from BF4 and PF6. In yet another further aspect, X is ClO4. In still a further aspect, X is TfO. In yet another further aspect, X is BF4. In yet another further aspect, X is PF6.

[0450] cR 7 Group

[0451] In one aspect, R 7 The phenyl group is selected from C1-C4 alkyl groups and phenyl groups substituted by 0, 1, 2 or 3 groups independently selected from the following groups: halogen and C1-C4 alkyl.

[0452] In a further aspect, R 7 It is a C1-C4 alkyl group. In a further aspect, R... 7 Selected from methyl, ethyl, n-propyl, and isopropyl. In a further aspect, R... 7 Selected from methyl and ethyl. In a further aspect, R 7 It is ethyl. In a further aspect, R 7 It is a methyl group.

[0453] In a further aspect, R 7 It is a phenyl group substituted with 0, 1, 2, or 3 independently selected from the following groups: halogens and C1-C4 alkyl groups. In a further aspect, R... 7 It is a phenyl group substituted with 0, 1, or 2 groups independently selected from halogens and C1-C4 alkyl groups. In a further aspect, R... 7 It is a phenyl group substituted with 0 or 1 of the following groups: halogens and C1-C4 alkyl groups. In a further aspect, R... 7 It is a phenyl group monosubstituted with a group selected from the following: halogens and C1-C4 alkyl groups. In a further aspect, R... 7 Unsubstituted phenyl group.

[0454] In a further aspect, R 7 It is a phenyl group substituted with 0, 1, 2, or 3 independently selected from the following groups: fluorine, chloro, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert-butyl. In a further aspect, R... 7 It is a phenyl group substituted with 0, 1, 2, or 3 independently selected from the following groups: fluorine, chloro, methyl, ethyl, n-propyl, and isopropyl. In a further aspect, R... 7It is a phenyl group substituted with 0, 1, 2, or 3 independently selected from the following groups: fluorine, chloro, methyl, and ethyl. In a further aspect, R... 7 It is a phenyl group that is substituted by 0, 1, 2 or 3 groups independently selected from the following groups: fluorine, chlorine and methyl.

[0455] In a further aspect, R 7 It is a phenyl group substituted with 0, 1, 2, or 3 independently selected from the following groups: methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert-butyl. In a further aspect, R... 7 It is a phenyl group substituted with 0, 1, 2, or 3 independently selected from the following groups: methyl, ethyl, n-propyl, and isopropyl. In a further aspect, R... 7 It is a phenyl group substituted with 0, 1, 2, or 3 independently selected from the following groups: methyl and ethyl. In a further aspect, R 7 It is a phenyl group that is substituted with 0, 1, 2 or 3 methyl groups.

[0456] dR 8A R 8B R 8C R 8D R 8A '、R 8B '、R 8C 'and R 8D 'group'

[0457] In one aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the groups in ' is independently selected from hydrogen, halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, C1-C4 dialkylamino and phenyl groups substituted with 0, 1, 2 or 3 groups independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino and (C1-C4)(C1-C4) dialkylamino.

[0458] In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8dEach of ' is independently selected from hydrogen, halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the following is independently selected from hydrogen, halogen, -CF3, -NH2, methyl, ethyl, n-propyl, isopropyl, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH(CH3)2, -NHCH3, -NHCH2CH3, -NHCH2CH2CH3, -NHCH(CH3)2, -N(CH3)2, -N(CH3)(CH2CH3), -N(CH3)(CH2CH2CH3), -N(CH3)(CH(CH3)2), -N(CH2CH3)2, -N(CH2CH3)(CH2CH2CH3), -N(CH2CH3)(CH(CH3)2), -N(CH2CH2CH3)2, -N(CH2CH2CH3)(CH(CH3)2), and -N(CH(CH3)2)2. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the following is independently selected from hydrogen, halogen, -CF3, -NH2, methyl, ethyl, -OCH3, -OCH2CH3, -OCH(CH3)2, -NHCH3, -N(CH3)2, -N(CH3)(CH2CH3), and -N(CH2CH3)2. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the following is independently selected from hydrogen, halogen, -CF3, -NH2, methyl, -OCH3, -OCH(CH3)2, -NHCH3 and -N(CH3)2.

[0459] In a further aspect, R 8a R 8b R 8cR 8d R 8a '、R 8b '、R 8c 'and R 8d Each of ' is independently selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, and C1-C4 dialkylamino. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the following is independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH(CH3)2, -NHCH3, -NHCH2CH3, -NHCH2CH2CH3, -NHCH(CH3)2, -N(CH3)2, -N(CH3)(CH2CH3), -N(CH3)(CH2CH2CH3), -N(CH3)(CH(CH3)2), -N(CH2CH3)2, -N(CH2CH3)(CH2CH2CH3), -N(CH2CH3)(CH(CH3)2), -N(CH2CH2CH3)2, -N(CH2CH2CH3)(CH(CH3)2), and -N(CH(CH3)2)2. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the terms ' is independently selected from hydrogen, methyl, ethyl, -OCH3, -OCH2CH3, -OCH(CH3)2, -NHCH3, -N(CH3)2, -N(CH3)(CH2CH3), and -N(CH2CH3)2. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the terms is independently selected from hydrogen, methyl, -OCH3, -OCH(CH3)2, -NHCH3 and -N(CH3)2.

[0460] In a further aspect, R 8a R8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of ' is independently selected from hydrogen and C1-C4 alkyl groups. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of ' is independently selected from hydrogen, methyl, ethyl, n-propyl, and isopropyl. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of ' is independently selected from hydrogen, methyl, and ethyl. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the terms in ' is independently selected from hydrogen and methyl.

[0461] In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of ' is independently selected from hydrogen and halogens. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of ' is independently selected from hydrogen, fluorine, and chlorine. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R8b '、R 8c 'and R 8d Each of the elements in ' is independently selected from hydrogen and fluorine. In a further aspect, R... 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the elements in ' is independently selected from hydrogen and chlorine.

[0462] In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the groups in ' is independently selected from hydrogen and phenyl groups substituted with 0, 1, 2 or 3 independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the groups in ' is independently selected from hydrogen and phenyl groups substituted with 0, 1, or 2 independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the groups in ' is independently selected from hydrogen and a phenyl group substituted with 0 or 1 of the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R8b '、R 8c 'and R 8d Each of the groups in ' is independently selected from hydrogen and a phenyl group monosubstituted with a group selected from: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the ' ' is independently selected from hydrogen and unsubstituted phenyl groups.

[0463] In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the groups in ' is independently selected from hydrogen and is a phenyl group substituted with 0, 1, 2 or 3 independently selected from the following groups: halogen, -CF3, -NH2, methyl, ethyl, n-propyl, isopropyl, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH(CH3)2, -NHCH3, -NHCH2CH3, -NHCH2CH2CH3, -NHCH(CH3)2, -N(CH3)2, -N(CH3)(CH2CH3), -N(CH3)(CH2CH2CH3), -N(CH3)(CH(CH3)2), -N(CH2CH3)2, -N(CH2CH3)(CH2CH2CH3), -N(CH2CH3)(CH(CH3)2), -N(CH2CH2CH3)2, -N(CH2CH2CH3)(CH(CH3)2) and -N(CH(CH3)2)2. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8dEach of the groups in ' is independently selected from hydrogen and is a phenyl group substituted with 0, 1, 2, or 3 independently selected from the following groups: fluorine, chlorine, -CF3, -NH2, methyl, ethyl, -OCH3, -OCH2CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -N(CH3)(CH2CH3), and -N(CH2CH3)2. In a further aspect, R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the groups in ' is independently selected from hydrogen and phenyl groups substituted by 0, 1, 2 or 3 independently selected from the following groups: fluorine, chlorine, -CF3, -NH2, methyl, -OCH3, -NHCH3 and -N(CH3)2.

[0464] eR 9 Group

[0465] In one aspect, R 9 Selected from C1-C4 alkyl, aryl, and heteroaryl groups, and substituted by 0, 1, 2, or 3 independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 Selected from C1-C4 alkyl, aryl, and heteroaryl groups, and substituted by 0, 1, or 2 independently selected groups from: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 Selected from C1-C4 alkyl, aryl, and heteroaryl groups, and substituted with 0 or 1 group selected from: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 Selected from C1-C4 alkyl, aryl, and heteroaryl groups, and monosubstituted with a group selected from: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is selected from C1-C4 alkyl, aryl and heteroaryl groups, and is not substituted.

[0466] In a further aspect, R 9The phenyl group is selected from C1-C4 alkyl groups and substituted with 0, 1, 2 or 3 groups independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino.

[0467] In a further aspect, R 9 It is a C1-C4 alkyl group. In a further aspect, R... 9 Selected from methyl, ethyl, n-propyl, and isopropyl. In a further aspect, R... 9 Selected from methyl and ethyl. In a further aspect, R 9 It is ethyl. In a further aspect, R 9 It is a methyl group.

[0468] In a further aspect, R 9 Selected from aryl and heteroaryl groups, and substituted by 0, 1, 2, or 3 independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 Selected from aryl and heteroaryl groups, and substituted by 0, 1, or 2 independently selected groups from: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 Selected from aryl and heteroaryl groups, and substituted with 0 or 1 group selected from: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 Selected from aryl and heteroaryl groups, and monosubstituted by a group selected from: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 Selected from aryl and heteroaryl groups, and not substituted.

[0469] In a further aspect, R 9 It is an aryl group substituted with 0, 1, 2, or 3 independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9It is an aryl group substituted with 0, 1, or 2 independently selected groups from the following: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is an aryl group substituted with 0 or 1 of the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is an aryl group monosubstituted with a group selected from the following: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is an unreplaced aryl group.

[0470] In a further aspect, R 9 It is a phenyl group substituted with 0, 1, 2, or 3 independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is a phenyl group substituted with 0, 1, or 2 independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is a phenyl group substituted with 0 or 1 of the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is a phenyl group monosubstituted with a group selected from the following: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is an unsubstituted phenyl group.

[0471] In a further aspect, R 9It is a phenyl group substituted with 0, 1, 2, or 3 independently selected from the following groups: fluorine, chlorine, -CF3, -NH2, methyl, ethyl, n-propyl, isopropyl, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH(CH3)2, -NHCH3, -NHCH2CH3, -NHCH2CH2CH3, -NHCH(CH3)2, -N(CH3)2, -N(CH3)(CH2CH3), -N(CH3)(CH2CH2CH3), -N(CH3)(CH(CH3)2), -N(CH2CH3)2, -N(CH2CH3)(CH2CH2CH3), -N(CH2CH3)(CH(CH3)2), -N(CH2CH2CH3)2, -N(CH2CH2CH3)(CH(CH3)2) and -N(CH(CH3)2)2. In a further aspect, R 9 It is a phenyl group substituted with 0, 1, 2, or 3 independently selected from the following groups: fluorine, chlorine, -CF3, -NH2, methyl, ethyl, -OCH3, -OCH2CH3, -OCH(CH3)2, -NHCH3, -NHCH2CH3, -N(CH3)2, -N(CH3)(CH2CH3), and -N(CH2CH3)2. In a further aspect, R... 9 It is a phenyl group that is substituted by 0, 1, 2 or 3 independently selected from the following groups: fluorine, chlorine, methyl, -CF3, -NH2, -OCH3, -NHCH3 and -N(CH3)2.

[0472] In a further aspect, R 9 It is a heteroaryl group substituted with 0, 1, 2, or 3 independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is a heteroaryl group substituted with 0, 1, or 2 independently selected groups from the following: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is a heteroaryl group substituted with 0 or 1 of the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9It is a heteroaryl group monosubstituted with a group selected from the following: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is an unsubstituted heteroaryl group.

[0473] In a further aspect, R 9 It is a 5-membered heteroaryl group substituted with 0, 1, 2, or 3 independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is a 5-membered heteroaryl group substituted with 0, 1, or 2 independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is a 5-membered heteroaryl group substituted with 0 or 1 of the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is a 5-membered heteroaryl group monosubstituted with a group selected from the following: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is an unsubstituted 5-membered heteroaryl group.

