Process for producing a nitrile oxide compound

Abstract

To provide a method of producing nitrile oxide compound capable of producing a stabilized nitrile oxide compound with ease even in industrial scale.SOLUTION: A method of producing a nitrile oxide compound represented by the following general formula (1) includes: a process (A) of obtaining a reaction solution by reacting a nitro compound represented by the following general formula (2) with an acid anhydride in the presence of an alicyclic amine; and a process (B) of isolating the nitrile oxide compound from the reaction solution. In the formula (1) and the formula (2), Z is an n-valent organic group, n is an integer of 1-10, and Q is an organic group represented by the following general formula (3) or (4). In the formula (3), R1 and R2 are each a 1-29C univalent organic group, a hydrogen atom, or a halogen atom. In the formula (4), Y is a 6-18C bivalent aromatic group, R3 is 1-29C univalent organic group, a hydrogen atom, or a halogen atom, and m is an integer of 0-12.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a method for producing a nitrile oxide compound.

Background Art

[0002] The nitrile oxide group undergoes an easy [2+3] cycloaddition reaction by heating without a catalyst and without generating by-products with an unsaturated bond. Therefore, a nitrile oxide compound having a nitrile oxide group is useful as a reactant in various applications, and is used, for example, as a crosslinking agent or a modifier for diene rubber. However, since the nitrile oxide group easily undergoes side reactions such as dimerization and isomerization and is extremely unstable, nitrile oxide compounds are usually used in various reactions without isolation.

[0003] In recent years, methods for stabilizing nitrile oxide compounds have been studied. For example, a nitrile oxide compound electronically stabilized by conjugating an aromatic ring with a nitrile oxide group, and a nitrile oxide compound stabilized by introducing a bulky substituent at the α-position carbon atom of the nitrile oxide group and protecting the nitrile oxide group by steric hindrance have been proposed. The stabilized nitrile oxide compound can cause an addition reaction with a multiple bond only by heating, so it has a low environmental impact, and can further construct a strong bond, and is useful as a reactant in various applications.

[0004] As a method for producing a stabilized nitrile oxide compound, a method of dehydrating a nitro compound using phenyl isocyanate (see, for example, Patent Document 1), a method of dehydrating a nitro compound using di-tert-butyl dicarbonate and 4-dimethylaminopyridine as a base catalyst (see, for example, Patent Document 2), etc. are known.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0006] However, in the method using phenyl isocyanate, by-products equivalent to one equivalent of the nitro compound as a raw material are generated, so it is necessary to remove them by a column or the like, and it is not suitable for producing a nitrile oxide compound on an industrial scale. In the case of the method using 4-dimethylaminopyridine, although the by-products can be removed by liquid separation, 4-dimethylaminopyridine remains, and the nitrile oxide compound tends to become unstable due to the remaining 4-dimethylaminopyridine. An object of the present invention is to provide a method for producing a nitrile oxide compound that can easily produce a stabilized nitrile oxide compound even on an industrial scale.

Means for Solving the Problems

[0007] The present invention has the following aspects. [1] A method for producing a nitrile oxide compound represented by the following general formula (1), a step (A) of reacting a nitro compound represented by the following general formula (2) with an acid anhydride in the presence of an alicyclic amine to obtain a reaction solution; a step (B) of isolating the nitrile oxide compound from the reaction solution; A method for producing a nitrile oxide compound, comprising:

[0008]

Chemical Formula

[0009] In Formula (1) and Formula (2), Z is an n-valent organic group, n is an integer from 1 to 10, and Q is an organic group represented by the following General Formula (3) or the following General Formula (4).

[0010] [Chemical Formula]

[0011] In Formula (3), R 1 and R 2 are each independently a monovalent organic group having 1 to 29 carbon atoms, a hydrogen atom, or a halogen atom, and R 1 and R 2 may be bonded to each other to form a ring. In Formula (4), Y is a divalent aromatic group having 6 to 18 carbon atoms, R 3 is a monovalent organic group having 1 to 29 carbon atoms, a hydrogen atom, or a halogen atom, m is an integer from 0 to 12, and when m is 2 or more, R 3 may be the same or different, and two or more R 3 may be bonded to each other in any combination to form a ring.

[0012] [2] A method for producing the nitrile oxide compound according to [1], wherein Q is an organic group represented by the general formula (3). [3] A method for producing the nitrile oxide compound according to [1] or [2], wherein the alicyclic amine is a monocyclic amine or a polycyclic amine having a 5-membered or 6-membered ring. [4] A method for producing the nitrile oxide compound according to any one of [1] to [3], wherein the alicyclic amine is at least one selected from the group consisting of N-methylpyrrolidine, 2,2,2-diazabicyclooctane, and N,N'-dimethylpiperazine. [5] A method for producing the nitrile oxide compound according to any one of [1] to [4], wherein the acid anhydride is at least one selected from the group consisting of di-tert-butyl dicarbonate, acetic anhydride, glutaric anhydride, and succinic anhydride. [6] A method for producing the nitrile oxide compound according to any one of [1] to [5], wherein the reaction temperature in the step (A) is 10 to 40 °C. [7] When the isolation method in the step (B) is precipitation, crystallization or sublimation when the nitrile oxide compound is solid, and distillation or liquid separation concentration when the nitrile oxide compound is liquid, the method for producing any one of the nitrile oxide compounds of [1] to [6] above. [Advantages of the Invention]

[0013] According to the present invention, it is possible to provide a method for producing a nitrile oxide compound capable of easily producing a stabilized nitrile oxide compound even on an industrial scale. [Embodiments for Carrying Out the Invention]

[0014] Hereinafter, the present invention will be described in detail. The following embodiments are merely examples for explaining the present invention, and it is not intended to limit the present invention only to these embodiments. The present invention can be implemented in various modes without departing from the gist thereof. Note that "~" indicating a numerical range means including the numerical values described before and after it as the lower limit value and the upper limit value.

