Novel One-Pot Synthesis of Methyl 4-Hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate: Synthetic and Crystallographic Studies

Abstract

A new suitable method of synthesis of methyl 4-hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate by condensation of methyl 2-isothiocyanatobenzoate and methyl malonate is described. The structure of the compound both and by-product methyl 2(methoxycarbonothioylamino)benzoate was confirmed by means of elemental analysis, 1H NMR, 13C NMR, LC/MS and single crystal X-ray diffraction. UV/Vis and IR spectra of compounds are described. The presence of a strong intramolecular hydrogen bond between the hydroxy group and the carbonyl oxygen atom of the ester group in methyl 4-hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate is shown. The crystal structure of product was stabilized through intermolecular hydrogen bonds.

Methylation of Methyl 4-Hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate: Synthetic, Crystallographic, and Molecular Docking Studies

“…Just S-alkylation was proved by the position of the singlet of SCH 3 protons at 2.65 ppm in 1 H-NMR spectrum of methyl 4-hydroxy-2-(methylthio)quinoline-3-carboxylate 3 and SCH 3 carbon at 15.6 ppm in 13 C-NMR spectrum. The broad peak of the OH proton was present at 11.60 ppm, but the signal of the thioamide proton near 13 ppm, that is characteristic for cyclic thioamides [ 19 ], was absent in 1 H -NMR spectrum of the product 3 . In the 1 H-NMR spectrum of methyl 4-methoxy-2-(methylthio)quinoline-3-carboxylate 4 , the new peak of the 4-OCH 3 protons appeared at 4.03 ppm, while the peak of the OCH 3 protons of ester group was shifted to 3.94 ppm.…”

“…Starting methyl 4-hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate 2 was obtained according to method [ 19 ]. CH 3 I, NaH, K 2 CO 3 and solvents are commercially available, were reagent grade and were used without further purification.…”

“…Previously we developed a new simple method of one-pot synthesis of methyl 4-hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate 2 via condensation of methyl 2-isothiocyanatobenzoate 1 and methyl malonate [19] (Scheme 1). Scheme 1.…”

Crystal structure, Hirshfeld analysis and a molecular docking study of a new inhibitor of the Hepatitis B virus (HBV): ethyl 5-methyl-1,1-dioxo-2-{[5-(pentan-3-yl)-1,2,4-oxadiazol-3-yl]methyl}-2H-1,2,6-thiadiazine-4-carboxylate

“…Heterocyclic homologues of 2H-1,2,6-thiadiazine-1,1-dioxides are inhibitors of human cytomegalovirus (Martínez et al, 2003), Cruzi triposome (Á lvarez et al, 2010) and diuretics (Goya et al, 1992). In a continuation of our efforts to obtain new HBV inhibitors for the treatment and prevention of human HBV infections (Ivachtchenko et al, 2019;Ivashchenko et al, 2019;Kovalenko et al, 2019), we initiated the design, synthesis, and anti-hepatitis B virus activity testing of the new 2H-1,2,6thiadiazine 1,1-dioxide derivative, ethyl 5-methyl-1,1-dioxo-2-{[5-(pentan-3-yl)-1,2,4-oxadiazol-3-yl]methyl}-2H-1,2,6-thiadiazine-4-carboxylate (3).…”