SU355801A1 - METHOD OF OBTAINING BENZOLSULPHONYLMOLOVA - Google Patents

Description

The invention relates to a "process for the preparation of a previously unknown benzenesulfonylurea of the general formula

L-co-i H-Y-y-sog-kk-s-in-k

or its salts,

where R is lower alkyl or alkenyl, preferably methyl; X is a methyl acyl, trnfluoromethyl, nitro, cyano- or methyl mercapto group, phenyl, benzyl, and the prince X is in position 4 or mainly in position 5 with respect to the carbamide group;

Y - CH2CH2 ::, - CH - CHj-,

SNS

- CH2 - CH-; I CH,

R is an alkyl or alcatene

5-8 carbon atoms, cyclohexenyl, cyclohexylmethyl.

Lower alkyl, lower alkenyl or lower acyl always contain a carbon atom in a straight or branched chain.

The novel compounds can be used in pharmacology as a means of reducing the sugar content of the protein. Moreover, these compounds are superior in efficiency to the well-known analogous active substances.

the same class of compounds, for example N- (4-Methylbenzene sulfonyl l) -N-butyl urea.

The proposed method consists in the fact that the sulfonamide of the general formula

20

or its salts, where X, Y and R are as defined above, are reacted with R-substituted isocyanate, R-substituted urea, chlorine anhydride or ether, respectively, of a substituted carbamic acid-carbamic acid (R has the above-mentioned values). Transformations can be carried out in the absence or in the presence of solvents at room or elevated temperatures. The desired product is isolated from the reaction mass by conventional means or converted into salts by treatment with alkaline agents such as alkali metal or alkaline earth metal hydroxides, alkali metal carbonates or bicarbonates. Example 1. M- {4-p- (2-ethoxy-5-acetylbenzamido) -ethyl-benzenesulfonyl) -N- (4-methylcyclohexyl) -urea (face). 8 g of (2-ethoxy-5-acetylbenzamido) -ethyl benzenesulfonamide (m.p. 197-198C), obtained from 2-ethoxy-5-acetylbenzoic acid and 4- (p-aminoethyl) -benzenesulfonamide, are dissolved in 10, 5 ml 2 n. alkaline sodium and 40 ml of acetone and 3.1 g of 4-Methylcyclohexyl isocyanate (trans) are added dropwise at 0-5 ° C with stirring. It is further stirred for 3 hours at room temperature, diluted with water and methanol, filtered from the insoluble part and the filtrate is acidified with dilute hydrochloric acid. The crystalline form of N- {4 p- (2-ethoxy-5-acetylbenzamido) -ethyl-benzenesulfonyl} -N- (4-methylcyclohexyl) -urea (trans) is melted after recrystallization from methanol at 162-164 ° C. Similarly, L- {4-p- (2-ethoxy-5 acetylbenzamido) -ethyl-benzenesulfonyl} N-cyclohexylurea, t. Nl. 161-162 ° C (from methanol). In a similar way, from (2-methoxy-5-propionylbenzamido) -ethyl-benzene-sulfone-Med (m.p. 203-205 ° C), N- {4-p- (2-methoxy-5-propionylbenzamido) -ethyl-benzenesulfonyl} -N-cyclohexylurea, m.p. 136--138 ° C (.from methanol) and (3- (2-methoxy-b-propionylbenzamido) -ethyl-benzenesulfonyl} -N- (4-methylcyclohexyl) - urea (trans), mp 137-139 ° C (from methanol); from 4 - | 3 - (2-allyloxy-5-acetyl-benzamido) ethyl-benzenesulfs-amide (m.p. 169-171 ° C), you get Y- {4- | 3- (2-allyloxy- 5-acetylbenzamido) -ethyl-benzenesulfonyl} -N-cyclohexylurea, t.nl 154-155 ° C (from methanol) and N- {4- j3- (2 - alloxlox-B-acetylbenzamido) ethyl - benzenesulfonyl} - N - (4-methylcyclohexyl) urea (trans), mp 143-145 ° C (from methanol); from (2-methoxy-4-trifluoromethylbenzamido) is ethyl benzene sulfonamide (mp 172-174 ° C) P N- {4-p- (2-Metoxy-4-trifluorometh1Ido Ido) -ethyl-benzenesulfonamide (m.p. 172-174 ° C) is obtained; N- {4- p- (2-MeTOKCH-4-trifluoromethylbenzamido) is obtained -ethyl-benzenesulfonyl} -N-cyclohexylurea, mp 182-183 ° C (from methanol) and N- {4- p- (2-methoxy-4-trifluoromethylbenzamido) -ethyl-benzenesulfonyl} -N- (4 - methylcyclo-6 logex) urea (trans), mp 191-193 ° C (from methanol); from (2-methoxy-5-phenylbenzamido) -ethyl-benzenesulfonamide (m.p. 213-214 ° C), we obtain N- {4- | 3- (2-methoxy-5-phenylbenzamido) .. ethyl-benzenesulfonyl - Ncyclohexylurea t. pl. 194-195 ° C (from a mixture of methanol with dimethylformamide), N- {4 | 3- (2-methoxy-5-phenylbenzamido) - ethyl-benzenesulfonyl} - | - (4-methylcyclohecoyl) - urea (trans), t. square 189-190 ° С (from a mixture of methanol-dimethylformamide) and N- {4- p- (2-Metoxy-5-phenylbenzene "do) - ethyl - benzenesulfonyl - N - (4 - ethylcyclohexyl) - urea (trans), t pl. 183-184 ° C (from