[0015] [Method for Producing Nitrile Oxide Compound] The method for producing a nitrile oxide compound of the present invention includes the following step (A) and step (B).

[0016] <Step (A)> Step (A) is a step of reacting a nitro compound and an acid anhydride in the presence of an alicyclic amine to obtain a reaction solution.

[0017] (Reaction Conditions) The reaction between the nitro compound and the acid anhydride is carried out in the presence of an alicyclic amine. The reaction temperature in step (A) is preferably 10 to 40°C, more preferably 15 to 35°C. If the reaction temperature is at least the above lower limit value, the reaction is completed in a short time, so the productivity is increased. If the reaction temperature is at most the above upper limit value, the generation of by-products can be suppressed. The reaction time is not particularly limited, but usually 1 to 15 hours is preferred, 1 to 12 hours is more preferred, and 1 to 6 hours is even more preferred. If the reaction time is at least the above lower limit value, the operation becomes simple and the productivity increases. If the reaction time is at most the above upper limit value, the generation of by-products can be suppressed.

[0018] The reaction between the nitro compound and the acid anhydride is carried out in an organic solvent. Examples of the organic solvent include dichloromethane, toluene, tetrahydrofuran, acetone and the like. These organic solvents may be used alone, or two or more of them may be mixed at an arbitrary ratio and used.

[0019] The amount of the alicyclic amine used is preferably 0.01 to 1 mol, more preferably 0.1 to 0.3 mol, per 1 mol of the nitro compound. If the amount of the alicyclic amine used is at least the above lower limit value, the reaction can be completed in a short time, so an improvement in productivity and suppression of the generation of by-products can be expected. If the amount of the alicyclic amine used is at most the above upper limit value, the number of washing times in step (B) can be reduced. The amount of the acid anhydride used is preferably 1 to 3 mol, more preferably 1.1 to 2.5 mol, per 1 mol of the nitro compound. If the amount of the acid anhydride used is at least the above lower limit value, the reaction can be completed in a short time, so an improvement in productivity and suppression of the generation of by-products can be expected. If the amount of the acid anhydride used is at most the above upper limit value, the number of washing times in step (B) can be reduced.

[0020] (alicyclic amine) The alicyclic amine is a base catalyst. As the alicyclic amine, a monocyclic amine or polycyclic amine having a 5-membered ring or 6-membered ring is preferred, and a monocyclic tertiary amine or polycyclic tertiary amine having a 5-membered ring or 6-membered ring is more preferred. In the present invention, "polycyclic" means that two or more monocycles are present in one molecule. In particular, the case where two or more monocycles are condensed is also referred to as "condensed polycyclic".

[0021] The molecular weight of the alicyclic amine is preferably from 50 to 500, more preferably from 60 to 300. If the molecular weight of the alicyclic amine is at least the above lower limit, the possibility that the alicyclic amine volatilizes during the reaction of step (A) is low, which is preferable. If the molecular weight of the alicyclic amine is at most the above upper limit, the solubility in the reaction solution of step (A) increases, so that the catalytic effect is easily exerted. Further, in step (B), the solubility of the alicyclic amine in water in the washing operation is high, and removal by washing becomes easy. Also, since the boiling point of the alicyclic amine is not extremely high, it can be easily removed even in the drying operation.

[0022] The solubility of the alicyclic amine in water at 25 °C is preferably 200 g / L or more, more preferably 400 g / L or more. If the solubility of the alicyclic amine in water at 25 °C is at least the above lower limit, it can be easily removed by liquid separation. The higher the solubility of the alicyclic amine in water at 25 °C, the more preferable it is, and miscibility is more preferable, but usually it is about 600 g / L or less.

[0023] Examples of the alicyclic amine include N-methylpyrrolidine (molecular weight: 85.15, solubility: miscible), 2,2,2-diazabicyclooctane (molecular weight: 112.18, solubility: 450 g / L), N,N'-dimethylpiperazine (molecular weight: 114.19, solubility: miscible), N-methylmorpholine (molecular weight: 101.15, solubility: miscible), N-methylpiperidine (molecular weight: 99.18, solubility: miscible), and the like. Among these, from the viewpoints of the high nucleophilicity of the amine reagent and the ease of removal by an acid, N-methylpyrrolidine, 2,2,2-diazabicyclooctane, and N,N'-dimethylpiperazine are preferable. These alicyclic amines may be used alone, or two or more of them may be mixed and used at an arbitrary ratio.

[0024] (Acid anhydride) Examples of the acid anhydride include di-tert-butyl dicarbonate, acetic anhydride, glutaric anhydride, succinic anhydride, trifluoroacetic anhydride, phthalic anhydride, maleic anhydride, benzoic anhydride and the like. Among these, di-tert-butyl dicarbonate, acetic anhydride, glutaric anhydride, and succinic anhydride are preferable from the viewpoints of high reactivity and ease of removal after the reaction, and di-tert-butyl dicarbonate is more preferable.

[0025] (Nitro compound) The nitro compound is a compound represented by the following general formula (2).

[0026] [Chemical formula]

[0027] In formula (2), Q is an organic group represented by the following general formula (3) or the following general formula (4). From the viewpoint that the nitrile oxide compound is more easily stabilized due to electronic factors and steric hindrance factors, the organic group represented by the following general formula (3) is preferable as Q.

