Hydroxymethylaniline Photocages for Carboxylic Acids and Alcohols

Abstract

ortho -, meta - and para -Hydroxymethylaniline methyl ethers 3–5-OM e and acetyl derivatives 3–5-OAc were investigated as potential photocages for alcohols and carboxylic acids, respectively. The measurements of photohydrolysis efficiency showed that the decaging from ortho - and meta -derivatives takes place efficiently in aqueous solution, but not for the para -derivatives. Contrary to previous reports, we show that the meta -derivatives are better photocages for alcohols, whereas ortho -derivatives are better protective groups for carboxylic acids. The observed differences were fully disclosed by mechanistic studies involving fluorescence measurements and laser flash photolysis (LFP). Photoheterolysis for the para -derivatives does not take place, whereas both meta - and ortho -derivatives undergo heterolysis and afford the corresponding carbocations 3-C and 4-C . The ortho -carbocation 4- o -C was detected by LFP in aqueous solution (λ max = 410 nm, τ ≈ 90 μs). Moreover, spectroscopic measurements for the meta -acetyl derivative 3- m -OAC indicated the formation of cation in the excited state. The application of an ortho- aniline derivative as a protective group was demonstrated by synthesizing several derivatives of carboxylic acids. In all cases, the photochemical deprotection was accomplished in high yields (>80%). This mechanistic study fully rationalized the photochemistry of aniline photocages which is important for the design of new photocages and has potential for synthetic, biological, and medicinal applications.