A Simple Synthesis of Photolabile α‐Methyl Nitrobenzyl Compounds

Abstract

α‐Methyl nitrobenzyl compounds have demonstrated superior photochemical release properties when compared to nitrobenzyl compounds lacking α‐methyl substitution at the benzylic position. The synthesis of 4‐(1‐hydroxy‐ethyl)‐3‐nitro‐benzoic acid ethyl ester and 4‐(1‐amino‐ethyl)‐3‐nitro‐benzoic acid ethyl ester was each carried out in four steps. The efficient oxidation of 4‐ethyl‐3‐nitro‐benzoic acid to 4‐acetyl‐3‐nitro‐benzoic acid by 3 mol% chromium trioxide/periodic acid in acetonitrile provides a common, crystallizable precursor from which both hydroxy and amine substituted α‐methyl nitrobenzyl compounds may be synthesized. This oxidative methodology will be useful in synthesizing a broad array of nitrobenzyl protecting groups.

Keywords:

• Nitrobenzyl compounds
• Oxidation
• Photolabile protecting groups
• α‐Methyl groups
• Ultraviolet light
• Caged compounds
• Hemiacetal
• Hemiaminal

Notes

^aNitrating conditions included fuming HNO₃ at −10°C, HNO₃/H₂SO₄, HNO₃/Ac₂O.