Synthesis of 1-[2-Methyl-6(8)-R-quinolin-4-yl]thiosemicarbazides

Abstract

1-(2-Methylquinolin-4-yl)thiocemicarbazides and S- (2-methylquinolin-4-yl)thiosemicarbazide hydrochlorides were synthesized by reaction of 6(8)-substituted 4-chloro-2-methylquinolines with thiosemicarbazide under different conditions. Alkaline hydrolysis of the hydrochlorides afforded substituted 1-(2-methylquinolin-4-yl)thiosemicarbazides. † Deceased.In continuation of our studies on nucleophilic substitution in 4-chloro-2-methyl-6(8)-methyl(methoxy)-quinolines Ia-Ie [1][2][3][4][5] in the present work we examined their reactions with thiosemicarbazide under different conditions and found optimal conditions for these reactions. By heating equimolar amounts of the reactants in ethanol in the presence of a catalytic amount of hydrochloric acid (reaction time 15-16 h) we obtained the corresponding quinolylthiosemicarbazide dihydrochlorides IIa-IIe in high yields (Scheme 1). The concentration of HCl in the isolated salts was determined by titration. Treatment of aqueous solutions of dihydrochlorides IIa-IIe with alkali gave the corresponding free bases, substituted 1-(2-methylquinolin-4-yl)thiosemicarbazides IIIa-IIIe in almost quantitative yield.The reaction of 4-chloro-2,6-dimethylquinoline Ib with thiosemicarbazide in acetone on heating for 30 h gave S-(2,6-dimethylquinolin-4-yl)isothiosemicarbazide hydrochloride (IVb) as the only product in almost quantitative yield. However, compounds Ia and Ic-Ie under analogous conditions gave rise to mixtures of the corresponding S-(2-methylquinolin-4-yl)isothiosemicarbazide hydrochlorides IVa and IVc-IVe and 1-(2-methylquinolin-4-yl)thiosemicarbazide dihydrochlorides IIa and IIc-IIe (Scheme 2). Alkaline hydrolysis of isothiosemicarbazide hydrochloride IVb or mixtures II/IV led to the formation of 1-(2-methylquinolin-4-yl)thiosemicarbazides IIIa-IIIe. EXPERIMENTALThe IR spectra were recorded on a UR-20 spectrometer from samples dispersed in mineral oil. The 1 H NMR spectra were measured on a Varian Mercury-300 instrument from solutions in DMSO-d 6 . The purity of the isolated compounds was checked by TLC on Silufol UV-254 plates; spots were visualized by treatment with iodine vapor. 2-(2-Methylquinolin-4-yl)hydrazinecarbothioamide dihydrochlorides IIa-IIe (general procedure).A mixture of 0.01 mol of 4-chloro-2-methylquinoline

The Proton Sponge Effect: Substitution of Quino[7,8‐h]quinoline and the First Structurally Characterised Derivatives

“…This arrangement of molecules is not possible in 6 where instead the lone electron pairs on the heteroatoms are orientated towards the chloroform solvent molecules. [15] In these papers, the tautomerism was reversible; however, as a result of the basicity of 10, 11a and 11b, the thermodynamic equilibrium sits firmly in favour of one of the two aniline groups present adopting the imino form, as evidenced in both the solution and solid-state studies. The substitution of the 4,9-chlorides on 6 with anilines was attempted; p-toluidine was used to test the reaction methodology, as it was hoped that the methyl group would provide improved solubility.…”