Organophosphorus Azoles Incorporating a Tetra-, Penta-, and Hexacoordinated Phosphorus Atom: NMR Spectroscopy and Quantum Chemistry

The review presents extensive data (from the author’s work and the literature) on the stereochemical structure of functionalized organophosphorus azoles (pyrroles, pyrazoles, imidazoles and benzazoles) and related compounds, using multinuclear 1H, 13C, 31P NMR spectroscopy and quantum chemistry. 31P NMR spectroscopy, combined with high-level quantum-chemical calculations, is the most convenient and reliable approach to studying tetra-, penta-, and hexacoordinated phosphorus atoms of phosphorylated N-vinylazoles and evaluating their Z/E isomerization.


Introduction
Phosphorus compounds are attracting considerable research attention due to their wide application in life sciences, agrochemistry and materials science. Over the last decades, the chemistry of organophosphorus compounds is progressing rapidly, owing to their broad utility in the national economy. Diverse biological activity and easy degradation on the simplest non-toxic products allows the organophosphorus compounds (OPC) to be ranked among the top products for chemical plant protection. Phosphorus-containing compounds are reported to be in drugs, insecticides, fungicides, polymer plasticizers and stabilizers, catalysts and components for improvement of lubricating oils' quality; however, there is more [1][2][3]. Organophosphorus complexes have gained widespread acceptance in science and engineering [4][5][6][7]. However, so far, only a small amount (less than 10%) of the produced phosphorus is spent on the synthesis of organic derivatives. Moreover, organophosphorus compounds are mainly phosphoric acid esters, and only some of them contain one or more P-C bonds. -depth insight into the chemical behavior and biological activity of these systems is impossible without elucidation of structural peculiarities, spectral properties and tautomeric rearrangements.
A well-known method for the preparation of compounds with a P-C bond is the interaction of phosphorus pentachloride with various nucleophiles (alkenes, alkadienes, alkynes, ethers and esters and tertiary amines including functionalized azoles, etc.). The availability of initial reagents, mild reaction conditions and the ability to vary the structure of the final OPC are advantages of this method. This reaction has not exhausted its synthetic capabilities in terms of the covering of new nucleophiles. Therefore, research in this area still remains a challenge.
The search for new low-waste ways to obtain the phosphorus-containing derivatives of heterocycles, including azoles, through the direct phosphorylation of C-H bonds is a relevant topic. In recent years, phosphorylated azoles have attracted much attention because of the presence of their structural motif in many bioactive naturally occurring and synthetic molecules [8][9][10][11]. Organophosphorus azoles exhibit antiblastic, insecticidal, Molecules 2023, 28 antihypertensive, hypoglycemic, neurodegenerative and antiexudative activities, among others [10][11][12]. Our ongoing research on functionalized azoles and related compounds has been presented in a monograph on nitroazoles [13] and several reviews devoted to the chemistry of five-membered azoles and their benzannelated analogs [14][15][16][17], organosilicon azoles [18], NMR spectroscopy and mass-spectrometry of nitroazoles [19,20], and structure and electronic effects of five-membered nitrogenated heterocycles [21]. Furthermore, tautomerism and the stereochemical structure of functional azoles have been comprehensively researched [22][23][24][25][26]. The problems of prototropy of NH-unsubstituted azoles [23] and silylotropy of N-silylated analogs [25,26] have been discussed and analyzed in detail using the methods of multinuclear and dynamic NMR spectroscopy and quantum chemistry. The results of the study of the structural peculiarities and tautomerism of functionalized azoles in the solid state using the nuclear quadrupole resonance method [24] summarized.
Azole derivatives are a structural core of numerous biologically important compounds, such as hemoglobin, chlorophyll, antibiotics and vitamin B12. Additionally, they are involved in solar energy fixation, oxygen transfers in natural conditions (in vivo) and other life-sustaining processes. Many medicinal products, plant growth regulators and organic synthesis intermediates are obtained from azoles [13,27].
The stereochemistry of functionalized azoles incorporating phosphorus atoms is a challenging topic in heterocyclic chemistry because the correct interpretation of their chemical behavior and biological activity depends on understanding the factors that determine the stereochemical features and relative stability of their isomers. The study of the structure of phosphorylated N-vinilazoles is very important for understanding the reactivity and mechanism of their bioactivity. One of the possible ways of assembling the biologically active organophosphorus and azole moieties in one molecule is the phosphorylation of 1-vinylazoles with phosphorus pentachloride. N-vinyl-substituted azoles are usually phosphorylated on a double bond. The lone electron pair (LEP) of the nitrogen atom in 1-vinilazoles, as in vinyl pyrroles, is included in the π-system of the heterocycle. An increase in number of nitrogen atoms in the azole ring, in contrast to pyrroles, enhances the acceptor properties of the heterocycle with respect to the N-vinyl moiety.
The decrease of nucleophilicity of the N-vinyl fragment of 1-vinilazoles compared with N-vinylpyrroles should reduce the side reactions of chlorination and resinification upon phosphorylation with phosphorus pentachloride. Meanwhile, the presence of pyridine nitrogen atoms in the azole cycles with enhanced nucleophilicity can direct the attack of phosphorus pentachloride in the ring to furnish donor-acceptor complexes containing a hexacoordinated phosphorus atom. Thus, vinyl derivatives of azoles can be the objects of both the donor-acceptor interaction of the azole nucleus with electron-acceptors, and of electrophilic reactions through the double bond of 1-vinylazoles. The reaction course depends on such parameters as the basicity of different sites, the π-electron charge value of pyridine nitrogen, the final charge of pyrrole nitrogen and the polarization of a double bond.
An evaluation of the basicity of 1-vinylazole derivatives shows that imidazole heterocycles have the highest basicity, while that of pyrazoles and 1,2,3-triazoles is reduced, owing to the mutual inductive influence of heteroatoms in the cycle [28,29]. In addition, the basicity of azoles is usually lowered by benzoannelation. The basicity of pyrazoles is much lower than that of imidazoles, and this is a common property of heterocycles with two adjacent nitrogen atoms in the ring ( Table 1).
The phosphorylation reaction involving the vinyl group plays the main role in the interaction of N-vinylpyrazoles with phosphorus pentachloride by reducing the basicity of the heterocycle.
The Z-configuration of the compounds 1-4 is stable at room temperature, while upon heating, a partial Z-E-isomerization occurs. The isomerization proceeds much more easily in passing from enaminotrichlorophosphonium hexachlorophosphates (1-4) to 2-(N-pyrazolyl)ethenylphosphonic acid chloroanhydrides (5)(6)(7)(8), and occurs during storage of phosphonic acid chloroanhydrides. This process is facilitated by a decrease in the electron-withdrawing properties of the dichlorophosphoryl moiety compared with the trichlorophosphonic group. Apparently, the presence of hydrogen chloride in the reaction medium promotes Z-E-isomerization due to the possible reversible hydrochlorination of the double bond of the compounds 5-8. The analogous conversions are observed in the phosphorylation of 2-vinylindazole (9, 10) (Scheme 1). In this case, the pyridine nitrogen atom has a higher basicity than that of 1-vinylindazole, as in the methylated analogs [28] ( Table 1).
Meanwhile, the electron-withdrawing action of the nitro group reduces the basicity of the heterocycle; therefore, phosphorylation of 1-vinyl-3,5-dimethyl-4-nitropyrazole (13,14) produces E-isomers [22,28,31,33] (Scheme 3). The Z-configuration of the compounds 1-4 is stable at room temperature, while upon heating, a partial Z-Е-isomerization occurs. The isomerization proceeds much more easily in passing from enaminotrichlorophosphonium hexachlorophosphates (1-4) to 2-(N-pyrazolyl)ethenylphosphonic acid chloroanhydrides (5)(6)(7)(8), and occurs during storage of phosphonic acid chloroanhydrides. This process is facilitated by a decrease in the electron-withdrawing properties of the dichlorophosphoryl moiety compared with the trichlorophosphonic group. Apparently, the presence of hydrogen chloride in the reaction medium promotes Z-Е-isomerization due to the possible reversible hydrochlorination of the double bond of the compounds 5-8. The analogous conversions are observed in the phosphorylation of 2-vinylindazole (9, 10) (Scheme 1). In this case, the pyridine nitrogen atom has a higher basicity than that of 1-vinylindazole, as in the methylated analogs [28] ( Table 1).
The donor-acceptor interaction in the Z-isomers of the compounds (1)(2)(3)(4)9) manifests itself so strongly that positive charge is delocalized with the participation of the ring, and the phosphorus atom in the trichlorophosphonic group turns out to be pentacoordinated. In the 31 P NMR spectra, this leads to the appearance of a signal in the range of −  ppm that is indicative of significant shielding of the phosphorus nucleus; consequently, there is a shift of positive charge towards the heterocyclic nitrogen atom (Table 2). Meanwhile, the electron-withdrawing action of the nitro group reduces the basicity of the heterocycle; therefore, phosphorylation of 1-vinyl-3,5-dimethyl-4-nitropyrazole (13,14) produces E-isomers [22,28,31,31]  Apparently, the low basicity of the pyridine nitrogen atom of compounds (11, 13) does not allow the formation of a stable donor-acceptor bond under experimental conditions; therefore, it is not possible to detect the Z-isomers of these azoles.
The donor-acceptor interaction in the Z-isomers of the compounds (1)(2)(3)(4)9) manifests itself so strongly that positive charge is delocalized with the participation of the ring, and the phosphorus atom in the trichlorophosphonic group turns out to be pentacoordinated. In the 31 Р NMR spectra, this leads to the appearance of a signal in the range of −  ppm that is indicative of significant shielding of the phosphorus nucleus; consequently, there is a shift of positive charge towards the heterocyclic nitrogen atom (Table 2).   Apparently, the low basicity of the pyridine nitrogen atom of compounds (11, 13) does not allow the formation of a stable donor-acceptor bond under experimental conditions; therefore, it is not possible to detect the Z-isomers of these azoles.
The donor-acceptor interaction in the Z-isomers of the compounds (1)(2)(3)(4)9) manifests itself so strongly that positive charge is delocalized with the participation of the ring, and the phosphorus atom in the trichlorophosphonic group turns out to be pentacoordinated. In the 31 Р NMR spectra, this leads to the appearance of a signal in the range of −  ppm that is indicative of significant shielding of the phosphorus nucleus; consequently, there is a shift of positive charge towards the heterocyclic nitrogen atom ( Table 2). Apparently, the low basicity of the pyridine nitrogen atom of compounds (11, 13) does not allow the formation of a stable donor-acceptor bond under experimental conditions; therefore, it is not possible to detect the Z-isomers of these azoles.
The donor-acceptor interaction in the Z-isomers of the compounds (1)(2)(3)(4)9) manifests itself so strongly that positive charge is delocalized with the participation of the ring, and the phosphorus atom in the trichlorophosphonic group turns out to be pentacoordinated. In the 31 Р NMR spectra, this leads to the appearance of a signal in the range of −  ppm that is indicative of significant shielding of the phosphorus nucleus; consequently, there is a shift of positive charge towards the heterocyclic nitrogen atom ( Table 2). Apparently, the low basicity of the pyridine nitrogen atom of compounds (11, 13) does not allow the formation of a stable donor-acceptor bond under experimental conditions; therefore, it is not possible to detect the Z-isomers of these azoles.
The donor-acceptor interaction in the Z-isomers of the compounds (1)(2)(3)(4)9) manifests itself so strongly that positive charge is delocalized with the participation of the ring, and the phosphorus atom in the trichlorophosphonic group turns out to be pentacoordinated. In the 31 Р NMR spectra, this leads to the appearance of a signal in the range of −  ppm that is indicative of significant shielding of the phosphorus nucleus; consequently, there is a shift of positive charge towards the heterocyclic nitrogen atom (Table 2).