[0028] [Chemical formula]

[0029] In formula (3), R 1 and R 2 are each independently a monovalent organic group having 1 to 29 carbon atoms, a hydrogen atom, or a halogen atom. The monovalent organic group contains a carbon atom as an essential element, and may contain a hydrogen atom, an oxygen atom, a chlorine atom, a nitrogen atom, a fluorine atom, a sulfur atom, etc. as necessary. Examples of the monovalent organic group include a hydrocarbon group (alkyl group, aryl group, etc.), a combination of a hydrocarbon group and various bonds (-O-, -C(=O)-, -S-, -S(=O) 2 -, etc.), a combination of a hydrocarbon group and a polar functional group (hydroxy group, mercapto group, carboxy group, amino group, amide group, alkoxy group, etc.), a combination of a hydrocarbon group, various bonds, and a polar functional group, and the like. Specific examples of the monovalent organic group include hydrocarbon groups such as methyl group, ethyl group, propyl group, tert-butyl group, isobutyl group, phenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2,4-dimethylphenyl group, 3,4-dimethylphenyl group, naphthyl group, anthracenyl group; aromatic halogenated hydrocarbon groups such as 4-chlorophenyl group, 4-fluorophenyl group; halogenated hydrocarbon groups such as trifluoromethyl group, pentafluoroethyl group, perfluorobutyl group, perfluoropentyl group, perfluorohexyl group; heteroaromatic groups such as a group having furan, a group having pyridine, a group having indole, a group having thiophene, a group having pyrrole, a group having pyrazine, and the like. Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, an iodine atom and the like.

[0030] R 1 and R 2 As, the melting point of the nitrile oxide compound tends to be high and the nitrile oxide group is less likely to dimerize, an aryl group having 6 to 8 carbon atoms is preferable. Examples of the aryl group having 6 to 8 carbon atoms include a phenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2,4-dimethylphenyl group, 4-chlorophenyl group and the like. Among these, a phenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2,4-dimethylphenyl group are preferable, and a phenyl group is more preferable. R 1 and R 2 may be the same or different. R 1 and R 2 are preferably the same in view of high molecular symmetry, easy solidification of the nitrile oxide compound, and excellent storage stability at room temperature. R 1 and R 2 may be bonded to each other to form a ring.

[0031] In formula (4), Y is a divalent aromatic group having 6 to 18 carbon atoms. The divalent aromatic group only needs to have an aromatic ring structure. The aromatic ring structure may be monocyclic or polycyclic. Examples of the divalent aromatic group include a phenylene group, a biphenylene group, a naphthylene group, etc. However, m hydrogen atoms in the divalent aromatic group are replaced by R 3 .

[0032] In formula (4), R 3 is a monovalent organic group having 1 to 29 carbon atoms, a hydrogen atom or a halogen atom. R 3 Examples of the monovalent organic group in R 1 and R 2 include the monovalent organic groups exemplified above in the description of R R 3 Examples of the monovalent organic group and the halogen atom in R 1 and R 2 include the monovalent organic groups and the halogen atoms exemplified above in the description of R

[0033] In formula (4), m is an integer from 0 to 12. As m, an integer from 4 to 12 is preferable, and an integer from 6 to 10 is more preferable. When m is 0, Y is preferably a divalent aromatic group having no substituent, more preferably a phenylene group or a naphthylene group. When m is 2 or more, R 3 may be the same or different, and two or more R 3 may be bonded to each other in any combination to form a ring.

[0034] In formula (2), n is an integer from 1 to 10. As n, an integer from 1 to 3 is preferable, 1 or 2 is more preferable, and 2 is even more preferable, from the viewpoint that the nitrile oxide group is less likely to dimerize in the molecule.

[0035] In formula (2), Z is an n-valent organic group. The n-valent organic group must contain a carbon atom and may optionally contain a hydrogen atom, an oxygen atom, a chlorine atom, a nitrogen atom, a fluorine atom, a sulfur atom, etc. Examples of the n-valent organic group include hydrocarbon groups (alkyl groups, alkylene groups, aryl groups, arylene groups, etc.), combinations of hydrocarbon groups with various bonds (-O-, -C(=O)-, -S-, -S(=O) 2 - etc.), combinations of hydrocarbon groups with polar functional groups (hydroxy group, mercapto group, carboxy group, amino group, amide group, alkoxy group, etc.), combinations of hydrocarbon groups with various bonds and polar functional groups, and the like.

[0036] When n is 1, Z is preferably a group represented by the following general formula (5). R 4 -X 1 - ···(5) In formula (5), R 4 is a monovalent organic group containing one or more selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom, and X 1 is a divalent hydrocarbon group, -O-, -S-, or -N(R 5 )-, and R 5 is a hydrogen atom or a hydrocarbon group having 1 to 6 carbon atoms.

[0037] In formula (5), X 1 is preferably -O- or -S- from the viewpoint of easier synthesis of the nitrile oxide compound, more preferably -O-, and preferably a divalent hydrocarbon group from the viewpoint of heat resistance. X 1 Examples of the divalent hydrocarbon group in X include an alkylene group having 1 to 3 carbon atoms, an arylene group having 6 to 8 carbon atoms, and combinations thereof. 5 Examples of the hydrocarbon group having 1 to 6 carbon atoms in R 5 include a methyl group, an ethyl group, a propyl group, a butyl group, a hexyl group, and the like. R

[0038] In formula (5), R 4It is preferably a group represented by the following general formula (6). R 41 -R 42 - ···(6) In formula (6), R 41 is a polar functional group, and R 42 is an alkylene group having 1 to 5 carbon atoms or an arylene group having 6 to 10 carbon atoms.

[0039] In formula (6), examples of the polar functional group in R 41 include a hydroxy group, a mercapto group, a carboxy group, an amino group, an amino group having a substituent, an amide group, a terminal cyclic acetal group, a terminal chain acetal group, -OR 6 (wherein R 6 is a hydrogen atom, a hydrocarbon group having 1 to 6 carbon atoms or an aryl group having 6 to 10 carbon atoms, and is preferably a hydrogen atom or an alkyl group having 1 to 6 carbon atoms.), a heterocycle, and the like. The heterocycle is a cyclic substituent having a heteroatom such as a boron atom, a nitrogen atom, an oxygen atom, or a sulfur atom. Examples of the heterocycle include a furyl group, a thienyl group, a pyrrolyl group, an imidazolyl group, a pyranyl group, a pyridinyl group, a pyrimidinyl group, a pyrazinyl group, a pyrrolidinyl group, a piperidinyl group, a piperazinyl group, a morpholinyl group, a carbazolyl group, an imidazolidonyl group, and the like. The heterocycle may have a substituent. R 41 From the viewpoint of increasing the melting point of the nitrile oxide compound, a hydroxy group, a mercapto group, a carboxy group, an amino group, an amino group having a substituent, an amide group, and a heteroaryl ring are preferable, and a hydroxy group, a mercapto group, a carboxy group, an amino group, and an amino group having a substituent are more preferable. Further, from the viewpoint of increasing the reactivity of the nitrile oxide compound with a filler or another resin, a hydroxy group, an amino group, an amino group having a substituent, a mercapto group, a carboxyl group, and a heterocycle are preferable for R 41 .

