Method for producing organic iodine compound

Abstract

[Problem] To provide a method by which an organic iodine compound that is useful as, for example, a polymerization initiator and a raw material for synthesizing various chemicals can be industrially advantageously produced with good yield and good purity. [Solution] A method for producing an organic iodine compound represented by general formula (IV), the method comprising reacting a polyhydric alcohol represented by general formula (I) with a halogenocarboxylic acid represented by general formula (II) in the presence of an acid to obtain an ester compound represented by general formula (III), and reacting the ester compound with an iodide salt in the presence of a Lewis acid. (In the formulae, L represents a C2-C20 n-valent organic group, X represents a chlorine atom or a bromine atom, and R1 and R2 each independently represent a C1-C6 alkyl group or in combination represent a C2-C6 alkylene group; n is an integer of 2-6; and a is a positive number of 0 or greater but less than n, and b is a positive number greater than 0 but not greater than n, with the proviso that a+b=n.)

Description

Method for producing organic iodine compounds

[0001] The present invention relates to a method for producing an organic iodine compound, and more particularly to an industrially advantageous method for producing an organic iodine compound using a polyhydric alcohol as a raw material.

[0002] Organic iodine compounds, such as low-molecular-weight alkyl iodine compounds, are useful as synthetic raw materials for various chemical products, such as pharmaceutical intermediates, and for a variety of applications, such as radical reaction initiators and radical polymerization initiators that utilize the radical species generated by cleavage of their carbon-iodine bonds. Furthermore, with a view to producing functional polymers, such as block copolymers, star polymers, and telechelic polymers, organic iodine compounds capable of generating multiple tertiary radical species have attracted attention from the perspective of controlling the activity of radical species. For example, Non-Patent Document 1 discloses the results of a study into the Ka value, molecular weight distribution, and other aspects of the radical polymerization of methyl methacrylate using various low-molecular-weight alkyl iodine compounds synthesized as initiators.

[0003] Atsushi Goto, et al. , Macromolecules, 2014, 47, pp. 6610-6618

[0004] The method for producing an organic iodine compound disclosed in Non-Patent Document 1 involves reacting, for example, ethylene glycol with bromoisobutyryl bromide in dichloromethane to obtain ethylene glycol bis(2-bromoisobutyrate), which is then reacted with sodium iodide in acetonitrile. However, the yield is low at 35%, and improvement is required from an industrial viewpoint. An object of the present invention is to provide a method for producing an organic iodine compound in high yield, industrially advantageously, and with high purity. As a result of extensive research, the present inventors have found that the above-mentioned problems can be solved by using a polyhydric alcohol as a raw material and applying a halogen exchange reaction under specific conditions, and have thus completed the present invention.

[0005] The present invention has the following aspects: [1] A compound represented by the following general formula (I):

[0006]

[0007] (wherein L represents an n-valent organic group, and n represents an integer of 2 to 6) and a polyhydric alcohol represented by the following general formula (II) (hereinafter also referred to as "polyhydric alcohol (I)"):

[0008]

[0009] (wherein X represents a chlorine atom or a bromine atom, R １ and R ２ each independently represents an alkyl group having 1 to 6 carbon atoms, or together represent an alkylene group having 2 to 6 carbon atoms.) in the presence of an acid to obtain a halogenocarboxylic acid represented by the following general formula (III):

[0010]

[0011] (In the formula, L, X, R １ and R ２ is as defined above, a is a positive number of 0 or more and less than n, b is a positive number of more than 0 and less than n, and n is an integer of 2 to 6, provided that a+b=n.), and reacting the ester compound with an iodide salt in the presence of a Lewis acid to obtain an ester compound represented by the following general formula (IV):

[0012]

[0013] (In the formula, L, R １ , R ２ , a and b are as defined above) (hereinafter also referred to as "organic iodine compound (IV)").

[0014] [2] A polyhydric alcohol (I) and a compound represented by the following general formula (V):

[0015]

[0016] (Wherein, X and X ａ each independently represents a chlorine atom or a bromine atom, R １ and R ２each independently represent an alkyl group having 1 to 6 carbon atoms, or together represent an alkylene group having 2 to 6 carbon atoms.) in the presence of a base to obtain an ester compound (III), and then reacting the ester compound (III) with an iodide salt in the presence of a Lewis acid.

[0017] [3] A method for producing an organic iodine compound (IV), comprising reacting an ester compound (III) with an iodide salt in the presence of a Lewis acid. [4] The method according to [1] or [2], wherein the polyhydric alcohol (I) is at least one selected from the group consisting of ethylene glycol, glycerin, trimethylolethane, trimethylolpropane, pentaerythritol, and dipentaerythritol. [5] The method according to any one of [1] to [4], wherein the Lewis acid is a metal salt. [6] The method according to [5], wherein the metal salt is an iron compound.

[0018] According to the present invention, an organic iodine compound can be produced in good yield, industrially advantageously, and with high purity.

[0019] The present invention relates to a method for producing an organic iodine compound (IV), which comprises reacting a polyhydric alcohol (I) with a halogenocarboxylic acid (II) in the presence of an acid to obtain an ester compound (III), and then reacting the ester compound (III) with an iodide salt in the presence of a Lewis acid. The present invention also relates to a method for producing an organic iodine compound (IV), which comprises reacting a polyhydric alcohol (I) with an acid halide (V) in the presence of a base to obtain an ester compound (III), and then reacting the ester compound (III) with an iodide salt in the presence of a Lewis acid and a solvent. The present invention also relates to a method for producing an organic iodine compound (IV), which comprises reacting the ester compound (III) with an iodide salt in the presence of a Lewis acid. According to the present invention, a tertiary radical species can be generated by dissociation of a carbon-iodine bond, and an organic iodine compound useful as an initiator for precise radical polymerization, a raw material for synthesizing various chemical products, and the like can be produced industrially advantageously and with high purity.