[0474] In a further aspect, R 9 It is a 6-membered heteroaryl group substituted with 0, 1, 2, or 3 independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is a 6-membered heteroaryl group substituted with 0, 1, or 2 independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is a 6-membered heteroaryl group substituted with 0 or 1 of the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9It is a 6-membered heteroaryl group monosubstituted with a group selected from the following: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino. In a further aspect, R 9 It is an unsubstituted 6-membered heteroaryl group.

[0475] 2. Exemplary photocatalyst structure

[0476] In one aspect, acridine-onium photocatalysts can exist in the following forms:

[0477]

[0478] In one aspect, acridine-onium photocatalysts can exist in the following forms:

[0479]

[0480] In one aspect, acridine-onium photocatalysts can exist in the following forms:

[0481]

[0482] In one aspect, acridine-onium photocatalysts can exist in the following forms:

[0483]

[0484]

[0485] In one aspect, acridine-onium photocatalysts can exist in the following forms:

[0486]

[0487] E. Methods for preparing disclosed compounds

[0488] In one aspect, a method for preparing compounds having a structure represented by the following formula is disclosed:

[0489] Ar 1 -Z,

[0490] Z is selected from halogens, -CN, -NH2, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino, provided that when Z is -NH2, C1-C4 alkylamino, or (C1-C4)(C1-C4)dialkylamino, Z contains a radioactive isotope; where Ar 1Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 15b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 30 and R 32 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 31a and R 31b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Ar... 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0491]

[0492] The method includes making aromatic hydrocarbons having a structure represented by the following formula:

[0493] Ar 1 -E,

[0494] Where E is selected from the following electron-donating groups: -OR 20 -SO3R 20 -SR 20 -NR 21a R 21b -OC(=O)R 20 -OC(=O)OR 20-OC(=O)SR 20 and -OC(=O)NHR 20 ;where R 20 R 21a and R 21b When present, it is independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkenyl, and Ar. 3 ; and among them Ar 3 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino.

[0495] The compound is formed by reacting a nucleophile selected from halides, cyanides, and amines in the presence of a catalytically effective amount of acridinium photocatalyst under anaerobic conditions. In a further aspect, the compound is prepared by replacing the E group with a Z group. Thus, in various aspects, the group designated as "E" in the aromatic hydrocarbon is no longer present in the resulting compound.

[0496] In one aspect, a method for preparing compounds having a structure represented by the following formula is disclosed:

[0497] Ar 1 -Z,

[0498] Z is selected from halogens, -CN, -NH2, C1-C4 alkylamino and (C1-C4)(C1-C4) dialkylamino, and Z contains a radioactive isotope; Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Ar... 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0499]

[0500] The method includes making aromatic hydrocarbons having a structure represented by the following formula:

[0501] Ar 1 -E,

[0502] Where E is hydrogen or an electron-donating group selected from the following: -OR 20 -SO3R 20 -SR 20 -NR 21a R 21b -OC(=O)R 20 -OC(=O)OR 20 -OC(=O)SR 20 and -OC(=O)NHR 20 ;where R 20 R 21a and R 21b When present, it is independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkenyl, and Ar. 3 ; and among them Ar 3The compound is formed by reacting a nucleophile selected from aryl and heteroaryl groups, in the presence of 0, 1, 2, or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino, with a catalytically effective amount of acridineonium photocatalyst. In a further aspect, the compound is prepared by replacing the E group with a Z group. Therefore, in various aspects, the group designated as "E" in the aromatic hydrocarbon is no longer present in the resulting compound.

[0503] In one aspect, a method for preparing compounds having a structure represented by the following formula is disclosed:

[0504] Ar 1 -Z,

[0505] Z is selected from halogens, -CN, -NH2, C1-C4 alkylamino and (C1-C4)(C1-C4) dialkylamino, and Z contains a radioactive isotope; Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; wherein R 16 When present, it is a hydroxyl protecting group; and Ar is present in it.2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0506]

[0507] The method includes making aromatic hydrocarbons having a structure represented by the following formula:

[0508] Ar 1 -E,

[0509] Where E is hydrogen or an electron-donating group selected from the following: -OR 20 -SO3R 20 -SR 20 -NR 21a R 21b -OC(=O)R 20 -OC(=O)OR 20 -OC(=O)SR 20 -OC(=O)NHR 20 ;where R 20 R 21a and R 21b When present, it is independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkenyl, and Ar. 3 ; and among them Ar 3 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino.

[0510] The compound is formed by reacting a nucleophile selected from halides, cyanides, and amines in the presence of a catalytically effective amount of acridine-onium photocatalyst.

[0511] In one aspect, a method for preparing compounds having a structure represented by the following formula is disclosed:

[0512] Ar 1 -Z,

[0513] Where Z is a halogen, and Z contains a radioactive isotope; where Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these groups, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; wherein R 16 When present, it is a hydroxyl protecting group; and Ar is present in it. 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0514]

[0515] The method includes making aromatic hydrocarbons having a structure represented by the following formula:

[0516] Ar 1 -H,

[0517] The steps of reacting halides with an LED having a wavelength of approximately 425 nm, a TBPA, and a catalytically effective amount of an acridine-onium photocatalyst having the following structure:

[0518]

[0519] This forms the compound.

[0520] In one aspect, a method for preparing compounds having a structure represented by the following formula is disclosed:

[0521] Ar 1 -X,

[0522] Where X is a halogen and X contains a radioactive isotope; where Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Ar... 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0523]

[0524] The method includes making aromatic hydrocarbons having a structure represented by the following formula:

[0525] Ar 1 -X',

[0526] Where X' is a halogen and X' does not contain a radioactive isotope.

[0527] The compound is formed by reacting a nucleophile selected from halides, cyanides, and amines in the presence of a catalytically effective amount of acridinium photocatalyst. In a further aspect, the compound is prepared by replacing an X' group with an X group. Thus, in various aspects, the group designated as "X'" in the aromatic hydrocarbon is no longer present in the resulting compound.

[0528] In one aspect, a method for preparing compounds having a structure represented by the following formula is disclosed:

[0529] Z-Ar 1 -E,

[0530] Z is selected from halogens, -CN, -NH2, C1-C4 alkylamino and (C1-C4)(C1-C4) dialkylamino, and Z contains a radioactive isotope; Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Ar... 2When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0531]

[0532] The method includes making aromatic hydrocarbons having a structure represented by the following formula:

[0533] Ar 1 -E,

[0534] Where E is hydrogen or an electron-donating group selected from the following: -OR 20 -SO3R 20 -SR 20 -NR 21a R 21b -OC(=O)R 20 -OC(=O)OR 20 -OC(=O)SR 20 and -OC(=O)NHR 20 ;where R 20 R 21a and R 21b When present, it is independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkenyl, and Ar. 3 ; and among them Ar 3 The compound is formed by reacting a nucleophile selected from aryl and heteroaryl groups, in the presence of 0, 1, 2, or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino, and (C1-C4)(C1-C4)dialkylamino, with a catalytically effective amount of acridineonium photocatalyst. In a further aspect, the reaction is carried out under anaerobic conditions. In yet another further aspect, the reaction is carried out under aerobic conditions.

[0535] In a further aspect, E is opposite to Z. In an even further aspect, E is adjacent to Z. In a still further aspect, E is not between Z.

[0536] In a further aspect, the catalytically effective amount is from about 0.01 mol% to about 15 mol%. In yet another further aspect, the catalytically effective amount is from about 0.01 mol% to about 12 mol%. In still a further further aspect, the catalytically effective amount is from about 0.01 mol% to about 10 mol%. In an even further further aspect, the catalytically effective amount is from about 0.01 mol% to about 7 mol%. In yet another further aspect, the catalytically effective amount is from about 0.01 mol% to about 5 mol%. In yet another further aspect, the catalytically effective amount is from about 0.01 mol% to about 2 mol%. In an even further further aspect, the catalytically effective amount is from about 0.01 mol% to about 1 mol%. In yet another further aspect, the catalytically effective amount is from about 0.01 mol% to about 0.1 mol.

[0537] In a further aspect, the catalytically effective amount is from about 0.1 mol% to about 10 mol%. In an even further aspect, the catalytically effective amount is from about 0.1 mol% to about 7 mol%. In yet another further aspect, the catalytically effective amount is from about 0.1 mol% to about 5 mol%. In still a further aspect, the catalytically effective amount is from about 0.1 mol% to about 2 mol%. In an even further aspect, the catalytically effective amount is from about 0.1 mol% to about 1 mol%. In yet another further aspect, the catalytically effective amount is 5 mol%.

[0538] In a further aspect, the catalytically effective amount is about 0.1 mol% to about 15 mol%. In yet another further aspect, the catalytically effective amount is about 1 mol% to about 15 mol%. In still a further further aspect, the catalytically effective amount is about 2 mol% to about 15 mol%. In an even further further aspect, the catalytically effective amount is about 5 mol% to about 15 mol%. In yet another further aspect, the catalytically effective amount is about 7 mol% to about 15 mol%. In yet another further aspect, the catalytically effective amount is about 10 mol% to about 15 mol%. In an even further further aspect, the catalytically effective amount is about 12 mol% to about 15 mol%.

[0539] In a further aspect, the acridine-onium photocatalyst has a structure represented by the following formula:

[0540]

[0541] Q is selected from O and NR. 9 ;where R 9The phenyl group is selected from C1-C4 alkyl groups and substituted with 0, 1, 2 or 3 groups independently selected from the following: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino; wherein X is selected from BF4, TfO, PF6 and ClO4; wherein R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the groups in ' is independently selected from hydrogen, halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, C1-C4 dialkylamino and phenyl groups substituted with 0, 1, 2 or 3 groups independently selected from: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino; and wherein R 10 The phenyl group is selected from C1-C4 alkyl groups and phenyl groups substituted by 0, 1, 2 or 3 groups independently selected from the following groups: halogen and C1-C4 alkyl.

[0542] In a further aspect, the acridine-onium photocatalyst has a structure represented by the following formula:

[0543]

[0544] Where X is selected from BF4, TfO, PF6, and ClO4; where R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the following groups is independently selected from hydrogen, halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, C1-C4 dialkylamino, and phenyl groups substituted with 0, 1, 2, or 3 groups independently selected from: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino; wherein R 9 The phenyl group is selected from C1-C4 alkyl groups and substituted with 0, 1, 2 or 3 groups independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino; and wherein R 10The phenyl group is selected from C1-C4 alkyl groups and phenyl groups substituted by 0, 1, 2 or 3 groups independently selected from the following groups: halogen and C1-C4 alkyl.

[0545] In a further aspect, the acridine-onium photocatalyst has a structure selected from the following:

[0546]

[0547] In a further aspect, the acridine-onium photocatalyst has the following structure:

[0548]

[0549] As used herein, the term "nucleophile" refers to a molecule, atom, or ion capable of forming a chemical bond with its reaction partner by donating an electron. Exemplary nucleophiles are well known to those skilled in the art and include, but are not limited to, water, ammonia, halides, cyanides, alcohols, thiols, amines, hydrazine, carbamates, carboxylic acids, and alkenes. In a further aspect, the nucleophile is selected from halides, cyanides, and amines.

[0550] In a further aspect, the nucleophile is isotopically labeled. In yet another further aspect, the nucleophile is not isotopically labeled.

[0551] In a further aspect, the nucleophile is a halide. Exemplary halides are well known to those skilled in the art and include, but are not limited to, ammonium fluoride, cesium fluoride, lithium chloride, triethylamine hydrochloride, and triethylamine hydrofluoride. In a further aspect, the nucleophile is a halide. In yet another further aspect, the nucleophile is a fluoride. Exemplary fluorides include, but are not limited to, ammonium fluoride, cesium fluoride, triethylamine hydrofluoride, and tetrabutylammonium fluoride.

[0552] In a further aspect, the nucleophile is an amine. Exemplary amines include, but are not limited to, ammonium bicarbonate.

