Method of fluorination, reagents, fluorinated composition, and method of production

Abstract

This specification provides compositions useful for producing fluorinated products and methods for producing such compositions.

Description

[Technical Field]

[0001] cross reference

[0001] This application claims the benefit of priority of U.S. Provisional Application No. 63 / 521,147, filed on 15 June 2023, which is incorporated herein by reference. [Background technology]

[0002]

[0002] Using hazardous and toxic reagents such as HF to manufacture and produce fluorinating reagents is dangerous and harmful to the environment. This specification provides a process for manufacturing fluorinating reagents or reagent compositions that reduces and / or eliminates the use of hazardous reagents. [Overview of the project] [Means for solving the problem]

[0003]

[0003] In one embodiment, a method for producing a fluorinating reagent is provided herein. In some embodiments, the fluorinating reagent is a crude fluorinating reagent which can be further purified to yield a purified fluorinating reagent. In some embodiments, the fluorinating reagent is a purified fluorinating reagent. In some embodiments, the method provided herein includes the step of combining a first salt with a second salt to form a mixed composition. In some embodiments, the first salt may contain calcium and fluorine. In some embodiments, the method provided herein includes the step of applying mechanical force to the combination of the first and second salts to form a mixed composition. In some embodiments, the method provided herein includes the step of subjecting the mixed composition to a fluid composition and the step of collecting the resulting fluid. In some embodiments, the step of subjecting the mixed composition to a fluid composition produces a solid component and the resulting fluid.

[0004]

[0004] In some embodiments, the method provided herein includes a step of concentrating the resulting fluid. In some embodiments, the step of concentrating the resulting fluid forms a crude fluorinating reagent which can be further purified to yield a purified fluorinating reagent. In some embodiments, the step of concentrating the resulting fluid produces a reagent concentrate or precipitate. In some embodiments, the method provided herein includes a step of washing the fluorinating reagent with a solvent to produce a reagent wash. In some embodiments, the step of washing the fluorinating reagent yields a second solid component and a fluid reagent wash. In some embodiments, the reagent wash contains the fluorinating reagent. In some embodiments, the reagent wash contains a purified fluorinating reagent.

[0005]

[0005] In some embodiments, the method provided herein includes the step of concentrating the reagent wash to form a fluorinating reagent. In some embodiments, the step of concentrating the reagent wash yields a purified fluorinating reagent. In some embodiments, the purified fluorinating reagent has a higher concentration of fluorine compared to the crude fluorinating reagent. In some embodiments, the method provided herein includes the step of contacting the fluorinating reagent with a starting reagent to obtain a fluorination product. In some embodiments, the fluorinating reagent is a crude fluorinating reagent which can be further purified to yield a purified fluorinating reagent. In some embodiments, the fluorinating reagent is a purified fluorinating reagent. In some embodiments, the step of contacting the fluorinating reagent with a starting reagent fluorinates the starting reagent.

[0006]

[0006] In one embodiment, a method for fluorinating a starting reagent using a fluorinating reagent is provided herein. In some embodiments, the fluorinating reagent is a crude fluorinating reagent which can be further purified to yield a purified fluorinating reagent. In some embodiments, the fluorinating reagent is a purified fluorinating reagent. In some embodiments, the step of fluorinating a starting reagent using a fluorinating reagent yields a fluorinated product. In some embodiments, the method provided herein includes the step of preparing the fluorinating reagent and the starting reagent. In some embodiments, the fluorinating reagent comprises an alkali metal, a fluoride, and at least one additional ion. In some embodiments, the alkali metal may include lithium, potassium, or sodium. In some embodiments, the fluorinating reagent may contain a certain amount of phosphorus.

[0007]

[0007] In some embodiments, the amount of phosphorus in the fluorinating reagent is about 1 ppm to about 25 ppm (e.g., about 1 ppm, about 10 ppm, about 20 ppm, or about 25 ppm). In some embodiments, the amount of phosphorus in the fluorinating reagent is 0.015% by weight to about 12.5% ​​by weight (wt%). In some embodiments, the fluorinating reagent can be characterized by at least one of the 2θ values ​​reported in any one of Tables 5, 6A, 8, 9, 12, 15-18, 20, 21, 23, 25-28 (e.g., at least 2, at least 3, at least 5, at least 10, at least 20, at least 50, and / or at least 70). In some embodiments, the method provided herein includes the step of contacting a starting reagent with a fluorinating reagent to fluorinate the starting reagent to obtain a fluorination product. In some embodiments, the step of contacting a starting reagent with a fluorinating reagent yields a fluorination product.

[0008] In some embodiments, a method for producing a fluorination reagent provided herein can include adjusting the pH of the resulting fluid before the step of concentrating said resulting fluid. In some embodiments, the resulting fluid can be adjusted to a pH of from about 6 to about 8. In some embodiments, the amount of phosphorus in the fluorination reagent is from about 0.015 wt% to about 12.5 wt%. In some embodiments, the fluorination reagent is a crude fluorination reagent that can be further purified to yield a purified fluorination reagent. In some embodiments, the fluorination reagent is a purified fluorination reagent. In some embodiments, a method for producing a fluorination reagent provided herein and a method for fluorinating a starting reagent can include including an amount of calcium in the fluorination reagent.

[0009]

[0009] In some embodiments, the fluorinating reagent is a purified fluorinating reagent. In some embodiments, the fluorinating reagent is a crude fluorinating reagent which can be further purified to yield a purified fluorinating reagent. In some embodiments, the crude fluorinating reagent is at least partially purified using a filtration process. In some embodiments, the filtrate is concentrated and / or dried in any step or process of any method described herein. In some embodiments, the filtration process includes passing any solution described herein through the same or more filtration modules multiple times (e.g., by passing through the same module three or more times consecutively, and / or by passing through three consecutively connected modules once each). In some embodiments, the fluorine recovery rate of the filtration process used herein is greater than 90% (e.g., greater than 95% or greater than 99%). In some embodiments, the removal rate of one or more contaminants by the filtration process used in any method described herein is greater than 90% (e.g., greater than 95% or greater than 99%). In some embodiments, the amount of calcium in the fluorinating reagent is from about 0.01% by weight to about 15% by weight (wt%). In some embodiments, the method for producing the fluorinating reagent provided herein may further include the step of providing a mixed composition subjected to a fluid composition as a first salt. In some embodiments, the first salt is recovered waste material. In some embodiments, the first salt comprises low-purity calcium and fluoride. In some embodiments, the first salt may contain less than 80% by weight of calcium and fluorine in total.

[0010]

[0010] In some embodiments, the pH of the resulting fluid is adjusted with an acid. In some embodiments, the acid can include strong acids, weak acids, polyprotic acids, and / or combinations thereof. In some embodiments, the acid can include phosphoric acid, hydrochloric acid, boric acid, silicic acid, formic acid, acetic acid, benzoic acid, oxalic acid, sulfuric acid, sulfurous acid, carbonic acid, and / or combinations thereof. In some embodiments, the acid can include hydrochloric acid, phosphoric acid, sulfuric acid, and / or combinations thereof.

[0011]

[0011] In some embodiments, the resulting fluid can be adjusted to a pH of from about 5 to about 10 (e.g., from about 6 to about 9). In some embodiments, the fluid composition has a pH of about 7 or higher (e.g., about 10 or higher). In some embodiments, the fluid composition has a pH of from about 12 to about 13. In some embodiments, the combination of the fluid composition and the mixed composition is at any suitable temperature. In some embodiments, the combination of the fluid composition and the mixed composition is at a temperature of from about zero to about 120 °C. In some embodiments, the combination of the fluid composition and the mixed composition is at a temperature of 80 °C or higher.

[0012]

[0012] In some embodiments, the combination of the fluid composition and the mixed composition is at a temperature of 110 °C or lower. In some embodiments, the mixed composition is subjected to the fluid composition for any suitable time. In some embodiments, the mixed composition is subjected to the fluid composition for from about zero hours to about 8 hours. In some embodiments, the mixed composition is subjected to the fluid composition for about 1 hour or longer. In some embodiments, the mixed composition is subjected to the fluid composition for about 6 hours or shorter. In some embodiments, the mixed composition is subjected to the fluid composition for about 2 hours.

[0013]

[0013] In some embodiments, the fluid composition has a boiling point of about 30°C or higher (e.g., about 70°C or higher, about 120°C or higher). In some embodiments, the fluid composition has a boiling point of about 240°C or lower. In some embodiments, the combination of solvent and fluorinating reagent is at any suitable temperature. In some embodiments, the fluorinating reagent is a crude fluorinating reagent which can be further purified to yield a purified fluorinating reagent. In some embodiments, the fluorinating reagent is a purified fluorinating reagent. In some embodiments, the combination of solvent and fluorinating reagent is at a temperature of about 20 to about 240°C. In some embodiments, the combination of solvent and fluorinating reagent is at a temperature of about 80°C or higher. In some embodiments, the combination of solvent and fluorinating reagent is at a temperature of about 60°C. In some embodiments, the combination of solvent and fluorinating reagent is at a temperature of about 235°C or lower.

[0014]

[0014] In some embodiments, the fluorinating reagent is washed in a solvent for about 4 to about 48 hours (e.g., about 8 to about 36 hours, about 10 to about 28 hours). In some embodiments, the fluorinating reagent is washed in a solvent for about 8 hours or longer. In some embodiments, the fluorinating reagent is washed in a solvent for about 36 hours or shorter. In some embodiments, the fluorinating reagent is washed in a solvent for about 18 hours. In some embodiments, the solvent has a boiling point of about 30°C or higher (e.g., about 70°C or higher, about 120°C or higher). In some embodiments, the solvent has a boiling point of about 240°C or lower. In some embodiments, the solvent is an organic solvent, water, alcohol, polar aprotic solvent, halocarbon, and / or a combination thereof. In some embodiments, the fluid composition is an organic solvent, water, alcohol, polar aprotic solvent, halocarbon, and / or a combination thereof.

[0015]

[0015] In some embodiments, the solvent is acetonitrile, propionitrile, butyronitrile, toluene, 1,2-dichlorobenzene, chlorobenzene, fluorobenzene, 1,2-difluorobenzene, dichloroethane, trifluorotoluene, chloroform, sulfolane, DMF, DMSO, alcohol (e.g., tert-butanol, tert-amyl alcohol), water, and / or combinations thereof. In some embodiments, the fluid composition is acetonitrile, propionitrile, butyronitrile, toluene, 1,2-dichlorobenzene, chlorobenzene, fluorobenzene, 1,2-difluorobenzene, dichloroethane, trifluorotoluene, chloroform, sulfolane, DMF, DMSO, alcohol (e.g., tert-butanol, tert-amyl alcohol), water, and / or combinations thereof. In some embodiments, the solvent is acetonitrile, propionitrile, butyronitrile, and / or combinations thereof.

[0016]

[0016] In some embodiments, the fluid composition is acetonitrile, propionitrile, butyronitrile, and / or a combination thereof. In some embodiments, the second salt is a metal hydroxide, metal sulfite, metal sulfate, carbonate, or inorganic phosphate (e.g., pyrophosphate). In some embodiments, the second salt is NaOH, KOH, Na2SO3, K2SO3, KHSO4, CaCO3, H2CO3, K2CO3, Na2CO3, K4P2O7, Na4P2O7, Na3PO4, Li3PO4, KHCO3, K2CO3, NaHCO3, Cs2CO3, K2HPO4, KH2PO4, K3PO4, KPO3, K5P3O 10 This includes K2SO4, titanium phosphate, aluminum phosphate, uranium phosphate, and / or combinations thereof.

[0017]

[0017] In some embodiments, the methods for producing fluorinating reagents and methods for fluorinating starting reagents provided herein may include a fluorinating reagent having a certain amount of phosphorus. In some embodiments, the fluorinating reagent is a purified fluorinating reagent. In some embodiments, the fluorinating reagent is a crude fluorinating reagent which can be further purified to yield a purified fluorinating reagent. In some embodiments, the amount of phosphorus in the fluorinating reagent is about 1 ppm to 25 ppm (e.g., about 1 ppm to about 10 ppm, about 5 ppm to about 15 ppm, about 10 ppm to about 20 ppm, or about 15 ppm to about 25 ppm). In some embodiments, the amount of phosphorus in the fluorinating reagent is about 0.02 wt% to about 10 wt% (e.g., about 0.05 wt% to about 8 wt%, about 0.1 wt% to about 6 wt%, about 0.5 wt% to about 5 wt%, or about 1 wt% to about 4 wt%). In some embodiments, the amount of phosphorus in the fluorinating reagent is about 0.015 wt% or more (for example, about 0.05 wt% or more, about 0.1 wt% or more, or about 0.5 wt% or more).

[0018]

[0018] In some embodiments, the amount of phosphorus in the fluorinating reagent is about 5% by weight (wt%) or less (e.g., about 3 wt% or less, about 2 wt% or less, about 1 wt% or less, about 0.5 wt% or less, about 0.1 wt% or less, about 0.05 wt% or less). In some embodiments, the powder X-ray diffraction spectrum of the fluorinating reagent includes characteristic 2θ reflectances of about 5.2°, 31.5°, 36.8°, and / or a combination thereof. In some embodiments, the method for producing the fluorinating reagent provided herein may include the fluorinating reagent, in which about 10 to about 80% (e.g., about 30 to about 60%) of the fluoride in the first salt is converted to the fluoride of the fluorinating reagent. In some embodiments, the fluorinating reagent is a purified fluorinating reagent. In some embodiments, the fluorinating reagent is a crude fluorinating reagent, which can be further purified to yield a purified fluorinating reagent.

[0019]

[0019] In some embodiments, the methods for producing fluorinating reagents and methods for fluorinating starting reagents provided herein may include activated fluorinating reagents. In some embodiments, the activated fluorinating reagents may be used in that form as fluorinating agents. In some embodiments, the methods for fluorinating starting reagents provided herein may include starting reagents (e.g., organic compounds).

