Urethane compounds

Abstract

A urethane compound represented by formula (0). [l is 0 or 1, m is an integer of 1-4, n is an integer of 1-4, R1 and R2 are substituents with an 'R10-CR2-' structure, R3 is a hydrogen atom or a substituent with an 'R10-CR2-' structure, R4 is a substituent selected from the group consisting of substituents with an 'R10-CR2-' structure, substituents with an 'R10-At16-' structure and substituents with an 'R102-At15-' structure, At15 is a group 15 atom, At16 is a group 16 atom, and n is an integer of 1-4. R and R10 are groups containing atoms selected from carbon, hydrogen, a group 15 element, a group 16 element and a group 17 element, the number of carbon atoms is 0-17, the number of heteroatoms is 0-4, R1-R4 and R can be bonded with each other to form a monocyclic or polycyclic bond, and R and R10 can be bonded with each other to form a monocyclic, polycyclic or multiple bond. ]

Description

Technical Field

[0001] This invention relates to carbamate compounds. Background Technology

[0002] Carbamate compounds are known to be used not only as solvents, intermediates in pharmaceuticals and pesticides, but also as raw materials for nylon. Additionally, there are reports of Mg-supported titanium catalysts used in olefin polymerization.

[0003] For catalysts used in olefin polymerization, Ziegler reported in 1953 that ethylene could polymerize even at low pressures by combining titanium tetrachloride with organoaluminum compounds. Subsequently, Natta reported the first propylene polymerization using a combination of titanium trichloride and halogenated organoaluminum compounds. This discovery of the so-called Ziegler-Natta catalyst has paved the way for significant advancements in propylene polymerization. Notably, it was found that catalysts containing titanium tetrachloride, magnesium compounds, and Lewis bases, known as third-generation catalysts, could balance high polymerization activity (high productivity) and high stereoregularity in propylene polymerization. This presented an opportunity for the global expansion of propylene polymers (polypropylene).

[0004] In addition, Lewis bases (hereinafter referred to as "internal donors"), which are one of the main components of the aforementioned third-generation catalyst components (hereinafter also referred to as "solid titanium catalyst components"), have been found to have a significant impact on catalyst performance, and various Lewis bases have been developed to date.

[0005] Lewis bases used in Ziegler-Natta catalysts have been reported, including ethyl benzoate, phthalates, 1,3-diketones (Patent Document 1), malonates (Patent Document 2), succinates (Patent Document 3), 2,4-pentanediol diesters (Patent Document 4), naphthalene glycol diesters (Patent Document 5), and catechol diesters (Patent Document 6), and are currently a field of active research and development, primarily by companies. Additionally, carbamate compounds with specific structures have been reported as suitable (Patent Documents 7-9).

[0006] Existing technical documents

[0007] Patent documents

[0008] Patent Document 1: Japanese Patent Application Publication No. 2005-226076

[0009] Patent Document 2: Japanese Patent Publication No. 2000-516987

[0010] Patent Document 3: Japanese Patent Publication No. 2002-542347

[0011] Patent Document 4: Japanese Patent Publication No. 2005-517746

[0012] Patent Document 5: Japanese Patent Publication No. 2011-529888

[0013] Patent Document 6: Japanese Patent Publication No. 2014-500390

[0014] Patent Document 7: International Patent Publication No. 2016 / 184884

[0015] Patent Document 8: U.S. Patent No. 10005859

[0016] Patent Document 9: U.S. Patent No. 10,836,847 Summary of the Invention

[0017] The problem that the invention aims to solve

[0018] Propylene polymers have heat resistance and rigidity close to those of general engineering plastics. On the other hand, since they are basically composed of only carbon and hydrogen, they have the advantage of producing less toxic gas even when burned.

[0019] Due to recent advancements in molding technology, using propylene polymers with higher stereoregularity than before can potentially result in superior physical properties (rigidity, heat resistance, etc.). Therefore, the market demands propylene polymers with higher stereoregularity. Furthermore, from the perspective of resource conservation and environmental protection, there is a need for manufacturing methods for propylene polymers with high productivity.

[0020] Therefore, the objective of this invention is to provide an internal donor component that is suitable for use primarily in solid titanium catalyst components to produce propylene polymers with extremely high stereoregularity at high productivity (high activity).

[0021] Methods for solving problems

[0022] In order to solve the above-mentioned problems, the inventors conducted in-depth research and discovered that urethane compounds with specific structures are suitable as Lewis bases, for example, components of solid titanium catalysts, thus completing the present invention. Examples of the present invention are shown below.

[0023] [1] A carbamate compound represented by the following formula (0).

[0024] [Chemistry 1]

[0025]

[0026] In equation (0),

[0027] l is 0 or 1.

[0028] m is an integer from 1 to 4.

[0029] n is an integer from 1 to 4.

[0030] R 1 and R 2 They are respectively those with "R" 10 Substituents in the "-CR2-" structure

[0031] R 3 It is a hydrogen atom or has "R" 10 Substituents in the "-CR2-" structure

[0032] R 4 To be selected from those with "R" 10 Substituents with the "-CR2-" structure, and those with "R" 10 -At 16 Substituents with the "-" structure and having "R" 10 2-At 15 Substituents in the "-" structure

[0033] At 15 For atoms in group 15 of the periodic table, At 16 These are atoms belonging to group 16 of the periodic table.

[0034] R and R 10 These are groups containing atoms selected from carbon, hydrogen, and elements from groups 15, 16, and 17 of the periodic table, with 0 to 17 carbon atoms and 0 to 4 atoms of elements from groups 15, 16, and 17 of the periodic table.

[0035] R 1 ~R 4 And R can bond with each other to form single or multiple rings.

[0036] Multiple R, R 10 They can bond with each other to form single or multiple rings, and can also form multiple bonds.

[0037] [2] The carbamate compound according to [1] is represented by the following formula (1).

[0038] [Chemistry 2]

[0039]

[0040] In equation (1), n ​​is an integer from 2 to 4, and m and R are... 1 R 2 R 3 R 4 And R and m and R in the above equation (0) 1 R 2 R 3 R4 Synonymous with R.

[0041] [3] The carbamate compound according to item [1] or [2], wherein the above-mentioned R 3 For having "R 10 Substituents in the "-CR2-" structure.

[0042] [4] The carbamate compound according to any one of items [1] to [3], wherein the above R 4 For having "R 10 Substituents in the "-CR2-" structure.

[0043] [5] The carbamate compound according to any one of items [1] to [4], wherein the above At... 15 It is a nitrogen atom.

[0044] [6] The carbamate compound according to any one of items [1] to [5], wherein the above At 16 It is an oxygen atom.

[0045] Invention Effects

[0046] The carbamate compounds of the present invention can be used, for example, as pesticides or other agents or intermediates thereof, as raw materials for fillers of optical dividing columns, as raw materials for Ziegler-Natta catalysts, etc. Detailed Implementation

[0047] [Carbamate compounds]

[0048] The carbamate compounds of the present invention are represented by the following formula (0).

[0049] [Chemistry 3]

[0050]

[0051] In equation (0),

[0052] l is 0 or 1.

[0053] m is an integer from 1 to 4.

[0054] n is an integer from 1 to 4.

[0055] R 1 and R 2 They are respectively those with "R" 10 Substituents in the "-CR2-" structure

[0056] R 3 It is a hydrogen atom or has "R" 10 Substituents in the "-CR2-" structure

[0057] R4 To be selected from those with "R" 10 Substituents with the "-CR2-" structure, and those with "R" 10 -At 16 Substituents with the "-" structure and having "R" 10 2-At 15 Substituents in the "-" structure

[0058] At 15 For atoms in group 15 of the periodic table, At 16 These are atoms belonging to group 16 of the periodic table.

[0059] R and R 10 These are groups containing atoms selected from carbon, hydrogen, and elements from groups 15, 16, and 17 of the periodic table, with 0 to 17 carbon atoms and 0 to 4 heteroatoms.

[0060] R 1 ~R 4 And R can bond with each other to form single or multiple rings.

[0061] Multiple R, R 10 They can bond with each other to form single or multiple rings, and can also form multiple bonds.

[0062] One preferred embodiment of the above structure is a compound specified by the following formula (1). In this case, n is an integer from 2 to 4. Other symbols are synonymous with the above formula (0).

[0063] [Chemistry 4]

[0064]

[0065] The atoms of group 15 in the aforementioned periodic table, At... 15 Preferably, the atoms are selected from nitrogen, phosphorus, arsenic, antimony, etc., more preferably from nitrogen and phosphorus, and especially preferably from nitrogen atoms.

[0066] The group 16 atoms At in the aforementioned periodic table 16 Preferably, the atoms are selected from oxygen, sulfur, selenium, etc., more preferably from oxygen and sulfur, and particularly preferably from oxygen atoms.

[0067] It should be noted that the "-" symbol mentioned above represents a covalent bond, and the term "atom" sometimes refers to the atom itself, but it is used to describe structures with covalent bonds, including compounds and substituents. For example, in the case of oxygen atoms, the form "-O-" is sometimes referred to as an oxygen atom.

[0068] The above R and R 10These are groups containing atoms selected from carbon, hydrogen, and elements in groups 15, 16, and 17 of the periodic table, respectively. The number of carbon atoms is 0-17, and the number of atoms in the aforementioned group 15, 16, and 17 elements is 0-4. Examples of the aforementioned group 15 and 16 elements can be found in the At group. 15 At 16 The same elements. Among the aforementioned group 17 elements, fluorine, chlorine, bromine, and iodine are preferred examples, more preferably atoms selected from fluorine, chlorine, and bromine, and even more preferably atoms selected from fluorine and chlorine, especially chlorine.

[0069] The preferred lower limit for the number of carbon atoms is 1, while the preferred upper limit is 15, more preferably 13, even more preferably 11, and particularly preferably 9.

[0070] The preferred upper limit for the number of atoms of elements in groups 15, 16, and 17 of the periodic table is 3, and more preferably 2.

[0071] These substituents (R) 1 R 2 R 3 R 4 R 10 The two bonds (R and R) can bond together to form ring structures, heterocyclic structures, aromatic structures, etc. It should be noted that, in this invention, unless otherwise specified, double and triple bonds are considered as binary rings and are regarded as a type of ring structure.

[0072] Regarding the existence of multiple R and R mentioned above 10 These substituents can bond with each other to form cyclic, heterocyclic, and aromatic structures. Furthermore, when adjacent carbon atoms bonded to these substituents form double bonds, these R, R... 10 It can also be viewed as a direct bond forming a double bond.

[0073] The above R, R 10 Sometimes multiple substituents exist, but they can be of the same structure or different structures. Specific examples of such substituents are hydrocarbon groups with 1 to 17 carbon atoms, either substituted or unsubstituted. Examples of such substituents include aliphatic substituents, alicyclic substituents, and hydrocarbon groups with 6 to 20 carbon atoms having an aryl group. They can also be structures containing atoms from groups 15 to 17 of the periodic table (sometimes referred to as heteroatoms in this invention), as described above. Preferably, the hydrocarbon group consists only of carbon and hydrogen.

[0074] Examples of the aforementioned hydrocarbon groups include monovalent hydrocarbon groups with a preferred number of carbon atoms of 0 to 15, more preferably 0 to 13, more preferably 1 to 11, and even more preferably 1 to 9. In this invention, when the number of carbon atoms is 0, it refers to hydrogen atoms or covalent bonds forming double bonds.

[0075] Specifically, examples of such hydrocarbon groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, hexyl, heptyl, octyl, 2-ethylhexyl, decyl, dodecyl, tetradecyl, hexadecyl, octadecyl, eicosyl, cyclohexyl, phenyl, and other substituted or unsubstituted aryl, substituted or unsubstituted cycloalkenyl, and other aliphatic, alicyclic, or aromatic hydrocarbon groups. Among these, n-butyl, isobutyl, hexyl, octyl, and phenyl are preferred, and n-butyl, isobutyl, and phenyl are even more preferred.

