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.

GRAPHICAL ABSTRACT

KEYWORDS:

• Green chemistry
• transalkylidation
• thiosemicarbazones
• ¹⁵N-NMR
• 1,2,4-triazolidine-3-thione
• 2-amino-1,3,4-thiadiazoline

Acknowledgements

The authors thank Mr Pasquale Illiano (UNIMI) for doing some NMR spectrum.

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes on contributors

Mohamed A. El-Atawy, an Assistant Professor of Organic Chemistry, his research interest is focused on synthestic methods and structure elucidation of heterocyclic compounds. Moreover, experimental and theoretical studies of the reaction mechanism of certain reactions. Among his recent research “new synthetic methodolgy for pyrroles from nitrodienes”.

Alaa Z. Omar, an Assistant Professor of Organic Chemistry. He currently is the principal investigator for a research group that has ten postgraduate students. His current research interests include the synthesis of unique polymers for solar cell applications, synthesis of novel dyes for industrial applications, design and specified synthesis for antiviral agents, and the synthesis of anticorrosive agents.

Mohamed Hagar, an Associate Professor of Organic Chemistry. His current research interests include the synthesis and structure elucidation of heterocyclic compounds, synthesis of variety of materials used for liquid crystal applications.

Essam M. Shashira, a Professor of Organic Chemistry. His research interest is focused on both photochemistry and synthesis of heterocyclic compounds with evaluation of their biological activities.

ORCID

Mohamed A. El-Atawy http://orcid.org/0000-0002-5042-5221

Mohamed Hagar http://orcid.org/0000-0003-0169-7738