SU1077888A1 - Process for preparing 2-cycloalkylamino-1,3,4-thiadiazoles - Google Patents

Abstract

METHOD FOR PREPARING 2-CYCLBALKYLAMINO-1, 3,4-TIADIAZOLES The general formula Jf-Df R-, г gDe R-cyclopentyl, cyclohexyl, R-hydrogen, lower alkyl, in a medium of sulfuric acid at a temperature in which, and that, in order to increase the yield of the desired α-products and reduce the duration of the pro-process, 2-amino-5-K-1,3,4-thiadiazole, where R1 has the indicated values, it is subjected to alkylation with cyclopentyl sg or cycorexyl alcohol at 55- 65c in the medium of 80-90 wt.% Sulfur f / J acid.

Description

 vj

OO SH) 00

The invention relates to methods for producing 2-cycloalkylamino-1,3,4-thiadiazoles with an o € jteft formula

IfIf

. tl II 5 dxC-l HR

where R is cyclopentyl, cycloexyl;

R

hydrogen, lower alkyl.

Can be used as stabilizers for rubber, rubber, plastics, components of physiologically active preparations for the synthesis of fungicides.

It is known that 1,3,4-thiadiazoles and their derivatives, including 15 2-cycloalkylamino-1,3,4-thiadiazoles, can be obtained from thiosemicarbazides, thiocarbazides, dithiourea dithiocarbazates and some other substances 1.20

However, the very process of obtaining these starting materials is a series of long-term sequential syntheses (as a rule, at least three) using difficult-to-25 substances. Thus, the preparation of the corresponding starting 2-cycloalkylamino-substituted thioscleiocarbazides can be carried out in three stages. For example, a 4-cyclo-30 pentylthiosemicarbazide preparation scheme can be represented as follows: preparation of cyclopentylamine; obtaining cyclopentyl isothiocyanate, obtaining 4-cyclopentylthiosemicarbazide. If, for example, the production of the desired product is accomplished by cyclizing thiosemicarbazide with acetyl chloride, another step is added to obtain acetyl chloride. Each of the specified Q steps typically lasts from several hours to several days and is characterized by low yields of reaction products.

The final stages of the process (proper preparation of the desired product) are characterized by a considerable duration (6-40 hours) and low yields (up to 70%.

If we take into account the entire cycle of obtaining the target product, 50 including the stages of the synthesis of the starting materials, then the total duration of the process. The production time is several days (100 hours or more). In addition, due to the low yields at 55 of each stage, the total yield of the target products is 2-15%.

These reasons (duration, low output) also determine the high cost of the target products. 60 A known method of producing 2-alkylamino-1, 3,4-thiadiazoles by the interaction of equimolar amounts of the alkyl derivative of 3-thiosemicarbazide corresponds to (aliphatic acid)

lots at l6o-120 ° C in the presence of a mixture of 15-35 wt.% - sulfuric acid and 65-85 wt.% - polyphosphoric acid C2 as cyclodehydrating agent.

To obtain the corresponding 2-cycloalkylamino-1, 3,4-thiazoles by the indicated method, it is also necessary to obtain 4-cycloalkylthiosemicarbazide according to the described multistage schemes

In addition, the method uses polyphosphoric acid, which is not produced domestically. This requires an additional step of preparing polyphosphoric acid, starting from phosphoric acid and phosphoric anhydride.

The closest to the present invention is a method for preparing 2-cycloalkylamino-1, 3,4-thiadiazoles of the general formula

1Г-Ж

II

Bs .. r

where k is cyclohexyl;

R is hydrogen, lower alkyl, by cyclization of 4-cyclohexylthiosemicarbazide with the corresponding carboxylic acid in a medium of concentrated 198 MgS%) sulfuric acid while boiling the reaction medium for two hours HZ.

The yield of the target products by this method averages about 70%.

The initial thiosemicarbazide in this case can be obtained in two stages: I - obtaining the amine, II - obtaining the thiosemicarbazide. At the same time, the average yield of substances according to stages is: stage I - 50%, stage P - 90%. The total yield of 2-cycloalkylamino-1,3,4-thiadiazoles (O, 5x0.9x0.7) 100 32% of the total duration of the process, including the steps for preparing the initial thiosemicarbazide, is no less than 10 hours. The cost of the target products is also high.

The purpose of the invention is to increase the yield of the price of the first products and shorten the duration of the process.

This goal is achieved by the fact that according to the method for preparing 2-cycloalkylamino-1,3,4-thiadiazoles of the general formula

 Nn

And And Ri-c.gxC-NHR

where R is cyclopentyl, cyclohexyl;

R-hydrogen, lower alkyl, in an environment of sulfuric acid at elevated temperature, 2-amino-5-Rl, 3,4 thiadiazole, where R has the indicated values, is subjected to alkylation with cyclopentyl yp cyclohexyl alcohol at 55-65 ° C in 80-90 medium wt.% sulfuric acid. .

An increase in the temperature of the alkylroaany process of 2-amino-1,3,4-R-thiadiazoles above 65 ° C leads to an intensive resin formation and a decrease in the yield of the target products. When the temperature of the alkylation process is lower, the yield of 2-cycloalkylginino- / 3,4-thiadiazole also drops sharply.

With a decrease in the concentration of sulfuric acid below 80 wt.%, As well as an increase in it above 90 wt.%, The yield of the target product also decreases.

The essence of the proposed process for the preparation of 2-cycloalkylamino-1,3,4-thiadiazoloB by alkylation of 2-amino-5-R-1, 3,4-thiaviazols is explained

Specific embodiments are carried out according to the following general scheme,

To a solution of 0.1 gm mol of the corresponding 2-amino-5-R-l, 3,4-thiadiazole in 100 ml of 85% sulfuric acid at

60 ° C and 0.11 g-mol of the corresponding cycloalkanol is added via vigorous stirring from a dropping funnel. The mixture is stirred under the specified conditions for 4 hours, after which

cooled to room temperature, poured onto 200 g of ice, alkalinized with concentrated aqueous ammonia. The separated product is filtered and dried.

The conditions for the implementation of examples of specific performance and the results of the experiments are given in Table. 1. 71077888 Table 2 shows the data on the time course of the target products depending on you. 8 concentrations of sulfuric acid Table

Claims (2)

METHOD FOR PRODUCING 2-Cycloalkylamino-1,3,4-thiadiazoles of the General formula N — N, |) II R 'where R is cyclopentyl, cyclohexyl ·, R * is hydrogen, lower alkyl, in sulfuric acid at a higher temperature, characterized in that, in order to increase the yield of target products and reduce the duration of the process, 2-aMHHo-5-Rl, 3,4-thiadiazole, where R has the indicated values, is subjected to alkylation with cyclopentyl or cyclohexyl alcohol at 55-65 ° C in a medium of 80-90 wt.% Sulfuric acid. • 1077888