[0076] As described above, the aforementioned hydrocarbon group can be a hydrocarbon group containing heteroatoms such as nitrogen, oxygen, phosphorus, and halogen. Oxygen and nitrogen are particularly important heteroatoms. Such substituents can be selected from known structures. More specifically, preferred examples include carboxylic acid ester groups, aldehyde or acetyl groups, groups containing carbonyl structures such as oxycarbonylalkyl groups, alkoxy groups, substituted or unsubstituted alkoxy groups, substituted or unsubstituted alkenoxy groups, substituted or unsubstituted cycloalkoxy groups, substituted or unsubstituted cycloalkenoxy groups, substituted or unsubstituted aryloxy groups, substituted or unsubstituted heteroaryl groups, substituted or unsubstituted heteroaryloxy groups, and siloxy groups.

[0077] The above R 1 and R 2 They are respectively those with "R" 10 Substituents with the "-CR2-" structure. Examples of such substituents are substantially similar to the aforementioned R, R... 10 The substituents illustrated are generally the same, but the site of the nitrogen bond to the urethane group described later is limited to carbon. For example, structures in which oxygen and nitrogen are bonded to other groups via alkoxy, amino, etc., are not desired. Preferred examples of such substituents include ethyl, propyl, isopropyl, n-butyl, isobutyl, hexyl, octyl, phenyl, etc., more preferably ethyl, propyl, isopropyl, n-butyl, isobutyl, phenyl, and particularly preferably ethyl, propyl, isopropyl, phenyl.

[0078] The above R 3 In the above R 1 R 2 The definition includes the hydrogen atom. Preferably, it contains "R". 10 Substituents in the "-CR2-" structure. Therefore, specific examples of preferred substituents are also related to R. 1 R 2 same.

[0079] The above R 4 To be selected from those with "R" 10 Substituents with the "-CR2-" structure, and those with "R" 10 -At 16 Substituents with the "-" structure and those with "R" 10 2-At 15Substituents in the substituents of the "-" structure. As the R 4 Specific examples, similar to R and R mentioned above 10 R 1 R 2 The substituents illustrated are largely the same. As for the At mentioned above... 16 Oxygen is preferred as At 15 Nitrogen is a preferred example. As a specific "R" 10 -At 16 The "-" structure can include alkoxy and aryloxy groups. More specific preferred substituents include ethoxy, propoxy, butoxy, acetoxy, ethyl carbonyloxy, metal acyloxy, phenoxy, and substituted phenoxy groups.

[0080] As a specific "R" 10 -At 15 Examples of structures with the "-" structure include dimethylamino, diethylamino, dipropylamino, diisopropylamino, dibutylamino, methylethylamino, methylpropylamino, diphenylamino, xylylamino, etc.

[0081] The carbamate compounds of the present invention are characterized by having, as shown in formula (1), a structure with substituents having a carbamate structure and substituents having an amide structure. In particular, they are characterized in that the substituents having a carbamate structure are bonded to A via oxygen (O-), and the substituents having an amide structure are bonded to A via nitrogen (N-). In the present invention, the carbamate group and amide group are sometimes simply referred to as functional groups. It should be noted that the amide group is based on R... 4 The structure of is sometimes referred to as a substituent under other names such as urethane group.

[0082] The carbamate compound of the present invention, as specified by formula (0), is characterized in that it is a structure formed by bonding substituents of the carbamate structure and substituents of the amide structure to a divalent group of a structure as shown in formula (0'). Furthermore, the carbamate compound specified by formula (1) is characterized in that it is a structure formed by bonding substituents of the carbamate structure and substituents of the amide structure to a divalent group of a structure as shown in formula (1').

[0083] [Chemistry 5]

[0084]

[0085] The symbols C, R, etc. in the above equations (0') and (1') are synonymous with the symbols in the above equations (0) and (1).

[0086] In the above formulas (0) and (0'), l is 0 or 1, preferably 1.

[0087] As a molecular skeleton, the case where l is 1 in equation (0) is equivalent to equation (1), and similarly, the case where l is 1 in equation (0') is equivalent to equation (1').

[0088] m is an integer from 1 to 4. In the case of equation (0) above, the preferred value of m is 1 or 2, more preferably 1. In the case of equation (1) above, the preferred lower limit value of m is 2, and the preferred upper limit value is 3.

[0089] n is an integer from 1 to 4. In the case of the above formula (0), the preferred value of n is 1 or 2, and more preferably 1. In the above formula (1), the value of n is also from 1 to 4, which is also within the scope of the present invention. The preferred value of n is 2 to 4, more preferably 2 to 3, and even more preferably 2.

[0090] In the case of equation (0), the sum of m and n is 2 to 8, preferably 2 to 7, more preferably 2 to 6, and particularly preferably 2 to 5.

[0091] In the case of formula (1), the sum of m and n is 3 to 8, more preferably 3 to 7, even more preferably 3 to 6, and particularly preferably 3 to 5.

[0092] In the above equation (0), when l=0, R 1 R 2 R 4 Preferably, it contains substituents with two or more carbon atoms. Especially R 1 R 2 R 4 Preferably, it is a hydrocarbon group consisting only of carbon and hydrogen, and more specifically, it is aliphatic hydrocarbon group, branched aliphatic hydrocarbon group, alicyclic hydrocarbon group, or aromatic hydrocarbon group with 2 to 10 carbon atoms.

[0093] In the above, R 1 R 2 Preferably, the substituent is an aliphatic hydrocarbon group, a branched aliphatic hydrocarbon group, or an alicyclic hydrocarbon group with 2 to 10 carbon atoms, more preferably 2 to 6, further preferably 2 to 4, and particularly preferably 2 to 3. Examples of preferred substituents include ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl, pentyl, hexyl, octyl, and decyl, more preferably ethyl, propyl, butyl, and hexyl, further preferably ethyl and butyl, and particularly preferably ethyl.

[0094] As mentioned above, R 4 More preferably, it is an aromatic hydrocarbon group, even more preferably phenyl or substituted phenyl, and particularly preferably phenyl.

[0095] Ring structures like those in formulas (0') and (1') can be alicyclic or aromatic. In the case of alicyclic structures, it is believed that a wider variety of stereoconformities can be formed, and therefore, the diverse active species described later can be expected. On the other hand, in the case of aromatic structures, it is believed that they are rigid structures that facilitate electron movement, and therefore, the effects of negative electron uniformity described later can be expected to be significant.

[0096] In the case of the aforementioned alicyclic structure containing double bonds, it may appear at first glance that the R atoms have disappeared. However, since the R atoms bonded to adjacent carbon atoms can be considered as directly bonding to each other to form double bonds (or binary rings), it falls within the scope of this invention. Structures where such double bonds are formed at specific positions are aromatic structures, and therefore aromatic structures also fall within the scope of this invention.

[0097] As described above, the carbamate compounds of the present invention are suitable for use as internal donor compounds (Lewis bases) in solid titanium catalyst compositions. Solid titanium catalyst compositions containing carbamate compounds with such specific structures tend to exhibit an excellent balance of activity, stereospecificity, molecular weight controllability, reaction control, etc. The reasons for such effects are not currently clear, but the inventors speculate as follows.

[0098] Consider the following possibility: As mentioned above, among the functional groups bonded to A, the atoms directly bonded to A are different elements such as nitrogen and oxygen. The carbamate compound is electronically unbalanced, resulting in a structure with active electron movement due to electron cloud segregation. Furthermore, these functional groups are groups containing structures with two or more heteroatoms bonded via a single carbon atom. From this perspective, it is also considered a structure that may cause electron cloud segregation. That is, it can be considered an electronically active structure in a dual or triple sense. Additionally, since it can also be an asymmetric structure in terms of molecular structure, it is expected that a greater variety of active species can be formed. As mentioned above, in the case where the structure of formula (1') is an aromatic structure, electron segregation may become more pronounced.

[0099] On the other hand, when the structure of formula (1') is an alicyclic structure, it is expected that a variety of active species will be formed due to the main reason of stereoconformity.

[0100] Because such a diverse range of active species can be formed, it is expected that polymers with a wide molecular weight distribution will be generated. Furthermore, the expected electron bias will activate the appropriate electron supply to the titanium compound components described later. This is likely one of the main reasons for the increased polymerization activity. Additionally, due to this high activity, active species capable of high molecular weight can also be formed; therefore, as described later, when using the solid titanium catalyst components of the present invention, it is considered easy to obtain olefin polymers with a molecular weight distribution extended towards the high molecular weight side.

[0101] On the other hand, in the case of forming too many active species, it may be easy to obtain active species with low activity and stereospecificity. Therefore, in the structure of formula (1'), a heterocyclic structure that is somewhat rigid should be advantageous.

[0102] As such carbamate compounds, structures like the following can be exemplified. It should be noted that the structural formulas of the exemplified compounds below have stereoisomers, some of which are explicitly described in the isomer structures, but sometimes are also included in the isomer structures not shown.

[0103] [Chemistry 6]

[0104]

[0105] [Chemistry 7]

[0106]

[0107] [Chemistry 8]

[0108]

[0109] [Chemistry 9]

[0110]

[0111] [Chemistry 10]

[0112]

[0113] [Chemistry 11]

[0114]

[0115] [Chemistry 12]

[0116]

[0117] [Chemistry 13]

[0118]

[0119] [Chemistry 14]

[0120]

[0121] [Chemistry 15]

[0122]

[0123] [Chemistry 16]

[0124]

[0125] [Chemistry 17]

[0126]

[0127] [Chemistry 18]

[0128]

[0129] [Chemistry 19]

[0130]

[0131] [Chemistry 20]

[0132]

[0133] [Chemistry 21]

[0134]

[0135] It should be noted that in the above structural formulas, methyl is represented by "Me", ethyl by "Et", propyl by "Pr", butyl by "Bu", phenyl by "Ph", benzyl by "Bn", cyclohexyl by "Cy", and trifluoromethyl by "CF3". Additionally, "n" represents "normal", "i" represents "iso", and "t" represents "tertiary".

[0136] Furthermore, the structure contains carbon atoms at intersections and the ends of lines. This method of representing compound structures is well-known to those skilled in the art.

[0137] <Methods for manufacturing carbamate compounds>

[0138] The method for producing the carbamate compounds of the present invention is not particularly limited; for example, the "synthetic examples" described later can be used. Alternatively, the above-mentioned carbamate compounds can be produced using known reactions. The above-mentioned carbamate compounds can be synthesized by synthesizing each part using known synthetic methods and bonding them using known methods. More specifically, a method for synthesizing carbamate compounds by synthesizing an amide alcohol as described below can be illustrated. Furthermore, R' in the following formulas refers to a substituent bonded to an adjacent atom via a carbon atom.

[0139] (Synthetic method of N-amide moiety)

[0140] In reaction (2) below, for example, an amide compound can be synthesized by reacting an amino alcohol compound with one equivalent of an acyl chloride in the presence of a base. The amino alcohol used can also be the corresponding hydrochloride salt. There are no particular limitations on the base used, and examples include sodium hydroxide, potassium hydroxide, pyridine, N,N-dimethyl-4-aminopyridine, and triethylamine.

[0141] [Chemistry 22]

[0142]

[0143] Alternatively, as another method, the amide compound corresponding to reaction formula (2) above can also be synthesized as shown in reaction formula (3) below by reacting an amino alcohol compound with an acyl chloride of 2 equivalents or more in the presence of a base, followed by reaction with a base. The amino alcohol used in the synthesis of the N-amide / O-ester compound can also be the corresponding hydrochloride salt, and there is no particular limitation on the base. Examples of bases include sodium hydroxide, potassium hydroxide, pyridine, N,N-dimethyl-4-aminopyridine, and triethylamine. In addition, as a method for synthesizing the N-amide / O-ester compound, methods such as reacting an amino alcohol compound with a carboxylic acid in the presence of an acid catalyst, and methods using condensing agents such as N,N'-dicyclohexylcarbodiimide (DCC) can also be mentioned (see reaction formula (4) below). In addition, there is no particular limitation on the base used in the synthesis of the amide compound. For example, inorganic bases such as sodium hydroxide and potassium hydroxide, and organic bases such as piperidine and pyrrolidine can be used.