[0020]

[0020] In some embodiments, the starting reagent may include an organic compound (e.g., an aromatic organic compound). In some embodiments, the organic compound may include 1-chloro-4-nitrobenzene, 1,2-dichloro-4-nitrobenzene, 1,2-dichloro-4-nitrobenzene, 1-chloro-2,4-dinitrobenzene, 1,4-dichloro-2-nitrobenzene, 2-chloro-5-nitropyridine, 2-chloronicotinonitrile, 2,3,5,6-tetrachloroterephthalonitrile, 2,6-dichlorobenzonitrile, pentachloropyridine, 2,3,5,6-tetrachloroterephthalonitrile, 2,6-dichlorobenzonitrile, 2,3,5,6-tetrachloro-4-fluoropyridine, 2,4,6-trichloro-1,3,5-triazine, 1,3-dinitrobenzene, or 2,4-dichloro-1-nitrobenzene. In some embodiments, the at least one additional ion of the purified fluorinating reagent comprises (i) at least one cation and at least one anion; or (ii) at least one zwitterion (e.g., psilocybin). In some embodiments, the at least one cation is K + kaNa + Ca 2+ Li + , or Cs + Includes.

[0021]

[0021] In some embodiments, at least one anion comprises a hydroxide, sulfate, carbonate, phosphate, or pyrophosphate ion. In some embodiments, the fluorinating reagent is brought into contact with the starting reagent under mechanochemical conditions (e.g., ball mill). In some embodiments, the fluorinating reagent is brought into contact with the starting reagent in a reaction mixture. In some embodiments, the reaction mixture comprises a reaction solvent (e.g., organic solvent, water, alcohol, polar aprotic solvent, halocarbon, and / or combination thereof). In some embodiments, the reaction solvent is acetonitrile, DMF, DMSO, sulfolane, and / or combination thereof.

[0022]

[0022] In some embodiments, the reaction mixture further comprises an ammonium salt (e.g., TMAC). In some embodiments, the reaction mixture is at a temperature of about 50 to about 200°C. In some embodiments, the reaction mixture is at a temperature of about 50°C or higher (e.g., about 70°C or higher, about 110°C or higher, about 140°C or higher). In some embodiments, the reaction mixture is refluxed at the reaction temperature. In some embodiments, the reaction temperature and / or reflux temperature is about 100 to about 175°C. In some embodiments, the reaction mixture is stirred in a pressure vessel. In some embodiments, the reaction is carried out in a heated twin-screw extruder. In some embodiments, the fluorinating reagent is contacted with the starting reagent for about 1 hour to about 36 hours (e.g., about 2 hours to about 6 hours, about 12 hours to about 24 hours). In some embodiments, the fluorinating reagent is contacted with the starting reagent for about 24 hours or less (e.g., about 12 hours or less, about 6 hours or less). In some embodiments, the fluorinating reagent is brought into contact with the starting reagent for about 1 hour or longer (e.g., about 2 hours or longer, about 16 hours or longer).

[0023]

[0023] In one embodiment, a composition comprising a fluorinating reagent is provided herein. In some embodiments, the fluorinating reagent is a crude fluorinating reagent which can be further purified to yield a purified fluorinating reagent. In some embodiments, the fluorinating reagent is a purified fluorinating reagent. In some embodiments, the fluorinating reagent comprises an alkali metal, a fluoride, and at least one additional ion. In some embodiments, the alkali metal may include lithium, potassium, or sodium. In some embodiments, the fluorinating reagent may contain a certain amount of phosphorus. In some embodiments, the amount of phosphorus in the fluorinating reagent ranges from 0.015% by weight to about 12.5% ​​by weight (wt%). In some embodiments, the fluorinating reagent can be characterized by at least one of the 2θ values ​​reported in any one of Tables 5, 6A, 8, 9, 12, 15-18, 20, 21, 23, 25-28 (e.g., at least 2, at least 3, at least 5, at least 10, at least 20, at least 50, and / or at least 70). In some embodiments, the fluorinating reagent can be used to fluorinate the starting reagent to provide a fluorinated product.

[0024] In some embodiments, a composition comprising a fluorination reagent provided herein can contain calcium in an amount from about 0.01 wt% to about 15 wt%. In some embodiments, the fluorination reagent can be a crude fluorination reagent that can be further purified to yield a purified fluorination reagent. In some embodiments, the fluorination reagent is a purified fluorination reagent. In some embodiments, the amount of phosphorus in the fluorination reagent is from about 1 ppm to 25 ppm (e.g., from about 1 ppm to about 10 ppm, from about 5 ppm to about 15 ppm, from about 10 ppm to about 20 ppm, or from about 15 ppm to about 25 ppm). In some embodiments, the amount of phosphorus in the fluorination reagent is from about 0.02 wt% to about 10 wt% (e.g., from about 0.05 wt% to about 8 wt%, from about 0.1 wt% to about 6 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 4 wt%). In some embodiments, the amount of phosphorus in the fluorination reagent is about 0.015 wt% or more (e.g., about 0.05 wt% or more, about 0.1 wt% or more, about 0.5 wt% or more). In some embodiments, the amount of phosphorus in the fluorination reagent is about 5 wt% or less (e.g., about 3 wt% or less, about 2 wt% or less, about 1 wt% or less, about 0.5 wt% or less, about 0.1 wt% or less, about 0.05 wt% or less). In some embodiments, at least one additional ion comprises (i) at least one cation and at least one anion, or (ii) at least one zwitterion (e.g., silibinin). In some embodiments, at least one cation is K<> + , Na<> + , Ca<> 2+ , Li<> + , or Cs<> + . In some embodiments, at least one anion comprises ions of hydroxide, sulfate, carbonate, phosphate, pyrophosphate. <> <>

[0025] <>

[0025] Novel features of the present invention are described in particular in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by referring to the following detailed description and the accompanying drawings (hereinafter also referred to as "Figures" and "FIG.") which describe exemplary embodiments in which the principles of the present invention are utilized. [Brief explanation of the drawing]

[0026] [Figure 1]

[0026] An exemplary schematic diagram shows a mechanochemical method for combining one or more salts provided herein to form a mixed composition. [Figure 2]

[0027] An exemplary schematic diagram of the process for producing the fluorinating reagents provided herein is shown. [Figure 3]

[0028] An exemplary schematic diagram of the process for producing the fluorinating reagents provided herein is shown. [Figure 4]

[0029] An exemplary schematic diagram of the process for producing the fluorinating reagents provided herein is shown. [Figure 5]

[0030] An exemplary schematic diagram of the process for producing the fluorinating reagents provided herein is shown. [Figure 6]

[0031] An exemplary schematic diagram is shown of a process for screening various mixed compositions provided herein, having either K+ or Cs+ as a counterion. [Figure 7]

[0032] An exemplary schematic diagram of a process for screening various mixed compositions provided herein that have Na+ as a counterion is shown. Na3PO4 or NaHCO3 was subjected to modification conditions that take into account the resulting decrease in the solubility of the fluorinating reagent in water (increase in the volume of water and decrease in the volume of methanol). [Figure 8]

[0033] An exemplary schematic diagram of a process for screening the mixed compositions provided herein, having Li+ as a counterion derived from Li3PO4, is shown. The mixed compositions were subjected to modification conditions according to the resulting decrease in the solubility of the fluorinating reagent in water. [Figure 9]

[0034] An exemplary schematic diagram of a screening process for producing the fluorinating reagents provided herein at various pH values ​​is shown. [Figure 10]

[0035] An illustrative schematic diagram shows the process for producing the fluorinating reagent provided herein from the first salt provided herein. [Figure 11]

[0036] A simplified, exemplary schematic process for producing the fluorinating reagents provided herein is shown. [Figure 12]

[0037] An illustrative schematic diagram shows a method for fluorinating aromatic compounds using the fluorinating reagents provided herein. [Figure 13]

[0038] A schematic diagram shows a method for fluorinating aromatic compounds using the fluorinating reagents provided herein. [Figure 14]

[0039] An exemplary schematic diagram of the process for producing the fluorinating reagents provided herein is shown. [Modes for carrying out the invention]

[0027] A certain definition

[0040] As used herein and in the appended claims, the singular forms “a,” “an,” and “the” include multiple references unless otherwise explicitly stated by the context. Thus, for example, a reference to “an agent” includes multiple such agents, and a reference to “the cell” includes references to one or more cells (or to more cells) and their equivalents and similars known to those skilled in the art. Where a range is used herein with respect to physical properties such as molecular weight or chemical properties such as chemical formula, it includes all combinations and partial combinations of the range, as well as specific embodiments therein. The term “about” means, when referring to a number or range of numbers, that the number or range referred to is an approximation within the range of experimental variability (or statistical experimental error), and therefore the number or range may vary between 1% and 15% of the number or range referred to. The terms “comprising” (and related terms, e.g., “comprise,” “comprises,” “having,” or “including”) do not preclude, in other particular embodiments, embodiments of any combination of, for example, the substances, compositions, methods, or processes described herein, or similar, from the described features

[0028] Detailed explanation

[0041] This specification provides fluorinating reagents and compositions, as well as methods for preparing and using such fluorinating reagents and compositions. In some cases, such reagents and compositions are useful for producing fluorinated products in high yield and / or without the need to use toxic reagents such as HF.

[0029]

[0042] In some embodiments, a method for producing a fluorinating reagent is provided herein. In certain embodiments, the method includes the steps of (1) combining a first salt containing a fluoride (e.g., and calcium) with a second salt (e.g., in a solid state); and (2) subjecting the combination of the first and second salts to a fluid composition (e.g., aqueous). In some embodiments, the resulting fluid composition is subsequently concentrated (e.g., by evaporation or other suitable method) to produce a fluorinating reagent composition.

[0030]

[0043] In certain embodiments, the fluorinating reagent composition is further washed with a (e.g., organic) solvent (e.g., an alcohol such as methanol) to produce a reagent wash. In certain embodiments, the (e.g., purified) fluorinating reagent composition is recovered from the reagent wash (e.g., after filtering out residual solids from the reagent wash). In some embodiments, the steps of separating the purified fluorinating reagent from the residual solids and / or separating contaminants from the resulting solution may independently include: centrifugation (e.g., using decanter centrifugation and / or disk stack centrifugation), pressure filtration, microfiltration, nanofiltration, ultrafiltration, cross-flow membrane filtration, and / or combinations thereof.

[0031]

[0044] In some embodiments, the crude fluorinating reagent is purified at least partially using a filtration process. In some embodiments, the filtrate is concentrated and / or dried in any step or process of any method described herein. In some embodiments, the filtration process includes passing any solution described herein through the same or more filtration modules multiple times (e.g., by passing through the same module three or more times consecutively, and / or by passing through three consecutively connected modules once each). In some embodiments, the fluorine recovery rate of the filtration process used herein is greater than 90% (e.g., greater than 95%, or greater than 99%). In some embodiments, the removal rate of one or more contaminants by the filtration process used in any method described herein is greater than 90% (e.g., greater than 95%, or greater than 99%). In some embodiments, a method for producing a purified fluorinating reagent, a. A step of combining a first salt containing calcium and fluoride with a second salt to form a mixed composition; b. A step of subjecting the mixed composition to a fluid composition (to produce solid components and the resulting fluid), and collecting the resulting fluid; c. A step of concentrating the resulting fluid to produce a crude fluorinating reagent (e.g., reagent concentrate or precipitate); d. Washing the crude fluorinating reagent with a solvent (e.g., alcohol) to produce a reagent wash (a second solid component and a fluid reagent wash); and e. A step of concentrating the reagent wash to form a purified fluorinating reagent (for example, a purified fluorinating reagent having a higher concentration of fluorine compared to the crude fluorinating reagent). Methods including the above are provided herein.

[0032]

[0045] In a particular embodiment, a method for producing a purified fluorinating reagent: a. A step of combining a first salt containing calcium and fluoride with a second salt to form a mixed composition; b. A step of applying mechanical force to the mixed composition; c. A step of subjecting the mixed composition to a fluid composition (to produce solid components and the resulting fluid), and collecting the resulting fluid; d. A step of concentrating the resulting fluid to produce a crude fluorinating reagent (e.g., reagent concentrate or precipitate); e. Washing the crude fluorinating reagent with a solvent (e.g., alcohol) to produce a reagent wash (a second solid component and a fluid reagent wash); and f. A step in which the reagent wash is concentrated to form a purified fluorinating reagent (for example, a purified fluorinating reagent having a higher concentration of fluorine compared to the crude fluorinating reagent). Methods including the above are provided herein.

[0033]

[0046] In certain embodiments, methods for providing (e.g., preparing, manufacturing, etc.) a composition comprising a reagent or reagent composition are provided herein. In some embodiments, the reagent or reagent composition provided herein is a high-purity and / or low-phosphorus reagent or reagent composition. In some embodiments, the presence of high purity and / or low phosphorus (e.g., a purified fluorinating reagent provided herein) enables the use of a reagent or reagent composition that produces a high yield of fluorination (e.g., compared to a similar reagent / composition having lower purity and / or higher phosphorus content). In certain embodiments, the reagent or reagent composition provided herein provides an improved fluorination rate (e.g., improved by at least about 10%). In certain embodiments, the (e.g., purified) reagent or reagent composition provided herein has a higher fluorine content compared to the (e.g., crude) reagent or reagent composition provided herein. In some embodiments, the (e.g., purified) reagent or reagent composition provides a higher fluorination rate of a starting reagent (e.g., an aromatic compound) compared to the fluorination rate provided by the (e.g., crude) reagent or reagent composition provided herein.

[0034]

[0047] In some embodiments, any reagent or reagent composition provided herein contains a metal (e.g., alkali metal, alkaline earth metal). In certain embodiments, the reagent or reagent composition contains an alkali metal. In certain embodiments, the reagent or reagent composition provided herein contains an alkali metal (e.g., lithium, potassium, or sodium), a fluoride, and (e.g., at least one additional) ions.

[0035]

[0048] In certain embodiments, any composition provided herein contains ions (e.g., at least one additional ions as provided herein). In some embodiments, reagents provided herein (e.g., fluorinating reagents such as purified or crude fluorinating reagents) or (e.g., reagent) compositions (e.g., any reagent or mixed composition used in the preparation of reagents) contain ions (e.g., at least one additional). In certain embodiments, reagents or reagent compositions provided herein contain at least one additional ions. In certain embodiments, compositions provided herein (e.g., salt compositions or salts containing compositions) contain ions (e.g., at least one additional). In certain embodiments, compositions provided herein (e.g., salt compositions or salts containing compositions) contain at least one additional ions.

