SE447106B - PROCEDURE FOR PREPARING 10-OXO-10, 11-DIHYDRO-5H-DIBENS / B, F / AZEPIN-5-CARBOXAMIDE - Google Patents

Description

10 15 20 -ZS 30 K3S 447 106 z The disadvantage of this in itself already cumbersome procedure for the production of the required starting material lies in particular in the relatively high consumption of bromine, used exclusively for the introduction and transformation of national groups.

These disadvantages are avoided in the context of the procedure the present invention by using the present invention. for the required starting material, which is prepared according to it German Offenlegungsschrift 2 S42 335 either by turnover of S-acetyl-SH-dibenzib, phazazepine with chlorine to 5-acetyl-10,11-dichloro- -10,11-dihydro-SH-dibenz [b, f7azepine, its conversion by a tertiary organic base, such as diisopropylethylamine, to S-acetyl- -10-chloro-SH-dibenz [b, f] azepine, followed by its hydrolysis by hydrobromic acid to 10-kkn <5H-dibenz [b, f7azepine, its turnover with phosgene to the corresponding 5-carbonyl chloride and finally its reaction with ammonia, or by adding chlorine to 5H-di- benzβ, f7azepine-5-carboxamide and treatment of obtained 10,11-di- chloro-10,11-dihydro-SH-dibenzob, f] azepine-S-carboxamide with a tertiary organic base, such as 1,5-diazabicycloyl.3.Q] non-5-ene.

From Helv. chim. Acta, vol 55, pp. 451-460 (1972) is a conversion of 2-oxo-3- (2-nitro-3-chlorophenyl) dissolved in methylene chloride - -5-chloro-5-hexenoic acid ethyl ester by means of sulfuric acid cooled to -15 ° C to 2,5-S-dioxo-3- (2-nitro-3-chlorophenyl) -hexanoic acid ethyl ester known.

In J. Amer. Chem. Soc. §§, 4290-91 (1966) have described one simple process for the production of cycloalkanones with various ring size, by in a useful nucleophilic compound ß-chloro- the allyl group is introduced, which by hydrolysis by formic acid or 90% sulfuric acid is converted to the corresponding saturated ketone.

Thus, e.g. 1- (2-chloroallyl) -indene by 97% formic acid and subsequent treatment with water to 3, S- (o-. -phenylene) -cyclohexanone. Depending on the starting material used structure, the use of 90% sulfuric acid at 0 ° C in instead of formic acid be more beneficial. Surprisingly, it has now been found that by means of according to the present invention, the hydrolysis of 10-chloro- -SH-dibenz [b, f] azepine-5-carboxamide to 10-oxo-10,11-dihydro-5H-di- benz fi b, f7azepine-5-carboxamide is carried out by concentrated sulfuric acid at normal temperature. With concentrated sulfuric acid a 90 to 96 percent, preferably a 96 percent 10 15 20 25 30 35 40 s 447 106 tig sulfuric acid. The reaction temperature is about 10-30 ° C, preferably typically at 1s-zs ° c.

It could not be expected that under the conditions of the process of the present invention does not contain the urea group would be attacked, since it is known that urea compounds lysed by aqueous acids, especially at elevated temperatures Peratur. This is the case from "Ber fl jme der Deutschen Chemischen Gesell- schaft "2, p. 397 (1878) known, that asymmetric diphenylurea when heated with sulfuric acid gives a blue solution, which caused by diphenylamine, since according to the Merck Index, published Rahway, N.J., U.S.A., 9, ed. (1976), vol diphenylamine with sulfuric acid a deep blue color.

The technological progress achieved with the new procedure further consists in the fact that the hydrolysis according to the invention is essentially by Merck & Co., Inc. occurs at room temperature, hence the risk of corrosion damage on used metallic reaction vessels is reduced, while the known hydrolysis process by means of mineral acids takes place in flow temperature, whereby the corrosion load becomes high enlarged.

On the other hand, by means of the method according to the invention 10-oxo-10,11-dihydro-5H-dibenzyl, f7azepine-S-carboxamide with a yield of 64% calculated on the starting material traded and with polite purity.

The following examples illustrate the process of the invention.

Temperatures are given in degrees Celsius.

Example. In a drying tube filled with calcium chloride through a In a round flask, stir a mixture of 0.5 g of 10-chloro-5H-dibenzene Lb, f] azepine-5-carboxamide and 5 ml of concentrated sulfuric acid (96- percent) for 10 minutes at room temperature, after which a clear yellow such solution is obtained. Stirring is continued for 76 hours at room temperature. temperature, whereby a clear brown solution is obtained. Reactional the mixture is poured onto 100 g of ice and 100 ml of methylene chloride, the the organic phase is separated, the aqueous solution is washed 4 times with 80 ml of methylene chloride each time, then the combined organic solutions (480 ml) are washed three times with semi-saturated aqueous sodium chloride solution, dried over sodium sulfate and evaporated to dryness under reduced pressure. Re- the column is recrystallized from methylene chloride / ether, after which it is obtained pure 10-oxo-10,11-dihydro-5H-dibenzyl, f] azepine-5-carboxamide with mp 213-215 ° C; yield calculated on traded starting material: 64% of theoretical yield.

Claims (1)

447 106 Patent claims Process for the preparation of 10-oxo-10,11-dihydro-5H-dibenz fib, thiazepine-5-carboxamide of the formula I || n (I), CONH is characterized in that with 90-96% sulfuric acid at a temperature of H% $ 0 ° C 10-chloro-SH-dibenzol íO \! O; O \ 'ü (n). Oš-x O <