Synthesis of 2-substituted aminothiazol-4(5H)-ones proceeding from carboxylactones

Abstract

New representatives of 2,2,4-trisubstituted butano-4-lactones were synthesized. By a series of transformations the corresponding γ-carboxylactones were obtained. The latter served as starting compounds for preparation of heteryl-linked lactones, 5-[5-{(alkoxymethyl)-2-oxotetrahydrofuran-3-yl}methyl]-2-arylaminothiazol-4(5Н)-ones.Carboxylactones are known to be successfully used in the synthesis of compounds of various classes. In particular, some carboxylactone esters are used as additives to rocket propellants [1], in the synthesis of oxazolines [2], prostaglandins derivatives [3], and triazolyllactones [4-8] exhibiting hypotensive and antitumor action.The aim of this study was the extension of the choice of carboxylactones, the development of the procedures for the preparation therefrom of new heterocyclic compounds, and the investigation of the useful practical properties of the latter. To fulfi ll this goal we selected as initial compounds ethyl 5-alkoxymethyl-2-oxotetrahydrofuran-3-carboxylates Iа-Ic, being good CH-acids. We carried out the condensation of compounds Iа-Ic with methyl acrylate in the conditions of Michael reaction. As a result we obtained in high yields ethyl 5-(alkoxymethyl)-3-(3-methoxy-3-oxopropyl)-2-oxotetrahydro furan-3-carboxylates IIа-3 ONa O ROH 2 C COOEt O Ia _ Ic O ROH 2 C COOEt O IIa _ IIc CH 2 CH 2 COOCH 3 CH 2 =CHCOOCH 3 O ROH 2 C O IIIa _ IIIc CH 2 CH 2 COOH (2) H + , _ CO 2(1) OH _ IIc which by the alkaline hydrolysis were converted into 3-[5-(alkoxymethyl)-2-oxotetrahydrofuran-3-yl]-propionic acids IIIа-IIIc (Scheme 1). The best results were obtained in the condensation catalyzed with sodium methylate followed by the hydrolysis with 30% solution of NaOH.Taking into consideration that the halo-substituted γ-lactones are successfully used for preparation of compounds of various classes [9, 10], analogs of natural substances [11,12], carboxylactones IIIа-IIIc were converted into the corresponding acyl chlorides IVа-IVc by the treatment with thionyl chloride in the presence of catalytic quantity of DMF (Scheme 2). Further the bromination of compounds IVа-IVc and the subsequent reaction of the obtained chlorides of α-bromoacids with anhydrous ethanol afforded in a high yield ethyl 2-bromo-3-(5-alkoxymethyl 2-oxotetrahydrofuran-3-yl) propanoates Vа-Vc (Scheme 2). Scheme 1. R = C 2 H 5 (a), iso-C 3 H 7 (b), C 5 H 11 (c).

Synthesis and transformations of 5,5-disubstituted 3-alkenyloxolan-2-ones

“…Previously we [12][13][14][15] developed new methods of preparation of mono-and dibutanolides fused with various heterocycles, among which compounds were discovered demonstrating antitumor, antioxidant, and antimutagenic properties. In continuation of research in the field of 4-butanolides aiming at widening the choice of compounds containing the butanolide ring, exploring the chemical and physical properties and developing new methods of synthesis of various compounds classes we selected as initial compounds in this study ethyl 5,5-disubstituted 2-oxooxolane-3carboxylate.…”