[0036]

[0049] In some embodiments, the ions provided herein (e.g., at least one additional) include cations, anions, and / or zwitterions. In some embodiments, the cations provided herein (e.g., at least one) include alkali metals, alkaline earth metals, transition metals, other metals, cationic complexes or ligands, or the like. In certain embodiments, the cations provided herein (e.g., at least one) include K + kaNa + , Rb + Ca 2+ Mg 2+ Fe 2+ Fe 3+ Cu + Cu2+ Ag + Li + NH4 + Sr + Ba 2+ Zn 2+ , Cd 2+ , Al 3+ [Co(NH3)6] 3+ Co 3+ Co 2+ , U 2+ , U 4+ , U 6+ Ni 2+ , and / or Cs + In a more specific embodiment, the cation (for example, at least one) is K + kaNa + Ca 2+ Li + , and / or Cs + That is the case.

[0037]

[0050] In certain embodiments, the anions provided herein (e.g., at least one) include ions of hydroxides, sulfates, carbonates, phosphates, pyrophosphates, halides, chlorates, nitrates, carbonates, hydrides, sulfites, or the like. In certain embodiments, the anions provided herein (e.g., at least one) are ions of hydroxides, sulfates, carbonates, phosphates, and / or pyrophosphates.

[0038]

[0051] In certain embodiments, the zwitterions provided herein (e.g., at least one) include amino acids, betaines, sulfamic acids, acids, aromatic compounds, and / or phospholipids. In certain embodiments, the zwitterions provided herein (e.g., at least one) are amino acids, trimethylglycine, cocamidopropyl betaine, sulfamic acids, anthranilic acids, psilocybin, and / or phosphatidylcholine. In even more specific embodiments, the zwitterions provided herein (e.g., at least one) are psilocybin.

[0039]

[0052] In certain embodiments, reagents and reagent compositions having high purity and / or low levels of impurities (e.g., phosphorus, calcium, etc.) are provided herein. In some embodiments, high purity and low phosphorus content enables the use of reagents or reagent compositions that result in high-yield fluorination compared to other reagents or reagent compositions having low purity and / or higher phosphorus content. In certain embodiments, high purity and low calcium content enables the use of reagents or reagent compositions that result in high-yield fluorination compared to other reagents or reagent compositions having low purity and / or higher calcium content. In some cases, low calcium and / or phosphorus content and high purity reagents or reagent compositions enable substantially improved fluorination capabilities.

[0040]

[0053] In some embodiments, any reagent or reagent composition provided herein (and / or produced or used herein) contains a low amount of phosphorus. In certain embodiments, any reagent or reagent composition provided herein (and / or produced or used herein) contains phosphorus in an amount ranging from about 0.015% by weight to about 12.5% ​​by weight (wt%) (w / w). In some embodiments, the reagent or reagent composition provided herein contains phosphorus in an amount of about 0.015% by weight (wt%) or more (e.g., about 0.05 wt% or more, about 0.1 wt% or more, about 0.5 wt% or more). In certain embodiments, the reagent or reagent composition provided herein contains phosphorus in an amount of about 1% by weight or less (e.g., about 1 wt% or less, about 0.5 wt% or less, about 0.1 wt% or less, about 0.05 wt% or less).

[0041]

[0054] In some embodiments, the reagents or reagent compositions provided herein contain phosphorus in an amount of about 0.05% to about 10 wt% (e.g., about 0.1 wt% to about 6 wt%, about 0.5 wt% to about 5 wt%, about 1 wt% to about 4 wt%). In certain embodiments, the reagents or reagent compositions provided herein contain phosphorus in an amount of about 5 wt% or less (e.g., about 3 wt% or less, about 2 wt% or less, about 1 wt% or less, about 0.5 wt% or less, about 0.1 wt% or less).

[0042]

[0055] In certain embodiments, the reagents or reagent compositions provided herein contain phosphorus in an amount of about 0.05 wt% to about 0.2 wt%.

[0056] In some embodiments, any reagent or reagent composition provided herein (and / or produced or used herein) contains a low content of calcium. In certain embodiments, any reagent or reagent composition provided herein (and / or produced or used herein) contains calcium in amounts ranging from about 0.01% by weight to about 15% by weight (wt%) (w / w). In some embodiments, the reagent or reagent composition provided herein contains calcium in amounts ranging from about 0.01% by weight (wt%) or more (e.g., about 0.05 wt% or more, about 0.1 wt% or more, about 0.5 wt% or more, about 1 wt% or more). In certain embodiments, the reagent or reagent composition provided herein contains calcium in amounts ranging from about 2% by weight or less (e.g., about 1 wt% or less, about 0.5 wt% or less, about 0.1 wt% or less, about 0.05 wt% or less).

[0043]

[0057] In some embodiments, the reagents or reagent compositions provided herein contain calcium in an amount ranging from about 0.05 wt% to about 12 wt% (e.g., about 0.1 wt% to about 8 wt%, about 0.5 wt% to about 4 wt%). In certain embodiments, the reagents or reagent compositions provided herein contain calcium in an amount ranging from about 6 wt% or less (e.g., about 4 wt% or less, about 2 wt% or less, about 1 wt% or less, about 0.5 wt% or less, about 0.1 wt% or less, about 0.05 wt% or less).

[0044]

[0058] In certain embodiments, the reagents or reagent compositions provided herein contain calcium in an amount of about 0.01% to about 0.05 wt%.

[0059] In certain embodiments, the powder X-ray diffraction spectrum of the reagent or reagent composition provided herein includes a characteristic 2θ reflectance of about 5.2°. In some embodiments, the powder X-ray diffraction spectrum of the reagent or reagent composition provided herein includes characteristic 2θ reflectances of 5.2°, 31.5°, and / or 36.8°. In certain embodiments, the powder X-ray diffraction spectrum of the reagent or reagent composition provided herein may further include peaks where ±0.2°2θ corresponds to one or more 2θ values ​​from Tables 5, 6A, 8, 9, 12, 14-18, 20, 21, 23, and / or 25-28. In certain embodiments, the powder X-ray diffraction spectrum of the reagent or reagent composition provided herein includes characteristic 2θ reflectances of 5.2°, 31.5°, and 36.8°.

[0045]

[0060] In certain embodiments, any reagent or reagent composition provided herein contains a high content of fluorine. In some embodiments, the fluorine conversion rate (or F conversion rate) refers to the relative proportion or percentage (%) of fluorine from the (e.g., first) salt or salt composition provided herein that is converted into the reagent or reagent composition provided herein. In some embodiments, about 10% to about 80% of the fluorine from the (e.g., first) salt or salt composition provided herein is converted into the (e.g., fluorinated) reagent or reagent composition provided herein. In certain embodiments, about 30% to about 60% of the fluorine from the (e.g., first) salt or salt composition provided herein is converted into the (e.g., fluorinated) reagent or reagent composition provided herein.

[0046]

[0061] In certain embodiments, fluorine wt% or Fwt% refers to the fluorine content by weight in the reagent or reagent composition provided herein. In certain embodiments, fluorine wt% or Fwt% refers to any suitable method (e.g., quantitatively) 19 Fluorine is measured by 14F NMR. In some embodiments, the weight percentage (Fwt%) of fluorine in the reagents or reagent compositions provided herein (e.g., fluorinating reagents) is about 8% to about 75% (e.g., about 10% to about 70%, about 20% to about 60%, about 30% to about 50%, about 45% to about 55%). In certain embodiments, the weight percentage (Fwt%) of fluorine in the reagents or reagent compositions provided herein (e.g., fluorinating reagents) is about 20% or more (e.g., about 30% or more, about 40% or more, about 50% or more, about 60% or more, about 70% or more). In even more specific embodiments, the weight percentage (Fwt%) of fluorine in the reagents or reagent compositions provided herein (e.g., fluorinating reagents) is about 75% or less.

[0047]

[0062] In certain embodiments, the reagents or reagent compositions provided herein (e.g., fluorinated) can be characterized by X-ray powder diffraction (XRPD) using Cu Kα1 (λ=1.5406 Å) and / or Cu Kα2 (λ=1.5444 Å). Due to differences in equipment, samples, and sample preparation, peak values ​​are often reported with the modifier "±0.2°²θ". This is a common practice in the field of solid-state chemistry due to the inherent variability in peak values.

[0048]

[0063] In certain embodiments, a reagent or reagent composition provided herein (e.g., fluorinating) may have an XRPD pattern in which ±0.2°2θ corresponds to at least 1, at least 2, at least 3, at least 5, at least 10, at least 20, at least 50, and / or at least 70 of the 2θ values ​​reported in any one of Tables 5, 6A, 8, 9, 12, 15-18, 20, 21, 23, 25-28 provided herein. In some embodiments, a reagent or reagent composition provided herein (e.g., fluorinating) may have an XRPD pattern in which ±0.2°2θ corresponds to at least 10%, at least 30%, at least 50%, at least 70%, at least 90%, and / or 100% of the 2θ values ​​reported in any one of Tables 5, 6A, 8, 9, 12, 15-18, 20, 21, 23, 25-28 provided herein. In certain embodiments, the reagents or reagent compositions provided herein (e.g., fluorinating reagents) may have an XRPD pattern in which ±0.2°2θ corresponds to at least 30% of the 50 2θ values ​​reported in Table 5 provided herein ((e.g., the reagents or reagent compositions may have an XRPD pattern in which ±0.2°2θ corresponds to at least 15 2θ values ​​modified by ±0.2°2θ in Table 5).

[0049]

[0064] Table 5 shows X-ray powder diffraction using CuKα1 (λ=1.5406 Å) and / or CuKα2 (λ=1.5444 Å) for the reagents or reagent compositions provided herein (e.g., fluorinated reagents) (e.g., mixed composition C provided herein in Example 3B).

[0050]

[0065] In certain embodiments, the method provided herein includes the step of combining a first salt and a second salt.

[0066] In some embodiments, the first salt provided herein contains a fluoride. In certain embodiments, the first salt contains calcium and a fluoride. In some embodiments, the first salt further contains additional ions, such as cations and / or anions provided herein. In certain embodiments, the first salt contains CaF2, Ca5(PO4)3F, and / or combinations thereof.

[0051]

[0067] In some embodiments, the first salt or the composition containing the first salt contains a fluoride. In certain embodiments, the first salt or the composition containing the first salt contains calcium and a fluoride. In some embodiments, the first salt or the composition containing the first salt further contains additional ions, such as cations and / or anions provided herein. In certain embodiments, the first salt or the composition containing the first salt contains CaF2, Ca5(PO4)3F, and / or combinations thereof.

[0052]

[0068] In some embodiments, the first salt provided herein (e.g., the first salt provided herein) or a composition comprising the first salt is supplied from a material having a low value, low purity, such as waste material. In certain embodiments, the first salt provided herein is supplied from waste material (e.g., calcium fluoride). In even more specific embodiments, the composition comprising the first salt provided herein is supplied from waste material. In certain embodiments, a method for producing a reagent or reagent composition together with waste material is provided herein. In some embodiments, the waste material (e.g., the waste material provided herein) includes untreated, processed, and / or treated waste material. In certain embodiments, the waste material provided herein is (e.g., recovered) waste product (e.g., supplied from an industrial process). In some embodiments, the waste material herein is (e.g., recovered) waste product from an industrial process, such as semiconductor manufacturing, fluorochemical manufacturing, pharmaceutical manufacturing, or similar. In certain embodiments, the waste materials provided herein include fluorine (or fluorinated salts), fluorinated lime, calcium fluoride (e.g., in low purity), CFC-12, per- and polyfluoroalkyl substances (PFAs), or similar. In certain embodiments, the waste materials provided herein include fluorine or fluorinated salts (e.g., in low purity). In even more specific embodiments, the waste materials provided herein include fluorine and calcium (e.g., in low purity). In certain cases, the waste materials provided herein may be used as untreated, processed, or treated waste materials to provide the reagents or reagent compositions provided herein.

[0053]

[0069] In certain embodiments, the first salt or the composition containing the first salt contains calcium and fluoride in an amount of about 20% or less, combined. In some embodiments, the first salt or the composition containing the first salt contains calcium and fluoride in an amount of about 30% or less, combined. In certain embodiments, the first salt or the composition containing the first salt contains calcium and fluoride in an amount of about 40% or less, combined. In certain embodiments, the first salt or the composition containing the first salt contains calcium and fluoride in an amount of about 50% or less, combined. In some embodiments, the first salt or the composition containing the first salt contains calcium and fluoride in an amount of about 60% or less, combined. In some embodiments, the first salt or the composition containing the first salt contains calcium and fluoride in an amount of about 70% or less, combined. In some embodiments, the first salt or a composition containing the first salt contains calcium and fluoride in a combined amount of about 80% or less.

[0054]

[0070] In certain embodiments, the first salt contains about 20% or less of calcium and fluoride combined. In some embodiments, the first salt contains about 30% or less of calcium and fluoride combined. In certain embodiments, the first salt contains about 40% or less of calcium and fluoride combined. In certain embodiments, the first salt contains about 50% or less of calcium and fluoride combined. In some embodiments, the first salt contains about 60% or less of calcium and fluoride combined. In some embodiments, the first salt contains about 70% or less of calcium and fluoride combined. In some embodiments, the first salt contains about 80% or less of calcium and fluoride combined.

[0055]

[0071] In some embodiments, the second salt as provided herein (e.g., the second salt provided) comprises a metal such as an alkali metal or alkaline earth metal. In certain embodiments, the second salt comprises a metal (e.g., an alkali metal or alkaline earth metal) and an anion (e.g., ions of phosphates, hydroxides, sulfates, carbonates, and / or sulfites). In some embodiments, the second salt comprises sodium, lithium, cesium, potassium, and / or combinations thereof. In certain embodiments, the second salt further comprises phosphates (e.g., inorganic phosphates or pyrophosphates, etc.), hydroxides, carbonates, sulfites, and / or sulfates. In certain embodiments, the second salt comprises NaOH, Na2SO3, K2SO3, KOH, KHSO4, K2HPO4, KH2PO4, K3PO4, Na3PO4, Li3PO4, K2CO3, Na2CO3, NaHCO3, Cs2CO3, K2SO4, KPO3, K5P3O 10 These include K4P2O7, Na4P2O7, titanium phosphate, aluminum phosphate, uranium phosphate, and / or one or more combinations thereof. In some embodiments, the second salt further comprises additional ions, such as cations and / or anions provided herein.

