Synthesis of 2-Benzylidene and 2-Hetarylmethyl Derivatives of 2H-1,4-Benzoxazin-3-(4H)-ones as Neuroprotecting Agents

Abstract

A wide variety of the title compounds were synthesized by conventional and microwave methods in which the main step is a condensation of an aldehyde with a 1,4-benzoxazin-3-(4H)-one. In all cases, the Z diasteromers were the major products. Of particular importance is the synthesis of novel 2-(3,5-dibromo-4-hydroxy) and 2-(4-acetoxy-3,5-dibromobenzylidene derivatives of 2H-1,4-benzoxazin-3-(4H)-ones, four of which were shown in a previous publication to exhibit potent neuroprotecting properties. The yields of titled compounds ranged from 25 to 83%.

Keywords:

• 2-Benzylidene-2H-1,4-benzoxazin-3-(4H)-one derivatives
• 2-hetarylmethyl derivatives of 2H-1,4-benzoxazin-3-(4H)-ones
• hydrolysis
• neuroprotecting compounds

ACKNOWLEDGMENTS

This work was supported in part by grants from the Welch Foundation (N-118, to E. R. B.), Defense Advanced Research Projects Agency (HR0011-06-1-0032, to E. R. B.), and the National Institutes of Health (NS047201, to S. R. D.).

Notes

^a CH, conventional heating, 7 h reflux.

^b MW, microwave heating, 180 °C for 20 min.

^c Isolated yields by recrystallization.