[0144] [Chemistry 23]

[0145]

[0146] [Chemistry 24]

[0147]

[0148] (Synthetic method of N-carbamate moiety)

[0149] The N-carbamate compound shown in reaction formula (5) below can be synthesized, for example, by reacting an amino alcohol compound with one equivalent of chloroformate in the presence of a base. The amino alcohol used can also be the corresponding hydrochloride salt. There are no particular limitations on the base, and examples include pyridine, N,N-dimethyl-4-aminopyridine, and triethylamine.

[0150] [Chemistry 25]

[0151]

[0152] Alternatively, as another method, the N-carbamate compound corresponding to reaction formula (5) above can also be synthesized by reacting an amino alcohol compound with 2 equivalents or more of chloroformate in the presence of a base, as shown in reaction formula (6) below, followed by reaction with a base. The amino alcohol used in the synthesis of the N-carbamate compound / O-carbonate compound can also be the corresponding hydrochloride salt. There are no particular limitations on the base, for example, pyridine, N,N-dimethyl-4-aminopyridine, and triethylamine. In addition, there are no particular limitations on the base used in the synthesis of the N-carbamate compound, for example, inorganic bases such as sodium hydroxide and potassium hydroxide, and organic bases such as piperidine and pyrrolidine can be used.

[0153] [Chemistry 26]

[0154]

[0155] (Synthetic method of diamino carbonyl moiety)

[0156] The diaminocarbonyl compound shown in formula (7) below can be synthesized, for example, by reacting an amino alcohol compound with one equivalent of carbamoyl chloride in the presence of a base. The amino alcohol used can also be the corresponding hydrochloride salt. There are no particular limitations on the base, and examples include sodium hydroxide, potassium hydroxide, pyridine, N,N-dimethyl-4-aminopyridine, and triethylamine.

[0157] [Chemistry 27]

[0158]

[0159] Alternatively, the diaminocarbonyl compound shown in reaction formula (7) above can also be synthesized as shown in reaction formula (8) below by reacting an amino alcohol compound with a 1 equivalent of an imidazolium salt in the presence of a base. The amino alcohol used can also be the corresponding hydrochloride salt. There are no particular limitations on the base, and examples include pyridine, N,N-dimethyl-4-aminopyridine, triethylamine, n-butyllithium, etc.

[0160] [Chemistry 28]

[0161]

[0162] (Synthetic method of O-carbamate moiety)

[0163] The compound shown in reaction formula (9) below can be synthesized, for example, by reacting the above-mentioned phenols with chloroformates in the presence of a base. No particular base is specified, but examples include pyridine, N,N-dimethyl-4-aminopyridine, and triethylamine.

[0164] [Chemistry 29]

[0165]

[0166] (Synthetic methods for N-alkyl moieties)

[0167] The compound shown in reaction formula (10) below can be synthesized, for example, by reacting the above compound with a base followed by a reaction with a haloalkyl group. The base is not particularly limited; examples include organolithium reagents and sodium hydride.

[0168] [Chemistry 30]

[0169]

[0170] These compounds can be used for various applications described later. At this time, one compound can be used alone, or two or more can be used in combination. Furthermore, these carbamate compounds can also be used in combination with other compounds, provided that the purpose of the invention is not impaired. For example, when used as an internal donor in a solid titanium catalyst component, they can be used in combination with electron donors such as alcohols, known esters, and ethers described later.

[0171] In addition, when urethane compounds are used as components of solid titanium catalysts, they can be formed during the preparation of the aforementioned solid titanium catalyst components.

[0172] In addition to being internal donor components of the solid titanium catalyst used in the aforementioned olefin polymerization catalysts, the carbamate compounds of the present invention are also expected to have pharmaceutical applications, including pesticides, pharmaceuticals, pesticide intermediates, and raw materials. Furthermore, due to their expected characteristic polarity, they are also expected to be suitable as column packing agents for optical isomer separation columns, etc. Additionally, they are considered to have the potential to be used as raw materials for condensation polymers such as nylon.

[0173] Example

[0174] (Analytical methods for compounds)

[0175] 1 The structure was determined by H-NMR spectroscopy (400 MHz, JNM-ECZ400S / L1 type measuring instrument manufactured by Nippon Electronics Co., Ltd.), peak allocation was performed using conventional methods.

[0176] [Example 1]

[0177] <Synthesis of Compound 1>

[0178] Compound 1, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0179] [Chemistry 31]

[0180] (Compound 1)

[0181] [Chemistry 32]

[0182]

[0183] In a heated and dried 300 mL three-necked flask equipped with a stirrer, 2.93 g of 8-amino-1-naphthol hydrochloride (15.0 mmol, 1 equivalent) and 60 mL of chloroform (dehydrated) were added under a nitrogen atmosphere. Then, 6.04 mL of pyridine (dehydrated) (75.0 mmol, 5 equivalent) was slowly added dropwise at room temperature. After cooling the reaction solution in an ice bath, 3.87 mL of benzoyl chloride (33.0 mmol, 2.2 equivalent) was slowly added dropwise. After the addition was complete, the mixture was heated to room temperature and stirred for 5 hours. After the reaction was complete, the reaction solution was cooled again in an ice bath, and 15 mL of methanol was added. The mixture was stirred at room temperature for 30 minutes. Water, dichloromethane, and methanol were added to the reaction solution, and the mixture was extracted three times with dichloromethane. The collected organic layer was dried over sodium sulfate and concentrated using a rotary evaporator. The obtained 8.81 g crude product was purified by silica gel column chromatography (developing solvent: hexane:dichloromethane = 50:50 to 0:100 gradient) to give 3.60 g intermediate 1'. 3.60 g intermediate 1' and 70 mL methanol, 1.76 g potassium carbonate (12.7 mmol), were added to a 500 mL pear-shaped flask, and the mixture was stirred at 40 °C for 2 hours. After the reaction was complete, water and dichloromethane were added, and the mixture was extracted three times with dichloromethane. Then, ammonium chloride was added to the aqueous layer to make it acidic, and the mixture was extracted three more times with dichloromethane. The collected organic layer was dried over sodium sulfate and concentrated using a rotary evaporator. The solution was suspended in hexane and purified by filtration, yielding 2.53 g of compound 1 (9.61 mmol, yield 64%).

[0184] <Synthesis of Compound 2>

[0185] Compound 2, as shown below, was synthesized using the method described later.

[0186] [Chemistry 33]

[0187] (Compound 2)

[0188] In a heated and dried 1L three-necked flask equipped with a stirrer, 27.5 g of compound 1 (104.4 mmol, 1 equivalent) and 349 mL of pyridine were added under a nitrogen atmosphere, and the mixture was stirred at room temperature. 33.1 mL of diethylcarbamoyl chloride (261.1 mmol, 2.5 equivalent) was slowly added dropwise. After the addition was complete, the reaction solution was refluxed for 1 hour. After the reaction was complete, the reaction solution was cooled to room temperature. Then, the reaction solution was added to 800 mL of ice-cooled distilled water. The mixture was extracted twice with diethyl ether, and the resulting organic layer was washed once each with 1 equivalent of hydrochloric acid and saturated sodium bicarbonate aqueous solution, and dried over anhydrous magnesium sulfate. The mixture was concentrated using a rotary evaporator to give 23.8 g of crude product. The crude product was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate = 4:1 to 2:1 gradient) to give 15.1 g of compound 2 (41.7 mmol, yield 40%).

[0189] <Preparation of solid titanium catalyst composition [α1]>

[0190] After thoroughly purging a 1L glass container with nitrogen, add 85.8g of anhydrous magnesium chloride, 321g of decane, and 352g of 2-ethylhexanol. Heat the mixture at 130°C for 3 hours to prepare a homogeneous solution. Add 241g of this solution and 6.43g of ethyl benzoate to the glass container and stir to mix at 50°C for 1 hour.

[0191] After cooling the resulting homogeneous solution to room temperature, 38.3 ml of this homogeneous solution was added dropwise over 45 minutes with stirring to 100 ml of titanium tetrachloride maintained at -20°C. After addition, the temperature of the mixture was raised to 80°C over 3.8 hours. At 80°C, 1.83 g of the aforementioned compound 2 was added to the mixture. The temperature was then raised to 120°C over 40 minutes and maintained at the same temperature with stirring for 35 minutes. After the reaction, the solid fraction was collected by hot filtration. This solid fraction was resuspended in 100 ml of titanium tetrachloride and then heated again at 120°C with stirring for 35 minutes. After the reaction, the solid fraction was collected again by hot filtration and thoroughly washed with 100°C decane and room temperature decane until no free titanium compounds were detected in the washings. The solid titanium catalyst component [α1] prepared by the above operations was stored in the form of a decane slurry. A portion of this slurry was dried to investigate the catalyst composition. The solid titanium catalyst [α1] thus obtained has the following composition: 0.42% by mass of titanium, 1.4% by mass of magnesium, and 0.11% by mass of 2-ethylhexanol residues.

[0192] Formal Aggregation

[0193] In a 2-liter polymerizer, 500g of propylene and 1NL of hydrogen were added at room temperature. Then, a mixture prepared by mixing 7ml of heptane, 0.5 mmol of triethylaluminum, 0.1 mmol of cyclohexylmethyldimethoxysilane, and 0.004 mmol (titanium atom conversion) of solid titanium catalyst [α1] was added at 25°C for 10 minutes. The polymerizer temperature was rapidly increased to 70°C while stirring. After polymerization at 70°C for 1.5 hours, the reaction was stopped with a small amount of ethanol, and the propylene was purged. The resulting polymer particles were further dried under reduced pressure at 80°C overnight. The activity, specific gravity, MFR, decane insoluble content, Tm, Tmf, and MWD are as follows.

[0194] Activity: 34.1 Kg-PP / g-catalyst

[0195] Specific gravity: 470 kg / m³ 3

[0196] MFR: 1.1g / 10 minutes

[0197] Content of decane-insoluble components: 1.72% by mass

[0198] Tm: 163.7℃, 148.2℃

[0199] Tc: 117.1℃

[0200] Tmf: 172.4℃

[0201] ΔH: 91.1 J / g

[0202] Mw / Mn: 11.22

[0203] Mz / Mw: 5.45

[0204] The methods for determining the above-mentioned physical properties are as follows.

[0205] (1) Specific gravity:

[0206] The measurements were performed according to JIS K-6721.

[0207] (2) Melt Flow Rate (MFR):

[0208] According to ASTM D 1238E, the test temperature is set at 230°C with a load of 2.16 kg for the case of propylene polymer.

[0209] (3) Amount of decane soluble (insoluble) components:

[0210] Add approximately 3 grams of propylene polymer to a small glass measuring container (measured up to 10). -4The unit is grams, and the weight is expressed as b (grams) in the following formula. 500 ml of decane and a heat-resistant stabilizer soluble in decane were heated to 150°C over 2 hours with stirring under a nitrogen atmosphere to dissolve the propylene polymer. After maintaining the temperature at 150°C for 2 hours, the mixture was slowly cooled to 23°C over 8 hours. The resulting liquid containing the propylene polymer precipitate was filtered under reduced pressure using a 25G-4 glass filter manufactured by Tokyo Glass Equipment Co., Ltd. 100 ml of the filtrate was taken and dried under reduced pressure to obtain a portion of the decane-soluble component, and its weight was determined to 10. -4 The unit is grams (the weight is expressed as a (grams) in the following formula). After this operation, the amount of decane-soluble components is determined by the following formula.

[0211] The content of soluble components of decane = 100 × (500 × a) / (100 × b)

[0212] The percentage of decane-insoluble components = 100 - 100 × (500 × a) / (100 × b)

[0213] (4) Molecular weight distribution (MWD):

[0214] Gel permeation chromatograph: HLC-8321 GPC / HT model manufactured by Tosoh Corporation

[0215] Detector: Differential refractometer

[0216] Column: Connect two TSKgel GMH6-HT and two TSKgel GMH6-HTL tubes manufactured by Tosoh Corporation in series.