[0040] In formula (6), R 42Examples of the alkylene group having 1 to 5 carbon atoms include a 1,1-methylene group, a 1,2-ethylene group, a 1,3-propylene group, a 1,4-butylene group, a 1,5-pentylene group, and the like. R 42 Examples of the arylene group having 6 to 10 carbon atoms include a phenylene group, a naphthylene group, and the like. R 42 A 1,2-ethylene group, a 1,3-propylene group, a 1,4-butylene group, or a phenylene group is preferable. In the case of an alkylene group, the shorter the carbon chain, the higher the melting point of the nitrile oxide compound tends to be.

[0041] When n is 2, Z is preferably a group represented by the following general formula (7). -X 2 -(R 8 -O) s -R 7 -(O-R 9 ) t -X 3 - ···(7) In formula (7), R 7 is an alkylene group having 2 to 10 carbon atoms, a group represented by the following general formula (8), or a group represented by the following general formula (9), R 8 and R 9 are each independently an alkylene group having 2 to 4 carbon atoms, X 2 and X 3 are each independently a divalent hydrocarbon group, -O-, -S-, or -N(R 10 )-, R 10 is a hydrogen atom or a hydrocarbon group having 1 to 6 carbon atoms, s is an integer of 0 or 1, and t is an integer of 0 or 1.

[0042] In formula (7), X 2 and X 3 are each independently preferably -O- or -S- from the viewpoint of further facilitating the synthesis of the nitrile oxide compound, more preferably -O-, and preferably a divalent hydrocarbon group from the viewpoint of heat resistance. X 2 and X 3 Examples of the divalent hydrocarbon group in include X in the general formula (5) above1 Examples of the divalent hydrocarbon group exemplified above in the description include those mentioned above. R 10 Examples of the hydrocarbon group having 1 to 6 carbon atoms in R include the hydrocarbon groups having 1 to 6 carbon atoms exemplified above in the description of X in the general formula (5). 1 Examples of the hydrocarbon group having 1 to 6 carbon atoms in R include the hydrocarbon groups having 1 to 6 carbon atoms exemplified above in the description of X in the general formula (5). X 2 and X 3 may be the same or different, but are preferably the same.

[0043] In formula (7), examples of R 8 and R 9 each independently include a 1,2-ethylene group, a 1,3-propylene group, etc. From the viewpoint that the melting point of the nitrile oxide compound can be increased as the carbon number of R 8 and R 9 is smaller, a 1,2-ethylene group is preferred. R 8 and R 9 may be the same or different, but are preferably the same.

[0044] From the viewpoint of ease of production of the nitrile oxide compound, s and t are each preferably 1, and from the viewpoint of the melting point of the nitrile oxide compound, s and t are each preferably 0.

[0045] In formula (7), R 7 is an alkylene group having 2 to 10 carbon atoms, a group represented by the following general formula (8), or a group represented by the following general formula (9). R 7 From the viewpoint of easy synthesis of the nitrile oxide compound, an alkylene group having 2 to 10 carbon atoms is preferred for R

[0046] R 7 From the viewpoint of high melting point expression by the nitrile oxide compound, the following general formula (8) is preferred for R R 7 Examples of the alkylene group having 2 to 10 carbon atoms in R include 1,2-ethylene group, 1,3-propylene group, 2-methyl-1,3-propylene group, 2,2-dimethyl-1,3-propylene group, 1,4-butylene group, 1,5-pentylene group, 1,6-hexylene group, 1,7-heptylene group, 1,8-octylene group, 3-methyl-1,5-pentylene group, 1,4-cyclohexylene group, 1,4-cyclohexanedimethylene group, 1-methyl-1,2-ethylene group, 1-methyl-1,3-propylene group, and the like. Among these, 1,3-propylene group, 1,4-butylene group, 1,6-hexylene group, 1,4-cyclohexanedimethylene group, 1,4-cyclohexylene group, 3-methyl-1,5-pentylene group are preferable, and 1,4-butylene group, 1,6-hexylene group, 3-methyl-1,5-pentylene group are more preferable.

[0047]

Chemical formula

[0048] In formula (8), R 11 ~R 14 are each independently a hydrogen atom, a hydrocarbon group having 1 to 6 carbon atoms, or a halogen atom, and R 11 and R 12 may be bonded to each other to form a ring, and R 13 and R 14 may be bonded to each other to form a ring.

[0049] In formula (8), examples of the hydrocarbon group having 1 to 6 carbon atoms in R 11 ~R 14 include a methyl group, an ethyl group, a propyl group, a butyl group, a hexyl group, a cyclohexyl group, a phenyl group, and the like. Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, and the like. R 11 ~R 14Each independently, a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, a phenyl group, or a chlorine atom is preferable; a hydrogen atom, a methyl group, an isopropyl group, or a tert-butyl group is more preferable; and a hydrogen atom or a methyl group is even more preferable. R 11 ~R 14 They may be the same or different, but it is preferable that they are the same.