=CH-PCl 3
The donor-acceptor interaction in the Z-isomers of the compounds (1)(2)(3)(4)9) manifests itself so strongly that positive charge is delocalized with the participation of the ring, and the phosphorus atom in the trichlorophosphonic group turns out to be pentacoordinated. In the 31 Р NMR spectra, this leads to the appearance of a signal in the range of −  ppm that is indicative of significant shielding of the phosphorus nucleus; consequently, there is a shift of positive charge towards the heterocyclic nitrogen atom (Table 2).  The NMR spectral data of Е-and Z-isomers of 2-(N-azolyl)-ethenylphosphonic acid dichloroanhydrides are presented in Table 4 [30,31,33]. Z-isomers of alkenylphosphonates show an insignificant high-field shift of the resonance signals of the phosphorus nucleus. The low value of this shift points to the absence of prominent donor-acceptor interactions between the pyridine nitrogen atom and dichlorophosphoryl group of the 5Z-8Z, 10Z.  The NMR spectral data of Eand Z-isomers of 2-(N-azolyl)-ethenylphosphonic acid dichloroanhydrides are presented in Table 4 [30,31,33]. Z-isomers of alkenylphosphonates show an insignificant high-field shift of the resonance signals of the phosphorus nucleus. The low value of this shift points to the absence of prominent donor-acceptor interactions between the pyridine nitrogen atom and dichlorophosphoryl group of the 5Z-8Z, 10Z.  The decrease in the nucleophilicity of the adjacent pyridine nitrogen atom in 1-vinylbenzotriazole also increases the competitiveness of the N-vinyl group in the reaction with phosphorus pentachloride. 1-vinylbenzotriazole is phosphorylated by phosphorus pentachloride to form benzotriazolyl-N-ethenyltrichlorophosphonium hexachlorophosphorate (18), which is easily transformed into enaminophosphonic (19) and enaminophosphinic (20) derivatives [22,30,33]  The decrease in the nucleophilicity of the adjacent pyridine nitrogen atom in 1-vinylbenzotriazole also increases the competitiveness of the N-vinyl group in the reaction with phosphorus pentachloride. 1-vinylbenzotriazole is phosphorylated by phosphorus pentachloride to form benzotriazolyl-N-ethenyltrichlorophosphonium hexachlorophosphorate (18), which is easily transformed into enaminophosphonic (19) and enaminophosphinic (20) derivatives [22,30,33] (Scheme 5). The decrease in the nucleophilicity of the adjacent pyridine nitrogen atom in 1-vinylbenzotriazole also increases the competitiveness of the N-vinyl group in the reaction with phosphorus pentachloride. 1-vinylbenzotriazole is phosphorylated by phosphorus pentachloride to form benzotriazolyl-N-ethenyltrichlorophosphonium hexachlorophosphorate (18), which is easily transformed into enaminophosphonic (19) and enaminophosphinic (20) derivatives [22,30,33]  The decrease in the nucleophilicity of the adjacent pyridine nitrogen atom in 1-vinylbenzotriazole also increases the competitiveness of the N-vinyl group in the reaction with phosphorus pentachloride. 1-vinylbenzotriazole is phosphorylated by phosphorus pentachloride to form benzotriazolyl-N-ethenyltrichlorophosphonium hexachlorophosphorate (18), which is easily transformed into enaminophosphonic (19) and enaminophosphinic (20) derivatives [22,30,33] (Scheme 5). The 1 H, 13 C, and 31 P NMR spectra of the phosphorylation products of 1-vinylbenzotriazole indicate the formation of exclusively Е-isomers of the phosphorylated 18-20 (Tables 2 and 4). Apparently, this fact is explained by the reduced basicity of the pyridine nitrogen atom (N-2) in 1-vinylbenzotriazole that is typical of 1-alkylsubstitutes ( Table 1).
The data of 31 P NMR spectra show that the reaction mixture after the action of SO2 on hexachlorophosphorates 1-4, 9 contains, along with the major compounds 5-8, 10, hydrochlorination products 21-25 in minor amounts (Table 5) [33]. The 1 H, 13 C, and 31 P NMR spectra of the phosphorylation products of 1-vinylbenzotriazole indicate the formation of exclusively E-isomers of the phosphorylated 18-20 (Tables 2 and 4). Apparently, this fact is explained by the reduced basicity of the pyridine nitrogen atom (N-2) in 1-vinylbenzotriazole that is typical of 1-alkylsubstitutes ( Table 1).

Compound 21 22 23 24 25
Structure 1-vinylbenzotriazole indicate the formation of exclusively Е-isomers of the phosphorylated 18-20 (Tables 2 and 4). Apparently, this fact is explained by the reduced basicity of the pyridine nitrogen atom (N-2) in 1-vinylbenzotriazole that is typical of 1-alkylsubstitutes ( Table 1). The data of 31 P NMR spectra show that the reaction mixture after the action of SO2 on hexachlorophosphorates 1-4, 9 contains, along with the major compounds 5-8, 10, hydrochlorination products 21-25 in minor amounts (Table 5) [33]. The multiple signals of the phosphorus atom of compounds 21-25 appear in a lower field than the signals of the compounds 5-8, 10. In this case, small variations in 21-25 insignificantly change the chemical shifts (33-35 ppm) and coupling constants ( Table 5).
1-vinylbenzotriazole indicate the formation of exclusively Е-isomers of the phosphorylated 18-20 (Tables 2 and 4). Apparently, this fact is explained by the reduced basicity of the pyridine nitrogen atom (N-2) in 1-vinylbenzotriazole that is typical of 1-alkylsubstitutes ( Table 1).
The data of 31 P NMR spectra show that the reaction mixture after the action of SO2 on hexachlorophosphorates 1-4, 9 contains, along with the major compounds 5-8, 10, hydrochlorination products 21-25 in minor amounts (Table 5) [33]. The multiple signals of the phosphorus atom of compounds 21-25 appear in a lower field than the signals of the compounds 5-8, 10. In this case, small variations in 21-25 insignificantly change the chemical shifts (33-35 ppm) and coupling constants ( Table 5).
1-vinylbenzotriazole indicate the formation of exclusively Е-isomers of the phosphorylated 18-20 (Tables 2 and 4). Apparently, this fact is explained by the reduced basicity of the pyridine nitrogen atom (N-2) in 1-vinylbenzotriazole that is typical of 1-alkylsubstitutes ( Table 1).
The data of 31 P NMR spectra show that the reaction mixture after the action of SO2 on hexachlorophosphorates 1-4, 9 contains, along with the major compounds 5-8, 10, hydrochlorination products 21-25 in minor amounts (Table 5) [33]. The multiple signals of the phosphorus atom of compounds 21-25 appear in a lower field than the signals of the compounds 5-8, 10. In this case, small variations in 21-25 insignificantly change the chemical shifts (33-35 ppm) and coupling constants ( Table 5).
1-vinylbenzotriazole indicate the formation of exclusively Е-isomers of the phosphorylated 18-20 (Tables 2 and 4). Apparently, this fact is explained by the reduced basicity of the pyridine nitrogen atom (N-2) in 1-vinylbenzotriazole that is typical of 1-alkylsubstitutes ( Table 1).
The data of 31 P NMR spectra show that the reaction mixture after the action of SO2 on hexachlorophosphorates 1-4, 9 contains, along with the major compounds 5-8, 10, hydrochlorination products 21-25 in minor amounts (Table 5) [33]. The multiple signals of the phosphorus atom of compounds 21-25 appear in a lower field than the signals of the compounds 5-8, 10. In this case, small variations in 21-25 insignificantly change the chemical shifts (33-35 ppm) and coupling constants ( Table 5).
1-vinylbenzotriazole indicate the formation of exclusively Е-isomers of the phosphorylated 18-20 (Tables 2 and 4). Apparently, this fact is explained by the reduced basicity of the pyridine nitrogen atom (N-2) in 1-vinylbenzotriazole that is typical of 1-alkylsubstitutes ( Table 1).
The data of 31 P NMR spectra show that the reaction mixture after the action of SO2 on hexachlorophosphorates 1-4, 9 contains, along with the major compounds 5-8, 10, hydrochlorination products 21-25 in minor amounts (Table 5) [33]. The multiple signals of the phosphorus atom of compounds 21-25 appear in a lower field than the signals of the compounds 5-8, 10. In this case, small variations in 21-25 insignificantly change the chemical shifts (33-35 ppm) and coupling constants ( Table 5).

