RU2448955C1 - Method of producing 1,3-di(r-thio)adamantanes - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to the chemistry of adamantane derivatives, specifically to a method of producing 1,3-di(R-thio)adamantanes of general formula:

, where

(1);

(2);

(3). The method involves binding disulphides to 1,3-dehydroadamantane, said disulphides being selected from: diphenyl sulphide, n,n'-bis-(4-bromophenyl)disulphide, n,n'-bis-(4-aminophenyl)-disulphide with molar ratio of reactants equal to 1:1.1, in a melt of the initial disulphide at temperature 100-110°C or in benzene at 80°C for 2-9 hours.

EFFECT: method of producing novel 1,3-di(R-thio)adamantanes, which enables to obtain compounds of the disclosed structural formula with sufficiently high output.

1 cl, 3 ex

Description

The invention relates to a method for producing 1,3-di (R-thio) adamantanes of the general formula

Where

;

;

;

;

which may be of interest as intermediates in the synthesis of biologically active substances, and also act as objects of supramolecular chemistry [Dendrimers Designed for Functions: From Physical, Photophvsical, and Supramolecular Properties to Applications in Sensing, Catalysis, Molecular Electronics, Photonics, and Nanomedicine / / Didier Astmc, Elodie Boisselier and Ctia Ornelas. / Chem. Rev. 2010, 110 (4), pp. 1857-1959].

A known method of producing bisulfides, based on the interaction of disulfides with unsaturated compounds, catalyzed by compounds based on ruthenium, palladium, rhodium, titanium and other inaccessible compounds. These interactions proceed at 100 ° C. for 8 hours [Teruyuki Kondo, Shin-ya Uenoyama Ken-ichi Fujita, Take-aki Mitsudo // J. Am. Chem. Soc., 1999, 121, pp. 482-483].

The disadvantage of this method is the long reaction time, elevated temperature, and the high cost of the catalysts.

A known method of producing bisulfides, which consists in the interaction of disulfides with cyclohexene catalyzed by metal montmorillonites, for 3-24 hours at 50 ° C [Takahiro Nishimura, Tomoaki Yoshmaka, SakaeUemura // Bull. Chem. Soc. Jpn. 78, 1138-1141 (2005)].

The disadvantage of this method is the inability to obtain compounds of the claimed structural formulas.

The closest is a method for producing 1,3- (4-R-phenylseleno) adamantanes [RF patent 2333214, IPC C07F 11/00, published September 10, 2008] by reacting 1,3-dehydroadamantane with the corresponding dyslenide followed by the introduction of an adamantyl fragment in communication Se-Se.

The disadvantage of this method is the inability to obtain compounds of the claimed structural formulas.

The task of the invention is to develop a technologically advanced, universal and low-stage method for the synthesis of 1,3-di (R-thio) adamantanes, proceeding with a high yield according to the initial 1,3-dehydroadamantane.

The technical result is to expand the range of chemical compounds, in particular 1,3-di (R-thio) adamantanes, with a high yield in one stage.

The technical result is achieved in a new method for producing 1,3-di (R-thio) adamantanes of the general formula

Where

;

;

;

;

consisting in the addition of disulfides to 1,3-dehydroadamantane selected from the series: diphenyl sulfide, n, n'- bis - (4-bromophenyl) disulfide, n, n'- bis - (4-aminophenyl) disulfide at a molar ratio of reagents equal to 1: 1.1, in the melt of the starting disulfide at a temperature of 100-110 ° C or in benzene at 80 ° C for 2-9 hours.

The essence of the method is the reaction of obtaining 1,3-di (R-thio) adamantanes according to the reaction of incorporation of 1,3-dehydroadamantane via S-S bond into the corresponding disulfide.

The reaction is based on previously unknown properties of 1,3-dehydroadamantane to disulfide disulfides at the S-S bond at a temperature of 80-110 ° С. The reaction is unknown, since there is no information in the literature on the interaction of 1,3-dehydroadamantane with disulfides or related compounds. There is also no information on the preparation and properties of the compounds of the claimed structural formula. The interaction is possible due to the high reactivity of 1,3-dehydroadamantane, as well as the high lability of the S-S bond. This reaction is the first example of the introduction of a hydrocarbon at the S-S bond in disulfides with the formation of bisulfides of the claimed formula under mild conditions. The SS bond cleavage reactions described in the literature proceed under the influence of sodium hydrosulfite, metal hydrides, atomic hydrogen, hot water under pressure, cyanides, alkalis in the presence of heavy metal salts, monothiophosphoric acid, tertiary phosphines, some thiols, thio-dithioglycols, as well as chlorine, bromine sulfuryl halides [Chemical Encyclopedia / ed. I.L. Knunyantsa. M .: Soviet Encyclopedia, 1990. - T.II. p. 89].

The advantage of this method is the high yield (50-52%) of the resulting 1,3-di (R-thio) adamantanes, as well as a simple method for the synthesis of these compounds.

At a disulfide melting point below 110 ° С, its interaction with 1,3-dehydroadamantane was carried out in the melt, followed by recrystallization of the reaction products. At a disulfide melting point above 110 ° C, the reaction with 1,3-dehydroadamantane was carried out in an inert solvent (benzene) at 80 ° C.