[0553] In a further aspect, the nucleophile is a cyanide. Exemplary cyanides include, but are not limited to, tetrabutylammonium cyanide, sodium cyanide, potassium cyanide, and acetone cyanohydrin.

[0554] In a further aspect, the reaction is carried out under anaerobic conditions. Therefore, in various aspects, the reaction is carried out in the absence of an oxidizing agent or oxidizing reagent. As used herein, the terms "oxidizing agent" and "oxidizing reagent" refer to any species capable of accepting or acquiring electrons from another species. Exemplary oxidizing agents are well known to those skilled in the art and include, but are not limited to, molecular oxygen, 2,2,6,6-tetramethyl-1-piperidinyloxy radical (TEMPO), ozone, and hydrogen peroxide. In a further aspect, the oxidizing agent is molecular oxygen. In yet another further aspect, the oxidizing agent is TEMPO.

[0555] In a further aspect, the reaction is carried out under an inert atmosphere. Therefore, in various aspects, the reaction is carried out in the presence of an inert gas (e.g., argon, nitrogen). In various further aspects, the reaction is carried out in the absence of oxygen or carbon dioxide.

[0556] In a further aspect, the reaction takes place in the presence of a visible light source. Examples of visible light sources include, but are not limited to, lasers, light-emitting diodes (LEDs), non-LED lamps, light generated by up-conversion particles, phosphorescent materials, and light generated by X-rays. In a further aspect, the light source is a bioluminescent source, a chemiluminescent source, or an electroluminescent source.

[0557] In a further aspect, the wavelength of the visible light source is from about 365 nm to about 480 nm. In yet another aspect, the wavelength of the visible light source is from about 365 nm to about 450 nm. In a still further aspect, the wavelength of the visible light source is from about 365 nm to about 420 nm. In yet another aspect, the wavelength of the visible light source is from about 365 nm to about 400 nm. In yet another aspect, the wavelength of the visible light source is from about 365 nm to about 380 nm. In yet another aspect, the wavelength of the visible light source is from about 380 nm to about 480 nm. In yet another aspect, the wavelength of the visible light source is from about 400 nm to about 480 nm. In yet another aspect, the wavelength of the visible light source is from about 420 nm to about 480 nm. In yet another aspect, the wavelength of the visible light source is from about 450 nm to about 480 nm. In a further aspect, the wavelengths of visible light sources are approximately 365 nm, 380 nm, 400 nm, 420 nm, 450 nm, or 480 nm.

[0558] In a further aspect, the reaction takes place in the presence of a visible light source. In an even further aspect, the visible light source is a light-emitting diode (LED). In yet another further aspect, the wavelength of the visible light source is from approximately 365 nm to approximately 480 nm.

[0559] In further aspects, the wavelengths of the visible light sources are approximately 415 nm, 420 nm, 425 nm, 430 nm, 435 nm, 440 nm, 445 nm, or 450 nm. In various further aspects, the wavelength of the visible light sources is approximately 425 nm.

[0560] In a further aspect, the reaction is carried out in the presence of an oxidizing agent. Examples of oxidizing agents include, but are not limited to, tert-butyl peroxybenzoate (TBPB), tert-butyl peracetate (TBPA), benzoyl peroxide (BPO), tert-butyl hydroperoxide (TBHP), and pyridinium chlorochromate (PCC). In various further aspects, the oxidizing agent is TBPA.

[0561] In a further aspect, the reaction is carried out in the presence of a solvent. Examples of solvents include, but are not limited to, tert-butanol, acetonitrile, dimethyl sulfoxide, toluene, dichloromethane, tetrahydrofuran, N,N-dimethylformate, 1,4-dioxane, and methanol. In various further aspects, the solvent is tert-butanol.

[0562] In addition to other standard operations known in the literature, illustrated in the experimental section, or apparent to those skilled in the art, the compounds of the present invention can be prepared by using the reactions shown in the following scheme. For clarity, examples with a single substituent are shown, wherein multiple substituents are permitted under the definitions disclosed herein.

[0563] The reactions used to produce the compounds of the present invention are prepared by using the reactions shown in the following reaction schemes, as described and illustrated below. In some specific examples, the disclosed compounds can be prepared by pathways I and II, as described and illustrated below. The following examples are provided to provide a fuller understanding of the invention; these examples are illustrative only and should not be construed as limiting.

[0564] 1. Pathway I

[0565] In one aspect, the disclosed compound can be prepared as follows.

[0566] Option 1A.

[0567]

[0568] The compounds are represented in a general form, where LG is a leaving group having a Z substituent and substituents as described elsewhere in the compound descriptions herein. More specific examples are illustrated below.

[0569] Option 1B.

[0570]

[0571] In one aspect, compounds of type 1.3 and similar compounds can be prepared according to reaction scheme 1B described above. Therefore, compounds of type 1.6 can be prepared by the aromatic CO functionalization reaction of a suitable aromatic hydrocarbon (e.g., 1.4 as shown above). Suitable aromatic hydrocarbons are commercially available or prepared by methods known to those skilled in the art. The aromatic CO functionalization reaction is carried out under anaerobic conditions (e.g., under a nitrogen atmosphere) in the presence of a suitable nucleophile (e.g., 1.5 as shown above, which is commercially available or prepared by methods known to those skilled in the art), a suitable catalyst (e.g., 5 mol% acridine nitrogen photocatalyst), at a suitable temperature (e.g., 23 °C), in a suitable solvent system (e.g., acetonitrile:tert-butanol (4:1, 0.1 M)) for a suitable time period (e.g., 30 minutes). Alternatively, the aromatic CO functionalization reaction may be carried out in the presence of a suitable nucleophile (e.g., 1.5 as shown above), a suitable catalyst (e.g., 5 mol% acridine nitrogen photocatalyst), in air, at a suitable temperature (e.g., 0 °C), in a suitable solvent system (e.g., acetonitrile:tert-butanol:1,2-dichloroethane (4:1:3, 800 μL)) for a suitable time period (e.g., 30 minutes). Those skilled in the art will understand that the above reaction provides an example of a general method in which compounds with structures similar to the specific reactants described above (compounds similar to those of types 1.4 and 1.5) may be substituted in the reaction to provide compounds similar to formula 1.6.

[0572] 2. Route II

[0573] In one aspect, the disclosed compound can be prepared as follows.

[0574] Option 2A.

[0575]

[0576] The compounds are represented in a general form, where LG is a leaving group having a Z substituent and substituents as described elsewhere in the compound descriptions herein. More specific examples are illustrated below.

[0577] Option 2B.

[0578]

[0579] In one aspect, compounds of type 1.3 and similar compounds can be prepared according to reaction scheme 2B described above. Therefore, compounds of types 2.2a and 2.2b can be prepared by the aromatic CH functionalization reaction of a suitable aromatic hydrocarbon (e.g., 2.1 as shown above). Suitable aromatic hydrocarbons are commercially available or prepared by methods known to those skilled in the art. The aromatic CH functionalization reaction is carried out in the presence of a suitable nucleophile (e.g., 1.5 as shown above, which is commercially available or prepared by methods known to those skilled in the art), a suitable catalyst (e.g., 5 mol% acridine nitrogen photocatalyst), in the presence of TEMPO, under aerobic conditions (e.g., under molecular oxygen), and at a suitable temperature (e.g., 23 °C). Those skilled in the art will understand that the above reactions provide an example of a general method in which compounds with structures similar to the specific reactants described above (compounds similar to those of types 1.5 and 2.1) can be substituted in the reaction to provide compounds similar to formulas 2.2a and 2.2b.

[0580] Each disclosed method is expected to further include additional steps, operations, and / or components. It is also expected that any one or more steps, operations, and / or components may be optionally omitted from this invention. It should be understood that the disclosed methods can be used to provide the disclosed compounds. It should also be understood that the products of the disclosed methods can be used in the disclosed methods of use.

[0581] F. Catalyst system

[0582] In one aspect, a catalyst system comprising an acridine-onium photocatalyst and a nucleophile selected from halides, cyanides and isotopically labeled amines is disclosed, wherein the catalyst system is anaerobic.

[0583] In one aspect, a catalyst system comprising an acridine-onium photocatalyst, an isotopically labeled halide, and an oxidant is disclosed.

[0584] In a further aspect, the acridine-onium photocatalyst has a structure represented by the following formula:

[0585]

[0586] Q is selected from O and NR. 9 ;where R 9 The phenyl group is selected from C1-C4 alkyl groups and substituted with 0, 1, 2 or 3 groups independently selected from the following: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino; wherein X is selected from BF4, TfO, PF6 and ClO4; wherein R 7The phenyl group is selected from C1-C4 alkyl groups and substituted with 0, 1, 2 or 3 groups independently selected from the group consisting of halogens and C1-C4 alkyl groups; and wherein R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the groups in ' is independently selected from hydrogen, halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, C1-C4 dialkylamino and phenyl groups substituted with 0, 1, 2 or 3 groups independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino and (C1-C4)(C1-C4) dialkylamino.

[0587] In a further aspect, the acridine-onium photocatalyst has a structure represented by the following formula:

[0588]

[0589] Where X is selected from BF4, TfO, PF6, and ClO4; where R 7 The phenyl group is selected from C1-C4 alkyl groups and phenyl groups substituted by 0, 1, 2 or 3 groups independently selected from the following groups: halogen and C1-C4 alkyl; wherein R 8a R 8b R 8c R 8d R 8a '、R 8b '、R 8c 'and R 8d Each of the groups in ' is independently selected from hydrogen, halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, C1-C4 dialkylamino and phenyl groups substituted with 0, 1, 2 or 3 groups independently selected from: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino; and wherein R 9 The phenyl group is selected from C1-C4 alkyl groups and phenyl groups substituted by 0, 1, 2 or 3 groups independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino.

[0590] In a further aspect, the acridine-onium photocatalyst has a structure selected from the following:

[0591]

[0592] In a further aspect, the acridine-onium photocatalyst has the following structure:

[0593]

[0594] In a further aspect, the acridine-onium photocatalyst has the following structure:

[0595]

[0596] In a further aspect, the acridine triium photocatalyst is present in a catalytically effective amount. Therefore, in various aspects, the catalytically effective amount is about 0.01 mol% to about 15 mol%, about 0.01 mol% to about 12 mol%, about 0.01 mol% to about 10 mol%, about 0.01 mol% to about 7 mol%, about 0.01 mol% to about 5 mol%, about 0.01 mol% to about 2 mol%, about 0.01 mol% to about 1 mol%, or about 0.01 mol% to about 0.1 mol%. In various further aspects, the catalytically effective amount is about 0.1 mol% to about 10 mol%, about 0.1 mol% to about 7 mol%, about 0.1 mol% to about 5 mol%, about 0.1 mol% to about 2 mol%, or about 0.1 mol% to about 1 mol%. In yet another further aspect, the catalytically effective amount is 5 mol%.

[0597] In a further aspect, the catalytically effective amount is about 0.1 mol% to about 15 mol%. In yet another further aspect, the catalytically effective amount is about 1 mol% to about 15 mol%. In still a further further aspect, the catalytically effective amount is about 2 mol% to about 15 mol%. In an even further further aspect, the catalytically effective amount is about 5 mol% to about 15 mol%. In yet another further aspect, the catalytically effective amount is about 7 mol% to about 15 mol%. In yet another further aspect, the catalytically effective amount is about 10 mol% to about 15 mol%. In an even further further aspect, the catalytically effective amount is about 12 mol% to about 15 mol%.

[0598] As used herein, the term "nucleophile" refers to a molecule, atom, or ion capable of forming a chemical bond with its reaction partner by donating an electron. Exemplary nucleophiles are well known to those skilled in the art and include, but are not limited to, water, ammonia, halides, cyanides, alcohols, thiols, amines, hydrazine, carbamates, carboxylic acids, and alkenes. In a further aspect, the nucleophile is selected from halides, cyanides, and isotopically labeled amines.

