JPS58222049A - Synthetic method for ester derivative - Google Patents

Abstract

PURPOSE:To obtain the titled compound in high yield, by condensing a carboxylic acid halide with an alcohol in the presence of a polyvinylpyridine type resin as a dehalogenating agent, and removing the dehalogenating agent easily from the reaction system. CONSTITUTION:A carboxylic acid halide of the formula RCOX [R is (substituted) alkyl or (substituted) phenyl; X is F, Cl Br or I], e.g. a catechol-4-carboxylic acid halide, is condensed with a halogenated aliphatic or aromatic alcohol, e.g. 2,2,2-trifluoroethanol or menthol preferably in a solvent in the presence of a polyvinylpyridine type resin at -80-+80 deg.C to give the aimed compound. A polymer of 4-vinylpyridine, a copolymer of the 4-vinylpyridine and styrene or divinylbenzene, etc. may be used as the polyvinylpyridine type resin, and the amount thereof is 1.0-10 base equivalents based on one mole carboxylic acid halide.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for total synthesis of ester derivatives by reacting a carboxylic acid halide with alcohol ffi in the presence of a polyvinylpyridine resin.

As methods for synthesizing ester derivatives, acid-catalyzed dehydration condensation of alcohol and carboxylic acid, transesterification, and the like are well known. On the other hand, when synthesizing an ester derivative with a complex structure or which is thermally unstable, a method of dehydrogenation-condensation of a carboxylic acid ~-ride and an alcohol in the presence of a basic substance is recommended. well known. However, such basic substances (de...
[Hydrogenating agent] For example, it has been pointed out that pyridine and triethylamine have drawbacks such as complicated removal operations from the reaction system and large losses during recovery and reuse.

The present inventors searched for compounds that do not have the drawbacks of conventional dehydrogenating agents in the condensation reaction of carboxylic acid halides and alcohols, and found that polyvinylpyridine resins such as 4-vinylpyridine polymers I was able to find out that this is superior. Furthermore, it has been found that the use of this compound not only facilitates the removal operation from the reaction system, but also has the excellent effect of allowing repeated reuse. That is, the method of the present invention relates to a method for total synthesis of ester derivatives by a condensation reaction between a carboxylic acid halide and an alcohol, which is characterized in that the condensation reaction is carried out in the presence of a polyvinylpyridine resin. be.

The carboxylic acid halide in the present invention has the general formula RCO
It is a compound represented by No M9. carboxylic acid or carboxylic ester or acid anhydride. It can be obtained by a conventional method such as by reacting an acid with hydrogen halide, or by reacting an acid or a halide with hydrogen halide or carboxylic acid Hk. Specifically, saturated - without substituents such as acetyl halides and alkanoic acid (03~+,s) halides
acid halides of carboxylic acids, or acid halides of halogen carboxylic acids such as chloroacetyl chloride, fluorofluoroacetyl trichloroacetic acid chloride, trinororoacetic acid chloride, perfluoropentanoic acid chloride, or 0
-Acid halides having various substituents on the alkyl group of the above general formula R such as -fluorophenoxyacetic acid chloride, ○-methyl-mandelic acid chloride, or benzoyl chloride, 0-
These include acid halides of nucleic carboxylic acids with or without substituents such as tolyl chloride, 0-trifluoromethylbenzoyl chloride, P-phenoxybenzoyl chloride, meditoyl chloride, and catechol-4-carboxylic acid chloride.

).

Examples of the alcohol in the present invention include methanol, ethanol, furoyl alcohol, furoyl alcohol,
aliphatic saturated alcohols such as C5-38 alkanols,
or allyl alcohol, crotyl alcohol, C5++
+8 aliphatic unsaturated alcohols such as alkenyl alcohol and propargyl alcohol;
etc., rogenated aliphatic alcohols, havensyl alcohol, menthol, 6-phenyl-1-butyne-6-
These include aromatic alcohols such as alcohol, halogenated aromatics such as chlorobenzyl alcohol and fluorobenzyl alcohol, and flucol.

