Process for producing aromatic amino compounds

Abstract

This invention provides a novel method for manufacturing an aromatic amino compound, which is useful as a manufacturing intermediate for agricultural pharmaceuticals and electronic materials, and has at least one multiple bond selected from carbon-carbon, carbon-nitrogen, and carbon-oxygen in the portion outside the aromatic ring. A method for manufacturing an aromatic amino compound is characterized by catalytic reduction of an aromatic nitro compound having at least one multiple bond selected from carbon-carbon, carbon-nitrogen, and carbon-oxygen in the portion outside the aromatic ring using a Pt / C catalyst in the presence of at least one phosphorus compound (A) selected from the phosphorus compounds shown in formula (1), formula (2), and formula (3). P(R) 1 )3 (1), PO(R) 2 )3 (2), (R 3 )2P-R 4 -P(R) 3 )2 (3) The meanings of the symbols in the above formulas (1) to (3) are as defined in the instruction manual.

Description

Technical Field

[0001] The present invention relates to a method for manufacturing aromatic amino compounds that are useful as intermediates in the manufacture of agricultural pharmaceuticals or electronic materials, having at least one multiple bond selected from carbon-carbon, carbon-nitrogen, and carbon-oxygen in a portion other than the aromatic ring. Background Technology

[0002] It is known that aromatic amino compounds can be produced by reducing aromatic nitro compounds. On the other hand, when amino compounds are produced by reducing aromatic nitro compounds that have at least one multiple bond selected from carbon-carbon, carbon-nitrogen, and carbon-oxygen in the part outside the aromatic ring, the multiple bond is also reduced depending on the conditions. Therefore, it is usually difficult to reduce only the nitro group to the amino group while leaving the multiple bond. Methods are being explored to selectively reduce only the nitro group of the aromatic nitro compound to the amino group.

[0003] For example, Patent Document 1 discloses a method for producing a substituted aromatic amino compound containing at least one of carbon-carbon, carbon-nitrogen, or carbon-oxygen multiple bonds in the aromatic moiety or side chain by catalytic hydrogenation of a relatively substituted aromatic nitro compound in the presence of a modified noble metal catalyst, wherein the noble metal catalyst is rhodium, ruthenium, iridium, platinum, or palladium modified with an oxidation state of less than 5 by an inorganic or organophosphorus compound.

[0004] In addition, Patent Document 2 proposes a method for selectively hydrogenating aromatic nitro compounds to aromatic amino compounds using a catalyst that has been poisoned with trace amounts of iron to a Pt / C catalyst.

[0005] Existing technical documents Patent documents Patent Document 1: Japanese Patent Publication No. 2001-501201 Patent Document 2: Description of German Patent Application Publication No. 102011003590 Summary of the Invention The technical problem that the invention aims to solve Thus, a method was proposed to selectively reduce only the nitro group of aromatic nitro compounds to amino groups, but a method is desired that can reduce only the nitro group of aromatic nitro compounds to amino groups with higher selectivity and without impairing the reaction rate.

[0006] In view of the above, the technical problem of the present invention is to provide a novel method for manufacturing aromatic amino compounds, which are useful as intermediates in the manufacture of agricultural and pharmaceutical products and electronic materials, and can reduce aromatic nitro compounds having at least one multiple bond selected from carbon-carbon, carbon-nitrogen and carbon-oxygen in the part outside the aromatic ring to amino groups with higher selectivity and without impairing the reaction rate.

[0007] Technical solutions for solving technical problems In view of this situation, the inventors conducted in-depth research and discovered the following method: catalytic reduction of an aromatic nitro compound having at least one multiple bond selected from carbon-carbon, carbon-nitrogen, and carbon-oxygen in the portion other than the aromatic ring using a specific noble metal supported catalyst in the presence of a specific phosphorus compound, thereby selectively reducing only the nitro group, thus completing the present invention.

[0008] That is, the present invention finds that the above-mentioned technical problems can be solved by the following configuration.

[0009] [1] A method for manufacturing an aromatic amino compound, characterized in that, in the presence of at least one phosphorus compound (A) selected from the phosphorus compounds shown in formula (1), formula (2) and formula (3) below, an aromatic nitro compound having at least one multiple bond selected from carbon-carbon, carbon-nitrogen and carbon-oxygen in a portion other than the aromatic ring is catalytically reduced using a Pt / C catalyst.

[0010] P(R 1 )3 (1) (In equation (1), multiple R) 1 Each of these groups independently represents a hydrogen atom, an alkyl group with 1 to 18 carbon atoms, an alkenyl group with 1 to 18 carbon atoms, an alkoxy group with 1 to 18 carbon atoms, an aryl group with 6 to 24 carbon atoms, an aryloxy group with 6 to 24 carbon atoms, a cycloalkyl group with 3 to 18 carbon atoms, or a cycloalkoxy group with 3 to 18 carbon atoms; they may have substituents. PO(R 2 )3 (2) (In equation (2), multiple R) 2 Each of these groups independently represents a hydrogen atom, an alkyl group with 1 to 18 carbon atoms, an alkenyl group with 1 to 18 carbon atoms, an alkoxy group with 1 to 18 carbon atoms, an aryl group with 6 to 24 carbon atoms, an aryloxy group with 6 to 24 carbon atoms, a cycloalkyl group with 3 to 18 carbon atoms, or a cycloalkoxy group with 3 to 18 carbon atoms; they may have substituents. (R 3 )2P-R 4 -P(R 3 )twenty three) (In equation (3), multiple R) 3 Each of the following groups independently represents an alkyl group with 1 to 18 carbon atoms, an alkenyl group with 1 to 18 carbon atoms, an alkoxy group with 1 to 18 carbon atoms, an aryl group with 6 to 24 carbon atoms, an aryloxy group with 6 to 24 carbon atoms, a cycloalkyl group with 3 to 18 carbon atoms, or a cycloalkoxy group with 3 to 18 carbon atoms, and may have substituents. In formula (3), R 4 This refers to alkylene, alkenyl, alkyldioxy, aryl, aryldioxy, cycloalkylene, or cycloalkyldioxy groups having 1 to 18 carbon atoms, which may have substituents. [2] According to the method for manufacturing the aromatic amino compound described in [1], wherein the phosphorus compound (A) is P(OMe)3 or P(OEt)3.