Computation of 31 P NMR Chemical Shifts of Tetra-, Penta-and Hexacoordinated Phosphorus Atom in Phosphorylated N-Vinylpyrazoles
Advances in the theoretical methods used to calculate NMR parameters have led to a major breakthrough in NMR computational applications for structural studies of organic molecules including organophosphates. This has stimulated top-level investigations of conformational and configurational manifestations (tasks) in molecular, intramolecular and intermolecular interactions, along with spectral assignment and structural explanation. Key attention is paid to the study of 31 P NMR chemical shifts that allow us to shed a light on various structural aspects of organophosphorus compounds. The range of phosphorus chemical shifts is known to exceed 500 ppm, which evidences the importance of 31 P NMR spectroscopy for structural studies of organophosphorus compounds [35][36][37][38].
One of the most intriguing features of 31 Р NMR spectroscopy relates to the effects originating from the intra-and intermolecular coordination of phosphorus with heteroatoms containing a lone electron pair. In this case, the coordination effect can reach significant values comparable to the full range of changes in the chemical shifts of phosphorus. So, for example, phosphorus pentachloride, a well-known electrophilic Scheme 6. The phosphorylation of 1-acetyl-3,5-dimethylpyrazole.

Computation of 31 P NMR Chemical Shifts of Tetra-, Penta-and Hexacoordinated Phosphorus Atom in Phosphorylated N-Vinylpyrazoles
Advances in the theoretical methods used to calculate NMR parameters have led to a major breakthrough in NMR computational applications for structural studies of organic molecules including organophosphates. This has stimulated top-level investigations of conformational and configurational manifestations (tasks) in molecular, intramolecular and intermolecular interactions, along with spectral assignment and structural explanation. Key attention is paid to the study of 31 P NMR chemical shifts that allow us to shed a light on various structural aspects of organophosphorus compounds. The range of phosphorus chemical shifts is known to exceed 500 ppm, which evidences the importance of 31 P NMR spectroscopy for structural studies of organophosphorus compounds [35][36][37][38].
One of the most intriguing features of 31 P NMR spectroscopy relates to the effects originating from the intra-and intermolecular coordination of phosphorus with heteroatoms containing a lone electron pair. In this case, the coordination effect can reach significant values comparable to the full range of changes in the chemical shifts of phosphorus. So, for example, phosphorus pentachloride, a well-known electrophilic phosphorylating agent, both in the crystalline state and in polar solvents dissociates into ions, and in non-polar solvents exists in a pentacoordinated state; meanwhile, the chemical shift of phosphorus varies from -300 to +80 depending on the degree of coordination (Equation (1)) [33] (Table 6).
2PCl 5 PCl + 4 + PCl − 6 (1) Indeed, an increase in the coordination number of phosphorus from 3 to 6 leads to a dramatic shielding of the 31 P nucleus from approximately +200 to −300 ppm [39]. The theoretical study of this interesting effect seems to be a challenging task of great practical importance. In addition to the available experimental data, modern quantum chemical calculations allow a deeper understanding of the nature of the relationship between the 31 P NMR chemical shifts and the structure of phosphoroorganic compounds with different coordination numbers.
The obtained experimental data show that in the 31 P NMR spectrum of compound 1Z, a signal is observed at −55.2 ppm, which, in comparison with the chemical shift of its configurational isomer 1E (+94.4 ppm), indicates a significant shielding of the phosphorus nucleus due to the possible appearance of a donor-acceptor interaction between the phosphorus atom of the chlorophosphonium group and the pyridine nitrogen atom, that is, a structure with a pentacoordinated phosphorus atom. Such a donor-acceptor interaction in 15Z contributes to the formation of a structure with a hexacoordinated phosphorus atom (δ 31 P = −216.2 ppm). To confirm the conclusions about intramolecular coordination obtained from the analysis of experimental data, ab initio calculations of the shielding constant of the phosphorus nucleus in these compounds were carried out. The Z configuration of isomer 1 is stable at room temperature, and the Z-E-isomerization occurs only upon heating. The presence of hydrogen chloride in the reaction medium facilitates Z-E-isomerization due to the possibility of reversible hydrochlorination of the double bond of this compound.
The obtained experimental data show that in the 31 P NMR spectrum of compound 1Z, a signal is observed at −55.2 ppm, which, in comparison with the chemical shift of its configurational isomer 1E (+94.4 ppm), indicates a significant shielding of the phosphorus nucleus due to the possible appearance of a donor-acceptor interaction between the phosphorus atom of the chlorophosphonium group and the pyridine nitrogen atom, that is, a structure with a pentacoordinated phosphorus atom. Such a donor-acceptor interaction in 15Z contributes to the formation of a structure with a hexacoordinated phosphorus atom (δ 31 P = −216.2 ppm). To confirm the conclusions about intramolecular coordination obtained from the analysis of experimental data, ab initio calculations of the shielding constant of the phosphorus nucleus in these compounds were carried out.
The shielding constants were calculated for the preferred conformations of azoles 1 and 15 localized at the B3LYP/6-311G(d,p) level for the gas phase, alongside using the polarizable continuum model (PCM) to take into account effect of the medium, in this case nitromethane. The structures of the most stable conformers and relative energies of compounds 1 and 15 are shown in Figure 1 [40,41]. According to the results of the theoretical conformational analysis at the B3LYP/6-311G(d,p) level, internal rotation around the N-C bond in 1E, 1Z and 15Z leads to the existence of two stable rotational conformations, s-cis and s-trans, with dihedral angle values NNCC = 0° and 180°, respectively. The only exception is the s-trans conformer of 15Z, for which this angle is 170°. This is explained by steric interactions between the bulky group of PCl4 and the pyrazole ring.
Characteristically, for compounds 1Z and 15Z, both in the gas phase and taking into account the solvent field, the s-cis conformation is the most favorable, the energy of which is much lower than the corresponding values for the s-trans conformers, which leads to almost 100% content of the s-cis-form. The relative stability of the E-and Z-isomers of 1 (s-cis conformers) depends on the solvent's nature. In the gas phase, the Z-isomer is more stable than the E-isomer by 1.6 kcal/mol, whereas calculations that take into account the solvent field gave almost similar energies for both isomers. Thus, the possibility for experimentally observable Z-E-isomerization of salt 1 at elevated temperature was theoretically substantiated.
Fundamentally important information about the nature of intramolecular coordination in phosphorylated N-vinylpyrazoles can be obtained from calculations of the shielding constant of the 31 P nucleus, which were carried out in terms of the density functional theory (DFT) by the B3LYP method [42,43] within the framework of the gradient-invariant atomic orbital (GIAO) approach [44]. It has been shown earlier [37,45]  According to the results of the theoretical conformational analysis at the B3LYP/6-311G(d,p) level, internal rotation around the N-C bond in 1E, 1Z and 15Z leads to the existence of two stable rotational conformations, s-cis and s-trans, with dihedral angle values NNCC = 0 • and 180 • , respectively. The only exception is the s-trans conformer of 15Z, for which this angle is 170 • . This is explained by steric interactions between the bulky group of PCl 4 and the pyrazole ring.
Characteristically, for compounds 1Z and 15Z, both in the gas phase and taking into account the solvent field, the s-cis conformation is the most favorable, the energy of which is much lower than the corresponding values for the s-trans conformers, which leads to almost 100% content of the s-cis-form. The relative stability of the Eand Z-isomers of 1 (s-cis conformers) depends on the solvent's nature. In the gas phase, the Z-isomer is more stable than the E-isomer by 1.6 kcal/mol, whereas calculations that take into account the solvent field gave almost similar energies for both isomers. Thus, the possibility for experimentally observable Z-E-isomerization of salt 1 at elevated temperature was theoretically substantiated.