[0050] In formula (9), R 15 ~R 22 each independently represents a hydrogen atom, a hydrocarbon group having 1 to 6 carbon atoms, or a halogen atom, W represents -C(R 23 )(R 24 )-, -C(=O)-, -S-, or -S(=O) 2 -, R 23 and R 24 each independently represent a hydrogen atom, a hydrocarbon group having 1 to 6 carbon atoms, or a halogen atom, u is 0 or 1, R 15 and R 16 may be bonded to each other to form a ring, R 17 and R 18 may be bonded to each other to form a ring, R 19 and R 20 may be bonded to each other to form a ring, R 21 and R 22 may be bonded to each other to form a ring, R 23 and R 24 may be bonded to each other to form a ring.

[0051] In formula (9), examples of the hydrocarbon group having 1 to 6 carbon atoms for R 15 ~R 22 include a methyl group, an ethyl group, a propyl group, a butyl group, a hexyl group, a cyclohexyl group, a phenyl group, and the like. Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, and the like. R 15 ~R 22Examples thereof preferably include a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, a phenyl group, and a chlorine atom; more preferably include a hydrogen atom, a methyl group, an isopropyl group, and a tert-butyl group; and still more preferably include a hydrogen atom and a methyl group. R 15 ~R 22 may be the same or different, but are preferably the same.

[0052] In formula (9), u is 0 or 1, and 1 is preferable from the viewpoint of excellent solubility in a resin, particularly a polyolefin. In formula (9), W is preferably -C(R 23 )(R 24 )- from the viewpoints of excellent solubility in a resin, particularly a polyolefin, and high solubility in a polyolefin during melt kneading. R 23 and R 24 Examples of the hydrocarbon group having 1 to 6 carbon atoms in R R 23 and R 24 include, for example, a methyl group, an ethyl group, a propyl group, a butyl group, a hexyl group, a cyclohexyl group, and a phenyl group. R 23 and R 24 Examples of the halogen atom in R R 23 and R 24 each independently preferably include a hydrogen atom, a methyl group, an ethyl group, and a phenyl group. R 23 and R 24 may be the same or different, but are preferably the same.

[0053] As the nitro compound, the following nitro compounds (i) to (iii) are preferable from the viewpoint that the melting point of the nitrile oxide compound tends to be high and the storage stability at room temperature is excellent. (i) In the general formula (1), n is 2, Z is a group represented by the general formula (7), Q is an organic group represented by the general formula (3), and in the general formula (7), R 7 is an alkylene group having 2 to 10 carbon atoms, s is 0, and t is 0 nitro compound. (ii) In the general formula (1), n is 2, Z is a group represented by the general formula (7), Q is an organic group represented by the general formula (3), and in the general formula (7), R 7 is a group represented by the general formula (8) or a group represented by the general formula (9) nitro compound. (iii) In the general formula (1), n is 1, Z is a group represented by the general formula (5), and Q is an organic group represented by the general formula (3) nitro compound.

[0054] The nitro compound in which Q is an organic group represented by the general formula (3) can be produced, for example, by the following scheme.

[0055]

Chemical formula

[0056] Compound 3 is obtained by reacting Compound 1 with a base such as sodium hydride and then reacting with Compound 2. Examples of Compound 1 include alcohols having 1 to 4 hydroxy groups, thiols having 1 to 4 mercapto groups, amines having 1 to 4 amino groups, and the like. Examples of Compound 2 include 1-nitro-2,2-diphenylethylene and the like. By replacing the phenyl group of 1-nitro-2,2-diphenylethylene with another group, various substituents can be introduced to the carbon atom at the α-position of the nitrile oxide group.

[0057] <Step (B)> Step (B) is a step of isolating the nitrile oxide compound from the reaction solution. In step (A), by reacting a nitro compound with an acid anhydride, a reaction solution containing a reaction product, an alicyclic amine, unreacted nitro compound and acid anhydride, and an organic solvent used in the reaction, etc. is obtained. The reaction product contains by-products in addition to the target nitrile oxide compound.

[0058] Hereinafter, an example of a method for isolating a nitrile oxide compound from the reaction solution will be described. First, the reaction solution is washed with hydrochloric acid. By washing the reaction solution with hydrochloric acid, the alicyclic amine is mainly extracted into the hydrochloric acid phase and removed from the reaction solution. Also, although the alicyclic amine may decompose to such an extent that it does not affect the catalytic action during the reaction between the nitro compound and the acid anhydride, the decomposition products of the alicyclic amine are also extracted into the hydrochloric acid phase.

[0059] Next, the reaction solution washed with hydrochloric acid is further washed with water. The washing with water is preferably carried out until the reaction solution becomes neutral.

[0060] Next, the nitrile oxide compound is isolated from the reaction solution washed with water. When the nitrile oxide compound is solid, examples of the method for isolating the nitrile oxide compound include precipitation, crystallization, sublimation, etc. Among these, crystallization is preferred. Specifically, a poor solvent such as methanol is added to the reaction solution to crystallize the nitrile oxide compound, and the nitrile oxide compound is recovered by solid-liquid separation by filtration. These isolation methods may be used alone, or two or more of them may be used in combination.

[0061] When the nitrile oxide compound is liquid, examples of the method for isolating the nitrile oxide compound include distillation, liquid separation and concentration, etc. These isolation methods may be used alone, or two or more of them may be used in combination.

[0062] <Nitrile oxide compound> The nitrile oxide compound obtained by the present invention is a compound represented by the following general formula (1).

[0063]

Chemical formula

[0064] In formula (1), Z is an n-valent organic group, n is an integer from 1 to 10, and Q is an organic group represented by the general formula (3) or the general formula (4). Z, Q, and n in formula (1) are the same as Z, Q, and n in formula (2) exemplified above in the description of the nitro compound, and the description thereof is omitted.

[0065] Preferred specific examples of the nitrile oxide compound include the following compounds. In the structural formula, "Ph" means a phenyl group.

[0066]

Chemical formula

[0067]

Chemical formula

[0068]

Chemical formula

[0069]

Chemical formula

[0070]

Chemical formula

[0071] In addition to the compounds exemplified above, structures in which the phenyl group at the α-position of the nitrile oxide group is substituted with a methylphenyl group or a dimethylphenyl group can also be exemplified in the same manner.