[0011] [3] The method for manufacturing the aromatic amino compound according to [1] or [2], wherein the amount of the phosphorus compound (A) used is 5 to 50 moles relative to the aromatic amino compound.

[0012] [4] A method for manufacturing an aromatic amino compound according to any one of [1] to [3], wherein the aromatic nitro compound is represented by any one of the following structures (1) to (3).

[0013] [Chemistry 1] (In the formula, R5, R6, R8, and R9 each independently represent a single bond or a divalent group, R7 represents a hydrogen atom or a monovalent group, and n represents an integer from 1 to 2.) [5] The method for manufacturing an aromatic amino compound according to any one of [1] to [4], wherein the loading of platinum in the above-mentioned Pt / C catalyst is 0.5 to 5 wt% relative to the total weight of the Pt / C catalyst.

[0014] [6] The method for manufacturing an aromatic amino compound according to any one of [1] to [5], wherein the above-mentioned Pt / C catalyst is an iron-poisoned Pt / C catalyst.

[0015] [7] The method for manufacturing an aromatic amino compound according to any one of [1] to [6], wherein the amount of the Pt / C catalyst used is 1 to 20 by weight relative to the aromatic nitro compound.

[0016] [8] The method for manufacturing an aromatic amino compound according to any one of [1] to [7], wherein the reaction temperature in the above catalytic reduction is 0 to 100°C and the reaction time is 0.5 hours to 20 hours.

[0017] [9] The method for manufacturing an aromatic amino compound according to any one of [1] to [8], wherein a vanadium compound is further present.

[0018]

[10] The method for manufacturing aromatic amino compounds according to [9], wherein the vanadium compound is VO(acac)2.

[0019]

[11] The method for manufacturing aromatic amino compounds according to [9] or

[10] , wherein the amount of vanadium compound used is 0.1 to 1.0 mol relative to the aromatic nitro compound.

[0020] Invention Effects According to the manufacturing method of the present invention, the nitro group of an aromatic nitro compound (hereinafter also simply referred to as "compound (DN)") having at least one multiple bond selected from carbon-carbon, carbon-nitrogen, and carbon-oxygen in the portion outside the aromatic ring can be selectively reduced without impairing the reaction rate. Therefore, it is possible to inexpensively and efficiently manufacture aromatic amino compounds having at least one multiple bond selected from carbon-carbon, carbon-nitrogen, and carbon-oxygen in the portion outside the aromatic ring, useful as manufacturing intermediates for agricultural pharmaceuticals and electronic materials. Detailed Implementation

[0021] Throughout this instruction manual, the following terms and abbreviations have the following meanings.

[0022] The numerical range indicated by "~" refers to the range of values ​​before and after "~" that serve as both lower and upper limits. Within the numerical ranges described in this specification, the upper or lower limit value recorded in a particular numerical range may be replaced with the upper or lower limit value of another numerical range described in another stage. Furthermore, within the numerical ranges described in this specification, the upper or lower limit value recorded in a particular numerical range may be replaced with the values ​​shown in the embodiments.

[0023] Me represents methyl, Et represents ethyl, Pr represents propyl, Bu represents butyl, n- represents n-, t- represents tert-, o- represents ortho-, Cy represents cyclohexyl, Ph represents phenyl, Bn represents benzyl, Tol represents tolyl, and acac represents acetylacetonate.

[0024] The method for manufacturing the aromatic amino compounds of the present invention will be described below.

[0025] In describing the detailed method for manufacturing the aromatic amino compounds of the present invention, specific examples are given, but the implementation is not limited to the following content as long as it does not depart from the spirit of the present invention, and appropriate modifications can be made.

[0026] As a manufacturing method of the present invention, for example, a method for manufacturing an aromatic amino compound as shown in reaction formula 1 below can be cited.

[0027] [Chemistry 2] In the formula, L represents a single bond or a divalent group, and X represents CR. 11 Y represents O and NR 12 or CR 13 R 14 R 11 R 12 R 13 and R 14 Each can independently represent a hydrogen atom or a monovalent group, where R can also be used. 11 R 12 R 13 and R 14 Instead of bonding, the X and Y bonds become triple bonds. Multiple R... 1 Each is independently identical to the definition above.

[0028] In addition, when the bond between X and Y is a double bond, X and Y can also form a 5-membered ring or a 6-membered ring or other cyclic structure together. Specific examples of the above-mentioned cyclic structures include: cyclohexene, cyclohexadiene, pyran, dihydropyran, dihydrofuran, cyclohexen-1-one, dihydropyrrole, dihydropyridine, tetrahydropyridine and other cyclic alkenes.

[0029] That is, when the compound (DN) is an aromatic nitro compound, for example, when it is a compound having cyclohexene as the above-mentioned cyclic structure, it is a compound having the following structure.

[0030] [Chemistry 3] (In the formula, L represents a single bond or a divalent group.) In addition, when the bond between X and Y is a double bond, Y can be bonded to a nitro-substituted benzene ring. As a specific example, compounds with the following structure can be cited.

