Selective oxidation of aldehydes to carboxylic acids with sodium chlorite-hydrogen peroxide

Abstract

Several methods for the oxidation of aldehydes to the corresponding carboxylic acids are known.1,2 However, no one seems to be completely satisfactory, the major drawbacks being high costs, low selectivities, and complex operating conditions. Their application to large-scale preparations is therefore difficult.We thus addressed our attention to the use of the inexpensive sodium chlorite,1 23 which reacts with aldehydes under very mild conditions to give carboxylic acids (eq 1).RCHO + HC102 -RCOOH + HOC1(1)However, hypochlorite ion must be removed in order to avoid side reactions, since the redox pair HOC1/CT is a more powerful oxidant than C102"/H0C1.4 5Another drawback is the oxidation of C102™ to C102 according to eq 2.38,5 HOC1 + 2C1CV -2C102 + Cl" + OH*(2) 2-Methyl-2-butene,78,8 resorcinol,38•7 and sulfamic acid38•9 have been tested as HOC1 scavengers. 2-Methyl-2-butene must be used in a very large excess. Resorcinol is converted into 4-chloro-1,3-dihydroxybenzene, which must be removed from the reaction mixture. Sulfamic acid works well in the oxidation of hydroxylated aromatic aldehydes, but it gave poor results in the case of ,/3-unsaturated aldehydes (see below).

Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin

“…Several methods reported to convert primary alcohols to carboxylic acids in one step (24,25) produced complex mixtures from compound 2, presumably due to interaction with the olefinic linkage at the 4-position. Thus a two-step oxidation sequence was employed in which SO 3 pyridine complex (26) oxidized compound 2 to aldehyde compound 3 (76.4%) followed by treatment of compound 3 with the oxidant NaOCl 2 in DMSO (27,28) to form compound 4 (79.9%). The use of DMSO as the solvent was crucial because the NaOCl formed in the reaction preferentially reacts with it, thus protecting the double bond at the 4-position.…”

“…5, compound 3), which is subsequently oxidized to dihydroartemisinic acid (Fig. 5, compound 4) with inexpensive inorganic reagents (26)(27)(28).…”

Synthesis of the algicide bacillamide

“…7 The seemingly simple task of coupling tryptamine 2a with acid 3, to form bacillamide in good yield, proved to be unexpectedly difficult. For example, the following three mild methods involving activated carboxylic acid derivatives of 3 derived from a) benzotriazole, 8 b) carbonyl diimidazole, 9 or c) via Mitsunobu reaction, 10 all failed to give the requisite product 1 in acceptable yields.…”

Total synthesis of the cytotoxic cyclodepsipeptide (-)-doliculide: The “ester” effect in acyclic 1,3-induction of deoxypropionates

“…Thus, 14 was esterified with the iodotyrosine derivative 15 (32) in the presence of 1,3-dicyclohexylcarbodiimide and 4-dimethylaminopyridine to afford 16 in 77% yield in contrast to the reported 95% (32). Ozonolysis of the double bond, followed by oxidation of the resulting aldehyde with sodium chlorite͞H 2 O 2 in aqueous acetonitrile (70), afforded the corresponding acid. Cleavage of the N-Boc group with trifluoroacetic acid, followed by macrolactam formation gave 17, which was subjected to a final deprotection as described by Ghosh and Liu (32) to give (Ϫ)-doliculide 1, the spectroscopic data of which were identical to those reported in the literature (14,32).…”