[0072] <Effect> It is known that in nitrile oxide compounds, the CNO group dissociates and recombines as an NCO group, or decomposition due to the dissociation of the CNO group proceeds. As described above, when 4-dimethylaminopyridine is used as a base catalyst in the production of a nitrile oxide compound, the nitrile oxide compound tends to be unstable. The reason is considered as follows. That is, 4-dimethylaminopyridine is difficult to decompose and is difficult to dissolve in hydrochloric acid or water, so it tends to remain in the nitrile oxide compound without being removed. It is considered that the remaining 4-dimethylaminopyridine acts nucleophilicly on the dissociation of the CNO group of the nitrile oxide compound, thereby promoting the dissociation of the CNO group.

[0073] On the other hand, according to the method for producing a nitrile oxide compound of the present invention, the above-mentioned nitro compound and acid anhydride are reacted in the presence of an alicyclic amine. Since the alicyclic amine hardly acts nucleophilicly on the dissociation of the CNO group, the nitrile oxide compound is unlikely to become unstable even if the alicyclic amine remains in the nitrile oxide compound. Moreover, the alicyclic amine decomposes to such an extent that it does not affect the catalytic action during the reaction between the nitro compound and the acid anhydride. In addition, since the alicyclic amine and its decomposition products can be extracted with hydrochloric acid, they can be easily removed if one tries to remove the alicyclic amine and its decomposition products from the reaction solution, and it is difficult for the alicyclic amine to remain in the nitrile oxide compound isolated from the reaction solution. If the nitrile oxide compound is isolated from the reaction solution, when the nitrile oxide compound is used as a reactant in various applications, for example, the operability is excellent when kneading with an organic material.

[0074] Thus, according to the method for producing a nitrile oxide compound of the present invention, a stabilized nitrile oxide compound can be easily produced. Moreover, this nitrile oxide compound can be isolated from the reaction solution by a simple isolation operation without using a column, so that a stabilized nitrile oxide compound can be easily produced from a small-scale test to an industrial scale.

[0075] <Use> The nitrile oxide compound obtained by the present invention is useful as a reactant in various applications, for example, as a crosslinking agent or a modifier for organic materials. The nitrile oxide compound obtained by the present invention is stable even when exposed to a high temperature (for example, 200 ° C or higher) when kneaded with an organic material. Examples of the organic material include resins and rubbers. Examples of the resin include polyolefins such as polyethylene and polypropylene; polyacrylonitrile and the like. Examples of the rubber include resins such as polyethylene, polypropylene, and polyacrylonitrile; diene rubbers such as styrene-butadiene rubber, nitrile rubber, butadiene rubber, isoprene rubber, natural rubber, chloroprene rubber, acrylonitrile-butadiene rubber, butyl rubber, and ethylene-propylene-diene rubber.

Example

[0076] Hereinafter, the present invention will be described more specifically based on examples, but the present invention is not limited to the following examples as long as the gist thereof is not exceeded.

[0077] [Physical property measurement, analysis method] <Measurement of melting point and decomposition peak temperature> The melting point and decomposition peak temperature of the nitrile oxide compound were determined by thermogravimetry-differential thermal simultaneous measurement (TG-DTA). For TG-DTA, "Thermo plus EVO2 differential thermal balance TG-DTA8122" manufactured by Rigaku Corporation was used. TG-DTA was performed using an aluminum pan with a diameter of 5 mm and a height of 2.5 mm under a nitrogen stream of 300 mL / min. After isothermal treatment of the measurement sample at 30 °C for 30 minutes, the temperature was raised to 550 °C at a rate of 30 °C / min, and the peak top of the endothermic melting peak of the solid was taken as the melting point of the nitrile oxide compound. Similarly, the peak top of the endothermic peak observed when the temperature was raised to 550 °C at a rate of 30 °C / min was taken as the decomposition peak temperature of the nitrile oxide compound.

[0078] [Example 1] The nitrile oxide compound was produced as follows according to the following scheme.

[0079] [Chemical formula]

[0080] 14.17 g (120 mmol) of 1,6-hexanediol was dissolved in 120 mL of dehydrated THF and cooled to 0 °C. To this solution, 16 g (400 mmol) of sodium hydride was added under nitrogen gas, and the mixture was stirred at 0 °C for 1 hour. To this solution, 60 g (266 mmol) of 1-nitro-2,2-diphenylethylene was added, and the mixture was stirred at 20 °C for 16 hours. After cooling the solution to 0 °C, it was neutralized with a 2 mol / L aqueous hydrogen chloride solution until the pH reached 6 - 7. The neutralized solution was extracted with dichloromethane. The dichloromethane solution was washed with saturated brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated and purified. The obtained solid was washed with ethyl acetate to obtain 50 g of a white solid compound A-1 (yield 70%). NMR spectrum of compound A-1: 1 H-NMR (400 MHz, CDCl 3 ): δ 7.36 - 7.24 (m, 20H), 5.34 (s, 4H), 3.35 (t, 4H), 1.74 - 1.61 (m, 4H), 1.47 - 1.32 (m, 4H) ppm.

