SI8911364A8 - Process for obtaining novel intermediate useful for preparing oxo compound - Google Patents

Description

A process for the preparation of a new intermediate useful in the process for the preparation of an oxo compound

FIELD OF THE INVENTION

The invention relates to the field of organic chemical synthesis and relates to a process for the preparation of 5-cyano-10-isonitroso-10,11 dihydro-5H-dibenz / b, f / azepine of the formula

NOH

CN (VI) which can be used in a new and technically advanced process for the preparation of 5-carbamoyl-10-oxo-10,11-dihydro-5H-dibenz / b, f / azepine of formula III.

The entire reaction scheme for the preparation of 5-carbamoyl-10-oxo10,11-dihydro-5H-dibenz / b, f / azepine is as follows:

A technical problem

There was a need to prepare a new intermediate for the more technically advanced preparation of the oxo compound of formula III, following a technologically fatal process.

The state of the art

The intermediates of formula (VI) are novel compounds and therefore no processes exist for them.

From DE-OS 2 011 087 0® with ³¹ ® ³¹ process for the preparation of 5carbamyl-10-oxo-10, 11-dihydro-5H-dibenz [b, f] azepine by hydrolysis of 10-methoxy-5H-dibenz [b, f ] azepine-5-carboxamide using aqueous mineral acids. The availability of this starting material is given in BE-PS no. 597 795, according to which e.g. 5acetyl-5H-dibenz [b, f Jazepine is brominated in 5-acetyl-10,11-dihydro-10,11-dibromo-5H-dibenz [b, f] azepine, which is converted to 5acetyl-10-bromo-5H-dibenz [b, f Jazepin and from this they prepare 10methoxy-i? H-dibenz [b, f Jazepin. This is then treated with phosgene to the corresponding carbonyl chloride, from which the ammonia metabolite gives 3 ° 10-methoxy-S-dibenzCb ^ fHazepine-5-carboxamide. Compared to this preparation process, which is disadvantageous because it has to be carried out for a very long time due to the relatively S-tAvi intermediate rates, and also because of the high consumption of bromine, which serves only for intermediate conversion of the intermediate products, of the invention from only a few steps of the process, which are carried out in a simple and transparent manner, avoiding expensive reagents, and in addition lead to a high yield to the final product of formula III, which is obtained in excellent purity.

Description of solution to a technical problem with implementation examples

The process of the invention is carried out such that 5-cyano-10nitro-5H-dibenz / b, f / azepine of the formula

is reduced by catalytically activated or nascent hydrogen.

The resulting 5-cyano-10-isonitroso-10,11-dihydro-5H-dibenz / b, f / azepine can then be hydrolyzed to give 5-carbamoyl-10-oxo-10,11-dihydro-5H-dibenz / b , f / azepine in pure form.

The starting material of formula II can be obtained from 5-cyano-5Hdibenz / b, f / azepine by treatment with conventional nitriding agents, e.g. nitrous trioxide (N ^ O), optionally in admixture with kits, e.g. air _? or by the use of nitrous tetroxide (N ^ O ^) or the recovery of such compounds, and additionally by the use of nitric acid. The metabolism is carried out in a suitable solvent, in particular one that is stable under stable nitration conditions and does not lead to adverse reactions with the nitride agent. In particular, lower alkanecarboxylic or halogenated arylcarbocarboxylic acids, but not acidic with up to 4 carbon atoms each, e.g. trifluoro- or three-chloroacetic acid, optionally in admixture with water, or their anb2dridL, eg acetic anhydride, propionic, n-butyric, isobutyric or trifluoroacetic acid, or mixtures of such carboxylic acids with the corresponding anhydrides. According to a preferred embodiment of the process according to the invention, the solvents used for the anhydride.e of the aforementioned alaccarboxylic acids, e.g. acetanchicLrid, optionally in admixture with lowering unitscarboxyl k-ί gl -ϊno, e.g. acetic acid.

The ratio of starting material to the amount of solvent used (weight / volume) can vary within wide limits. The ratio of starting material to solvent in the range of 1: 5 to 1:50 is advantageously used. The reaction temperature is in the range of about 0 to 120 °, in particular 40 to 80 °.

The reduction of the nitro group in a compound of formula II is carried out e.g. by means of zinc powder in acid, e.g. a lower alkanecarboxylic acid of said species, such as acetic acid, optionally in the presence of an inert solvent, than a lower alkanol of said species, e.g. ethanol, or by hydrogen in the presence of an 'anhydrous catalyst, such as a precious metal catalyst, e.g. a palladium catalyst on charcoal, in a suitable solvent, e.g. a solvent of an aromatic character, e.g. pyridine, and the resulting 5-cyano-10-isonitroso-10,11-dihydro-5H-dibenz / b, f / azepine of formula VI is isolated in pure form. It is obtained with good profit and excellent purity. The compound is novel and has not been described in the literature. The compound of formula VI can then be easily hydrolyzed and the resulting finished product of formula III isolated in pure form. Following this reaction variant, the 5-cyano group as well as the 10-isonitroso group are hydrolyzed in the compound of formula VI in the same reaction sequence. Thus, e.g. in the compound of formula VI a 10-isonitrose group by acidic agents, e.g. as stated, e.g. with a mineral acid, such as hydrochloric acid, is converted to a 10-oxo group and then the reaction mixture, e.g. as described, hydrolyzed with an acid, e.g. a mineral acid such as sulfuric or polyphosphoric acid, or with a carboxylic acid, e.g. lower alkanecarboxylic or halogenoalkanecarboxylic acid, such as acetic or trifluoroacetic acid, or Lewis acid, such as boron trifluoride in the presence of a carboxylic acid, e.g. acetic acids, or mixtures of such acids, optionally in the presence of a further inert solvent such as a lower alkanol of up to 5 carbon atoms, such as methanol or ethanol, and the final product of formula III is isolated in pure form.

