SU414787A3 - METHOD OF OBTAINING SUBSTITUTED BIS- (BENZYLIDENAMINO) -GUANIDINES - Google Patents

Description

one

The invention relates to a process for the production of new guanidines, in particular substituted bis (benzylideneamino) guanidines, having biologically active properties.

A known method for producing benzylidene aminoguanidines by reacting substituted benzaldehyde with aminoguanidine salts in aqueous alcohol in the presence of acetic acid.

Known benzylideneguanidines, which have bactericidal properties, are not sufficiently active for the treatment of protozoal diseases in tenloclores.

In order to obtain new guanidine derivatives, exceeding in their properties known analogues, a method has been proposed for the preparation of compounds of the general formula

Kz G

C lN -N-C-N-N C I II I R, NHRg

where Ri and RS are halogen, trifluoromethyl, cyano;

R2 and Re are hydrogen, halogen;

Rs, R4, R and Rg are hydrogen, lower alkyl, or their salts.

The proposed method is based on the known reaction of the interaction of aldehydes with salts.

guanidine and is that the compound of the general formula

O II-C-R.

10 where RI, R2 and Rs are as defined above,

subjected to interaction with the compound of the General formula

HjN-N-C-NH-HX

7 (K8)

where R and Rs are as defined above;

X is the acid anion.

From guanidine salts, for example, nitrates, chlorohydrates, bromohydrates, methosulfates can be obtained.

The process is conducted in a mixed state environment.

water organic solvent for example

ethanol. The mixture is heated at a temperature of

Mainly 50-80 ° C, maintained with it 1 -10 mip, and then cooled to room temperature. The precipitated product is filtered, washed with ethanol: M and / or ether, and then dried. The resulting compounds are crystalline solids ranging from white to pale yellow pvet.

Example 1. Nitrate, hydrochloride and methosulfate 1,3-bis- (4-chlorobenzylpdenamino) -guanidine.

A boiling solution of 14.1 g of 4-chlorobenzaldehyde (slight excess) in 250 ml of ethanol is thoroughly mixed with 6.1 g of 1,3-diaminoguanide nitrate in solution and then 0.5 ml of concentrated nitric acid in 50 ml of water is added. The reaction mixture is stirred until it is cooled to room temperature, after which it is kept for several hours. The resulting precipitate is collected, washed with hot ethanol and dried with air flow, and then at 60 ° C in vacuum. The yield of 14.0 g, t. Kip. (with different).

The hydrochloride or metosulfate is prepared similarly, using the corresponding guanidipate salts and 0.5 ml of the corresponding acid. Melting point of hydrochloride is 289-290 ° C (with decomposition); m.p. methosulphate 217- 224 ° C (with decomp.).

PRI mme R 2. 1,3-Bis- (4-chloro-benzylidenamino) -guanidine.

The free base of this compound is obtained by suspending 8 g of the nitrate from Example 1 in 200 ml of anhydrous eta} yla, followed by the addition of 2.5 L of 10 n. NaOH, unmixing and heating to homogeneous state of the mixture. The resulting solution is cooled and the precipitate separated is filtered. The melting point of the free base is 187-188 ° C.

Example 3. Pitrate 1,3-bis- (4-bromobenzylideneamino) -guanidine.

A boiling solution of 20.0 g of 4-bromobenzaldehyde in 250 ml of ethanol is thoroughly unmixed with 6.1 g of 1,2-diamino-guanidine nitrate in solution, after which 0.5 ml of concentrated nitric acid in 50 ml of water is added. The reaction mixture is stirred until it is cooled to room temperature, and then allowed to stand for several hours. The resulting precipitate is treated as in Example 1. The yield of the desired product is 165 g; m.p. 178-180 ° C (with decomp.).

Example 4. Pitrate 1,3-bis- (3,4-dichlorobenzylidepamino) -guapidine.

A boiling solution of 17.6 g of 3,4-dichloroisaldehyde in 250 ml of ethanol is thoroughly mixed with 6.1 g of 1,3-diamimoguanidine nitrate and then 0.5 ml of concentrated nitric acid in 50 ml of water is added in one portion. The reaction mixture is stirred until it is well cooled to room temperature, after which it is kept for several

hours The resulting precipitate is treated but for example 1. The yield of the desired product is 17.5 g, 1. kip. 195-19Q ° C (with decomp.). Example 5. 1,3-bis- (4-cyanobenzylidepamino) -guanidine nitrate.