[0031] [Chemistry 4] The present invention is a method for producing aromatic amino compounds by catalytic reduction of an aromatic nitro compound having at least one multiple bond selected from carbon-carbon, carbon-nitrogen and carbon-oxygen in a portion other than the aromatic ring using a Pt / C catalyst in the presence of at least one phosphorus compound (A) selected from the phosphorus compounds shown in formula (1), formula (2) and formula (3).

[0032] The aromatic nitro compounds used in this invention are aromatic nitro compounds having at least one multiple bond selected from carbon-carbon, carbon-nitrogen, and carbon-oxygen in the portion outside the aromatic ring.

[0033] As aromatic nitro compounds, aromatic mononitro compounds or aromatic dinitro compounds are preferred.

[0034] Among the aforementioned multiple bonds, the preferred option is... α , β -Unsaturated carbonyl group. As a group with... α , β - Unsaturated carbonyl groups are aromatic nitro compounds with multiple bonds, for example, compounds having the following structures can be cited as (I) to (III).

[0035] [Chemistry 5] (In the formula, R5, R6, R8, and R9 each independently represent a single bond or a divalent group, R7 represents a hydrogen atom or a monovalent group, R...) 10 R 11 R 12 R 13 R 14 R 15 R 16 R 17 R 18 R 19 Each atom can be independently represented by a hydrogen atom or a methyl group, and n represents an integer from 1 to 2. In addition, the following compounds (1) to (3) are preferred as compounds represented by the above formulas (I) to (III).

[0036] [Chemistry 6] (In the above formula, R5, R6, R8, and R9 each independently represent a single bond or a divalent group, and R7 represents a hydrogen atom or a monovalent group. n represents an integer from 1 to 2.) As divalent groups among R5, R6, R8, and R9 mentioned above, alkylene groups with 1 to 20 carbon atoms that are either unsubstituted or substituted with fluorine atoms can be substituted. The -CH2- or -CF2- groups in the aforementioned alkylene groups with 1 to 20 carbon atoms can be substituted with groups selected from -O-, -COO-, -OCO-, -NHCO-, -CONH-, -NH-, divalent carbon rings, and divalent heterocycles (wherein groups selected from these groups are not adjacent to each other). Preferably, unsubstituted alkylene groups with 1 to 6 carbon atoms are used (the -CH2- group on the side of the alkylene group bonded to the benzene ring can be substituted with groups selected from -O-, -COO-, -OCO-, -NHCO-, -CONH-, and -NH- (wherein groups selected from these groups are not adjacent to each other)).

[0037] Examples of monovalent groups in R7 above include alkyl groups with 1 to 20 carbon atoms that are either unsubstituted or substituted with fluorine atoms. The -CH2- or -CF2- group in the alkyl groups with 1 to 20 carbon atoms can be substituted with groups selected from -O-, -COO-, -OCO-, -NHCO-, -CONH-, -NH-, divalent carbon rings, and divalent heterocycles (wherein the groups selected from these groups are not adjacent to each other). Preferably, unsubstituted alkyl groups with 1 to 6 carbon atoms are used (the -CH2- group in the alkyl group can be substituted with groups selected from -O-, -COO-, -OCO-, -NHCO-, -CONH-, and -NH- (wherein the groups selected from these groups are not adjacent to each other)).

[0038] As the phosphorus compound used in this invention, at least one phosphorus compound (A) selected from the phosphorus compounds shown in formula (1), formula (2), and formula (3) below can be cited.

[0039] P(R 1 )3 (1) (In equation (1), multiple R) 1 Each of these groups independently represents a hydrogen atom, an alkyl group with 1 to 18 carbon atoms, an alkenyl group with 1 to 18 carbon atoms, an alkoxy group with 1 to 18 carbon atoms, an aryl group with 6 to 24 carbon atoms, an aryloxy group with 6 to 24 carbon atoms, a cycloalkyl group with 3 to 18 carbon atoms, or a cycloalkoxy group with 3 to 18 carbon atoms; they may have substituents. PO(R 2 )3 (2) (In equation (2), multiple R) 2 Each of these groups independently represents a hydrogen atom, an alkyl group with 1 to 18 carbon atoms, an alkenyl group with 1 to 18 carbon atoms, an alkoxy group with 1 to 18 carbon atoms, an aryl group with 6 to 24 carbon atoms, an aryloxy group with 6 to 24 carbon atoms, a cycloalkyl group with 3 to 18 carbon atoms, or a cycloalkoxy group with 3 to 18 carbon atoms; they may have substituents. (R 3 )2P-R 4 -P(R 3 )twenty three) (In equation (3), multiple R) 3 Each of the following groups independently represents an alkyl group with 1 to 18 carbon atoms, an alkenyl group with 1 to 18 carbon atoms, an alkoxy group with 1 to 18 carbon atoms, an aryl group with 6 to 24 carbon atoms, an aryloxy group with 6 to 24 carbon atoms, a cycloalkyl group with 3 to 18 carbon atoms, or a cycloalkoxy group with 3 to 18 carbon atoms, and may have substituents. In formula (3), R 4 This refers to alkylene, alkenyl, alkyldioxy, aryl, aryldioxy, cycloalkylene, or cycloalkyldioxy groups having 1 to 18 carbon atoms, which may have substituents. R in the above equation (1) 1 Specific examples include methyl, ethyl, n-propyl (n-Pr), isopropyl (i-Pr), n-butyl (n-Bu), tert-butyl (t-Bu), phenyl (Ph), benzyl (Bn), methoxy (OMe), ethoxy (OEt), n-propyloxy (On-Pr), n-butyloxy (On-Bu), phenoxy (OPh), benzyloxy, etc., with n-Bu and Ph being preferred. 、 Among OMe, OEt, On-Bu, and OPh, OMe and OEt are preferred based on their higher selection rates.

