Synthesis of some oxygen-containing heterocycles from methyl 3-hydroxyphenylcarbamate

Abstract

SHORT COMMUNICATIONSIt is well known that phenols readily undergo condensations with various carbonyl compounds. Among these transformations, the most interesting are those leading to oxygen-containing heterocyclic compounds which exhibit significant biological activity. We previously reported on reactions of methyl 3-hydroxyphenylcarbamate (I) with ethyl acetoacetate, ethyl benzoylacetate, and L-malic acid in the presence of concentrated sulfuric acid, which afforded 23-87% of carbamate coumarin derivatives [1].While developing studies in this line, we examined the condensation of methyl 3-hydroxyphenylcarbamate (I) with ethyl 4-chloro-3-oxobutanoate in concentrated sulfuric acid and 85% polyphosphoric acid (PPA). The reaction in concd. H 2 SO 4 was carried out at room temperature (reaction time 24 h). The reaction in PPA was carried out under different conditions with variation of the temperature (70-90°C) and time. The optimal conditions were heating of the reaction mixture for 1 h at 70°C, followed by keeping for 24 h at 25°C. Raising the temperature and reaction time led to the formation of a lot of tars. In both cases, the condensation product was identified by IR and 1 H NMR spectroscopy as methyl 2-oxo-4-chloromethyl-2H-chromen-7-ylcarbamate (II) which was obtained in 58 and 35% yield, respectively (Scheme 1). The 1 H NMR spectrum of II, apart from other signals, contained a singlet at δ 3.71 ppm from three protons in the carbamate fragment and a singlet at δ 4.55 ppm from two protons in the chloromethyl group. Thus carbamate I behaved similarly to resorcinol in analogous reaction [2].It is known that an allylic chlorine atom can be replaced by nucleophiles. The reaction of chloromethyl-substituted chromene II with morpholine in dioxane at room temperature gave the expected product, methyl 4-(morpholin-4-ylmethyl)-2-oxo-2H-chromen-7-ylcarbamate (III) whose structure was confirmed by the IR, 1 H NMR, and mass spectra (Scheme 1).