Fundamentally important information about the nature of intramolecular coordination in phosphorylated N-vinylpyrazoles can be obtained from calculations of the shielding constant of the 31 P nucleus, which were carried out in terms of the density functional theory (DFT) by the B3LYP method [42,43] within the framework of the gradient-invariant atomic orbital (GIAO) approach [44]. It has been shown earlier [37,45] that relativistic effects are of decisive importance in the calculation of δ 31 P for molecules containing elements of the third or more periods. For example, in the series of phosphines (CH 3 ) 3 PX, where X = O, S, and Se for trimethylphosphine sulfide and trimethylphosphine selenide, the value of the spin-orbital contribution reaches 10 and 40 ppm, respectively. On the other hand, for PCl 4 + cation, the spin-orbital interaction also results in a high-field shift of the phosphorus resonance signal by 40-50 ppm. These data indicate that the calculation of the 31 P NMR chemical shifts in the chlorophosphonium group of compounds 1 and 15 requires allowance for the spin-orbital interaction.
The contribution of spin-orbital interaction is taken into account in terms of the zeroorder regular approximation (ZORA) for the relativistic effects [46,47] implemented in the ADF 2009 software package [48]. As basis sets for nonrelativistic calculations, the triple-split Kutzelnigg IGLO-III was used [49], which showed the best results in calculating 31 P NMR chemical shifts in phosphines and phosphine oxides [50]. For calculations taking into account the spin-orbit interaction, a double-split Slater-type basis set DZP [51,52] was employed. The method for calculating the relativistic values of the 31 P NMR chemical shifts within the framework of the ZORA approach included the calculation of the nonrelativistic value of the chemical shift δNR and the spin-orbit contribution δSO, the sum of which leads to the relativistic value δR. The medium was taken into account in the framework of the COSMO continuum model [53,54]. Theoretical values of 31 P NMR chemical shifts δcalc (ppm) are given relative to 75% H 3 PO 4 aqueous solution, recalculated according to Equation (2) and given in [55]: Here, σ calc is the absolute shielding constant of the phosphorus nucleus of the studied phosphine, and σ calc (PH 3 ) is the absolute shielding constant of the phosphorus nucleus PH 3 , calculated at the same level of theory.
The calculated 31 P NMR chemical shift values for the s-cis and s-trans conformations of compounds 1 and 15 are shown in Table 7. The results of the GIAO-B3LYP/DZP calculations are in good agreement with the experimental values for the respective preferred conformations of compounds 1E and 15Z. The calculation error does not exceed 25 ppm, both in the case of calculation in the gas phase and with allowance for the effects of the medium. However, in the case of the s-cis conformer 1Z, the calculated value of the 31 P NMR chemical shift by 160 ppm exceeds the experimental value, which indicates that in the gas phase and under conditions of nonspecific solvation, the formation of the intramolecular N→P coordination bond does not occur. Indeed, geometry optimization of the s-cis-conformer does not lead to a change in the distance between the phosphorus and nitrogen atoms.
The fundamental moment in the formation of an intramolecular coordination bond in compound 1Z is the influence of the solvent, in this case nitromethane. In this regard, an additional theoretical study of the structure of the complex of compound 1Z with one nitromethane molecule was carried out, which included optimization of the geometry in the gas phase and in the solvent medium ( Figure 2). The fundamental moment in the formation of an intramolecular coordination bond in compound 1Z is the influence of the solvent, in this case nitromethane. In this regard, an additional theoretical study of the structure of the complex of compound 1Z with one nitromethane molecule was carried out, which included optimization of the geometry in the gas phase and in the solvent medium ( Figure 2). The formation of the 1Z complex with a nitromethane molecule reduces the energy of the system, while in the gas phase, an intramolecular dative bond between the phosphorus atom and the pyridine-type nitrogen atom is not formed. The P-N interatomic distance shortens to 2.018 Å upon passing from the gas phase to the solution, which indicates the presence of a donor-acceptor interaction between the phosphorus and nitrogen atoms, and the stabilization of this structure by the solvent. Calculations of the 31 Р The formation of the 1Z complex with a nitromethane molecule reduces the energy of the system, while in the gas phase, an intramolecular dative bond between the phosphorus atom and the pyridine-type nitrogen atom is not formed. The P-N interatomic distance shortens to 2.018 Å upon passing from the gas phase to the solution, which indicates the presence of a donor-acceptor interaction between the phosphorus and nitrogen atoms, and the stabilization of this structure by the solvent. Calculations of the 31 P NMR chemical shift for this complex indeed indicate a significant low-frequency shift of the phosphorus resonance signal due to the formation of an intramolecular dative bond. Exceeding the calculated value of the 31 P NMR chemical shift by 45 ppm may be due to the insufficient theoretical level of the used solvation model. Perhaps, for a correct description of intramolecular coordination bonding, it is necessary to use a larger number of solvent molecules to model the solvate shell [40,41].
The change in the phosphorus signal can be assessed by comparing the δP values for the s-cis and s-trans conformers of the respective isomers. Both 1Z conformers are characterized by almost the same δP values, which may be due to the lack of coordination. Upon transition to the 1Z complex with nitromethane, the formation of an intramolecular dative N→P bond leads to a low-frequency shift of the phosphorus signal by 120 ppm. The coordination effect for compound 15Z is estimated at 155 ppm for the gas phase and 170 ppm for solution. The spin-orbit interaction makes a significant contribution to the overall coordination shift of the phosphorus signal. The formation of a dative bond in 1Z and 15Z is accompanied by an increase in the spin-orbit contribution by 9.5 and 25 ppm, respectively; these values are 8 and 15% of the coordination induced shift.
Thus, the results of this study indicate the need to take into account the relativistic corrections and medium effects when calculating the shielding constants for phosphorus nuclei.

The Structural Features of Molecular Complexes of Vinylazoles with Phosphorus Pentachloride
N-vinylpyrazoles, as well as the corresponding indazoles and benzotriazoles, are phosphorylated at the double bond by phosphorus pentachloride to provide azoles containing the tetra-, penta-, or hexacoordinated phosphorus atom. N-vinylimidazoles or N-vinylbenzimidazoles, having highly basic isolated (separated) pyridine nitrogen atoms, interact in the cycle with phosphorus pentachloride in a different way. Donor-acceptor complexes in these reactions are initially generated.
The reaction of N-vinylimidazole with phosphorus pentachloride, even with its excess, produces the donor-acceptor complex 28 with the involvement (participation) of the pyridine nitrogen atom [32]. Consequently, the electron-withdrawing properties of the ring are enhanced and the nucleophilicity of the N-vinyl group decreases, which hinders its phosphorylation. The interaction of the vinylimidazole with the phosphorus pentachloride in benzene solution saturated by hydrogen chloride gives the complex 29, containing the protonated nitrogen atom in the position 3 (Scheme 8).
Molecules 2023, 28, x FOR PEER REVIEW 16 of 36 The coordination effect for compound 15Z is estimated at 155 ppm for the gas phase and 170 ppm for solution. The spin-orbit interaction makes a significant contribution to the overall coordination shift of the phosphorus signal. The formation of a dative bond in 1Zand 15Z is accompanied by an increase in the spin-orbit contribution by 9.5 and 25 ppm, respectively; these values are 8 and 15% of the coordination induced shift. Thus, the results of this study indicate the need to take into account the relativistic corrections and medium effects when calculating the shielding constants for phosphorus nuclei.

