A novel four-component reaction involving ring-opening/recyclization of 1,3-thiazolidinedione

Abstract

The multicomponent reactions of 1,3-thiazolidinedione, malononitrile, aromatic aldehydes and -phenylethylamine or -phenylethylamine in acetonitrile at room temperature produce dihydrothiophene ureidoformamide derivatives in moderate yields through a domino ring-opening/recyclization reaction of 1,3-thiazolidinedione. On treatment with DDQ, dihydrothiophenes are dehydrogenated to convert efficiently to thiophenes in the mild condition.

Synthetic Routes to Chiral Nonracemic and Racemic Dihydro- And Tetrahydrothiophenes

“…This approach proved to run efficiently with a wide range of aldehydes and amines regardless of their substitution patterns, − providing the S -heterocycles exclusively as trans -isomers, in good yields, as depicted in Figure for representative derivatives 418 – 424 .…”

New One Pot and Efficient Four‐Components Reaction for Synthesis of 2,3‐Dihydrothiophene Carbamate Derivatives

“…All of these methods consist of a fourcomponent reaction between aromatic aldehydes, malononitrile, 2,3-thiazolinedione and amino derivatives such as αaminoesters, primary and secondary aliphatic or cyclic amines, in the presence of a variety of catalysts and under different conditions. [14,[36][37][38][39][40][41][42][43][44][45] It has been described that a mixture of arylidenemalononitrile and 1,3-thiazolidinedione brought to reflux in ethanol in the presence of piperidine leads to pyrano [2,3-d][1,3]thiazole derivatives with good yields. [46][47] Given that arylidenemalonitrile can be easily formed in situ, via the condensation of Knovenogel between an aromatic aldehyde with malononitrile, and in the continuation of our research of new methods of synthesis in heterocyclic series, we set out to study the threecomponent reaction between an aromatic aldehyde, malonotrile and 1,3-thiazolidinedione, refluxed in ethanol, in the presence of N,N-dimethylaminopyridine, as a catalyst.…”

“…This unexpected result is important to us not only because we believe to establish a new one-pot four-component domino reaction, but also because of the biological interest of 2,3dihydrothiophene derivatives while all the described preparation procedures of dihydrothiophenes and the like have suffered from synthetic restriction to only a limited range of dihydrothiophene ureidoformamides. [14,[36][37][38][39][40][41][42][43][44][45]…”

“…Only a few multicomponent methods have been disclosed for the construction of dihydrothiophene derivatives. All of these methods consist of a four‐component reaction between aromatic aldehydes, malononitrile, 2,3‐thiazolinedione and amino derivatives such as α‐aminoesters, primary and secondary aliphatic or cyclic amines, in the presence of a variety of catalysts and under different conditions [14,36–45] …”

Synthesis of Functionalized Thiophenes by Four‐component Reactions of 1,3‐Thiazolidinedione, Aromatic Aldehydes, Cyanoacetamide and Cyclic Secondary Amines

“…[15][16][17][18][19] Recently, we developed an unprecedented and efficient synthetic protocol for the polysubstituted dihydrothiophens via domino reaction of 1,3-thiazolidinedione, malononitrile, aromatic aldehydes and amines. [20][21][22] The reaction showed very interesting molecular diversity when one or two reaction components were changed. The reactions of ethyl cyanoacetate and pivaloylacetonitrile still gave the corresponding functionalized dihydrothiophenes.…”