Synthesis and properties of esters of benzothiazolylamino(imino)propionic acids

Abstract

The reaction of 2-aminobenzothiazole (Ia) and its derivatives (Ib, c) with methyl acrylate has been investigated in the present work as a continuation of the study of ambifunetional heterocyclic amines in. nucleophilic substitution and addition reactions [1].The reactions of unsaturated acid esters with compound (Ia) have been described using esters of fl-aminocrotonic [2], ethox.ymethylenemalonic [3, 4], 2-aminofumaric [5], and ethoxyacrylic acids [6] as examples. In all cases, reaction was observed at the ester group, the double bond was not affected. Nucleophilic addition of 2-aminobenzothiazoles to propiolic acid ester [6][7][8][9] and to acetylenedicarboxylic acid ester [5, 9, 10] has been effected. The formation of 2-oxopyrimidobenzothiazoles in these reactions indicated that addition to the C --= C bond occurs with the participation of the endocyclic nitrogen atom of the beterosystem. Reactions of 2-(R-amino)benzothiazoles with unsaturated acid esters have not been studied up to the present time.On boiling amines (Ib, c) in methyl acrylate solution, N-alkyl-N-(fl-methoxycarbonylethyl)-2-aminobenzothiazoles (IIIb, c) were isolated in place of the expected 2-(alkylamino)-3-(fl-methoxycarbonylethyl)benzothiazolines (Hb, c). In the case of the unsubstituted amine (Ia) 2-oxo-3,4-dihydro-2H-pyrimido[2,1-b]benzothiazole (IV) was isolated under these conditions in addition to compound (IIIa). The cyclization product (IV) is probably formed from the intermediate iminoester (Ha). Carrying out the latter reaction at 50-550C enabled the isolation of the aminoester (IRa) in addition to the cyclic product (IV).An alternate synthesis of compound (IV) was effected by the cyclization of 3-(fl-carboxyethyl)-2-iminobenzothiazoline (Va) by the action of thionyl chloride. For comparison, 4-oxo-2,3-dihydro-4H-pyrimido[2,1-b]benzothiazole (VI) was synthesized by treating 2-(fl-carboxyethylamino)benzothiazole with phosphorus pentachloride.Supposing that the amino compounds (IIIb, c) are formed as a result of imine-amine isomerization, as took place with carboxyethyl derivatives of aminobenzothiazoles [11], we reacted amines (Ia-c) with methyl acrylate at room temperature. Significant quantities of imino products (Ha-d) [amine (Ia) forms products of mono and bis addition] and also dihydro-2H-pyrimidobenzothiazole (IV) were detected in the reaction mixtures in addition to the amino isomers (IIIa-c). The esters (IIb-d) were isolated from the mixtures and were also obtained by alternate syntheses, viz. the esterifieation of the appropriate acids (Vb-d) with dimethyl sulfate. SOCI z IV R=H I]/a-cWe did not succeed in isolating ester (IIa) in a pure state since an equimolar mixture of esters (IIa) and (lib) (from PMR data) was formed on esterifying acid (Va). The corresponding acid was obtained on attempting to purify (IIa) by column chromatography, as in the case of compounds (Ilb-d).The amino esters (IIIa-c) were not saponified on the chromatographic column. They were also obtained by an alternate synthesis by the alkylation of me...

Efficient Conversion of Substituted Aryl Thioureas to 2-Aminobenzothiazoles Using Benzyltrimethylammonium Tribromide

“…Acetonitrile, 1,2-dimethoxyethane, and tetrahydrofuran were also found to be effective (Table , entries 3−5), whereas polar solvents, such as methanol and dimethylformamide, gave little (<5%) or no product (Table , entries 6 and 7). To investigate the compatibility of the ester functional group, thiourea 7 was prepared from aniline and methyl 3-(isothiocyanato)propionate in refluxing methanol and reacted with PhCH 2 NMe 3 Br 3 in acetic acid to give an 84% yield of aminobenzothiazole 8 (Table , entry 1). When the cyclization was conducted in dichloromethane, 8 was isolated in 77% yield (Table , entry 2).…”