The following examples serve to illustrate the invention; temperatures are given in degrees Celsius.

EXAMPLE 1

1.0 g (0.004 mol) of 5-cyano-10-nitro-5H-dibenz [b, f] azepine were dissolved at 60 ° in a mixture of 40 ml of ethanol and. 20 ml of acetic acid and vigorously stirring for 10 minutes add 2.0 g of zinc powder. The mixture is allowed to stir for 15 minutes, filtered undissolved in warm water and washed with ethanol and water. The filtrate was evaporated to dryness and taken up in 5θ ml of water. After suction, washing with water and drying, crude 5-cyano-10 Oisonitroso-10, 11-dihydro-5H-dibenz [b, f] azepine is obtained. melts at 185 ° after decaying from ethanol at decay. The analytical and spectroscopic data are consistent with the assumed structure. Yield: 0.9 g, 95% theory.

The starting material can be obtained as follows:

6.0 g (0.02 mol) of 5-cyano-5H-dibenz [b, f3azepine are dissolved in a mixture of 80 ml of acetic acid anhydride and 20 ml of acetic acid. Heat to 50 [deg.] And a solution of 5.6 g (0.08 mol) of sodium nitrite in 10 ml of water is added dropwise over 1 1/2 hours without allowing the temperature to rise above 55 [deg.]. It is kept at 5θ ° for 2 hours and then the solvent is distilled off under reduced pressure and a bath temperature of 50 °. The residue was digested twice with 100 ml of ice water each and taken up in 80 ml of ethanol. After an evening condition at 0 °, suction off the separated yellow crystals and wash with little ethanol. The resulting 5-cyano-10-nitro-5H-dibenzCb, f] azepine melts at 175 to 176 ° on decay.

Yield: 5.2 g, 72% of theory.

The analytical and spectroscopic data are consistent with the assumed structure.

EXAMPLE 2 g (0.19 mol) of 5-cyano-10-nitro-5H-dibenz [b, f] azepine was dissolved in 500 ml of pyridine, and after addition of 10 g of palladium on charcoal (5%) was hydrogenated at room temperature. and normal pressure. After 2 hours, the hydrogen uptake was 7960 ml (95% of theory,) and the hydrogenation was gone. The catalyst was filtered off, the solvent was evaporated in vacuo and the crude product obtained was recrystallized from methanol / water to give 5-cyano-10-isonitroso 10,11-dihydro-5H-dibenzCb, f] azepyr.

Yield: 55.6 g, 75.2% of theory.

EXAMPLE 3

2.5 g (0.01 mol) of 5-cyano-10-isonitroso-10,11-dihydro5H-dibenz [b, f] azepine were suspended in a mixture of 25 ml of toluene, ml of ethanol and 10 ml of conc. hydrochloric acids. The suspension of 50 mi is stirred at 5θθ, the toluene phase is determined and it is vacuum in ηρarin »? to dryness. The crystalline residue was suspended in 10 ml of isopropanol, filtered off with suction and washed twice with isopropanol to give 5-cyano-10-oxo-10,11-dihydro-5H-dibenz [b, f] azepine.

Yield: 0.8 g, 55% theory.

EXAMPLE 4

To a suspension of 44.7 6 (O »O5 mol) of 5-cyano-40-oxo-40,44 dihydro-5H-dibenz [b, f] azepine in 60 ml of acetic acid

40.5 S (° »θ55 moles) of the BP ^ complex. 2 CH ^ COOH and allow the temperature to rise to 55 ° without external cooling, slowly dissolving the starting material. After about 4 hours the BP ^ -duct begins to crystallize. The mixture was stirred at peat tenperature for 4 hours, filtered and washed with acetic acid. The intermediate was suspended in 400 ml of water and stirred for 4 hours after addition of sodium acetate to pH 6. Suction extraction with water gave 9.0 g of 5-carbamyl ~ 4O-oxo-4O, 44-dihydro-5H-dibenz [b, f] azepine, which is identical to the IB material on the basis of the IB spectrum. a further 4.2 g of product can be obtained after evaporation with fractional crystallization from methanol / water.

Claims (3)

PATENT APPLICATIONS A process for the preparation of a novel intermediate useful in the process for the preparation of an oxo compound of formula (VI), characterized in that the 5-cyano-10-nitro-5H-dibenz / b, f / azepine sf ormula is reduced by catalytic of activated or nascent hydrogen. A process according to claim 1, characterized in that the reduction is carried out by treatment with hydrogen in the presence of a palladium carbon catalyst in an aromatic solvent such as pyridine. 3- Process according to claim 1, characterized in that the reduction is carried out by treatment with zinc in an acidic environment.