Kinetics and Mechanism of Desulfurization Reaction of 1-Methyl-2-phenylquinazoline-4(1H)-thiones

Abstract

Kinetics and mechanism of desulfurization reaction of 1-methyl-2-(substituted phenyl)-quinazoline-4(1H)-thiones in sodium methoxide solutions have been studied, giving the corresponding 1-methyl-2-(substituted phenyl)quinazolin-4(1H)-ones. The reaction proceeds in two steps. The first step involves splitting off of sulfur in the form of SH- and is much faster than the second step, whose rate is almost independent of the concentration of water in methanol. At lowest concentrations of methoxide, the rate of the first step increases linearly, but at higher concentrations a gradual decrease in the rate takes place. The rate of the second step, i.e. the transformation of the intermediate formed In into 1-methyl-2-(substituted phenyl)quinazolin-4(1H)-one (2a-2e), is independent of the methoxide concentration but increases with increasing concentration of water in methanol. On the basis of the kinetic dependences, the mechanism for both steps of desulfurization and the structure of intermediate In were proposed.

2-Amino- and 2-Alkylthio-4H-3,1-benzothiazin-4-ones: Synthesis, Interconversion and Enzyme Inhibitory Activities

“…On the other hand, the benzothiazinone 5i was the main product of the reaction of 4i with TFAA while the corresponding benzoxazinone 9i was only formed in traces. The formation of 8h is envisaged to occur by a nucleophilic attack of the carboxyl oxygen at the activated thiocarbonyl carbon [ 31 , 32 , 33 , 34 , 35 , 36 ]. Further investigations are needed to clarify the mechanism of this desulphurisation-cyclisation.…”

Cyclization of 2-benzoylamino-N-methyl-thiobenzamides to 3-methyl-2-phenylquinazolin-4-thiones

“…In our previous paper [10] we studied the kinetics and mechanism of base catalyzed cyclization giving analogous 1-methyl-2-(subst.phenyl)quinazoline-4-thiones. Studying this reaction, we found out [11] that in this case consecutive desulfurization reaction in methanolic sodium methoxide at room temperature took place leading to the corresponding quinazoline-4-one. Similar desulfurization reaction of 3-methyl-2-(subst.phenyl)quinazoline-4-thiones proceeds very slowly even at elevated temperature which is probably connected with different tautomeric forms of quinazoline-4-thione (1H vs. 3H form).…”

“…In some cases it is also possible to make use of the reactivity of suitably substituted isothiocyanates [8]. In our previous papers [9][10][11] we dealt with the synthesis, structure and reactivity of 2-benzoylaminothiobenzamides, 2-[(Nmethyl-N-benzoyl)amino]thiobenzamides and products of their cyclization in both basic and acidic medium.…”

Unexpected formation of 5,5-diethoxy-5H-1,2,3-dithiazoles from 5H-1,2,3-dithiazole-5-thiones

“…6 The formation of gem-dialkoxy heterocyclic derivatives was proposed only for 1-methyl-2-(substituted phenyl)-quinazoline-4(1H)-thiones. 7 The plausible mechanism for the formation of 5,5-diethoxy-5H-1,2,3-dithiazoles 2 from thiones 1 is given in Scheme 2. The reaction could start with nucleophilic attack of ethoxide anion at the 5-position of the dithiazole ring followed by its opening into S-S bond and the formation of thioester 8.…”