A Simple Synthesis of Photolabile α-Methyl Nitrobenzyl Compounds

• Published in: Synthetic communications Vol. 34; no. 13; pp. 2379 - 2386
• Main Authors: Salerno, Charles P., Cleaves, Henderson J.
• Format: Journal Article
• Language: English
• Published: PHILADELPHIA Taylor & Francis Group 2004; Taylor & Francis
• Subjects: Caged compounds; Chemistry; Chemistry, Organic; Hemiacetal; Hemiaminal; Nitrobenzyl compounds; Oxidation; Photolabile protecting groups; Physical Sciences; Science & Technology; Ultraviolet light; α-Methyl groups; ORGANIC-SYNTHESIS; ACID; nitrobenzyl compounds; SOLID-PHASE SYNTHESIS; alpha-methyl groups; oxidation; photolabile protecting groups; RELEASE; ultraviolet light; hemiaminal; PRODUCT; caged compounds; hemiacetal; PHOTOLYSIS; LINKER
• ISSN: 0039-7911; 1532-2432
• DOI: 10.1081/SCC-120039491

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.