[0020] In the above general formula, the n-valent organic group represented by L is a group having n (i.e., 2 to 6) bonds capable of bonding to hydroxyl groups. The number of carbon atoms in the n-valent organic group is not particularly limited and can be, for example, in the range of 2 to 500, preferably in the range of 2 to 100, and one or more of the carbon atoms may be substituted with other atoms such as oxygen atoms. Among these, n-valent organic groups having 2 to 20 carbon atoms are more preferred. As such n-valent organic groups having 2 to 20 carbon atoms, groups derived from linear, branched, or cyclic alkyl groups such as ethyl, propyl, isopropyl, butyl, pentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, and undecyl groups, and one or more of the carbon atoms may be substituted with oxygen atoms, are preferred. In the above general formula, R １ and R ２ Examples of the alkyl group having 1 to 6 carbon atoms that R each independently represent include linear or branched alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, pentyl, and hexyl. １ and R ２ Examples of the alkylene group having 2 to 6 carbon atoms represented by these groups together include an ethylene group, a propylene group, a butylene group, a pentylene group, etc. Each step will be described below.

[0021] <1> A step (step 1) of reacting a polyhydric alcohol (I) with a halogenocarboxylic acid (II) in the presence of an acid to obtain an ester compound (III). Examples of the polyhydric alcohol (I) used in step 1 include dihydric alcohols such as ethylene glycol, propylene glycol, 1,4-butanediol, neopentyl glycol, 1,6-hexanediol, 1,8-octanediol, 1,9-nonanediol, tricyclodecane dimethanol, diethylene glycol, triethylene glycol, tetraethylene glycol, polyethylene glycol, and polypropylene glycol; trihydric alcohols such as glycerin, trimethylolethane, and trimethylolpropane; and tetrahydric to hexahydric alcohols such as pentaerythritol, ditrimethylolpropane, and dipentaerythritol. Among these, from the viewpoints of reactivity, ease of reaction control, and stability of the finally obtained organic iodine compound (IV), at least one selected from the group consisting of ethylene glycol, glycerin, trimethylolethane, trimethylolpropane, pentaerythritol, and dipentaerythritol is preferred, and ethylene glycol, glycerin, trimethylolethane, and pentaerythritol are more preferred.

[0022] Specific examples of the halogenocarboxylic acid (II) used in step 1 include α-bromoisobutyric acid, α-chloroisobutyric acid, 2-bromo-2-methylpropionic acid, 2-chloro-2-methylpropionic acid, 2-bromo-2-methylbutyric acid, 2-chloro-2-methylbutyric acid, 2-bromo-2-methylvaleric acid, 2-chloro-2-methylvaleric acid, 2-bromo-2-methylcaproic acid, 2-chloro-2-methylcaproic acid, 2-bromo-2-methylenanthic acid, 2-chloro-2-methylenanthic acid, 2-bromo-2-ethylpropionic acid, 2-chloro-2-ethylpropionic acid, 2- Bromo-2-ethylbutyric acid, 2-chloro-2-ethylbutyric acid, 2-bromo-2-ethylvaleric acid, 2-chloro-2-ethylvaleric acid, 2-bromo-2-ethylcaproic acid, 2-chloro-2-ethylcaproic acid, 2-bromo-2-ethylenanthic acid, 2-chloro-2-ethylenanthic acid, 2-bromo-2-propylpropionic acid, 2-chloro-2-propylpropionic acid, 2-bromo-2-propylbutyric acid, 2-chloro-2-propylbutyric acid, 2-bromo-2-propylvaleric acid, 2-chloro-2-propylvaleric acid, 2-bromo-2-propylcaproic acid, 2-chloro-2 -propylcaproic acid, 2-bromo-2-propylenanthic acid, 2-chloro-2-propylenanthic acid, 2-bromo-2-butylpropionic acid, 2-chloro-2-butylpropionic acid, 2-bromo-2-butylbutyric acid, 2-chloro-2-butylbutyric acid, 2-bromo-2-butylvaleric acid, 2-chloro-2-butylvaleric acid, 2-bromo-2-butylcaproic acid, 2-chloro-2-butylcaproic acid, 2-bromo-2-butylenanthic acid, 2-chloro-2-butylenanthic acid, 2-bromo-2-pentylpropionic acid, 2-chloro-2-pentylpropionic acid, 2- Bromo-2-pentyl butyric acid, 2-chloro-2-pentyl butyric acid, 2-bromo-2-pentyl valeric acid, 2-chloro-2-pentyl valeric acid, 2-bromo-2-pentyl caproic acid, 2-chloro-2-pentyl caproic acid, 2-bromo-2-pentylenanthic acid, 2-chloro-2-pentylenanthic acid, 2-bromo-2-hexyl propionic acid, 2-chloro-2-hexyl propionic acid, 2-bromo-2-hexyl butyric acid, 2-chloro-2-hexyl butyric acid, 2-bromo-2-hexyl valeric acid, 2-chloro-2-hexyl valeric acid, 2-bromo-2-hexyl caproic acid,Examples of suitable ester compounds include 2-chloro-2-hexylcaproic acid, 2-bromo-2-hexylenanthic acid, and 2-chloro-2-hexylenanthic acid. Among these, α-bromoisobutyric acid and α-chloroisobutyric acid are preferred, and α-bromoisobutyric acid is more preferred, from the viewpoints of reactivity, ease of reaction control, and ease of obtaining ester compound (III).

[0023] The amount of halogenocarboxylic acid (II) used can be appropriately selected depending on the amount of hydroxyl groups derived from the polyhydric alcohol (I) remaining in the ester compound (III). From the viewpoint of facilitating isolation of the ester compound (III) from the reaction mixture after completion of the reaction, it is usually preferably in the range of 0.1n to 1.5n moles relative to the n-valent polyhydric alcohol (I). When producing an ester compound (III) in which hydroxyl groups derived from the polyhydric alcohol (I) remain, the amount of halogenocarboxylic acid (II) used is more preferably in the range of 0.2n to 0.8n moles relative to the n-valent polyhydric alcohol (I). On the other hand, when no hydroxyl groups derived from the polyhydric alcohol (I) remain in the ester compound (III) (i.e., all are converted to esters), the amount of halogenocarboxylic acid (II) used is preferably in the range of 1.05n to 1.5n moles relative to the n-valent polyhydric alcohol (I), more preferably in the range of 1.1n to 1.3n moles.