[0217] Mobile phase medium: o-dichlorobenzene

[0218] Flow rate: 1.0 ml / min

[0219] Measurement temperature: 140℃

[0220] Method for preparing the standard curve: Use a standard polystyrene sample.

[0221] Sample concentration: 0.1% (w / w)

[0222] Sample solution volume: 0.4 ml

[0223] The results were analyzed using known methods under the above conditions to calculate the weight-average molecular weight (Mw), number-average molecular weight (Mn), Z-average molecular weight (Mz), and the Mw / Mn and Mz / Mw values ​​as indicators of molecular weight distribution (MWD). The measurement time for each sample was 60 minutes.

[0224] (5) Melting point (Tm) of the polymer:

[0225] The melting point (Tm), crystallization temperature (Tc), and heat of fusion (ΔH) of the polymer in this invention were determined using a differential scanning calorimeter (DSC) with a PerkinElmer DSC8000 apparatus. 3–10 mg of the sample was sealed in an aluminum dish and heated from room temperature to 200°C at a rate of 100°C / min. The sample was held at 200°C for 5 minutes, then cooled to 30°C at a rate of 10°C / min. The peak temperature observed in this cooling test was designated as the crystallization temperature (Tc), and the heat release determined by the peak area was designated as ΔH. Next, after being held at 30°C for 5 minutes, the sample was heated a second time to 200°C at a rate of 10°C / min. The peak temperature observed in this second heating test was designated as the melting point (Tm).

[0226] The final melting point (Tmf) of the polymer in this invention was determined using a differential scanning calorimeter (DSC) with a PerkinElmer DSC8000 apparatus. 3–10 mg of sample was sealed in an aluminum dish and heated from room temperature to 240°C at 80°C / min. The sample was held at 240°C for 1 minute, then cooled to 0°C at 80°C / min. After holding at 0°C for 1 minute, the sample was heated to 150°C at 80°C / min and held for 5 minutes. Finally, the sample was heated to 180°C at 1.35°C / min, and the intersection of the tangent at the inflection point on the high-temperature side of the peak obtained in this final heating test and the baseline was taken as the final melting point (Tmf).

[0227] Tmf can be considered a parameter for evaluating the crystal structure of components exhibiting very high stereoregularity, the ease of crystallization of polymers in the ultra-high molecular weight region that are considered to have a tendency to be difficult to crystallize, and the crystal structure. More specifically, the higher the Tmf value, the easier it is for the ultra-high molecular weight polymer component to form crystals with high heat resistance.

[0228] [Example 2]

[0229] <Synthesis of Compound 3>

[0230] Compound 3, as shown below, was synthesized using the method described later.

[0231] [Chemistry 34]

[0232] (Compound 3)

[0233] In a heated and dried 2L three-necked flask equipped with a stirrer, 15.1 g of compound 2 (41.7 mmol, 1 equivalent) and 417 mL of dehydrated THF were added under a nitrogen atmosphere, and the mixture was stirred while ice-cooled. 4.55 g of sodium hydride (55%, liquid paraffin dispersion, 104.2 mmol, 2.5 equivalent) was slowly added, and the mixture was stirred for 30 minutes while ice-cooled. Next, 5.19 mL of iodomethane (83.4 mmol, 2 equivalent) was added, and the resulting reaction solution was stirred at room temperature for 4 hours. The mixture was cooled again in an ice bath, and 200 mL of distilled water was added. The mixture was extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solution was concentrated using a rotary evaporator, yielding 19.5 g of crude product. The crude product was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate = 2:1 to 1:1 gradient) and recrystallization using a mixed solution of hexane and ethyl acetate, yielding 14.0 g of compound 3 (37.2 mmol, yield 89%, pale yellow crystals). The obtained compound 3... 1 The H-NMR data are shown below.

[0234] 1 ¹H NMR (400MHz, CDCl₃, TMS as internal standard): δ 7.70 (dt, J=8.3, 1.5Hz, 2H), 7.50 (t, J=7.9Hz, 1H), 7.36–7.32 (m, 2H), 7.29–7.25 (m, 1H, overlapping with CHCl₃ peak), 7.22 (dd, J=8.3, 7.3Hz, 1H), 7.13–7.08 (m, 1H), 7.06–6.97 (m, 3H), 3.76–3.65 (m, 1H), 3.52–3.31 (m, 6H), 1.28 (t, J=7.2Hz, 3H), 1.18 (t, J=7.2Hz, 3H).

[0235] [Example 3]

[0236] <Synthesis of Compound 4>

[0237] Compound 4, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0238] [Chemistry 35]

[0239] (Compound 4)

[0240] [Chemistry 36]

[0241]

[0242] In a heated and dried 300 mL three-necked flask equipped with a stirrer, 2.93 g of 8-amino-1-naphthol hydrochloride (15.0 mmol, 1 equivalent) and 60 mL of chloroform (dehydrated) were added under a nitrogen atmosphere. Then, 5.93 g of pyridine (dehydrated) (75.0 mmol, 5 equivalent) was added dropwise at room temperature. After cooling the reaction solution in an ice bath, 5.52 g of o-toluyl chloride (35.7 mmol, 2.4 equivalent) was added dropwise. The mixture was stirred at room temperature for 20 hours after the addition was complete. After the reaction was complete, the reaction solution was cooled again in an ice bath, and 15 mL of methanol was added. The mixture was stirred at room temperature for 30 minutes. Water and dichloromethane were added, and the mixture was extracted four times with dichloromethane. The collected organic layer was dried over sodium sulfate and concentrated using a rotary evaporator. The obtained 9.00 g crude product was purified by silica gel column chromatography (using a hexane to ethyl acetate mixture continuously varied from 95:5 to 90:10 as the developing solvent) to give 5.03 g intermediate 2. 5.03 g of intermediate 2, 100 mL of methanol, and 2.29 g of potassium carbonate (16.6 mmol) were added to a 300 mL round-bottom flask, and the mixture was stirred at 40 °C for 2 hours. After the reaction was complete, water and ethyl acetate were added, and the mixture was extracted four times with ethyl acetate and twice with dichloromethane. The collected organic layer was dried over sodium sulfate and concentrated using a rotary evaporator to give a crude product as a brown solid. The above reaction was further repeated on a 1 / 3 scale to give the crude product. The crude products from the two reactions were combined, ultrasonically washed with hexane, and filtered to give 4.54 g of compound 4 (16.4 mmol). The obtained compound 4... 1 The H-NMR data are shown below.

[0243] 1 H-NMR (400MHz, CDCl3, TMS as internal standard): δ2.53 (s, 3H), 6.75 (dd, J=1.0, 7.6Hz, 1H), 7.18–7.27 (m, 4H, overlapping with CHCl3 peak), 7.33 (td, J=1.3, 7.4Hz, 1H), 7.40–7.49 (m, 2H), 7.52–7.60 (m, 2H), 8.82 (d, J=7.3Hz, 1H), 11.00 (s, 1H).

[0244] <Synthesis of Compound 5>

[0245] Compound 5, shown below, was synthesized using the method described later, according to the following reaction formula.

[0246] [Chemistry 37]

[0247] (Compound 5)

[0248] [Chemistry 38]

[0249]

[0250] In a heated and dried 300 mL three-necked flask equipped with a stirrer, 3.19 g of compound 4 (11.5 mmol, 1 equivalent) and 60 mL of pyridine (dehydrated) were added under a nitrogen atmosphere. Then, 3.90 mL of diethylcarbamoyl chloride (30.8 mmol, 2.7 equivalent) was added dropwise at room temperature, and the mixture was refluxed for 16 hours. After the reaction was complete, the reaction solution was cooled in an ice bath, 30 mL of water was added, and the mixture was stirred at room temperature for 30 minutes. After the addition of water and ethyl acetate, the mixture was extracted three times with ethyl acetate. The collected organic layer was washed three times with water, further washed once with saturated brine, dried over sodium sulfate, and concentrated using a rotary evaporator. The resulting 4.61 g of crude product was purified by silica gel column chromatography (using a continuously varying hexane to ethyl acetate ratio from 90:10 to 80:20 as the developing solvent) to give 3.51 g of compound 5 (9.32 mmol, 81% yield). The obtained compound 5... 1 The H-NMR data are shown below.

[0251] 1 ¹H NMR (400MHz, CDCl₃, TMS as internal standard): δ 0.93–1.06 (m, 6H), 2.52 (s, 3H), 2.80–2.99 (m, 2H), 3.15–3.26 (m, 2H), 7.05 (br d, J = 7.6 Hz, 1H), 7.18–7.29 (m, 2H, overlapping with CHCl₃ peak), 7.32–7.38 (m, 1H), 7.39–7.44 (m, 1H), 7.47–7.57 (m, 2H), 7.66 (dd, J = 0.9, 8.2 Hz, 1H), 7.72 (dd, J = 0.9, 8.2 Hz, 1H), 8.66 (m, 1H), 9.52 (br s, 1H).

[0252] [Example 4]

[0253] <Synthesis of Compound 6>

[0254] Compound 6, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0255] [Chemistry 39]

[0256] (Compound 6)

[0257] [Chemistry 40]

[0258]

[0259] In a heated and dried 200 mL three-necked flask equipped with a stirrer, 2.45 g of compound 5 (6.50 mmol, 1 equivalent), 36 mL of tetrahydrofuran (dehydrated), and 4 mL of N,N′-dimethylformamide (dehydrated) were added under a nitrogen atmosphere. The reaction solution was cooled in an ice bath, and then 0.37 g of sodium hydride (55%, liquid paraffin dispersion, 8.50 mmol, 1.3 equivalent) was added. After stirring for 50 minutes, 1.11 mL of iodomethane (17.8 mmol, 2.7 equivalent) was added dropwise. After stirring for 20 minutes, the mixture was heated to room temperature and stirred for 18.5 hours. After the reaction was complete, the reaction solution was cooled again in an ice bath, and 10 mL of water was added. The mixture was stirred at room temperature for 30 minutes. After adding water and ethyl acetate, the mixture was extracted three times with ethyl acetate. The collected organic layer was washed three times with water, and then once with saturated brine. After drying with sodium sulfate, the mixture was concentrated using a rotary evaporator to give 3.13 g of crude product. This was combined with 1.74 g of crude product obtained by separately carrying out the same reaction on a small scale, and purified by silica gel column chromatography (using a hexane to ethyl acetate mixture continuously varied from 80:20 to 70:30 as the developing solvent) to give 3.75 g of compound 6 (9.16 mmol). The obtained compound 6... 1 The H-NMR data are shown below.

[0260] 1 1H-NMR (400MHz, CDCl3, TMS as internal standard): δ 1.29 (dt, J=7.2, 25.1Hz, 6H), 2.46 (s, 3H), 3.33–3.44 (m, 5H), 3.58 (m, 1H), 3.86 (m, 1H), 6.62–6.67 (m, 1H), 6.91 (td, J=7.3, 8.3Hz, 1H), 6.98–7.05 (m, 3H), 7.17 (dd, J=7.3, 8.3Hz, 1H), 7.29 (dd, J=1.1, 7.7Hz, 1H), 7.48 (t, J=7.9Hz, 1H), 7.63–7.68 (m, 2H).

[0261] [Example 5]

[0262] <Synthesis of Compound 7>

[0263] Compound 7, shown below, was synthesized using the method described later, according to the following reaction formula.

