Photochemical cleavage and release of carboxylic acids and substituted phenols from alpha-keto amides

Chicheng Ma, Marquette University


α-Keto amides with various leaving groups at the position α to the keto group were synthesized. Leaving groups such as carboxylates were photochemically cleaved under aqueous conditions to give carboxylic acids in 70-90% yields with quantum yields of 0.3. Based on mechanistic studies, the elimination of the carboxylate leaving groups was proposed to occur in photogenerated zwitterionic intermediates produced upon hydrogen transfer from an N -alkyl group to the keto group. The major cleavage coproduct was an oxazolidinone hemiacetal, which was accompanied by minor amounts of an α-methyleneoxazolidinone. This latter photoproduct was exclusively formed in the case of N,N -diisopropyl amides. In pure CH3 CN an aminal photoproduct is observed via ion pair return. In water the aminal converts to the aforementioned hemiacetal. γ-Aminobutyrate (GABA) was released within 30 ms according to time-resolved FT-IR spectroscopic studies. Time-resolved pH jump studies with N,N -diethyl α-keto amides gave time constants for carboxylate release ranging from 18-136 μs, depending on leaving group ability of a series of carboxylate groups, and an inverse solvent isotope effect was observed. N,N -Diisopropyl α-keto amides, in contrast, showed only a weak leaving group effect and a small normal solvent isotope effect which means that proton release in a subsequent step is rate determining. Cleavage and release of para -substituted phenols is observed for Y = CN, CF3 , or H and the cleavage coproduct is an α-methyleneoxazolidinone; a hemiacetal coproduct is only observed for Y = CN, CF3 in the case of N,N -diethylamides. 1,3-Photorearrangement of the phenolic group becomes increasingly important for Y = CH3 , OCH 3 . The 1,3-photorearrangements involve radical pair intermediates produced upon excited state homolysis of the ArO-C bond, according to laser flash photolysis studies. Total quantum yields are essentially constant, ca. 0.2-0.3, as the substituent Y is varied. Carboxylate groups are not released in photolyses of N,N -diisopropyl 3-phenyl-2-oxoamide in aqueous CH3 CN. The major photoproduct is a β-lactam, which is likely produced via a nonplanar 1,4-diradical formed upon hydrogen transfer from an N -isopropyl group. Laser flash photolyses show a transient intermediate ascribable to the biradical, which decays on the nanosecond timescale.

Recommended Citation

Ma, Chicheng, "Photochemical cleavage and release of carboxylic acids and substituted phenols from alpha-keto amides" (2004). Dissertations (1962 - 2010) Access via Proquest Digital Dissertations. AAI3154000.