RU2455294C2 - Method of producing 2,5-dialkyl-3-phenyl(benzyl)-1,3,4-thiadiazolidines - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and particularly to a method of producing 2,5-dialkyl-3-phenyl(benzyl)-1,3,4-thiadiazolidines of formula (I)

where R¹=Me, Et, ⁿPr, ⁿBu, ⁿPent; R²=Ph, Bz. The method involves preliminary saturation of an alkyl-substituted aldehyde (acetic, propionic, butyric, valeric, caproic) with hydrogen sulphide followed by addition of phenyl hydrazine (benzyl hydrazine) and stirring at temperature 0°C and atmospheric pressure for 2-4 hours. Output of 2,5-dialkyl-3-phenyl(benzyl)-1,3,4-thiadiazolidines (1) is equal to 48-83%.

EFFECT: obtaining compounds which can be used as antibacterial, antifungal and antiviral agents, as biologically active complexing agents, selective sorbents and extractants of precious metals, special reagents for inhibiting bacterial activity in different process media.

1 cl, 1 tbl, 1 ex

Description

The present invention relates to the field of organic chemistry, in particular to a method for producing 2,5-dialkyl-3-phenyl (benzyl) -1,3,4-thiadiazolidines of the general formula (I):

R ¹ = Me, Et, ⁿ Pr, ⁿ Bu, ⁿ Pent; R ² = Ph, Bz

Thiadiazolidine compounds are known as antibacterial, antifungal, and antiviral agents (Stillings MR, Welbourn AP, Walter DJ Substituted 1,3,4-thiadiazoles with anticonvulsant activity // Med. Chem. - 1986. - 29. - P.2280-2284. Kidwai M., Negi N., Chaudhary SR Cyclothiomethylation of arge hydrazines with formaldehyde.// Acta Pharma. - 1995. - 45. - P. 511. Tyukavkina HA, Zurabyan S.E., Beloborodov V.L. et al. Organic Chemistry. - M.: Bustard, 2008 .-- 66-67). They are promising as catalysts, biologically active complexing agents, selective sorbents and extractants of precious metals [Deutsche Gold- und Silber-Scheideanstalt vormals Roessler. F.P. 1341792/1963 (Chem. Abs., 1964, 60, 5528d)], special reagents for inhibiting the activity of bacteria in various technical environments (from light industry to oil) (Dzhemilev U.M., Aleev RS, Dalnova Yu. S., Kunakova R.V., Hafizova S.R., Kovtunenko S.V., Kalimullin A.A., Andrianov V.M., Ismagilov F.R., Gafiatullin R.R. Means for inhibiting the growth of sulfate-reducing bacteria Pat.RF No. 2160233, 2000; Dzhemilev U.M., Aleev R.S., Dalnova Yu.S., Kunakova R.V., Khafizova S.R. Means for inhibiting the growth of sulfate-reducing bacteria. Pat. RF No. 2206726 , 2003).

Known methods for producing 2,5-alkyl substituted 1,3,4-thiadiazolidines of the general formula (2) by condensation of carbonyl compounds, hydrazine and hydrogen sulfide (Buter J., Wassenaar S., Kellogg RM Thiocarbonyl Ylides. Generation, Properties and Reactions. // J Org. Chem. - 1972. - Vol.37.- No. 25 - P.4045-4060; Rűhlmann K. Űfer die Synthese von 1,3,4-Thiadiazolidinen und 1,3,4-Thiadiazolen // J. Prakt Chem. 1959. - No. 5-6 - P.285-291) or by mixing hydrogen sulfide with azines (Neureiter NP Monomeric formaldazin - synthesis of 1,3,4-thiadiazolidine - a new heterocycle // J. Am. Chem. Soc . - 1959 - V.81 - P.2910; Kellogg RM, Noteboom M, Kaiser JK Thiocarbonyl Ylides. Stereochemical Properties of 4-tret-Butylcyclohexyl Derivatives. // J. Org. Chem. - 1975. - Vol.40. - No. 17. - P.2573-2574).

The known method does not allow to obtain 2,5-dialkyl-3-phenyl (benzyl) -1,3,4-thiadiazolidines of the General formula (1).

The known method (V.R. Akhmetova, G.R. Nadyrgulova, S.R. Khafizova, R.R. et al., Journal of Organ. Chemistry, 2006, 1, p. 151) for the production of 3-phenyl-1, 3,4-thiadiazolidine of formula (3) by the interaction of phenylhydrazine hydrochloride with CH ₂ O and H ₂ S in a ratio of 1: 3: 2 (pH 0.45-0.5) at 0 ° C with a yield of 35% according to the scheme:

In a known manner, 2,5-dialkyl-3-phenyl (benzyl) -1,3,4-thiadiazolidines of the general formula (1) cannot be obtained.

The known method (V.R.Akhmetova, G.R. 4-thiadiazolidine (4) and 1,3,5-dithiazinane (5) series by cyclothiomethylation of benzylhydrazine with CH ₂ O and H ₂ S in a neutral medium (ratio of starting reagents, respectively, 1: 3: 2, temperature ~ 20 ° С )

The known method does not allow to obtain 2,5-dialkyl-3-phenyl (benzyl) -1,3,4-thiadiazolidines of the General formula (1).