[0024] Examples of the acid used in step 1 include organic acids such as p-toluenesulfonic acid and methanesulfonic acid; and inorganic acids such as sulfuric acid, hydrochloric acid, boron trifluoride, and phosphoric acid. Among these, sulfuric acid, hydrochloric acid, and phosphoric acid are preferred, and sulfuric acid is more preferred, from the viewpoints of reactivity, ease of reaction control, and ease of separation from the ester compound (III) after the reaction. There are no particular restrictions on the amount of acid used, but from the viewpoints of reactivity, productivity, and ease of handling of the residue after completion of the reaction, it is usually preferably 5 mol% or more, and more preferably 10 mol% or more, relative to the polyhydric alcohol (I). The amount of acid used is preferably 150 mol% or less, and more preferably 90 mol% or less, relative to the polyhydric alcohol (I). One type of acid may be used alone, or two or more types may be used in combination.

[0025] Step 1 is preferably carried out by mixing the polyhydric alcohol (I), the halogenocarboxylic acid (II), and the acid. The order of mixing the polyhydric alcohol (I), the halogenocarboxylic acid (II), and the acid is not particularly limited. The polyhydric alcohol (I) and the halogenocarboxylic acid (II) may be mixed together and then the acid may be added, or these components may be mixed all at once. Furthermore, Step 1 is preferably carried out while removing water generated as the reaction proceeds. Examples of means for removing water include a method using a Dean-Stark apparatus and a method for carrying out Step 1 while distilling off the generated water under reduced pressure. Step 1 may be carried out under either an air atmosphere or an inert gas atmosphere such as nitrogen, helium, or argon. Step 1 can be carried out under atmospheric pressure, elevated pressure, or reduced pressure. From the viewpoints of ease of operation and ease of removing by-produced water, it is preferable to carry out Step 1 under atmospheric pressure or reduced pressure, and more preferably under reduced pressure.

[0026] Step 1 may be carried out in the presence of a solvent such as a hydrocarbon, ether, ketone, nitrile, amide, or ester. From the viewpoint of productivity, it is preferably carried out in the absence of a solvent. The reaction temperature in Step 1 varies depending on the types and amounts of the polyhydric alcohol (I) and halogenocarboxylic acid (II) used, but from the viewpoint of industrially advantageously proceeding with the reaction, it is preferably in the range of 10°C to 120°C, more preferably in the range of 40°C to 100°C. The reaction time varies depending on the types and amounts of the polyhydric alcohol (I) and halogenocarboxylic acid (II) used, and the reaction temperature, but is usually in the range of 10 minutes to 24 hours.

[0027] The ester compound (III) thus obtained can be isolated and purified by a method commonly used for isolating and purifying organic compounds. For example, the reaction mixture obtained in step 1 is diluted with a water-insoluble solvent such as toluene, if necessary, and then washed with water, saline, a basic aqueous solution, or the like to remove residual water-soluble components such as the polyhydric alcohol (I) and acid. The organic layer is dried over anhydrous sodium sulfate or the like and then concentrated to obtain a crude product containing the ester compound (III). The crude product may be further purified by a conventional purification means such as distillation, chromatography, or recrystallization to increase the purity of the ester compound (III). Alternatively, the crude product may be dissolved in a solvent, which may be optionally present in step 2 described below, without purification, and directly subjected to step 2.

[0028] <1'> A step of reacting a polyhydric alcohol (I) with an acid halide (V) in the presence of an acid to obtain an ester compound (III) (Step 1'). Details of the polyhydric alcohol (I) used in Step 1' are the same as those described in the above-mentioned Step 1. Specific examples of the acid halide (V) used in Step 1' include 2-bromo-2-methylpropionyl bromide, 2-chloro-2-methylpropionyl bromide, 2-bromo-2-methylbutyryl bromide, 2-chloro-2-methylbutyryl bromide, 2-bromo-2-methylvaleric acid bromide, 2-chloro-2-methylvaleric acid bromide, 2-bromo-2-methylcaproic acid bromide, 2-chloro-2-methylcaproic acid bromide, 2-bromo-2-methylenanthic acid bromide, 2-chloro- 2-Methylenanthic acid bromide, 2-bromo-2-ethylpropionic acid bromide, 2-chloro-2-ethylpropionic acid bromide, 2-bromo-2-ethylbutyric acid bromide, 2-chloro-2-ethylbutyric acid bromide, 2-bromo-2-ethylvaleric acid bromide, 2-chloro-2-ethylvaleric acid bromide, 2-bromo-2-ethylcaproic acid bromide, 2-chloro-2-ethylcaproic acid bromide, 2-bromo-2-ethylenanthic acid bromide, 2-chloro-2-ethylenanthic acid bromide, 2 -Bromo-2-propylpropionic acid bromide, 2-chloro-2-propylpropionic acid bromide, 2-bromo-2-propylbutyric acid bromide, 2-chloro-2-propylbutyric acid bromide, 2-bromo-2-propylvaleric acid bromide, 2-chloro-2-propylvaleric acid bromide, 2-bromo-2-propylcaproic acid bromide, 2-chloro-2-propylcaproic acid bromide, 2-bromo-2-propylenanthic acid bromide, 2-chloro-2-propylenanthic acid bromide, 2-bromo-2 -butylpropionic acid bromide, 2-chloro-2-butylpropionic acid bromide, 2-bromo-2-butylbutyric acid bromide, 2-chloro-2-butylbutyric acid bromide, 2-bromo-2-butylvaleric acid bromide, 2-chloro-2-butylvaleric acid bromide, 2-bromo-2-butylcaproic acid bromide, 2-chloro-2-butylcaproic acid bromide, 2-bromo-2-butylenanthic acid bromide, 2-chloro-2-butylenanthic acid bromide, 2-bromo-2-pentylpropionic acid bromide,2-Chloro-2-pentylpropionic acid bromide, 2-bromo-2-pentylbutyric acid bromide, 2-chloro-2-pentylbutyric acid bromide, 2-bromo-2-pentylvaleric acid bromide, 2-chloro-2-pentylvaleric acid bromide, 2-bromo-2-pentylcaproic acid bromide, 2-chloro-2-pentylcaproic acid bromide, 2-bromo-2-pentylenanthic acid bromide, 2-chloro-2-pentylenanthic acid bromide, 2-bromo-2-hexylpropionic acid bromide acid bromides such as 2-chloro-2-hexylpropionic acid bromide, 2-bromo-2-hexylbutyric acid bromide, 2-chloro-2-hexylbutyric acid bromide, 2-bromo-2-hexylvaleric acid bromide, 2-chloro-2-hexylvaleric acid bromide, 2-bromo-2-hexylcaproic acid bromide, 2-chloro-2-hexylcaproic acid bromide, 2-bromo-2-hexylenanthic acid bromide, and 2-chloro-2-hexylenanthic acid bromide;

