REACTIONS OF 4-ISOTHIOCYANATO-4-METHYL-2-PENTANONE WITH AMINES HAVING FUNCTIONAL GROUP AT β POSITION AND ANTI-INFLAMMATORY EVALUATION OF RESULTING HETEROCYCLIC COMPOUNDS

Abstract

The reaction of 4-isothiocyanato-4-methyl-2-pentanone with o-phenylenediamine at room temperature yielded isomeric mixture of 1-(2′-aminophenyl)-4,4,6-trimethyl-1,4,5,6-tetrahydro-6-hydroxypyrimidine-2(3H)-thione (I), which on refluxing in MeOH with catalytic amount of sulphuric acid cyclizes to yield the known pyrimidobenzimidazole (IIa). The same product was also obtained by direct condensation of o-phenylenediamine with 4-isothiocyanato-4-methyl-2-pentanone in the presence of catalytic amount of acid and heating under reflux for 8 h. The reaction of 4-nitro-1,2-phenylenediamine with 4isothiocyanato-4-methyl-2-pentanone gave IIb. The reaction of o-aminophenol with 4-isothiocyanato4-methyl-2-pentanone at pH 4.3 gave 1-(2′-hydroxyphenyl)-4,4,6-trimethyl-1,4-dihydro-pyrimidine-2(3H) thione (III), however the same reaction under strongly acidic conditions (pH ∼ 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 and VI, respectively. The structures of these compounds are supported by IR, ¹H NMR and HRMS. Anti-inflammatory evaluation of I, IIa, IIb, III, 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.

Key Words:

• Isothiocyanato pentanone
• Amines
• Heterocyclic
• anti-inflammatory activity
• NMR
• HRMS.