[0081] 2.0 g (3.52 mmol) of Compound A-1 was dissolved in 10 mL of dehydrated dichloromethane, and the resulting solution was adjusted to 25°C. To this solution, 1.9 g (8.70 mmol) of di-tert-butyl dicarbonate as an acid anhydride and 78 mg (0.70 mmol) of 2,2,2-diazabicyclooctane as a base catalyst were added, and the mixture was stirred at 25°C for 4 hours to obtain a reaction solution. The completion of the reaction was confirmed by LC (liquid chromatography). Subsequently, 10 mL of 1N hydrochloric acid was added to the reaction solution to wash the reaction solution, and after separating the organic phase (dichloromethane phase) and the aqueous phase, the organic phase was washed with pure water until the pH of the organic phase became neutral. By adding 50 mL of methanol to the washed organic phase (reaction solution), the nitrile oxide compound was crystallized, and solid-liquid separation was performed by filtration to obtain 1.6 g of a white solid nitrile oxide compound A-2 (isolation yield 85%, HPLC purity: over 98%). The melting point and decomposition peak temperature of the obtained nitrile oxide compound A-2 were measured. The results are shown in Table 1. NMR spectrum of nitrile oxide compound A-2: 1 H-NMR (400 MHz, CDCl 3 ): δ 7.44 - 7.30 (m, 20H), 3.45 (t, 4H), 1.69 (m 4H), 1.41 (m, 4H) ppm.

[0082] [Example 2] 1.6 g of nitrile oxide compound A-2 (isolation yield 85%, HPLC purity: over 98%) was obtained in the same manner as in Example 1, except that 34 mg (0.40 mmol) of N-methylpyrrolidine was used as the base catalyst. The melting point and decomposition peak temperature of the obtained nitrile oxide compound A-2 were measured. The results are shown in Table 1.

[0083] [Comparative Example 1] 1.6 g of nitrile oxide compound A-2 (isolation yield 85%, HPLC purity: over 98%) was obtained in the same manner as in Example 1, except that 48 mg (0.40 mmol) of 4-dimethylaminopyridine was used as the base catalyst and the stirring time was changed to 2.5 hours. The melting point and decomposition peak temperature of the obtained nitrile oxide compound A-2 were measured. The results are shown in Table 1.

[0084] [Comparative Example 2] Using 33 mg (0.40 mmol) of 1-methylimidazole as the base catalyst and changing the stirring time to 10 hours, an attempt was made to obtain the nitrile oxide compound A-2 in the same manner as in Example 1. However, the nitrile oxide compound A-2 decomposed and could not be isolated.

[0085]

Table 1

[0086] In Table 1, the amount of the base catalyst used is the molar equivalent (eq) relative to 1 mol of Compound A-1. As is clear from Table 1, the nitrile oxide compounds of Examples 1 and 2 using an alicyclic amine as the base catalyst had high melting points and decomposition peak temperatures and were stable. On the other hand, the nitrile oxide compound of Comparative Example 1 using 4-dimethylaminopyridine as the base catalyst had a low decomposition peak temperature and was unstable. In the case of Comparative Example 1, since 4-dimethylaminopyridine remained in the nitrile oxide compound without being removed, it is considered that the nitrile oxide compound was easily decomposed and the melting point and decomposition peak temperature decreased. Hereinafter, a test on the stability of the nitrile oxide compound due to the presence of the base catalyst was conducted.

[0087] [Test Example 1] Compound A-1 was obtained in the same manner as in Example 1. 25 g (44.0 mmol) of Compound A-1 was dissolved in 750 mL of dehydrated dichloromethane. To this solution, 22.5 mL (176 mmol) of 4-chlorophenyl isocyanate, 26.90 g (266 mmol) of triethylamine, and 50 g of molecular sieves 4A were added, and the mixture was stirred at 20 °C for 16 hours under nitrogen gas. The solution was filtered, and after concentrating the filtrate, it was purified by column chromatography (acidic silica gel, solvent: n-hexane / ethyl acetate 1 / 0, 3 / 1) to obtain 7.87 g of the nitrile oxide compound A-3 as a white solid (isolation yield 34%, HPLC purity: over 98%). The melting point and decomposition peak temperature of the obtained nitrile oxide compound A-3 were measured. The results are shown in Table 2.

[0088] [Test Example 2] The nitrile oxide compound A-3 was obtained in the same manner as in Test Example 1. With respect to 100 parts by mass of the obtained nitrile oxide compound A-3, 1 part by mass of 2,2,2-diazabicyclooctane was added, and the melting point and decomposition peak temperature were measured. The results are shown in Table 2.

[0089] [Test Example 3] The nitrile oxide compound A-3 was obtained in the same manner as in Test Example 1. With respect to 100 parts by mass of the obtained nitrile oxide compound A-3, 1 part by mass of N-methylpyrrolidine was added, and the melting point and decomposition peak temperature were measured. The results are shown in Table 2.

[0090] [Test Example 4] The nitrile oxide compound A-3 was obtained in the same manner as in Test Example 1. With respect to 100 parts by mass of the obtained nitrile oxide compound A-3, 1 part by mass of N-methylmorpholine was added, and the melting point and decomposition peak temperature were measured. The results are shown in Table 2.

[0091] [Test Example 5] The nitrile oxide compound A-3 was obtained in the same manner as in Test Example 1. With respect to 100 parts by mass of the obtained nitrile oxide compound A-3, the melting point and the decomposition peak temperature were measured with 1 part by mass of N,N'-dimethylpiperazine added. The results are shown in Table 2.

[0092] [Test Example 6] The nitrile oxide compound A-3 was obtained in the same manner as in Test Example 1. With respect to 100 parts by mass of the obtained nitrile oxide compound A-3, the melting point and the decomposition peak temperature were measured with 1 part by mass of 4-dimethylaminopyridine added. The results are shown in Table 2.

[0093] [Test Example 7] The nitrile oxide compound A-3 was obtained in the same manner as in Test Example 1. With respect to 100 parts by mass of the obtained nitrile oxide compound A-3, the melting point and the decomposition peak temperature were measured with 1 part by mass of 1-methylimidazole added. The results are shown in Table 2.

[0094]

Table 2

[0095] In Table 2, the addition amount of the base catalyst is the amount (parts by mass) relative to 100 parts by mass of the nitrile oxide compound A-3. Note that Test Example 1 is a control example, Test Examples 2 to 5 are reference examples, and Test Examples 6 and 7 are reference comparative examples.