The Structural Features of Molecular Complexes of Vinylazoles with Phosphorus Pentachloride
N-vinylpyrazoles, as well as the corresponding indazoles and benzotriazoles, are phosphorylated at the double bond by phosphorus pentachloride to provide azoles containing the tetra-, penta-, or hexacoordinated phosphorus atom. N-vinylimidazoles or N-vinylbenzimidazoles, having highly basic isolated (separated) pyridine nitrogen atoms, interact in the cycle with phosphorus pentachloride in a different way. Donoracceptor complexes in these reactions are initially generated.
The reaction of N-vinylimidazole with phosphorus pentachloride, even with its excess, produces the donor-acceptor complex 28 with the involvement (participation) of the pyridine nitrogen atom [32]. Consequently, the electron-withdrawing properties of the ring are enhanced and the nucleophilicity of the N-vinyl group decreases, which hinders its phosphorylation. The interaction of the vinylimidazole with the phosphorus pentachloride in benzene solution saturated by hydrogen chloride gives the complex 29, containing the protonated nitrogen atom in the position 3 (Scheme 8). Analogously, the action of PCl5 on N-vinylbenzimidazole provides a donor-acceptor complex 30, whereas 3-Н-1-vinylbenzimidazolinium hexachlorophosphate 31 is formed in the presence of hydrogen chloride. 1 Н, 13 С, and 31 Р NMR data of complexes 28-31 are shown in Table 8. Analogously, the action of PCl 5 on N-vinylbenzimidazole provides a donor-acceptor complex 30, whereas 3-H-1-vinylbenzimidazolinium hexachlorophosphate 31 is formed in the presence of hydrogen chloride. 1 H, 13 C, and 31 P NMR data of complexes 28-31 are shown in Table 8.       The presence of three proton signals of N-vinyl groups in the 1 H NMR spectra of compounds (28)(29)(30)(31) in nitromethane indicates that the vinyl group does not participate in the phosphorylation reaction. The signals recorded in the region −(258-296) ppm in the 31 Р NMR spectra are typical for the hexacoordinated phosphorus atom.
1-allyl-3,5-dimethylpyrazole [32] and the corresponding 1-propyl and 1-isopropyl derivatives interact with phosphorus pentachloride exclusively with the participation of the pyridine nitrogen atom of heterocycle. The presence of a pyridine nitrogen atom with increased nucleophilicity in the azole ring directs the attack of phosphorus pentachloride into the heterocycle to form the donor-acceptor complexes 32, 32-1 and 32-2 (Scheme 9). The presence of three proton signals of N-vinyl groups in the 1 H NMR spectra of compounds (28)(29)(30)(31) in nitromethane indicates that the vinyl group does not participate in the phosphorylation reaction. The signals recorded in the region −(258-296) ppm in the 31 Р NMR spectra are typical for the hexacoordinated phosphorus atom.
1-allyl-3,5-dimethylpyrazole [32] and the corresponding 1-propyl and 1-isopropyl derivatives interact with phosphorus pentachloride exclusively with the participation of the pyridine nitrogen atom of heterocycle. The presence of a pyridine nitrogen atom with increased nucleophilicity in the azole ring directs the attack of phosphorus pentachloride into the heterocycle to form the donor-acceptor complexes 32, 32-1 and 32-2 (Scheme 9). The presence of three proton signals of N-vinyl groups in the 1 H NMR spectra of compounds (28)(29)(30)(31) in nitromethane indicates that the vinyl group does not participate in the phosphorylation reaction. The signals recorded in the region −(258-296) ppm in the 31 Р NMR spectra are typical for the hexacoordinated phosphorus atom.
1-allyl-3,5-dimethylpyrazole [32] and the corresponding 1-propyl and 1-isopropyl derivatives interact with phosphorus pentachloride exclusively with the participation of the pyridine nitrogen atom of heterocycle. The presence of a pyridine nitrogen atom with increased nucleophilicity in the azole ring directs the attack of phosphorus pentachloride into the heterocycle to form the donor-acceptor complexes 32, 32-1 and 32-2 (Scheme 9).  The presence of three proton signals of N-vinyl groups in the 1 H NMR spectra of compounds (28)(29)(30)(31) in nitromethane indicates that the vinyl group does not participate in the phosphorylation reaction. The signals recorded in the region −(258-296) ppm in the 31 Р NMR spectra are typical for the hexacoordinated phosphorus atom.
1-allyl-3,5-dimethylpyrazole [32] and the corresponding 1-propyl and 1-isopropyl derivatives interact with phosphorus pentachloride exclusively with the participation of the pyridine nitrogen atom of heterocycle. The presence of a pyridine nitrogen atom with increased nucleophilicity in the azole ring directs the attack of phosphorus pentachloride into the heterocycle to form the donor-acceptor complexes 32, 32-1 and 32-2 (Scheme 9). The presence of three proton signals of N-vinyl groups in the 1 H NMR spectra of compounds (28)(29)(30)(31) in nitromethane indicates that the vinyl group does not participate in the phosphorylation reaction. The signals recorded in the region −(258-296) ppm in the 31 Р NMR spectra are typical for the hexacoordinated phosphorus atom.
1-allyl-3,5-dimethylpyrazole [32] and the corresponding 1-propyl and 1-isopropyl derivatives interact with phosphorus pentachloride exclusively with the participation of the pyridine nitrogen atom of heterocycle. The presence of a pyridine nitrogen atom with increased nucleophilicity in the azole ring directs the attack of phosphorus pentachloride into the heterocycle to form the donor-acceptor complexes 32, 32-1 and 32-2 (Scheme 9). The presence of three proton signals of N-vinyl groups in the 1 H NMR spectra of compounds (28)(29)(30)(31) in nitromethane indicates that the vinyl group does not participate in the phosphorylation reaction. The signals recorded in the region −(258-296) ppm in the 31 P NMR spectra are typical for the hexacoordinated phosphorus atom.
1-allyl-3,5-dimethylpyrazole [32] and the corresponding 1-propyl and 1-isopropyl derivatives interact with phosphorus pentachloride exclusively with the participation of the pyridine nitrogen atom of heterocycle. The presence of a pyridine nitrogen atom with increased nucleophilicity in the azole ring directs the attack of phosphorus pentachloride into the heterocycle to form the donor-acceptor complexes 32, 32-1 and 32-2 (Scheme 9). The phosphorus singlet signals in the 31 Р NMR spectra of compounds 32, 32-1 and 32-2 appear in the −(260-264) ppm region and characterize the hexacoordinated phosphorus atom ( Table 8).

Quantum-Chemical Calculations of 31 P NMR Chemical Shifts of Molecular Complexes of Azoles
Theoretical examination of molecular complexes of phosphorus pentachloride with 1-vinylimidazole (28) and 1-allyl-3,5-dimethylpyrazole (32) have been carried out [41,56]. The phosphorus atom of the chlorophosphonium group can form a donor-acceptor bond with a pyridine nitrogen atom containing the lone electron pair (i.e., an sp2-hybridized nitrogen atom). As a result, the coordination number of phosphorus atom increases to 5 or 6, and its resonant signal in the 31 P NMR spectrum is shifted up-field. In addition, the presence in the heterocycle of nitrogen atoms of the pyridine type having increased nucleophilicity makes it possible to direct the attack of phosphorus pentachloride not to the double bond of the vinyl group, but to the heterocycle, with the formation of the corresponding intermolecular donor-acceptor complexes 28 and 32 [32,34,56] (Schemes 8 and  9). The 31 P NMR spectra of 28 and 32 contain a singlet in the region δ 31 P from −258 to −296 ppm, which is typical of six-coordinate phosphorus atoms. Quantum chemical calculations of 31 P NMR chemical shifts in 28 and 32 were carried out for the gas phase and taking into account the effect of the solvent in order to evaluate the effect of intermolecular coordination on the 31 P shielding constants (chemical shifts) ( Table 9). The phosphorus singlet signals in the 31 P NMR spectra of compounds 32, 32-1 and 32-2 appear in the −(260-264) ppm region and characterize the hexacoordinated phosphorus atom ( Table 8).