[0040] R in the above equation (2) 2 Specific examples include hydrogen, methyl, ethyl, n-Pr, i-Pr, n-Bu, t-Bu, n-octyl, cyclohexyl, Ph, p-methylphenyl, p-methoxyphenyl, benzyl, OMe, OEt, n-propyloxy, n-butyloxy, OPh, benzyloxy, etc. From the perspective of higher selectivity, hydrogen, methyl, n-Bu, n-octyl, and Ph are preferred, and hydrogen, methyl, and Ph are even more preferred.

[0041] R in the above equation (3) 3 Specific examples include hydrogen, methyl, ethyl, n-Pr, i-Pr, n-Bu, t-Bu, n-octyl, cyclohexyl, Ph, p-methylphenyl, p-methoxyphenyl, benzyl, OMe, OEt, n-propyloxy, n-butyloxy, OPh, benzyloxy, etc. From the perspective of higher selectivity, methyl, ethyl, OMe, OEt, and Ph are preferred, and from the perspective of higher selectivity, methyl, OMe, OEt, and Ph are even more preferred.

[0042] R in the above equation (3)4 Specific examples include methylene, ethylene, propylene, butylene, pentylene, hexylene, 1,2-phenylene, 1,3-phenylene, 2,2′-biphenylene, 2,2′-binaphthylene, 1,8-naphthylene, 1,8-(9,9-dimethyl)xanthine, and 1,1′-ferrocenylene. Among these, methylene, ethylene, propylene, butylene, 1,2-phenylene, 2,2′-biphenylene, 2,2′-binaphthylene, 1,8-naphthylene, and 1,1′-ferrocenylene are preferred. From the perspective of higher selectivity, methylene, ethylene, propylene, butylene, and 2,2′-binaphthylene are more preferred.

[0043] R in the formula 1 R 2 R 3 The substituents that can be present include, for example: methyl, ethyl, isopropyl, tert-butyl, phenyl, hydroxyl, methoxy, isopropoxy, tert-butoxy, amino, dimethylamino, cyano, formyl, carboxyl, sulfonyloxy, fluorine, chloro, bromine, and iodo.

[0044] Specific examples of phosphorus compounds (A) include: PMe3, PEt3, P(n-Pr)3, P(n-Bu)3, P(t-Bu)3, P(n-C6H 13 3. P(n-C8H) 17 )3, PCy3, PBn3, PPh3, P(o-Tol)3, P(OMe)3, P(OEt)3, P(On-Pr)3, P(On-Bu)3, P(OPh)3, P(OBn)3, P(O)(n-Bu)3, P(O)Ph3, (±)-BINAP(2,2′-bis(diphenylphosphino)-1,1′-binaphthyl), (+)-BINAP, (-)-BINAP, depe(1,2-bis(diethyl) Phosphine ethane), dppm (1,1-bis(diphenylphosphine)methane), dppe (1,2-bis(diphenylphosphine)ethane), dppp (1,3-bis(diphenylphosphine)propane), dppb (1,4-bis(diphenylphosphine)butane), dppbz (1,2-bis(diphenylphosphine)benzene), dppf (1,1′-bis(diphenylphosphine)ferrocene), 4,5-bisdiphenylphosphine-9,9-dimethyloxanthracene (Xantphos), etc.

[0045] Among them, P(n-Bu)3 and PPh are preferred. 3、 From the perspective of higher selection rate, P(OMe)3, P(OEt)3, P(On-Bu)3, and P(OPh)3 are preferred over P(OMe)3 and P(OEt)3.

[0046] Regarding the amount of phosphorus compound (A) used in this invention, from the viewpoint of easy removal after reaction, it is preferably 50 mol% or less, more preferably 35 mol% or less, relative to the compound (DN) which is an aromatic nitro compound. From the viewpoint of excellent selectivity, it is preferably 5 mol% or more, more preferably 10 mol% or more.

[0047] In this reaction, the amount of Pt / C catalyst used relative to the compound (DN) as an aromatic nitro compound is preferably 1% by weight or more, more preferably 3% by weight or more, more preferably 20% by weight or less, and more preferably 10% by weight or less.

[0048] The platinum loading in the Pt / C catalyst is preferably 0.5 to 5% by weight relative to the total weight of the Pt / C catalyst, more preferably 1 to 5% by weight.

[0049] In this reaction, a Pt / C catalyst poisoned by S, Cu, V, or Fe is preferred, and a catalyst poisoned by Fe is more preferred. Based on the total weight of the Fe-poisoned Pt / C catalyst, from the viewpoint of suppressing side reactions, the amount of Fe used for poisoning is preferably 0.05% by weight or more, more preferably 0.1% by weight or more, and from the viewpoint of not reducing catalytic activity, preferably 1.0% by weight or less, more preferably 0.5% by weight or less.

[0050] In this reaction, from the viewpoint of suppressing the formation of azo compounds, it is preferable to further coexist with vanadium compounds. Preferred vanadium compounds include VO(acac)3, VO(acac)2, NH4VO3, V2O5, VOCl3, VCl6, and [VO(SCN)4]. 2- VOSO4, LiVO3, NaVO3, KVO3, VCl3, and more preferably VO(acac)2.