[0056]

[0072] In some embodiments, the second salt or the composition containing the second salt contains a metal such as an alkali metal or alkaline earth metal. In certain embodiments, the second salt or the composition containing the second salt contains a metal (e.g., an alkali metal or alkaline earth metal) and anions (e.g., ions of phosphates, hydroxides, sulfates, carbonates, and / or sulfites). In some embodiments, the second salt or the composition containing the second salt contains sodium, lithium, cesium, potassium, and / or combinations thereof. In certain embodiments, the second salt further comprises phosphates (e.g., inorganic phosphates or pyrophosphates), hydroxides, carbonates, sulfites, and / or sulfates. In certain embodiments, a composition containing a second salt or a second salt may include NaOH, Na2SO3, K2SO3, KOH, KHSO4, K2HPO4, KH2PO4, K3PO4, Na3PO4, Li3PO4, K2CO3, Na2CO3, NaHCO3, Cs2CO3, K2SO4, KPO3, and K5P3O 10 These include K4P2O7, Na4P2O7, titanium phosphate, aluminum phosphate, uranium phosphate, and / or one or more combinations thereof. In some embodiments, the second salt or the composition comprising the second salt further comprises additional ions, such as cations and / or anions provided herein.

[0057]

[0073] In some embodiments, compositions or methods are provided herein that include the step of combining a first salt (or a composition containing the first salt) with a second salt (or a composition containing the second salt) (for example, the first or second salt provided herein). In certain embodiments, the ratio of a first ion in the first salt (or a composition containing the first salt) provided herein to a second ion in the second salt (or a composition containing the second salt) provided herein is about 0.1:5 to about 5:0.1. In certain embodiments, the ratio of a first ion in the first salt (or a composition containing the first salt) to a second ion in the second salt (or a composition containing the second salt) is about 1:1. In even more specific embodiments, the ratio of a first ion in the first salt (or a composition containing the first salt) to a second ion in the second salt (or a composition containing the second salt) is about 1:2.

[0058]

[0074] In certain embodiments, the first salt (or a composition containing the first salt) and the second salt (or a composition containing the second salt) of any method provided herein are combined by any suitable method (e.g., thereby providing the mixed composition described herein). In some embodiments, both the first salt (or a composition containing the first salt) and the second salt (or a composition containing the second salt) are combined as solid components. In certain embodiments, the first salt (or a composition containing the first salt) and the second salt (or a composition containing the second salt) are combined to form a combination of solid salts. In some embodiments, the method provided herein includes the step of applying mechanical force to the mixed composition provided herein (e.g., including the first salt or a composition containing the first salt, and the second salt or a composition containing the second salt). In certain embodiments, any suitable mechanical force provided herein is used.

[0059]

[0075] In certain embodiments, the composition (e.g., a mixture) provided herein comprises a first salt. In certain embodiments, the first salt comprises a fluoride. In certain embodiments, the first salt comprises calcium and a fluoride. In certain embodiments, the composition (e.g., a mixture) provided herein comprises a second salt.

[0060]

[0076] In certain embodiments, mechanical force (e.g., mechanical force provided herein) includes any suitable mechanical force, such as by using a ball mill, planetary mill, mortar and pestle, twin-screw extruder, attritor, drum mill, ultrasonic bath, mechanical press, and / or a combination of one or more of these. In certain embodiments, mechanical force is applied using a high-shear mixer, in-line homogenizer, one or more bead mills, and / or a combination thereof. In certain embodiments, mechanical force provided herein is provided by a ball mill. In some embodiments, mechanical force is applied by increasing the pressure in a sealed tank (e.g., to a value greater than 100, 200, or 2000 kPa). In some embodiments, the ball mill provided herein includes a jar and balls (e.g., weighing from about 1 g to about 20 g). In certain embodiments, a first (e.g., salt) composition and a second (e.g., salt) composition provided herein are combined in a jar and balls are added. In some embodiments, the mechanical force provided herein is provided by a twin-screw extruder, for example, by extruding combinations of compositions (e.g., salt) provided herein at various screw speeds, screw temperatures, or residence times. The twin-screw extruder provided herein is equipped with a gravimetric single-screw feeder (e.g., a hopper) for programmed addition of the compositions (e.g., salt) provided herein.

[0061]

[0077] In certain embodiments, the mechanical force is applied under any suitable conditions, such as selected or varying frequencies, time, temperature, or cycles. In some embodiments, the mechanical force provided herein is applied at a frequency from about 0.5 Hz to about 60 kHz (e.g., from about 10 Hz to about 20 kHz). In certain embodiments, the mechanical force provided herein is applied at a frequency of about 5 Hz or greater (e.g., about 10 Hz or greater, about 20 Hz or greater, about 30 Hz or greater). In certain embodiments, the mechanical force provided herein is applied at about 35 Hz. In certain embodiments, the mechanical force provided herein is applied over a period of about 1 cycle to about 50 cycles (e.g., about 5 to about 40 cycles, about 10 to about 30 cycles). In some embodiments, the mechanical force provided herein is applied for a period of 1 cycle or longer. In certain embodiments, the mechanical force provided herein is applied over a period of 10 cycles. In some embodiments, the mechanical force is applied to one or more compositions in the solution phase. In some embodiments, a mechanical force is applied to one or more compositions in the solid phase.

[0062]

[0078] In certain embodiments, the mechanical force provided herein is applied at a temperature of about 20 to about 300°C (e.g., about 50 to about 250°C, about 100 to about 200°C). In some embodiments, the mechanical force provided herein is applied at a temperature of about 20°C or higher (e.g., about 50°C or higher, about 100°C or higher, about 150°C or higher). In some embodiments, the reaction mixture is refluxed at the reaction temperature. In some embodiments, the reaction temperature and / or reflux temperature is about 100 to about 175°C. In some embodiments, the reaction mixture is stirred in a pressure vessel. In some embodiments, the reaction is carried out in a heated twin-screw extruder. In certain embodiments, the mechanical force provided herein is applied at a temperature of about 25°C (e.g., room temperature).

[0063]

[0079] In certain embodiments, the mechanical force provided herein is applied for about 5 minutes to about 3 hours (e.g., about 10 minutes to about 2.5 hours, about 20 minutes to about 2 hours, about 30 minutes to about 1.5 hours). In some embodiments, the mechanical force provided herein is applied for about 5 minutes or longer (e.g., about 15 minutes or longer, about 30 minutes or longer, about 45 minutes or longer, about 1 hour or longer, about 2 hours or longer). In certain embodiments, the mechanical force provided herein is applied for about 45 minutes.

[0064]

[0080] In some cases, by varying the time, frequency, temperature, and / or similar of the mechanical force (e.g., the mechanical force provided herein), high yields of reagents (e.g., fluorinating reagents such as purified or crude fluorinating reagents) or compositions (e.g., any reagent or mixed composition such as those used in the preparation of reagents) provided herein are available.

[0065]

[0081] In certain embodiments, the method provided herein includes the step of combining a first composition comprising a first salt and a second composition comprising a second salt. In more specific embodiments, the first and / or second compositions are waste materials provided herein (e.g., untreated, processed, or treated waste materials).

[0066]

[0082] In some embodiments, compositions or methods are provided herein that include the step of subjecting a (e.g., mixed) composition to a (e.g., fluid) composition. In certain embodiments, a (e.g., mixed) composition of any method provided herein is subject to a (e.g., fluid) composition (e.g., thereby forming a reagent or reagent composition as described herein). In some embodiments, a (e.g., mixed) composition is subject to a (e.g., fluid) composition by any suitable conditions, for example, at any selected temperature, by stirring or by other means, at any selected pH (e.g., using a buffer), over any selected period of time, etc.

[0067]

[0083] In certain embodiments, the (e.g., fluid) composition provided herein comprises any suitable solvent. In certain embodiments, the fluid composition (e.g., the fluid composition provided herein) comprises a solvent. In certain embodiments, the fluid composition provided herein comprises any suitable solvent (e.g., water or an organic solvent). In certain embodiments, the fluid composition provided herein comprises a solvent (e.g., water).

[0068]

[0084] In some embodiments, the solvent (e.g., the solvents provided herein) is any suitable solvent, such as polar aprotic solvents, water, alcohols, halocarbons, and / or combinations thereof. In certain embodiments, the solvents provided herein are acetonitrile, propionitrile, butyronitrile, toluene, 1,2-dichlorobenzene, chlorobenzene, fluorobenzene, 1,2-difluorobenzene, dichloroethane, trifluorotoluene, chloroform, sulfolane, DMF, DMSO, tert-butanol, tert-amyl alcohol, water, and / or combinations thereof.

[0069]

[0085] In some embodiments, the solvents provided herein are selected according to their characteristics, such as boiling point, ability to solubilize the compositions provided herein, polarity, pH, or the like.

[0070]

[0086] In certain embodiments, the solvents provided herein have a boiling point of about 30°C or higher. In some embodiments, the solvents provided herein have a boiling point of about 70°C or higher. In certain embodiments, the solvents or (e.g., fluid) compositions provided herein have a boiling point of about 120°C or higher. In some embodiments, the solvents or (e.g., fluid) compositions provided herein have a boiling point of about 240°C or lower.

[0071]

[0087] In some embodiments, the (e.g., mixed) composition provided herein is subjected to the (e.g., fluid) composition provided herein for about 0 to about 8 hours. In certain embodiments, the (e.g., mixed) composition is subjected to the (e.g., fluid) composition for about 1 hour or longer. In some embodiments, the (e.g., mixed) composition is subjected to the (e.g., fluid) composition for about 6 hours or shorter. In certain embodiments, the (e.g., mixed) composition is subjected to the (e.g., fluid) composition for about 2 hours.

[0072]

[0088] In certain embodiments, the combination of the (e.g., mixed) composition and the (e.g., fluid) composition provided herein is at a temperature of about 0 to about 120°C. In some embodiments, the combination of the (e.g., mixed) composition and the (e.g., fluid) composition is at a temperature of about 80°C or higher. In certain embodiments, the combination of the (e.g., mixed) composition and the (e.g., fluid) composition is at a temperature of about 110°C or lower. In some cases, the selected temperature of the combination of the (e.g., mixed) composition and the (e.g., fluid) composition provided herein increases the yield of the reagent or reagent composition provided herein.

[0073]

[0089] In certain embodiments, the (e.g., mixed) compositions provided herein are supplied to the (e.g., fluid) compositions at a selected pH of about 3 to about 12. In some embodiments, the pH of the (e.g., fluid) compositions provided herein can be modified by any suitable method (e.g., by using a buffer). In certain embodiments, the selected pH is about 4 or higher. In some embodiments, the selected pH is about 7 or higher. In certain embodiments, the selected pH is about 10 or higher.

[0074]

[0090] In certain embodiments, a composition (e.g., a mixture) of any method provided herein is subjected to a composition (e.g., a fluid) provided herein, thereby forming a fluid (e.g., including a crude reagent or reagent composition, which can be further purified to yield a purified reagent or reagent composition) and a washed (e.g., mixed) composition. In some embodiments, the washed (e.g., mixed) composition is solid. In certain embodiments, the resulting fluid includes a reagent or reagent composition as described herein. In certain embodiments, the resulting fluid includes a crude reagent or reagent composition provided herein.

[0075]

[0091] In certain embodiments, the methods provided herein include the step of adjusting the pH of the fluid described herein (e.g., the resulting fluid) (e.g., by any suitable method). In some embodiments, the pH of the resulting fluid of any method provided herein is adjusted (e.g., using acids, bases, and / or buffers).

[0076]

[0092] In certain embodiments, the pH of the resulting fluid provided herein is adjusted to a pH of about 5 to about 10. In some embodiments, the pH of the resulting fluid is adjusted to a pH of about 6 to about 9. In certain embodiments, the pH of the resulting fluid is adjusted to a pH of about 6 to about 8 (e.g., thereby neutralizing the resulting fluid). In certain embodiments, the pH of the resulting fluid is adjusted based on the presence of alkaline impurities in the first salt (e.g., to a pH of about 6). In certain embodiments, the pH of the resulting fluid is adjusted to a pH suitable for one or more downstream processes described herein (e.g., the pH may be adjusted to about 7, about 8, or about 9 for processes requiring a neutral or slightly basic solution, such as when using a pH-sensitive filter medium). In some cases, the pH of the resulting fluid is adjusted for compatibility with one or more ion exchange columns and / or for separation in such ion exchange columns.

[0077]

[0093] In some embodiments, the pH of the resulting fluid provided herein is adjusted to a pH of about 8 to about 14. In certain embodiments, the pH of the resulting fluid is adjusted to a pH of about 12 to about 13.

[0078]

[0094] In certain embodiments, the pH of the fluid provided herein (e.g., the resulting fluid) is adjusted with any suitable acid or base. In some embodiments, the pH of the resulting fluid is adjusted (e.g., neutralized) with an acid (e.g., polyproton). In certain embodiments, the resulting fluid described herein is neutralized.

[0079]

[0095] In certain embodiments, the acid (e.g., the acid provided herein) is any suitable acid, such as a strong acid, a weak acid, a polyprotonic acid, and / or a combination thereof. In some embodiments, the acid provided herein is phosphoric acid, hydrochloric acid, formic acid, acetic acid, sulfuric acid, sulfurous acid, carbonic acid, benzoic acid, boric acid, silicic acid, oxalic acid, and / or a combination thereof. In certain embodiments, the use of a polyprotonic acid (e.g., phosphoric acid) provided herein avoids the release of additional anions.

[0080]

[0096] In certain embodiments, the base (e.g., the bases provided herein) is any suitable base, such as a strong base, a weak base, an organic base, or the like. In some embodiments, the bases provided herein include hydroxides, amines, ammonia, pyridine, and / or combinations thereof. In certain embodiments, the bases provided herein are NaOH, KOH, or LiOH. In certain embodiments, the base provided herein is KOH.

[0081]

[0097] In certain embodiments, the washed (e.g., mixed) composition comprises a salt (e.g., a first salt as described herein). In some embodiments, the method provided herein comprises the step of combining the washed (e.g., mixed) composition with a second salt as provided herein (e.g., thereby forming a mixed composition as described herein). In certain embodiments, the mixed composition provided herein comprises a washed (e.g., mixed) composition. In certain embodiments, the washed (e.g., mixed) composition described herein is provided as a first salt as provided herein (e.g., thereby providing a sustainable manufacture of the reagent or reagent composition as described herein). In some cases, the step of providing the washed (e.g., mixed) composition described herein as a first salt in the method and composition described herein provides a sustainable manufacture of the reagent or reagent composition. In some cases, the step of providing the washed (e.g., mixed) composition described herein as a first salt in the method and composition described herein reduces the cost of waste disposal and / or the cost of manufacturing the reagent or reagent composition as described herein.

