Reaction of 1,3-dihalopropan-2-ones with 2-sulfanylbenzoic acid mono- and disodium salts

Abstract

Well known biological activity of benzoic acid derivatives [1] prompted us to examine the possibility for building up novel heterocyclic systems by reactions of 2-sulfanylbenzoic acid monoand disodium salts with α,α′-dihalo ketones of the general formula XCH2C(=O)CH2X (Ia–Ic, X = Cl, Br, I). Initial sodium 2-sulfanylbenzoate (II) was prepared in situ according to the procedure described in [2] and was brought into reaction with 1,3-dichloropropan-2-one (Ia) in aqueous acetone at room temperature. The reaction occurred as intermolecular O-alkylation of sodium 2-sulfanylbenzoate (II) (Williamson reaction [3]) and led to the formation of 76% of previously unknown 2-oxo-3-(2-sulfanylbenzoyloxy)propyl 2-sulfanylbenzoate (III) (Scheme 1). The structure of compound III was confirmed by its elemental composition and IR and NMR spectra. The IR spectrum of III contained absorption bands belonging to stretching vibrations of S–H (2567 cm), ester carbonyl (1690 cm), and ketone carbonyl groups (1723 cm). Two methylene units in molecule III gave rise to signals at δ 5.38 ppm in the H NMR spectrum and at δC 67.58 ppm in the C NMR spectrum. In order to construct a heterocyclic system, bisbenzoate III was treated with 1,3-dihalopropan-2-ones Ia–Ic with a view to obtain S-alkylation products. However, these reactions resulted in the formation of sulfur-containing oligomers which were insoluble in organic solvents. We succeeded in synthesizing the desired monomeric cyclization product, compound V, only by reaction of disodium salt IV with dihalo ketones Ia–Ic (Scheme 2). Macrocyclic 5H,7H,11H,17Hdibenzo[g,n][1,5,9,13]dioxadithiacyclohexadecine5,8,11,18(9H,19H)-tetraone (V) was formed in 63%