[0264] [Chemistry 41]

[0265] (Compound 7)

[0266] [Chemistry 42]

[0267]

[0268] In a heated and dried 200 mL three-necked flask equipped with a stirrer, 2.89 g of compound 2 (7.9 mmol, 1 equivalent), 45 mL of tetrahydrofuran (dehydrated), and 9 mL of N,N-dimethylformamide (dehydrated) were added under a nitrogen atmosphere. The mixture was then cooled in an ice bath, and 0.44 g of sodium hydride (55%, liquid paraffin dispersion, 10.0 mmol, 1.3 equivalent) was slowly added, followed by stirring for 30 minutes. Then, 1.36 g of iodomethane (8.7 mmol, 1.1 equivalent) was added dropwise. After the addition was complete, the mixture was heated to room temperature and stirred for 19 hours. After the reaction was complete, the reaction solution was cooled again in an ice bath, and 3 mL of water was added, followed by stirring at room temperature for 30 minutes. Water and ethyl acetate were added to the reaction solution, followed by extraction with ethyl acetate once. The organic phase was washed three times with water and once with saturated brine. The collected organic layer was dried over magnesium sulfate and concentrated using a rotary evaporator. The crude product was purified by silica gel column chromatography (using a continuously varying hexane and ethyl acetate mixture from 100:0 to 70:30 as the developing solvent) and ODS column chromatography (using a continuously varying water and methanol mixture from 100:0 to 55:45 as the developing solvent) to give 1.59 g of compound 7 (4.1 mmol, 51% yield, white crystals). The obtained compound 7... 1 The H-NMR data are shown below.

[0269] 1 ¹H-NMR (400MHz, CDCl₃, TMS as internal standard): δ 7.74–7.69 (m, 2H), 7.52 (t, J = 7.9 Hz, 1H), 7.35–7.29 (m, 3H), 7.19 (dd, J = 8.3, 7.3 Hz, 1H), 7.11 (tt, J = 7.3, 1.7 Hz, 1H), 7.03 (tt, J = 7.4, 1.5 Hz, 2H), 6. 87 (dd, J=7.3, 1.2Hz, 1H), 4.58 (td, J=13.7, 6.7Hz, 1H), 3.69 (td, J=14.4, 7.1Hz, 1H), 3.51-3 .33(m, 3H), 3.23(dt, J=20.3, 7.0Hz, 1H), 1.25(t, J=7.2Hz, 3H), 1.18(td, J=7.0, 4.0Hz, 6H).

[0270] [Example 6]

[0271] <Synthesis of Compound 8>

[0272] Compound 8, shown below, was synthesized according to the reaction formula described below and the method described later.

[0273] [Chemistry 43]

[0274] (Mixed 8)

[0275] [Chemistry 44]

[0276]

[0277] In a heated and dried 2L three-necked flask equipped with a stirrer, 51.4 g of 1,8-diaminonaphthalene (324.6 mmol) and 171.2 mL of ethanol were added under a nitrogen atmosphere and stirred at room temperature. Then, 342.4 mL of a saturated aqueous solution of sodium bisulfite was added dropwise at room temperature. After the addition was complete, the mixture was refluxed for 24 hours. Then, it was allowed to cool naturally to room temperature, and 171.2 mL of a 6 mol / L aqueous solution of potassium hydroxide was added, followed by reflux for 3.5 hours. Then, it was allowed to cool naturally to room temperature, and 2.5 L of 2 mol / L hydrochloric acid was added. The resulting aqueous solution was extracted three times with 500 mL of ethyl acetate, and the target compound was extracted from the collected organic layer to the aqueous layer using 500 mL of 1 mol / L hydrochloric acid. 300 mL of a saturated aqueous solution of sodium carbonate was added to the aqueous layer, and the mixture was extracted with 500 mL of ethyl acetate. The collected organic layer was dried with magnesium sulfate and concentrated using a rotary evaporator to obtain 33.81 g of 8-amino-1-naphthol (yield 65%).

[0278] <Synthesis of Compound 9>

[0279] Compound 9, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0280] [Chemistry 45]

[0281] (Compound 9)

[0282] [Chemistry 46]

[0283]

[0284] In a heated and dried 1L three-necked flask equipped with a stirrer, 15.6 g of compound 8 (98.1 mmol, 1 equivalent) and 156 mL of ethanol were added under a nitrogen atmosphere, with stirring while cooling in a water bath. Next, 21.3 mL of diethyl dicarbonate (147.2 mmol, 1.5 equivalent) and 1.41 g of guanidine hydrochloride (14.7 mmol, 0.15 equivalent) were added, and the mixture was stirred at room temperature for 1.5 hours. The reaction solution was concentrated, and 300 mL of distilled water and 300 mL of ethyl acetate were added to the residue. The mixture was extracted three times with ethyl acetate, and the collected organic layers were dried over magnesium sulfate and concentrated using a rotary evaporator. The crude product was purified by two silica gel column chromatography operations (first solvent: chloroform / methanol, second solvent: hexane / ethyl acetate) to give 16.2 g of compound 9 (70.1 mmol, yield 71%).

[0285] <Synthesis of Compound 10>

[0286] Compound 10, as shown below, was synthesized using the method described below, according to the following reaction formula.

[0287] [Chemistry 47]

[0288] (Compound 10)

[0289] [Chemistry 48]

[0290]

[0291] In a heated and dried 1L three-necked flask equipped with a stirrer, 16.2 g of compound 9 (69.9 mmol, 1 equivalent) and 300 mL of pyridine (dehydrated) were added under a nitrogen atmosphere, followed by 9.30 mL of N,N-diethylcarbamoyl chloride (73.4 mmol, 1.05 equivalent). The mixture was heated to 120 °C and refluxed. After 4 hours, the reaction solution was allowed to cool naturally to room temperature, and 500 mL of distilled water was added. The aqueous layer was extracted three times with diethyl ether. The collected organic layer was washed once each with hydrochloric acid (1 mol / L) and saturated sodium bicarbonate aqueous solution, respectively. The organic layer was dried over magnesium sulfate and concentrated using a rotary evaporator. The crude product was purified twice by silica gel column chromatography (first time with chloroform / methanol, second time with hexane / ethyl acetate), and further washed with a 9:1 mixture of hexane / ethyl acetate to give 13.95 g of compound 10 (60% yield). The obtained compound 10 1 The H-NMR data are shown below.

[0292] 1H-NMR (500 MHz, CDCl3, TMS as internal standard): δ 1.25 (t, J = 7.5 Hz, 3H), 1.31 (t, J = 7.0 Hz, 3H), 1.37 (t, J = 7.5 Hz, 3H), 3.46 (q, J = 7.5 Hz, 2H), 3.61 (q, J = 7.5 Hz, 2H), 4.23 (q, J = 7.0 Hz, 2H), 7.08–7.10 (m, 1H), 7.39–7.46 (m, 2H), 7.57–7.58 (m, 1H), 7.68–7.70 (m, 1H), 8.20 (br s, 1H), 8.50 (br s, 1H).

[0293] [Example 7]

[0294] <Synthesis of Compound 11>

[0295] Compound 11, as shown below, was synthesized using the method described below, according to the following reaction formula.

[0296] [Chemistry 49]

[0297] (Compound 11)

[0298] [Transformation 50]

[0299]

[0300] In a heated and dried 3L three-necked flask equipped with a stirrer, 21.6 g of compound 10 (65.5 mmol) and 655 mL of dehydrated tetrahydrofuran were added under a nitrogen atmosphere, and the reaction solution was ice-cooled. 3.43 g of sodium hydride (55%, liquid paraffin dispersion, 78.6 mmol, 1.2 equivalents) was slowly added, followed by the dropwise addition of 4.28 mL of iodomethane (67.8 mmol, 1.05 equivalents) after 1 hour. After the addition was complete, the mixture was heated to room temperature and stirred for 1 hour. The reaction solution was ice-cooled again, and 300 mL of distilled water was added dropwise. The reaction solution was extracted three times with ethyl acetate. The collected organic layers were washed with saturated brine, dried over magnesium sulfate, and concentrated using a rotary evaporator. The crude product was purified by repeated silica gel column chromatography to give 5.35 g of compound 11 (yield 24%).

[0301] 1H NMR (500 MHz, CDCl3, TMS as internal standard): δ 0.98–1.37 (m, 9H), 3.23–4.29 (m, 9H), 7.12–7.14 (m, 1H), 7.26–7.34 (overlapping with CHCl3 signal, m, 1H), 7.42–7.47 (m, 2H), 7.74–7.75 (m, 1H), 7.80–7.82 (m, 1H).

[0302] *Because it includes rotational isomers, the sum of the integral values ​​of the signals from protons from the same part of the structure is an integer value.

[0303] [Example 8]

[0304] <Synthesis of Compound 12>

[0305] Compound 12, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0306] [Chemistry 51]

[0307] (Compound 12)

[0308] [Chemistry 52]

[0309]

[0310] In a heated and dried 200 mL three-necked flask equipped with a stirrer, 3.61 g of compound 10 (10.9 mmol, 1 equivalent) and 54 mL of dehydrated tetrahydrofuran were added under a nitrogen atmosphere. The mixture was then cooled in an ice bath, and 0.50 g of sodium hydride (55%, liquid paraffin dispersion, 11.6 mmol, 1.1 equivalent) was slowly added, followed by stirring for 30 minutes. Then, 1.88 g of iodomethane (12.0 mmol, 1.1 equivalent) was slowly added dropwise. After the addition was complete, the mixture was heated to room temperature and stirred for 20 hours. After the reaction was complete, the reaction solution was cooled again in an ice bath, and 0.53 g of ethanol (11.6 mmol, 1.1 equivalent) was added, followed by stirring for 30 minutes at room temperature. The reaction solution was then concentrated using a rotary evaporator. The crude product was purified by silica gel column chromatography (using a continuously varying hexane to ethyl acetate mixture from 100:0 to 76:24 as the developing solvent), followed by purification by recrystallization from a hexane and dichloromethane mixture to give 2.57 g of compound 12 (7.18 mmol, 66% yield, white crystals). The obtained compound 12... 1 The H-NMR data are shown below.

[0311] 1H-NMR (400MHz, CDCl3, TMS as internal standard): δ 7.83 (dd, J=8.3, 1.0Hz, 1H), 7.74 (dd, J=8.3, 1.0Hz, 1H), 7.44 (q, J=7.6Hz, 2H), 7.23 (dd, J=7.3, 1.2Hz, 1H), 7.13 (dd, J=7.6, 1.0Hz, 1H), 4.16–3.96 (m, 3H), 3.79–3.17 (m, 5H), 1.28 (t, J=7.2Hz, 3H), 1.22 (t, J=7.1Hz, 3H), 1.17 (t, J=7.2Hz, 3H), 1.01 (t, J=7.2Hz, 3H).

[0312] [Example 9]

[0313] Synthesis of imidazolium salt 1

[0314] For use in the synthesis of compound 13 described later, the imidazolium salt 1 shown below was synthesized using the method described later according to the following reaction formula.

[0315] [Chemistry 53]

[0316] (Imidazolium salt 1)

[0317] [Chemistry 54]

[0318]

[0319] In a heated and dried 500 mL three-necked flask equipped with a stirrer, 53.5 g of carbonyl diimidazole (330 mmol, 1.1 equivalents) and 200 mL of dehydrated dichloromethane were added under a nitrogen atmosphere. The reaction solution was then ice-cooled. After cooling, 21.9 g of diethylamine (300 mmol, 1 equivalent) was added dropwise over 20 minutes. After the addition was complete, the reaction solution was slowly heated to room temperature and stirred at room temperature for 24 hours. The reaction solution was then ice-cooled again, and 200 mL of water was added dropwise. After extraction with dichloromethane four times, the collected organic layer was dried over sodium sulfate and concentrated using a rotary evaporator to give 56.3 g of intermediate 3 with a purity of 78%.

[0320] The intermediate 3 obtained by the above method was transferred to a 1 L reaction vessel, and after purging the interior with nitrogen, 500 mL of acetonitrile (dehydrated) and 181.4 g of iodomethane (1.28 mol, 4.9 equivalents) were added. The mixture was stirred at room temperature for 24 hours. Subsequently, the total volume was concentrated to obtain 111.7 g of imidazolium salt 1 with a purity of 81.3%.

[0321] <Synthesis of Compound 13>

[0322] Compound 13, as shown below, was synthesized using the method described below, according to the following reaction formula.