A solution of 13.1 g of 4-cyanobenzaldehyde in 250 ml of ethiol is thoroughly mixed with 6.1 g of 1,3-diamino-guanidine nitrate in solution, and then 0.5 ml of concentrated nitric acid in 50 ml of water is added. The reaction mixture is stirred until it is cooled to room temperature, after which it is kept for several hours. The resulting precipitate is treated by

for example 1. Product yield 15.1 g; t. kin. 205-210 C (with decomp.).

Example 6. 1,3-bis- (4-chloro-a-methyl-di-isylidene-amino) -guanidine nitrate.

Boiling solution of 15.4 g of 4-chloroacetophenone

in 250 ml of ethanol, do not thoroughly mix with 6.1 g of 1,3-dinaminoguanidine nitrate in solution, then add 0.5 ml of concentrated nitric acid in 50 ml of water. The reaction mixture is not stirred until the temperature drops to room temperature, after which it is kept for several hours. The resulting precipitate is treated as described in Example 1. Yield: 8.7 g; m.p. 215 ° C (with decomp.). Example 7. 1,3-bis- (4-iodobenzylideneamipo) -guanidine hydrochloride.

This compound is prepared under the conditions of Example 1 from 4-iodobenzaldehyde and 1,2-diaminoguapidine hydrochloride. Its melting point is 288-29GS (with decomp.).

Example 8: 1,3-bis- (4-fluorobenzylideneamino) -guanidine nitrate.

This compound is prepared under the conditions of Example 1 from 4-fluorobenzaldehyde and 1,2-diamipoguapidipa nitrate. Melting point 169-170 ° C (with decomp.).

Example 9. 1- (4-Bromobenzylideneamino) -3- (4-chlorobenzylideneamino) -guanidine hydrochloride. A solution of 1.85 g of 4-bromobenzaldehyde in 10 ml

ethanol is added to a solution of 2.48 g of 1-amino-3- {4-chlorobenzylideneamino) -guanidine hydrochloride in 25 ml of boiling 95% ethanol. The reaction mixture is cooled, the precipitate is filtered off and dried with a stream of air.

Similarly, receive:

1 - (4-Bromobenzylideamino) -3 (4-chlorobenzylideneamino) -guanidine methosulfate using 1-amino-3- (4-Bromobenzylideneamino) -guanidine methosulfate and 4-chlorobenzaldehyde;

1- (4-chlorobenzylideneamino) -3- (4 cyanobenzylideneamino) -guanidine iodide hydrate from 1-amino-3- (4-pianobenzylideneamino) -guanidine iodine hydrate and 4-chloro benzaldehyde; 1- (4-chlorobenzylideneamino) -3 (3,4-dichlorobenzylideneamipo) -guanidine hydrobromide using 1-amino-3- (3,4-dichlorobenzylidenemino) -guanide hydrobromide and p-chlorobenzaldehyde. Pr, immer 10. Bromhydrate 1,3-bis- (4-chlorobenzylideneamino) -1-methylguanidine. 5 This compound is obtained using the procedure of nimer 1, but instead of nitrate of 1,3-diaminoguanidine 1,3-diamino-1-1 methylguanidine hydrobromide is used and 0.5 ml of 48% aqueous solution of hydrobromic acid is used as a catalyst. The output of pellovogo product 15.4 g; m.p. 276-278 ° C. The subject of the invention. A process for the preparation of substituted bis- (benzylideneamino) -guanidines of the general formula R is C-y-C-C-N-N C, where Ri and Rs are halogen, trifluoromethyl, cyano-20 group; R2 and Re are hydrogen, halogen; Rs, R4, R and Rs are hydrogen, lower alkyl, or their salts, characterized in that the compounds of the general formula 25 10 where the RI, R2 and Rs have the aforementioned values, are reacted with a compound of the general formula H, NN-C NH-HX where R and Rg are as defined above; X is the anion of the acid in an environment of a water-miscible organic solvent, followed by isolation of the target product by known methods.