[0082]

[0098] In certain embodiments, a composition or method is provided herein that includes a step of concentrating the resulting fluid described herein (e.g., a reagent or reagent composition such as those described herein). In some embodiments, the resulting fluid provided herein is concentrated by any suitable method and / or to any suitable endpoint provided herein. In certain embodiments, the step of concentrating the resulting fluid described herein results in a (e.g., crude) reagent or reagent composition (e.g., a reagent concentrate or precipitate). In certain embodiments, the step of concentrating the resulting fluid described herein results in a crude reagent or reagent composition (e.g., a reagent concentrate or precipitate). In even more specific embodiments, the (e.g., crude) reagent or reagent composition is useful for fluorinating an organic compound provided herein (e.g., a starting reagent).

[0083]

[0099] In certain embodiments, any suitable concentration method is used, such as drying, freeze-drying, evaporation (e.g., using a rotary evaporator), distillation, or similar methods. In some embodiments, any fluid or washing solution provided herein is concentrated to any suitable endpoint (e.g., about 10% or greater). In certain embodiments, the resulting fluid described herein is concentrated by drying, evaporation, and / or a combination thereof. In even more specific embodiments, the resulting fluid described herein is concentrated under reduced pressure. In even more specific embodiments, the resulting fluid described herein is concentrated under reduced pressure, thereby providing the (e.g., crude) reagent or reagent composition provided herein.

[0084]

[0100] In some embodiments, alternative concentration methods may be performed before, during, after, or instead of drying, freeze-drying, evaporation, distillation, or similar methods. In some embodiments, alternative concentration methods include reverse osmosis, ultra-high pressure reverse osmosis, drip-film evaporation, agitated thin-film evaporation, spray drying, and / or any combination of two or more of these (e.g., up to a combination of all of these methods, and combinations of all of these methods).

[0085]

[0101] In some embodiments, compositions or methods are provided herein that include the step of washing a (e.g., crude) reagent or reagent composition with a (e.g., solvent) composition. In certain embodiments, the (e.g., solvent) composition is any suitable solvent. In some embodiments, the (e.g., solvent) composition is any (e.g., organic) solvent provided herein. In certain embodiments, a (e.g., crude) reagent or reagent composition of any method provided herein is washed with a (e.g., organic) solvent (e.g., thereby forming a reagent or reagent composition such as those described herein). In some embodiments, a (e.g., crude) reagent or reagent composition provided herein is washed with a (e.g., organic) solvent under any suitable conditions, e.g., at a target temperature, with any selected volume of the fluid composition, with agitation or other means, at any selected pH (e.g., using a buffer), at any selected temperature, for any selected period of time, or under similar conditions. In certain embodiments, a (e.g., crude) reagent or reagent composition provided herein is washed with an organic solvent (e.g., alcohol).

[0086]

[0102] In some embodiments, the (e.g., crude) reagents or reagent compositions provided herein are washed with a (e.g., organic) solvent for about 4 to about 48 hours. In certain embodiments, the (e.g., crude) reagents or reagent compositions provided herein are washed with a (e.g., organic) solvent for about 8 to about 36 hours. In some embodiments, the (e.g., crude) reagents or reagent compositions provided herein are washed with a (e.g., organic) solvent for about 10 to about 28 hours. In certain embodiments, the (e.g., crude) reagents or reagent compositions provided herein are washed with a (e.g., organic) solvent for about 8 hours or longer. In some embodiments, the (e.g., crude) reagents or reagent compositions provided herein are washed with a (e.g., organic) solvent for 36 hours or less. In certain embodiments, the (e.g., crude) reagents or reagent compositions provided herein are washed with a (e.g., organic) solvent for about 18 hours.

[0087]

[0103] In certain embodiments, the combination of (e.g., crude) reagents or reagent compositions and (e.g., organic) solvents provided herein is at a temperature of about -20 to about 240°C. In some embodiments, the combination of (e.g., crude) reagents or reagent compositions and (e.g., organic) solvents is at a temperature of about 80°C or higher. In certain embodiments, the combination of (e.g., crude) reagents or reagent compositions and (e.g., organic) solvents is at a temperature of about 235°C or lower.

[0088]

[0104] In some embodiments, a (e.g., crude) reagent or reagent composition of any method provided herein is washed with a (e.g., organic) solvent described herein, thereby providing a reagent wash (e.g., a fluid reagent wash) and a washed (e.g., reagent) composition. In certain embodiments, a (e.g., crude) reagent or reagent composition of any method provided herein is washed with a (e.g., organic) solvent, thereby yielding a reagent wash (e.g., including a (e.g., purified) reagent or reagent composition). In some embodiments, the (e.g., fluid) reagent wash includes a reagent or reagent composition as described herein. In certain embodiments, the (e.g., fluid) reagent wash includes a purified reagent or reagent composition provided herein.

[0089]

[0105] In certain embodiments, a composition or method is provided herein that includes a step of concentrating a reagent wash (e.g., a fluid) as described herein (e.g., thereby forming a reagent or reagent composition as described herein). In some embodiments, the reagent wash (e.g., a fluid) provided herein is concentrated by any suitable method provided herein and / or to any suitable endpoint. In certain embodiments, the step of concentrating the reagent wash (e.g., a fluid) provided herein yields and / or produces a (e.g., purified) reagent or reagent composition (e.g., a reagent wash concentrate or reagent precipitate). In certain embodiments, the (e.g., purified) reagent or reagent composition is useful for fluorinating an organic compound (e.g., a starting reagent) provided herein.

[0090]

[0106] In certain embodiments, the reagents or reagent compositions provided herein are activated so that they can be used to fluorinate (e.g., fluorinate) a starting reagent (e.g., an organic compound) in which they take form. In some embodiments, any reagent or reagent composition provided herein includes a fluorinating reagent or reagent composition. In certain embodiments, a (e.g., crude) reagent or reagent composition provided herein includes a fluorinating reagent or reagent composition provided herein. In even more specific embodiments, a (e.g., purified) reagent or reagent composition provided herein includes a fluorinating reagent or reagent composition provided herein.

[0091]

[0107] In certain embodiments, a method for fluorinating a starting reagent (e.g., an organic compound) is provided herein. In some embodiments, the starting reagent (e.g., the starting reagent provided herein) is an organic compound. In certain embodiments, the starting reagent provided herein is an aromatic organic compound. In certain embodiments, the starting reagent provided herein contains a leaving group (e.g., chlorine, iodine, bromine, nitro). In certain embodiments, the leaving group of the starting reagent provided herein is chlorine. In even more specific embodiments, the leaving group of the starting reagent is nitro. In some embodiments, the starting reagent (e.g., the starting reagent provided herein) contains an aliphatic and / or aromatic organic compound substituted with one or more halogens selected from the group Cl, Br, and I, or the same. In certain embodiments, the starting reagent includes haloaromatics (e.g., chloroaromatics), haloalkyl compounds (e.g., monohaloalkyl compounds, dihaloalkyl compounds, trihaloalkyl compounds), chlorobenzenes, and haloheteroaromatics, each compound which may be optionally substituted with an electron-withdrawing group (e.g., CN, nitro, or the same). In some embodiments, the starting reagents provided herein are 1-chloro-4-nitrobenzene, 1,2-dichloro-4-nitrobenzene, 1,2-dichloro-4-nitrobenzene, 1-chloro-2,4-dinitrobenzene, 1,4-dichloro-2-nitrobenzene, 2-chloro-5-nitropyridine, 2-chloronicotinonitrile, 2,3,5,6-tetrachloroterephthalonitrile, 2,6-dichlorobenzonitrile, pentachloropyridine, 2,3,5,6-tetrachloro-4-fluoropyridine, 2,4,6-trichloro-1,3,5-triazine, 1,3-dinitrobenzene, and / or 2,4-dichloro-1-nitrobenzene.

[0092]

[0108] In some cases, the reagents or reagent compositions provided herein are used to fluorinate starting reagents provided herein in order to provide high-value, high-yield fluorinating reagents without using toxic chemicals such as HF.

[0093]

[0109] In certain embodiments, compositions or methods are provided herein that include the step of contacting a starting reagent provided herein with a reagent or reagent composition described herein (for example, fluorinating the starting reagent to provide a fluorinated product). In some embodiments, the starting reagent provided herein, which is contacted with the reagent or reagent composition provided herein, provides a fluorinated (e.g., organic) compound (e.g., a fluorinated product provided herein). In some embodiments, the starting reagent is contacted with the reagent or reagent composition at any selected temperature, with or without stirring, at any selected pH, for any selected period of time, or under any suitable conditions such as the like.

[0094]

[0110] In certain embodiments, the combination of the reagent or reagent composition and the starting reagent is at a temperature of about 50 to about 200°C. In some embodiments, the combination of the reagent or reagent composition and the starting reagent is at a temperature of about 50°C or higher. In certain embodiments, the combination of the reagent or reagent composition and the starting reagent is at a temperature of about 70°C or higher. In some embodiments, the combination of the reagent or reagent composition and the starting reagent is at a temperature of about 110°C or higher. In certain embodiments, the combination of the reagent or reagent composition and the starting reagent is at a temperature of about 140°C or higher. In certain embodiments, the combination of the reagent or reagent composition and the starting reagent is at a temperature of about 80°C. In even more specific embodiments, the combination of the reagent or reagent composition and the starting reagent is at a temperature of about 150°C. In more specific embodiments, the combination of the (e.g., fluorinating) reagent or reagent composition and the starting reagent is at a temperature of about 120°C.

[0095]

[0111] In certain embodiments, the starting reagent is contacted with the reagent (e.g., fluorinating) or reagent composition for about 1 to 36 hours (e.g., about 2 to 6 hours, about 12 to 24 hours). In some embodiments, the starting reagent is contacted with the reagent (e.g., fluorinating) or reagent composition for about 24 hours or less (e.g., about 12 hours or less, about 6 hours or less). In certain embodiments, the starting reagent is contacted with the reagent (e.g., fluorinating) or reagent composition for about 1 hour or more (e.g., about 2 hours or more, about 16 hours or more). In certain embodiments, the starting reagent is contacted with the reagent (e.g., fluorinating) or reagent composition for about 3 hours. In even more specific embodiments, the starting reagent is contacted with the reagent (e.g., fluorinating) or reagent composition for about 18 hours.

[0096]

[0112] In certain embodiments, the amount of reagent or reagent composition to be brought into contact with the starting reagent is calculated based at least in part on the number of fluorine atoms that will be added to the starting reagent to obtain the resulting fluorinated compound (e.g., the fluorinated product provided herein). In some embodiments, the amount of the reagent or reagent composition provided herein (e.g., fluorinated) is the number of fluorine atoms that will be added multiplied by about 0.5 to about 10 equivalents of the starting reagent. In certain embodiments, the amount of reagent or reagent composition contains about 1 equivalent or more per fluorine atom that will be added. In even more specific embodiments, the amount of reagent or reagent composition contains about 1.5 equivalents or more per fluorine atom that will be added. In even more specific embodiments, the amount of reagent or reagent composition contains about 2 equivalents per fluorine atom that will be added.

[0097]

[0113] In some embodiments, a starting reagent provided herein (e.g., an aromatic organic compound) is brought into contact with a reagent or reagent composition provided herein (e.g., a fluorinating reagent) under mechanochemical conditions that provide a fluorinated (e.g., organic) compound. In certain embodiments, any suitable mechanical force is used as provided herein and under any suitable conditions provided herein. In even more specific embodiments, a starting reagent (e.g., a starting reagent provided herein) is combined with a reagent or reagent composition provided herein (e.g., a fluorinating reagent) in a laboratory mixer mill (e.g., milled at 35 Hz for 2 hours) to obtain a fluorinated compound.

[0098]

[0114] In certain embodiments, a starting reagent (e.g., an aromatic organic compound) is brought into contact with a reagent or reagent composition (e.g., a fluorinating agent) provided herein in a reaction mixture. In some embodiments, the reaction mixture provided herein comprises a starting reagent (e.g., an aromatic organic compound), a reagent or reagent composition (e.g., a fluorinating agent), and a reaction (e.g., an organic) solvent. In certain embodiments, the reaction solvent is any suitable solvent (e.g., an organic solvent) provided herein. In certain embodiments, the reaction solvent is DMSO, acetonitrile, DMF, and / or sulfolane.

[0099]

[0115] In some embodiments, the starting reagent is brought into contact with the reagent or reagent composition (e.g., fluorinating) together with a reaction solvent of any selected constitution. In certain embodiments, the reaction mixture provided herein further comprises an ammonium salt. In certain embodiments, the reaction mixture provided herein comprises a starting reagent (e.g., an aromatic organic compound), a reagent or reagent composition (e.g., fluorinating), a reaction (e.g., an organic) solvent, and an ammonium salt. In certain embodiments, the ammonium salt provided herein includes ammonium sulfate, ammonium bicarbonate, ammonium chloride (e.g., tetramethylammonium chloride (TMAC)), ammonium iodide, ammonium benzoate, benzyltrimethyl, ammonium hydroxide, ammonium carbonate, ammonium dichromate, ammonium acetate, ammonium bromide, sodium tetradecyl sulfate, and / or combinations thereof, and ammonium iodide. In certain embodiments, the ammonium salt provided herein is TMAC. In some cases, the addition of an ammonium salt to the reaction mixture (e.g., the reaction mixture provided herein) results in a high yield of the fluorinated product (e.g., the fluoride provided herein).

[0100]

[0116] In certain embodiments, the amount of ammonium salt (e.g., ammonium salts provided herein) is about 0 to about 5 equivalents of the starting reagent provided herein (e.g., about 0.5 to about 4 equivalents, about 1 to about 3 equivalents). In some embodiments, the amount of ammonium salt is about 0.5 equivalents or more of the starting reagent (e.g., about 0.75 equivalents or more, about 1 equivalent or more, about 2 equivalents or more, about 3 equivalents or more). In certain embodiments, the amount of ammonium salt is about 4 equivalents or less of the starting reagent (e.g., about 3 equivalents or less, about 2 equivalents or less, about 1 equivalent or less, about 0.5 or less). In certain embodiments, the amount of ammonium salt is about 1 equivalent of the starting material.

