SU1097618A1 - Process for preparing cyclic dicarboxylic acid n-oxyimides - Google Patents

Abstract

A method for producing cyclic N-hydroxides of dicarboxylic acids by reacting a hydroxtamine derivative with dicarboxylic anhydrides by heating in the presence of a dioxane solvent, in that, in order to increase the yield and purity of the target product, an arsenic is used as an anhydroxylamine-γ-0, which is used in the body of an arsenic. a) hydroxylamine and the process is carried out in an anhydrous medium. (L

Description

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This invention relates to a process for the preparation of dicarboxylic acid cyclic N-oxyimides, specifically to a process for the preparation of N-oxysuccinimide and N-oxyphthalimide, widely used in the synthesis of biologically active peptides for the preparation of activated esters (N-oxysuccinimide and N-Oxyphthalimide N)). amino acids and peptides with high reactivity and in most cases crystalline products of Cl. The closest to the present invention is a method for the preparation of N-oxysuccinimide and N-oxyphthalim ida by reacting hydroxylamine hydrochloride with succinic and phthalic anhydrides, respectively, in an aqueous medium when heated to 95 ° C for 15 minutes for N-hydroxyphthalimide and in an aqueous dioxane medium when heated to 160 ° C in vacuum for 15 minutes for N -oxysuccinimide C2. However, this method is not without drawbacks, which makes it difficult to implement in a commercial scale, since it is difficult to achieve stable and reproducible results in relation to the yield of the target products. This is due to the fact that the reaction is carried out in an aqueous-organic system and at alkaline pH values, the likelihood of a side reaction of hydrolysis of the anhydrides of the corresponding acids (succinic and phthalic) is not excluded, as a result of which the N-oxysuccinimide yield is only about 40-45%, and the yield of N-oxyphthalimide does not exceed 75% 2, and the resulting products need thorough purification by recrystallization from ethyl acetate and / or isopropanol. The purpose of the invention is to increase the yield and purity of the target products. The goal is achieved according to the method of obtaining cyclic N-oxyimides of dicarboxylic acids by reacting a hydroxylamine derivative with dicarboxylic anhydrides when heated in the presence of a solvent, dioxane, and N, 0-6HC- (trimethylsilyl hydrochloride hydroxylamine hydrochloride) is used t in an anhydrous environment. 18 The process is carried out, as a rule, in vacuum and at a temperature of usually 100 ° C. Example 1. Preparation of N-hydroxyphthalimide, To a solution of 5.0 g (33.8 mmol) of phthalic anhydride in 20 ml of dioxane, at 22–23 0, add 6.0 g (33.8 mmol) S, 0-dis- (trimethylsilyl) hydroxylamine. After 15 minutes, volatile compounds are distilled off in vacuo, the cyclization is carried out in vacuo for 30 minutes. The resulting crystalline product is washed with ether and dried in vacuo. 5.5-g (100%) of chromatographically homogeneous N-hydroxyphthalimide are obtained. Rr 0.6 in the system benzene-acetone-acetic acid (80: 40; 1), R | 0.75 in the system chloroform-methanol-benzene (85: 10: 5), so pl. 235-238 0, (lt.t.pl.230 ° C). H 3.0, with 58.45; Found,% j N 7,84. CgHjN O.. Calculated,%: C 58.90; H 3.10 N 8.10. IR spectrum, cm- .: 3100, 1780, 1720, 1420, 1220, 1070, 655. Example 2. Preparation of N-oxysuccinimide. To a solution of 5.0 g (5.0 mmol) of succinic anhydride in 20 ml of dioxane, at 22-23, 8.85 g (60.0 mmol) of N, 0-6HC (TpHMeTrtncHnHH) hydroxylamine were added. After 15 minutes, volatile compounds are distilled off in vacuo. The cyclization is carried out in vacuum at 100 ° C for 30 minutes. The resulting product is crystallized from ethyl acetate ,. dried .in vacuum. 4.89 g (85%) of N-oxycJ5-cycinim a, m.p. 99100 ° С, (lit.t.pl. 99-1 b) 2. Calculated:%: 41.7; H 4.35; N 12.17. . Found,%: C 41.36} H 4.12-; N 12.05. IR spectrum, cm: 3100-3000, 1780, T710, 1600J 1470, 1380, 1225, 950, 700. Thus, the proposed method for the preparation of N-oxysuccinimide and N-oxyphthalimide using N, .0-6Hc (trimethylsilyl) hydroxylamine allows to obtain them without additional purification in high yield of 100 and 85% for N-hydroxyphthalimide and N-hydroxysuccin E1097618 "

Ymida respectively. In addition, organic solvent, that

used in the reaction of K, 0-bis- (tri-eliminates the possibility of the flow of labeled by silyl) hydroxylamine allows the working reaction of the hydrolysis of the anhydride

to conduct it in the medium of anhydrous aproton-dicarboxylic acid.

Claims (1)

METHOD FOR PRODUCING CYCLIC N-OXYMIMDS OF DICARBOXYLIC ACIDS by reacting a hydroxylamine derivative with dicarboxylic anhydrides when heated in the presence of a solvent - dioxane, characterized in that, in order to increase the yield and purity of the target product,-, три, ) hydroxylamine and the process is carried out in an anhydrous medium. 9192601