[0029] 2-Bromo-2-methylpropionyl chloride, 2-chloro-2-methylpropionyl chloride, 2-bromo-2-methylbutyryl chloride, 2-chloro-2-methylbutyryl chloride, 2-bromo-2-methylvaleric acid chloride, 2-chloro-2-methylvaleric acid chloride, 2-bromo-2-methylcaproic acid chloride, 2-chloro-2-methylcaproic acid chloride, 2-bromo-2-methylenanthic acid chloride, 2-chloro-2-methylenanthic acid chloride, 2-bromo-2-ethylpropionic acid chloride, 2-chloro-2-ethylpropionic acid chloride 2-Bromo-2-ethylbutyric acid chloride, 2-chloro-2-ethylbutyric acid chloride, 2-bromo-2-ethylvaleric acid chloride, 2-chloro-2-ethylvaleric acid chloride, 2-bromo-2-ethylcaproic acid chloride, 2-chloro-2-ethylcaproic acid chloride, 2-bromo-2-ethylenanthic acid chloride, 2-chloro-2-ethylenanthic acid chloride, 2-bromo-2-propylpropionic acid chloride, 2-chloro-2-propylpropionic acid chloride, 2-bromo-2-propylbutyric acid chloride, 2-chloro-2-propylbutyric acid chloride, 2-bromo-2-ethylpropionic acid chloride, Bromo-2-propyl valeric acid chloride, 2-chloro-2-propyl valeric acid chloride, 2-bromo-2-propyl caproic acid chloride, 2-chloro-2-propyl caproic acid chloride, 2-bromo-2-propyl enanthic acid chloride, 2-chloro-2-propyl enanthic acid chloride, 2-bromo-2-butylpropionic acid chloride, 2-chloro-2-butylpropionic acid chloride, 2-bromo-2-butylbutyric acid chloride, 2-chloro-2-butylbutyric acid chloride, 2-bromo-2-butyl valeric acid chloride, 2-chloro-2-butyl valeric acid chloride, 2-bromo 2-bromo-2-butylcaproic acid chloride, 2-chloro-2-butylcaproic acid chloride, 2-bromo-2-butylenanthic acid chloride, 2-chloro-2-butylenanthic acid chloride, 2-bromo-2-pentylpropionic acid chloride, 2-chloro-2-pentylpropionic acid chloride, 2-bromo-2-pentylbutyric acid chloride, 2-chloro-2-pentylbutyric acid chloride, 2-bromo-2-pentylvaleric acid chloride, 2-chloro-2-pentylvaleric acid chloride, 2-bromo-2-pentylcaproic acid chloride, 2-chloro-2-pentylcaproic acid chloride,Acid chlorides such as 2-bromo-2-pentyl enanthic acid chloride, 2-chloro-2-pentyl enanthic acid chloride, 2-bromo-2-hexylpropionic acid chloride, 2-chloro-2-hexylpropionic acid chloride, 2-bromo-2-hexylbutyric acid chloride, 2-chloro-2-hexylbutyric acid chloride, 2-bromo-2-hexylvaleric acid chloride, 2-chloro-2-hexylvaleric acid chloride, 2-bromo-2-hexylcaproic acid chloride, 2-chloro-2-hexylcaproic acid chloride, 2-bromo-2-hexylenanthic acid chloride, and 2-chloro-2-hexylenanthic acid chloride are mentioned.

[0030] Among these, from the viewpoints of reactivity, ease of reaction control, ease of obtaining ester compound (III), and the like, 2-bromo-2-methylpropionyl bromide, 2-bromo-2-methylpropionyl chloride, 2-chloro-2-methylpropionyl bromide, and 2-chloro-2-methylpropionyl chloride are preferred as acid halides (V). The amount of acid halide (V) used can be appropriately selected depending on the amount of hydroxyl groups derived from the polyhydric alcohol (I) remaining in ester compound (III). From the viewpoint of facilitating isolation of ester compound (III) from the reaction mixture after completion of the reaction, it is usually preferable that the amount of acid halide (V) be in the range of 0.1n to 1.5n moles relative to the n-hydric polyhydric alcohol (I). When producing ester compound (III) in which hydroxyl groups derived from the polyhydric alcohol (I) remain, it is more preferable that the amount of acid halide (V) be in the range of 0.2n to 0.8n moles relative to the n-hydric polyhydric alcohol (I). On the other hand, when no hydroxyl groups derived from the polyhydric alcohol (I) remain in the ester compound (III) (i.e., when all of the hydroxyl groups are converted to an ester), the amount of the acid halide (V) used is preferably in the range of 1.05n to 1.5n moles, more preferably in the range of 1.1n to 1.3n moles, relative to the n-valent polyhydric alcohol (I).

[0031] Examples of the base used in step 1' include organic bases such as aliphatic amines such as trimethylamine, triethylamine, methyldiethylamine, triisopropylamine, trioctylamine, and diazabicycloundecene; aromatic amines such as pyridine, picoline, quinoline, and imidazole; and inorganic bases such as sodium hydroxide, potassium hydroxide, and magnesium hydroxide. Among these, organic bases are preferred from the viewpoints of ease of handling and reaction control, and ease of separation from the ester compound (III) after the reaction, with aliphatic amines or aromatic amines being more preferred, and pyridine being even more preferred. The amount of base used is not particularly limited, but from the viewpoints of reactivity, productivity, and ease of handling of the residue after completion of the reaction, it is usually preferably 100 mol% or more, more preferably 200 mol% or more, and even more preferably 400 mol% or more, relative to the acid halide (V). One type of base may be used alone, or two or more types may be used in combination.

