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

Article abstract of DOI:10.1021/jo00099a017

The Friedel-Crafts alkylation of hydroxy and methoxy aromatics with 4-hydroxybutan-2-one (γ-KB) in the presence of a cation-exchanged montmorillonite (M(n+)-mont; M(n+) = Zr(4+), Al(3+), Fe(3+), and Zn(2+)) was investigated.Phenol was C-alkylated regiospecifically with γ-KB in the presence of Zr(4+)-, Al(3+)-, or Fe(3+)-mont to produce 4-(4-hydroxyphenyl)butan-2-one (raspberry ketone) in 31-35percent 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.Al(3+)- and Fe(3+)-mont were the most effective catalysts in these cases (13-58percent isolated yield). γ-KB could be used as an alkylating agent instead of the highly toxic 3-buten-2-one (MVK) which also polymerizes easily.