[0101]

[0117] In certain embodiments, the reaction mixture provided herein further comprises a scavenger (e.g., a scavenger provided herein). In certain embodiments, the reaction mixture provided herein comprises a starting reagent (e.g., an aromatic organic compound), a (e.g., fluorinating) reagent or reagent composition, a reaction (e.g., an organic) solvent, and a scavenger. In certain embodiments, the scavenger comprises phthaloyl chloride.

[0102]

[0118] In certain embodiments, the amount of the scavenger (e.g., the scavenger provided herein) is about 0 to about 5 equivalents of the starting reagent provided herein (e.g., about 0.5 to about 4 equivalents, about 1 to about 3 equivalents). In some embodiments, the amount of the scavenger is about 0.5 equivalents or more of the starting reagent (e.g., about 0.75 equivalents or more, about 1 equivalent or more, about 2 equivalents or more, about 3 equivalents or more). In certain embodiments, the amount of the scavenger is about 4 equivalents or less of the starting reagent (e.g., about 3 equivalents or less, about 2 equivalents or less, about 1 equivalent or less, about 0.5 equivalents or less). In certain embodiments, the amount of the scavenger is about 1 equivalent of the starting reagent.

[0103]

[0119] In certain embodiments, a starting reagent provided herein, when contacted with a reagent or reagent composition provided herein (e.g., fluorinating), fluorinates the starting reagent and provides a fluorinated product (e.g., a fluorinated aromatic compound). In some embodiments, the leaving group (e.g., chlorine) of the starting reagent provided herein is replaced with fluorine. In certain embodiments, the step of contacting the starting reagent with a reagent or reagent composition provided herein (e.g., fluorinating) provides a fluorinated product in a yield of about 10% or higher (e.g., about 20% or higher, about 30% or higher, about 40% or higher, about 50% or higher, about 60% or higher, about 70% or higher, about 80% or higher, about 90% or higher). In certain embodiments, the yield of the fluorinated product provided herein is about 10% to about 95% (e.g., about 20% to about 80%, about 30% to about 70%, about 40% to about 60%).

[0104]

[0120] In some embodiments, the fluorinated products provided herein include haloarochemicals (e.g., fluoroarochemicals), haloalkyl compounds (e.g., monohaloalkyl compounds, dihaloalkyl compounds, trihaloalkyl compounds), fluorobenzenes, and haloheteroarochemicals, each of which may be optionally substituted with electron-withdrawing groups (e.g., CN, nitro, or similar). In some embodiments, the fluorinated products provided herein are 2-chloro-1-fluoro-4-nitrobenzene, 1-fluoro-4-nitrobenzene, 1-fluoro-2-nitrobenzene, 1-fluoro-2,4-dinitrobenzene, 4-chloro-1-fluoro-2-nitrobenzene, 2-fluoro-5-nitropyridine, 2-fluoronicotinonitrile, 2,3,5,6-tetrafluoroterephthalonitrile, 2,6-difluorobenzonitrile, 2-chloro-6-fluorobenzonitrile, 3,5-dichloro-2,4,6-trifluoropyridine, 2,3,5-trichloro-4,6-difluoropyridine, 2,3,5,6-tetrachloro-4-fluoropyridine, 2,4,6-trifluoro-1,3,5-triazine, 1-fluoro-3-nitrobenzene, and / or 2,4,6-trifluoro-1,3,5-triazine.

[0105]

[0121] In certain embodiments, any of the steps provided herein may include any of the methods provided herein.

[0122] Preferred embodiments of the present invention have been illustrated and described herein, but it will be apparent to those skilled in the art that such embodiments are provided merely as examples. Numerous modifications, alterations, and substitutions will be conceivable to those skilled in the art without departing from the present invention. It should be understood that various alternatives to the embodiments of the present invention described herein may be used in carrying out the present invention. The following claims define the scope of the present invention, and methods and structures within the scope of these claims, as well as their equivalents, are intended to be encompassed thereby. [Examples]

[0106] Example 1

[0123] The step of applying mechanical force to the combination of the first and second salts to form a mixed composition.

[0124] Calcium fluoride, CaF2 (1 equivalent), and the activator shown in Table 1(1) were placed in a 50 mL stainless steel milling jar. The jar was tightened by hand and secured in an MM500 Vario, and then milling was performed for 10 cycles (1 hour at 35 Hz, followed by 45 minutes at 5 Hz). For mixed composition B only, an additional K2HPO4 (1 equivalent) was added to the mixture in the stainless steel milling jar. The jar was tightened by hand and secured in an MM500 Vario, and a second milling cycle of 10 cycles was performed (1 hour at 35 Hz, followed by 45 minutes at 5 Hz). The jar was removed from the mill, placed in a fume hood, and then opened. The solid residue was removed and collected. An exemplary scheme is shown in Figure 1.

[0107] [Table 1]

[0108] Example 2

[0125] Formation of reagents or reagent compositions

[0126] The mixed compositions shown in Table 1 were suspended in water (1-5 mL / g of each composition), the pH was measured, and adjusted if necessary. The suspension was stirred and heated at 100°C for 2 hours. After the mixture cooled to room temperature, the pH was adjusted to 7. Methanol (2-20 vol) was added, and the suspension was stirred for 30 minutes. The mixture was filtered and washed with methanol. The filtrate was evaporated under reduced pressure. An off-white solid was collected and dried.

[0109]

[0127] If necessary, the resulting off-white solid was subjected to an additional purification step by stirring in methanol (30-40 mL / g) at 50°C for 1 hour, then cooled to room temperature and filtered. The filtrate was collected, evaporated under reduced pressure, and dried to obtain the purified fluorinating reagent.

[0110] Example 3A

[0128] Formation of reagents or reagent compositions

[0129] Mixed composition C (10.0 g, 34.4 mmol) shown in Table 1 was stirred in water (20.0 mL, pH = 12-13) and heated at 100°C for 2 hours. After the mixture cooled to room temperature, the pH was adjusted to 7 by adding aqueous H3PO4. 200 ml of methanol was added, and the suspension was stirred for 30 minutes. The mixture was filtered and washed with methanol. The filtrate was evaporated under reduced pressure. The off-white solid fluorinating reagent was collected and quantified. 19 The fluoride content was determined by analysis using 1F NMR (2.80g, fluorine conversion rate 54%, 25F wt%), and the results are shown in Table 2 below.

[0111] [Table 2]

[0112]

[0130] The off-white solid was stirred in methanol (115 mL) at 50°C for 1 hour, then cooled to room temperature and filtered. The filtrate was collected, evaporated under reduced pressure, and dried to obtain an off-white purified solid of the fluorinating reagent. The purified solid of the fluorinating reagent was collected and quantified. 19 The fluoride content was determined by analysis using 1F NMR, and the results are shown in Table 3 below. An exemplary reaction scheme is shown in Figure 2.

[0113] [Table 3]

[0114] Example 3B

[0131] Formation of reagents or reagent compositions

[0132] Mixed composition C (49.0 g, 168 mmol) shown in Table 1 was stirred in water (150 mL, pH = 12-13) and heated at 100°C for 2 hours. The mixture was cooled to room temperature, and then the pH was adjusted to 7 by adding approximately 20 mL of H3PO4 20% (aqueous solution). 300 mL of methanol was added, and the suspension was stirred for 30 minutes. The mixture was filtered and washed with methanol. The filtrate was concentrated to a small volume under reduced pressure. 100 mL of methanol was added to the flask, and the suspension was stirred at 50°C for 1 hour, then cooled to room temperature and filtered. The filtrate was concentrated to a small volume under reduced pressure. 100 mL of methanol was added to the flask, and the suspension was stirred at 50°C for 1 hour, then cooled to room temperature and filtered. The filtrate was collected, evaporated under reduced pressure, and dried to obtain an off-white purified solid fluorinating reagent. The purified solid fluorinating reagent was collected and quantified. 19 The fluoride content was determined by analysis using 1F NMR, and the results are shown in Table 4 below. An exemplary reaction scheme is shown in Figure 2. Powder X-ray diffraction data for the prepared fluorinating reagents can be found in Table 5 below.

[0115] [Table 4]

[0116] [Table 5-1]

[0117] [Table 5-2]

[0118] Example 3C

[0133] Formation of reagents or reagent compositions

[0134] Mixed composition D (10.0 g, 34.4 mmol) shown in Table 1 was stirred in water (20.0 mL, pH = 12-13) and heated at 100°C for 2 hours. After the mixture cooled to room temperature, the pH was adjusted to 7 by adding aqueous H3PO4. 200 ml of methanol was added, and the suspension was stirred for 30 minutes. The mixture was filtered and washed with methanol. The filtrate was evaporated under reduced pressure. The off-white fluorinating reagent was collected and quantified. 19 The fluoride content was determined by analysis using 1F NMR (3g, fluorination conversion rate 55%, 25F wt%), and the results are shown in Table 6A below. The powder X-ray diffraction data for the prepared fluorinating reagent is shown in Table 6B below.

[0119] [Table 6]

[0120] [Table 7-1]

[0121] [Table 7-2]

[0122] [Table 7-3]

[0123] Example 4A

[0135] Formation of reagents or reagent compositions

[0136] Mixed composition A (10.00 g, 39.64 mmol) as exemplified in Table 1 was mixed with (50.0 mL) and the pH was adjusted to >12 by adding aqueous KOH. The mixture was heated at 100°C for 2 hours. After the mixture cooled to room temperature, it was adjusted to neutral by adding aqueous H3PO4. 500 ml of methanol was added and the suspension was stirred for 30 minutes. The mixture was filtered and washed with methanol. The filtrate was evaporated under reduced pressure, the filter residue was collected and dried separately. The dried filtrate was collected as an off-white solid fluorinating reagent (2.20 g, fluorine conversion rate 28%, 18F wt%).

[0124]

[0137] The off-white solid was stirred in methanol (150 mL) at 50°C for 1 hour, then cooled to room temperature and filtered. The filtrate was collected, evaporated under reduced pressure, and dried to obtain an off-white purified fluorinating reagent solid (1.20 g, 23% fluorine conversion rate, 28 wt%).

[0125]

[0138] The process was repeated with mixed composition A (4.00 g), as illustrated in Table 1. The results for both are shown in Table 7 below. An exemplary reaction scheme is shown in Figure 3. Powder X-ray diffraction data for the fluorinating reagent prepared from mixed composition A can be found in Table 8 (10 g scale, 28 wt% fluorine) and Table 9 (4 g scale, 31 wt% fluorine).

[0126] [Table 8]

[0127] [Table 9-1]

[0128] [Table 9-2]

[0129] [Table 10]

[0130] Example 4B

[0139] Formation of reagents or reagent compositions from recycled first salts

[0140] The dried filter residue of Example 4A (9g) was mixed with K2HPO4 (1 equivalent, 3.5g) in a stainless steel milling jar. The stainless steel milling jar was tightened by hand and fixed in an MM500 Vario, and then milled for 10 cycles at 35Hz for 1 hour, followed by 45 minutes at 5Hz. The jar was removed from the mill and placed in a fume hood, which was then opened. The solid residue was removed and collected. The resulting solid (5.4g) was collected and mixed with water (10.0mL), and the pH was adjusted to >12 by adding aqueous KOH. The mixture was heated at 100°C for 2 hours. After the mixture cooled to room temperature, the pH was adjusted to 7 by adding aqueous H3PO4. 100ml of methanol was added, and the suspension was stirred for 30 minutes. The mixture was filtered and washed with methanol. The filtrate was evaporated, dried, and collected as an off-white solid (0.315g, 15F wt%).

[0131] Example 4C

[0141] Formation of a reagent or reagent composition purified from the recycled first salt.

[0142] The off-white solid of Example 4B can be further stirred in methanol (30-40 vol) at 50°C for 1 hour, then cooled to room temperature and filtered. The filtrate can be collected, evaporated under reduced pressure, and dried to obtain a purified fluorinating reagent.

[0132] Example 5A

[0143] Formation of reagents or reagent compositions

[0144] Mixture A (4.00 g, 15.9 mmol) was mixed with water (10.0 mL), and the pH was adjusted to >12 by adding aqueous KOH. The mixture was heated at 100°C for 2 hours. The mixture was allowed to cool to room temperature. The mixture was filtered and washed with methanol. The filtrate was evaporated under reduced pressure. The dried filtrate was collected as an off-white solid.

[0133]

[0145] The off-white solid was stirred in methanol (200 mL) at 70°C for 2 hours, then cooled to room temperature and filtered. The filtrate was collected, evaporated under reduced pressure, and dried to obtain an off-white solid. 19 Fluorine NMR was obtained to determine the fluoride content, and the results are shown in Table 10 below.

[0134] [Table 11]

[0135] Example 5B

[0146] Formation of reagents or reagent compositions

[0147] Mixture B (4.00 g, 15.9 mmol) was mixed with water (10.0 mL), and the pH was adjusted to >12 by adding aqueous KOH. The mixture was heated at 100°C for 2 hours. The mixture was allowed to cool to room temperature. The mixture was filtered and washed with methanol. The filtrate was evaporated under reduced pressure. The dried filtrate was collected as an off-white solid.

[0136]

[0148] The off-white solid was stirred in methanol (200 mL) at 70°C for 2 hours, then cooled to room temperature and filtered. The filtrate was collected, filtered under reduced pressure, and dried to obtain an off-white solid. 19 The fluoride content was determined by obtaining 1F NMR, and the results are shown in Table 11 below. The powder X-ray diffraction data of the prepared fluorinating reagent are shown in Table 12 below.

[0137] [Table 12]

[0138] [Table 13]

[0139] Example 5C

[0149] Formation of reagents or reagent compositions

[0150] Mixture A (4.00 g, 15.9 mmol) was mixed with water (10.0 mL). The mixture was heated at 100°C for 2 hours. The mixture was allowed to cool to room temperature. The mixture was filtered and washed with methanol. The filtrate was evaporated under reduced pressure. The dried filtrate was collected as an off-white solid.

[0140]

[0151] The off-white solid was stirred in methanol (200 mL) at 70°C for 2 hours, then cooled to room temperature and filtered. The filtrate was collected, evaporated under reduced pressure, and dried to obtain an off-white solid. The pH was maintained at 9 throughout the process. 19 Fluorine NMR was obtained to determine the fluoride content, and the results are shown in Table 13 below.

