The double H-atom acceptability of the P=O group in newXP(O)(NHCH₂C₆H₄-2-Cl)₂phosphoramidates [X= C₆H₅O– and CF₃C(O)NH–]: a database analysis of compounds having a P(O)(NHR) group

Abstract

In the hydrogen-bond patterns of phenyl bis(2-chlorobenzylamido)phosphinate, C(20)H(19)Cl(2)N(2)O(2)P, (I), and N,N'-bis(2-chlorobenzyl)-N''-(2,2,2-trifluoroacetyl)phosphoric triamide, C(16)H(15)Cl(2)F(3)N(3)O(2)P, (II), the O atoms of the related phosphoryl groups act as double H-atom acceptors, so that the P=O···(H-N)(2) hydrogen bond in (I) and the P=O···(H-N(amide))(2) and C=O···H-N(C(O)NHP(O)) hydrogen bonds in (II) are responsible for the aggregation of the molecules in the crystal packing. The presence of a double H-atom acceptor centre is a result of the involvement of a greater number of H-atom donor sites with a smaller number of H-atom acceptor sites in the hydrogen-bonding interactions. This article also reviews structures having a P(O)NH group, with the aim of finding similar three-centre hydrogen bonds in the packing of phosphoramidate compounds. This analysis shows that the factors affecting the preference of the above-mentioned O atom to act as a double H-atom acceptor are: (i) a higher number of H-atom donor sites relative to H-atom acceptor centres in molecules with P(=O)(NH)(3), (N)P(=O)(NH)(2), C(=O)NHP(=O)(NH)(2) and (NH)(2)P(=O)OP(=O)(NH)(2) groups, and (ii) the remarkable H-atom acceptability of this atom relative to the other acceptor centre(s) in molecules containing an OP(=O)(NH)(2) group, with the explanation that the N atom bound to the P atom in almost all of the structures found does not take part in hydrogen bonding as an acceptor. Moreover, the differences in the H-atom acceptability of the phosphoryl O atom relative to the O atom of the alkoxy or phenoxy groups in amidophosphoric acid esters may be illustrated by considering the molecular packing of compounds having (O)(2)P(=O)(NH) and (O)P(=O)(NH)(N)groups, in which the unique N-H unit in the above-mentioned molecules almost always selects the phosphoryl O atom as a partner in forming hydrogen-bond interactions. The P atoms in (I) and (II) are in tetrahedral coordination environments, and the phosphoryl and carbonyl groups in (II) are anti with respect to each other (the P and C groups are separated by one N atom). In the crystal structures of (I) and (II), adjacent molecules are linked via the above-mentioned hydrogen bonds into a linear arrangement parallel to [100] in both cases, in (I) by forming R(2)(2)(8) rings and in (II) through a combination of R(2)(2)(10) and R(2)(1)(6) rings.

Structural and Molecular Packing study of Three New Amidophosphoric Acid Esters and Assessment of Their Inhibiting Activity Against SARS‐CoV‐2 by Molecular Docking

“…The asymmetric unit has three molecules P1, P16 and P31 in 1 (Figure 1 ) and one entire molecule in 2 and 3 (Figure 2 ). The phosphorous atom has in all structures a distorted tetrahedral O=P[−O] 2 [−N] environment as evidenced from the bond lengths and angles around the P atom (Table S1), being in the same range as in the structures of similar amidophosphoric acid esters[ 19 , 20 ]…”

“…[ 17 , 18 ] The various intermolecular interactions in the structures of amidophosphoric acid esters have been investigated before in the presence or absence of N−H…O hydrogen bond. [ 19 , 20 ] The formation of 3D architectures in their molecular aggregations via weak interactions such as π‐effects contacts and non‐covalent forces has also been considered. [ 19 , 21 ]…”