[0051] In this reaction, if too much vanadium compound is used, the possibility of it remaining in the product increases. Therefore, it is preferable to use 1.0 mol% or less relative to the compound (DN), and more preferably 0.2 mol% or less. Furthermore, from the viewpoint of sufficiently suppressing the formation of azo compounds, the amount of vanadium compound used is preferably 0.1 mol% or more.

[0052] This reaction can be carried out in a solvent. Any solvent that is stable, inert, and does not hinder the reaction under the reaction conditions can be used as the reaction solvent. As reaction solvents, water, alcohols, amines, aprotic polar organic solvents (DMF (dimethylformamide), DMSO (dimethyl sulfoxide), DMAc (dimethylacetamide), NMP (N-methylpyrrolidone), etc.), ethers (Et2O, i-Pr2O, TBME (tert-butyl methyl ether), CPME (cyclopentyl methyl ether), THF (tetrahydrofuran), dioxane, etc.), aliphatic hydrocarbons (pentane, hexane, heptane, petroleum ether, etc.), aromatic hydrocarbons (benzene, toluene, xylene, mesitylene, chlorobenzene, dichlorobenzene, nitrobenzene, tetrahydronaphthalene, etc.), halogenated hydrocarbons (chloroform, dichloromethane, carbon tetrachloride, dichloroethane, etc.), lower fatty acid esters (methyl acetate, ethyl acetate, butyl acetate, methyl propionate, etc.), and nitriles (acetonitrile, propionitrile, butyronitrile, etc.) can be used. These solvents can be appropriately selected considering the ease of reaction, and one or more can be used alone or in combination. In addition, depending on the circumstances, the above solvents can also be used as water-free solvents by using appropriate dehydrating agents and drying agents.

[0053] The reaction temperature during catalytic reduction is typically -90℃ to 200℃, preferably 0℃ to 100℃.

[0054] The reaction time for catalytic reduction is typically 0.05 hours to 100 hours, preferably 0.5 hours to 20 hours, and more preferably 0.5 hours to 10 hours.

[0055] The reaction pressure during catalytic reduction is typically atmospheric pressure to 10 MPaG, preferably atmospheric pressure to 0.8 MPaG.

[0056] Example The present invention will now be described in more detail through embodiments, but the interpretation of the present invention is not limited to these embodiments. It should be noted that the analytical apparatus and analytical conditions used in the embodiments are as follows.

[0057] 1 H-NMR; Device: ECZ (400MHz) manufactured by Nippon Electronics Co., Ltd. Determination solvent: CDCl3 Reference material: Tetramethylsilane (TMS) (TMS) 1 The δ value of H was set to 0.0 ppm.

[0058] HPLC; Apparatus: HPLC, LC-20AD manufactured by Shimadzu Corporation Column: Inertsil ODS-3 (GL Science), 5 mm Φ4.6×250mm Column temperature: 40℃ Elution buffer: (A) Acetonitrile / (B) 50mM potassium phosphate buffer (pH=7) A / B = 35 / 65 (0-10 minutes) - 60 / 40 (13-30 minutes) (v / v) Flow rate: 1.0 mL / min Detection method: UV (254nm) Data collection time: 30 minutes.

[0059] [Examples of the synthesis of aromatic amino compounds] <Synthetic Example 1> Preparation of 2-(3,5-diaminobenzoyloxy)ethyl methacrylate (Compound DA-1) [Chemistry 7] The nitro compounds used here are known compounds and can be synthesized according to known methods described in the literature. For example, 2-(3,5-dinitrobenzoyloxy)ethyl methacrylate can be obtained by reacting according to the method described in Japanese Patent No. 5560715.

[0060] (Synthetic Example 1-a-1) Add 2-(3,5-dinitrobenzoyloxy)ethyl methacrylate (5.00 g, 15.4 mmol), toluene (50.0 g), triethyl phosphite (0.512 g, 3.08 mmol), 1% Pt / C catalyst (55.0% aqueous type, 0.556 g) poisoned by 0.2% iron, and vanadium diacetylacetone oxide (8.94 mg, 30.8 mmol) to a 200 mL pressure vessel. m The mixture (mmol) was stirred at 40°C for 4 hours under a hydrogen atmosphere with a gauge pressure of 0.60 MPa.

[0061] The HPLC analysis of the reaction solution showed that the relative area percentage of DA-1 was 98.8%, the reaction yield was 100%, and no over-reduced form (DA-1′) was detected.

[0062] After the reaction was complete, ethyl acetate (20.0 g) was added. After filtering the catalyst, the filtrate was washed twice with ethyl acetate (5.00 g). Water (20.0 g) was added to the filtrate, and the process of removing the aqueous layer was repeated twice. The organic layer was concentrated to 41.2 g, toluene (50.0 g) was added, and the mixture was concentrated again to 41.2 g. The mixture was then cooled to 0 °C, and the precipitated crystals were filtered. The crystals were washed twice with toluene (15.0 g) and twice with water (5.0 g). The mixture was dried under reduced pressure at 40 °C to obtain powdered crystals (DA-1) (3.44 g, 86.5% yield).

[0063] The HPLC analysis of the obtained crystals showed that the relative area percentage of DA-1 was 100.0%, and no over-reduced form (DA-1′) was detected.

