Transalkylidation reaction: green, catalyst-free synthesis of thiosemicarbazones and solving the NMR conflict between their acyclic structure and intramolecular cycloaddition products

Abstract

A series of arylidene thiosemicarbazides have been prepared by a new method, which was titled as transalkylidation. This method is an effective, fast, green and clean method. The mechanism of this reaction has been discussed. Moreover, we clarified the divergences of the structural assignments reported in the literature for the reaction of thiosemicarbazide and aldehydes or ketones in the presence of different catalysts. Where 1,2,4-triazolidine-3-thiones were incorrectly reported as sole product of such reaction, based on occurance of intramolecular cycloaddition of thiosemicarbazones formed in situ. Our findings proved that the reaction stops at earlier stage of thiosemicarbazone and neither cyclization to 1,2,4-triazolidine-3-thiones nor 2-amino-1,3,4-thiadiazoline take place. We have removed the confusion of the NMR interpretation of thiosemicarbazone and their cycloaddition product by carrying out 1H-NMR, 13C-NMR, 15N-NMR and 1H-15N HSQC experiments with temperature gradient. Furthermore, DFT-NMR calculations have been done to make structural distinguish between the three possible structural isomers for this reaction, namely, 1,2,4-triazolidene-3-thione, 2-amino-1,3,4-thiadiazoline and thiosemicarbazone.