[0141] [Table 14]

[0142] Example 6

[0152] Formation of reagents or reagent compositions

[0153] Mixture A (10.00 g, 39.64 mmol) was mixed with methanol (500.0 mL). The mixture was heated at 70°C for 18 hours. The mixture was filtered and washed with methanol. The filtrate was evaporated under reduced pressure. The dried filtrate was collected as an off-white solid (0.61 g, 10% F conversion rate, 24 F wt%). An exemplary reaction scheme is shown in Figure 4.

[0143] Example 7

[0154] Formation of reagents or reagent compositions

[0155] Mixed composition A (30.00 g, 1 equivalent, 120 mmol) was mixed with water (75.0 mL), and the pH was adjusted to >12 by adding aqueous KOH. The mixture was heated at 100°C for 2 hours. After the mixture cooled to room temperature, it was adjusted to neutral by adding 1 M HCl. The mixture was filtered, and the filtrate was evaporated under reduced pressure. The residue was then stirred in methanol (500 mL) at 70°C for 18 hours, and then filtered. The filtrate was collected, evaporated under reduced pressure, and dried to obtain an off-white solid (4.0 g, yield 17%, 19F wt%). An exemplary reaction scheme is shown in Figure 5.

[0144] Example 8

[0156] The second salt forms various reagents or reagent compositions.

[0157] 10.00 g of the mixed composition shown in Table 1 (here, mixed compositions M, H, G, and K) was mixed with water (20.0 mL), the pH was measured, and adjusted to >12 by adding aqueous KOH if necessary. The mixture was heated at 100°C for 2 hours. After the mixture cooled to room temperature, the pH was adjusted to neutral by adding aqueous H3PO4. 200 L of methanol was added, and the suspension was stirred for 30 minutes. The mixture was filtered and washed with methanol. The filtrate was evaporated under reduced pressure. The fluorinating reagent, an off-white solid, was collected and quantified. 19 The fluoride content was determined by analysis using 1F NMR, and the results are shown in Table 14 below. An exemplary reaction scheme is shown in Figure 6. Powder X-ray diffraction data for the prepared fluorinating reagents can be found in Tables 15-18 below.

[0145] [Table 15]

[0146] [Table 16-1]

[0147] [Table 16-2]

[0148] [Table 17-1]

[0149] [Table 17-2]

[0150] [Table 17-3]

[0151] [Table 18-1]

[0152] [Table 18-2]

[0153] [Table 19-1]

[0154] [Table 19-2]

[0155] Example 9

[0158] The second salt forms various reagents or reagent compositions.

[0159] 5.00 g of the mixed compositions shown in Table 1 (here, mixed compositions E and J) were mixed with water (100.0 mL), the pH was measured, and adjusted to >12 by adding aqueous NaOH if necessary. The mixture was heated at 100°C for 2 hours. After the mixture cooled to room temperature, the pH was adjusted to neutral by adding aqueous H3PO4. 25 ml of methanol was added, and the suspension was stirred for 30 minutes. The mixture was filtered and washed with methanol. The filtrate was evaporated under reduced pressure. The fluorinating reagent and off-white solid were collected and quantified. 19 The fluoride content was determined by analysis using 1F NMR, and the results are shown in Table 19. An exemplary reaction scheme is shown in Figure 7. Powder X-ray diffraction data for the prepared fluorinating reagents can be found in Tables 20-21 below.

[0156] [Table 20]

[0157] [Table 21-1]

[0158] [Table 21-2]

[0159] [Table 21-3]

[0160] [Table 22-1]

[0161] [Table 22-2]

[0162] Example 10

[0160] Formation of various reagents or reagent compositions by the second salt

[0161] Mixture composition F shown in Table 1 was mixed with water (200.0 mL). The mixture was heated at 100°C for 2 hours. The mixture was allowed to cool to room temperature, and the suspension was filtered. The filtrate was evaporated under reduced pressure. The fluorinating reagent and off-white solid were collected and quantified. 19 The fluoride content was determined by analysis using 1F NMR, and the results are shown in Table 22. An exemplary reaction scheme is shown in Figure 8. Powder X-ray diffraction data for the prepared fluorinating reagents can be found in Table 23 below.

[0163] [Table 23]

[0164] [Table 24-1]

[0165] [Table 24-2]

[0166] Example 11

[0162] Formation of reagent or reagent composition

[0163] The mixed composition shown in Table 1 (5.0 g, 17.2 mmol) was mixed with water (10.0 mL), and the pH was adjusted to the desired value as shown in Table 6 using either aqueous KOH or aqueous H3PO4. The mixture was then heated at 100°C for 2 hours. After the mixture cooled to room temperature, it was adjusted to neutral. 100 ml of methanol was added, and the suspension was stirred for 30 minutes. The mixture was filtered and washed with methanol. The filtrate was evaporated under reduced pressure. The fluorinating reagent and off-white solid were collected and quantified. 19 The fluoride content was determined by analysis using 1F NMR, and the results are shown in Table 24. An exemplary reaction scheme is shown in Figure 9. Powder X-ray diffraction data for the prepared fluorinating reagents can be found in Tables 25-28 below.

[0167] [Table 25]

[0168] [Table 26-1]

[0169] [Table 26-2]

[0170] [Table 27]

[0171] [Table 28-1]

[0172] [Table 28-2]

[0173] [Table 29-1]

[0174] [Table 29-2]

[0175] Example 12

[0164] Formation of reagent or reagent composition

[0165] CaF2 (4.00 g, 1 equivalent, 51.2 mmol) and KOH (5.75 g, 2 equivalents, 102 mmol) were stirred in water (100 ml) at 100°C for 18 hours. The mixture was filtered, and the filtrate was neutralized with aqueous H3PO4 and then evaporated under reduced pressure. The crude product was redissolved in methanol (200 mL) and stirred overnight at 70°C. The suspension was filtered, and the filtrate was evaporated to obtain 100 mg of material containing fluoride. The fluorine conversion rate was 3%. An exemplary reaction scheme is shown in Figure 10.

[0176]

[0166] Additional purified reagents were prepared using a scheme similar to that shown in Figure 14. Tripotassium phosphate was added to the reactor described herein, and mechanical force was applied according to the method described herein. Calcium fluoride was added to the reactor, heated under reflux, aged, and then cooled to room temperature while mechanical force was continued to be applied.

[0177]

[0167] The obtained suspension was placed in a benchtop centrifuge. The solids were then separated and combined with water to form a slurry, which was then circulated to a centrifuge. The liquid was placed in a container equipped with an overhead stirrer and stirring was started. The solution was added along with phosphoric acid until a pH of 6 was obtained, and stirring was carried out for 1 hour.

[0178]

[0168] The liquid was introduced into a rotary evaporator and concentrated using the rotary evaporator to obtain a white crystalline powder. Methanol was introduced into the reactor described herein, mechanical force was applied, and the white crystalline powder was introduced into the reactor. The stirred suspension was heated, aged, cooled to room temperature, and released from the reactor. The resulting suspension was drawn into a Buchner funnel and filtered. The filter cake was slurred again in methanol and filtered again.

[0179]

[0169] Next, the combined filtrate was introduced into a rotary evaporator and vacuum concentrated to obtain a crystalline solid containing the purified fluorinating reagent.

[0170] The production of the purified fluorinating reagent was achieved by using a high-temperature reaction (including 150°C) in a pressurized flask, as described herein, as well as by using a high-shear mixer and / or homogenizer as the reactor.

[0180]

[0171] For example, using a reactor equipped with an in-line homogenizer, the production of the purified fluorinating reagent involved adding it to the reactor, sealing the reactor, and applying mechanical force. The reaction cong was then cooled to room temperature. The resulting suspension was purified using a method similar to that described throughout this example. Further spray drying was tested for purification and yielded similar results.

[0181] Example 13

[0172] Formation of fluorinated compounds using purified fluorinating reagent

[0173] The purified fluorinating reagent (1.5 to 6 equivalents) and TMAC (1 equivalent) prepared from mixed composition C in Table 1 were stirred in a reaction solvent containing an aromatic compound (1 equivalent) under the conditions shown in Table 7. An exemplary scheme for the preparation of the purified fluorinating reagent from mixed composition C is shown in Figure 11.

[0182]

[0174] Reaction Procedure: Solids were added to a furnace-dried screw-cap vial, followed by the addition of the solvent, and then the vial was sealed under a nitrogen atmosphere. The mixture was heated to the desired temperature for the required duration. After this, the mixture was cooled, and an internal standard (p-fluoroanisole or α,α,α-trifluorotoluene) was added for quantitative analysis. 19 Analysis was performed by 1F NMR. An exemplary reaction scheme is shown in Figure 12. Exemplary results are shown in Table 29.

[0183] [Table 30-1]

[0184] [Table 30-2]

[0185] Example 14

[0175] Formation of fluorinated compounds using purified fluorinating reagent

[0176] A purified fluorinating reagent prepared from mixed composition C (6 equivalents of fluorine per aromatic compound) and phthaloyl dichloride (1 equivalent) in Table 1 was stirred with an aromatic compound (1 equivalent) in sulfolane at 150°C for 3 hours. The concentration of the aromatic compound in the reaction mixture was 0.25 M. The fluorinated compound was recovered in a yield of 10%. The reaction scheme is shown in Figure 13.

Claims

1. (a) A step of combining a first salt containing calcium and fluoride with a second salt to form a mixed composition, (b) A step of subjecting the mixed composition to a fluid composition (to produce solid components and the resulting fluid), and collecting the resulting fluid, (c) A step of concentrating the resulting fluid to produce a crude fluorinating reagent (e.g., reagent concentrate or precipitate), (d) Washing the crude fluorinating reagent with a solvent (e.g., water or alcohol) to produce a reagent wash (a second solid component and a fluid reagent wash), and (e) A step of concentrating the reagent wash to form a purified fluorinating reagent (for example, a purified fluorinating reagent having a higher concentration of fluorine compared to the crude fluorinating reagent). A method for producing a purified fluorinating reagent containing [the specified substance].

2. (a) A step of combining a first salt containing calcium and fluoride with a second salt, (b) A step of applying mechanical force to the combination of the first salt and the second salt to form a mixed composition, (c) A step of applying the mixed composition to a fluid composition (to produce solid components and the resulting fluid), and collecting the resulting fluid, (d) A step of concentrating the resulting fluid to produce a crude fluorinating reagent (e.g., reagent concentrate or precipitate), (e) Washing the crude fluorinating reagent with a solvent (e.g., water or alcohol) to produce a reagent wash (a second solid component and a fluid reagent wash), and (f) A step of concentrating the reagent wash to form a purified fluorinating reagent (for example, a purified fluorinating reagent having a higher concentration of fluorine compared to the crude fluorinating reagent). A method for producing a purified fluorinating reagent containing [the specified substance].

3. (a) A step of combining a first salt containing calcium and fluoride with a second salt to form a mixed composition, (b) The steps of applying the mixed composition to a fluid composition (to produce solid components and the resulting fluid), and collecting the resulting fluid, (c) A step of concentrating the resulting fluid to produce a purified fluorinating reagent (e.g., reagent concentrate or precipitate). A method for producing a purified fluorinating reagent containing [the specified substance].

4. (a) A step of combining a first salt containing calcium and fluoride with a second salt, (b) A step of applying mechanical force to the combination of the first salt and the second salt to form a mixed composition, (c) The steps of applying the mixed composition to a fluid composition (to produce solid components and the resulting fluid), and collecting the resulting fluid, (d) The step of concentrating the resulting fluid to produce a purified fluorinating reagent (e.g., reagent concentrate or precipitate). A method for producing a purified fluorinating reagent containing [the specified substance].

5. The method according to any one of claims 1 to 4, further comprising the steps of (a), (b), and (c) being carried out substantially simultaneously, (a), (b), and (c) being carried out sequentially, or (c) being carried out before (b), and / or adjusting the pH of the resulting fluid (for example, from a pH of about 6 to about 8) before the step of concentrating the resulting fluid.

6. The method according to any one of claims 1 to 5, wherein the amount of phosphorus in the purified fluorinating reagent is about 0.015% by weight to about 12.5% ​​by weight (wt%), or about 1 ppm to about 25 ppm (for example, about 1 ppm, about 10 ppm, about 20 ppm, or about 25 ppm).

7. The method according to any one of claims 1 to 6, wherein the amount of calcium in the purified fluorinating reagent is about 0.01% by weight to about 15% by weight (wt%), or about 1 ppm to about 25 ppm (for example, about 1 ppm, about 10 ppm, about 20 ppm, or about 25 ppm).

8. (a) A step of preparing a purified fluorinating reagent comprising an alkali metal, fluoride, and at least one additional ion, wherein the amount of phosphorus in the purified fluorinating reagent is about 0.015% by weight to about 12.5% ​​by weight (wt%), or about 1 ppm to about 25 ppm (for example, about 1 ppm, about 10 ppm, about 20 ppm, or about 25 ppm), (b) Step of preparing the starting reagents, (c) A step of contacting a starting reagent with a purified fluorinating reagent, thereby fluorinating the starting reagent and thereby obtaining a fluorinated product. A method for obtaining a fluorinated product by fluorinating a starting reagent using a purified fluorinating reagent containing [a specific substance].

9. (a) A step of preparing a purified fluorinating reagent comprising an alkali metal including lithium, potassium, or sodium, a fluoride, and at least one additional ion, wherein the purified fluorinating reagent is characterized by at least one of the 2θ values ​​reported in any one of Tables 5, 6A, 8, 9, 12, 15-18, 20, 21, 23, 25-28 (e.g., at least 2, at least 3, at least 5, at least 10, at least 20, at least 50, and / or at least 70), (b) Step of preparing the starting reagents, (c) A step of contacting a starting reagent with a purified fluorinating reagent, thereby fluorinating the starting reagent and thereby obtaining a fluorinated product. A method for obtaining a fluorinated product by fluorinating a starting reagent using a purified fluorinating reagent containing [a specific substance].