[0599] In a further aspect, the nucleophile is selected from halides and cyanides and is isotopically labeled. In yet another further aspect, the nucleophile is selected from halides and cyanides and is not isotopically labeled.

[0600] In a further aspect, the nucleophile is a halide. Exemplary halides are well known to those skilled in the art and include, but are not limited to, ammonium fluoride, cesium fluoride, lithium chloride, triethylamine hydrochloride, and triethylamine hydrofluoride. In a further aspect, the nucleophile is a halide. In yet another further aspect, the nucleophile is a fluoride. Exemplary examples of fluorides include, but are not limited to, ammonium fluoride, cesium fluoride, triethylamine hydrofluoride, and tetrabutylammonium fluoride.

[0601] In a further aspect, the nucleophile is an isotopically labeled amine. Exemplary isotopically labeled amines include, but are not limited to, isotopically labeled ammonium bicarbonate.

[0602] In a further aspect, the nucleophile is a cyanide. Exemplary cyanides include, but are not limited to, tetrabutylammonium cyanide, sodium cyanide, potassium cyanide, and acetone cyanohydrin.

[0603] In a further aspect, the catalyst system is anaerobic. Therefore, in various aspects, the catalyst system lacks an oxidant or oxidizing agent. As used herein, the terms "oxidant" and "oxidizing agent" refer to any species capable of accepting or acquiring electrons from another species. Exemplary oxidants are well known to those skilled in the art and include, but are not limited to, molecular oxygen, 2,2,6,6-tetramethyl-1-piperidinyloxy radical (TEMPO), ozone, and hydrogen peroxide. In a further aspect, the oxidant is molecular oxygen. In yet another further aspect, the oxidant is TEMPO.

[0604] In a further aspect, the catalyst system further includes a visible light source. In an even further aspect, the visible light source is a light-emitting diode (LED). In a still further aspect, the wavelength of the visible light source is from about 365 nm to about 480 nm.

[0605] In further aspects, the wavelengths of the visible light sources are approximately 415 nm, 420 nm, 425 nm, 430 nm, 435 nm, 440 nm, 445 nm, or 450 nm. In various further aspects, the wavelength of the visible light sources is approximately 425 nm.

[0606] In a further aspect, the catalyst system includes an oxidant. Examples of oxidants include, but are not limited to, tert-butyl peroxybenzoate (TBPB), tert-butyl peracetate (TBPA), benzoyl peroxide (BPO), tert-butyl hydroperoxide (TBHP), and pyridinium chlorochromate (PCC). In various further aspects, the oxidant is TBPA.

[0607] In a further aspect, the catalyst system further includes a solvent. Examples of solvents include, but are not limited to, tert-butanol, acetonitrile, dimethyl sulfoxide, toluene, dichloromethane, tetrahydrofuran, N,N-dimethylformate, 1,4-dioxane, and methanol. In various further aspects, the solvent is tert-butanol.

[0608] In a further aspect, the system further includes the disclosed compounds. In yet another further aspect, the system further includes compounds having a structure represented by the following formula:

[0609] Ar 1 -E,

[0610] Among them, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Ar... 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0611] as well as

[0612] Where E is selected from the following electron-donating groups: -OR 20 -SO3R 20 -SR 20 -NR 21a R 21b -OC(=O)R 20 -OC(=O)OR 20 -OC(=O)SR 20 and -OC(=O)NHR 20 ;where R 20 R 21a and R 21b When present, it is independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkenyl, and Ar. 3 ; and among them Ar 3 When present, it is selected from aryl and heteroaryl groups and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino.

[0613] In a further aspect, the system further includes compounds having a structure represented by the following formula:

[0614] Ar 1 -E,

[0615] Among them, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Ar... 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0616] as well as

[0617] Where E is hydrogen or an electron-donating group selected from the following: -OR 20 -SO3R 20 -SR 20 -NR 21a R 21b -OC(=O)R 20 -OC(=O)OR 20 -OC(=O)SR 20 and -OC(=O)NHR 20 ;where R 20 R 21a and R 21b When present, it is independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkenyl, and Ar. 3 ; and among them Ar 3 When present, it is selected from aryl and heteroaryl groups and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino.

[0618] In a further aspect, the catalyst system further includes compounds having a structure represented by the following formula:

[0619] Ar 1 -E,

[0620] Among them, Ar 1Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 ;where R 10 R 11 R 12a R 12b R 13 and R 15 Each of these, when present, is independently selected from hydrogen and C1-C4 alkyl groups; wherein R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; wherein R 16 When present, it is a hydroxyl protecting group; and Ar is present in it. 2 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; or wherein Ar 1 The structure is represented by the following formula:

[0621] as well as

[0622] E represents hydrogen.

[0623] G. Other References

[0624] Radiosynthesis and Evaluation of [18F]Selectfluor bis(triflate) by H. Teare et al. Angewandte Chemie International Edition, 49, 6821-6824.

[0625] S. Preshlock, M. Tredwell, V. Gouverneur, 18F-Labeling of Arenes and Heteroarenes for Applications in Positron Emission Tomography. Chem. Rev. 116, 719-766 (2016).

[0626] CNNeumann, JMHooker, T. Ritter 19 F - and 18 F - Concerted nucleophilic aromatic substitution with 19 F - and 18 F - ). Nature 534, 369-373 (2016).

[0627] MK Narayanam, G. Ma, PA Champagne, KN Houk, JMMurphy, Synthesis of [18F]Fluoroarenes by Nucleophilic Radiofluorination of N-Arylsydnones. Angewandte Chemie International Edition, 56, 13006-13010.

[0628] Ring-Closing Synthesis of Dibenzothiophene Sulfonium Salts and Their Use as Leaving Groups for Aromatic 18F-Fluorination (J. Am. Chem. Soc., 2018), doi:10.1021 / jacs.8b06730.

[0629] E. Lee et al., A Fluoride-Derived Electrophilic Late-Stage Fluorination Reagent for PET Imaging. Science 334, 639-642 (2011).

[0630] E. Lee, J. H. Brooker, T. Ritter, Nickel-Mediated Oxidative Fluorination for PET with Aqueous [18F] Fluoride. Journal of the American Chemical Society (J. Am. Chem. Soc.) 134, 17456-17458 (2012).

[0631] N. Ichiishi et al., Copper-Catalyzed Fluorination of (Mesityl)(aryl)iodonium Salts. Organic Chemistry Letters, 16, 3224-3227 (2014).

[0632] MSMcCammant et al., Cu-Mediated C–H 18F-Fluorination of Electron-Rich (Hetero)arenes. Organic Chemistry Letters, 19, 3939-3942 (2017).

[0633] Synthesis of [18F]Arenes via the Copper-Mediated Fluorination of Boronic Acids (AVMossine et al.). Organic Chemistry Letters 17, 5780-5783 (2015).

[0634] M. Tredwell et al., A General Copper-Mediated Nucleophilic 18F Fluorination of Arenes. Angewandte Chemie International Edition, 53, 7751-7755.

[0635] KJMakaravage, AFBrooks, AVMossine, MSSanford, PJHScott. Copper-mediated radiofluorination of arylstannanes with [18F]KF. Organic Chemistry Letters 18, 5440-5443 (2016).

[0636] H. Example

[0637] The following examples are provided to offer a complete disclosure and description to those skilled in the art of how to prepare and evaluate the compounds, compositions, articles, apparatus, and / or methods claimed herein, and are intended purely as examples of the invention and not to limit the scope of what the inventors consider to be their invention. Efforts have been made to ensure accuracy regarding figures (e.g., quantities, temperatures, etc.), but some errors and deviations should be accounted for. Unless otherwise stated, parts are by weight, temperatures are in °C or ambient temperature, and pressures are atmospheric or near atmospheric pressure.

[0638] This document provides examples to illustrate the invention and should not be construed as limiting the invention in any way.

[0639] 1. Introducing radioactive isotopes through phenol derivatives

[0640] Positron emission tomography (PET) is a powerful imaging technique used in cancer prognosis, patient screening and treatment monitoring, as well as drug discovery and development. Despite the extraordinary promise of PET imaging, the availability of PET reagents remains limited in many cases due to the lack of effective and simple labeling methods for modifying bioactive molecules / drugs. Typically, radioactive isotopes such as [ 18 F] and [ 11 [C] can be introduced via chemical reactions to modify molecules of interest, thereby creating radiolabeled probe molecules for PET imaging purposes. However, there are few reliable chemical transformations that allow the introduction of these two important radioisotopes.

[0641] In order to solve [ 18 F] By introducing molecules of interest, the direct conversion of phenolic derivatives to aromatic fluorides was developed (see [F]). Figure 1 Nucleophilic aromatic substitution (S) was catalyzed using a single-electron photo-oxidation catalyst. N Ar). The Nicewicz laboratory recently described a route for adding nitrogen heterocycles and ammonia to the methoxylated carbon atom of anisole derivatives under anaerobic conditions (Tay and Nicewicz (2017) J. Am. Chem. Soc. 139: 16100-16104). However, this previously described catalyst system does not allow for the addition of methoxylated aromatics to the carbon atom. N Ar fluorination. Here, the direct fluorination of phenolic derivatives using an acridine-based single-electron photo-oxidation catalyst is described.

[0642] Phenolic derivatives with leaving groups such as sulfonates, carbonates, thiocarbonates, and phenoxy groups can be directly converted to their corresponding derivatives with excellent separation radiochemical yields (RCY) under an inert atmosphere (N2 or Ar). 18 F-aryl compounds, excellent isolated radiochemical yields ( Figure 2A-2C ClO4 using catalyst 2.3 - Salt acquisition 18 F-type aromatic compounds exhibit the highest specific activity. Biologically relevant molecules such as tyrosine and estrone can also be readily converted to RCY. 18 F derivatives.

[0643] A list of other potential catalyst structures that can be applied to this conversion can be found in Figure 3 The parent acridine onium salt (2.1) is an effective single-electron photooxidant (E... p / 2 = +1.87V vs. SCE), because both locally excited singlet (LES) and charge-transfer triplet (CTT) excited states exhibit high oxidizing power at +2.18V and +1.88V vs. SCE, respectively. Figure 3(Fukuzumi et al., (2004) *Journal of the American Chemical Society*, 126:1600-1601; Fukuzumi et al., (2014) *Acc. Chem. Res.*, 47:1455-1464; Benniston et al., (2005) *Journal of the American Chemical Society*, 127:16054-16064; Benniston et al., (2008) *Phys. Chem. Phys.*, 10:5156-5156). In the process of working with these specialized structures, many useful observations have been made regarding the derivatization of these oxidizing salts. For example, altering the aromatic group at the 9-position of acridine onium salts significantly affects the characteristics of the excited states in the molecule, which may exist in locally excited states or charge-transfer states, or in short-lived singlet or long-lived triplet states (Romero and Nicewicz (2014), *Journal of the American Chemical Society*, 136:17024-17035). Furthermore, the acridine onium ring itself most directly affects the reduction potential of the catalyst, with the introduction of electron-withdrawing groups contributing to ease of reduction. This effect can be seen in… Figure 3 The E of the acridine-onium derivatives listed in the table 1 / 2 red and *E 1 / 2 red As seen in [the previous section]. Finally, insulating the most electron-philic positions (i.e., positions 3 and 6) of the acridine ring is crucial for catalyst stability. The introduction of tert-butyl groups at positions 3 and 6 results in a more robust catalyst (2.3), which can now coexist in solution with effective nucleophiles, thus greatly increasing the possible conversion range. Importantly, the inclusion of these “blocking groups” has no substantial effect on the redox performance of the catalyst (see 2.3 and 2.4). More oxidizing xanthonium catalysts, such as the parent 9-mesotriphenylmethyl xanthonium salt (2.7), have excited-state reduction potentials as high as +2.79 V vs. SCE and can be used with a wider range of electron-deficient substrates.

