Synthesis of thiazol‐2‐imines from the reduction of single enantiomer 2‐imino‐thiazolidin‐4‐ones followed by a spontaneous water elimination

Abstract

Chiral hemiaminals (5‐8RR and 5‐8SS) have been synthesized from the corresponding 2‐iminothiazolidine‐4‐ones (1‐4RR and 1‐4SS) by LiAlH4 reductions stereoselectively and were then converted to single enantiomer thiazol‐2‐imines (9‐12RR and 9‐12SS) by a water elimination reaction. The kinetics of the dehydration reactions which occurred spontaneously both in the solid state and in the solution have been followed by time dependent 1H nuclear magnetic resonance spectroscopy. The corresponding first order rate constants and free energies of activation values for the conversions have been reported.

Axially chiral hemiaminals from nonracemic α‐amino acid derivatives (thiohydantoins): Synthesis and isomer identification

“…Thus, the starting racemic thiohydantoin yielded one diastereomeric pair in excess of the other. Moreover, the trans hydrogens were found to couple with each other with a smaller coupling constant ( 3 J = 2.0 Hz) than the cis ones ( 3 J = 6.4 Hz), as has been observed before 11 …”

“…Moreover, the trans hydrogens were found to couple with each other with a smaller coupling constant ( 3 J = 2.0 Hz) than the cis ones ( 3 J = 6.4 Hz), as has been observed before. 11 Nonracemic axially chiral thiohydantoin derivatives (1-6 and 8-13) were reduced to the corresponding hemiaminals (1a-6a and 8a-13a) in order to see the effect of the chiral axis on the reduction reaction. The products were identified by firstly 1 H NMR.…”

“…5 We had previously reported the reductions of several oxazolidin-and thiazolidin-4-one derivatives to stable racemic 1,9,10 and short-lived nonracemic hemiaminals. 11 Based on our experience on this topic, we presumed that thiohydantoins (2-thioxo-imidazolidin-4-ones) whose asymmetric synthesis has been shown recently 12 could be reduced to reach to stable nonracemic, axially chiral hemiaminals. Other hydantoin derivatives were recently exploited as scaffolds to obtain various α-amino acid derivatives.…”

Solid-phase reactive chromatography (SPRC): a sustainable method for the synthesis of benzimidazol-diphenyl-2-imino-thiazolidine-4-ols (hemiaminals) which are active against lung cancer

“…8 Compounds with a tetrahedral carbon attached to both amino nitrogen and hydroxyl groups are assigned as hemiaminals (carbinolamines). 9 These are highly unstable intermediates in the reaction of amine with carbonyl compounds. In the synthesis of thiazoles, hemiaminals appeared only in the mechanism point of view but were difficult to isolate as stable compounds.…”

“… 13 Not only Gunal et al isolated hemiaminals 10 but also Tuncel and Dogan synthesized chiral hemiaminals by the reduction of 2-iminothiazolidine-4-ones using LiAlH 4 . 9 Hemiaminals can be stabilized using synthetic receptors, 14 dendrimers 15 and triazole rings. 16 …”