[0323] [Chemistry 55]

[0324] (Compound 13)

[0325] [Chemistry 56]

[0326]

[0327] In a heated and dried 1L four-necked flask equipped with a stirrer, under a nitrogen atmosphere, 52.5 g of imidazolium salt 1 (138 mmol, 1.1 equivalents), 500 mL of acetonitrile (dehydrated), 19.9 g of compound 8 (125 mmol, 1 equivalent), and 15.2 g of triethylamine (150 mmol, 1.2 equivalents) were added sequentially. The reaction solution was heated to 78.5 °C and refluxed for 18 hours. The reaction solution was then allowed to cool naturally to room temperature and concentrated. 500 mL of dichloromethane was added to the resulting black oil, and the solid was filtered off. 400 mL of water was added to the filtrate, and the mixture was extracted four times with dichloromethane. The collected organic layer was washed three times with water, and further washed once with saturated brine. The mixture was dried over sodium sulfate and concentrated using a rotary evaporator. The crude product was purified by silica gel column chromatography (hexane:ethyl acetate = 50:50) to give 29.5 g of a mixture containing intermediate 4.

[0328] In a 1L four-necked flask equipped with a mechanical stirrer and heated and dried, 27.4 g (NMR purity 75%, 80 mmol, 1 equivalent) of a mixture containing intermediate 4 obtained in the above reaction and 500 mL of dehydrated tetrahydrofuran were added under a nitrogen atmosphere, and the flask was ice-cooled. Then, 56 mL of [unspecified substance] was added dropwise over 20 minutes. n BuLi (hexane solution, 1.57 mol / L, 88 mmol, 1.1 equivalents). After the addition was complete, the internal temperature was raised to 65 °C and directly refluxed for 17 hours. Then, the reaction solution was cooled in an ice bath and 100 mL of water was added. Extracted three times with ethyl acetate, the collected organic layer was washed three times with water, and further washed once with saturated brine. The organic layer was dried over sodium sulfate and concentrated using a rotary evaporator. The crude product was purified by repeated silica gel column chromatography to give 5.33 g of compound 13 (yield 19%).

[0329] [Example 10]

[0330] <Synthesis of Compound 14>

[0331] Compound 14, as shown below, was synthesized using the method described below, according to the following reaction formula.

[0332] [Chemistry 57]

[0333] (Compound 14)

[0334] [Chem.58]

[0335]

[0336] In a heated and dried 300 mL three-necked flask equipped with a stirrer, 3.03 g of compound 1 (11.5 mmol, 1 equivalent) and 60 mL of pyridine (dehydrated) were added under a nitrogen atmosphere. Then, 3.63 mL of 1-piperidinyl chloride (28.8 mmol, 2.5 equivalent) was slowly added dropwise at room temperature, and the mixture was heated under reflux for 26.5 hours (oil bath 115°C, internal temperature 115°C). After the reaction was complete, the reaction solution was cooled in an ice bath, and 30 mL of water was slowly added, followed by stirring at room temperature for 30 minutes. After adding water and ethyl acetate, the mixture was extracted twice with ethyl acetate and three times with dichloromethane. The collected organic layer was washed three times with water, and sodium bicarbonate was added to the aqueous layer, followed by extraction three times with dichloromethane. The collected organic layer was dried over sodium sulfate and concentrated using a rotary evaporator. The obtained 5.40 g of crude product was purified by silica gel column chromatography (using a continuously varying hexane to dichloromethane mixture from 50:50 to 0:100 as the developing solvent) to give 3.43 g of compound 14 (9.16 mmol, 80% yield). The obtained compound 14... 1 The H-NMR data are shown below.

[0337] 1 ¹H NMR (400MHz, CDCl₃, TMS as internal standard): δ 1.33 (br s, 2H), 1.48 (br s, 4H), 3.28 (m, 4H), 7.09 (dd, J=1.2, 7.6Hz, 1H), 7.32–7.45 (m, 1H), 7.48–7.60 (m, 4H), 7.70 (dd, J=1.0, 8.3Hz, 1H), 7.74 (dd, J=1.0, 8.3Hz, 1H), 7.88–7.93 (m, 2H), 8.32 (br d, J=6.8Hz, 1H), 9.41 (br s, 1H).

[0338] [Example 11]

[0339] <Synthesis of Compound 15>

[0340] Compound 15, as shown below, was synthesized using the method described below, according to the following reaction formula.

[0341] [Chemistry 59]

[0342] (Compound 15)

[0343] [Transformation 60]

[0344]

[0345] In a thoroughly heated and dried 200 mL three-necked flask equipped with a stirrer, 2.32 g of compound 14 (6.20 mmol, 1 equivalent), 36 mL of tetrahydrofuran (dehydrated), and 4 mL of N,N′-dimethylformamide (dehydrated) were added under a nitrogen atmosphere. The reaction solution was cooled in an ice bath, and 0.35 g of sodium hydride (55%, liquid paraffin dispersion, 8.10 mmol, 1.3 equivalent) was slowly added. After stirring for 40 minutes, 0.46 mL of iodomethane (7.40 mmol, 1.2 equivalent) was slowly added dropwise. After stirring for 20 minutes, the temperature was slowly raised to room temperature, and stirring was continued for 19 hours. After the reaction was complete, the reaction solution was cooled again in an ice bath, and 10 mL of water was slowly added, stirring at room temperature for 30 minutes. After adding water and ethyl acetate, the mixture was extracted three times with ethyl acetate. The collected organic layer was washed three times with water, and further washed once with saturated brine. After drying with sodium sulfate, the mixture was concentrated using a rotary evaporator. The obtained 2.77 g of crude product was purified by silica gel column chromatography (using a hexane to ethyl acetate mixture continuously varied from 85:15 to 75:25 as the developing solvent), yielding 2.26 g of compound 15 (6.20 mmol, yield 94%). The obtained compound 15... 1 The H-NMR data are shown below.

[0346] 1 ¹H NMR (400MHz, CDCl₃, TMS as internal standard): δ 1.52–1.81 (m, 6H), 3.39–3.79 (m, 7H), 6.98 (dd, J=1.2, 7.3Hz, 1H), 7.00–7.06 (m, 2H), 7.08–7.14 (m, 1H), 7.21 (dd, J=7.3, 8.0Hz, 1H), 7.28 (dd, J=1.1, 7.7Hz, 1H), 7.32–7.36 (m, 2H), 7.50 (t, J=7.9Hz, 1H), 7.71 (dd, J=3.5, 7.2Hz, 2H).

[0347] [Example 12]

[0348] <Synthesis of Compound 16>

[0349] Compound 16, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0350] [Chemistry 61]

[0351] (Compound 16)

[0352] [Chemistry 62]

[0353]

[0354] 50.0 g of 2,5-dimethylanisole (367 mmol) and 0.65 g of iron powder (11.6 mmol) were added to a heated and dried 300 mL four-necked flask equipped with a stirrer. While cooling in a water bath, 58.7 g of bromine (367 mmol) was added dropwise over 38 minutes at room temperature. The mixture was then stirred at room temperature for 2 hours. After cooling with ice water, 200 mL of hexane and 100 mL of water were added, followed by decolorization with a small amount of sodium thiosulfate. The reaction solution was then neutralized with sodium hydroxide. The reaction solution was extracted with hexane, and the collected organic layer was washed with brine, dried over sodium sulfate, and concentrated using a rotary evaporator. The resulting 84.4 g of crude product was distilled under reduced pressure to give 44.86 g of compound 16 (56% yield).

[0355] <Synthesis of Compound 17>

[0356] Compound 17, as shown below, was synthesized using the method described below, according to the following reaction formula.

[0357] [Chemistry 63]

[0358] (Compound 17)

[0359] [Chemistry 64]

[0360]

[0361] 3.65 g of magnesium (150 mmol) was added to a heated and dried 200 mL four-necked flask equipped with a stirrer. After heating and drying under reduced pressure, the flask was purged with nitrogen. 40 mL of tetrahydrofuran was added, followed by a few drops of 1,2-dibromoethane. The mixture was heated, and then 22.09 g of compound 16 (tetrahydrofuran solution, 100 mmol, 40 mL) was added dropwise through a dropping funnel while maintaining steady reflux. The mixture was then stirred and allowed to return to room temperature to obtain a solution containing intermediate 5.

[0362] In a heated and dried 500 mL four-necked flask equipped with a stirrer, 1.78 g of tri(acetylacetone)cobalt(III), 0.75 mL of tetramethylethylenediamine (5.00 mmol), and 14.0 mL of 2-bromopropane (149 mmol) were added under a nitrogen atmosphere, and the mixture was cooled in an ice-water bath. A solution of intermediate 5 prepared in the preceding step was added dropwise over 45 minutes via a dropping funnel. After stirring for 1 hour and 20 minutes while cooled in an ice-water bath, the reaction was stopped by adding 1 mol / L hydrochloric acid. The resulting solution was extracted with diethyl ether, and the collected organic layer was washed with an aqueous sodium carbonate solution and brine, dried over sodium sulfate, and concentrated using a rotary evaporator. The obtained 18.38 g of crude product was distilled under reduced pressure to give 15.9 g of compound 17 in 86% yield.

[0363] <Synthesis of Compound 18>

[0364] Compound 18, as shown below, was synthesized using the method described below, according to the following reaction formula.

[0365] [Chemistry 65]

[0366] (Compound 18)

[0367] [Chemistry 66]

[0368]

[0369] 18.38 g of compound 17 (93.9 mmol) and 125 mL of dichloromethane were added to a heated and dried 500 mL four-necked flask equipped with a stir bar, and the flask was cooled in an ice-water bath. While stirring, the internal temperature was maintained between 3°C and 7°C, and 100 mL of a boron tribromide solution in dichloromethane (1 mol / L) was added dropwise over 30 minutes. Then, after stirring at room temperature for 2 hours, water was added dropwise while cooling in an ice-water bath. The mixture was then extracted with dichloromethane, and the organic layer was washed with an aqueous solution of sodium bicarbonate and brine, dried over sodium sulfate, and concentrated using a rotary evaporator. The resulting 17.2 g of crude product was purified by silica gel column chromatography (using a 100:1 mixture of toluene and ethyl acetate as the developing solvent) to give 14.0 g of compound 18 in 88% yield.

[0370] <Synthesis of Compound 19>

[0371] Compound 19, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0372] [Chemistry 67]

[0373] (Compound 19)

[0374] [Chemistry 68]

[0375]

[0376] 41.9 g of compound 18 (249 mmol) and 290 mL of dichloromethane were added to a 1 L four-necked flask equipped with a stirrer after heating and drying. The mixture was stirred while cooling in an ice-water bath. While maintaining the internal temperature at 0.3 °C to 2.3 °C, 17.4 mL of nitric acid (70%, 274 mmol) was added dropwise over 36 minutes. The mixture was further stirred in an ice-water bath for 21 hours, followed by stirring at room temperature for 5 hours. Then, 300 mL of an aqueous sodium bicarbonate solution was added, and the organic layer was extracted with dichloromethane. The collected organic layer was dried over sodium sulfate and concentrated using a rotary evaporator to give 54.3 g of crude product. The crude product was diluted with 100 mL of hexane and allowed to stand at room temperature for 64 hours to remove precipitated crystals. The supernatant was purified by silica gel column chromatography (using a 95:5 mixture of hexane and acetone) to give 17.69 g of compound 19 in 33% yield.