[0096] As is clear from Table 2, even when an alicyclic amine is added to the nitrile oxide compound as a base catalyst (Test Examples 2 to 5), the melting point and the decomposition peak temperature of the nitrile oxide compound hardly changed compared to the case where no base catalyst was added (Test Example 1). On the other hand, when 4-dimethylaminopyridine was added to the nitrile oxide compound as a base catalyst (Test Example 6), the melting point and the decomposition peak temperature of the nitrile oxide compound decreased compared to Test Example 1. When 1-methylimidazole was added to the nitrile oxide compound as a base catalyst (Test Example 7), the melting point of the nitrile oxide compound decreased slightly compared to Test Example 1. Also, when attempting to measure the decomposition peak temperature, the nitrile oxide compound decomposed and could not be measured. From these results, it was shown that even when an alicyclic amine coexists with the nitrile oxide compound, it has no effect on the melting point and decomposition peak temperature of the nitrile oxide compound, and the nitrile oxide compound is stable. On the other hand, it was shown that when a base catalyst other than the alicyclic amine (4-dimethylaminopyridine, 1-methylimidazole) coexists with the nitrile oxide compound, the nitrile oxide compound is easily decomposed.

[0097] [Test Example 8] Compound A-1 was obtained in the same manner as in Example 1. 100 mg (0.56 mmol) of Compound A-1 was dissolved in 2 mL of dehydrated dichloromethane, and the resulting solution was adjusted to 25°C. To this solution, 182 mg (0.83 mmol) of di-tert-butyl dicarbonate as an acid anhydride and 5 mg (0.056 mmol) of N-methylpyrrolidine as a base catalyst were added, and the mixture was stirred at 25°C for 4 hours to obtain a reaction solution. The completion of the reaction was confirmed by LC (liquid chromatography). Thereafter, 2 mL of 1N hydrochloric acid was added to the reaction solution to wash the reaction solution. After separating the organic phase (dichloromethane phase) and the aqueous phase, the organic phase was washed with pure water until the pH of the organic phase became neutral. By adding 5 mL of methanol to the washed organic phase (reaction solution), the nitrile oxide compound was crystallized, and solid-liquid separation was performed by filtration to obtain 76 g of a white solid nitrile oxide compound A-4 (isolation yield 85%, HPLC purity: over 98%). The melting point and decomposition peak temperature of the obtained nitrile oxide compound A-4 were measured. The results are shown in Table 3.

[0098] [Test Example 9] The nitrile oxide compound A-4 was obtained in the same manner as in Test Example 8. The melting point and decomposition peak temperature were measured while adding 1 part by mass of 4-dimethylaminopyridine to 100 parts by mass of the obtained nitrile oxide compound A-4. The results are shown in Table 3.

[0099] [Test Example 10] The nitrile oxide compound A-4 was obtained in the same manner as in Test Example 8. The melting point and decomposition peak temperature were measured while adding 1 part by mass of N-methylpyrrolidine to 100 parts by mass of the obtained nitrile oxide compound A-4. The results are shown in Table 3.

[0100]

Table 3

[0101] Table 3. The addition amount of the base catalyst is the amount (parts by mass) relative to 100 parts by mass of the nitrile oxide compound A-4. Note that Test Example 8 is a comparative example, Test Example 9 is a reference comparative example, and Test Example 10 is a reference example.

[0102] As is clear from Table 3, the alicyclic amine has a smaller influence on the stability when added to the nitrile oxide compound than 4-dimethylaminopyridine, indicating that the nitrile oxide compound is less likely to decompose.

Industrial Applicability

[0103] According to the method for producing a nitrile oxide compound of the present invention, a stabilized nitrile oxide compound can be easily produced even on an industrial scale, and the method for producing a nitrile oxide compound of the present invention has extremely high industrial value. The nitrile oxide compound obtained by the present invention can be used as a crosslinking agent or a modifier such as a resin or rubber, and is very useful from an industrial perspective.

Claims

1. A method for producing a nitrile oxide compound represented by the following general formula (1), comprising: a step (A) of reacting a nitro compound represented by the following general formula (2) with an acid anhydride in the presence of an alicyclic amine to obtain a reaction solution; a step (B) of isolating the nitrile oxide compound from the reaction solution; wherein the acid anhydride is at least one selected from the group consisting of di-tert-butyl dicarbonate, acetic anhydride, glutaric anhydride, succinic anhydride, trifluoroacetic anhydride, phthalic anhydride, maleic anhydride, and benzoic anhydride. A method for producing a nitrile oxide compound. 【Chemical 1】 In formulas (1) and (2), Z is an n-valent organic group, n is an integer from 1 to 10, and Q is an organic group represented by the following general formula (3). 【Chemical Formula 2】 In formula (3), R １ and R ２ are each independently a monovalent organic group having 1 to 29 carbon atoms, a hydrogen atom, or a halogen atom, and R １ and R ２ may be bonded to each other to form a ring.

2. The method for producing a nitrile oxide compound according to claim 1, wherein the alicyclic amine is a monocyclic amine or a polycyclic amine having a 5-membered or 6-membered ring.

3. The method for producing a nitrile oxide compound according to claim 1 or 2, wherein the alicyclic amine is at least one selected from the group consisting of N-methylpyrrolidine, 2,2,2-diazabicyclooctane, and N,N'-dimethylpiperazine.

4. The method for producing a nitrile oxide compound according to any one of claims 1 to 3, wherein the acid anhydride is at least one selected from the group consisting of di-tert-butyl dicarbonate, acetic anhydride, glutaric anhydride, and succinic anhydride.

5. The method for producing a nitrile oxide compound according to any one of claims 1 to 4, wherein the reaction temperature in the step (A) is 10 to 40°C.

6. The method for producing a nitrile oxide compound according to any one of claims 1 to 5, wherein the isolation method in the step (B) is precipitation, crystallization, or sublimation when the nitrile oxide compound is solid, and distillation or liquid separation and concentration when the nitrile oxide compound is liquid.

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