Quantum-Chemical Calculations of 31 P NMR Chemical Shifts of Molecular Complexes of Azoles
Theoretical examination of molecular complexes of phosphorus pentachloride with 1-vinylimidazole (28) and 1-allyl-3,5-dimethylpyrazole (32) have been carried out [41,56]. The phosphorus atom of the chlorophosphonium group can form a donor-acceptor bond with a pyridine nitrogen atom containing the lone electron pair (i.e., an sp 2 -hybridized nitrogen atom). As a result, the coordination number of phosphorus atom increases to 5 or 6, and its resonant signal in the 31 P NMR spectrum is shifted up-field. In addition, the presence in the heterocycle of nitrogen atoms of the pyridine type having increased nucleophilicity makes it possible to direct the attack of phosphorus pentachloride not to the double bond of the vinyl group, but to the heterocycle, with the formation of the corresponding intermolecular donor-acceptor complexes 28 and 32 [32,34,56] (Schemes 8 and 9). The 31 P NMR spectra of 28 and 32 contain a singlet in the region δ 31 P from −258 to −296 ppm, which is typical of six-coordinate phosphorus atoms. Quantum chemical calculations of 31 P NMR chemical shifts in 28 and 32 were carried out for the gas phase and taking into account the effect of the solvent in order to evaluate the effect of intermolecular coordination on the 31 P shielding constants (chemical shifts) ( Table 9). The phosphorus shielding constants were calculated at the GIAO-B3LYP/DZP level of theory, taking into account the spin-orbital relativistic interaction in terms of the ZORA [46,47]. The theoretical 31 P chemical shifts δ calc (ppm) were recalculated according to Equation (1) and are given relative to 85% aqueous H 3 PO 4 [55]. All calculations were performed for molecular complexes, with geometric parameters optimized in terms of the density functional theory using B3LYP hybrid functional and a 6-311G(d,p) basis set for the gas phase, and with account taken of the solvent field (nitromethane). The solvent effect was simulated according to the polarizable continuum model (PCM); nitromethane was selected as a solvent, and the experimental 31 P NMR spectra were recorded in this solvent. The most favorable conformations of complexes 28 and 32 and their relative energies are shown in Figures 3 and 4.  The phosphorus shielding constants were calculated at the GIAO-B3LYP/DZP level of theory, taking into account the spin-orbital relativistic interaction in terms of the ZORA [46,47]. The theoretical 31 P chemical shifts δcalc (ppm) were recalculated according to Equation (1) and are given relative to 85% aqueous H3PO4 [55]. All calculations were performed for molecular complexes, with geometric parameters optimized in terms of the density functional theory using B3LYP hybrid functional and a 6-311G(d,p) basis set for the gas phase, and with account taken of the solvent field (nitromethane). The solvent effect was simulated according to the polarizable continuum model (PCM); nitromethane was selected as a solvent, and the experimental 31 P NMR spectra were recorded in this solvent. The most favorable conformations of complexes 28 and 32 and their relative energies are shown in Figures 3 and 4.  The calculated 31 P NMR chemical shifts of complex 28 both in the gas phase and in solution are in good agreement with the experimental values (see Table 10). Deviations do not exceed 12 ppm, which may indicate the complexation of vinylimidazole with phosphorus pentachloride. The theoretical conformational analysis data also evidence the generation of an N→P bond, because the distance between the pyridine nitrogen atom and the phosphorus atom is not higher than 2 Å, and the configuration of the phosphorus atom is modified to be octahedral, which is typical for sp 3 d 2 hybridization. It should also be noted that consideration of the solvent effect in the geometry optimization leads to a shortening of the P-N distance in both conformers 28 by about 0.1 Å, which eventually favors more appropriate calculation of the 31 P chemical shift. The calculated 31 P NMR chemical shifts of complex 28 both in the gas phase and in solution are in good agreement with the experimental values (see Table 10). Deviations do not exceed 12 ppm, which may indicate the complexation of vinylimidazole with phosphorus pentachloride. The theoretical conformational analysis data also evidence the generation of an N→P bond, because the distance between the pyridine nitrogen atom and the phosphorus atom is not higher than 2 Å, and the configuration of the phosphorus atom is modified to be octahedral, which is typical for sp 3 d 2 hybridization. It should also be noted that consideration of the solvent effect in the geometry optimization leads to a shortening of the P-N distance in both conformers 28 by about 0.1 Å, which eventually favors more appropriate calculation of the 31 P chemical shift.    The calculated 31 P NMR chemical shifts of complex 28 both in the gas phase and in solution are in good agreement with the experimental values (see Table 10). Deviations do not exceed 12 ppm, which may indicate the complexation of vinylimidazole with phosphorus pentachloride. The theoretical conformational analysis data also evidence the generation of an N→P bond, because the distance between the pyridine nitrogen atom and the phosphorus atom is not higher than 2 Å , and the configuration of the phosphorus atom is modified to be octahedral, which is typical for sp 3 d 2 hybridization. It should also be noted that consideration of the solvent effect in the geometry optimization leads to a shortening of the P-N distance in both conformers 28 by about 0.1 Å , which eventually favors more appropriate calculation of the 31 P chemical shift.  The calculated 31 P NMR chemical shifts of complex 28 both in the gas phase and in solution are in good agreement with the experimental values (see Table 10). Deviations do not exceed 12 ppm, which may indicate the complexation of vinylimidazole with phosphorus pentachloride. The theoretical conformational analysis data also evidence the generation of an N→P bond, because the distance between the pyridine nitrogen atom and the phosphorus atom is not higher than 2 Å , and the configuration of the phosphorus atom is modified to be octahedral, which is typical for sp 3 d 2 hybridization. It should also be noted that consideration of the solvent effect in the geometry optimization leads to a shortening of the P-N distance in both conformers 28 by about 0.1 Å , which eventually favors more appropriate calculation of the 31 P chemical shift.   (Table 9). Based on calculations for the gas phase by means of B3LYP/6-311G(d,p), the distance between pyridine nitrogen atoms and phosphorus atoms exceeds 4 Å, while the PCl5 molecule retains the bipyramidal configuration. Thus, the formation of a molecular complex between 1-allyl-3,5-dimethylpyrazole and phosphorus pentachloride does not occur in the gas phase. Taking into account the influence of the solvent (nitromethane), the P-N distance shortens to 2 Å, and (as in complex 28) the steric configuration of the PCl5 molecule transforms from trigonal bipyramidal to octahedral. This is accompanied by an increase in the calculated 31 P NMR chemical shift (up to −282.5 ppm) in the energetically most favorable s-trans conformer.
Assessment of the 31 P chemical shifts of the starting phosphorus pentachloride and its molecular complexes with azoles shows that the creation of the N→P dative bond is attended by a low-frequency shift of the phosphorus signal by 220 ppm, of which 60 ppm is due to the contribution of the spin-orbit interaction [56].
The effect of the solvent must be taken into consideration when optimizing the geometric parameters and calculating the 31 P NMR chemical shifts for intra-and inter-  (Table 9). Based on calculations for the gas phase by means of B3LYP/6-311G(d,p), the distance between pyridine nitrogen atoms and phosphorus atoms exceeds 4 Å, while the PCl5 molecule retains the bipyramidal configuration. Thus, the formation of a molecular complex between 1-allyl-3,5-dimethylpyrazole and phosphorus pentachloride does not occur in the gas phase. Taking into account the influence of the solvent (nitromethane), the P-N distance shortens to 2 Å, and (as in complex 28) the steric configuration of the PCl5 molecule transforms from trigonal bipyramidal to octahedral. This is accompanied by an increase in the calculated 31 P NMR chemical shift (up to −282.5 ppm) in the energetically most favorable s-trans conformer.
Assessment of the 31 P chemical shifts of the starting phosphorus pentachloride and its molecular complexes with azoles shows that the creation of the N→P dative bond is  (Table 9). Based on calculations for the gas phase by means of B3LYP/6-311G(d,p), the distance between pyridine nitrogen atoms and phosphorus atoms exceeds 4 Å, while the PCl 5 molecule retains the bipyramidal configuration. Thus, the formation of a molecular complex between 1-allyl-3,5dimethylpyrazole and phosphorus pentachloride does not occur in the gas phase. Taking into account the influence of the solvent (nitromethane), the P-N distance shortens to 2 Å, and (as in complex 28) the steric configuration of the PCl 5 molecule transforms from trigonal bipyramidal to octahedral. This is accompanied by an increase in the calculated 31 P NMR chemical shift (up to −282.5 ppm) in the energetically most favorable s-trans conformer.
Assessment of the 31 P chemical shifts of the starting phosphorus pentachloride and its molecular complexes with azoles shows that the creation of the N→P dative bond is attended by a low-frequency shift of the phosphorus signal by 220 ppm, of which 60 ppm is due to the contribution of the spin-orbit interaction [56].
The effect of the solvent must be taken into consideration when optimizing the geometric parameters and calculating the 31 P NMR chemical shifts for intra-and intermolecular complexes formed with the participation of a phosphorus atom and a nitrogen atom in heteroaromatic systems. As in the case of intramolecular coordination in the 15Z isomer, allowance for the effect of the solvent is of decisive importance because the solvent is responsible for the stabilization of such complexes. Accounting for relativistic effects is essential for the accuracy of predicting 31 P chemical shifts. The contribution of the spin-orbit interaction is about 200 ppm, and neglecting this contribution would lead to incorrect predictions.

Theoretical 31 P NMR Chemical Shifts of Pyrazolylphosphine and Related Compounds
A similar theoretical approach was applied to the study of 31 P NMR chemical shifts and the stereochemical behavior of phosphonic acid dichlorides containing the POCl 2 group at the C=C and C=N double bonds, i.e., 2-(pyrazolyl)ethenylphosphonic acid dichloride (5) and the related compounds, N-dichlorophosphonylimin obenzoic acid chloride (37), N -dichlorophosphoryl-N,N-dimethylchloroformamidine (38). These were prepared by the phosphorylation of N,N-dimethylurea with phosphorus pentachloride [57] and 1-trichlorophosphazo-1-chloro-2-dichlorophosphoryl-2-azaethene (39) obtained by the interaction of urea with phosphorus pentachloride [58]. The 31 P NMR chemical shifts were also calculated by the GIAO-B3LYP-ZORA/DZP for the predominant conformation of compounds 5, 37-39 for the gas phase (Table 10) [59]. The theoretical 31 P NMR chemical shift values are also recalculated by the Equation (2).
Analysis of the NMR spectra shows that compound 5 existed in the form of two isomers which were assigned by the measurement of spin-spin coupling constants 3 J PH that sharply differed between the configurational isomers with respect to the double bond [33]. In addition to these data, it was interesting to test the possibility of using 31 P NMR chemical shifts for the configuration assignment of compounds containing a double bond C=C linked to a phosphorus atom. Therefore, we calculated the 31 P NMR chemical shifts and performed the theoretical conformational analysis of these compounds in order to explore the influence of configuration and the conformational effects on the 31 P NMR spectra. The results of these calculations, including the localization of the prevailing conformers, the calculation of the relative energies (E rel ) and 31 P NMR chemical shifts of compound 5, are presented in Table 11.
The internal rotation in both isomers 5 around the P-N bond as well as the rotation of the pyrazole ring around the C-N bond is allowed. The calculations show that four rotational conformers are localized for each isomer (Table 11). Theoretical data reveal that the E-isomer 5 is energetically more favorable than the Z-isomer in all probable conformations, as evidenced by the experimentally observed isomerization of the 5Zisomer into the E-isomer during heating or storage. The most stable conformations of the E-isomer are s-cis-s-cis and s-trans-s-cis, with an energy difference of 1.4 kcal/mol. The energy of the other two conformations, s-cis-gauche and s-trans-gauche, is much higher and, therefore, they are practically absent in the equilibrium mixture. The equilibrium in the 5Z-isomer is almost completely shifted to the s-cis-gauche conformation due to steric hindrances preventing the existence of other conformers (Table 11). Table 11. Theoretical values of 31 P NMR chemical shifts and relative energies of conformers of the compound 5.