10. (a) A step of combining a first salt containing calcium and fluoride with a second salt to form a mixed composition, (b) A step of subjecting the mixed composition to a fluid composition (to produce solid components and the resulting fluid), and collecting the resulting fluid, (c) A step of concentrating the resulting fluid to produce a crude fluorinating reagent (e.g., reagent concentrate or precipitate), (d) Washing the crude fluorinating reagent with a solvent (e.g., water or alcohol) to produce a reagent wash (a second solid component and a fluid reagent wash), and (e) A step of concentrating the reagent wash to form a purified fluorinating reagent (for example, a purified fluorinating reagent having a higher concentration of fluorine compared to the crude fluorinating reagent), (f) A step of contacting a purified fluorinating reagent with a starting reagent, thereby fluorinating the starting reagent and obtaining a fluorinating product. A method for producing a purified fluorinating reagent for obtaining a fluorination product, which includes [the specified substance].

11. (a) A step of combining a first salt containing calcium and fluoride with a second salt, (b) A step of applying mechanical force to the combination of the first salt and the second salt to form a mixed composition, (c) A step of applying the mixed composition to a fluid composition (to produce solid components and the resulting fluid), and collecting the resulting fluid, (d) A step of concentrating the resulting fluid to produce a crude fluorinating reagent (e.g., reagent concentrate or precipitate), (e) Washing the crude fluorinating reagent with a solvent (e.g., water or alcohol) to produce a reagent wash (a second solid component and a fluid reagent wash), (f) A step of concentrating the reagent wash to form a purified fluorinating reagent (e.g., a purified reagent concentrate or precipitate), (g) A step of contacting a purified fluorinating reagent with a starting reagent, thereby fluorinating the starting reagent and obtaining a fluorinating product. A method for producing a purified fluorinating reagent for obtaining a fluorination product, which includes [the specified substance].

12. The method according to any one of claims 1 to 11, further comprising the step of providing the mixed composition that has been subjected to the fluid composition as a first salt.

13. The method according to any one of claims 1 to 12, wherein the first salt is recovered waste material.

14. The method according to any one of claims 1 to 13, wherein the first salt comprises low-purity calcium and fluoride (for example, less than 80% by weight in total of calcium and fluorine).

15. The method according to any one of claims 1 to 14, wherein the pH of the resulting fluid is adjusted with an acid (e.g., a strong acid, a weak acid, a polyprotic acid, and / or a combination thereof).

16. The method according to any one of claims 1 to 15, wherein the acid comprises phosphoric acid, hydrochloric acid, boric acid, silicic acid, formic acid, acetic acid, benzoic acid, oxalic acid, sulfuric acid, sulfurous acid, carbonic acid, and / or a combination thereof.

17. The method according to any one of claims 1 to 16, wherein the acid comprises hydrochloric acid, phosphoric acid, sulfuric acid, and / or a combination thereof.

18. The method according to any one of claims 1 to 17, wherein the pH of the resulting fluid is adjusted to a pH of about 5 to about 10 (for example, about 6 to about 9).

19. The method according to any one of claims 1 to 18, wherein the fluid composition has a pH of about 7 or higher (e.g., about 10 or higher).

20. The method according to any one of claims 1 to 19, wherein the fluid composition has a pH of about 12 to about 13.

21. The method according to any one of claims 1 to 20, wherein the combination of the fluid composition and the mixed composition is at a temperature of about 0 to about 200°C.

22. The method according to any one of claims 1 to 21, wherein the combination of the fluid composition and the mixed composition is at a temperature of 80°C or higher.

23. The method according to any one of claims 1 to 22, wherein the combination of the fluid composition and the mixed composition is at a temperature of 110°C or lower.

24. The method according to any one of claims 1 to 23, wherein the mixed composition is subjected to the fluid composition for about 0 to about 8 hours.

25. The method according to any one of claims 1 to 24, wherein the mixed composition is applied to the fluid composition for about one hour or longer.

26. The method according to any one of claims 1 to 25, wherein the mixed composition is supplied to the fluid composition for about six hours or less.

27. The method according to any one of claims 1 to 26, wherein the mixed composition is subjected to the fluid composition for about two hours.

28. The method according to any one of claims 1 to 27, wherein the fluid composition has a boiling point of about 30°C or higher (e.g., about 70°C or higher, about 120°C or higher).

29. The method according to any one of claims 1 to 28, wherein the fluid composition has a boiling point of about 240°C or lower.

30. The method according to any one of claims 1 to 29, wherein the combination of the solvent and the crude fluorinating reagent is at a temperature of about -20 to about 240°C.

31. The method according to any one of claims 1 to 30, wherein the combination of the solvent and the crude fluorinating reagent is at a temperature of about 80°C or higher.

32. The method according to any one of claims 1 to 31, wherein the combination of the solvent and the crude fluorinating reagent is at a temperature of about 60°C.

33. The method according to any one of claims 1 to 32, wherein the combination of the solvent and the crude fluorinating reagent is at a temperature of about 235°C or lower.

34. The method according to any one of claims 1 to 33, wherein the crude fluorinating reagent is washed with a solvent for about 4 to about 48 hours (for example, about 8 to about 36 hours, or about 10 to about 28 hours).

35. The method according to any one of claims 1 to 34, wherein the crude fluorinating reagent is washed in a solvent for about 8 hours or longer.

36. The method according to any one of claims 1 to 35, wherein the crude fluorinating reagent is washed in a solvent for about 36 hours or less.

37. The method according to any one of claims 1 to 36, wherein the crude fluorinating reagent is washed with a solvent for about 18 hours.

38. The method according to any one of claims 1 to 37, wherein the solvent has a boiling point of about 30°C or higher (e.g., about 70°C or higher, about 120°C or higher).

39. The method according to any one of claims 1 to 38, wherein the solvent has a boiling point of about 240°C or lower.

40. The method according to any one of claims 1 to 39, wherein the solvent and / or fluid composition is an organic solvent, water, alcohol, polar aprotic solvent, halocarbon, and / or a combination thereof.

41. The method according to any one of claims 1 to 40, wherein the solvent and / or fluid composition is acetonitrile, propionitrile, butyronitrile, toluene, 1,2-dichlorobenzene, chlorobenzene, fluorobenzene, 1,2-difluorobenzene, dichloroethane, trifluorotoluene, chloroform, sulfolane, DMF, DMSO, alcohol (e.g., tert-butanol, tert-amyl alcohol), water, and / or a combination thereof.

42. The method according to any one of claims 1 to 41, wherein the solvent and / or fluid composition is acetonitrile, propionitrile, butyronitrile, and / or a combination thereof.

43. The method according to any one of claims 1 to 42, wherein the second salt is a metal hydroxide, metal sulfite, metal sulfate, carbonate, or inorganic phosphate (e.g., pyrophosphate).

44. The second salt is NaOH, KOH, Na １０ , ５ , ４ , ２ , ３ , ３ SO ３ , K ２ SO ３ , KHSO ４ , CaCO ３ , H ２ CO ３ , K ２ CO ３ , Na ２ CO ３ , K ４ P ２ O ７ , Na ４ P ２ O ７ , Na ３ PO ４ , Li ３ PO ４ , KHCO ３ , K ２ CO ３ , NaHCO ３ , Cs ２ CO ３ , K<000m029>HPO ４ , KH ２ PO ４ , K ３ PO ４ , KPO ３ , K ５ P ３ O<oo00038>, K ２ SO ４ The method according to any one of claims 1 to 43, comprising titanium phosphate, aluminum phosphate, uranium phosphate, and / or a combination thereof.

45. The method according to any one of claims 1 to 44, wherein the amount of phosphorus in the purified fluorinating reagent is about 0.02% by weight to about 10% by weight (wt%) (for example, about 0.05 wt% to about 8 wt%, about 0.1 wt% to about 6 wt%, about 0.5 wt% to about 5 wt%, about 1 wt% to about 4 wt%), or the amount of phosphorus in the purified fluorinating reagent is about 1 ppm to about 25 ppm (for example, about 1 ppm, about 10 ppm, about 20 ppm, or about 25 ppm).

46. The method according to any one of claims 1 to 45, wherein the amount of phosphorus in the purified fluorinating reagent is about 0.015% by weight (wt%) or more (e.g., about 0.05 wt% or more, about 0.1 wt% or more, about 0.5 wt% or more), or about 1 ppm to about 25 ppm (e.g., about 1 ppm, about 10 ppm, about 20 ppm, or about 25 ppm).

47. The method according to any one of claims 1 to 46, wherein the amount of phosphorus in the purified fluorinating reagent is about 5% by weight (wt%) or less (for example, about 3 wt% or less, about 2 wt% or less, about 1 wt% or less, about 0.5 wt% or less, about 0.1 wt% or less, about 0.05 wt% or less).

48. The method according to any one of claims 1 to 47, wherein the powder X-ray diffraction spectrum of the crude fluorinating reagent includes characteristic 2θ reflectances of about 5.2°, 31.5°, 36.8°, and / or a combination thereof.

49. The method according to any one of claims 1 to 48, wherein about 10 to about 80% (e.g., about 30 to about 60%) of the fluoride in the first salt is converted to the fluoride of the purified fluorinating reagent.

50. The method according to any one of claims 1 to 49, wherein the purified fluorinating reagent is activated (for example, can be used in that form as a fluorinating agent).

51. The method according to any one of claims 1 to 50, wherein the starting reagent is an organic compound (for example, an aromatic organic compound).

52. The method according to any one of claims 1 to 51, wherein the organic compound comprises 1-chloro-4-nitrobenzene, 1,2-dichloro-nitrobenzene, 1,2-dichloro-4-nitrobenzene, 1-chloro-2,4-dinitrobenzene, 1,4-dichloro-2-nitrobenzene, 2-chloro-5-nitropyridine, 2-chloronicotinonitrile, 2,3,5,6-tetrachloroterephthalonitrile, 2,6-dichlorobenzonitrile, pentachloropyridine, 2,3,5,6-tetrachloroterephthalonitrile, 2,6-dichlorobenzonitrile, 2,3,5,6-tetrachloro-4-fluoropyridine, 2,4,6-trichloro-1,3,5-triazine, 1,3-dinitrobenzene, or 2,4-dichloro-1-nitrobenzene.

53. The method according to any one of claims 1 to 52, wherein the at least one additional ion of the purified fluorinating reagent comprises (i) at least one cation and at least one anion, or (ii) at least one zwitterion (e.g., psilocybin).

54. At least one cation, K ＋ Na ＋ Ca ２＋ Li ＋ , or Cs ＋ The method according to any one of claims 1 to 53, including the method described in any one of claims 1 to 53.

55. The method according to any one of claims 1 to 54, wherein at least one anion comprises an ion of a hydroxide, sulfate, carbonate, phosphate, chloride, iodide, or pyrophosphate.

56. The method according to any one of claims 1 to 55, wherein a purified fluorinating reagent is brought into contact with a starting reagent under mechanochemical conditions (e.g., a ball mill).

57. The method according to any one of claims 1 to 56, wherein a purified fluorinating reagent is brought into contact with a starting reagent in a reaction mixture.

58. The method according to any one of claims 1 to 57, wherein the reaction mixture comprises a reaction solvent (for example, an organic solvent, water, an alcohol, a polar aprotic solvent, a halocarbon, and / or a combination thereof).

59. The method according to any one of claims 1 to 58, wherein the reaction solvent is acetonitrile, DMF, DMSO, sulfolane, and / or a combination thereof.

60. The method according to any one of claims 1 to 59, wherein the reaction mixture further comprises an ammonium salt (e.g., TMAC) and / or a phase transfer agent (e.g., crown ether).

61. The method according to any one of claims 1 to 60, wherein the reaction mixture is at a temperature of about 50 to about 200°C.

62. The method according to any one of claims 1 to 61, wherein the reaction mixture is at a temperature of about 50°C or higher (e.g., about 70°C or higher, about 110°C or higher, about 140°C or higher).

63. The method according to any one of claims 1 to 62, wherein a purified fluorinating reagent is contacted with a starting reagent for about 1 to about 36 hours (for example, about 2 to about 6 hours, or about 12 to about 24 hours).

64. The method according to any one of claims 1 to 63, wherein the purified fluorinating reagent is brought into contact with the starting reagent for about 24 hours or less (e.g., about 12 hours or less, about 6 hours or less).

65. The method according to any one of claims 1 to 64, wherein the purified fluorinating reagent is brought into contact with the starting reagent for about one hour or longer (e.g., about two hours or longer, about sixteen hours or longer).

66. A purified fluorinating reagent comprising an alkali metal including lithium, potassium, or sodium, a fluoride, and at least one additional ion, wherein the amount of phosphorus in the purified fluorinating reagent is about 0.015% by weight to about 12.5% ​​by weight (wt%).

67. A purified fluorinating reagent comprising potassium, fluoride, and at least one additional ion, characterized by at least one of the 2θ values ​​reported in any one of Tables 5, 6A, 8, 9, 12, 15-18, 20, 21, 23, 25-28 (e.g., at least 2, at least 3, at least 5, at least 10, at least 20, at least 50, and / or at least 70).

68. A purified fluorinating reagent according to any one of claims 1 to 67, wherein the amount of calcium in the purified fluorinating reagent is about 0.01% by weight to about 15% by weight (wt%).

69. A purified fluorinating reagent according to any one of claims 1 to 68, wherein the amount of phosphorus in the purified fluorinating reagent is about 0.02% by weight to about 10% by weight (wt%) (for example, about 0.05 wt% to about 8 wt%, about 0.1 wt% to about 6 wt%, about 0.5 wt% to about 5 wt%, and about 1 wt% to about 4 wt%).

70. A purified fluorinating reagent according to any one of claims 1 to 69, wherein the amount of phosphorus in the purified fluorinating reagent is about 0.015% by weight (wt%) or more (for example, about 0.05 wt% or more, about 0.1 wt% or more, about 0.5 wt% or more).

71. A purified fluorinating reagent according to any one of claims 1 to 70, wherein the amount of phosphorus in the purified fluorinating reagent is about 5% by weight (wt%) or less (for example, about 3 wt% or less, about 2 wt% or less, about 1 wt% or less, about 0.5 wt% or less, about 0.1 wt% or less, about 0.05 wt% or less).

72. A purified fluorinating reagent according to any one of claims 1 to 71, wherein at least one additional ion comprises (i) at least one cation and at least one anion, or (ii) at least one zwitterion (e.g., psilocybin).

73. At least one cation, K ＋ Na ＋ Ca ２＋ Li ＋ , or Cs ＋ A purified fluorinating reagent according to any one of claims 1 to 72, comprising:

74. A purified fluorinating reagent according to any one of claims 1 to 73, wherein at least one anion comprises ions of hydroxide, sulfate, carbonate, phosphate, or pyrophosphate.

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