[0064] 1 H-NMR (CDCl3): δ6.77 (d, J=2.4Hz, 2H, Ar), 6.19 (dd, J=2.4Hz, 2,2Hz, 1H, =CH), 6.14 (br, 1H, Ar ), 5.59 (dd, J=2.4Hz, 2,2Hz, 1H, =CH), 4.48 (m, 4H, CH2CH2), 3.59 (br, 4H, NH2), 1.95 (s, 3H, Me). (Comparative Synthesis Example) 2.00 g (6.17 mmol) of 2-(3,5-dinitrobenzoyloxy)ethyl methacrylate, 20.0 g of toluene, 0.163 g (1.23 mmol) of 50 wt% hypophosphite aqueous solution, and 0.444 g of 1 wt% Pt / C (55.0 wt% aqueous form, 0.444 g) poisoned with 0.2 wt% iron were added to a 200 mL pressure vessel. The mixture was stirred at 40 °C under a hydrogen atmosphere with a gauge pressure of 0.60 MPa. HPLC analysis of the reaction solution was performed 6 hours after stirring began. The results showed that the reaction was not yet complete, with the LC relative area percentage of DA-1 being 42.3% and the LC relative area percentage of the overreduced form (DA-1′) being 0.3%. Further stirring was performed, and HPLC analysis of the reaction solution was performed after a total of 24 hours. The results showed that the HPLC relative area percentage of DA-1 was 96.5%, the yield was 72%, and the HPLC relative area percentage of the overreduced form (DA-1′) was 1.0%.

[0065] The types of phosphorus compounds used as additives, the amount of DN-1 used, the amount of 1% Pt / C catalyst poisoned by 0.2% iron added, the amount of vanadium diacetylacetone oxide (VO(acac)2) added, and the amount of toluene used as solvent were changed. Otherwise, the synthesis of Synthesis Examples 1-a-2 to 1-a-8 was carried out according to the method described in Synthesis Example 1-a-1.

[0066] Table 1 records the types of additives used in Synthetic Examples 1-a-1 to 1-a-8 and the comparative synthetic examples, the amount of DN-1 used, the amount of 1% Pt / C catalyst added, the amount of vanadium diacetylacetone oxide (VO(acac)2) added, the amount of toluene and ethyl acetate used as solvents, the LC relative area percentage of DA-1, the HPLC relative area percentage of the overreduced form (DA-1′), the selectivity, and the reaction yield.

[0067] It should be noted that the method for determining the selection rate in the table is as follows.

[0068] Selection rate (%)=DA-1 / (DA-1+DA-1′)×100 [Table 1] As shown in Table 1, it can be seen that in Synthesis Examples 1-a-1 to 1-a-8, by using a Pt / C catalyst for catalytic reduction in the presence of phosphorus compound (A), the nitro group of the aromatic nitro compound can be reduced to an amino group with high selectivity and short reaction time without impairing the reaction rate.

[0069] <Synthetic Example 2> Preparation of (E)-4-(6-(methacryloyloxy)hexyloxy)cinnamic acid (2-(2,4-diaminophenyl)ethyl) ester (compound DA-2) [Chemistry 8] The nitro compounds used here are known compounds and can be synthesized according to known methods described in the literature. For example, (E)-4-(6-(methacryloyloxy)hexyloxy)cinnamic acid (2-(2,4-dinitrophenyl)ethyl) ester can be obtained by reacting according to the method described in Japanese Patent No. 6733552.

[0070] (Synthesis example 2) Add (E)-4-(6-(methacryloyloxy)hexyloxy)cinnamic acid (2-(2,4-dinitrophenyl)ethyl) ester (2.00 g, 3.80 mmol), toluene (10.0 g), THF (10.0 g), triethyl phosphite (0.200 g, 1.20 mmol), and 1% Pt / C (55.0% aqueous type, 0.444 g) poisoned by 0.2% iron to a 200 mL pressure vessel, and stir at 40 °C for 2 hours under a hydrogen atmosphere with a gauge pressure of 0.30 MPa.

[0071] The HPLC analysis of the reaction solution showed that the relative area percentage of DA-2 was 97.8%, the reaction yield was 96%, and no over-reduced form (DA-2′) was detected.

[0072] After the reaction was complete, the catalyst was filtered off, and the filtrate was washed twice with THF (2.00 g). Water (20.0 g) was added to the filtrate, and the process of removing the aqueous layer was repeated twice. The organic layer was concentrated to 10.0 g, toluene (20.0 g) was added, and the mixture was concentrated again to 10.0 g. The mixture was then cooled to 0 °C, and the precipitated crystals were filtered off. The crystals were washed twice with toluene (2.00 g) and twice with water (2.00 g). The mixture was then dried under reduced pressure at 40 °C to obtain powdered crystals (DA-2) (yield 1.40 g, 78.8%).

[0073] The HPLC analysis of the obtained crystals showed that the relative area percentage of DA-2 was 98.2%, and no over-reduced form (DA-2′) was detected.

[0074] <Synthetic Example 3> Preparation of (E)-4-aminocinnamate ethyl ester (compound DA-3) [Chemistry 9] Ethyl (E)-4-nitrocinnamate can be made from commercially available products such as those manufactured by Tokyo Chemical Industry Co., Ltd.

[0075] (Synthesis example 3) Ethyl (E)-4-nitrocinnamate (2.00 g, 9.04 mmol), THF (20.0 g), triethyl phosphite (0.200 g, 1.20 mmol), and 1% Pt / C catalyst (55.0% aqueous type, 0.444 g) poisoned by 0.2% iron were added to a 200 mL pressure vessel and stirred at 40 °C for 3 hours under a hydrogen atmosphere with a gauge pressure of 0.30 MPa.

[0076] The HPLC analysis of the reaction solution showed that the LC relative area percentage of DA-3 was 99.5%, the reaction yield was 98%, and no over-reduced form (DA-3′) was detected.

