Synthesis and effect on free radical processes on some substituted morpholine derivatives with potential biologic activity.

Since a number of 2-hydroxy(alkoxy)-2-phenyl-4(5,6)-(tri)alkyl-morpholines presented antioxidant and interesting biologic activity which may implicate free radical processes, some 2-hydroxy(alkoxy)-2-biphenyl-4-methyl-morpholine derivatives were prepared in an attempt to synthesize more potent antioxidants with interesting biologic action. The 2-hydroxy-2-biphenyl-4-methyl-morpholine was prepared by reacting the N-methyl-ethanolamine with the p-phenyl-phenacylbromide, the 2-hydroxy-derivative formed after spontaneous cyclisation gave the 2-alkoxy-2-biphenyl-4-methyl morpholines by an acid catalyzed ketal formation. The lipophilicity of the synthesized compounds was determined by the reversed phase TLC technique as RM values. The synthesized 2-biphenyl substituted morpholines were evaluated for their antioxidant activity on hepatic microsomal lipid peroxidation and on hydroxyl radical mediated oxidation of dimethylsulfoxide. The synthesized compounds were found to possess potent antioxidant activity. A possible mechanism was proposed for the antioxidant properties while lipophilicity was found not to be an important determinant of this property.