Reactions of ketene dithioacetal for a new versatile synthesis of 4,5-substituted 3-aminothiophene-2-carboxylate derivatives

Abstract

Poly substituted 3-aminothiophenes were successfully synthesized in good yields by using a one-pot protocol via ketene S,S-acetal as an intermediate in basic medium (K 2 CO 3 /N,N-dimethylformamide) followed by Dieckmann condensation with ethyl bromoacetate. Further, chemistry of thiophenes was explored using active functional groups such as C 3 -NH 2 , C 4 -CN and C 5 -SCH 3 on the thiophene nucleus.Synthesis of ethyl 3-acetamido-4-cyano-5-(methylthio)thiophene-2-carboxylate derivatives and ethyl 3-amino-4-carbamoyl-5-(methylt hio)thiophene-2-carboxylate derivatives. S COOEt NH-R S H2N O S COOEt NC S NH-R S COOEt NC S NH2 O NH Ar O NH Ar Ar = C6H5, 4-MeOC6H4, 4-ClC6H4 R = H, Acetyl, chloroacetyl, pyrrolyl ARTICLE HISTORY

Copper-Catalyzed Radical C–C Bond Cleavage and [4+1] Annulation Cascade of Cycloketone Oxime Esters with Enaminothiones

“…Synthesis of functionalized thiophenes are often achieved by modification of an existing thiophene ring or through ring-closure reactions. − In this area, considerable advance has been made in the establishment of amino-substituted thiophenes. , Base-promoted multiple-component Gewald reactions and those of β-ketothio-amides have been employed for the synthesis of 2-aminothiophenes. 3-Aminothiophenes are also considered as the important small molecules for drug development, but only a few methods have been reported for their synthesis. , Enaminothiones, that is, α-thioxo ketene N , S -acetals, have been known to react with activated methylene compounds in the presence of stoichiometric Hg­(OAc) 2 or with diazo compounds under Rh­(II) catalysis, affording 3-aminothio-phenes.…”

[4+1] Cycloaddition of Enaminothiones and Aldehyde N‐Tosylhydrazones Toward 3‐Aminothiophenes

“…The domino reaction of vinyl azides and 1,4‐dithiane‐2,5‐diol, and phase transfer catalysis assisted Thorpe reaction of 3‐hydroxy‐2‐arylacrylonitriles and thioglycolates were reported for the preparation of functionalized 3‐aminothiophenes. The multistep reaction of a dicyano‐functionalized ketene dithioacetal was used for the same purpose . It has been known that α ‐oxo ketene S,S‐acetals can be used as the building blocks to establish a thiophene ring .…”