methanol); from (2-methox "-5-benzyl benz: Mndo) -ethyl-ben, zolsulfonamide (mp 158-160 ° C), N- {4-p - (2-methoxy - 5 - benzyl benzamido) ethyl - benzenesulfonyl} - N- (4-methylcyclohexyl) -urea (trans), so pl. 150-151 ° C (from methanol); from (2-methoxy-4-nitrobenzamido) -ethyl-benzenesulfonamide (mp 207-209 ° C), N- {4- 3- (2-methoxy-4-nitrobenzamido) -ethyl-benzenesulfonyl} -N cyclohexylurea, t pl. 196-198 ° C (from methanol), N- {4-p- (2-methoxy-4-nitrobenzamido) -ethyl-benzolsulfonyl} -N- (4-methylcyclohexyl) -urea (trans), T. Il. 197-198 ° C (from methanol) and N- {4- p- (2-MeTOKCH-4-H “Tpo6eH3amido) -ethyl-benzenesulfonyl} -N- (4-ethylcyclohexyl) -urea (trans), mp . 201 - 202 ° C (from methanol-dimethylformamide mixture); from 4- (3- (2-ethoxy-4-nitrobenzamido) -ethyl benzenesulfonamide (mp 213 ° C), N- {4- | 3- (2-ethoxy-4-nitrobenzamido) -ethyl benzenesulfonyl} - N - | 3 - cyclohexyl urea, mp 174-176 ° C (from methanol) and N- {4- | 3 (2-ethoxy-4-nitrobenzamido) -ethyl-benzenesulfonyl} -M- (4-methylcyclohexyl) - urea (trans), mp 195-197 ° C (from methanol-dimethylformamide), and from (2-methoxy5-nitrobenzamido) -ethyl-benzenesulfonamide (mp 174-176 ° C), N- { 4- p- (2-Metoxy-5-nitrobenzamido) -ethyl-benzene-sulfoalkyl} -N- :: poloIexyl jonevine, mp 146-148 ° C (nz methanol); from (2-ethoxy-4-trifluoromethylbe nzamido) - these l-benzene sulfonamide (m.p. 228-229 C) give N- {4- | 3- (2 ethoxy-4-trifluoromethylbenzamido) - ethyl-benzene sulfonyl} -1 - (p-phenylethyl) - urea, t mp 148-149 С (from methanol), N- {4- p- (2toxy-4-trfluoromethylbenzamido) .- ethyl benzene sulfonyl} - N-cyclohexylmethylurea, mp 194-195 ° С (from methanol) , N- {4-, 6- (2toxn-4-trifluoromethylbenzamndo) - ethyl -benolsulfonyl} -N-cyclopentyl urea, t. Pl. 143-144 ° C (from methanol), K- {4- | 3- (2-ethoxy-4pIfluoromethylbenzamido) -ethyl-benzenesulonyl} -N- (4-isopropoxycyclohexyl) -urea, t. Nl. 184-185 ° С (from methanol,) N- {4-p2-ethoxy - 4-trifluoromethylbenzamido) -ethyl-ethyl-benzylphenyl} -N-n-hydroxy-perchem, t. Pl. 73-174 ° C (from methanol) and N- {4- | 3- (2-ethoxy-trifluoromethylbenzamido) -ethyl-benzenesulonyl} -.-Cycloheptylurea, so pl. 162-64 ° C (from methanol); from (2-methokei-5-trifluoromethylbenzamido) -ethyl-benzenesulfonamide (t. pl. 19 HS) get N- {4- | 3- (2-methoxy-5-trifluoromethylbenzamido) -ethyl-benzenesulfonyl} - .L-cyclohexylurea t. pl. (with dec.) (from methanol), L- {4-p- (2-methoxy-5-trifluoromethylbenzamido) -ethyl-benzenesulfonyl} - 1-butylurea, m.p. 123-125 ° C (from methanol), M- {4- p- (2-methoxy-5-trifluoromethylbenzamido) -ethyl-benzenesulfonyl} -M- (4-methylcyclohexyl) - urea (facet), t. Pl. 168-170 ° C (from methanol) and N {4-p - (2-methoxy-5-trifluoromethylbenzamido) ethyl benzene sulfonyl} -Y-cycloheptylurea, m.p. 104-106 ° С (“3 metapols); from (2-ztoxy-5-trifluoromethylbenzamido) -ethyl benzenesulfonamide (mp. 200 ° C), N- {4-p- (2-ethoxy-5-trifluoromethylbenzamido) ethyl-benzenesulfonyl} -H-cyclohexylurea, m. square 140-142 ° C (from methanol), N- {4- p (2-ethoxy-5-trifluoromethylbenzamido) - ethyl benzenesulfonyl} -N - (4-methylcyclohexyl) urea (trans), so pl. 170-17GS (from methanol), N- (2-methoxy-5-nitrobenzamido) ethyl-benzenesulfonyl} - L- (4-methylcyclohexyl) -urea (trans), so pl. 163-164 ° C (from methanol); from (2-ethoxy-5-nptrobenzamido) -ethyl-benzenesulfonamide (t. Il. 178-180 ° C), K-4- (2-ethoxy-5-nitrobenzamido) is obtained. ethyl-benzenesulfonyl} -N - (4methylcyclohexyl) -urea (trans), so pl. 169-170 ° C (from methanol); from (2-ethoxy-4 trifluoromethylbenzamido) -ethyl-benzenesulfonamide (mp 228-229 ° C), we obtain N- {4 p- (2-ethoxy-4-trifluoromethylbenzamido) -ethyl benzenesulfonyl} - N-cyclohexylurea, m. square 172-174 ° C (izmethanol), N- {4-p- (2-ethoxy-4-trifluoromethylbenzamido) - ethyl-benzenesulfonyl} - N-butylurea, t.p. 151-153 ° C (from methanol) and Hr {4-p- (2-it.xy-4-trifluoromethylbenzamido) -ethyl-benzenesulfonyl} -M- (4-methylcyclohexyl) -urea, mp. 185-186 ° C; from (2-n-propoxy-5-acetylbenzamido) - ethylbenzenesulfonamide (mp 201-202 ° C), we obtain Hg {4-p- (2-n-propoxy5-acetylbenzamido - benzenesulfonyl} L- (4- methylcyclohex "l) - urea (trans), mp. 121-123 ° C (from methanol); from (2-nbutoxy-5-acetylbenzamido) -ethyl-benzenesulfonamide (mp. 187-188 ° C) receive N- {4 p- (2-n-butoxy-5-acetylbenzamido) -ethyl-benzenesulfonyl} -Y-cyclohexyl urea, mp 169-170 ° С (from methanol).

