Patent GB-729619-A (GB)
Title: Improvements in or relating to the manufacture of thio- or sulphonyl-substituted basic benzhydryl-ethers and thio-ethers
IPC: B21D13/04
Filed: 1953-05-08
Abstract: The invention comprises thio- or sulphonyl-substituted basic benzhydryl ethers and thioethers having sedative properties and represented by the formula <FORM:0729619/IV (b)/1> wherein R is hydrogen, chlorine, bromine or iodine; R1 and R2 are alkylsulphonyl, alkylmercapto, phenyl- or substituted phenylmercapto, cycloalkyl- or substituted cycloalkylmercapto or hydrogen, and may be the same except when one of them is hydrogen; Z is oxygen or sulphur; and X is dialkylaminoalkyl, morpholinyl-substituted alkyl, piperidyl-substituted alkyl or N-alkyl-substituted C-piperidyl; and their acid or quaternary ammonium salts.  They may be prepared by reacting a benzhydryl halide of the formula <FORM:0729619/IV (b)/2> with the appropriate amino-alcohol or amino-thio-alcohol or their alkali metal salts; or by reacting the amino-halide with an appropriately substituted benzhydrol or benzhydryl-thio-alcohol or an alkali metal salt thereof.  Solvents may be present.  Examples disclose the preparation of hydrochlorides or citrates of the following compounds: benzhydryl 2-dimethylaminoethyl sulphides in which the benzhydryl group is substituted by p-methyl, p-ethyl, p-isopropyl-, o-, m- and p-butyl-, m- and p-hexyl-, p-cyclohexyl-, p-octyl- and p-phenyl-mercapto groups and by p,p1-bis(n-hexyl-, propyl- and butyl-mercapto) groups and by p-butyl sulphonyl: the p-butyl- and m-bromo-p1-butylmercapto and p,p1-bis(butylmercapto)-benzyhydryl 2-diethyl aminoethyl sulphides: m- and p-butyl-mercapto-benzhydryl 2-dimethylaminoethyl ethers: p-butylmercaptobenzhydryl-4-dimethyl-aminobutyl ether: p-butylmercaptobenzhydryl 2-(4-morpholinyl) ethyl ether and sulphide; p-butyl mercaptobenzhydryl 2-dimethylaminopropyl ether and sulphide: p-butylmercaptobenzhydryl 4-(1-methyl)-piperidyl sulphide: p-methylmercaptobenzhydryl 2-(1 - piperidyl) - ethyl ether: p-hexylmercaptobenzhydryl 2-(4-morpholinyl)-ethyl sulphide.  The p-alkylmercaptobenzhydryl chlorides, used as starting materials, are prepared by reducing the p-alkyl mercaptobenzophenones (obtained from the p-alkylphenyl sulphides) with zinc and sodium hydroxide to the alcohol and then saturating with anhydrous HCl.  The p-phenylmercapto-derivative is similarly prepared.  The m-alkyl mercaptobenzhydryl chlorides are similarly prepared from the m-alkylmercaptobenzophenones which are obtained from the m-alkylmercaptobenzoyl chloride, benzene and anhydrous AlCl3 in CS2. The alkylmercaptobenzhydryl mercaptans are prepared by boiling the chloride with thiourea yielding the alkylmercaptobenzhydrylisothiouronium chloride which is then hydrolysed with aqueous sodium hydroxide.  p-Butyl sulphonylbenzophenone is obtained by oxidizing p-butyl mercaptobenzophenone with hydrogen peroxide in glacial acetic acid. m - Bromo - p1 - butylmercaptobenzhydryl chloride is prepared by reacting butyl phenyl sulphide with m-bromobenzoyl chloride by the Friedel-Crafts synthesis to yield m-bromo-p1-butylmercaptobenzophenone, which is reduced by zinc and KOH to the alcohol which is then treated with HCl.  p - Bromophenyl - n - butyl sulphide, prepared by brominating p-n-butyl phenyl sulphide, is converted to p-butyl mercaptobenzoic acid by carbonation of a Grignard derivative with CO2.  The acid chloride, obtained by treatment with thionyl chloride, is reacted with butyl phenyl sulphide as above, yielding p,p1-bis (butylmercapto)-benzophenone. This is reduced to give p,p1-bis(butylmercapto)-benzhydrol, which is treated with HCl to give the chloride.  Similar methods produce the p,p1-bis(propyl-and hexyl-mercapto)-derivatives.