[0644] Apart from[ 18 In addition to fluorination, preliminary data on the introduction of cyanide can be found in [F]. Figure 4A and Figure 4B Using tetrabutylammonium cyanide or acetone cyanohydrin (as depicted) as reagents, a series of methoxy aromatic derivatives readily undergo the conversion from methoxy to cyano groups. By using [ 11 C] Cyanide or [ 11 C] Acetone cyanohydrin, this method can be further refined to produce [ 11C] Cyanide adduct. This would significantly deviate from the prior art in this field, where [ 11 Cyanides have been used to prepare [from the corresponding aryl halides] 11 C] Cyano-aromatic compounds (Lee et al. (2015) Journal of the American Chemical Society (J. Am. Chem. Soc.) 137:648-651).

[0645] The general mechanism proposed for these transformations can be found in Figure 5 Blue photon excitation of the acridinium catalyst (Mes-Acr+) leads to the formation of a strong excited-state photooxidant (Mes-Acr+*). This excited state then oxidizes the phenolic derivative, resulting in the formation of an active cation radical 4.1. This intermediate is susceptible to nucleophilic addition (Nu), leading to the generation of a Meisenheimer-like intermediate 4.2. After losing the alkoxy group and gaining electrons from the reduced form of the catalyst (Mes-Acr·), the final S is obtained. N Ar adduct (4.3).

[0646] 2. Direct aromatic hydrocarbons (CH) 18 The development of F-fluorination

[0647] The development of direct aromatic hydrocarbons (CH) was initiated. 18 The research on F-fluorination aims to address the following challenges: (1) Fluorination should not require the complex synthesis of directing groups or special precursors; instead, it should utilize existing drug molecules, with minimal or no modification, for labeling reactions; (2) 18 The F- fluoride source should be readily available in the form of F- rather than F+, and the resulting reagent should have high specific activity; (3) the reaction conditions should be mild, and taking into account 18 F has a short half-life, and the reaction rate should be within 1 hour; (4) the reaction system may not involve a metal catalyst to simplify the quality control process of translation in the future. Inspired by the latest advances in organic photo-redox catalysis, the conversion of pure CH to CF bonds focuses on the use of visible light-mediated oxidation of CH fluorination.

[0648] The proposed mechanism begins with the single-electron oxidation of aromatics by the excited state (Mes-Acr+*) of the photocatalyst, after which the aromatic cation radical (1.1) can be intercepted by amines or alcohols present in solution, leading to the formation of radical 1.2. Figure 6 The exact nature of the following oxidation may not be clear, but it is speculated that the reaction of O2 with the cyclohexadienyl group results in the formation of an alkyl peroxide radical (1.3). This is in contrast to the reaction of O2 with the cyclohexadienyl radical (approximately 10...). 8 M -1 s -1 Compared to the reaction of eliminating type 1.3 free radicals to produce the corresponding aromatic compounds, the reaction is slow (approximately 10).3 s -1 This process typically involves the extraction of unwanted hydrogen atoms, and is often accompanied by an unwanted hydrogen atom extraction pathway. Niacinyl radicals (a typical example, 2,2,6,6-tetramethyl-1-piperidin-1-oxy (TEMPO)) react rapidly with cyclohexadienyl groups via hydrogen atom extraction (>10). 8 s -1 This produces the corresponding aromatic compounds (1.4). The CH bond enthalpy of the cyclohexadienyl radical is estimated to be approximately 50 kcal / mol. -1 The enthalpy of the OH bond in TEMPO-H is estimated to be 70 kcal / mol. -1 This increases the prospect of using nitryl radicals as a co-catalyst in the proposed conversion, since the re-oxidation of TEMPO-H to TEMPO with O2 is readily achievable.

[0649] The initial tests involved a modified photoredox system previously used for the oxidative amination and cyanidation of CH4. Figure 7 Considering its low volatility and widespread availability in drug skeletons, diphenyl ether (0.05 mmol) was chosen as a model substrate to explore photofluorination. For “cold” (i.e., non-radioactive) fluorination reactions, both CsF and TBAF (1 M, in THF) were selected as... 19 F - The photocatalyst A was selected, and a 20W 450nm LED lamp was used as the light source. Various solvents, phase transfer agents, and temperatures were investigated. Preliminary screening revealed that using 5% photocatalyst A, 50% TEMPO, DCE / H2O as solvent, TBAHSO4 as phase transfer agent, oxygen as oxidant, and 24 hours of 450nm LED light irradiation at room temperature could induce the formation of fluorinated diphenyl ethers with a yield of 17% and a p-:o- ratio of 13:1.

[0650] With these encouraging results, the labeling conditions can be extended to carrier-free conditions. 18 FF - Unfortunately, no radiolabeled products were detected after extensive attempts. The main difference between radiolabeling and "cold" reactions lies in the concentration and reaction ratio. In labeled reactions, high specific activity... 18 F is present in trace amounts (approximately 1-10 μM, reacting with cold reactions). 19 Compared to the approximately 100 mM range of F). In the "cold" labeled reaction, 19 FF - It is 10 times that of diphenyl ether; in comparison, diphenyl ether reacts with... 18 FF - This is far too much.

[0651] Clearly, with a good starting point in the "cold" reaction, CH must be re-optimized to C-. 18 The labeling conditions for the direct conversion of F. In fact, 24-hour light exposure is another obstacle that must be overcome: due to 18 F has a short half-life (110 minutes), and the actual labeling reaction may need to be completed within one hour. As shown in Table 1, different fluoride sources with various counterions were evaluated.

[0652] Table 1.

[0653]

[0654] a nd = Not measured

[0655] After removing TBAHSO4 from the system, 18 F-CsF results in trace amounts of the product (<0.1%). When using anhydrous... 18 FF - At that time, after 2.5 hours of light exposure, 18 The yield of F-TBAF can be increased to 0.57%, K[ 18 The yield of F]-F-kryptofix can be increased to 0.39%. It is noteworthy that all reports use the isolated yield, rather than the yield determined by radioactive TLC and radioactive HPLC integration: because... 18 FF-nonspecific binding to injectors, tubing, or columns allows for separation reactions with a potential yield exceeding 40% as determined by radioactive TLC, even at a rate of 30%. Unreacted... 18 F does not always show a consistent radioactive HPLC peak, which leads to an excessively high integrated radioactive HPLC yield. Separation yield is also more instructive for applications in tracer synthesis (in addition, small impurities or byproducts that are very close to the product on HPLC cannot be completely separated by radioactive TLC).

[0656] Then select 18F-[TBAF] was further explored as a fluorine source, and subsequent work focused on shortening the reaction time by increasing light intensity. A light tunnel was first constructed using four LED strips, and the reaction was carried out using a thin, transparent line. Alternatively, the light source could be a laser, LED lamp, upconverted particles, X-ray particles, chemiluminescence, or bioluminescence. Other examples of reaction vessels that can be used include, but are not limited to, vials, flasks, thin polymer lines for flow, and thin glass / polymer membranes. Although the yield only increased to 1.23% after 2.5 hours of irradiation, it does demonstrate that intensity plays a crucial role in accelerating the fluorination reaction. A blue diode laser coupled to an optical fiber was then used instead of LED lamps to promote the reaction. Using an acetone / ice-cold bath, a jump in separation yield to 28.6% was observed after 2.5 hours of irradiation (Table 2, entry 4).

[0657] Referring to Table 2, the CH to C- conversion was further optimized. 18 The direct conversion scheme of F. As shown in Entries 5-9, under these new conditions, fluorination proceeds gradually over time, and the separation yield is 2.67% after 0.5 hours of irradiation. Further increasing the laser power to 3.5 W, the yield triples at 0.5 hours, reaching 8.23% (Entry 10). However, the yield at 2 hours is slightly lower than that under the 1 W condition, which is likely mainly due to catalyst depletion under high power conditions. Considering 18 The short half-life of F (approximately 110 minutes) necessitates a focus on irradiation times of 0.5–1 hour. Doubling the catalyst loading to 10% did not significantly alter the labeling yield (entries 15–16). Interestingly, bubbling oxygen into the reaction solution, rather than simply fixing it in place, increased the yield to 25.84% under laser irradiation for only 0.5 hours. Converting oxygen to nitrogen significantly reduced the yield (i.e., to 2.79%), indicating that oxygen can greatly promote CH bond fluorination. Other conditions, such as the absence of TEMPO and the addition of water, did not quench the reaction but significantly reduced the yield (Table 2).

[0658] Table 2.

[0659]

[0660]

[0661]

[0662]

[0663] a. Without gas specification, all reactions were carried out with 0.05 mmol of 1 (0.1 M) catalyst, 5 mmol% of TEMPO, and 50 mmol% of TEMPO. b. 10 mmol% of catalyst. c. 1 eq of TEMPO.

[0664] d.O2 bubbling

[0665] A series of acridine-ium organic photo-oxidation-reduction catalysts were screened under optimized conditions. Figure 8 Catalyst A was found to remain the most effective catalyst among the other tested organic acridine onium salts. Catalysts L and KRu(bpy)3(PF6)2 did not produce detectable radiolabeled products. A was then used as the catalyst to screen reaction solvent systems. As shown in Table 3, DMSO, DMF, and MeOH did not produce any detectable products. THF produced only trace amounts of product 1. DCE produced approximately 9% of the product. Surprisingly, the addition of t-BuOH (400 μl) as a co-solvent for MeCN (100 μl) further increased the separation yield to 37.1 ± 12% (n = 4). When pure t-BuOH was used as the solvent, only 2% of product 1 was separated. Indeed, t-BuOH has previously been found to promote fluorination reactions. As expected, reducing the diphenyl ether concentration or catalyst loading decreased the separation yield (Table 3).

[0666] Table 3.

[0667]

[0668] entry catalyst <![CDATA[1a a Separation yield <![CDATA[1b a Separation yield 1 A 25.84％ 2.01％ 2 C 0.92％ nd 3 D 0.11％ nd 4 E 5.44％ 0.60％ 5 F nd nd 6 G nd nd 7 H 12.70％ 0.64％ 8 I 7.39％ Trace 9 J nd nd 10 K nd nd 11 L nd nd

[0669] Furthermore, the specific activity of the resulting compounds was determined. Since comparable yields could be obtained using catalyst A and either ClO4- or BF4- as counterparts, the focus was on the ClO4- catalyst to avoid [further degradation / damage]. 19 The F source was unnecessarily introduced into the reaction system. In fact, a specific activity of 1.37 Ci / μmol was obtained. 18 F-1. It was later discovered that by using laser irradiation reaction conditions, simply... 18 F-TBAF changed back 18 F-CsF, using tBuOH as the sole solvent, also yielded 1 in 21.2% and 2 in 0.8%. When K[ was used under optimized laser reaction conditions...] 18 When F]F-kryptofix replaced TBAF, 26.2% of 1 and 1.5% of 2 were also separated.

[0670] Photo-oxidation-reduction catalysis has been demonstrated to be directly applicable within 30 minutes under mild conditions. 18 FF -The CH bond in diphenyl ethers was effectively radiofluorinated, and the reaction was then extended to a variety of electron-rich aromatic hydrocarbons. The para-CH bond in bisphenol substrates was efficiently fluorinated to C-[ ] within 30 minutes. 18 The F]F bond was isolated with a yield of 44.2%. The CH bond in naphthalene could also be rapidly radiofluorinated at position 1, with a separation yield of 20.9%. Trimethylbenzene produced only a moderate yield when irradiated for 30 minutes under the above conditions. However, slightly modified photoredox conditions (2 eq. TEMPO with a nitrogen stream instead of an oxygen stream) successfully increased the isolation yield to 50%, with optimized irradiation time of 30 minutes.