Studies have shown that a prerequisite for a high yield of the resulting 1,3-di (R-thio) adamantanes is the use of a molar ratio of disulfide and 1,3-dehydroadamantane equal to 1.1: 1. A ten percent excess of disulfide is used to increase the conversion of 1,3-dehydroadamantane. A larger excess of disulfide leads to contamination of the target products and complicates the purification stage, and an excess of 1,3-dehydroadamantane leads to an increase in the proportion of by-products at the isolation stage.

It was found that the optimal synthesis time is 2-9 hours. A synthesis time of less than 2 hours leads to a decrease in the yield of the claimed compounds due to incomplete conversion of the starting 1,3-dehydroadamantane. The increase in the duration of synthesis to more than 9 hours does not lead to a significant increase in the yield of the target product.

The structure of the synthesized compounds is confirmed by the results of chromatography-mass spectrometry.

The invention is illustrated by the following examples.

Example 1

1,3-Di (phenylthio) adamantane

To a solution of 1.33 g (0.0061 mol) of phenyl disulfide in 10 ml of absolute diethyl ether in a dry nitrogen atmosphere at a room temperature, a solution of 0.74 g (0.0055 mol) of freshly-digested 1,3-dehydroadamantane (ratio phenyl disulfide: 1, 3-dehydroadamantane = 1.1: 1) in 10 ml of absolute diethyl ether. The ether is removed by distillation and the reaction is carried out for 2 hours at 100-110 ° C in a disulfide melt. The reaction mass is recrystallized from benzene.

Yield 0.98 g (50%). Appearance: tan crystals. Resin temperature 315 ° С.

Mass spectrum, m / z, (I,%): 352 (11%) [M] ⁺ , 243 (100%) [M ⁺ -PhS], 187 (33%) [M-PhSC ₄ H ₈ ] ⁺ , 133 (44%) [C ₁₀ H ₁₃ ] ⁺ , 109 (66%) [PS] ⁺ , 91 (53%) [C ₁₀ H ₁₄ -C ₃ H ₇ ] ⁺ , 77 (26%) [C ₆ H ₅ ] ⁺ .

Example 2

1,3-Di (n-bromophenylthio) adamantane

To a solution of 0.6 g (0.0016 mol) of n, n'- bis (bromophenyl) disulfide in 5 ml of tetrahydrofuran in a dry nitrogen atmosphere, a solution of 0.19 g (0.00145 mol) of freshly 1.3- dehydroadamantane (ratio n, n'- bis (bromophenyl) disulfide: 1,3-dehydroadamantane = 1.1: 1) in 5 ml of tetrahydrofuran. The solvent is distilled off and the reaction is carried out for 2 hours at 100-110 ° C in a disulfide melt. The reaction mass is boiled at a temperature of 35 ° C for 2 hours. The reaction mass is recrystallized from benzene.

Yield 0.37 g (50%). Appearance: tan crystals. Resin temperature 235 ° С. Mass spectrum, m / z, (I,%): 510 (6%) [M] ⁺ , 323 (87%) [M- (Br-C ₆ H ₄ -S)] ⁺ , 187 (49%) [Br-C ₆ H ₄ -S] ⁺ , 133 (82%) [C ₁₀ H ₁₃ ] ⁺ , 109 (73%) [PhS] ⁺ 91 (100%) [C ₁₀ H ₁₄ -C ₃ H ₇ ] ⁺ .

Example 3

1,3-Di (n-aminophenylthio) adamantane

To a solution of 0.1 g (0.0004 mol) of n, n'- bis (aminophenyl) disulfide in 10 ml of benzene in a dry nitrogen atmosphere at room temperature, a solution of 0.049 g (0.00037 mol) of freshly-digested 1,3-dehydroadamantane ( the ratio of n, n'- bis (aminophenyl) disulfide: 1,3-dehydroadamantane = 1.1: 1) in 10 ml of benzene. The reaction mixture is boiled at 80 ° C for 9 hours, benzene is removed by distillation, the residue is recrystallized from benzene.

Yield 0.08 g (52%). Appearance: white crystals. Melting point 215 ° C. Mass spectrum, m / z, (I,%): 382 (10%) [M] ⁺ , 258 (40%) [M- (NH ₂ -C ₆ H ₄ -S)] ⁺ , 135 (4% ) [C ₁₀ H ₁₅ ] ⁺ , 124 (100%) [NH ₂ -C ₆ H ₄ -S] ⁺ .

Thus, the above information indicates the fulfillment of the following set of conditions when using the claimed invention:

- a tool embodying the claimed invention in its implementation, is intended for use in various industries;

- for the claimed invention in the form described in the independent clause of the claims below, the possibility of its implementation using the means and methods described above or known prior to the priority date is confirmed;

- a tool embodying the claimed invention in its implementation is able to ensure the achievement of a technical result.

Therefore, the claimed invention meets the requirement of "industrial applicability".

findings

A new one-step method for producing 1,3-di (R-thio) adamantanes has been developed, which allows to obtain compounds of the claimed structural formula with fairly high yields. The structure of the obtained compounds was confirmed by chromatography-mass spectrometry.

Claims (1)

The method of obtaining 1,3-di (R-thio) adamantanes of the General formula

Where

;

;

consisting in the addition of 1,3-dehydroadamantane disulfides selected from the series: n, n'-bis (4-bromophenyl) disulfide, n, n'-bis- (4-aminophenyl) disulfide with a molar ratio of reagents equal to 1: 1.1, in the melt of the starting disulfide at a temperature of 100-110 ° C or in benzene at 80 ° C for 2-9 hours