JPH09104642A - Production of mixed acid anhydride - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a mixed acid anhydride useful for functional materials, dyes, medicines, agrochemicals or photographic chemicals, or as an intermediate therefor, without deposition of the hydrohalogenide salt of an amine as a dehydrohalogenating agent. SOLUTION: This mixed acid anhydride of e.g. the formula is obtained by reaction of a carboxylic acid and an acid halide with a >=9C (pref. >=12C)tertiary amine as a dehydrohalogenating agent (e.g. tributylamine) in a solvent (e.g. THF) at -50 to 30 deg.C. The carboxylic acid is a 1-40C compound (e.g. an aromatic carboxylic acid, aliphatic carboxylic acid), while the acid halide is a 1-40C compound (e.g. a carboxylic acrid halide, sulfonict acid halide).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a process for producing a mixed acid anhydride useful as an intermediate in the production of functional materials, dyes, pharmaceuticals, agricultural chemicals and photographic chemicals.

[0002]

BACKGROUND OF THE INVENTION Esters and amides, which are derivatives of carboxylic acid, are often useful as functional materials, dyes, pharmaceuticals, agricultural chemicals, photographic chemicals and their intermediates. In their synthesis, it is common to convert a carboxylic acid into an active derivative such as an acid halide, an active ester or an acid anhydride and then react with a hydroxy group or an amino group.

Mixed acid anhydrides are also useful as one of their active derivatives, and are described, for example, in Nobuo Izumiya et al., "Peptide Synthesis (published by Maruzen 1975)", Chapter 5. The amine compounds which are dehydrohalogenating agents used in the experimental examples described in the literature are triethylamine, N-methylmorpholine, pyridine and N-methylpiperidine, and in these cases, they are formed by the reaction. Often, the hydrogen halide salt of the amine is precipitated from the reaction solvent.

Considering the case where the resulting mixed acid anhydride solution is dropped into a solution of a compound having a hydroxy group or an amino group to carry out the reaction, the precipitation of the hydrogen halide salt of the amine is remarkably operability. Will be damaged.

[0005]

SUMMARY OF THE INVENTION Accordingly, it is an object of the present invention to provide a method for producing a mixed acid anhydride which does not cause precipitation of a hydrogen halide salt of an amine compound which is a dehydrohalogenating agent.

[0006]

As a result of intensive studies, the present inventors have found that the object of the present invention can be achieved by the following. (1) In the method of producing a mixed acid anhydride by dehydrohalogenation by reacting a carboxylic acid with an acid halide, the tertiary amine used as a dehydrohalogenating agent has a total carbon atom number of 9 or more. A method for producing a mixed acid anhydride, comprising:

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION Examples of the carboxylic acid in the present invention include translations by Kenzo Hirayama and Kazuo Hirayama, Nomenclature for Organic and Japanese Organic Chemistry [All], Area of Chemistry, Special Issue No. 97, 134-148.
The compounds and their derivatives described in Page (Nankodo, 1972), preferably the compounds having 1 to 40 carbon atoms can be mentioned. Specifically, for example, an aliphatic carboxylic acid [eg, a substituted or unsubstituted chain saturated aliphatic carboxylic acid (eg, acetic acid, propionic acid, N-acetylglycine, pivalic acid, 2-naphthalenehexanoic acid, heptanoic acid, heptane Diacids, 3- (carboxymethyl) heptanedioic acid, lauric acid, stearic acid, etc.), substituted or unsubstituted chain unsaturated aliphatic carboxylic acids (eg,
Acrylic acid, propiolic acid, crotonic acid, maleic acid,
Mesaconic acid, 2-hexene-4-ynedioic acid, cinnamic acid),
Substituted or unsubstituted alicyclic carboxylic acid (eg, cyclohexanecarboxylic acid, 3- (3-phenylpropyl)-
1-cyclobutanecarboxylic acid, camphoric acid, adamantanecarboxylic acid and the like], aromatic carboxylic acid (for example, benzoic acid, anisic acid, phthalic acid,
Isophthalic acid, terephthalic acid, naphthoic acid) and heterocyclic carboxylic acids (such as furancarboxylic acid, thiophenecarboxylic acid, nicotinic acid, isonicotinic acid) and their derivatives.

