SU1719396A1 - Method of producing 4-(adamantyl-1)-thiophenol - Google Patents

Abstract

The invention relates to derivatives of heterocyclic substances, in particular the preparation of 4- (adamantyl-1) -thiophenol, for the synthesis of antitumor agents and sulfur-containing compounds. The goal is to simplify the process. It is derived from a mixture of 1-bromadamantane and benzene in chloroform with chlorosulfonic acid at a molar ratio of 1: 1: (3-5) and (-15) -0 ° C, followed by reduction of the resulting product with zinc sulfuric acid. The output of 57.8-61%; m.p. 104-105.5 ° C; gross-la CieHaoS. These conditions significantly simplify the process by reducing the number of stages.

Description

The invention relates to a process for the preparation of 4- (diamantyl-1) -thiophenol (1), which is used as an intermediate in the synthesis of practically important inclusion compounds. In addition, alkylthiophenols are widely used in the synthesis of antitumor agents, as well as reagents in the preparation of various sulfur-containing compounds: sulfides, sulfenyl chlorides, etc.

An example of the implementation of the known method for the preparation of the target product (1) involves treating 4- (adamantyl-1) -phenol with dimethylthiocarbamoyl chloride in DMF with further Newman-Quart rearrangement and hydrolysis of the reaction product. The output of 4- (adamantyl-1) -thiophenol on the original 4- (adamantyl-1) -phenol 88%.

Although the target product is obtained in high yield, this method cannot be widely used due to the difficult availability of the starting 4- (adamantyl-1) -phenol. The disadvantages of this method include the multistage,

the use of high temperatures; the use of toxic dimethylthiol rbamoyl chloride as a reagent.

The purpose of the invention is to simplify the process.

This goal is achieved by treating chlorosulfonic acid with a mixture of benzene and 1-bromoamantane, followed by reduction of the resulting 4- (adamantyl-1) -benzenesulfonyl chloride with zinc in sulfuric acid. The preparative process is carried out as follows. Chlorosulfonic acid was added to a mixture of benzene and 1-bromoamantane in chloroform cooled to -15 ° C, keeping the temperature no higher than 0 ° C. The molar ratio of benzene: bromadamantane: chlorosulfonic acid is 1: 1: 3-5. After completion of the reaction, the reaction mixture is worked up and 4- (adamnyl-1) -benzenesulfonyl chloride is obtained in a yield of 92%, calculated as benzene. The resulting product is subjected to the recovery of zinc in sulfur

WITH

with

Yu

CJ

what about

acid. The yield of the desired 4- (adamantyl-1) - thiophenol 58-61%, calculated on benzene.

Example 1. To a mixture of 35.0 g (0.162 mol) of 1-bromoamantane and 12.7 g (0.162 mol) of benzene in 15 ml of chloroform, cooled to -15 ° C, 35 ml (0.49 mol) of chlorine were added. sulfonic acid, maintaining the temperature not higher than 0 ° C. After adding the total amount of acid, stirring is continued for 1 hour at 0 ° C, then the reaction mixture is allowed to spontaneously warm to room temperature. The reaction was monitored by TLC (Silufol and L-254, petrol. Ether: 6: 1 ether, the manifestation of UV radiation). After the reaction is complete, the mixture is poured onto crushed ice (200 g), the chloroform layer is separated, the aqueous is extracted with chloroform (3 x 50 ml). The organic solutions were combined, dried with Na2SO4, and the solvent was distilled off to obtain 46.2 g (92%) of the product. After purification by chromatography (silica gel 40/100, n-hexane), 4- (adamantyl-1) -benolic sulfate chloride was isolated as a white crystalline substance with mp. 177-178,5 ° C.

PMR, 250 MHz, SDS1z (5, ppm): 1.80-2.14 (m, 15H, Adi); 7.60 fa, 2H, Hz, and Nvar.); 7.98

3 (d, 2H, Na and Ne arom.) JHH - 9.0 Hz.

Found,%: C 61.57; H 6.10; C111.52; S 10.30.

SbN19SYu2.

Calculated,%: C, 61.82; H 6.16; C111.41; S 10.32.

Then the resulting sulfochloride is subjected to recovery. To a mixture of 47 ml of late c. H2SO2 and 250 g of crushed ice add 35.0 g of sulfochloride, and 43 g of zinc dust are carefully added. After heating to 90 ° C, the mixture is refluxed for about 4 hours. Water vapor distillation gives 18.35 g of a white crystalline substance, 4- (adamantyl-1) -thiophenol, m.p. 104-105,5 ° C (from alcohol).

PMR, 250 MHz, SDS1z (d, ppm): 1.7-2.2 (m, 15H, Adi); 3.40 (s, 1H, SH); 7.20-7.30 (m. 4H arom.).

Found,%: C 78.14: H 7.92; S 12.96.

CieH20S.

Calculated,%: C 78.60; H 8.20; S 13,10.

The yield of 4- (adamantyl-1) -thiophenol in terms of benzene is 61%.

Example 2. Under the conditions of example 1 of

35.0 g (0.162 mol) of 1-bromadomantane. 12.7 g

(0.162 mol) of benzene and 60 ml (0.74 mol) of chlorosulfonic acid get 43.8 g (87%)

4- (adamantyl-1) -benzenesulfonyl chloride, 35 g

which is restored in a mixture of 47 ml

conc. H2S04 and 250 g of zinc cracked ice

dust (43 g) and get 18.40 g of 4- (adamantyl-1) -thiophenol. The yield of the target product

is 58%, calculated on benzene.

The advantages of the proposed method are the reduction in the number of stages, the use of available reagents, which greatly simplifies the process of obtaining the desired product. In addition, the aforementioned reduction of stages makes it possible to eliminate energy-intensive and resource-intensive stages, which makes the whole process economical, highly efficient and energy-saving.

Claims (1)

DETAILED DESCRIPTION OF THE INVENTION A method for producing 4- (adamantyl-1) -thiophenol by reacting 1-bromo damantane with an arylating agent, characterized in that, in order to simplify the process, a mixture of 1-bromadomantane and benzene is treated with chlorosulfonic acid, taken at a molar ratio, equal to 1: 1: 3-5, at (-15) - 0 ° C, followed by reduction of 2- {adamantyl-1) -benzenesulfonyl chloride with zinc in sulfuric acid.