Use of natural aminoacids as efficient green catalyst in the synthesis of thiosemicarbazones

Urbain C. Kasséhin; Odilon Q. ASSAN; Fernand A. Gbaguidi; Julien R. C. Prévost; Raphaël Frédérick; Jacques H. Poupaert

Authors

Urbain C. Kasséhin Laboratoire de Chimie Pharmaceutique Organique (MOCL), Ecole de Pharmacie, Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Campus du Champ de Foire, 01 BP 188, Cotonou, Bénin.
Odilon Q. ASSAN Laboratoire de Chimie Pharmaceutique Organique (MOCL), Ecole de Pharmacie, Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Campus du Champ de Foire, 01 BP 188, Cotonou, Bénin.
Fernand A. Gbaguidi Laboratoire de Chimie Pharmaceutique Organique (MOCL), Ecole de Pharmacie, Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Campus du Champ de Foire, 01 BP 188, Cotonou, Bénin.
Julien R. C. Prévost Laboratoire de Chimie Pharmaceutique Organique (MOCL), Ecole de Pharmacie, Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Campus du Champ de Foire, 01 BP 188, Cotonou, Bénin.
Raphaël Frédérick Medicinal Chemistry Research Group (CMFA), Louvain Drug Research Institute (LDRI), Université catholique de Louvain., Av. E. Mounier, 73, Box B1.73.10, B-1200 Bruxelles, Belgium.
Jacques H. Poupaert Medicinal Chemistry Research Group (CMFA), Louvain Drug Research Institute (LDRI), Université catholique de Louvain., Av. E. Mounier, 73, Box B1.73.10, B-1200 Bruxelles, Belgium.

Keywords:

Natural alpha-aminoacids - Green efficient catalyst- Nucleophilic catalysis-Thiosemicarbazones

Abstract

In an effort to find improved conditions for the synthesis of medicinally relevant thiosemicarbazones basing our approach on green chemistry approach, we used ten natural alpha aminoacids as nucleophilic catalysts. We therefore hypothetized that aminoacid acid being amphoteric reagent, should be able to boost a reaction submitted to general acid-base catalysis. Using cyclohexanone 4-phenylthiosemicarbazone as target compound for our benchmark reaction, we were able to demonstrate the validity of our hypothesis. A plot of “hydrophobicity/lipophilicity” balance as reflected by logP and the net actual yield does not show any significant correlation, however it is remarkable to note that while L-phenylalanine shows opposite behavior in water (94%) and methanol (24%), glycine – the most concise alpha-amino-acid – performs equally very well in both solvents (95% and 90%, respectively). These green catalysts and specially glycine may be useful in the elaboration of a compound library.