The (E, Z) Isomerization of C-methoxycarbonyl-N-aryl Chlorohydrazones

Since chlorohydrazones are planar molecules, it is in principle possible to distinguish between their E and Z stereoisomers. Chlorohydrazones are known to preferentially assume the Z configuration around the C=N double bond, and their (E, Z) isomerization is almost suppressed at room temperature. The lack, or rather the difficulty, of such an isomerization has been conveniently addressed by the in-depth theoretical study of seven C-methoxycarbonyl-N-aryl chlorohydrazones (aryl = phenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 2-chlorophenyl, 2-bromophenyl, and 2-iodophenyl). DFT !B97M-D4/cc-pVTZ calculations of these C-methoxycarbonyl-N-aryl chlorohydrazones, supported by the XRD determination of the molecular structure, provided a complete picture of the isomerization processes in the studied compounds. The analysis of the energetics, molecular geometry, and electronic structure (the latter in the framework of the Quantum Theory of Atoms In Molecules) showed that the Z isomers are thermodynamically favored because, within the low-energy planar isomers with extensive ? conjugation, the electrostatic interactions between the dipoles of the C-O, C-Cl, and N-H bonds overcome the stabilization induced by the N-H ··· O bond present in the E isomers. We confirmed that the (E, Z) isomerization occurs by the umklapp mechanism, in which the -NHAr moiety rotates in the molecular plane towards a linear C=N-N configuration and then proceeds to the other isomer. The (E, Z) isomerization is very slow at room temperature because the umklapp interconversion has high barriers (?110 kJ/mol) despite the extended ? electron delocalization present in the transition state.