Patent GB-1112128-A (GB)
Title: New thiazolyl-diphenylmethane derivatives
Inventor: PESSON MARCEL
IPC: C07D277/56
Filed: 1965-12-22
Abstract: The invention comprises compounds of the formula <FORM:1112128/C4-C5/1> where R3 is hydroxy, alkoxy of 1-4 carbon atoms or acyloxy and R1 and R2 are hydrogen, alkyl of 1-4 carbon atoms mononuclear aryl of a N-containing ring, or R1 and R2 form an alkylene chain of up to 4 carbon atoms.  The compounds may be prepared (a) by condensing an a -halogenated ketone of the formula R1-CO-CHX-R2 where X is halogen, with a 4,41-dialkoxy-diphenyl thioacetamide; (b) by reacting two mols. of a p-alkoxyphenyl magnesium bromide with a compound of the formula <FORM:1112128/C4-C5/2> to give a carbinol which is then reduced; (c) by reacting a compound of the formula <FORM:1112128/C4-C5/3> with a 4,41-dialkoxybenzophenone and reducing the carbinol formed; (d) by reacting a tertiary amide of an acid of the formula <FORM:1112128/C4-C5/4> with two mols. of p-alkoxyphenyl magnesium bromide and reducing the carbinol formed; and (e) condensing the sodium derivative of 4,41-dialkoxy diphenyl acetonitrile with a compound of the formula <FORM:1112128/C4-C5/5> where X is halogen, to give a bis (p-alkoxyphenyl) - (2 - thiazolyl) - acetonitrile which is dealkylated and hydrolysed with 48% HBr in acetic acid to give bis (p-hydroxyphenyl)-(2-thiazolyl)-acetamide, the saponification of which with KOH accompanied by decarboxylation gives bis (p - hydroxyphenyl) - (2 - thiazolyl)-methane. The compounds wherein R3 is OH may be prepared by dealkylating the alkoxy derivatives, and those wherein R3 is acyloxy may be prepared by acylating the hydroxy compounds.ALSO:The invention comprises compounds of the formula <FORM:1112128/C2/1> where R3 is hydroxy, alkoxy of 1-4 carbon atoms or acyloxy and R1 and R2 are hydrogen, alkyl of 1-4 carbon atoms mononuclear aryl of a N-containing ring, or R1 and R2 form an alkylene chain of up to 4 carbon atoms.  The compounds may be prepared (a) by condensing an a -halogenated ketone of the formula R1-CO-CHX-R2 where X is halogen, with a 4,41-dialkoxy-diphenyl thiocetamide, (b) by reacting two mols of a p-alkoxy-phenyl magnesium bromide with a compound of the formula <FORM:1112128/C2/2> to give a carbinol which is then reduced, (c) by reacting a compound of the formula <FORM:1112128/C2/3> with a 4,41-dialkoxybenzophenone and reducing the carbinol formed, (d) by reacting a tertiary amide of an acid of the formula <FORM:1112128/C2/4> with two mols of p-alkoxyphenyl magnesium bromide and reducing the carbinol formed and (e) condensing the sodium derivative of 4,41-dialkoxy diphenyl acetonitrile with a compound of the formula <FORM:1112128/C2/5> where X is halogen, to give a bis(p-alkoxy-phenyl) -(2-thiazolyl)-acetonitrile which is dealkylated and hydrolysed with 48% HBr in acetic acid to give bis(p-hydroxyphenyl)-(2-thiazolyl)-acetamide the saponification of which with KOH accompanied by decarboxylation gives bis(p-hydroxyphenyl) - (2 - thiazolyl) - methane. The compounds wherein R3 is OH may be prepared by dealkylating the alkoxy derivatives, and those wherein R3 is acyloxy may be prepared by acylating the hydroxy compounds.  Certain of the compounds may be used in pharmaceutical compositions.