Comparative intramolecular dehydrative lactonization of 4- oxocarboxylic acids
Ferenc Csende
Taxus Research Laboratory, Vasvári. P. u. 61, H-4440 Tiszavasvári, Hungary,
E-mail: csende@nanaskabel.hu
Dedicated to Professor Giuseppe Bartoli on the occasion of his 65th birthday
Abstract
Reaction of 3-(p-toluoyl)propanoic acid, 1a (R = H) with refluxing acetic anhydride resulted quantitatively in 2, a ß,.-unsaturated .-lactone, which was then converted into 3a, an a,ß- unsaturated lactone by isomerization with triethylamine. The methyl- substituted compound 1b (R = Me), an analogue of 1a, afforded the 2(5H)-furanone 3b directly by heating with Ac2O. Similar reaction of the cycloalkane- containing oxocarboxylic acids (4,5) led in excellent yields to the fused furanones 6 and 7, while treatment of 2-formyl-, 2-acetyl- and 2-(p-toluoyl)benzoic acids (8a-c) with Ac2O gave the 3-acetoxy-1-(3H)-isobenzofuranones, 9a-c.
Keywords: 4-Oxocarboxylic acid, dehydration, furanones, isobenzofuranones
Introduction
We recently described several cyclocondensation reactions of 4- and 5-oxocarboxylic acids with amines1 and bifunctional amino derivatives, such as diamines, amino-alcohols and amino-thiols.2 Further studies of the reactivity of cis- and trans- cyclohexane- fused 4-oxocarboxylic acids with various dehydrating agents (H2SO4, PPA, H3PO4, AcCl, Ac2O, and DCC) led to formation of unsaturated lactones exclusively, instead of the expected saturated anthraquinone derivatives. These results prompted us to compare the reactivity of aromatic-, aliphatic-, and cycloalkane- condensed 4-oxocarboxylic acids with acetic anhydride as a mild and efficient reagent.
The chemistry, synthesis and properties of 2(3H)- and 2(5H)-furanones (butenolides) have been studied and reported in detail in the past few decades.3-5 These ring systems serve as important moieties or precursors of several natural products (e.g., avenaciolide, plumieride, digitoxin, patulin) and a series of pharmacologically active compounds (digoxin, rofecoxib, protoanemonin, phenolphthalein). A large variety of synthetic methods was reported earlier for the preparation of furanone and isobenzofuranone derivatives. Thus the readily enolized 3-
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