[0377] <Synthesis of Compound 20>

[0378] Compound 20, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0379] [Chemistry 69]

[0380] (Compound 20)

[0381] [Chemistry 70]

[0382]

[0383] 17.69 g of compound 19 (82.4 mmol), 2.0 g of Pd / C (5%, 55% aqueous), and 100 mL of ethanol were added to a heated and dried 200 mL reaction vessel equipped with a stir bar. The atmosphere was purged to nitrogen while stirring. The mixture was stirred at 50 °C while maintaining a hydrogen pressure of 0.6 to 0.9 MPa for 22 hours until the hydrogen pressure decreased. The hydrogen was then purged, and the atmosphere was purged to nitrogen. Tetrahydrofuran was added to the precipitate in the vessel to dissolve it, and the solution was filtered through a 1 μm hydrophilic PTFE membrane filter. The filtrate was concentrated using a rotary evaporator and transferred to a heated and dried 200 mL reaction vessel equipped with a stir bar. Another 100 mL of tetrahydrofuran and 1.0 g of Pd / C (5%, 55% aqueous) were added, and the atmosphere was purged to nitrogen while stirring. While stirring at 50°C, the mixture was pressurized by maintaining a hydrogen pressure of 0.6 to 0.9 MPa for 4.5 hours until the decrease in hydrogen pressure ceased. The hydrogen was then vented, and the atmosphere was replaced with nitrogen. The reaction solution was filtered through a 1 μm oleophilic PTFE membrane filter. The filtrate was concentrated using a rotary evaporator to obtain a crude solid product. This crude product was washed with hexane and dried under reduced pressure to give 14.72 g of compound 20 in 96% yield.

[0384] <Synthesis of Compound 21>

[0385] Compound 21, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0386] [Chemistry 71]

[0387] (Compound 21)

[0388] [Chemistry 72]

[0389]

[0390] In a heated and dried 200 mL three-necked flask equipped with a stirrer, 2.20 g of compound 20 (12.3 mmol, 1 equivalent) and 65 mL of dehydrated chloroform were added under a nitrogen atmosphere. The mixture was then cooled in an ice bath, and 1.07 g of pyridine (dehydrated, 13.5 mmol, 1.1 equivalent) and 1.82 g of benzoyl chloride (12.9 mmol, 1.1 equivalent) were slowly added, followed by stirring for 10 minutes. The ice bath was then removed, and the mixture was heated to room temperature and stirred for 6 hours. After the reaction was complete, the reaction solution was cooled again in an ice bath, and 2.0 mL of methanol (49.3 mmol, 4 equivalent) was added, followed by stirring at room temperature for 30 minutes. Water and ethyl acetate were added to the reaction solution, and the mixture was extracted with ethyl acetate, washed three times with water, and then further washed once with saturated brine. The solution was dried over magnesium sulfate and concentrated using a rotary evaporator. 17 mL of dichloromethane was added to dissolve the 3.50 g crude product, and then 70 mL of hexane was added while stirring. The mixture was cooled in an ice bath, causing the solid to precipitate. The solid was collected by filtration and washed three times with hexane to give 3.32 g of compound 21 (95% yield). The obtained compound 21... 1 The H-NMR data are shown below.

[0391] 1 1H-NMR (400MHz, CDCl3, TMS as internal standard): δ 7.95-7.92 (m, 2H), 7.89 (s, 1H), 7.81 (s, 1H), 7.63-7.59 (m, 1H), 7.56-7.51 (m, 2H), 7.02 (s, 1H), 3.16-3.06 (m, 1H), 2.31 (d, J=6.6Hz, 6H), 1.21 (d, J=6.8Hz, 6H).

[0392] <Synthesis of Compound 22>

[0393] Compound 22, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0394] [Chemistry 73]

[0395] (Compound 22)

[0396] [Chemistry 74]

[0397]

[0398] In a heated and dried 100 mL three-necked flask equipped with a stir bar, 3.32 g of compound 21 (11.7 mmol, 1 equivalent) and 40 mL of pyridine (dehydrated) were added under a nitrogen atmosphere. Then, while stirring at room temperature, 3.99 g of diethylcarbamoyl chloride (29.4 mmol, 2.5 equivalent) was added, and the mixture was heated to reflux in an oil bath at 120 °C for 17 hours. After the reaction was complete, the mixture was cooled to room temperature, and the reaction solution was added to 400 mL of ice-cooled pure water. The precipitate was filtered through a Kiriyama funnel, washed three times with pure water, and dried to give 3.32 g of crude product. The crude product was purified by silica gel column chromatography (using a continuously varying hexane to ethyl acetate ratio from 100:0 to 60:40 as the developing solvent) to give 1.35 g of compound 22. (3.5 mmol, 30% yield) 1 The H-NMR data are shown below.

[0399] 1 ¹H-NMR (400MHz, CDCl₃, TMS as internal standard): δ 7.91–7.88 (m, 2H), 7.80 (s, 1H), 7.56–7.52 (m, 1H), 7.49–7.44 (m, 2H), 7.07 (s, 1H), 3.37–3.30 (m, 4H), 3.20–3.10 (m, 1H), 2.23 (d, J = 2.2 Hz, 6H), 1.22 (d, J = 6.8 Hz, 6H), 1.07 (dt, J = 13.3, 5.9 Hz, 6H).

[0400] [Example 13]

[0401] <Synthesis of Compound 23>

[0402] Compound 23, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0403] [Chemistry 75]

[0404] (Compound 23)

[0405] [Chemistry 76]

[0406]

[0407] In a heated and dried 200 mL three-necked flask equipped with a stirrer, 2.66 g of compound 22 (6.9 mmol, 1 equivalent) and 45 mL of tetrahydrofuran (dehydrated) were added under a nitrogen atmosphere. The mixture was then cooled in an ice bath, and 0.32 g of sodium hydride (55%, liquid paraffin dispersion, 13.3 mmol, 1.9 equivalent) was slowly added, followed by stirring for 10 minutes. Then, 1.09 g of iodomethane (7.7 mmol, 1.1 equivalent) was slowly added dropwise, followed by stirring for 100 minutes. The mixture was then heated to room temperature and stirred for 18 hours. After the reaction was complete, the reaction solution was cooled again in an ice bath, and 1 mL of methanol (24.7 mmol, 3.6 equivalent) was added, followed by stirring for 10 minutes at room temperature. Then, 10 mL of saturated ammonium chloride aqueous solution was added to stop the reaction. The reaction solution was then extracted with pure water and ethyl acetate, washed twice with water, washed once with saturated brine, dried over magnesium sulfate, and concentrated using a rotary evaporator. The obtained 2.97 g crude product was suspended in 50 mL of hexane and filtered and washed three times with hexane to obtain 2.28 g of pale yellow crystals. The crude product was purified by silica gel column chromatography (using a continuously varying hexane:ethyl acetate ratio from 100:0 to 80:20 as the developing solvent) to give 2.22 g of compound 23 (5.60 mmol, yield 81%, white crystals). The obtained compound 23... 1 The H-NMR data are shown below.

[0408] 1 ¹H-NMR (400MHz, CDCl₃, TMS as internal standard): δ 7.30 (brs, 2H), 7.20 (tt, J=7.3, 1.6Hz, 1H), 7.13–7.08 (m, 2H), 6.95 (s, 1H), 3.52–3.31 (m, 4H), 3.27 (s, 3H), 2.96 (brs, 1H), 2.10 (brs, 6H), 1.28 (t, J=7.2Hz, 3H), 1.25–1.17 (m, 6H), 1.01 (d, J=5.6Hz, 3H).

[0409] [Example 14]

[0410] <Synthesis of Compound 24>

[0411] Compound 24, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0412] [Chemistry 77]

[0413] (Compound 24)

[0414] [Chemistry 78]

[0415]

[0416] In a heated and dried 500 mL three-necked flask equipped with a stirrer, 23.23 g of 4-isopropylphenol (170.6 mmol) and 65.1 mL of water were added under a nitrogen atmosphere, with stirring and ice cooling. Then, while maintaining the internal temperature below 2.9 °C, 18.6 mL of nitric acid (67%, 280.8 mmol) was added dropwise over 15 minutes. After stirring for 1.5 hours, 580 mL of water was added, and the reaction solution was extracted with ethyl acetate. The collected organic layer was dried over sodium sulfate and concentrated using a rotary evaporator to give 30.23 g of crude product. The crude product was purified by silica gel column chromatography (using a continuously varying hexane to dichloromethane ratio from 4:1 to 2:1 as the developing solvent) to give 23.80 g of compound 24 in 77% yield.

[0417] <Synthesis of Compound 25>

[0418] Compound 25, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0419] [Chemistry 79]

[0420] (Compound 25)

[0421] [Chemistry 80]

[0422]

[0423] In a heated and dried 2L single-necked flask equipped with a stirrer, 23.79 g of compound 24 (131.3 mmol) and 703.9 mL of ethanol were added. Next, 2.35 g of Pd / C (10%, 55% aqueous) was added, a hydrogen balloon was attached, and the interior was purged with hydrogen atmosphere. The mixture was stirred at room temperature for 3 hours. The reaction solution was filtered, the filtrate was concentrated, and hexane was added. The filtered solid was washed with hexane and dried to give 20.38 g of compound 25 in 93% yield.

[0424] <Synthesis of Compound 26>

[0425] Compound 26, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0426] [Chemistry 81]

[0427] (Compound 26)

[0428] [Chemistry 82]

[0429]

[0430] In a heated and dried 500 mL three-necked flask equipped with a stirrer, 3.02 g of compound 25 (20.0 mmol, 1 equivalent) and 100 mL of dehydrated chloroform were added under a nitrogen atmosphere. Then, 1.77 mL of dehydrated pyridine (22.0 mmol, 1.1 equivalent) was slowly added dropwise at room temperature. After cooling the reaction solution in an ice bath, 2.46 mL of benzoyl chloride (21.0 mmol, 1.05 equivalent) was slowly added dropwise. After the addition was complete, the mixture was heated to room temperature and stirred for 4 hours. After the reaction was complete, the reaction solution was cooled again in an ice bath, and 10 mL of methanol was added and stirred. After adding water and dichloromethane, the mixture was extracted three times with dichloromethane. The collected organic layer was washed once with brine, dried over sodium sulfate, and concentrated using a rotary evaporator. The obtained 5.49 g crude product was purified twice by silica gel column chromatography (developing solvent: 100% dichloromethane), yielding 4.90 g of compound 26 (19.2 mmol, 96%). The obtained compound 26... 1 The H-NMR data are shown below.

[0431] 1 H-NMR (400MHz, CDCl3, TMS as internal standard): δ 8.43 (s, 1H), 8.11 (br s, 1H), 7.93-7.89 (m 2H), 7.62-7.56 (m, 1H), 7.54-7.48 (m, 2H), 7.05-6.98 (m, 3H), 2.92-2.79 (m, 1H), 1.23 (d, J=7.1Hz, 6H).

[0432] <Synthesis of Compound 27>

[0433] Compound 27, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0434] [Chemistry 83]

[0435] (Compound 27)

[0436] [Chemistry 84]

[0437]

[0438] In a heated and dried 300 mL three-necked flask equipped with a stirrer, 3.83 g of compound 26 (15.0 mmol, 1 equivalent) and 100 mL of pyridine (dehydrated) were added under a nitrogen atmosphere. Then, 4.75 mL of diethylcarbamoyl chloride (37.5 mmol, 2.5 equivalent) was slowly added dropwise at room temperature, and the mixture was heated to reflux for 22.5 hours. After the reaction was complete, the reaction solution was cooled in an ice bath, and 30 mL of water was slowly added while stirring at room temperature. The mixture was then concentrated using a rotary evaporator, and after adding water and ethyl acetate, extracted three times with ethyl acetate. The collected organic layer was washed three times with water and once with brine, dried over sodium sulfate, and concentrated using a rotary evaporator. The resulting 6.36 g of crude product was purified by silica gel column chromatography (using a hexane to ethyl acetate mixture continuously varying from 100:0 to 85:15 as the developing solvent) to give 4.90 g of compound 27 (13.8 mmol, 92% yield). The resulting compound 27 1 The H-NMR data are shown below.

[0439] 1 1H-NMR (400MHz, CDCl3, TMS as internal standard): δ 8.44 (br s, 1H), 8.03 (br s, 1H), 7.90–7.85 (m, 2H), 7.54 (tt, J=7.3, 1.7Hz, 1H), 7.50–7.45 (m, 2H), 7.08–7.01 (m, 2H), 3.50–3.35 (m, 4H), 3.01–2.88 (m, 1H), 1.30–1.17 (m, 12H).