[0077] After the reaction was complete, the catalyst was filtered off, and the filtrate was washed twice with THF (2.00 g). The filtrate was concentrated to 10.0 g, toluene (20.0 g) was added, and the mixture was concentrated again to 10.0 g. Then, heptane (10.0 g) was added, and the mixture was cooled to 0 °C. The precipitated crystals were filtered off, and the crystals were washed twice with heptane (2.00 g). The mixture was then dried under reduced pressure at 40 °C to obtain powdered crystals (DA-3) (yield 1.48 g, 85.7%).

[0078] The HPLC analysis of the obtained crystals showed that the relative area percentage of DA-3 was 99.0%, and no over-reduced form (DA-3′) was detected.

[0079] <Synthetic Example 4> Preparation of (E)-4-aminochalcone (Compound DA-4) [Chemistry 10] 4-Nitrochalcone can be produced using commercially available products such as those manufactured by Tokyo Chemical Industry Co., Ltd.

[0080] (Synthesis Example 4) 4-Nitrochalcone (2.00 g, 7.90 mmol), THF (20.0 g), triethyl phosphite (0.200 g, 1.20 mmol), and 1% Pt / C catalyst (55.0% aqueous type, 0.444 g) poisoned with 0.2% iron were added to a 200 mL pressure vessel and stirred at 40 °C for 3 hours under a hydrogen atmosphere with a gauge pressure of 0.30 MPa.

[0081] The HPLC analysis of the reaction solution showed that the relative area percentage of DA-4 was 99.7%, the reaction yield was 100%, and no over-reduced form (DA-4′) was detected.

[0082] After the reaction was complete, the catalyst was filtered off, and the filtrate was washed twice with THF (2.00 g). Then, the filtrate was concentrated and dried. Toluene (10.0 g) was added to the obtained crystals, and the mixture was stirred at 20 °C for 1 hour. The crystals were then filtered off, washed twice with toluene (2.00 g), and dried under reduced pressure at 40 °C to obtain powdered crystals (DA-4) (yield 1.48 g, 84.2%).

[0083] The HPLC analysis of the obtained crystals showed that the relative area percentage of DA-4 was 97.3%, and no over-reduced form (DA-4′) was detected.

[0084] Synthetic Example 5: Preparation of (E)-4-aminobenzonitrile (Compound DA-5) [Chemistry 11] 4-Nitrobenzonitrile can be produced using commercially available products (such as those manufactured by Tokyo Chemical Industry Co., Ltd.).

[0085] (Synthesis Example 5) 4-Nitrobenzonitrile (2.00 g, 13.5 mmol), THF (20.0 g), triethyl phosphite (0.200 g, 1.20 mmol), and 1% Pt / C catalyst (55.0% aqueous type, 0.444 g) poisoned by 0.2% iron were added to a 200 mL pressure vessel and stirred at 40 °C for 12 hours under a hydrogen atmosphere with a gauge pressure of 0.30 MPa.

[0086] The HPLC analysis of the reaction solution showed that the relative area percentage of DA-5 was 99.5%, the reaction yield was 96%, and no over-reduced form (DA-5′) was detected.

[0087] (Synthetic Example 6) Preparation of 2,2-dimethyl-6-acetylamino-2H-1-benzopyran (compound DA-6-Ac) [Chemistry 12] The 2,2-dimethyl-6-nitro-2H-1-benzopyran (DN-6) used here can be reacted to obtain the compound by means of the method described in Japanese Patent No. 4258658.

[0088] 2,2-Dimethyl-6-nitro-2H-1-benzopyran (4.00 g, 19.5 mmol), toluene (40.0 g), triethyl phosphite (0.791 g, 4.76 mmol), and 1% Pt / C (55.0% aqueous form, 0.889 g) poisoned with 0.2% iron were added to a 200 mL pressure vessel and stirred at 40 °C for 3 hours under a hydrogen atmosphere with a gauge pressure of 0.30 MPa.

[0089] In the HPLC determination, the eluent was changed to (A) acetonitrile / (B) 10mM ammonium acetate A / B = 50 / 50 (0-30 minutes), otherwise the same method as in Synthesis Example 1 was used.

[0090] The HPLC analysis of the reaction solution showed that the relative area percentage of DA-6 was 99.7%, and no over-reduced form (DA-6′) was detected.

[0091] After the reaction was complete, the catalyst was filtered off, and the filtrate was washed twice with toluene (4.00 g). Acetic anhydride (2.09 g, 20.5 mmol) was added dropwise to the filtrate over 6 minutes at 25 °C, and then the mixture was stirred at 25 °C for 1 hour. Next, 4% sodium bicarbonate aqueous solution (40 g) was added and stirred, the aqueous layer was removed, water (20 g) was added and stirred, and the aqueous layer was removed. This process was repeated twice, and the organic layer was concentrated to 16.8 g. The mixture was cooled to 0 °C, and the precipitated crystals were filtered off. The crystals were washed twice with toluene (4.00 g) and dried under reduced pressure at 40 °C to obtain powdered crystals (DA-6-Ac) (3.21 g, 75.8% yield).

[0092] The obtained crystals were analyzed by HPLC, and the HPLC relative area percentage of DA-6-Ac was 99.6%, with no over-reduced form (DA-6′-Ac) detected.

[0093] (Synthesis Example 7) [Chemistry 13] The (DN-7) used here can be reacted to obtain the compound according to the method described in Japanese Patent No. 5737291.

[0094] Add DN-7 (3.00 g, 7.40 mmol), THF (30.0 g), triethyl phosphite (0.600 g, 3.61 mmol), and 1% Pt / C (55.0% aqueous form, 0.667 g) poisoned by 0.2% iron to a 200 mL pressure vessel, and stir at 40 °C for 6 hours under a hydrogen atmosphere with a gauge pressure of 0.30 MPa.

