SU448641A3 - Method for preparing benzenesulfonylurea - Google Patents

Description

X

 -NH- SNO-SNg

7

where Z is hydrogen, alkoxy with 1-4 carbon atoms, allyloxy, methoxymethoxy, ethoxymethoxy;

X is halogen, preferably chlorine, methyl, trifluoromethyl, methoxy group or hydrogen (if Z is alkoxy or alkenoxy).

A known method for producing benzenesulfonylurea by reacting a sulfonamide of the formula

-Sog-TSH-SO

(I)

bamic acid containing a cycloheptyl residue, n benzosulfonamidov, co5 holding in the position to the sulfonamide group Deputy

L4) -NH-OH.-CK2-,

ten

Z or their salts are reacted with cycloheptyl isocyanate, cycloheptylcarbamic acid ester, cycloheptylthiolcarbamic acid ester, cycloheptylcarbamic acid halides or cycloheptylurea. The product is isolated by conventional means or converted into salt by treatment with alkaline agents.

. ™ - ™ VY

NZSO

OCHN ASCI CO-C1 X. Go-BN

C1

TG T.

 wasps, l, (“)

 co 01 co cl co

OCH (SNZ) g OCHN OS4N9 (p)

UNGOCN: OCHgOCzHg

OSGND

CO-Bg. COCOCH In used as starting compounds, the residue of formula (I) 7 Vooi can have the following meanings

The preparation of the starting materials should be carried out according to known methods. Thus, for example, p-phenylethylamine can be acylated with an acyl chloride of the formula

and convert the resulting acylamidoethylbenzene compounds by treatment with chlorosulfonic acid into the corresponding acylamidoethylbenzenesulfonyl chlorides, which are converted with ammonia to the corresponding sulfamides.

Esters of benzenesulfonylcarbamic acid or thiolcarbamic acid may contain an alkyl, or aryl, or heterocyclic residue in the alcohol components. Since this residue is cleaved off during the reaction, its chemical structure does not affect the nature of the final products and

can therefore vary within wide limits. To the same extent, this refers to cycloheptyl-substituted carbamic esters or the corresponding thiol-carbamic esters. Cycloheptylurea can also have the second atom

nitrogen with acyl or aryl substituents that are removed during the reaction or subsequent hydrolysis. Chlorides are recommended primarily as carbamipic acid halides.

Substitution can be carried out with or without solvents at room or elevated temperatures.

Alkaline agents such as alkali oxides, alkaline earth metals, carbonates and bicarbonates can be used to form salts.

Example 1. M- {4-p- (2-methoxy-5-methylbenzamido) -ethyl-benzenesulfonyl} -Y - cycloheptylurea.

14 g of (2-methoxy-5-methylbenzamido) ethyl benzene sulphamide (m.p. 191 ° C) and 1.7 g of NaOH are dissolved in 50 ml of water in 150 ml of acetone and cooled to O-5 ° C. while stirring dropwise, 4.5 g of cycloheptyl isocyanate and stirring again at room temperature for 3 hours. The mixture is acidified with dilute hydrochloric acid and acetone is removed, and the substance is precipitated from 1% NHiOH. After suctioning, N- {4 p- (2-methoxy-5-methylbenzamido) -til-benzenesulfonyl} -H-cycloheptylurea is obtained, which after recrystallization from methanol and water melts at 166 ° C.

Similarly, they are obtained from (2-methoxy-5bromobenzamido) - ethylbenzenesulfonamide (mp 223-224 ° C) L - {4- | 3- (2-methoxy-5-bromobenzamido) ethyl-benzenesulfonyl} -Y - cycloheptylurea with t. PL. 150 ° С (from methanol and water), from (2,5-dimethoxybenzamido) ethyl benzene sulfamide (mp 169 ° С) N- {4 р- (2,5-dimethoxybenzamido) ethyl ethyl benzenesulfonyl} -M - cycloheptylurea with m. pl. 101 ° C (from methanol and water), from (2-allyloxy-5 - chlorobenzamido) -ethyl - benzenesulfamide (t. 183 ° C) M- {4- p- (2-allyloxy-5chlorobenzamido) - ethyl benzene sulphonyl} -cycycloheptyl urea with m. pl. 151 ° C (from methanol and water), from 4-) 3- (2-ethoxy-5-chlorobenzamido) -ethyl-benzenesulfamide (mp. 174 ° C) N- {4- p- (2-ethoxy- 5 - Chlorobenzamido) -ethyl benzenesulfonyl} -Y - cyclohexylurea with m.p. 140 ° C (from methanol and water).