[0032] Step 1' is preferably carried out by mixing the polyhydric alcohol (I), the acid halide (V), and the base. There are no particular restrictions on the order of mixing the polyhydric alcohol (I), the acid halide (V), and the base, but from the viewpoint of easy reaction control, it is preferable to mix the polyhydric alcohol (I) and the base and then add the acid halide (V). Step 1' may be carried out under either an air atmosphere or an inert gas atmosphere such as nitrogen, helium, or argon. Step 1' can be carried out under atmospheric pressure, elevated pressure, or reduced pressure.

[0033] Step 1' may be carried out in the presence of a solvent such as a hydrocarbon, ether, ketone, nitrile, amide, or ester. The reaction temperature in Step 1' varies depending on the types and amounts of the polyhydric alcohol (I) and acid halide (V) used, but is preferably in the range of 0°C to 120°C, more preferably 20°C to 100°C, from the viewpoint of industrially advantageously proceeding with the reaction. The reaction time varies depending on the types and amounts of the polyhydric alcohol (I) and acid halide (V) and the reaction temperature, but is usually in the range of 10 minutes to 12 hours. When producing the ester compound (III) using a polyhydric alcohol (I) in which n is 4 to 6 as a starting material, it is preferable to go through Step 1' from the viewpoint of good reactivity and easy improvement of productivity and yield.

[0034] The ester compound (III) thus obtained can be isolated and purified by a method commonly used for isolating and purifying organic compounds. For example, the reaction mixture obtained in step 1' is diluted with a water-insoluble solvent such as toluene, if necessary, and then washed with water, saline, a basic aqueous solution, or the like to remove by-product bromide salts, residual polyhydric alcohol (I), base, and other water-soluble components. The organic layer is dried over anhydrous sodium sulfate or the like and then concentrated to obtain a crude product containing ester compound (III). The crude product may be further purified by a conventional purification method such as distillation, chromatography, or recrystallization to increase the purity of ester compound (III). Alternatively, the crude product may be dissolved in a solvent, which may be optionally present in step 2 described below, without purification, and directly subjected to step 2.

[0035] <2> A step (step 2) of obtaining an organic iodine compound (IV) by reacting an ester compound (III) with an iodide salt in the presence of a Lewis acid. The Lewis acid used in step 2 is preferably a metal salt. Examples of metals constituting such metal salts include B, Mg, Al, Sc, Ti, Fe, Zn, Zr, Nb, In, Sn, Cu, Ag, Sb, Hf, and lanthanoids. Among these, a transition metal salt containing a transition metal is preferred. Examples of transition metal salts that can be used as Lewis acids include halogen salts such as fluorides, chlorides, bromides, and iodides of metals such as Ti, Fe, Zn, Zr, Nb, In, Sn, Cu, Sb, Hf, and lanthanoids; sulfates, nitrates, and trifluoromethanesulfonates. These transition metal salts may be hydrates. Among these, an iron compound such as ferrous chloride, ferric chloride, ferrous sulfate, or ferric sulfate is preferred as the transition metal salt. Although there is no strict limitation on the amount of Lewis acid used, it is usually preferably in the range of 0.1 to 20 mol % relative to the number of bromine atoms or chlorine atoms represented by X in ester compound (III), and more preferably in the range of 1 to 8 mol % from the viewpoint of smoothly proceeding the reaction and suppressing undesired side reactions. One Lewis acid may be used alone, or two or more Lewis acids may be used in combination.

[0036] Examples of the iodide salt used in step 2 include alkali metal iodide salts such as lithium iodide, sodium iodide, and potassium iodide; and alkaline earth metal iodide salts such as magnesium iodide, calcium iodide, and barium iodide. From the viewpoints of availability and smooth progress of the reaction in step 2, alkali metal iodide salts such as lithium iodide, sodium iodide, and potassium iodide are preferred, and sodium iodide is more preferred. There are no particular restrictions on the amount of iodide salt used, but from the viewpoints of smooth progress of the reaction and easy production of organic iodine compound (IV) with high purity and good productivity, the amount is usually preferably 1 molar or more, and more preferably 1.2 molar or more, relative to the number of bromine atoms or chlorine atoms represented by X in ester compound (III). From the viewpoints of ease of operation and economy, the amount of the iodide salt used is preferably 5 molar times or less, more preferably 2.5 molar times or less, and even more preferably 1.8 molar times or less, relative to the number of bromine atoms or chlorine atoms represented by X in ester compound (III).

[0037] Step 2 can be carried out in the absence or presence of a solvent. When the reaction is carried out in the presence of a solvent, examples of the solvent that can be used include hydrocarbons, ethers, ketones, nitriles, amides, and esters. Among these, at least one selected from ketones, nitriles, and esters is preferred. Examples of ketones include acetone, 2-butanone, methyl isopropyl ketone, and methyl isobutyl ketone. Examples of esters include ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, and methyl propionate. Examples of nitriles include acetonitrile and propionitrile. When a solvent is used, these solvents may be used alone or in combination of two or more. Among these, ketones such as acetone and 2-butanone are preferred, and acetone is more preferred, from the viewpoint of facilitating the smooth progression of the reaction in Step 2. When a solvent is used, the amount used is not particularly limited, but is generally preferably in the range of 0.1 to 50 times by mass, and more preferably 0.1 to 10 times by mass, relative to ester compound (III). When two or more solvents are used in combination, it is preferable that the total amount of the solvents used falls within the above range.

[0038] Step 2 can be carried out by mixing ester compound (III), a Lewis acid, and an iodide salt, if necessary, in the presence of a solvent. The order of addition is not particularly limited, and examples thereof include mixing ester compound (III), a Lewis acid, and an iodide salt in this order, followed by stirring.

[0039] Step 2 may be carried out under either an air atmosphere or an inert gas atmosphere such as nitrogen, helium, or argon. Step 2 can be carried out under atmospheric pressure, elevated pressure, or reduced pressure. From the viewpoint of ease of operation, it is preferably carried out under atmospheric pressure. The reaction temperature in Step 2 varies depending on the types and amounts of ester compound (III), Lewis acid, iodide salt, and optionally present solvent. From the viewpoint of industrially advantageously proceeding the reaction, it is preferably 0°C or higher, more preferably 20°C or higher, and even more preferably 30°C or higher. The reaction temperature in Step 2 is preferably 100°C or lower, more preferably 90°C or lower, and even more preferably 80°C or lower. The reaction time varies depending on the types and amounts of ester compound (III), Lewis acid, iodide salt, and optionally present solvent, as well as the reaction temperature, but is usually in the range of 10 minutes to 24 hours.

