Preparation of valeric acids, pentenoic acids, and γ-valerolactones labelled with deuterium

Abstract

[2-2H1]-, [2,3-2H2]-, [2,2,3-2H3]-, and [4,4,5,5,5-2H5]Valeric acids, and trans- and cis-2-[2-2H1]pentenoic acid and 4-[4,5,5-2H3]pentenoic acid have been synthesized from 2-bromovaleric acid, trans-2-pentenoic acid, 2,3-dibromovaleric acid, and 4-pentynoic acid in 78% to 95% isotopic purity by employing Raney alloys or Aluminium powder in alkaline deuterium oxide. The reductions of trans-3- and 4-pentenoic acids, while smoothly proceeding with 10% Pd-C as an additive in the reaction system, resulted in the formation of deuteriated valeric acid with over-introduction of deuterium atoms. Use of 3,4-dibromo-valeric acid resulted in the dehydrobromination between C-2 and C-3 and the subsequent hydrolysis of the bromine at C-4, to provide γ-[2,3-2H2]- lactone, which was also prepared from 4-bromo-trans-2-pentenoic acid in higher purity. Levulinic acid involves the incorporation of deuterium atoms at C-3 and C-5 upon the treatment with 10% NaOD-D2O, followed by Cu-Al alloy reduction, affording γ-[3,3,4,5,5,5-2H6]valerolactone.