Structure
Isomer Conformer E rel , kcal/mol Chemical Shift, ppm NMR chemical shifts for the configuration assignment of compounds containing a double bond С=С linked to a phosphorus atom. Therefore, we calculated the 31 Р NMR chemical shifts and performed the theoretical conformational analysis of these compounds in order to explore the influence of configuration and the conformational effects on the 31 Р NMR spectra. The results of these calculations, including the localization of the prevailing conformers, the calculation of the relative energies (Erel) and 31 Р NMR chemical shifts of compound 5, are presented in Table 11. NMR chemical shifts for the configuration assignment of compounds containing a double bond С=С linked to a phosphorus atom. Therefore, we calculated the 31 Р NMR chemical shifts and performed the theoretical conformational analysis of these compounds in order to explore the influence of configuration and the conformational effects on the 31 Р NMR spectra. The results of these calculations, including the localization of the prevailing conformers, the calculation of the relative energies (Erel) and 31 Р NMR chemical shifts of compound 5, are presented in Table 11. NMR chemical shifts for the configuration assignment of compounds containing a double bond С=С linked to a phosphorus atom. Therefore, we calculated the 31 Р NMR chemical shifts and performed the theoretical conformational analysis of these compounds in order to explore the influence of configuration and the conformational effects on the 31 Р NMR spectra. The results of these calculations, including the localization of the prevailing conformers, the calculation of the relative energies (Erel) and 31 Р NMR chemical shifts of compound 5, are presented in Table 11. bond [33]. In addition to these data, it was interesting to test the possibility of using Р NMR chemical shifts for the configuration assignment of compounds containing a double bond С=С linked to a phosphorus atom. Therefore, we calculated the 31 Р NMR chemical shifts and performed the theoretical conformational analysis of these compounds in order to explore the influence of configuration and the conformational effects on the 31 Р NMR spectra. The results of these calculations, including the localization of the prevailing conformers, the calculation of the relative energies (Erel) and 31 Р NMR chemical shifts of compound 5, are presented in Table 11. bond [33]. In addition to these data, it was interesting to test the possibility of using 31 Р NMR chemical shifts for the configuration assignment of compounds containing a double bond С=С linked to a phosphorus atom. Therefore, we calculated the 31 Р NMR chemical shifts and performed the theoretical conformational analysis of these compounds in order to explore the influence of configuration and the conformational effects on the 31 Р NMR spectra. The results of these calculations, including the localization of the prevailing conformers, the calculation of the relative energies (Erel) and 31 Р NMR chemical shifts of compound 5, are presented in Table 11. ble bond С=С linked to a phosphorus atom. Therefore, we calculated the 31 Р NMR chemical shifts and performed the theoretical conformational analysis of these compounds in order to explore the influence of configuration and the conformational effects on the 31 Р NMR spectra. The results of these calculations, including the localization of the prevailing conformers, the calculation of the relative energies (Erel) and 31 Р NMR chemical shifts of compound 5, are presented in Table 11. The internal rotation in both isomers 5 around the P-N bond as well as the rotation of the pyrazole ring around the C-N bond is allowed. The calculations show that four rotational conformers are localized for each isomer (Table 11). Theoretical data reveal that the E-isomer 5 is energetically more favorable than the Z-isomer in all probable  The internal rotation in both isomers 5 around the P-N bond as well as the rotation of the pyrazole ring around the C-N bond is allowed. The calculations show that four rotational conformers are localized for each isomer (Table 11). Theoretical data reveal that the E-isomer 5 is energetically more favorable than the Z-isomer in all probable Z s-trans-s-trans 6.5 16.6 The 31 P chemical shift values in the E-isomer 5 change within a fairly narrow range of 29-33 ppm, indicating the absence of any electronic effects at conformational variations. However, the range of 31 P NMR chemical shift variation in the Z-isomer is much larger, at 16-33 ppm. In the energetically more favorable s-cis-gauche and s-cis-s-trans conformers, a low-frequency shift seems to be due to the influence of the lone electron pair of the pyridine nitrogen atom. Nevertheless, in the s-trans-s-cis-conformer, where this interaction is absent, the chemical shift is the same as in the E-isomer, indicating an insignificant effect of the configuration change at the double bond on the 31 P NMR chemical shifts (Table 11) [59].
Compounds 37-39 exist in solution as individual isomers, the configuration assignment of which is a rather complicated problem and cannot be directly solved on the basis of NMR spectroscopy data. For this purpose, theoretical conformational analysis and calculation of the 31 P NMR chemical shifts were performed for each of the conformers of both isomers 37-39 containing the C=N-POCl 2 fragment (Tables 12-14, respectively).
The results of conformational analysis indicate that the Z-isomers of compounds 37-39 (Tables 12-14) are more favorable in terms of energy, and their energy is 2-9 kcal/mol lower than that of the E-isomers. The internal rotation around the N-P bond in the Z-isomers 37-39 points to the existence of three stable rotational conformers: s-cis, s-trans, and gauche. The three conformers are close in energy; however, in all cases the gauche form predominates, while the relative energy of s-cis and s-trans conformers is about 0.7 kcal/mol. This evidences almost equal content of these conformers in an equilibrium mixture. In the E-isomers of compounds 37-39, strong steric strains between the substituent and the bulky POCl 2 group were found. The gauche conformer is also the most stable in the E-isomers. However, in E-isomer 37, all three possible conformers can exist: s-cis, s-trans, and gauche (Table 12), and steric strain in s-cis and s-trans conformers leads to a significant deviation of the benzene ring from the double bond plane.
Conformational transitions in compound 39 (Table 14) occur due to the rotation of the N=PCl 3 fragment around C-N bond, which delivers two rotational conformations, s-cis and s-trans, while the s-cis forms in the Z-isomer are more favorable than the corresponding s-trans conformations by 3-5 kcal/mol. According to calculations in the E-isomer, only s-trans conformations with gauche and s-trans-orientations of the P=O bond can exist.
A similar influence on 31 P NMR chemical shifts is detected in compounds 37-39. Both isomers of compounds 37-39 in s-cisand gauche-forms have almost identical 31 P NMR chemical shifts. The only exclusions are s-cis-conformer 37E and gauche-conformer 38E which are characterized by a low-frequency shift of the resonance 31 P signal of about 10-15 ppm; this is perhaps attributable to the changes in the bond angles and bond lengths due to steric interactions compared with energetically favorable conformations. The upfield displacement of the phosphorus chemical shift in s-trans-conformations by approximately 15 ppm seems to be due to the formation of the C=N-P=O conjugated system, which may indicate a decrease in the length of the ordinary N-P bond by 0.2 Å compared with the s-cisand gauche-forms. An analogous effect was observed in compound 39Z during rotation around the C-N bond. At the s-trans-location of the P=N and C=N bonds, the position of the 31 P NMR signal has a low-frequency shift of 30 ppm, which can be explained by the conjugation effect.
Thus, there is good agreement between the theoretical and experimental 31 P NMR chemical shift values in the corresponding compounds in their prevailing conformations. In this case, taking into account the presence of the conformational equilibrium, the chemical shifts must be averaged with consideration of the occupancy of the rotational conformations. The theoretical 31 P chemical shift values averaged over all localized conformations of Eand Z-isomers of compounds 5, 37-39 are comparable with the experimental data (Table 10) [59]. Table 12. Theoretical values of 31 P NMR chemical shifts and relative energies of conformers 37.

