IL38256A - Process for the preparation of 10-amino-10,11-dihydro-dibenzo(b,f)azepines and intermediates for use therein - Google Patents

Description

PROCESS FOR FOR USE THERE The present invention provides a new process for the of in which each X isa hydrogen atom or one chlorine and the othere are and R and which may be identical or are each hydrogen or of 1 to 5 carbon Israel Patent It is known from our that the compounds of formula in which each X is hydrogen possess valuable pharmacodynamic in they are very active on the central nervous as convulsive agents and The compounds of formula in which one X is chlorine possess similar pharmacodynamic The compounds of formula in which and X are as defined above and R represents a hydrogen atom have hitherto been prepared by reduction of oximes of the in which and X are as defined the oximes themselves being obtained from the corresponding the preparation of these which can be carried out in different requires numerous so that the synthesis of the compounds of formula via the oximes of formula is where it is desired to prepare compounds of the formula in which R is an alkyl it is necessary to alkylate the product resulting from the reduction of the The present invention provides a novel process for the preparation of the compounds ot from of the formulat in which and X are as defined which comprises reacting the compounds of formula with a hydroborating agent to produce organoboranes of the in which X and are as defined which are new and then subjecting the said organoboranes to the action of an aminating Preferably and R both represent a lower alkyl radical such as the hydroborating agent is an and the aminating agent is a chloroamine of the formula in which R is defined as The dibenzo of formula in which is alkyl of 1 to carbon atoms can be obtained by alkylation of the dibenzo azepines of formula in which is the latter are known and can be obtained from the corresponding The hydroborating agents which can be used for the first stage of the new process are those used for hydroborating olefinic in particular mixtures of alkali metal borohydrides and complexes of boron trifluoride with alkyl diboranes and These last compounds are particularly suitable because of their stability to heat and to hydrolysis and their high solubility in water and in numerous other polar A description of the methods of preparation and the properties of these aminoboranes can be found in various publications Berichte pages 928 et and Patent Dimethylaminoborane and diethylaminoborane are preferably The reaction may be carried out in a solvent for such such for diethyl a glycol ether or It takes place by under substantially equinolecular amounts of the compound of formula and the The reaction is accompanied by the liberation of the amine constituent of the which can be removed from the reaction medium by simple washing with The second stage of the process consists of replacing the boron of the organoborane of formula thus by a primary or secondary amine This treatment is carried out with chloramine or a of formula in which R is as defined preferably in aqueous other equivalent aminating such as acid of formula may also be The amount of chloramine employed corresponds substantially to the stoichiometric This second stage can be carried out directly on the reaction mixture resulting from the first without it being necessary to isolate the organoborane the first stage of may be carried out in the presence of a catalytic amount of a phenolic such as hydroquinone or The unconverted can then be recovered and The examples which follow illustrate the EXAMPLE 1 Preparation of and anhydrous toluene 45 are introduced into a 100 flask equipped with a dropping a reflux condenser protected by a calcium chloride guard and a nitrogen The mixture is heated under reflux at for 22 hours and is then allowed to quinone 6 is and the mixture is evaporated to dryness at under reduced pressure 1 mm The residue is then recrystallised from a ether containing hydroquinone A white crystalline product 360 melting at and having a molecular weight of 221 is it is identified by and spectrography band at 2300 as of The above boron derivative toluene 15 and a 2 sodium hydroxide solution are introduced into a 100 flask equipped with a reflux condenser and a dropping A solution of chloraraine prepared by reaction of 10 N concentrated ammonia with a sodium hypochlorite solution containing litre 22 is Stirring is continued for 2 hours at about and the aqueous layer is then decanted and extracted with toluene times 10 The combined toluene extracts are washed with water until neutral and then extracted with 2N hydrochloric acid times lO The hydrochloric acid extracts are washed with diethyl ether and then rendered alkaline by adding a ION aqueous sodium hydroxide solution with The aqueous layer is then extracted with diethyl ether x and the ether phpse is dried over sodium filtered and precipitate The thus obtained weighs g after drying and melts at It is EXAMPLE 2 and freshly distilled toluene are introduced into a 500 flask equipped with a dropping funnel and a and protected against moisture by a calcium chloride guard The solution is heated under reflux for 22 hours under a nitrogen atmosphere and then A 2N aqueous sodium hydroxide solution is then run in followed by an N aqueous methylchloramine solution 190 the addition of which takes 9 The mixture is stirred one hour and then The organic layer is washed with water until it has a pH of 6 and is then extracted with 2N hydrochloric acid 5 times dried over sodium filtered and Recrystallisation of the residue from petroleum ether yields some unconverted The aqueous acid solution is rendered alkaline by adding 2N sodium hydroxide After extraction with diethyltether times drying the extracts over potassium treating them with decolourising filtering and evaporating the a yellowish oil identified as is obtained in a yield of Methylchloramine can be prepared by adding an aqueous solution of hypochlorite to an aqueous solution of methylamxne in accordance with the process described by 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Claims (1)

1. 58256/2 We Claims t« Process for the preparation of azepinea o the formulas in which each X is hydrogen or one is chlorine and the others are hydrogen and R and R^ are each hydrogen or alkyl of 1 to 5 carton atoms which comprises arolmting an organoborane of the formulas with an aminating agent selected from the group consisting of chloramines of the general formula RHBCl. wherein R is ¾defined above, and 0-hydroxylamine~ sulphoric acid* 2* Process according to claim 1 in which the amination is effected with a ehloramine of the fortaula ENBCl in which R is as defined in claim 1, 5. Process aocording to claim 1 or 2 in which the organoborane has been produced by reaction of a dibenzo£b,f]aeepine of the formulas in which Rf and X are as defined in claim 1, with a hydroborating agent. 4· ΡΓΟΟΘΒΒ according to claim 3 in which the hydroborating agent is an aminoborane. 5· Process according to claim 4 in which the aminoborane is dimethylamiiioboran© or diethylaminoborane. 6» Process according to any of claims 1 to 5 in which each X is hydrogen, is methyl and R is hydrogen or methyl* 7· Process according to claim 1 substantially as described in Example 1 or 2. 8. An organoborano of the formula: in which each X is hydrogen or one is chlorine and the other is hydrogen and is hydrogen or alkyl of 1 to 5 carbon atoms. 10. Process for the production of an organoborane as claimed in claim 8 which comprises reacting a dibenzo[b.flazepine of the formula: in which and X are as defined in claim 8,with a hydroborating agent. 11. Process according to claim 10 in which the hydroborating agent is an aminoborane. 12. Process according to claim 11 in which the aminoborane is dimethylaminoborane or diethylaminoborane. Examples.; 1 or 2. 14. Organoboranes as claimed in claim 8 when prepared by a process claimed in any of claims 10 to 13. a process as claimed in any of claims 1 to 7.