[0040] The organic iodine compound (IV) thus obtained can be isolated and purified by a method commonly used for isolating and purifying organic compounds. For example, the reaction mixture obtained in step 2 is washed with water, an aqueous sodium hydrogen sulfite solution, an acidic aqueous solution, or the like to separate the organic layer, which is then dried over anhydrous sodium sulfate or the like as needed, and concentrated to obtain a crude product containing the organic iodine compound (IV). The crude product can also be purified by a common purification method such as distillation, column chromatography, or recrystallization to further increase the purity of the organic iodine compound (IV).

[0041] The obtained organic iodine compound (IV) can be suitably used as a polymerization initiator for living radical polymerization or the like, for example, as a precision radical polymerization initiator for RCMP (reversible coordination mediated polymerization), RTCP (reversible chain transfer catalyzed polymerization), RAFT (reversible addition fragmentation chain transfer polymerization), ATRP (atom transfer radical polymerization), etc., for producing functional polymers with narrow molecular weight distributions, such as block copolymers and star polymers. For example, ethylene bis(2-iodo-2-methylpropanoate) obtained in the examples described below can be used as a polymerization initiator for RCMP. The present invention is particularly useful from the viewpoint of industrially advantageously producing such organic iodine compounds that have two or more iodine atoms and can generate multiple tertiary radical species. Furthermore, organic iodine compound (IV) can be effectively used as a raw material for synthesizing various chemical products, such as pharmaceutical intermediates.

[0042] Although the method for producing an organic iodide compound of the present invention has been described above, the present invention is not limited to the configurations of the above-described embodiments. For example, the method for producing an organic iodide compound of the present invention may additionally include any other configuration in the configurations of the above-described embodiments, or may be substituted with any other configuration that produces a similar effect.

[0043] The present invention will be specifically described below with reference to examples, but is not limited to these examples. In each example, the purity of the product was determined by quantitative NMR (qNMR) or high performance liquid chromatography (HPLC). The change in conversion rate during the reaction was tracked by sampling the reaction mixture at appropriate times. １ H NMR was used.

[0044] Example 1 Synthesis of ethylene glycol bis(2-iodo-2-methylpropanoate)

[0045] (1) 100 g (0.60 mol) of 2-bromo-2-methylpropionic acid, 16.9 g (0.27 mol) of ethylene glycol, and 5.4 g (0.05 mol) of 98% sulfuric acid were mixed and heated, and the mixture was maintained at 80 to 90°C while stirring and reacting under reduced pressure for 1 hour. The reaction mixture was cooled to room temperature (25°C), and 35.1 g of toluene was added. The solution was washed successively with 45 g of water, 156 g of a 3% by mass aqueous sodium hydroxide solution, and 35.5 g of water, and the organic layer was separated. The organic layer was concentrated under reduced pressure to obtain 83.0 g of ethylene glycol bis(2-bromo-2-methylpropanoate) (hereinafter referred to as "ester compound 1") (yield: 85%). (2) 83.0 g of ester compound 1 obtained in (1) above was mixed with 42.7 g of acetone, and then 87 g (0.58 mol) of sodium iodide and 2.3 g (0.01 mol) of ferric chloride were added and heated to 55°C, and the mixture was allowed to react for 1 hour with stirring. The reaction mixture was cooled to room temperature (25°C), and 85.4 g (ml) of ethyl acetate was added. This solution was washed with 83 g of water and 21 g of a 35% by mass aqueous solution of sodium hydrogen sulfite. The organic layer was separated and further washed again with 42 g of 1.3% by mass hydrochloric acid, and the organic layer was separated. This organic layer was concentrated under reduced pressure, and water was added to the resulting residue, followed by filtration. 71 g of methanol was added to the obtained crystals, and the mixture was heated to 40°C to dissolve them, and then cooled to 5°C. The precipitated crystals were collected by filtration and dried, yielding 89 g of ethylene glycol bis(2-iodo-2-methylpropanoate) (yield 85%, purity 99%).

[0046] Example 2: Synthesis of ethylene glycol bis(2-iodo-2-methylpropanoate) 149 kg (0.89 kmol) of 2-bromo-2-methylpropionic acid, 25.1 kg (0.27 mol) of ethylene glycol, and 8.1 g (0.08 kmol) of 98% sulfuric acid were mixed and heated. The mixture was maintained at 80-90°C and reacted under reduced pressure for 1 hour with stirring. The reaction mixture was cooled to room temperature (25°C), and 52.6 kg of toluene was added. The solution was washed sequentially with 66.9 kg of water, 232.4 kg of a 3% by mass aqueous sodium hydroxide solution, and 52.7 kg of water, and the organic layer was separated. The organic layer was concentrated under reduced pressure, and the resulting residue was diluted with 63.8 kg of acetone. Next, 129 kg (0.86 kmol) of sodium iodide and 3.3 kg (0.02 kmol) of ferric chloride were added to the diluted solution, which was heated to 55°C and reacted for 1 hour with stirring. The reaction mixture was cooled to room temperature (25°C), and 127.6 kg of ethyl acetate was added. To this solution, 124 kg of water and 31.3 kg of a 35% by mass aqueous solution of sodium hydrogen sulfite were added for washing. The organic layer was separated and washed again with 42 g of 1.3% by mass hydrochloric acid. The separated organic layer was concentrated under reduced pressure, and water was added to the resulting residue, followed by filtration. 106 kg of methanol was added to the resulting crystals, and the mixture was heated to 40°C to dissolve them, and then cooled to 5°C. The precipitated crystals were collected by filtration and dried, yielding 133 kg of ethylene glycol bis(2-iodo-2-methylpropanoate) (total yield 72%, purity 99%).