[0095] In the HPLC determination, the eluent was changed to (A) acetonitrile / (B) 10mM ammonium acetate A / B = 60 / 40 (0-30 min), otherwise the same method as in Synthesis Example 1 was used.

[0096] The HPLC analysis of the reaction solution showed that the HPLC relative area percentage of DA-7 was 99.9%, while the HPLC relative area percentage of the over-reduced body ((E)-DA-7′, or (Z)-DA-7′, or DA-7′′) was 0.1%.

[0097] After the reaction was complete, the catalyst was filtered off, and the filtrate was washed twice with THF (3.00 g). The filtrate was distilled at 50 °C to remove toluene, yielding 13.6 g of a solution. 12.1 g of the resulting solution was dried under reduced pressure at 100 °C to give a yellow glassy solid (DA-7) (2.45 g, 98.9% yield). 1H-NMR (CDCl3): δ6.66 (s, 1H, Ar), 6.57 (s, 2H, Ar), 4.45-4.37 (m, 2H, CH2), 4.06-3. 97 (m, 2H, CH2), 3.40 (br, 4H, 2NH2), 3.59 (br, 4H, NH2), 1.50-1.39 (m, 18H, 2t-Bu). It should be noted that the entire contents of the specification, claims and abstract of Japanese Patent Application No. 2023-202678, filed on November 30, 2023, and the entire contents of the specification, claims and abstract of Japanese Patent Application No. 2024-029919, filed on February 29, 2024, are incorporated herein by reference and are included as disclosure in this specification.

Claims

1. A method for manufacturing an aromatic amino compound, characterized in that, In the presence of at least one phosphorus compound (A) selected from the phosphorus compounds shown in formula (1), formula (2), and formula (3) below, an aromatic nitro compound having at least one multiple bond selected from carbon-carbon, carbon-nitrogen, and carbon-oxygen in a portion other than the aromatic ring is catalytically reduced using a Pt / C catalyst. P(R 1 )3 (1) In equation (1), multiple R 1 Each of the following groups independently represents a hydrogen atom, an alkyl group with 1 to 18 carbon atoms, an alkenyl group with 1 to 18 carbon atoms, an alkoxy group with 1 to 18 carbon atoms, an aryl group with 6 to 24 carbon atoms, an aryloxy group with 6 to 24 carbon atoms, a cycloalkyl group with 3 to 18 carbon atoms, or a cycloalkoxy group with 3 to 18 carbon atoms, with or without substituents. PO(R 2 )3 (2) In equation (2), multiple R 2 Each of the following groups independently represents a hydrogen atom, an alkyl group with 1 to 18 carbon atoms, an alkenyl group with 1 to 18 carbon atoms, an alkoxy group with 1 to 18 carbon atoms, an aryl group with 6 to 24 carbon atoms, an aryloxy group with 6 to 24 carbon atoms, a cycloalkyl group with 3 to 18 carbon atoms, or a cycloalkoxy group with 3 to 18 carbon atoms, with or without substituents. (R 3 )2P-R 4 -P(R 3 )2 (3) In equation (3), multiple R 3 Each of the following groups independently represents an alkyl group with 1 to 18 carbon atoms, an alkenyl group with 1 to 18 carbon atoms, an alkoxy group with 1 to 18 carbon atoms, an aryl group with 6 to 24 carbon atoms, an aryloxy group with 6 to 24 carbon atoms, a cycloalkyl group with 3 to 18 carbon atoms, or a cycloalkoxy group with 3 to 18 carbon atoms, which may or may not have substituents; in formula (3), R 4 The terms refer to alkylene, alkenyl, alkyldioxy, aryl, aryldioxy, cycloalkyl, or cycloalkyldioxy, having or not having substituents.

2. The method for manufacturing the aromatic amino compound according to claim 1, wherein, The phosphorus compound (A) is P(OMe)3 or P(OEt)3.

3. The method for manufacturing the aromatic amino compound according to claim 1, wherein, The amount of the phosphorus compound (A) used is 5 to 50 moles relative to the aromatic nitro compound.

4. The method for producing the aromatic amino compound according to any one of claims 1 to 3, wherein, The aromatic nitro compound is represented by any of the following structures (1) to (3). In the formula, R5, R6, R8, and R9 each independently represent a single bond or a divalent group, R7 represents a hydrogen atom or a monovalent group, and n represents an integer from 1 to 2.

5. The method for producing the aromatic amino compound according to any one of claims 1 to 3, wherein, The platinum loading in the Pt / C catalyst is 0.5 to 5 wt% relative to the total weight of the Pt / C catalyst.

6. The method for producing the aromatic amino compound according to any one of claims 1 to 3, wherein, The Pt / C catalyst is an iron-poisoned Pt / C catalyst.

7. The method for producing the aromatic amino compound according to any one of claims 1 to 3, wherein, The amount of the Pt / C catalyst used is 1 to 20% by weight relative to the aromatic nitro compound.

8. The method for producing the aromatic amino compound according to any one of claims 1 to 3, wherein, The reaction temperature in the catalytic reduction is 0–100°C, and the reaction time is 0.5–20 hours.

9. The method for producing the aromatic amino compound according to any one of claims 1 to 3, wherein, This further enables the coexistence of vanadium compounds.

10. The method for producing the aromatic amino compound according to claim 9, wherein, The vanadium compound is VO(acac)2.

11. The method for producing the aromatic amino compound according to claim 9, wherein, The amount of the vanadium compound used is 0.1 to 1.0 mol relative to the aromatic nitro compound.

Images