Work

Synthesis and structural characterization of β-phosphonated thiosemicarbazones: Investigation of their Z/E interconversion by NMR and DFT computing

Year: 2025

Type: article

Abstract: This work aims to present the synthesis of thiosemicarbazones (TSCs) bearing a Ph 2 P(=O)CH 2 - moiety, a yet unknown subclass of TSCs, along with their crystal structures and the Z / E interconversion occurring in solution. For this purpose, eight new phosphonated thiosemicarbazones Ph 2 P(=O)CH 2 {C=N-NH(C=S)-NH-R}CH 3 (4a R = Ph; 4b R = p -FC 6 H 4 ; 4c R = p -ClC 6 H 4 ; 4d R = 3,5-Me 2 C 6 H 3 ; 4e R = 2,5-(MeO) 2 C 6 H 3 ; 4f R = CH 2 C 6 H 5 ; 4 g R = C 6 H 11 ; 4h R = CH 2 -CH CH 2 ) were prepared by nucleophilic addition of β-phosphonated hydrazone Ph 2 P(=O)CH 2 (C=N-H 2 )CH 3 2 across various aromatic and aliphatic isothiocyanates R-N=C=S. The synthesis of 4 is accompanied by competing formation of the phosphonated azine Ph 2 P(=O)CH 2 {C(Me)=N-N=C(Me)}CH 2 P(=O)Ph 2 3 and of bis( N -arylthioureas) or bis( N -alkylhexylthioureas) 5 , lowering the overall yield of 4 . All products were characterized by multinuclear NMR, FT-IR spectroscopy and UV–vis spectroscopy. NMR spectroscopy of 4 at variable temperature indicates the coexistence of E and Z -isomers in solution with respect to the relative position of the substituents around the hydrazonic – C=N–NH- array. Several crystal structure determinations by single crystal X-ray diffraction (SC-XRD) reveal that in the solid state exclusively the E isomer is present, except for 4e which adopts a Z configuration due to an intramolecular C-O ··· H-N and P=O · ·· H-N hydrogen bonding. For all derivatives, also an intramolecular N-H ··· N bonding is evidenced. The individual molecules of 4a, 4b, 4d, 4f, 4 g and 4h are associated by strong intermolecular P=O ··· H-N hydrogen bonding in form of supramolecular macrocyclic dimers or 1D chains. These secondary interactions were further examined by a Hirshfeld surface analysis of 4f . For a comparison of the experimental SC-XRD parameters with the theoretical calculated ones and the preferred configuration, DFT calculations at the B3LYP/6–311 + G (d, p) level were performed both in solution and in the gas phase. A computing of the Intrinsic Reaction Coordinates (IRC) revealed that the E -isomer of 4a is energetically more stable than the Z -isomer, since there is less steric crowding.

Source: Journal of Molecular Structure

DOI: 10.1016/j.molstruc.2025.144576