[0047] Example 3 Synthesis of 2-hydroxyethyl 2-iodo-2-methylpropanoate

[0048] (1) To a mixture of 120 g (0.719 mol) of 2-bromo-2-methylpropionic acid, 178.4 g (2.87 mol) of ethylene glycol, and 480 mL of toluene, 14.1 g (0.144 mol) of sulfuric acid was slowly added dropwise at 25°C. After the addition was completed, the mixture was heated to 70-75°C and stirred for 4 hours. The reaction mixture was cooled to 25°C and washed successively with 400 mL of water, 120 mL of a 9% aqueous solution of sodium bicarbonate, and 120 mL of water to separate the organic layer. The organic layer was dried over sodium sulfate and then concentrated under reduced pressure to obtain 120 g of 2-hydroxyethyl 2-bromo-2-methylpropanoate (isolated yield: 79.1%). (2) 50 g (0.237 mol) of the 2-hydroxyethyl 2-bromo-2-methylpropanoate obtained above and 240 mL of acetone were mixed, and 56.8 g (0.38 mol) of sodium iodide and 1.54 g (9.48 mmol) of ferric chloride were added sequentially to this mixture, followed by stirring under reflux for 3 hours. The reaction mixture was filtered and concentrated under reduced pressure. 300 mL of dichloromethane was added to the residue, which was then washed sequentially with a 2% aqueous solution of sodium hydrogen sulfite, a 1N aqueous solution of hydrochloric acid, and saturated brine to separate the organic layer. The organic layer was dried over sodium sulfate, concentrated under reduced pressure, and further dried under vacuum to obtain 55.8 g of 2-hydroxyethyl 2-iodo-2-methylpropanoate (isolated yield 87.4%, purity 98%).

[0049] Example 4 Synthesis of trimethylolethane tris(2-iodo-2-methylpropanoate)

[0050] (1) 211.27 g (1.265 mol) of 2-bromo-2-methylpropionic acid was placed in a 1 L three-neck flask and heated to 55 ° C. to melt, then 40 g (0.333 mol) of trimethylolethane and 21.990 g (0.220 mol) of sulfuric acid were added, heated to 90 ° C., and the three-neck flask was depressurized to 8 kPa and reacted for 3 hours. The reaction mixture was cooled to 60 ° C., 144.2 mL of toluene was added, and the mixture was cooled to room temperature (25 ° C.). After that, the mixture was washed sequentially with 400 mL of water, 415 mL of 0.8 N aqueous sodium hydroxide solution, and 300 mL of water to separate the organic layer. The organic layer was concentrated under reduced pressure to obtain 170.9 g of crude crystals of trimethylolethane tris(2-bromo-2-methylpropanoate) (crude yield 90.52%). (2) 70 g of the crude crystals of trimethylolethane tris(2-bromo-2-methylpropanoate) obtained above, 45.7 mL of acetone, and 77.7 g (0.518 mol) of sodium iodide were mixed and heated to 40°C. Then, 0.2 g (0.0062 mol) of ferric chloride was added, and the mixture was heated to an internal temperature of 70°C and allowed to react under reflux for 1 hour and 30 minutes. The reaction mixture was cooled to room temperature (25°C), and 98.83 mL of methylene chloride was added. The mixture was washed sequentially with a mixed solution of 155.9 mL of water and 3.85 mL of saturated aqueous sodium hydrogen sulfite, 123.77 mL of 1N aqueous hydrochloric acid, and 125 mL of water, to separate the organic layer. The organic layer was concentrated under reduced pressure (30 kPa) at 30°C, and once the solvent no longer distilled, the pressure was returned to atmospheric pressure. To the residue was added 131.115 g of methanol, and the mixture was again concentrated under reduced pressure (30 kPa) at 40°C. Five minutes after it was confirmed that crystals had precipitated in the concentrate, the concentration operation was stopped, and the resulting slurry concentrate was gradually cooled from 40°C to 5°C or lower. The cooled concentrate was filtered and dried under vacuum to obtain 76.564 g of trimethylolethane tris(2-iodo-2-methylpropanoate) crystals (isolation yield 87.6%, purity 98%).

[0051] Example 5 Synthesis of pentaerythritol tetra(2-iodo-2-methylpropanoate)

[0052] (1) 6.5 g (0.048 mol) of pentaerythritol and 77.1 mL of pyridine were mixed and cooled to approximately 10°C, and then 54.879 g (0.239 mol) of 2-bromo-2-methylpropionyl bromide was slowly added dropwise so that the internal temperature did not exceed 30°C. After completion of the addition, the mixture was stirred while maintaining the internal temperature at 15°C, and after confirming the disappearance of pentaerythritol by NMR, 70 mL of toluene and 70 mL of water were added to the reaction mixture for washing, and the organic layer was separated. An additional 70 mL of toluene was added to the organic layer, and the mixture was washed sequentially with 140 mL of 0.5 N aqueous hydrochloric acid, 140 mL of 0.75 N aqueous sodium hydroxide, and 140 mL of water, and the organic layer was again separated. This organic layer was concentrated under reduced pressure (2 kPa) at 40°C. 139.8 g of methanol and 1.4 g of water were added to the resulting residue, and the mixture was again concentrated under reduced pressure (10 kPa) at 40°C. The concentration operation was stopped after confirming that crystals had precipitated in the concentrate, and the resulting slurry concentrate was gradually cooled from 40°C to 5°C or below. The cooled concentrate was filtered to obtain 32.4 g of crude crystals of pentaerythritol tetra(2-bromo-2-methylpropanoate) (crude yield: 92.70%). (2) 22 g of the crude crystals of pentaerythritol tetra(2-bromo-2-methylpropanoate) obtained above, 41 mL of acetone, and 25.2 g (0.168 mol) of sodium iodide were mixed and heated to 40°C. Then, 0.73 g (0.0045 mol) of ferric chloride was added, and the mixture was heated to an internal temperature of 60°C and allowed to react under reflux for 1 hour. The reaction mixture was cooled to room temperature (25°C), 85 mL of methylene chloride was added, and the mixture was washed sequentially with a mixed solution of 120 mL of water and 1.2 mL of saturated aqueous sodium hydrogen sulfite, 90 mL of 1N aqueous hydrochloric acid, and 100 mL of water to separate the organic layer. The organic layer was concentrated under reduced pressure (30 kPa) at 30°C, and once the solvent no longer distilled, the pressure was temporarily returned to atmospheric pressure. 82.95 g of methanol was added to the residue, and the mixture was again concentrated under reduced pressure (10 kPa) at 40°C. After confirming that crystals had precipitated in the concentrate, the concentration operation was stopped 5 minutes later, and the resulting slurry concentrate was gradually cooled from 40°C to below 5°C. The cooled concentrate was filtered and dried under vacuum to obtain 26.123 g of pentaerythritol tetrakis(2-iodo-2-methylpropanoate) crystals (isolation yield 94.5%, purity 95%).

