CH454164A - Process for the preparation of basic dibenzooxepine or dibenzothiepin derivatives and their salts - Google Patents

Description

  

  
 



  Process for the preparation of basic dibenzooxepine or dibenzothiepin derivatives and their salts
The subject of Swiss patent No. 419 172 is a process for the preparation of basic dibenzo ± b, ei-oxepin or thiepine derivatives of the formula I,
EMI1.1
 in which X is an oxygen or sulfur atom, R1 and R2 are hydrogen, halogen, trifluoromethyl, alkyl, alkoxy, alkylmercaptox or acylHR radicals, R3 is hydrogen or a lower alkyl radical and A is a basic group, their salts, which is characterized by that one dibeno- [b, e] -oxepin- resp.

   -thi epin-1 1-one of formula II
EMI1.2
 with Grignard compounds of the formula Hal-Mg-CH2 CH (R) -A and the reaction product is treated with what serabspaltendea agents, whereupon the alkylidene compounds (I) obtained are converted into their salts or quaternary ammonium compounds, if desired. Preferred basic radicals A here are tertiary amino groups, e.g. B. dialkylamino groups, or heterocyclic radicals such as piperidino, pyrrolidino, morpholino and piperazino radicals, which can optionally also be substituted.



   It has now been found that compounds of the above formula 1 which carry a monoalkylamino group -NHR4 as the basic radical A could be prepared in a particularly advantageous manner by benzyl compounds of the formula III,
EMI1.3
 in which R4 denotes a lower alkyl group, is reacted with a halogenamic acid ester Hal-COOR (R = lower alkyl radical) and from the compounds of the formula IV
EMI1.4
 the carbalkoxy group is split off hydrolytically.



   The reaction of the benzyl compounds (III) with the haloformic acid esters (e.g. ethyl chloroformate) is carried out by heating in an inert solvent, e.g. B. benzene causes. The N-carboxy compounds of the formula IV can be processed further without special isolation and purification; the hydrolytic cleavage of the carbalkoxy group can be effected both in an acidic and in an alkaline medium.



  The monoalkylaminoalkylidene compounds obtained can, if desired, be converted into their salts in a customary manner.



   The benzyl compounds of the formula III required as starting materials are new; they can be produced by the process described in the patent mentioned.



   Example I.
11- (3'-Monomethylamino-propylidene) -dibenzo [b, e] -thiepin
18.7 g (0.05 mol) of 11- [3 '- (N-benzyl-N-methyl) aminorprpyliden] -dibenzo- [b, e] -thiepine and 16.5 g (0.165 mol) of ethyl chloroformate are heated in Boil 40 ml of benzene for 5 hours and then remove the volatile components in a vacuum on a water bath. The resulting residue of crude 11- [3 '- (N-carbethoxy-N-methyl) aminopropylidene] -dibenzo- [b, e] -thiepin is refluxed in 100 ml of glacial acetic acid and 100 ml of 48% hydrobromic acid for 5 hours The contents of the flask are reduced to a small volume in vacuo. Water and ether are added, the aqueous acidic components are separated off, made alkaline with dilute sodium hydroxide solution and extracted with methylene chloride.

   The combined and dried methylene chloride components are freed from the solvent and the evaporation residue is distilled in a high vacuum.



  Yield: 10.6 g (= 75% of theory) of 11- (3'-monomethylaminopropylidene) -dibenzo- [b, e] -thiepin with a boiling point of 0.1 1.77 to 181 C; M.p. 70-72 ° C. (after trituration with ligroin).



   The hydrochloride, which is produced in the usual way in ether with ethereal hydrochloric acid, melts at 234-235 C (from isopropanol).



   Example 2
11- (3'-Monomethylamino-propylidene) -dibenzo [b, e] -oxepine
15 g of 11- [3 '- (N-benzyl-N-methyl) aminopropylidene] dibenzo- [b, e] -oxepine and 14 g of ethyl chloroformate in 35 ml of benzene are heated to boiling for 5 hours and then removed in vacuo on the Water bath the volatile components. The crude N-carbethoxy-N-methyl-aminopropylidene compound obtained in this way (14 g) is refluxed for 5 hours in a solution of 16 g of potassium hydroxide in 60 ml of 96% strength ethanol. After adding dilute hydrochloric acid and ether, the aqueous-acidic components are separated off. made alkaline with dilute potassium hydroxide and extracted with ether. The dried extract, freed from solvent, gives 7.2 g of 11- (3'-monomethylamino-propylidene) -dibenzo- [b, e] -oxepine with a boiling point of 0.05 mm / 158-164 ° C. and melting point on high vacuum distillation. 65-67 C (from ligroin).

   Yield; 64.5% d. Th.



  (based on the N-benzyl-N-methyl-aminopropylidene compound used). The hydrochloride prepared in the usual way has a melting point of 235-236 ° C. (from isopropanol or dioxane / ether).

 

Claims (1)

PATENT CLAIM Process for the preparation of basic dibenzo- [b, e] oxepin or thiepin derivatives of the formula I, EMI2.1 in which X is an oxygen or sulfur atom, R1 and R2 are hydrogen, halogen, trifluoromethyl, alkyl, alkoxy, alkylmercatpo or acyl radicals, R3 is hydrogen or a lower alkyl radical and A is a monoalkyl amino group of the formula -NH-R4 mean, where R4 represents a lower alkyl group, characterized in that benzyl compounds of the formula III EMI2.2 with a haloformic acid ester Hal-COOR (R = lower alkyl radical to react and from the resulting N-carbalkoxy compounds of formula IV EMI2.3 the carbalkoxy group is split off hydrolytically. SUBClaim Process according to claim, characterized in that the monoalkylamino alkylidene compounds (I) obtained are converted into their salts.