CATION-EXCHANGED MONTMORILLONITE-CATALYZED FACILE FRIEDEL-CRAFTS ALKYLATION OF HYDROXY AND METHOXY AROMATICS WITH 4-HYDROXYBUTAN-2-ONE TO PRODUCE RASPBERRY KETONE AND SOME PHARMACEUTICALLY ACTIVE COMPOUNDS

The Friedel-Crafts alkylation of hydroxy and methoxy aromatics with 4-hydroxybutan-2-one (gamma-KB) in the presence of a cation-exchanged montmorillonite (M(n+)-mont; M(n+) = Zr4+, Al3+, Fe3+, and Zn2+) was investigated. Phenol was C-alkylated regiospecifically with gamma-KB in the presence of Zr4+-, Al3+-, or Fe3+-mont to produce 4-(4-hydroxyphenyl)butan-2-one (raspberry ketone) in 31-35% GLC yield. Anisole, 2-methoxynaphthalene, and 1-methoxynaphthalene were regiospecifically C-alkylated to produce 4-(4-methoxyphenyl)butan-2-one, 4-(2-methoxy-1-naphthyl)butan-2-one (pharmaceutically active), and 4-(4-methoxy-1-naphthyl)butan-2-one, respectively. Al3+- and Fe3+-mont were the most effective catalysts in these cases (13-58%; isolated yield). gamma-KB could be used as an alkylating agent instead of the highly toxic 3-buten-2-one (MVK) which also polymerizes easily.