Synthesis of Substituted 2-Methyl-4-quinolyl Isothiocyanates and 4-Mercaptoquinolines

Abstract

Synthesis was performed of substituted 2-methyl-4-quinoline thiouronium salts by reaction of 2-methyl-4-chloroquinolines with thiourea. The alkaline hydrolysis of these salts afforded the corresponding 2-methyl-4-quinolyl isothiocyanates and 2-methyl-4-mercaptoquinolines.We formerly reported on the new route of the alkaline hydrolysis of 2-methyl-4-quinoline thiouronium salts affording 2-methyl-4-quinolyl isothiocyanate [1]. In extension of this research we studied here the reaction with thiourea of 2-methyl-4-chloroquinolines containing in the benzene ring different (electron-donor and electronacceptor) substituents. The reaction occurred at heating the initial components in the ratio quinoline to thiourea equal to 1:1.1 in anhydrous acetone resulting in the quinolylthiouronium salts in a nearly quantitative yield.The alkaline hydrolysis of the salts obtained took two pathways: an intramolecular rearrangement analogous to Smiles rearrangement [25] affording the corresponding quinolyl isothiocyanates, and a bimolecular cleavage of a SC bond giving rise to substituted 2-methyl-4-mercaptoquinolines. The ratio of the final products depended on the character and the position of substituents, and from the 6-methoxy derivative the substitution product was not obtained at all. As expected, the electronic effects of substituents in positions 6 and 8 of the benzene ring were identical. The observed increase in the yield of rearrangement products in the systems under study in all likelihood is due to the existence of the molecule in a conformation most feasible for the rearrangement. This fact apparently governs the lack of compound IVc in the hydrolysis products of S-(2-methyl-6-methoxy-4-quinolyl)thiouronium chloride.

Bioconjugation of Proteins with a Paramagnetic NMR and Fluorescent Tag

“…[13] The corresponding thiouronium bromide 6 was obtained from 5 and thiourea in refluxing acetone, similar to the published protocol. [14] The final product 4MTDA was obtained by hydrolysis of 6 in methanol/water. Accurate binding constants of 4MTDA and lanthanide ions were not determined by NMR spectroscopy due to slow exchange between the free ligand and its metal com-Scheme 1.…”

“…Starting from commercially available dipicolinic acid, compound 5 was synthesized according to a previous report 13. The corresponding thiouronium bromide 6 was obtained from 5 and thiourea in refluxing acetone, similar to the published protocol 14. The final product 4MTDA was obtained by hydrolysis of 6 in methanol/water.…”

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

“…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).…”