[0671] Alkyl-containing aromatic rings are among the most common motifs in bioactive compounds. Without further optimization, a rapid and direct method for converting ArCH bonds to C-[ 18 The catalyst system of F]F (Table 4). Under 30 min irradiation, 1-bromo-2-methoxy yielded a moderate separation yield (9.2%, pCH of fluorinated methoxy). The fluorination position was in excellent agreement with previous calculations, indicating that the para position of the MeO group would be a favorable site for nucleophilic reactions. Similarly, after substituting Br with Cl and cyano, the separation yields were 15.1% and 11.1% (30 min irradiation), respectively. Further studies showed that the CH to CF bond conversion was slightly more efficient when the methoxy group was coupled with electron-withdrawing functional groups (such as, for example, amide 10, ketone 8, ester 9, and aldehyde 11 groups) (separation yields of 13.8%, 24.6%, 23.5%, and 22.4%, respectively). CH fluorination was also achieved in methoxy- and TfO- disubstituted substrates, with a separation yield of 27.7% after 30 min irradiation. Notably, Br and OTf-substituted substrates may not be resistant to transition metal-mediated reactions. 18 F-fluorination. This photoredox system was also used to test aromatic substrates corresponding to product numbers 13 and 14. Moderate separation yields (i.e., 7.0% and 4.1% yields) were achieved, primarily due to the poor solubility of these solid substrates in the tBuOH / MeCN solvent system. Nevertheless, these separation yields are still acceptable for PET imaging applications. Trisubstituted substrates corresponding to product numbers 15 and 16 were also successfully fluorinated with 34.3% and 13% yields under irradiation for only 0.5 hours, which is very useful in synthesizing more complex tracers or structural units when one does not wish to be bound by theory.

[0672] Table 4.

[0673]

[0674]

[0675] When an electron-withdrawing group occupies the para position of a methoxy group, the ortho CH group is also directly affected. 18 F-fluorination (Table 5). Substrates corresponding to aldehyde 17, ketone 18, ester 19, and amide 20 yielded ortho-labeled RCYs under 30-minute light irradiation, with separation yields of 5.7%, 10.5%, 8.3%, and 3.9%, respectively. 1-(3-methoxyphenyl)ethyl ketones with meta-substituents of the MeO group were also successfully labeled, providing mixtures of 21 and 22, which were easily separated and... 19 F-standard analysis confirmed that the yields of RCY were 7.8 ± 0.9% and 14.8 ± 0.6%. Compound number 22 was the major product.

[0676] Table 5.

[0677]

[0678]

[0679] In summary, these results indicate that the disclosed photoredox system is compatible with a variety of functional groups commonly found in bioactive molecules. Both p- and o-ArCH bonds are directly fluorinated.

[0680] A photoredox CH fluorination system was also tested in the heterocyclic compound quinazolinidone, which was fluorinated at the para-position of the nitrogen atom, with a separation yield of 17.9% after 30 minutes (Table 6, No. 23). 3,5-Dimethoxypyridine was selectively labeled at the 2-position of the pyridine ring, with an RCY of 11.1%. A substituted quinoline labeled at the 5-position was the major product, with a yield of 6.0%. Direct fluorination of 1-methylindazole was also successful (14.4% separation yield, 30 minutes irradiation), with the major fluorination site at 3. Clearly, the disclosed method also has great potential for the direct fluorination of CH bonds in heterocyclic compounds.

[0681] Table 6.

[0682]

[0683]

[0684] Finally, the disclosed photoredox systems were evaluated in bioactive molecules (Table 7). The methyl esters of fenofofen X and flurbiprofen X (nonsteroidal anti-inflammatory drugs, NSAIDs) were labeled primarily on the unsubstituted benzene ring, with separation yields of 39.6% and 36.8% respectively after 30 minutes of irradiation. Clofibrate, a lipid-lowering drug used to control high cholesterol and triglyceride levels in the blood, was labeled at the ortho position of the alkoxy group, with a yield of 3.7%.

[0685] Table 7.

[0686]

[0687] The photochemical approach is also applicable to more complex bioactive molecules. Protected DOPA yielded para-fluorinated products after 30 minutes of irradiation, with a yield of 8.7% (Table 7, No. 32). Simply increasing the reaction time to 1 hour increased the yield to as high as 21.2%.

[0688] In summary, a convenient method for the rapid formation of Ar-CH bonds from Ar₂C₅ bonds under mild conditions with only 30 minutes of light irradiation is disclosed. This reaction does not require a metal catalyst and can be carried out in an open gas reactor. It is not necessary to be bound by theoretical constraints, the reaction conditions are compatible with a broad range of substrates, and it can be used as… 18 A general method for labeling compounds with F, which 18 F-labeled compounds are used as novel diagnostic agents or to provide crucial information about the in vivo fate / metabolites of targets of interest. The method reported here establishes a novel approach for rapid activation of CH bonds and can be further extended to... 11 C-marking or other slow reactions that are difficult to achieve.

[0689] 3. Synthesis of 1-(fluoro-) from phenol derivatives 18 F)-4-Methoxybenzene

[0690]

[0691] 4. Synthesis of 4-(fluorine- 18 F)-1,1'-biphenyl

[0692]

[0693] 5. Introducing radioactive isotopes from aromatic halide derivatives

[0694] a. Synthesis of 1-(fluorine- 18 F)-4-Methoxybenzene

[0695]

[0696] b. Synthesis of 2-(4-(fluorine-) 18 F) Ethyl phenoxy)-2-methylpropionate

[0697]

[0698] c. Synthesis of 1-(fluorine-) from aromatic halides 18 F)-4-Methoxybenzene

[0699]

[0700] 6. Direct radioactive fluorination of aromatic hydrocarbons (CH) via LED-irradiated photo-oxidation-reduction catalysis

[0701] Positron emission tomography (PET) is an important imaging modality that plays a crucial role in biomedical fields, including disease diagnosis, prognosis, treatment monitoring, and drug development (Simon et al., (2008) Chem. Rev. 108:1501-1516). A common method for generating novel PET contrast agents is the radiolabeling of drugs known to be active against biological processes or targets of interest. Due to the presence of fluorine-18 (… 18 F) is the most widely used PET isotope, and therefore a great deal of effort has been devoted to developing robust methods for radiofluorinated small molecule drugs (Tredwell and Gouverneur (2012) Angewandte Chemie International Edition 51:11426-11437).

[0702] Traditionally, electron-deficient aromatic hydrocarbons can be fluorinated via nucleophilic substitution (Neumann et al., (2016) *Nature* 534:369-373). More recently, deoxyfluorination (Schimler et al., (2017) *Journal of the American Chemical Society* 139:1452-1455), demetallization, copper-catalyzed cross-coupling (Truong et al., (2013) *Journal of the American Chemical Society* 135:9342-9345), and iodonium intermediates (McCammant et al., (2017) *Organic Letters* 19:3939-3942) have been developed for the radiofluorination of a wider range of aromatic hydrocarbons. This paper discloses the discovery of a photoredox system / device that allows for the direct radiofluorination of CH4 using readily available LED light.

[0703] To replace lasers with LEDs, the total light inflow must be significantly increased. Inspired by flow chemistry and microfluidic design, microtube reactors were created, which greatly increase the surface area exposed to the light source. Unfortunately, conducting reactions in closed microtube reactors makes oxygen bubbling impractical. Common oxidants were then screened to replace oxygen, and the results are summarized in Table 8 below.

[0704] Table 8.

[0705]

[0706] entry wavelength catalyst [O] Yield <![CDATA[1 [a] ]]> 450nm Cat-20 TBPB <![CDATA[9.7% [b] ]]> <![CDATA[2 [a] ]]> 450nm Cat-20 TBPA <![CDATA[15.7% [b] ]]> <![CDATA[3 [a] ]]> 450nm Cat-20 BPO <![CDATA[N.D. [b] ]]> <![CDATA[4 [a] ]]> 450nm Cat-20 TBHP <![CDATA[7.4% [b] ]]> <![CDATA[5 [a] ]]> 450nm Cat-20 <![CDATA[H2O2]]> <![CDATA[2.4% [b] ]]> <![CDATA[6 [a] ]]> 450nm Cat-20 <![CDATA[PhI(OAc)2]]> <![CDATA[0.5% [b] ]]> <![CDATA[7 [a] ]]> 450nm Cat-20 <![CDATA[KMnO4]]> <![CDATA[19.2% [b] ]]> <![CDATA[8 [a] ]]> 450nm Cat-20 PCC <![CDATA[N.D. [b] ]]> 9 365nm Cat-32 TBPA <![CDATA[7.7% [c] ]]> 10 385nm Cat-32 TBPA <![CDATA[4.6% [c] ]]> 11 410nm Cat-32 TBPA <![CDATA[12.6% [c] ]]> 12 425nm Cat-32 TBPA <![CDATA[20.2% [c] ]]> 13 450nm Cat-32 TBPA <![CDATA[17.4% [c] ]]>

[0707] [a]diphenyl ether (0.005 mmol), catalyst (0.00025 mmol), [O] 0.005 mmol, TEMPO (0.0025 mmol). The reaction mixture was then loaded into a capillary and sealed, and then irradiated at 0 °C for 40 min under an LED at 450 nm.

[0708] [b] The radiochemical yield (RCY) was calculated based on radioactive TLC analysis on silica gel 60 aluminum plates, with ethyl acetate / hexane as the eluent (v / v = 1 / 20).

[0709] [c]2-methoxybenzaldehyde (0.1 mmol), catalyst (0.025 mmol), [O] 0.05 mmol. The reaction mixture was then loaded into a capillary and sealed, and irradiated at 0 °C for 40 min under an LED at 450 nm. The RCY was separated by radioactive HPLC.

[0710] tert-butyl peroxybenzoate (TBPB), tert-butyl peracetate (TBPA), benzoyl peroxide (BPO), tert-butyl hydroperoxide (TBHP), and pyridinium chlorochromate (PCC)

[0711] By using diphenyl ether as a model substrate, and incubating the oxidant under LED light irradiation [ 18 [F]TBAF, rapid analysis of the reaction mixture using radioactive TLC. No target product was detected when benzoyl peroxide (BPO) or pyridinium chlorochromate (PCC) was used as the oxidant, and only trace amounts were detected when PhI(OAc)₂ or H₂O₂ were used as the oxidant. Tert-butyl peracetate (TBPA) was the second best oxidant tested, with an RCY of 15.7%. Tert-butyl peroxide (TBPB) and tert-butyl hydroperoxide (TBHP) were less reactive than TBPA, with yields of 9.7% and 7.4%, respectively. This suggests that the tert-butyl radical may play an important role in the reaction. The reaction with potassium permanganate as the oxidant yielded the highest yield (19.23%) in this first oxidant screening. However, potassium permanganate has poor solubility in the reaction system. This makes the reaction a heterogeneous mixture, and therefore leads to difficulties in sample loading and unstable yields. Although slightly less efficient than potassium permanganate, TBPA was easier to handle and was therefore chosen for the next screening. Nine solvents were evaluated as the main reaction medium, including tBuOH, acetonitrile, DMSO, toluene, dichloromethane, tetrahydrofuran, N,N-dimethylformate, 1,4-dioxane, and methanol. The reaction was determined to perform best in tBuOH. See Tables 9 and 10 below. Based on these results, further evaluation was conducted using 1 equivalent of TBPA in tBuOH.

[0712] Table 9.

[0713]

[0714]

[0715] [a] Irradiation with Cat-20 (0.00025 mmol), LED 450 nm for 40 minutes, diphenyl ether (0.005 mmol), TEMPO (0.0025 mmol), TBPB (0.01 mmol), 18 F-TBAF / CAN (0.1–0.5 mCi), 0 °C, and a primary solvent (40 μL) were selected. A small amount of the reaction mixture was loaded into a capillary tube and sealed to proceed with the reaction.

[0716] [b] RCY calculated from radioactive TLC.

[0717] Table 10.

[0718] <![CDATA[Equivalent [a] > <![CDATA[RCY [b] ]]> 0eq. 9.76％ 0.1eq. 17.92％ 0.5eq. 21.3％ 1.0eq. 22.87％ 2.0eq. 13.97％ 5.0eq. ND

[0719] [a] Irradiation with Cat-20 (0.00025 mmol), LED 450 nm for 40 minutes, diphenyl ether (0.005 mmol), TEMPO (0.0025 mmol), 18 F-TBAF / CAN (0.1~0.5mCi), sieved at 0℃ for [O] equivalents. A small amount of the reaction mixture was loaded into a capillary tube and sealed to proceed with the reaction.

