Patent GB-965305-A (GB)
Title: Thiazocine compounds
Filed: 1962-02-16
Abstract: The invention comprises compounds having the formula: <FORM:0965305/C1/1> wherein R represents hydrogen, halogen, trihalomethyl, lower alkoxy, trihalomethoxy, trihalomethylmercapto or lower alkyl and B represents a basic, saturated, nitrogen-containing radical of less than 12 carbon atoms consisting of amino, di-lower alkylamino, di(hydroxy-lower alkyl) amino, piperidyl, (lower alkoxy) piperidyl, (lower alkyl) piperidyl di(lower alkyl) piperidyl, pyrrolidyl, (lower alkyl) pyrrolidyl, di (lower alkyl) pyrrolidyl, (lower alkoxy) pyrrolidyl, morpholinyl, (lower alkyl) morpholinyl, (lower alkyl) morpholinyl, di (lower alkyl) morpholinyl, (lower alkoxy) morpholinyl, thiamopholinyl, (lower alkyl) thiamorpholinyl, di (lower alkyl)-thiamorpholinyl, (lower alkoxy) thiamorpholinyl, piperazinyl, (lower alkyl) piperazinyl, di (lower alkyl) piperazinyl, (lower alkoxy) piperazinyl, (hydroxy-lower alkyl) piperazinyl, (lower alkanoyloxy-lower alkyl) piperazinyl, (hydroxy-lower alkoxy, lower alkyl) piperazinyl and (carbo-lower alkoxy) piperazinyl, acid addition salts thereof and processes for the preparation thereof, characterised by: (a) reacting a compound of the formula: <FORM:0965305/C1/2> with a compound of the formula X-lower alkylene-B wherein X represents a halogen atom and R and B are as above defined; or (b) reacting a compound of the formula: <FORM:0965305/C1/3> with an amine in an organic solvent, X and R being as above defined; or (c) reducing a compound of the formula: <FORM:0965305/C1/4> to obtain a compound of the formula: <FORM:0965305/C1/5> wherein R and X are as defined above, and reacting the latter with an amine; or (d) reacting a compound of the formula: <FORM:0965305/C1/6> with an amine to obtain a compound of the formula: <FORM:0965305/C1/7> and reducing the latter, X, R and B being as defined above, and if desired, treating the resultant base with an acid to prepare the corresponding acid addition salt thereof. The compound having the formula: <FORM:0965305/C1/8> may be obtained initially by reacting a compound of the formula: <FORM:0965305/C1/9> with an amine, X, R and B being as defined above.  11, 12-Dihydro-6H-dibenzo[b, f] [1, 4]thiazocines having the formula: <FORM:0965305/C1/100> are obtained by reacting a , a 1-dihalo-o-xylene with an appropriately lar-substituted o-amino-benzenethiol.  3-Amino-p-toluenesulphonyl chloride is obtained by reacting 3-amino-p-toluenesulphonic acid with thionyl chloride.  2-Amino-p-toluenethiol is obtained by treating 3-amino-p-toluenesulphonyl chloride with zinc dust. 2-Amino-p-anisylsulphonic acid sodium salt is obtained by treating m-anisidine with chlorosulphonic acid followed by sodium hydroxide. 2-Amino-p-anisyl sulphonic chloride is obtained from the corresponding sulphonic acid with thionyl chloride. 2-Amino-p-anisylthiol is obtained by treating 2-amino-p-anisyl sulphonyl chloride with zinc dust.  Substituting m-nitrothioanisole for m-anisidine above there are obtained 2-nitro-p-thioanisylsulphonic acid sodium salt and the corresponding sulphonyl chloride.  2-Nitro-p-(trichloromethylmercapto) benzene sulphonyl chloride is obtained by chlorinating 2-nitro-p-thioanisylsulphonyl chloride. 2-Nitro-p-(trifluoromethylmercapto) benzene sulphonyl fluoride is obtained by treating the corresponding chloro compound with antimony trifluoride.  2-Amino-p-(trifluomethylmercapto) benzenethiol is obtained by treating the sulphonyl fluoride with zinc dust. Substituting 2-nitro-anisylsulphonyl chloride for 2-nitro-p-thioanisylsulphonyl chloride above there are obtained 2-nitro-p-(trichloromethoxy)-benzene sulphonyl chloride, the corresponding sulphonyl fluoride and 2-amino-p-(trifluoromethoxy)-benzenethiol.  Pharmaceutical compositions containing compounds having the first of the above formulae or a pharmaceutically acceptable acid addition salts thereof, e.g. an ascorbate, are useful as ataractic agents, antihistaminics or antispasmodics and may be administered orally or parenterally as tablets, capsules, elixirs or injectables.