SU364164A1 - - Google Patents

Description

METHOD OF OBTAINING (5-NITRO-2-TIAZOLYL) -GUANIDINES

one

The invention relates to the field of the preparation of new (5-nitro-2-thiazolyl) -guanidines, which have a valuable pharmacological activity that is superior to that of the known analogous nitrothiazoles.

A method for the production of guanidine derivatives by the interaction of guanidines with the corresponding halogen derivatives is described.

A method for the preparation of (5-nitro-2-thiazolyl) -guanidines of general formula I is provided.

(V

R4

where RI-R4 have the same or different meanings — lower alkyl groups, or from one to three of the radicals are hydrogen atoms, and the remaining radicals are lower alkyl groups, or RI and R2, or Ra and R4 together with the nitrogen atom can represent a morpholine residue. .

The method consists in the fact that 2-halogen-5nitrothiazole of the general formula II

o..4 /

Hal

IT

where Hal is a halogen atom, is subjected to interaction with a substituted guanidine of General formula III

/but.

/

 -2

 / Ro

N /

R.

one

where Ri-R4 have the above meaning.

The reaction is carried out in the presence of a solvent, the preferred solvents are ketones, for example acetone. To complete the reaction, the reaction mixture is briefly heated to the boiling point of the solvent used.

The products are isolated in a known manner in free form or in the form of salts with inorganic or organic acids.

The starting compounds II and III are known.

Example 1. M, S, S, S-Tetramethyl-S - (5nitro-2-thiazolyl) -guanidine.

10 g (0.061 mol of 2-chloro-5-nitrothiazole) are dissolved in 50 ml of acetone and 14 g (0.12 mol) of N, N, N, N-TeTpaMetilguanidine in 30 ml of acetone is added dropwise, which is in an exothermic reaction begins to boil. Then boil for another 15 minutes under reflux. The solution is concentrated to approximately 20 ml, cooled, and the precipitated crystals are sucked off. The crude product is recrystallized from ethyl acetate with the addition of activated carbon. mp 111 - 112 ° C.

Example 2. M, M-Dimethyl-L- (5-nitro-2thiazolyl) -guanidine.

1.68 g (0.01 mol) of 2-chloro-5-nitrothiazole is dissolved in 100 ml of dry acetone, 2.6 g (0.01 mol} N, N-dimethylguanidine and 1/2 H2SO4 are added, and 3, 4 g (0.025 mol} of potassium carbonate. The mixture is stirred for 2 hours at 20 ° C. Then it is boiled for 0.5 hour under reflux. Suction is removed from the dark fatty residue. The filtrate is concentrated to 50 ml and diluted with 70 ml A dark purple precipitate is precipitated, which is sucked off and recrystallized from a small amount of ethanol with the addition of activated carbon.The yield is 0.25 g (12% of theoretical); mp 203-204 ° C.

Subject invention

The method of obtaining (5-nitro-2-thiazolyl) -guanidines of formula I

V N / R3

-R4

where they have the same or different meanings — lower alkyl groups, or from one to three of the radicals are hydrogen atoms, and the remaining radicals are lower alkyl groups, or RI and R2, or Ra and R4 together with the nitrogen atom can denote morpholino residue, or salts, characterized in that 2-halogen-5-nitrothiazole of general formula II

L

Lnaa

ABOUT

tt

where Hal is a halogen atom,

interact with

guanidine of general formula III

/. /%

 2

AND

.

Well

where the radicals Rj-R4 are as defined above, in the presence of a solvent, followed by isolation of the products in the form of bases or salts in a known manner.