[0720] [b] RCY calculated from radioactive TLC.

[0721] Next, the library of 48 organic photocatalysts will be evaluated. Figure 10 The results are shown in Table 11. Generally, acridine-onium catalysts are more effective than xanthonium catalysts. No target product was detected when either xanthonium catalysts (Cat-21 to Cat-31) or 2,4,6-triphenylpyranium catalysts (Cat-13 to Cat-18) were used in the reaction. Cat-32 yielded good results with an RCY of 42.4% (Table 11). No significant difference was observed when the reaction was carried out at room temperature or 40°C. The effect of LED light wavelength on the reaction was also evaluated.

[0722] Table 11.

[0723]

[0724]

[0725] [a] The chemical structures of the catalysts are summarized in Figure S1. Diphenyl ether (0.005 mmol), Cat (0.00025 mmol), TEMPO (0.0025 mmol), TBPA (0.005 mmol), 18 F-TBAF / ACN (0.5–1.5 mCi) and tBuOH (40 μL). The reaction mixture was then loaded into a capillary tube and sealed, and then irradiated at 0 °C for 40 minutes under an LED at 450 nm.

[0726] [b] The radiochemical yield (RCY) was calculated based on radioactive TLC analysis on silica gel 60 aluminum plates, with ethyl acetate / hexane as the eluent (v / v = 1 / 20).

[0727] [c] The RCY is 36.43% when the reaction is carried out at room temperature and 43.32% when the reaction is carried out at 40°C.

[0728] The proposed mechanism begins with the single-electron oxidation of aromatics by the excited state (Cat-32*) of the photocatalyst, after which the aromatic cation radical (1.1) can be intercepted by amines or alcohols present in solution, leading to the formation of radical 1.2. Figure 11 The exact nature of the following oxidation is not well understood. Without being bound by theory, it is hypothesized that the oxidant reacts with the cyclohexadiene radical to generate an alkyl peroxy radical (1.3). Intramolecular hydrogen atom transfer (HAT) and extrusion of the alcohol unit (R'OH) then provide a fluorinated aromatic hydrocarbon. A nitryl radical (typically 2,2,6,6-tetramethyl-1-piperidin-1-oxy (TEMPO)) reacts rapidly with the cyclohexadiene radical via hydrogen atom extraction to produce the corresponding aromatic compound (1.4) (Xian-Ming Pan (1993), J. Chem. Soc. Perkin Trans. 2:9). The CH bond enthalpy of the cyclohexadiene radical is estimated to be approximately 50 kcal / mol. -1 The enthalpy of the OH bond in TEMPO-H is estimated to be 70 kcal / mol. -1 This increases the prospect of using nitro group radicals as a co-catalyst in the proposed conversion, since the re-oxidation of TEMPO-H to TEMPO by the oxidant is readily achievable.

[0729] After evaluating the extent of this radioactive fluorination, an attempt was made to eliminate the preparation [ 18 The azeotropic drying step in F-TBAF further simplifies the labeling procedure. Target water 18The F source was prepared by directly capturing it on a pre-activated mini-QMA. 5 mL of anhydrous acetonitrile was passed through the mini-QMA to wash away most of the water on the QMA. Not wanting to be bound by theory, it was found that elution was readily achieved by adding a small amount of TBAB solution (25 μL, 1.5 mg in ACN) to a mixture of substrate, catalyst, and oxidant solution in tBuOH. 18 F]-TBAF. The reaction mixture was then loaded into quartz microtubes and irradiated under an LED lamp at room temperature. Next, the activity was collected in 1.5 mL microcentrifuge tubes and further evaluated by radioactive HPLC. This process was carried out in Figure 13 As shown in the figure. Finally, using compound 23 as a starting material, the method was applied to obtain the product [ 18 F]-22, the separation rate of RCY was 22.8%.

[0730] In summary, an LED-irradiated photoredox system has been developed that allows for rapid and direct radioactive fluorination of aromatic hydrocarbons (CH). These mild reaction conditions can be used to synthesize novel... 18 F-labeled radioactive tracer.

[0731] a. General experimental details

[0732] The [This article uses] 19 F]-Standards and [ 18 The F-precursor is either synthesized according to the previously described method or commercially available.

[0733] b. General Procedure A

[0734] Photocatalyst (0.00125 mmol, 0.025 eq.), substrate (0.05 mmol, 1.0 eq.), TEMPO (1.9 mg, 0.012 mmol, 0.25 eq.), and oxidant (0.05 mmol, 1.0 eq.) were added to a 1.5 mL microcentrifuge tube and dissolved in 20–30 μL of anhydrous MeCN and 200 μL of t-BuOH. Immediately afterwards, 20–30 μL aliquots of the sample were pipetted into the solution. 18 F]TBAF / MeCN (typically 2-3 mCi) [total volume of MeCN 50 μL] is added to the reaction flask. [The rest of the text appears to be incomplete and requires further context.] 18 F] TBAF was monitored after addition to the substrate solution. 18 The activity of F]TBAF was decreased. The reaction mixture was then loaded into a quartz capillary and irradiated with an LED lamp for 40 minutes at room temperature. The resulting solution was injected into HPLC for analysis and separation. [Collection] 18 Fractionation and activity measurement of F-labeled products. All [ 18The radiochemical yields of F-labeled molecules were all based on HPLC separations, as shown in the substrate range. 18 [F]-Radiolabeled products were obtained by co-injection of commercial or synthetic products via HPLC. 19 F-standard verification. Separate quality control (QC) is performed to ensure the purity of the isolated radiolabeled compounds.

[0735] c. General Procedure B

[0736] In the target water 18 F- was captured on a pre-activated mini-QMA, followed by passing 5 mL of anhydrous acetonitrile through the QMA. Subsequently, a solution of Cat-32 (0.00125 mmol, 0.025 eq.), substrate (0.05 mmol, 1.0 eq.), TEMPO (1.9 mg, 0.012 mmol, 0.25 eq.), and TBPA (0.05 mmol, 1.0 eq.) in 200 μL of tBuOH and 50 μL of acetonitrile were used as the eluent. The resulting eluent was placed in a quartz tube and irradiated at room temperature under LED 425 nm light for 40 min. An aliquot of the reaction mixture (typically 400–800 μCi) was used for radioactive HPLC analysis.

[0737] d. Spectral evaluation of exemplary compounds

[0738] The exemplary compounds were evaluated using radioactive HPLC under the specific conditions detailed below. The purity of all compounds was determined to be >98%.

[0739] (i) Compound 1

[0740]

[0741] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: 20-45% solvent B, 2 to 22 min: 45-60% solvent B, 22 to 28 min: 60-95% solvent B, 28 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0742] (ii) Compound 2

[0743]

[0744] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250x4.6mm LC column: Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 45-60% solvent B, 22 to 28 min: 60-95% solvent B, 28 to 40 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0745] (iii) Compound 3

[0746]

[0747] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 12 min: isocratic 5% solvent B, 12 to 32 min: 5-95% solvent B, 32 to 40 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; Isocratic stability: 0 to 2 min: 5% solvent B, 2 to 22 min: 50-58% solvent B, 22 to 28 min: 58-95% solvent B, 28 to 40 min: 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0748] (iv) Compound 4

[0749]

[0750] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 50-58% solvent B, 22 to 28 min: 58-95% solvent B, 28 to 40 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0751] (V) Compound 5

[0752]

[0753] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 40 min: isocratic 55% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0754] (VI) Compound 6

[0755]

[0756] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: 5% isocratic solvent B, 2 to 22 min: 45-60% solvent B, 22 to 28 min: 60-95% solvent B, 28 to 40 min: 95% isocratic solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0757] (VII) Compound 7

[0758]

[0759] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: 5% isocratic, 2 to 22 min: 5-95% solvent B, 22 to 35 min: 95% isocratic solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; isocratic reaction 0 to 2 min: 5% solvent B, 2 to 40 min: 50% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0760] (VIII) Compound 8

[0761]

[0762] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 40 min: isocratic 50% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0763] (ix) compound 9

[0764]

[0765] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 40 min: isocratic 45% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0766] (X) Compound 10

[0767]

[0768] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; isocratic 35% solvent B for 0 to 40 min. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0769] (XI) Compound 11

[0770]

[0771] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; isocratic 35% solvent B for 0 to 40 min. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0772] (xii) compound 12

[0773]

[0774] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 40 min: isocratic 40% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0775] (xiii) Compound 13

[0776]

[0777] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; isocratic 40% solvent B for 0 to 40 min. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0778] (xiv) compound 14

[0779]

[0780] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 40 min: isocratic 40% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0781] (xv) compound 15

[0782]

[0783] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; isocratic 35% solvent B for 0 to 40 min. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0784] (xvi) compound 16

[0785]

[0786] HPLC conditions: (A) and (B) Columns: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (C) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: 5-30% solvent B, 2 to 22 min: 30-60% solvent B, 22 to 27 min: 60-95% solvent B, 27 to 40 min: 95% solvent B isocratic. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0787] (xvii) compound 17

[0788]

[0789] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 40 min: 70% isocratic solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0790] (xviii) compound 18

[0791]

[0792] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 40 min: isocratic 35% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0793] (xix) compound 19

[0794]

[0795] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 40 min: isocratic 30% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0796] (XX) compound 20

[0797]

[0798] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 50-58% solvent B, 22 to 28 min: 58-95% solvent B, 28 to 40 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0799] (xxi) compound 21

[0800]

[0801] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: 60% isocratic solvent B, 2 to 22 min: 60-85% solvent B, 22 to 28 min: 85-95% solvent B, 28 to 40 min: 95% isocratic solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0802] (xxii) compound 22

[0803]

[0804] HPLC conditions: (A) Column: Phenomenex, Gemini 5μm C18 110A, new column 250x4.6mm. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 22 min: 5-95% solvent B, 22 to 35 min: isocratic 95% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C. (B) and (C) Columns: Phenomenex, 5μm F5 250 x 4.6 mm LC column. Solvent A: 0.1% aqueous solution of TFA; Solvent B: 0.1% acetonitrile solution of TFA; 0 to 2 min: isocratic 5% solvent B, 2 to 40 min: isocratic 60% solvent B. Flow rate: 1 mL / min, column temperature: 19 to 21 °C.

[0805] It will be apparent to those skilled in the art that various modifications and variations can be made to the invention without departing from its scope or spirit. Other embodiments of the invention will become apparent to those skilled in the art upon consideration of the specification and practice of the invention disclosed herein. This specification and examples are intended to be considered merely exemplary, wherein the true scope and spirit of the invention are indicated by the appended claims.

Claims

1. A method for preparing a compound having a structure represented by the following formula: Ar 1 -Z, Where Z is selected from halogens or -CN; Among them, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ; Where R 10 R 11 R 12a R 12b R 13 and R 15 Each of them, when present, is independently selected from hydrogen and C1-C4 alkyl groups; Where R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Among them, Ar 2 When present, it is selected from aryl and heteroaryl groups and is substituted by 0, 1, 2 or 3 groups independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; Or Ar 1 The structure is represented by the following formula: The method includes making aromatic hydrocarbons having a structure represented by the following formula: The 1 -IN, Where E is an electron-donating group selected from the following: -OR 20 -OC(=O)R 20 -OC(=O)OR 20 -OC(=O)SR 20 and -OC(=O)NHR 20 ; Where R 20 R 21a and R 21b When present, it is independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkenyl, and Ar. 3 ;as well as Among them, Ar 3 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino. The compound is formed by reacting a nucleophile selected from halides and cyanides with an effective amount of acridine-onium photocatalyst under anaerobic conditions in place of the electron-donating group E.

2. The method according to claim 1, wherein Z contains a radioactive isotope.

3. The method according to claim 2, wherein the radioactive isotope is selected from... 18 F, 11 C 34 Cl、 76 Br、 123 I, 124 I, 131 I, 125 I and 211 At.

