CS275619B6 - Process for preparing epsilon-aminocaproic acid esters - Google Patents

Abstract

The present invention relates to a process for the preparation of esters of aminocaproic acid acids of formula H "N- - (CH 2) 2 -COO-R where R = C 1 -C 2 alkyl or C 1-7 cycloalkyl, wherein the C 1-7 cycloalkyl is C 1-7 cycloalkyl to ε-aminocaproic acid hydrochloride is treated with an excess of C 1 -C 12 primary alcohol or - C? cyclic alcohol or their equimolar amount in the environment solvents, preferably dimethylformamide, at a temperature of 5 to 40 ° C for a period of time 10 to 60 minutes, after which the ester is released ammonia. The production process is considerably shorter reaction time compared to previously published procedures for producing similar esters.

Description

The invention relates to esters of <£ aminocaproic acid of the formula H ₂ N - _CH2 - _CH2 - _CH2 - _CH2 - _CH2 - C00 - 9 wherein R = C - C alkyl or _2Q 0 ^ - C? cycloalkyl, which have antifibrinolytic (Nagamatsu, A. et al. J. Biochem. 54, 491-6, 1963) and antibacterial properties (Limanov, VE et al .: Chim.-Farm. 6. 18, 1214-17, 1984 ).

The preparation of ε-aminocaproic acid esters has been described in the literature, but is very time consuming. E.g. British Patent (British Pat. No. 934,965, Cl C07 c) discloses a reaction time of 22 hours for the reaction of ε-caprolactam with the corresponding alcohol in the presence of hydrogen chloride, Soviet authors (Limanov, VE et al .: Chim.-Farm. No. 113 , 1214-17, 1984) report 14 hour reaction times using a modified variant of the classical Curtie method, without isolating the final product.

The disadvantage of both mentioned processes is the relatively long reaction time and the relatively complicated execution of the reaction, which necessarily means technical complications in the practical implementation of the production.

The essence of the process according to the invention is that in the first phase the prepared C-aminocaproic acid chloride hydrochloride reacts rapidly and in high yield with primary or cyclic alcohols to form the hydrochloride ester of the corresponding amino acid. Temperature plays a decisive role here. When heated above 50 ° C, colored products are formed, while at temperatures up to a maximum of 40 ° C, the purity of the resulting esters is very high. E-aminocaproic acid ester is liberated by reaction with ammonia.

The object of the invention, which eliminates the above-mentioned disadvantages of the prior art processes for the synthesis of _{ε-aminocaproic acid esters, is a process for the preparation of ε-aminocaproic acid esters of the general formula H 2} N- (CH ₂ ) -COO-R, where R = -C 1-4 alkyl or C C 1 -C 4 cycloalkyl, characterized in that the ε-aminocaproic acid hydrochloride is treated with thionyl chloride and the product of this reaction with an excess of C 1 _{-C 2} θ primary alcohol or C ₄ -C 4? of a cyclic alcohol at 5 to 40 ° C for 10 to 60 minutes, after which the ester is liberated with ammonia.

The process according to the invention, with its simple design and high yields with high product purity, offers the most advantageous way so far to obtain a wide range of C-aminocaproic acid esters of interest from a theoretical and practical point of view.

The main significance is that the reaction time for the production of ε-aminocaproic acid esters is shortened from 22 and 22%, respectively. 14 hours to 2 hours, with a single crystallization being sufficient for the final purification of the products. This results in a considerable economy of production in terms of energy consumption and the working time required to carry out the synthesis.

The invention is further elucidated on the basis of exemplary embodiments, which, however, do not limit or exhaust its scope.

Example 1

E-aminocaproic acid hydrochloride hydrochloride g (30 mmol) E-aminocaproic acid hydrochloride was dissolved in 15 ml of thionyl chloride at room temperature and concentrated to dryness in vacuo. To the residue in the flask was added 20 mL of butanol, heated to 35 ° C for 30 minutes, and then the butanol was removed in vacuo. The residue was suspended in diethyl ether, and the colorless crystals were filtered off. Crystallization of butanol - diethyl ether.

Yield: 6.5 g, i.e. 90%, m.p. 38-45 ° C.

Example 2

E-aminocaproic acid cyclopentyl ester hydrochloride g (30 mmol) hydrochloride E. -aminocaproic acid was dissolved in 15 ml of thionyl chloride at room temperature and concentrated to dryness in vacuo. To the rest of the flask was

CS 275619 Β 6 20 ml of cyclopentanol are added, heated to 30 ° C for 60 minutes and then the cyclopentanol is removed in vacuo. The residue was suspended in diethyl ether, and the colorless crystals were filtered off.

Crystallization of cyclopentanol-diethyl ether.

Yield: 5.5 g, i.e. 78%, m.p. 33-35 ° C.

Example 3

6-Aminocaproic acid hexadecyl ester hydrochloride g (30 mmol) of 6-aminocaproic acid hydrochloride was dissolved in 15 ml of thionyl chloride at room temperature and concentrated to dryness in vacuo. A solution of 7.3 g (30 mmol) of hexadecanol in 30 ml of dimethylformamide was added to the residue in the flask. The reaction mixture was heated at 40 ° C for 50 minutes and then concentrated in vacuo. The residue in the flask was suspended in diethyl ether, and the colorless crystals were filtered off. Crystallization of dimethylformamide diethyl ether ..

Yield: 10.4 g, i.e. 85%, m.p. 112-115 ° C.

Example 4

6-Aminocaproic acid butyl ester g (5 mmol) of C-aminocaproic acid butyl ester hydrochloride was dissolved in 10 ml of dry chloroform, and a solution of ammonia in 10 ml of dry chloroform saturated at 0 ° C was added with cooling and stirring. After 10 minutes, the ammonium chloride was filtered off and the solution was concentrated.

Yield: 0.8 g, i.e. 100% in the form of an oil.

Claims (2)

PATENT CLAIMS A process for the preparation of α-aminocaproic acid esters of the general formula H ₂ N - CH ₂ - CH ₂ - CH ₂ - CH ₂ - CH ₂ - COO - R, where R = C 1 -C ₂ alkyl or C 1 -C 4 cycloalkyl, characterized in that the hydrochloride no. -aminocaproic acid is treated with thionyl chloride and the product of this reaction by an excess of a C 1 -C ₂ primary alcohol or a C 1 -C 4 cyclic alcohol at 5 to 40 ° C for 10 to 60 minutes or an equimolar amount of a C 1 -C ₂ primary alcohol or - C? of a cyclic alcohol in a solvent medium, preferably dimethylformamide, at a temperature of 5 to 40 ° C, after which the ester is liberated with ammonia. 2. The process according to claim 1, characterized in that the release of the ester is carried out by the action of ammonia, preferably in an anhydrous solvent.