In the method of the present invention, the polyvinylpyridine resins used as de-hydrogenation agents include 2-vinylpyridine, 4-vinylpyridine, 2-methyl-5-vinylpyridine, and 5-ethyl-2-vinylpyridine. It is a vinylpyridine homopolymer such as, or a copolymer of these and styrene, etc., and has a molecular weight of several thousand to several million. Divinylbenzene, divinyl ether, etc. may be included as a crosslinking component. Preferred examples include a 4-vinylpyridine homopolymer or a copolymer of 4-vinylpyridine and styrene or divinylbenzene. In the condensation reaction between carboxylic acid and alcohol, this polyvinylpyridine resin has a de-hydrogenating ability equal to or higher than that of conventional basic substances, and it is possible to obtain ester derivatives in high yields. be able to. Furthermore, compared to conventional basic substances, it can be easily separated from the reaction system and reused.

That is, polyvinylpyridine produced during the condensation reaction
Hydrogen halide salts can be easily separated by filtration, and the hydrogen halide salts can be easily regenerated with alkaline water such as sodium hydroxide or aqueous ammonia. Can be used. Furthermore, many of the basic substances conventionally used have an irritating odor, which is a problem in terms of the working environment, but the polyvinylpyridine resin used in the present invention is almost odorless, so there is no such concern.

The reaction may be carried out without a solvent, but it is usually carried out using a halogen-based solvent such as methylene chloride or chloroform, or habenzene. - Aromatic solvents such as luene, ether solvents such as tetrahedron, or amide solvents such as dimethylformamide are suitable. The reaction temperature is -80°C to 1-80°C, preferably -20°C to +50°C, and another major feature is that the reaction proceeds sufficiently at room temperature.Reaction of polyvinylpyridine resin The amount present in the system is usually selected from the range of 1.0 to 10 base equivalents, preferably 1.0 to 2.0 base equivalents per mole of carboxylic acid halide. If the amount is large, separation and reuse becomes complicated and uneconomical, which is meaningless.

Examples according to the present invention will be described in more detail below, but it goes without saying that such explanations do not limit the present invention in any way.

Example 1 In a 300 ml reaction vessel equipped with a stirrer, 2.
2.2- Trifluoroethanol (io, s 9
.

105 mmol), polyvinylpyridine resin (KEX-212 manufactured by Koei Kagaku Co., Ltd., a copolymer of 4-vinylpyridine and divinylbenzene, 25me), and methylene chloride (50ml) are added in advance.

A solution of catechol-4-carboxylic acid chloride (17.25f, 100 mmol) in methylene chloride (5 CJml) is gradually added to the mixture at 0°C in an ice bath. After removing the water bath and stirring for 60 minutes at room temperature, the polyvinylpyridine resin and its hydrochloride are poured out. Concentrate it under reduced pressure and recrystallize the residue from water-ethanol L, 2, 2.2
-) Lifluoroethylcatechol-4'-carboxylade was obtained in a yield of 97%.

Example 2 O-methyl-mandelic acid stearyl ester was obtained from 0-methyl-mandelic acid chloride and stearyl alcohol in a yield of 95% by the same method as in Example 1.

Example 6 By the same method as in Example 1, 85% perfluorohebbutanoic acid menthol ester was obtained from perfluorohebbutanoic acid chloride and menthol.

Claims (1)

[Claims] 1.) A method for synthesizing an ester derivative by a condensation reaction between a carboxylic acid halide and an alcohol, the method comprising carrying out the condensation reaction in the presence of a polyvinylpyridine resin. . 2) The synthesis method according to claim 1, wherein the polyvinylpyridine resin is a polymer of 4-vinylpyridine or a copolymer of 4-vinylpyridine and styrene or divinylbenzene. 3) The synthesis method according to claim 1, wherein the reaction temperature is selected from the range of 180°C to +80°C. 4) The synthesis method according to claim 1, wherein the amount of polyvinylpyridine resin present is selected from the range of 1.0 to 10 base equivalents per mole of carboxylic acid halide.