4. The method according to claim 2, wherein the radioactive isotope is selected from... 18 F and 11 C.

5. The method according to claim 1, wherein Z is a halogen.

6. The method of claim 5, wherein Z is -F.

7. The method of claim 5, wherein Z is -At.

8. The method of claim 1, wherein Z is -CN.

9. The method of claim 1, wherein Ar 1 It is an aryl group substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

10. The method of claim 9, wherein Ar 1 It is a phenyl group substituted with 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

11. The method of claim 9, wherein Ar 1 It is a naphthyl group that is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

12. The method of claim 1, wherein Ar 1 It is a heteroaryl group substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

13. The method of claim 12, wherein Ar 1 It is a pyridyl group substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

14. The method of claim 1, wherein Ar 1 Selected from 5-aryl, 6-aryl, 5-heteroaryl, and 6-heteroaryl, and substituted by 0, 1, 2, or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

15. The method of claim 1, wherein the electron-donating group is -OR 20 .

16. The method of claim 15, wherein the electron-donating group is -OCH3.

17. The method according to claim 1, wherein the aromatic hydrocarbon has a structure represented by the following formula:

18. The method according to claim 1, wherein the aromatic hydrocarbon has a structure represented by the following formula:

19. The method according to claim 1, wherein the aromatic hydrocarbon has a structure represented by the following formula:

20. The method of claim 1, wherein the nucleophile is isotopically labeled.

21. The method of claim 1, wherein the nucleophile is a halide.

22. The method of claim 21, wherein the halide is a fluoride.

23. The method of claim 22, wherein the fluoride is selected from ammonium fluoride, cesium fluoride, triethylamine hydrofluoride, and tetrabutylammonium fluoride.

24. The method of claim 1, wherein the nucleophile is a cyanide.

25. The method of claim 24, wherein the cyanide is selected from tetrabutylammonium cyanide, sodium cyanide, potassium cyanide and acetone cyanohydrin.

26. The method according to claim 1, wherein the acridine-onium photocatalyst has a structure represented by the following formula: Where Q is selected from O and NR 9 ; Where R 9 Selected from C1-C4 alkyl, aryl and heteroaryl groups and substituted by 0, 1, 2 or 3 groups independently selected from the following: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino; Where X is selected from BF4, TfO, PF6 and ClO4; Where R 7 Phenyl groups selected from C1-C4 alkyl groups and phenyl groups substituted with 0, 1, 2, or 3 groups independently selected from: halogens and C1-C4 alkyl groups; and Where R 8a R 8b R 8c R 8d R 8a' R 8b' R 8c' and R 8d' Each of the groups is independently selected from hydrogen, halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, C1-C4 dialkylamino and phenyl groups substituted with 0, 1, 2 or 3 groups independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino and (C1-C4)(C1-C4) dialkylamino.

27. The method according to claim 26, wherein the acridine nitrogen photocatalyst has the following structure:

28. The method of claim 1, wherein the compound has a structure selected from the group consisting of:

29. The method of claim 28, wherein the fluorine is 18 F.

30. The method according to claim 1, wherein the compound has a structure selected from the group consisting of:

31. The method of claim 30, wherein the cyanide is 11 CN.

32. The method of claim 1, wherein the reaction is carried out under an inert atmosphere.

33. The method of claim 1, wherein the reaction is carried out in the presence of a visible light source.

34. The method of claim 33, wherein the visible light source is a laser or a light-emitting diode (LED).

35. The method of claim 33, wherein the visible light source has a wavelength of 365 nm to 480 nm.

36. The method of claim 33, wherein the visible light source has a wavelength of 450 nm.

37. A catalyst system comprising an acridine-onium photocatalyst and a nucleophile selected from halides and cyanides, which replaces the electron-donating group, wherein the catalyst system is anaerobic, and Including compounds represented by the following formula: The 1 -IN, Among them, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ; Where R 10 R 11 R 12a R 12b R 13 and R 15 Each of them, when present, is independently selected from hydrogen and C1-C4 alkyl groups; Where R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Among them, Ar 2 When present, it is selected from aryl and heteroaryl groups and is substituted by 0, 1, 2 or 3 groups independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; Or Ar 1 The structure is represented by the following formula: as well as Where E is an electron-donating group selected from the following: -OR 20 -OC(=O)R 20 -OC(=O)OR 20 -OC(=O)SR 20 -OC(=O)NHR 20 ; Where R 20 R 21a and R 21b When present, it is independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkenyl, and Ar. 3 ;as well as Among them, Ar 3 When present, it is selected from aryl and heteroaryl groups and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino.

38. A method for preparing a compound having a structure represented by the following formula: Ar 1 -Z, Z is selected from halogens and -CN, and Z contains a radioactive isotope; Among them, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 ; Where R 10 R 11 R 12a R 12b R 13 and R 15 Each of them, when present, is independently selected from hydrogen and C1-C4 alkyl groups; Where R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; Where R 16 When present, it is a hydroxyl protecting group; and Among them, Ar 2 When present, it is selected from aryl and heteroaryl groups and is substituted by 0, 1, 2 or 3 groups independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; Or Ar 1 The structure is represented by the following formula: The method includes making aromatic hydrocarbons having a structure represented by the following formula: The 1 -IN, Where E is hydrogen or an electron-donating group selected from the following: -OR 20 -OC(=O)R 20 -OC(=O)OR 20 -OC(=O)SR 20 -OC(=O)NHR 20 ; Where R 20 R 21a and R 21b When present, it is independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkenyl, and Ar. 3 ;as well as Among them, Ar 3 When present, it is selected from aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, -CHO, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino. The compound is formed by reacting a nucleophile selected from halides and cyanides in the presence of a catalytically effective amount of acridine-onium photocatalyst, an oxidant, a visible light source, and a solvent system containing tert-butanol.

39. The method of claim 38, wherein Z is a halogen and wherein the nucleophile is a halide.

40. The method of claim 39, wherein Z is 18 F and said nucleophile is 18 F-TBAF.

41. The method of claim 38, wherein E is hydrogen.

42. The method of claim 38, wherein Ar 1 It is an aryl group substituted by 0-6 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

43. The method of claim 42, wherein Ar 1 It is a phenyl group substituted with 0, 1, 2 or 3 independently selected from the following groups: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 .

44. The method of claim 38, wherein the acridine-onium photocatalyst has a structure represented by the following formula: Where Q is selected from O and NR 9 ; Where R 9 It is selected from C1-C4 alkyl, aryl and heteroaryl groups, and is substituted by 0, 1, 2 or 3 groups independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4)dialkylamino; Where X is selected from BF4, TfO, PF6 and ClO4; Where R 7 Phenyl groups selected from C1-C4 alkyl groups and phenyl groups substituted by 0, 1, 2 or 3 independently selected from the following groups: Halogens and C1-C4 alkyl groups; and Where R 8a R 8b R 8c R 8d R 8a' R 8b' R 8c' and R 8d' Each of the groups is independently selected from hydrogen, halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino, C1-C4 dialkylamino and phenyl groups substituted with 0, 1, 2 or 3 groups independently selected from the following groups: halogen, -CF3, -NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamino and (C1-C4)(C1-C4) dialkylamino.

45. The method according to claim 44, wherein the acridine nitrogen photocatalyst has the following structure:

46. ​​The method of claim 38, wherein the acridine-onium photocatalyst is present in an amount of 0.1 mol% to 10 mol%.

47. The method of claim 38, wherein the acridine-onium photocatalyst is present in an amount of 5 mol%.

48. The method of claim 38, wherein the compound is selected from:

49. The method of claim 38, wherein the visible light source is a light-emitting diode (LED).

50. The method of claim 38, wherein the visible light source has a wavelength of 365 nm to 480 nm.

51. The method of claim 38, wherein the visible light source has a wavelength of 425 nm.

52. The method of claim 38, wherein the oxidant is selected from tert-butyl peroxybenzoate (TBPB), tert-butyl peracetate (TBPA), benzoyl peroxide (BPO), tert-butyl hydroperoxide (TBHP), and pyridinium chlorochromate (PCC).

53. The method of claim 38, wherein the oxidant is TBPA.

54. The method of claim 38, wherein the solvent is tert-butanol.

55. A method for preparing a compound having a structure represented by the following formula: Ar 1 -Z, Where Z is a halogen and Z contains a radioactive isotope; Among them, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 ; Where R 10 R 11 R 12a R 12b R 13 and R 15 Each of them, when present, is independently selected from hydrogen and C1-C4 alkyl groups; Where R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; Where R 16 When present, it is a hydroxyl protecting group; and Among them, Ar 2 When present, it is selected from aryl and heteroaryl groups and is substituted by 0, 1, 2 or 3 groups independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; Or Ar 1 The structure is represented by the following formula: The method includes making aromatic hydrocarbons having a structure represented by the following formula: Ar 1 -H, The steps of reacting halides with an LED having a wavelength of 425 nm, TBPA, and a catalytically effective amount of an acridine-onium photocatalyst having the following structure: This forms the compound.

56. A catalyst system comprising an acridine-onium photocatalyst, an isotopically labeled halide, and an oxidant. And compounds having a structure represented by the following formula: The 1 -IN, Among them, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 -OAr 2 -C(=O)Ar 2 -OR 16 and -CH2CR 13 (NR 14a R 14b CO2R 15 ; Where R 10 R 11 R 12a R 12b R 13 and R 15 Each of them, when present, is independently selected from hydrogen and C1-C4 alkyl groups; Where R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; Where R 16 When present, it is a hydroxyl protecting group; and Among them, Ar 2 When present, it is selected from aryl and heteroaryl groups and is substituted by 0, 1, 2 or 3 groups independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; Or Ar 1 The structure is represented by the following formula: as well as Where E is hydrogen; The acridine-onium photocatalyst described herein has the following structure:

57. The system of claim 56, wherein the isotope-labeled halide is 18 F-TBAF.

58. The system according to claim 56, wherein the oxidant is TBPA.

59. The system according to claim 56, further comprising a visible light source.

60. The system according to claim 59, wherein the visible light source is an LED.

61. A method for preparing a compound having a structure represented by the following formula: Ar 1 -X, Where X is a halogen and X contains a radioactive isotope; Among them, Ar 1 Selected from aryl and heteroaryl groups, and substituted by 0-6 independently selected groups from the following: halogen, -CN, -NO2, C1-C8 alkyl, C1-C8 alkoxy, -O-(C1-C8 alkyl)-CO2-(C1-C8 alkyl), -C(=O)R 10 -C(=O)OR 11 -C(=O)NR 12a R 12b Ar 2 and -CH2CR 13 (NR 14a R 14b CO2R 15 ; Where R 10 R 11 R 12a R 12b R 13 and R 15 Each of them, when present, is independently selected from hydrogen and C1-C4 alkyl groups; Where R 14a and R 14b Each of these, when present, is independently selected from hydrogen, C1-C4 alkyl, and amine protecting groups; and Among them, Ar 2 When present, it is selected from aryl and heteroaryl groups and is substituted by 0, 1, 2 or 3 groups independently selected from the following groups: halogen, -CN, -NO2, -OH, -SH, -NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 alkoxy, C1-C4 hydroxy, C1-C4 thioalkoxy, C1-C4 alkylthio, C1-C4 aminoalkyl, C1-C4 alkylamino and (C1-C4)(C1-C4)dialkylamino; Or Ar 1 The structure is represented by the following formula: The method includes making aromatic hydrocarbons having a structure represented by the following formula: Ar 1 -X', Where X' is a halogen and X' does not contain a radioactive isotope. The compound is formed by reacting a nucleophile selected from halides in the presence of a catalytically effective amount of acridine-onium photocatalyst and under anaerobic conditions, or in the presence of a catalytically effective amount of acridine-onium photocatalyst, an oxidant, a visible light source, and a solvent system containing tert-butanol.

62. The method of claim 61, wherein X is selected from... 18 F, 11 C 34 Cl、 76 Br、 123 I, 124 I, 131 I, 125 I and 211 At.

63. The method of claim 61, wherein X is 18 F.

64. The method of claim 61, wherein X' is a fluoride.

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