Patent GB-1163485-A (GB)
Title: Dibenzothiepine Derivatives and their preparation
Inventor: FOUCHE JEAN CLEMENT LOUIS
IPC: C07D337/14
Filed: 1967-08-16
Abstract: 1,163,485. Dibenzo[b,f]thiepines. RHONEPOULENC S.A. 16 Aug., 1967 [17 Aug., 1966 (2)], No. 37786/67. Heading C2C. Novel compounds (including acid addition salts thereof and when R<SP>1</SP> is other than a hydrogen atom quaternary ammonium derivatives thereof) of the general Formula I wherein X represents a hydrogen or halogen atom or an alkyl, alkoxy or alkylthio radical, the symbols R each represent a hydrogen atom in which case Z represents the piperidyl radical II in which R<SP>1</SP> represents a hydrogen atom or an alkyl or phenylalkyl radical in which the phenyl nucleus is optionally substituted by one or more halogen atoms or alkyl, alkoxy, amino or alkylamino radicals, or, the symbols R together form a valence bond in which case Z represents the above piperidyl radical or the 1,2,3,6-tetrahydro-pyridyl radical III the alkyl radicals and the alkyl portions of the various other radicals each containing from 1 to 5 carbons, are prepared: (a) by dehydration of an intermediate compound of the general Formula IV (b) by reduction of an intermediate compound of the general Formula V wherein Y represents a reactive ester residue, e.g. a halogen atom or a sulphuric or sulphonic ester residue, and R<SP>2</SP> represents an alkyl radical or a phenylalkyl radical optionally substituted as described above, with an alkali metal borohydride, thus affording products in which the symbols R together form a valence bond and Z represents a 1-substituted 1,2,3,6-tetrahydropyridyl radical; (c) by hydrogenation of a compound V, thus affording products in which the symbols R each represent hydrogen atoms and Z represents an N-substituted piperidyl radical; (d) by reacting a compound I in which R<SP>1</SP> represents a hydrogen atom with the reactive ester Y-R<SP>2</SP> and (e) by dealkylation of a compound I in which R<SP>1</SP> is other than a hydrogen atom. 2 - (4 - Chlorophenylthio) - benzyl alcohol { obtained by the action of excess LiBH 4  on methyl 2 - (4 - chloro - phenylthio) benzoate, said benzoate arising from the corresponding free acid which in turn is derived from 2-iodobenzoic acid and 4-chlorothiophenol } treated with SOCl 2  yields the corresponding -benzyl chloride which is converted to 2-(4-chlorophenylthio) phenylacetic acid via the benzyl nitrite. Treatment of the foregoing acid with polyphosphorio acid at 130‹ C. affords 2-chloro-11-oxo-10,11- dihydrodibenzo[b,f]thiepine which reacts with 4 - pyridyl - lithium to yield 2 - chloro - 11 - hydroxy - 11 - (4 - pyridyl) - 10,11 - dihydrodibenzo[b,f]thiepine which in turn is converted to 4 - (2 - chloro - 11 - hydroxy - 10,11 - dihydro - 11 -  dibenzo[b,f]thiepinyl)- 1 - methyl - pyridinium bromide { the corresponding -1-(4-methoxy. benzyl)-pyridinium bromide is also described }. 10 - Hydroxy - 10 - (4 - pyridyl) - 10,11 - dihydro - dibenzo[b,f]thiepine (also described in the form of its pyridinium salt in conjunction with methyl bromide), obtained from 10-oxo-10,11- 1- dihydrodibenzo[b,f]thiepine and 4-pyridyl-lithium, is dehydrated in the presence of excess acetic anhydride, perchloric acid and acetic acid, thereby giving 10-(4-pyridyl)dibenzo[b,f]thiepine (also described in the form of its methyl bromide pyridinium salt solvated by one molecule of ethanol). 2 - Chloro - 11 - (4 - pyridyl)dibenzo[b,f] thiepine is obtained by dehydration of the corresponding 11-hydroxy compound and is also described in the form of its methyl bromide pyridinium salt and 4-methoxybenzyl bromide pyridinium salt. Pharmaceutical preparations particularly active on the central nervous system as neuroleptics, sedatives and tranquillizers and having antihistaminic, antiserotonin, spasmolytic and antiemetic activity contain as active ingredient compounds I; administration may be orally, parenterally or rectally.