Example 2. N- {4-p- (2-methoxy - 5-chlorobenzamido) -ethyl-benzenesulfonyl} -Y - cycloheptylurea.

3.9 g (2-methoxy-5-chlorobenzamido) ethyl benzene sulphamide sodium and 4.4 g of N-cycloheptylcarbamic acid phenyl ester are dissolved in 100 ml of dimethylformamide. Heat for 45 minutes to 110 ° C, allow to cool and add approximately 0.5% aqueous ammonia solution. The undissolved precipitate is filtered off and the filtrate is acidified. The precipitated crystalline precipitate of M- {4- | 3- (2-methoxy-5-chloro-benzamido) -ethyl-benzenesulfonyl} -Y-cycloheptylurea is sucked off, washed, and dried. After recrystallization from methanol, the solution melts at 140 ° C.

Example 3. M- {4-p- (2-methoxy-5-chlorobenzamido) -ethyl-benzenesulfonyl} -Y - cycloheptylurea.

3.9 g of (2-methoxy-5-chlorobenzamido) ethyl benzene sulphamide sodium and 4.26 g of cycloheptylurea, m.p. 187 ° C is well mixed in a mortar and heated for 10 minutes in an Erlenmeyer flask to 200 ° C in a preheated oil bath. After

X

f С О -МТ- СН 2 - о rNK- С О -M-t - / j /

where Z is hydrogen, alkoxy group with 1-4 carbon atoms, allyloxy, methoxymethoxy, ethoxymethoxy group;

cooling the melt is treated with approximately 0.5% ammonia and heated in a steam bath. The filtrate is filtered and acidified. The precipitation is sucked off and treated with 0.5% ammonia. After re-acidification of the filtrate, the resulting precipitate is filtered off ((- methoxy - 5 chlorobenzamido) ethyl) benzenesulfonyl N-cycloheptylurea, dried and recrystallized from methanol. The substance melts at 140 ° C.

Example 4. L- {4-p- (2-methoxy-5-chlorobenzamido) -ethyl-benzenesulfonyl} -N-cycloheptylurea.

3.9 g of (2-methoxy-5-chlorobenzamido) ethyl benzene sulphamide sodium and 3.7 g of N-acetyl-1x-cycloheptyl urea are heated in 100 ml of dimethylformamide to 110 ° C for 2 hours.

The resulting solution is concentrated in vacuo to 2/3 volume, then mixed with water and hydrochloric acid. Sucked off and treated with 0.5% aqueous solution of ammonia. After filtration, the filtrate is acidified and the resulting precipitate, - {4-p- (2-methoxy-5-chlorobenzamido) -ethyl benzenesulfonyl} -N-cycloentyl urea, is sucked off, washed and dried. After recrystallization from methanol and water, N- {4- p- (2methoxy-5-chlorobenzamido) -ethyl-benzenesulfonyl} -N-cycloheptylurea with m.p. 140 ° C. Example 5. M- {4- p- (3-chlorobenzamido) ethyl benzosulfonyl} -1 - cycloheptylurea.

3.0 g of (3-chlorobenzamido) sodium ethylbenzenesulfamide, 5.9 g N, N-diphenyl-N-cycloheptylurea and 100 ml of dimethylformamide are heated to 110 ° C for 45 minutes (after a few minutes a clear solution is obtained). Leave to cool, add water and add 0.5% ammonia solution. The filtrate is filtered and acidified. The resulting precipitate is filtered off with suction and treated with a 0.5% ammonia solution. After

filtration and acidification of the filtrate get a crystalline precipitate of M- {4- p- (3-chlorobenzamido) -ethyl-benzene sulfonyl} -N - cycloheptylurea, which is sucked off, washed and dried first in air,

and then in an oven at 60 ° C. After recrystallization from methanol and water, the substance melts at 162 ° C.

The subject of the invention. A process for the preparation of benzenesulfonylureas of the formula

kT Н1ППЛЛ7 ПК1

X is halogen, preferably chlorine, methyl, trifluoromethyl, methoxygroup or hydrogen (if Z is an alkoxy or alkepoxy group).

about tl and that the benzenesulfamide formula

X

-co-NH- CH2-CH2: jVsoo-K4 ..

or its salts are reacted with cycloheptylisocyanate, cyclohetylcarbamic acid ester, cycloheptylthiolcarbamic acid ester, cycloheptylcarbamic acid halides or cycloheptylurea and the reaction product is isolated by conventional means or converted into a salt by treatment with alkaline agents.