SU632693A1 - Method of obtaining 3,3'-disubstituted n,n'-dimethyl-2,2'diindolealdehydes - Google Patents

Description

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The invention relates to an improved process for the preparation of diindolyl disulfides, which can be used as semi-products for the preparation of drugs.

A known method for the preparation of 3.3 disubstituted N, l-dimethyl-2,2-diindolyl disulfides by the action of sulfur dichloride on the corresponding N methylene with a yield of the desired product from 30 to 50% depending on the structure of the starting indole.

The disadvantages of this method are the need to use sulfur dioxide ' monochloride, the use of 3-substituted M-methylindoles, the synthesis of which presents great difficulties, the production of 2-chloridols and various dimers as by-products, which leads to a decrease in the yield and contamination of disulfides .

The aim of the invention is to simplify the process by using more affordable and non-toxic starting materials.

The goal is achieved by the proposed method, Zachocho1SCl1ms in action on N-methyl-I-phenylhydrazides of substituted phenylacetic acids sequentially with phosphorous phosphorus oxychloride and phosphorus oxychloride in an inert solvent, for example dioxane or methylene chloride, during boiling.

The described cyclization of thiohydrazides is unknown. It is known that hydrazides of phenylacetic acids with

The action of Lewis acids on them is formed by the hydrochloric salts of 2-aminoind | loE. However, under these conditions, cyclization was first performed.

The purity of the products was controlled by thin layer chromatography on a fixed layer of Kieselgel H with rhodamine 6K as an indicator in the hexane: acetone:: benzene system in a ratio by volume

0 2: 1: 1. The constants and UV spectra of the substances obtained correspond to the literature data. The process can be carried out without the addition of phosphorus oxychloride, however, the yield of disulfide is lower (Example 3).

The proposed method, in contrast to the known, allows the process to be carried out in one stage, and it is also considerably simpler than the known one, since it allows using more available and / or non-toxic f -methyl-M-phenylhydraides as the starting material, Example 1. Preparation 3, 3-biphenyl-N / N-dimethyl-2,2-diindolyl disulfide, To a solution of 1 g (0.004 g-mol) of N-methyl-X-phenylhydrazide phenylacetic acid in 20 MP dioxane, 0.3 g (0, 0015 g of phosphate n-colored phosphorus and the mixture was boiled for 1 h. Then 1.1 ml (1: 3 by weight) of phosphorus oxychloride and boil for 2 hours. After completion of the reaction, the solution is evaporated, the residue is washed with water until neutral, the washings are extracted twice with benzene, which is added to the bulk of the product. The benzene is evaporated, and the residue is recrystallized from absolute ethanol with coal. 3-diphenyl-M, M-dimethyl-2,2-diindoles dr1sulfide 480mg {45%), mp.142-143 (literature data 141-143 0. And initial hydrazide 0.35; Ri disulfide 0.60. UV-spectrum L ..- ,,,., N / 1l: 227, 258, 355. Similarly, 3, (p-norrophenyl) -N, N -dimethyl-2,2-diindolyl disulfide was obtained. Yield 78%, t, pl. 276278 ° С (literature data 276278 ° С). R i initial hydrazide 0.32 fUf disulfide 0.58. UV spectrum, L, 2H1: 225 360. Example 2. Preparation of 3, (p-methoxyphenyl-I, -dimethyl-2,2-diindolyl disulfide. The process is carried out analogously to example 1 using methylene chloride as a solvent. Boiling. 62% , tpl, 171 173 ° C (literature data 171 173s). Ri of the starting hydrazide 11.38; H disulfide 0.65. UV spectrum, d HMS 230, 350. Example Z. To a solution of 1 g of 1 {-methyl -M-phenyl p-methoxyphenylacetic acid idrazide in 20 ml of methylene chloride is added with stirring 0.5 g of tetrous phosphate and boiled for 6 hours. Then it is diluted with water and the organic is separated the layer is washed with water and the solvent is evaporated, and the residue is recrystallized from alcohol with coal. Yield 42%, mp 169-172 C. The remaining constants correspond to example 2, Formula of the invention. Method for preparing 3,3-disubstituted To .and -dimethyl-2 , 2 -diindolyl disulfides, characterized in that, in order to simplify the process, N-methyl-M-phenylhydrazides of phenylacetic acids are subjected to the sequential action of phosphorous phosphorus and phosphorus oxychloride in an inert solvent at the boil.