Condensation of Benzoxa(thia)zolyl-2-guanidines with Dicarbonyl Compounds

Abstract

Heterocyclizations of benzoxa(thia)zolyl-2-guanidines with b-dicarbonyl compounds, such as diketones and derivatives of acetoacetic ether, were studied.The high reactivity of guanidine and its derivatives allows them to be brought into a great number of heterocyclizations, thereby preparing azaheterocycles of various degree of complexity [1]. Much evidence is available on the reactions of amidines and guanidines with a,b-unsaturated carbonyl and b-dicarbonyl compounds, leading to pyrimidines and aminopyrimidines [234]. Compounds of these classes exhibit bactericide and antiviral activity, in particular, are anti-HIV preparations [537].The aim of the present work was to study the re-ÄÄÄÄÄÄÄÄÄÄÄÄ activity of benzoxa(thia)zolyl-2-guanidines Ia and Ib in heterocyclizations with b-dicarbonyl compounds: diketones IIa3IIf and keto esters IVa3IVh.To effect condensation of compounds I with diketones requires fairly rigid conditions: boiling for 3310 h (depending on the reactivity of the diketone) in xylene with azeotropic distillation of water. The reaction products, 2-[benzoxa(thia)zol-2-ylamino]pyrimidines IIIa3IIIi, are generally less soluble and precipitate already from a hot reaction mixture or on its cooling. Ia, IbIIa!IIf IIIa!IIIi g H g H I, Q = O (a), S (b); II, R 1 = R 3 = CH 3 , R 2 = H (a); R 1 = R 2 = R 3 = CH 3 (b); R 1 + R 2 = (CH 2 ) 3 , R 3 = CH 3 (c); R 1 + R 2 = (CH 2 ) 4 , R 3 = C 2 H 5 (d); R 1 = CF 3 , R 2 = H, R 3 = CH 3 (e); R 1 = CF 3 , R 2 = H, R 3 = thienyl (f); III, Q = O, R 1 = R 3 = CH 3 , R 2 = H (a); Q = S, R 1 = R 3 = CH 3 , R 2 = H (b); Q = O, R 1 = R 2 = R 3 = CH 3 (c); Q = O, R 1 + R 2 = (CH 2 ) 3 , R 3 = CH 3 (d); Q = S, R 1 + R 2 = (CH 2 ) 3 , R 3 = CH 3 (e); Q = O, R 1 + R 2 = (CH 2 ) 4 , R 3 = C 2 H 5 (f); Q = S, R 1 + R 2 = (CH 2 ) 4 , R 3 = C 2 H 5 (g); Q = O, R 1 = CF 3 , R 2 = H, R 3 = CH 3 (h); Q = S, R 1 = CF3, R 2 = H, R 3 = thienyl (i). ÄÄÄÄÄÄÄÄÄÄÄÄBenzoylacetone under prolonged heating in the above conditions provides only traces of the reaction product. As the reaction time is increased, stronger tarring is observed. Dibenzoylmethane failed to react. The reactivity of the diketones with respect to guanidine I decreases in the order CF

In the pursuit of novel therapeutic agents: synthesis, anticancer evaluation, and physicochemical insights of novel pyrimidine-based 2-aminobenzothiazole derivatives

“…14 Further diversication is achieved by the reaction of 2-benzothaizolyl guanidine with different chalcones, diethyl malonate, or b-ketoester, either in aqueous or acidic medium. 13,[15][16][17][18] Triuoromethyl-substituted N-(pyrimidin-2-yl) benzo[d]thiazol-2-amines are prepared through the cyclocondensation reaction of 2-benzothaizolyl guanidine with 4alkoxy-4-alkyl(aryl/heteroaryl)-1,1,1-triuoroalk-3-en-2-ones or 2,2,2-triuoro-1-(2-methoxycyclohexen-1-en-1-yl)ethanone. 19 Moreover, a series of pyrimidine-base 2-aminobenzothiazoles is obtained by reacting 2-benzothaizolyl guanidine with ethyl 2butylacetoacetate, diethyl ethoxymethylenemalonate, ethyl ethoxymethylenecyanoacetate, and ethoxymethylenemalononitrile in a basic medium.…”