N-Benzhydrylformamides are pharmacologically active compounds with anticonvulsant, enzyme-inducing, antihypoxic, and other types of biological activity. The conformational behavior of benzhydrylformamides is determined to a great extent by the presence of substituents at the nitrogen atom and in the ortho-position(s) of the diphenylmethane moiety. Particularly, the NMR spectra of these compounds often contain two sets of signals originating from different orientations of the formyl group. With the use of the dynamic NMR method and DFT calculations, we investigated the internal rotations of aromatic and formyl fragments and estimated the corresponding rotational barriers in N-benzhydrylformamide (BHFA), N-methyl-N-benzhydrylformamide (BHFA-NMe), and in a series of ortho-halogen-substituted N-benzhydrylformamides. It was found that the DFT method at M06-2X/6-311+G* level of theory satisfactorily reproduces the experimental barrier $\Delta G_{298}^{\ne }$(Formyl) of the formyl group rotation in BHFA-NMe. In BHFA, BHFA-NMe, and in the ortho-halogen derivatives, the calculated $\Delta G_{298}^{\ne }$(Formyl) values are close to each other and lie within 20–23 kcal/mol. On the other hand, the ortho-substituents significantly hinder the rotation of aryl fragment with $\Delta G_{298}^{\ne }$(Aryl) values varying from 2.5 kcal/mol in BHFA to 9.8 kcal/mol in ortho-iodo-N-benzhydrylformamide.

A wide variety of acyclic ureas comprising alkyl, arylalkyl, acyl, and aryl functional groups are investigated by nuclear magnetic resonance spectroscopy. In general, spectral characteristics of more than 130 substances based on acyclic ureas dissolved in deuterated dimethyl sulfoxide at room temperature are studied. The results obtained based on the studies of H-1 and C-13 NMR spectra of urea and its N-alkyl-, N-arylalkyl-, N-aryl- and 1,3-diaryl derivatives are presented, and the effect of these functional groups on the chemical shifts in carbonyl and amide moieties in acyclic urea derivatives is discussed. An introduction of any type of substituent (electron-withdrawing or electron-donating) into urea molecule is stated to result in a strong upfield shift in C-13 NMR spectra relatively to unsubstituted urea. A strong sensitivity of NH protons to the presence of acyl and aryl groups in nuclear magnetic resonance spectra is pointed out. In some cases, qualitative dependencies between the chemical shifts in the NMR spectra and the structure of the studied acyclic ureas are revealed. A summary of the results on chemical shifts in the NMR spectra of the investigated substances allows determining the ranges of chemical shift variations of the key protons and carbon atoms in acyclic ureas. The literature describing the synthesis procedures are provided. The results obtained significantly expand the methods of reliable identification of biologically active acyclic ureas and their metabolites that makes it promising to use NMR spectroscopy both in biochemistry and in clinical practice.