Structure
Isomer Conformer E rel , kcal/mol Chemical Shift, ppm chemical shifts (Table 11) [59]. Compounds 37-39 exist in solution as individual isomers, the configuration assignment of which is a rather complicated problem and cannot be directly solved on the basis of NMR spectroscopy data. For this purpose, theoretical conformational analysis and calculation of the 31 Р NMR chemical shifts were performed for each of the conformers of both isomers 37-39 containing the C=N-POCl2 fragment (Tables 12-14 (Table 11) [59]. Compounds 37-39 exist in solution as individual isomers, the configuration assignment of which is a rather complicated problem and cannot be directly solved on the basis of NMR spectroscopy data. For this purpose, theoretical conformational analysis and calculation of the 31 Р NMR chemical shifts were performed for each of the conformers of both isomers 37-39 containing the C=N-POCl2 fragment (Tables 12-14      The results of conformational analysis indicate that the Z-isomers of compounds 37-39 (Tables 12-14) are more favorable in terms of energy, and their energy is 2-9 kcal/mol lower than that of the E-isomers. The internal rotation around the N-P bond in the Z-isomers 37-39 points to the existence of three stable rotational conformers: s-cis, s-trans, and gauche. The three conformers are close in energy; however, in all cases the gauche form predominates, while the relative energy of s-cis and s-trans conformers is about 0.7 kcal/mol. This evidences almost equal content of these conformers in an equilibrium mixture. In the E-isomers of compounds 37-39, strong steric strains between the substituent and the bulky POCl2 group were found. The gauche conformer is also the most stable in the E-isomers. However, in E-isomer 37, all three possible conformers can exist: s-cis, s-trans, and gauche (Table 12), and steric strain in s-cis and s-trans conformers leads to a significant deviation of the benzene ring from the double bond plane.
Conformational transitions in compound 39 (Table 14) occur due to the rotation of the N=PCl3 fragment around C-N bond, which delivers two rotational conformations, s-cis and s-trans, while the s-cis forms in the Z-isomer are more favorable than the corresponding s-trans conformations by 3-5 kcal/mol. According to calculations in the E-isomer, only s-trans conformations with gauche and s-trans-orientations of the P=O bond can exist.
A similar influence on 31 Р NMR chemical shifts is detected in compounds 37-39. Both isomers of compounds 37-39 in s-cis-and gauche-forms have almost identical 31 Р NMR chemical shifts. The only exclusions are s-cis-conformer 37Е and gauche-conformer 38Е which are characterized by a low-frequency shift of the resonance 31 Р signal of about Z s-cis-s-trans 0.5 −18.1

The Stereochemical Structure of Phosphorylated Pyrroles and Their Annulated Analogs
1-vinylpyrroles and their annulated analogs, indoles and carbazoles have also been phosphorylated by the reaction with phosphorus pentachloride to provide various phosphorylation products both at the vinyl group and at the pyrrole cycle [60][61][62][63]. The introduction of a phosphorus-containing fragment into the pyrrole rings is a structural motif of bioactive natural products and pharmaceutical drugs [64][65][66][67]. It allows us to expect the appearance of unusual biological activity in the phosphorylated pyrroles. The natural compound psilocybin, dimethyltryptamine-4-phosphate, is known to have strong hallucinogenic activity [62].
The 31 P NMR signals of E-2-(2-dichloromethyl-1-pyrrol-1-yl)vinylphosphonyl dichlorides 44, 45 are in the region of 31.9-34.4 ppm (dd, J PH = 23.1-24.8 Hz) and belong to the POCl 2 fragment. The 31 P NMR spectrum of dichloride 44 exhibits a low intensity signal at 20.7 ppm, which evidences the presence of the corresponding cyclic phosphinyl chloride 43 (6%, 31P NMR). In addition, phosphonyl chloride 44 is readily transformed to the corresponding phosphonic acid 46. It should be noted that the values of the 1 H and 13 C NMR chemical shifts of the pyrrole ring atoms in the considered phosphorylated series are weakly sensitive to the influence of a substituent (to substituent change).
The 31 P NMR signals of E-2-(2-dichloromethyl-1-pyrrol-1-yl)vinylphosphonyl dichlorides 44, 45 are in the region of 31.9-34.4 ppm (dd, JPH = 23.1-24.8 Hz) and belong to the POCl2 fragment. The 31 P NMR spectrum of dichloride 44 exhibits a low intensity signal at 20.7 ppm, which evidences the presence of the corresponding cyclic phosphinyl chloride 43 (6%, 31P NMR). In addition, phosphonyl chloride 44 is readily transformed to the corresponding phosphonic acid 46. It should be noted that the values of the 1 Н and 13 С NMR chemical shifts of the pyrrole ring atoms in the considered phosphorylated series are weakly sensitive to the influence of a substituent (to substituent change).
The NMR data confirm that E-isomerism is retained upon passing from complex salts 47, 48 to the corresponding phosphonic acid dichlorides 49, 50 and dichlorophosphines 51, 52.
The phosphorylation of N-vinylpyrroles which do not contain strong electron-withdrawing groups in the ring, as well as their annulated analogues, N-vinylindole and N-vinylcarbazole, has been studied [61]. The interaction of these pyrroles with phosphorus pentachloride yields various products of phosphorylation both at the pyrrole ring and at the vinyl group (Scheme 13, Table 17).  Similarly, the phosphorus signals in the NMR spectra of salts 47, 48 297 ppm and 95.7-97.1 ppm, related to PCl6 -and PCl3 + , correspondently, signals are observed as doublets 2 JPH = 33 Hz and 3 JPH = 35 Hz, wh E-configuration. The proton constant 3 JHH =16 Hz (vinyl group) in the 1 also points to the E-isomer.
The phosphorylation of N-vinylpyrroles which do not conta tron-withdrawing groups in the ring, as well as their annula N-vinylindole and N-vinylcarbazole, has been studied [61]. The interacti roles with phosphorus pentachloride yields various products of phospho the pyrrole ring and at the vinyl group (Scheme 13, Table 17).  Similarly, the phosphorus signals in the NMR spectra of salts 47, 48 297 ppm and 95.7-97.1 ppm, related to PCl6 -and PCl3 + , correspondently, signals are observed as doublets 2 JPH = 33 Hz and 3 JPH = 35 Hz, wh E-configuration. The proton constant 3 JHH =16 Hz (vinyl group) in the also points to the E-isomer.
The phosphorylation of N-vinylpyrroles which do not conta tron-withdrawing groups in the ring, as well as their annul N-vinylindole and N-vinylcarbazole, has been studied [61]. The interact roles with phosphorus pentachloride yields various products of phosph the pyrrole ring and at the vinyl group (Scheme 13, Table 17).     Hexachlorophosphates 53-55 after the action of SO 2, are converted into the corresponding pyrrolo [1,2-a]-1oxo-1,3-dichloro-4,1-azaphospholanes 56-58 (Table 17). The reaction of the salts 53-55 and triethylamine proceeds via the elimination of hydrogen chloride to give rise the corresponding phosphol-2-enes 59, 60, the structure of which was confirmed by 1 H, 13 C and 31 P NMR spectroscopy data [61].
The phosphorylation of indoles and carbazoles occurs exclusively at the vinyl group, as evidenced by the NMR data [61]. The indole and carbazole fragments of the latter are not attacked by phosphorus pentachloride (Scheme 14). 31

Conclusions
Azoles are the structural core of the most popular drugs used for the treatment of various diseases. Interest in organophosphorus compounds, including those containing azolyl moieties, increases every year due to their high and unusual (specific) biological activity [69][70][71][72][73][74][75][76][77][78][79][80]. In recent years, in connection with the rapid development of experimental technology, previously very problematic studies that are of key importance for the stereochemistry of heterocycles have become rather more possible and routine. This has greatly expanded the possibilities of and increased the information potential of NMR spectroscopy. The use (involvement) of multinuclear NMR spectroscopy, in particular 31 P, and quantum chemistry (high-level quantum chemical calculations) simplifies the problems associated with stereochemical behavior, for example, Z/E-isomerization of chlorophosphorylated N-vinylazoles. Increasing the coordination number of phosphorus from 3 to 6 leads to a dramatic shielding of the 31 P nucleus from about +200 to −300 ppm. Theoretical study of this extraordinary effect in combination (supplement) with experimental data allows a deeper understanding of the nature of the relationship between 31 Р NMR chemical shifts and the structure of organophosphorus compounds with different coordination numbers. 31 P NMR spectroscopy is the most convenient, powerful and straightforward express method for the recognition of tetra-, penta-, and hexacoordinated phosphorus atoms in phosphorylated N-vinylazoles, and for the identification of the stereochemical structure of isomeric forms of organophosphorus products.

Conclusions
Azoles are the structural core of the most popular drugs used for the treatment of various diseases. Interest in organophosphorus compounds, including those containing azolyl moieties, increases every year due to their high and unusual (specific) biological activity [69][70][71][72][73][74][75][76][77][78][79][80]. In recent years, in connection with the rapid development of experimental technology, previously very problematic studies that are of key importance for the stereochemistry of heterocycles have become rather more possible and routine. This has greatly expanded the possibilities of and increased the information potential of NMR spectroscopy. The use (involvement) of multinuclear NMR spectroscopy, in particular 31 P, and quantum chemistry (high-level quantum chemical calculations) simplifies the problems associated with stereochemical behavior, for example, Z/E-isomerization of chlorophosphorylated N-vinylazoles. Increasing the coordination number of phosphorus from 3 to 6 leads to a dramatic shielding of the 31 P nucleus from about +200 to −300 ppm. Theoretical study of this extraordinary effect in combination (supplement) with experimental data allows a deeper understanding of the nature of the relationship between 31 P NMR chemical shifts and the structure of organophosphorus compounds with different coordination numbers. 31 P NMR spectroscopy is the most convenient, powerful and straightforward express method for the recognition of tetra-, penta-, and hexacoordinated phosphorus atoms in phosphorylated N-vinylazoles, and for the identification of the stereochemical structure of isomeric forms of organophosphorus products. Acknowledgments: Dedicated to anniversary of Vladimir Rozinov, renowned expert in the chemistry of organophosphorus compounds. This work was carried out within the framework of the research project of Russian Academy of Sciences # 121021000264-1.