Thus, in the literature there is no information on the preparation of 2,5-dialkyl-3-phenyl (benzyl) -1,3,4-thiadiazolidines of the formula (1).

A new method is proposed for producing 2,5-dialkyl-3-phenyl (benzyl) -1,3,4-thiadiazolidines of the general formula (1).

The essence of the method consists in the preliminary saturation of the alkyl substituted aldehyde (acetic, propionic, butyric, valerianic, kapron) hydrogen sulfide at a temperature of 0 ° C followed by the addition of phenylhydrazine (benzylhydrazine) taken in the molar ratio aldehyde: hydrogen sulfide: phenylhydrazine: 10 = 20) 10. The mixture is stirred for 2-4 hours at a temperature of 0 ° C and atmospheric pressure, 2,5-dialkyl-3-phenyl (benzyl) -1,3,4-thiadiazolidines of the formula (1) are isolated in a yield of 48-83%. The reaction proceeds according to the scheme:

R ¹ = Me, Et, ⁿ Pr, ⁿ Bu, ⁿ Pent; R ² = Ph, Bz

2,5-Dialkyl-3-phenyl (benzyl) -1,3,4-thiadiazolidines (1) are formed only with the participation of alkyl substituted aldehydes, hydrogen sulfide and phenylhydrazine (benzylhydrazine), taken in a molar ratio of 20:10:10. With a different ratio of the starting reagents, the selectivity of the reaction decreases. In the presence of other aldehydes (e.g., aryl-substituted aldehydes), other sulfur-containing compounds (e.g., carbon disulfide, sulfur dioxide) or other substituted hydrazines (e.g., dialkylhydrazines, diarylhydrazines, alkylarylhydrazines), the desired products (1) are not formed.

The reaction was carried out at a temperature of 0 ° C. At temperatures above 0 ° C (for example, 40 ° C), the selectivity of the reaction decreases and energy consumption increases, and at temperatures below 0 ° C (for example, -10 ° C) the reaction rate decreases.

Significant differences of the proposed method:

In the known method, the reaction proceeds with the participation as starting compounds of benzylhydrazine, formaldehyde and H ₂ S, taken in a molar ratio of 1: 3: 2, at a temperature of ~ 20 ° C. The known method does not allow to obtain 2,5-dialkyl-3-phenyl (benzyl) -1,3,4-thiadiazolidines of the General formula (1).

In the proposed method, alkyl substituted aldehydes, hydrogen sulfide and phenylhydrazine (benzylhydrazine) taken in a molar ratio of 20:10:10 are used as starting reagents; the reaction proceeds at a temperature of ~ 0 ° C. In contrast to known methods, the proposed method allows to obtain individual 2,5-dialkyl-3-phenyl (benzyl) -1,3,4-thiadiazolidines of the general formula (1).

The method is illustrated by the following examples.

EXAMPLE 1. In a glass reactor equipped with a mechanical stirrer, a gas supply tube and a dropping funnel at a temperature of 0 ° C, 20 mmol of acetic aldehyde are placed, saturated with hydrogen sulfide (10 mmol) for 15 minutes, 10 mmol of phenylhydrazine is added. The reaction mixture was stirred at ~ 0 ° C for 3 h, extracted with chloroform, 2,5-dimethyl-3-phenyl-1,3,4-thiadiazolidine was isolated in 65% yield. Other examples confirming the method are given in table 1.

Table 1 №№ Starting aldehyde Source hydrazine Reaction time, hour Yield (1),% one acetaldehyde phenylhydrazine 3 65 2 - "- - "- four 72 3 - "- - "- 2 48 four propionic - "- 3 68 5 oil - "- 3 73 6 valerian - "- 3 77 7 kapron - "- 3 83 8 acetaldehyde benzylhydrazine 3 71 9 propionic - "- 3 75 10 oil - "- 3 77 eleven valerian - "- 3 79 12 kapron - "- 3 82

All experiments were carried out at a temperature (~ 0 ° C).

Spectral characteristics of 2,5-dialkyl-3-phenyl (benzyl) -1,3,4-thiadiazolidines of the general formula (I):

Claims (1)

The method of obtaining 2,5-dialkyl-3-phenyl (benzyl) -1,3,4-thiadiazolidines of the general formula (1):

where R ¹ is Me, Et, ⁿ Pr, ⁿ Bu, ⁿ Pent; R ² - Ph, Bz,
characterized in that the alkyl-substituted aldehyde saturated with hydrogen sulfide (acetic, propionic, butyric, valerianic, caproic) is reacted with phenylhydrazine (benzylhydrazine) at a molar ratio of the starting reagents aldehyde: hydrogen sulfide: phenylhydrazine (benzylhydrazine at 10 ° C: 10 ° C: 10 ° C: 10 ° C) = 20 ° C: = 20 ° C: and atmospheric pressure for 2-4 hours