Synthesis of Dihydrothiophenes or Spirocyclic Compounds by Domino Reactions of 1,3-Thiazolidinedione

Abstract

The domino reactions of 1,3-thiazolidinedione, malononitrile, and aromatic aldehydes in the presence of different organic amines were studied. Secondary amines such as pyrrolidine, piperidine, morpholine, and dimethylamine and primary amines such as benzylamine yield dihydrothiophene derivatives through a domino ring-opening/recyclization reaction of 1,3-thiazolidinedione. Bulky diethylamine, diisopropylamine, and 1,4-diazabicyclo[2.2.2]octane give spirocyclohexano-1,3-thiazole through a double Michael addition/spirocyclization reaction.

Triethylamine‐Catalyzed Domino Reactions of 1,3‐Thiazolidinedione: A Facile Access to Functionalized Dihydrothiophenes

“…Note that under these new reaction conditions aromatic amines usually gave higher yields of dihydrothiophenes than the aliphatic amines studied in our previous work. [14] This domino reaction proceeds in a very straightforward manner. To explain the formation of dihydrothiophenes by this one-pot domino multicomponent reaction, we have proposed a plausible reaction mechanism, which is illustrated in Scheme 1.…”

“…[10][11][12][13] Recently we reported a novel domino reaction involving 1,3-thiazolidinedione, malononitrile, aromatic aldehydes, and amines. [14] The reaction is unique because the ring-opening/ recyclization or spiro-cyclization process unexpectedly occurs at the 1,3-thiazolidinedione ring with different kinds of amines, and dihydrothiophene or spirocyclohexane [1,3]thiazole derivatives, which are normally difficult to prepare, [15][16][17] are obtained in a very convenient manner. To been synthesized in high yields.…”

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

“…Secondary amines such as pyrrolidine, piperidine, morpholine, and dimethylamine, and primary amines such as benzylamine yield dihydrothiophene derivatives through a domino ring-opening/recyclization reaction of 1,3-thiazolidinedione. Bulky amines such as diethylamine, diisopropylamine, and 1,4-diazabicyclo[2.2.2]octane give spirocyclohexano-1,3-thiazole through a double Michael addition/spirocyclization reaction [14]. It is very interesting to investigate the reactivity of primary amines with large alkyl substituents such as -phenylethylamine or -phenylethylamine.…”

“…Here this one-pot, multicomponent reaction clearly went through with a domino procedure. [14] Initally Knoevenagel condensation of aromatic aldehyde with malononitrile gave arylidenemalononitrile. Then Michael addition of the carbanion of 1,3-thiazolidinedione to arylidenemalononitrile yielded an adduct.…”

“…In this regard, the development of new domino reaction methodologies is very important in the fields of organic and medicinal chemistry [10][11][12][13]. Recently we have reported a novel domino reaction of 1,3-thiazolidinedione, malononitrile, aromatic aldehydes and amines [14]. The reaction is very unique because the ring-opening/recyclization or spirocyclization process unexpectedly occurs at the ring of 1,3-thiazolidinedione with different kinds of amines, and novel dihydrothiophene or spirocyclohexano [1,3]thiazole derivatives, which are normally difficult to prepare, are obtained in a very convenient manner.…”