Patent GB-948766-A (GB)
Title: Trifluoromethylphenylpiperazine derivatives
Inventor: ASH ANTHONY STANLEY FENTON
IPC: C07D263/22
Filed: 1959-10-20
Abstract: The invention comprises bases of the general formula: <FORM:0948766/C2/1> in which R1 represents a hydrogen atom or a trifluoromethyl group and R2 is in the meta- or para-position and is hydrogen, nitro, amino, mono- or di-alkylamino, mono- or di-(hydroxyalkyl) amino or aliphatic acylamino (including sulphonamido), and their acid-addition salts, and pharmaceutical compositions containing them in association with a significant amount of a pharmaceutical carrier, and the preparation of the bases by (a) reacting a compound of the general formula: <FORM:0948766/C2/2> with a compound of the general formula: <FORM:0948766/C2/3> (wherein Y represents a reactive ester residue) or with p-nitrostyrene (for compounds in which R2 is a p-nitro group), or (b) reacting a compound of the general formula <FORM:0948766/C2/4> with a compound of the general formula: <FORM:0948766/C2/5> or (c) (for compounds in which R2 is a m-nitro group) reductively deaminating a diazo compound derived from a corresponding m-nitro-p-amino compound, a (d) (for compounds in which R2 is NH2) reducing a corresponding compound in which R2 is a nitro group, or by the processes of the examples which comprise additionally (e) acylation of compounds in which R2 is NH2 and (f) alkaline hydrolysis of compounds in which R2 is -NHCOOCH2CH2Cl to compounds in which R2 is -NHCH2CH2OH. Reference is also made to the conversion of compounds in which R2 is acylamino to compounds in which R2 is NH2 by hydrolysis and to compounds in which R2 is monoalkylamino by reduction, and reaction of compounds in which R2 is NH2 with one or two molecular proportions of an alkylene oxide. According to the Provisional Specification the substituents may be in any positions in the benzene rings.  The pharmaceutical compositions, which are useful for the treatment of psychiatric disorders, may be in the form of tablets, pills, dispersible powders, granules, emulsions, solutions, suspensions, syrups, elixirs and capsules.  2 -p- Methanesulphonamidophenylethyl bromide is prepared by catalytic hydrogenation of 2-p-nitrophenylethyl bromide in methanol containing methanesulphonic acid to form 2-p-aminophenylethyl bromide methanesulphonate and treatment of this with methanesulphonyl chloride in benzene in the presence of triethylamine.  m-N, N-Di-b -chloroethylaminobenzotrifluoride is prepared by reacting m-aminobenzotrifluoride with ethylene oxide and treating the resulting m - N,N - di - b -hydroxyethylaminobenzotrifluoride with phosphorus oxychloride.  1 - (2 - p - N - b  - Chloroethoxycarbonylaminophenylethyl) -4- (m-trifluoromethylphenyl)-piperazine is prepared by reacting 1-(2-p-aminophenylethyl) -4- (m-trifluoromethylphenyl)-piperazine with 2-chloroethyl chloroformate.  1 - 21 - (4 - Amino -3- nitrophenyl)-ethyl -4-(m-trifluoromethylphenyl) - piperazine is prepared by acetylating 2-p-aminophenylethyl bromide methanesulphonate, condensing the product with N-m-trifluoromethylphenylpiperazine to form 1 - 21 - (4-acetamido -3- nitrophenyl)-ethyl -4-m-trifluoromethylphenylpiperazine and hydrolysing the acetamido group.  Specification 894,767 is referred to.