[0440] [Example 15]

[0441] <Synthesis of Compound 28>

[0442] Compound 28, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0443] [Chemistry 85]

[0444] (Compound 28)

[0445] [Chemistry 86]

[0446]

[0447] In a heated and dried 300 mL three-necked flask equipped with a stirrer, 3.01 g of compound 27 (8.50 mmol, 1 equivalent), 45 mL of tetrahydrofuran (dehydrated), and 5 mL of N,N'-dimethylformamide (dehydrated) were added under a nitrogen atmosphere. After cooling the reaction solution in an ice bath, 0.48 g of sodium hydride (55%, liquid paraffin dispersion, 11.1 mmol, 1.3 equivalent) was slowly added. After stirring for 30 minutes, 0.63 mL of iodomethane (10.2 mmol, 1.2 equivalent) was slowly added dropwise. The mixture was slowly heated to room temperature and stirred for 23 hours. After the reaction was complete, the reaction solution was cooled again in an ice bath, and 10 mL of water was slowly added while stirring at room temperature. After adding water and ethyl acetate, the mixture was extracted three times with ethyl acetate. The collected organic layer was washed three times with water and once with brine, dried over sodium sulfate, and concentrated using a rotary evaporator. The obtained 3.43 g of crude product was purified by silica gel column chromatography (using a hexane to ethyl acetate mixture continuously varied from 90:10 to 75:25 as the developing solvent) to give 2.76 g of compound 28 (7.49 mmol, yield 88%). The obtained compound 28... 1 The H-NMR data are shown below.

[0448] 1 ¹H NMR (400MHz, CDCl₃, TMS as internal standard): δ 7.35 (br d, J = 7.3Hz, 2H), 7.24–7.09 (m, 3H), 7.02 (br s, 2H), 6.80 (br s, 1H), 3.51–3.29 (m, 7H), 2.79–2.65 (m, 1H), 1.31–1.15 (m, 6H), 1.11–0.96 (m, 6H).

[0449] [Example 16]

[0450] <Synthesis of Compound 29>

[0451] Compound 29, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0452] [Chemistry 87]

[0453] (Compound 29)

[0454] [Chemistry 88]

[0455]

[0456] In a heated and dried 3L three-necked flask equipped with a stirrer, 75.0 g of 2,5-dimethylphenol, 950 mL of diethyl ether, and 950 mL of water were added under a nitrogen atmosphere, with stirring and ice cooling. Then, while maintaining the internal temperature below 4.8°C, 79.8 g of fuming nitric acid (97%) was added dropwise over 1 hour. After the addition was complete, the mixture was stirred for 30 minutes, and the reaction solution was extracted with diethyl ether. The collected organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated using a rotary evaporator to give 96.7 g of crude product. The crude product was purified by silica gel column chromatography (using a 4:1 mixture of hexane and ethyl acetate) to give 25.8 g of compound 29 (25% yield, reddish-yellow solid).

[0457] <Synthesis of Compound 30>

[0458] Compound 30, as shown below, was synthesized using the method described below, according to the following reaction formula.

[0459] [Chemistry 89]

[0460] (Compound 30)

[0461] [Chemistry 90]

[0462]

[0463] In a heated and dried 3L three-necked flask equipped with a stirrer, 25.8 g of compound 29 (155.2 mmol), 1014 mL of ethanol, and 136.6 mg of 10% Pd / C (55% aqueous) were added. A hydrogen balloon was attached to the flask, and the internal atmosphere was purged with hydrogen three times. After stirring at room temperature for 3 hours, the hydrogen balloon was replaced, and the flask was refilled with hydrogen atmosphere and stirred at room temperature for 3 hours. The reaction solution was then filtered through diatomaceous earth and washed with ethanol. The filtrate was concentrated using a rotary evaporator to give 20.89 g of crude product. The crude product was purified by silica gel column chromatography (using a mixture of dichloromethane and methanol as the developing solvent, with a mixing ratio of 1:0 to 19:1), concentrated, and the resulting solid was washed with toluene at 45°C and dried to give 16.76 g of compound 30 in 79% yield.

[0464] <Synthesis of Compound 31>

[0465] Compound 31, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0466] [Chemistry 91]

[0467] (Compound 31)

[0468] [Chemistry 92]

[0469]

[0470] In a heated and dried 500 mL three-necked flask equipped with a stirrer, 3.43 g of compound 30 (25.0 mmol, 1 equivalent) and 100 mL of chloroform (dehydrated) were added under a nitrogen atmosphere. Then, 2.22 mL of pyridine (dehydrated, 27.5 mmol, 1.1 equivalent) was slowly added dropwise at room temperature. After cooling the reaction solution in an ice bath, 3.07 mL of benzoyl chloride (26.3 mmol, 1.05 equivalent) was slowly added dropwise. After the addition was complete, the mixture was heated to room temperature and stirred for 4.5 hours. After the reaction was complete, the reaction solution was again cooled in an ice bath, and 10 mL of methanol was added and stirred. Water and dichloromethane were added, and the mixture was filtered to give compound 31 as a solid. The filtrate was concentrated using a rotary evaporator, and dichloromethane was added again, followed by filtration to give compound 31 as a solid. The same operation was repeated, and the resulting solid was collected to give 5.73 g (23.8 mmol, 95% yield) of compound 31. The obtained compound 31... 1 The H-NMR data are shown below.

[0471] 1 ¹H NMR (400MHz, CDCl₃, TMS as internal standard): δ 8.44 (s, 1H), 7.95–7.90 (m, 2H), 7.82 (brs, 1H), 7.61 (tt, J=7.4, 1.6Hz, 1H), 7.57–7.50 (m, 2H), 7.00 (d, J=7.6Hz, 1H), 6.72 (d, J=7.6Hz, 1H), 2.34 (s, 3H), 2.30 (s, 3H).

[0472] <Synthesis of Compound 32>

[0473] Compound 32, as shown below, was synthesized using the method described later, according to the following reaction formula.

[0474] [Chemistry 93]

[0475] (Compound 32)

[0476] [Chemistry 94]

[0477]

[0478] In a heated and dried 300 mL three-necked flask equipped with a stirrer, 5.72 g of compound 31 (23.7 mmol, 1 equivalent) and 130 mL of pyridine (dehydrated) were added under a nitrogen atmosphere. Then, 7.51 mL of diethylcarbamoyl chloride (59.3 mmol, 2.5 equivalent) was slowly added dropwise at room temperature, and the mixture was heated to reflux for 24 hours. After the reaction was complete, the reaction solution was cooled in an ice bath, and 30 mL of water was slowly added while stirring at room temperature. The mixture was then concentrated using a rotary evaporator, and after adding water and ethyl acetate, extracted three times with ethyl acetate. The collected organic layer was washed three times with water, once with brine, dried over sodium sulfate, and concentrated using a rotary evaporator. The resulting 8.17 g of crude product was purified by silica gel column chromatography (using a continuously varying hexane to ethyl acetate ratio from 100:0 to 70:30 as the developing solvent) to give 4.03 g of compound 32 (11.8 mmol, 50% yield). The obtained compound 32... 1 The H-NMR data are shown below.

[0479] 1 ¹H NMR (400MHz, CDCl₃, TMS as internal standard): δ 7.93–7.85 (m, 2H), 7.82 (br s, 1H), 7.56–7.51 (m, 1H), 7.49–7.42 (m, 2H), 7.07 (q, J = 8.0 Hz, 2H), 3.41–3.29 (m, 4H), 2.28 (s, 3H), 2.23 (s, 3H), 1.16–0.99 (m, 6H).

[0480] [Example 17]

[0481] <Synthesis of Compound 33>

[0482] Compound 33, as shown below, was synthesized using the method described below, according to the following reaction formula.

[0483] [Chem. 95]

[0484] (Compound 33)

[0485] [Chemistry 96]

[0486]

[0487] In a heated and dried 300 mL three-necked flask equipped with a stirrer, 4.02 g of compound 32 (11.8 mmol, 1 equivalent), 60 mL of tetrahydrofuran (dehydrated), and 6 mL of N,N'-dimethylformamide (dehydrated) were added under a nitrogen atmosphere. After cooling the reaction solution in an ice bath, 0.67 g of sodium hydride (55%, liquid paraffin dispersion, 15.3 mmol, 1.3 equivalent) was slowly added. After stirring for 30 minutes, 0.88 mL of iodomethane (14.2 mmol, 1.2 equivalent) was slowly added dropwise. The mixture was slowly heated to room temperature and stirred for another 5 hours. After the reaction was complete, the reaction solution was cooled again in an ice bath, and 10 mL of water was slowly added while stirring at room temperature. After adding water and ethyl acetate, the mixture was extracted three times with ethyl acetate. The collected organic layer was washed three times with water and once with brine, dried over sodium sulfate, and concentrated using a rotary evaporator. The obtained crude product of 4.45 g was purified by silica gel column chromatography (using a continuously varying hexane to ethyl acetate mixture from 90:10 to 70:30 as the developing solvent), and further recrystallized with methanol to give 3.24 g (9.14 mmol, yield 78%) of compound 33. The obtained compound 33... 1 The H-NMR data are shown below. (It should be noted that since two rotational isomers were produced, they are designated as the major and minor components, respectively. Their ratio is major:minor = 92:8.)

[0488] 1 H NMR (400MHz, CDCl3, TMS as internal standard):

[0489] Main components: δ 7.35 (br s, 2H), 7.25-7.20 (m, 1H), 7.17-7.10 (m, 2H), 6.99 (br d, J=7.8Hz, 1H), 6.87 (br d, J=7.8Hz, 1H), 3.64-3.22 (m, 7H), 2.26-1.99 (m, 6H), 1.33-1.15 (m, 6H).

[0490] Minor components: δ 7.55-7.50 (m, 2H), 7.46-7.41 (m, 3H), 7.17-7.10 (m, 1H), 7.07 (br d, J=8.0Hz, 1H), 3.64-3.22 (m, 4H), 3.14 (s, 3H), 2.30 (s, 3H), 2.26-1.99 (m, 3H), 1.33-1.15 (m, 6H).

Claims

1. A carbamate compound represented by the following formula (0), [Chemistry 1] In equation (0), l is 0 or 1. m is an integer from 1 to 4. n is an integer from 1 to 4. R 1 and R 2 They are respectively those with "R" 10 Substituents in the "-CR2-" structure R 3 It is a hydrogen atom or has "R" 10 Substituents in the "-CR2-" structure R 4 To be selected from those with "R" 10 Substituents with the "-CR2-" structure, and those with "R" 10 -At 16 Substituents with the "-" structure and having "R" 10 2-At 15 Substituents in the "-" structure At 15 For atoms in group 15 of the periodic table, At 16 These are atoms belonging to group 16 of the periodic table. R and R 10 These are groups containing atoms selected from carbon, hydrogen, and elements from groups 15, 16, and 17 of the periodic table, with 0 to 17 carbon atoms and 0 to 4 atoms of elements from groups 15, 16, and 17 of the periodic table. R 1 ~R 4 And R can bond with each other to form single or multiple rings. Multiple R, R 10 They can bond with each other to form single or multiple rings, or even multiple bonds.

2. The carbamate compound according to claim 1, which is represented by the following formula (1), [Chemistry 2] In equation (1), n ​​is an integer from 2 to 4, and m and R are... 1 R 2 R 3 R 4 And R and m, R in the above equation (0) 1 R 2 R 3 R 4 Synonymous with R.

3. The carbamate compound according to claim 1 or 2, wherein, The R 3 For having "R 10 Substituents in the "-CR2-" structure.

4. The carbamate compound according to claim 1 or 2, wherein, The R 4 For having "R 10 Substituents in the "-CR2-" structure.

5. The carbamate compound according to claim 1 or 2, wherein, The At 15 It is a nitrogen atom.

6. The carbamate compound according to claim 1 or 2, wherein, The At 16 It is an oxygen atom.

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