Example 2.; Y.- {4-p-2-ethoxy-5-acetylbenzamido) -ethyl-benzenesulfonyl} -N-cyclehexylurea.

4.1 2 (2-ethoxy-5-acetylbenzamido-ethylbenzenesulfonyl amide sodium and 4.4 g of N-cyclohexylcarbamidic acid phenyl ester are dissolved in 100 ml of dimethylformamide heated for 45 minutes to 110 ° C. The reaction mixture is then cooled to 0.5% The aqueous ammonia is diluted, filtered and the filtrate is acidified. The precipitate formed is filtered off with suction and recrystallized.

Example 3. N- {4- p- (2-methoxy-5-propionylbenzamido) -ethyl-benzenesulfonyl} -Ncyclohexyl urea.

4.1 g of (2-methoxy-5-propiopylbenzamido) -ethyl-benzenesulfonamide sodium is heated from 5.9 g of H, 1-difepil-: N-cyclohexylurea in 100 ml of dimethylformamide 45 minutes to 110 ° C. After cooling, the reaction mixture is treated with a 0.5% ammonia solution, filtered, and the filtrate is acidified. The resulting precipitate is again precipitated from a 0.5% ammonia solution and then recrystallized from methanol. N- {4-p- (2methoxy-5-propionylbepzamndo) -ethyl-benzenesulfonyl} -Y-cyclohexylurea melts at 136-138 ° C.

Subject invention

The method of obtaining benzenesulfonyl urea of the general formula

3 CO-NH-Y- (3 S07-l H-C-} flH-B OBO or its salts,

where R is lower alkyl or alkenyl, preferably methyl;

R4 / hr; -8 carbon atoms, cyclohexenyl, cyclohexenylmethyl;

X is lower acyl, phenyl, benzyl, trifluoromethyl, nitro, cyano or methyl mercapto group, X being in position 4 or mainly in position 5 in relation to the carbamide group;

Y-CHA-CH, -CH-CHg-,

I CH,

-sn -snznz

characterized in that the sulfonamide of the general formula

3 CO- NH-Y- (3y SO -NHz OR 7 urea, R-substituted carbamic acid ester, with thiocarbamic acid ester or carbamic acid halide, where R has the above values, followed by separation of the Target product by known methods or by translating it in salt by treatment with alkaline agents.