Synthesis and structural study of five new phosphoric triamides: interplay between classical and non-classical intermolecular interactions

Phosphoric triamides are attractive to investigate because of their extensive applications in various fields, especially in medicine. Five new phosphoric triamides with the main parts [N]P(O)[NH]2 and [C(O)NH]P(O)[N]2 have been structurally analyzed by single crystal MoKα/synchrotron-based X-ray diffraction and characterized by spectroscopic methods (FT-IR and 1H, 13C, 31P NMR). Compounds crystallize in orthorhombic (1 with space group Pnma) and monoclinic (2 (P21/a), 3 (C2/c), 4 (P21/n) and 5 (P21/c)) crystal systems. The asymmetric unit of all structures consists of one phosphoric triamide molecule, except for 1 with one half of molecule. X-ray crystallography data reveal that the molecular architectures constructed by classical N—H … O hydrogen bonds are as 1D linear (building the R 2 1 ( 6 ) ${R}\_{2}^{1}(6)$ , C(4) and R 2 2 ( 10 ) / R 2 1 ( 6 ) ${R}\_{2}^{2}(10)/{R}\_{2}^{1}(6)$ motifs, respectively, for 1–3) or dimeric (the R 2 2 ( 8 ) ${R}\_{2}^{2}(8)$ ring motif for 4 and 5). A detailed investigation of the intermolecular interactions using Hirshfeld surface (HS) analysis illustrates that the H … H, O … H/H … O and C … H/H … C contacts for all compounds, and Cl … H/H … Cl and F … H/H … F contacts for 3–5, are the most significant contributors to the crystal packing. Moreover, based on the calculated enrichment ratios (E), the O … H/H … O contacts including the classical N—H … O hydrogen bonds for all structures are considered as favoured contacts.

Evaluation of N–H···O hydrogen bond interactions in two new phosphoric triamides with a P(O)[NHCH(CH3)2]2 segment by means of topological (AIM) calculations, Hirshfeld surface analysis and 3D energy framework approach

Two new phosphoric triamides having a common part XP(O)[NHCH(CH3)2]2, with X =[2,3,6-F3–C6H2C(O)NH] (1) and [C6H11(CH3)N] (2), were prepared and characterized by spectroscopic techniques (FT-IR and 1H-, 13C-, 31P-NMR) and single crystal X-ray diffraction. The asymmetric unit of 1 is composed of one molecule, whereas for 2 it consists of six symmetry independent molecules. In all molecules, the P atoms are in a distorted tetrahedral environment of one oxygen and three nitrogen atoms. The latter have mainly sp2 character and a nearly planar environment. The crystal structures are stabilized via N–H · · · O hydrogen bond interactions, forming a linear arrangement for 1 and three independent parallel linear chains for 2, along the b and a axis, respectively. The intermolecular interactions in the molecular packing were analyzed using the Hirshfeld surface methodology, two-dimensional (2D) fingerprint plots and enrichment ratios (E). The prevalent interactions revealed by Hirshfeld surfaces are O · · · H type interactions for both structures 1 and 2, additionally C · · · O for 1 and H · · · H interactions for 2. The most favored contacts responsible for the molecular packing are C · · · F, N · · · H and O · · · H for 1 confirmed by E values greater than 1.30, whereas for 2, O · · · H and N · · · H intermolecular interactions with E values about 1.04 representing the favored contacts. Thus, the N–H · · · O hydrogen bond interactions are the dominant interactions in both compounds. For more details, a topological AIM analysis of N–H · · · O hydrogen bond interactions was performed: NCP–H · · · O=C hydrogen bond (the NCP is referred to the nitrogen atom within the C(O)NHP(O) segment) interactions in 1 are stronger than N–H · · · O=P interactions in both 1 and 2. Furthermore, a 3D topology of the molecular packing via the energy framework approach showed that the N–H · · · O hydrogen bond interactions in C(O)NHP(O)-based phosphoric triamide are predominantly electrostatic based, while they are electrostatic-dispersion based for other phosphoric triamides with a [N]P(O)[NH]2 skeleton.

Chiral one-dimensional hydrogen-bonded architectures constructed from single-enantiomer phosphoric triamides

The two single-enantiomer phosphoric triamides N-(2,6-difluorobenzoyl)-N′,N′′-bis[(S)-(−)-α-methylbenzyl]phosphoric triamide, [2,6-F2-C6H3C(O)NH][(S)-(−)-(C6H5)CH(CH3)NH]2P(O), denoted L-1, and N-(2,6-difluorobenzoyl)-N′,N′′-bis[(R)-(+)-α-methylbenzyl]phosphoric triamide, [2,6-F2-C6H3C(O)NH][(R)-(+)-(C6H5)CH(CH3)NH]2P(O), denoted D-1, both C23H24F2N3O2P, have been investigated. In their structures, chiral one-dimensional hydrogen-bonded architectures are formed along [100], mediated by relatively strong N—H...O(P) and N—H...O(C) hydrogen bonds. Both assemblies include the noncentrosymmetric graph-set motifs R 2 2(10), R 2 1(6) and C 2 2(8), and the compounds crystallize in the chiral space group P1. Due to the data collection of L-1 at 120 K and of D-1 at 95 K, the unit-cell dimensions and volume show a slight difference; the contraction in the volume of D-1 with respect to that in L-1 is about 0.3%. The asymmetric units of both structures consist of two independent phosphoric triamide molecules, with the main difference being seen in one of the torsion angles in the OPNHCH(CH3)(C6H5) part. The Hirshfeld surface maps of these levo and dextro isomers are very similar; however, they are near mirror images of each other. For both structures, the full fingerprint plot of each symmetry-independent molecule shows an almost asymmetric shape as a result of its different environment in the crystal packing. It is notable that NMR spectroscopy could distinguish between compounds L-1 and D-1 that have different relative stereocentres; however, the differences in chemical shifts between them were found to be about 0.02 to 0.001 ppm under calibrated temperature conditions. In each molecule, the two chiral parts are also different in NMR media, in which chemical shifts and P–H and P–C couplings have been studied.