Ring Transformation Reactions, I. Conversion of 6‐Aryl‐4‐(methylthio)‐2‐oxo‐2H‐pyran‐3‐carbonitriles to pyrazoles

Abstract

A new ring transformation reaction has been studied by treating 6-or 5,6-disubstituted 4-(methylthio)-2-0~0-2H-pyran-3-carbonitriles 2 with hydrazine and methylhydrazine leading to polysubstituted pyrazoles 4, 5, 6.In view of a subsequent synthesis, we intended to develop a simple procedure for the preparation of 5(3)-aryl-3(5)-(cyanomethyl)-Imethyl-1 H-pyrazoles. Procedures in vogue for the synthesis of pyrazoles involve, in general, cyclocondensation between a hydrazine system and a three-carbon component with electrophilicity at terminal carbon atoms. A substrate fulfilling the above conditions and bearing a built-in potentiality for eventual elaboration of a CH,CN side chain was sought for. The 6-aryl-4-(methylthio)-2-0~0-2H-pyran-3-carbonitriles 2, endowed with two sets of such functionalities, (2-4-C-3 -CN and C-4-C-5 -(2-6, in the molecule, was recognized attractive. 2 has earlier been reported to react with hydrazine to afford 1 and 3'), a claim which could not be substantiated in our hands. On the contrary, a reexamination of the procedure under strictly reported conditions') gave invariably pyrazoles 4. The authenticity of this reaction was further checked by replacing hydrazine with methylhydrazine which afforded 5 and 6. These observations suggest the involvement of C-4 and C-6 in pyrazole formation instead of C-4 and CN as claimed earlier. The reaction seems to be initiated by a Michael addition of hydrazines at C-4 in 2 with expulsion of methanethiol and simultaneous ring opening followed by recyclisation and decarboxylation to yield the (cyanomethy1)pyrazoles (Scheme 1). Nevertheless, the initial attack at C-6 by hydrazines cannot be excluded as well.Both the positional isomers 5 and 6 were separated from the reaction mixture by column chromatography. Their structures were established by 'H-and 13C-NMR analyses. The downfield resonances for aryl and heteroaryl protons of demethylpyrazoles resembled in pattern and position to those of 6 whereas, in cases of isomers 5, the NCH3 invariably exerted a shielding effect on protons of aryl and heteroaryl substituents at C-5. This diagnostic feature, bearing a testimony to an earlier observation in case of n i~o t i n e~,~) , may be utilized for distinguishing the isomers 5 and 6.The reaction between 5-(3,4-dimethoxyphenyl)-6-methyl-4-(methylthio)-2-oxo-2H-pyran-3-carbonitrile (2c) and methylhydrazine gave a single product whose structure as 5 e was established by observing a strong NOE between 5-CH3 and NCH3 groups.This observation constitutes the first example of such a ring transformation reaction.

Direct alkenylation of indolin-2-ones by 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles: a novel approach

“…The precursor 3 was prepared from the reaction of methyl 2-cyano-3,3-dimethylthioacrylate [39–40] ( 1 ) and aryl methyl ketone ( 2 ) in the presence of powdered KOH in DMF at room temperature as reported earlier [41–42] (Scheme 1). …”

“…Further, in order to generalize the reaction, attempts were made for the alkenylation of indolin-2-one with 6-aryl-4- sec -amino-2 H -pyran-2-one-3-carbonitriles 9 [41–42], obtained by the amination of 3 with sec -amine in boiling ethanol to yield a sec -amino substituted alkenylated chain on position 3 of the indolin-2-one ( 4 ). But to our utmost surprise the expected alkenylated product 11 could not be isolated.…”

Design, synthesis and docking studies of new furobenzopyranones and pyranobenzopyranones as photoreagent towards DNA and as antimicrobial agents

“…4,9-Dimethoxy-7-oxo-5-methyl-7H-furo [3,2-g]benzopyrane-6-carbonitrile 2 was synthesized directly, in good yield, by refluxing 1-(6-hydroxy-4,7-dimethoxybenzofuran-5-yl) ethanone 1 with ethyl cyanoacetate in sodium ethoxide [38,39]. Compound 2 was routinely hydrolyzed to the corresponding 4,9-Dimethoxy-7-oxo-5-methyl-7H-furo[3,2-g]benzopyrane-6-carboxylic acid 3 by refluxing with 15% sodium hydroxide for three hours then acidified [40].…”

“…The same pathway was performed for the synthesis of pyranobenzopyranone derivatives, Scheme 2. 2(1H)-oxo-4-methyl-(2(1H)oxo-4-phenyl-pyrano)[2,3-f]benzopyran-3-carbonitrile 9 was synthesized through refluxing 8-Acetyl-7-hydroxy-4-phenyl-2H-1-benzopyran-2-one 8 with ethyl cyanoacetate in sodium ethoxide [38,39], followed by its hydrolysis to give 2(1H)-oxo-4-methyl-(2(1H)oxo-4-phenyl-pyrano)[2,3-f] benzopyran -3-car boxylic acid 10 [40]. It was then estrified to afford Methyl-2(1H)-oxo-4-methyl-(2(1H)oxo-4-phenyl-pyrano) [2,3-f] [1]benzopy ran-3-carboxylate 11 [40].…”

Carbanion induced synthesis of pyrido[2,1-b] benzothiazoles through ring transformation reactions

“…8 It has also been obtained by 1,4-dipolar cycloaddition reactions of pyridiniumolates with ynamines. 9 Our approach to pyrido[2,1-b]benzothiazoles 10 here is a singlestep carbanion-induced ring transformation reaction involving 6-aryl-4-methylsulfanyl-2-oxo-2H-pyran-3-carbonitrile 11 (1) and 2-benzothiazoleacetonitrile (2). The electronic topography of lactone (1) shows the presence of three electrophilic centres C 2 , C 4 and C 6 of which the last is the most susceptible to nucleophilic attack, followed by C 4 and C 2 .…”