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

Abstract

International audienceThis work aims to present the synthesis of thiosemicarbazones (TSCs) bearing a Ph2P(=O)CH2- 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 Ph2P(=O)CH2{C=N-NH(C=S)-NH-R}CH3 (4a R = Ph; 4b R = p-FC6H4; 4c R = p-ClC6H4; 4d R = 3,5-Me2C6H3; 4e R = 2,5-(MeO)2C6H3; 4f R = CH2C6H5; 4g R = C6H11; 4h R = CH2-CHdouble bondCH2) were prepared by nucleophilic addition of β-phosphonated hydrazone Ph2P(=O)CH2(C=N-H2)CH3 2 across various aromatic and aliphatic isothiocyanates R-N=C=S. The synthesis of 4 is accompanied by competing formation of the phosphonated azine Ph2P(=O)CH2{C(Me)=N-N=C(Me)}CH2P(=O)Ph2 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, 4g 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