REACTIONS OF 4-ISOTHIOCYANATO-4-METHYL-2-PENTANONE WITH AMINES HAVINGFUNCTIONAL-GROUP AT BETA-POSITION AND ANTIINFLAMMATORY EVALUATION OF RESULTING HETEROCYCLIC-COMPOUNDS

The reaction of 4-isothiocyanato-4-methyl-2-pentanone with o-phenylene diamine at room temperature yielded isomeric mixture of 1,4,5,6-tetrah ydro-6-hydroxyprimidine-2(3H)-thione (I), which on refluxing in MeOH w ith catalytic amount of sulphuric acid cyclizes to yield the known pyr imidobenzimidazole (IIa). The same product was also obtained by direct condensation of o-phenylenediamine with 4-isothiocyanato-4-methyl-2-p entanone in the presence of catalytic amount of acid and heating under reflux for 8 h. The reaction of 4-nitro-1,2-phenylenediamine with 4-i sothiocyanato-4-methyl-2-pentanone gave IIb. The reaction of o-aminoph enol with 4-isothiocyanato-4-methyl-2-pentanone at pH 4.3 gave 1-(2'-h ydroxyphenyl) -4,4,6-trimethyl-1,4-dihydro-pyrimidine-2(3H) thione (II I), however the same reaction under strongly acidic conditions (pH sim ilar to 1) gave the known pyrimidobenzoxazole (IV). The reaction of 4- isothiocyanato-4-methyl-2-pentanone with o-aminothiophenol and 2-amino ethanol under different pH conditions gave the known heterocycles V a nd VI, respectively. The structures of these compounds are supported b y IR, H-1 NMR and HRMS. Antiinflammatory evaluation of I, IIa, IIb, II I, IV, V and VI at 100 mg/kg showed that compounds I, IIa, III, and IV are inactive whereas, compounds IIb, V and VI showed 13%, 11%, and 21 % activity, respectively.