Examples of the acid halide in the present invention include those having 1 to 40 carbon atoms, preferably 1 to 10 carbon atoms. For example, carboxylic acid halides (eg, acetyl chloride, acetyl bromide, propionyl chloride, butyroyl chloride). , Trifluoroacetyl chloride)),
Sulfonic acid halides (eg, methanesulfonyl chloride, ethanesulfonyl chloride, trifluoromethanesulfonyl chloride, tosyl chloride, 4-fluorobenzenesulfonyl chloride, etc.), chloroformic acid esters (eg, methyl chloroformate, chloroformic acid) Ethyl, isopropyl chloroformate, isobutyl chloroformate) can be mentioned.

The total number of carbon atoms used in the present invention is 9
Or more, preferably 12 or more, as the tertiary amine,
The total number of carbon atoms is preferably 45 at the maximum, and more preferably 21. Specific examples include, for example, chain amines (eg, tripropylamine, tributylamine, trihexylamine, trioctylamine, tridecylamine, N, N-dimethyloctylamine), cyclic amines (eg, N- Octylpiperidine, N-decylmorpholine are included), and aromatic amines (eg, N, N-diethylaniline, N, N-dibutylaniline, N-methyl-N-propylaniline are included).

Solvents that can be used for producing the mixed acid anhydride in the present invention are, for example, N, N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO).
Can be selected from a range of polar solvents such as benzene and non-polar solvents such as hexane. Halogenated solvents such as dichloromethane and chloroform, methyl acetate,
Esters such as butyl acetate, tetrahydrofuran,
Ethers such as 1,2-dimethoxyethane are preferable, and a mixed solvent can be used.

The reaction temperature during the production of the mixed acid anhydride in the present invention is preferably -50 ° C to 30 ° C, more preferably -30 ° C to 15 ° C. Specific examples of the compound that can be produced by the present invention will be given below.

[0012]

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[0013]

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[0014]

EXAMPLES The present invention will be described in more detail based on examples. Example 1 In a 50 ml three-necked flask equipped with a stirrer, a thermometer and a dropping funnel, 1.15 g (10 mmol) of methanesulfonyl chloride and 5.1 ml of tetrahydrofuran (THF) were weighed and used as a cryogen at -10 ° C or lower. Cooled to. With stirring, 2.64 g (10 mmol) of 4- (4-
Acryloyloxybutoxy) benzoic acid, 1.85 g
(10 mmol) tributylamine and 9.3 ml
A solution of THF in (1) was added dropwise at 0 ° C or lower. Then, the mixture was continuously stirred under ice cooling for 30 minutes. The reaction solution was transparent without any precipitation. After pouring a part of the reaction solution into a large excess of methanol and leaving it at room temperature for 10 minutes,
The formation of methyl ester was confirmed by high performance liquid chromatography (HPLC). From this, it is clear that the desired mixed acid anhydride was produced by the above reaction.

Example 2 Instead of the tributylamine used in Example 1, tripropylamine was used and trioctylamine was also used to carry out the same reaction as in Example 1. Table 1 shows the results.

Comparative Example The same reaction as in Example 1 was carried out using triethylamine and diisopropylethylamine in place of tributylamine used in Example 1 and N-methylmorpholine. Table 1 shows the results.

[0017]

[Table 1]

[0018]

As is apparent from the examples, according to the method of the present invention, a mixed acid anhydride can be produced without precipitation of a hydrogen halide salt of an amine.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Internal reference number FI Technical indication C07C 309/65 7419-4H C07C 309/65 309/73 7419-4H 309/73

Claims (1)

[Claims] 1. A method for producing a mixed acid anhydride by dehydrohalogenation by reacting a carboxylic acid and an acid halide, wherein the tertiary amine used as a dehydrohalogenating agent has a total number of carbon atoms of 9 The above is the method for producing a mixed acid anhydride, which is characterized by the above.