NO153368B - PROCEDURE FOR THE PREPARATION OF 10-OXO-10,11-DIHYDRO-5H-DIBENZ (B, F) -ASEPINE-5-CARBOXAMIDE - Google Patents

Description

The object of the invention is a new and advantageous process for the preparation of 1O-oxo-10,11-dihydro-5H-dibenz(b,f)azepine-5-<k>arboxamide with the formula

in that the method is characterized by the fact that 10-chloro-5H-dibenz (b, f) azepine-5-carboxamide with the formula

is hydrolyzed using 90-96% sulfuric acid at a temperature of 10-30°C.

From German off. publication no. 2.01 1.087, a method for the production of 10-oxo-10,11-dihydro-5H-dibenz(b,f,)azepine-5-carboxamide is known, wherein 10-methoxy-5H-dibenz(b, f) azepine-5-carboxamide is hydrolysed with the aid of a mineral acid, e.g. dilute hydrochloric acid at reflux temperature. The production of this starting material takes place as indicated by reaction of 10-methoxy-5H-dibenz(b,f)azepine with phosgene or corresponding 5-carbonyl chloride and its reaction with ammonia to 10-methoxy-5H-dibenz(b,f)azepine- 5-carboxamide. The necessary 10-methoxy-5H-dibenz(b,f)-azepine again, according to indications in Belgian patent no. 597,793, is available from 5-acetyl-5H-dibenz(b,f)-azepine and the derivative by means of addition of bromine, preparable 5-acetyl-10,11-dihydro-10,11-dibromo-5H-dibenz(b,f)-azepine, its transsaturation with potassium hydroxide to 5-acetyl-10-bromo-5H-dibenz (b, f)azepine and its reactions with sodium methylate or direct reaction

of the above-mentioned bromine addition product, with at least the double molar amount, preferably a larger excess of sodium methylate.

Disadvantages of this, in and of itself, already cumbersome method for producing the necessary starting material, lie in particular also in the relatively high consumption of bromine, which only serves for the introduction and conversion of functional groups.

These disadvantages are avoided in connection with the method according to the invention, by using the necessary starting material which, according to DOS 2,542,335, is either available by reacting 5-acetyl-5H-diben;z (b,f)azepine with chlorine to 5-acetyl -10,11-dichloro-10,11, dihydro-5H-diben:z(b,f)azepine, its conversion by means of a tertiary organic base, such as diisopropylethylamine, to 5-acetyl-10-chloro-5H-dibenz(b,f)azepine, followed by its hydrolysis with hydrobromic acid to 10-chloro-5H-dibenz(b,f)azepine, its reaction with phosgene to the corresponding 5-carbonyl chloride and finally its reaction with ammonia, or by addition of chlorine to 5H-dibenz (b,f)azepine-5-carboxamide and treatment of the formed 10,11-dichloro-10,11-dihydro-5H -dibenz(b,f)-azepine-5-carboxamide, with a tertiary organic base, such as e.g. 1,5-diasabicyclo(4,3,0)non-5-ene.

From Heiv.chim.Acta Vol. 55, pages 451-60, (1972),

it is known the conversion of 2-oxo-3-(2-nitro-3-chloro-phenyl)-5-chloro-5-hexenoic acid ethyl ester dissolved in methylene chloride by means of -15°C cooled concentrated sulfuric acid to 2,5- dioxo-3-chlorophenyl)hexane acid ethyl ester.

In J. Amer. Chem. Sos. 88, 4290-91 (1966) one is mentioned

simple method for the preparation of cycloalkanones of different ring sizes, by introducing the B-chlorallyl group into a suitable nucleophilic compound which, by hydrolysis with the aid of formic acid or 90% sulfuric acid, is converted into the corresponding saturated ketone. Thus, e.g. 1 -(2-chloro-allyl)-indene by

using 97% formic acid and subsequent treatment with water to 3,5-(o-phenylene)-cyclohexanone.

Depending on the starting material structure used, the use of 97% sulfuric acid at 0°C may be more advantageous instead of formic acid.

Surprisingly, it was now found that with the method according to the invention, the hydrolysis of 10-chloro-5H-dibene I(b,f)azepine 5-carboxamide is carried out to 10-oxo-10,11-dihydro-5H-dibene z(b,f )azepin-5-

carboxamide using concentrated sulfuric acid at normal temperatures By concentrated sulfuric acid is meant here 90-96% preferably 96% sulfuric acid. The reaction temperature is e.g. at 10-30°C, preferably at 15-25°C.

It could not be expected that under the conditions of the method according to the invention the urea groups would not be attacked, as it is known that urea compounds hydrolyze with the aid of aqueous acids, especially at too high a temperature. Thus it is from the "Berichte der Deutschen Chemischen Gesellschaft"

9 (1978), page 397, it is known that unsymmetrical diphenylurea when heated with sulfuric acid gives a blue solution, which is evidently caused by diphenyl-

amine, for, according to the Merck Index published by Merck & Co.,

Inc. Rahway, N.J. (USA), 9th ed., (1976), p

443-444 diphenylamine gives a deep blue color with sulfuric acid. The technical progress achieved with the new method further consists in the fact that the hydrolysis according to the invention essentially takes place at room temperature, so that the risk of corrosion damage to the metallic reaction vessels used is reduced, while the known hydrolysis method takes place with the help of mineral acid at reflux temperature where the corrosion load is increased greatly.

In contrast, the method according to the invention obtains 10-oxo-10,11-dihydro-5H-dibenz(b,f)azepine-5-carboxamide in a yield of 64%, referred to reacted starting material, and in good purity.

The invention shall be explained in more detail by means of

the following example.

Example

Stir the mixture of 0.5g of 10-chloro-5H-dibenz(b,f)azepine-5-carboxamide and 5 ml of concentrated sulfuric acid (96%) in a round flask closed using a drying tube filled with calcium chloride for 10 minutes at room temperature, after which a clear yellowish solution is obtained. Stirring is continued over 76 hours at room temperature, as a clear, brown solution is formed. The reaction mixture is poured onto 100 g of ice and 100 ml of methylene chloride, the organic phase is separated, the aqueous solution is washed four times with 80 ml of methylene chloride each time, and the finished organic solutions (480 ml) are washed three times with half-saturated aqueous sodium chloride solution, dried over sodium sulfate and evaporate under reduced pressure to dryness.

The residue is recrystallized from methylene chloride/ether, after which pure 10-oxo-11-dihydro-5H-dibenz(b,f)azepine-5-carboxamide of melting point 213-215°C is obtained. Yield referred to converted starting material 6 4% of the theoretical.

Claims (1)

1. Process for the preparation of 10-oxb-10,11-dihydro-5H-dibenz(b,f)azepine-5-carboxamide with formula characterized in that 10-chloro-5H-dibenz(b,f)azepine-5-carboxamide with formula is hydrolyzed using 96% sulfuric acid at a temperature of 10-30°C.