[0053] Example 6 Synthesis of dipentaerythritol hexakis(2-iodo-2-methylpropanoate)

[0054] (1) 5.086 g (0.020 mol) of dipentaerythritol and 51.7 mL of pyridine were mixed and cooled to approximately 10°C, and then 36.787 g (0.160 mol) of 2-bromo-2-methylpropionyl bromide was slowly added dropwise so that the internal temperature did not exceed 30°C. After completion of the addition, the mixture was stirred while maintaining the internal temperature at 15°C, and after confirming the disappearance of dipentaerythritol by NMR, 40 mL of toluene and 40 mL of water were added to the reaction mixture for washing, and the organic layer was separated. An additional 40 mL of toluene was added to the organic layer, and the mixture was washed sequentially with 80 mL of 0.5 N aqueous hydrochloric acid, 80 mL of 0.75 N aqueous sodium hydroxide, and 80 mL of water, and the organic layer was again separated. This organic layer was concentrated under reduced pressure (2 kPa) at 40°C, and 91.88 g of methanol was added to the resulting residue, followed by concentration again under reduced pressure (10 kPa) at 40°C. After confirming that crystals had precipitated in the concentrate, the concentration operation was stopped, and the resulting slurry concentrate was gradually cooled from 40°C to 5°C or lower. The cooled concentrate was filtered to obtain 17.15 g of crude crystals of dipentaerythritol hexakis(2-bromo-2-methylpropanoate) (crude yield 74.68%). (2) 9 g of the crude crystals of dipentaerythritol hexakis(2-bromo-2-methylpropanoate) obtained above, 16.8 mL of acetone, and 10.530 g (0.070 mol) of sodium iodide were mixed and heated to 40°C. Then, 0.271 g (0.0017 mol) of ferric chloride was added, and the mixture was heated to an internal temperature of 55°C and allowed to react under reflux for 1 hour. The reaction mixture was cooled to room temperature (25°C), and 70 mL of methylene chloride was added. The mixture was washed sequentially with a mixed solution of 100 mL of water and 1 mL of saturated aqueous sodium hydrogen sulfite, 70 mL of 1N aqueous hydrochloric acid, and 50 mL of water, to separate the organic layer. The organic layer was concentrated under reduced pressure (30 kPa) at 30°C, and once the solvent no longer distilled, the pressure was returned to atmospheric pressure. 30 g of methanol was added to the residue, and the mixture was again concentrated under reduced pressure (10 kPa) at 40°C. Five minutes after it was confirmed that crystals had precipitated in the concentrate, the concentration operation was stopped, and the resulting slurry concentrate was gradually cooled from 40°C to 5°C or lower. The cooled concentrate was filtered and dried under vacuum to obtain 9.132 g of dipentaerythritol hexakis(2-iodo-2-methylpropanoate) crystals (isolation yield 76.34%, purity 95%).

[0055] The organic iodide compounds obtained by the production method of the present invention can generate tertiary radical species by dissociation of carbon-iodine bonds, and are therefore useful, for example, as polymerization initiators for precision radical polymerization and as raw materials for synthesizing various chemical products.

Claims

1. A compound represented by the following general formula (I): (wherein L represents an n-valent organic group, and n represents an integer of 2 to 6) and a polyhydric alcohol represented by the following general formula (II): (wherein X represents a chlorine atom or a bromine atom, R １ and R ２ each independently represents an alkyl group having 1 to 6 carbon atoms, or together represent an alkylene group having 2 to 6 carbon atoms.) in the presence of an acid to produce a halogenocarboxylic acid represented by the following general formula (III): (In the formula, L, X, R １ and R ２ is as defined above, a is a positive number of 0 or more and less than n, b is a positive number of more than 0 and less than n, and n is an integer of 2 to 6, provided that a+b=n.), and reacting the ester compound with an iodide salt in the presence of a Lewis acid, (In the formula, L, R １ , R ２ , a and b are as defined above.

2. A compound represented by the following general formula (I): (wherein L represents an n-valent organic group, and n represents an integer of 2 to 6) and a polyhydric alcohol represented by the following general formula (V): (Wherein, X and X ａ each independently represents a chlorine atom or a bromine atom, R １ and R ２ each independently represents an alkyl group having 1 to 6 carbon atoms, or together represent an alkylene group having 2 to 6 carbon atoms.) in the presence of a base to produce an acid halide represented by the following general formula (III): (In the formula, L, X, R １ and R ２ is as defined above, a is a positive number of 0 or more and less than n, b is a positive number of more than 0 and less than n, and n is an integer of 2 to 6, provided that a+b=n.), and reacting the ester compound with an iodide salt in the presence of a Lewis acid, (In the formula, L, R １ , R ２ , a and b are as defined above.

3. The following general formula (III): (wherein L represents an n-valent organic group, X represents a chlorine atom or a bromine atom, and R １ and R ２ each independently represents an alkyl group having 1 to 6 carbon atoms, or together represent an alkylene group having 2 to 6 carbon atoms, a represents a positive number of 0 or more and less than n, b represents a positive number of more than 0 and less than n, and n represents an integer of 2 to 6, provided that a+b=n. (In the formula, L, R １ , R ２ , a and b are as defined above.

4. The method according to claim 1 or 2, wherein the polyhydric alcohol is at least one selected from the group consisting of ethylene glycol, glycerin, trimethylolethane, trimethylolpropane, pentaerythritol, and dipentaerythritol.

5. The method according to any one of claims 1 to 3, wherein the Lewis acid is a metal salt.

6. The method of claim 5, wherein the metal salt is an iron compound.

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