Structure of 3(5)-[(4-diphenylphosphinoyl)phenyl]pyrazole in the solid state (X-ray and CPMAS NMR) and in solution (NMR): tautomerism and hydrogen bonds

The structure of 3(5)-[(4-diphenylphosphinoyl)phenyl]pyrazole has been determined by X-ray crystallography. The compound crystallizes from DMF as the 1 H -3-substituted tautomer (monoclinic, space group P 2 1 / c ). The complete characterization by means of 13 C, 31 P and 15 N CPMAS NMR allowed us to confirm that at the solid state only such tautomer is found, with strong intermolecular hydrogen bonds between the pyrazole-NH donor and the phosphine oxide group acceptor. At 300 K in DMSO-d 6 solution, the two tautomers were detected in a ratio 3-tautomer versus 5-tautomer of 86:14. According to DFT calculations (B3LYP/6-31G** + ZPE), the 3-[(4-diphenylphosphinoyl)phenyl]-1 H -pyrazole tautomer is more stable by about 3.8 kJ mol –1 .

Concerning tautomerism, we have found that in 3(5)-substituted pyrazoles alkyl groups prefer to occupy position 5 (tautomer b), while aryl groups seem to prefer position 3 (tautomer a).The secondary structure, resulting from the hydrogen bonds between molecules in the crystal, leads to the formation of dimers or tetramers in alkyl substituted pyrazoles and trimers or catemers for the aryl ones.In general the substituent at position 4 plays a minor role by pushing away the adjacent substituents (buttressing effect).We have found a few number of exceptions: the 3( 5)-(1-adamantyl)pyrazole (1) where the simultaneous presence of both tautomers a and b in the crystal gives rise to a catemer, 2 and the 3(5)-phenylpyrazole (2) where it is possible to isolate the two independent tautomers in the solid state, the most stable one 5-phenyl-1H-pyrazole (2b) forming a catemer of order 2, 5 and the 3phenyl-1H-pyrazole (2a) hexamers. 6n order to advance in the understanding of the problem, we decided to study the case of the 3(5)-[(4-diphenylphosphinoyl)phenyl]pyrazole (3).

X-Ray crystal and molecular structure
The values of the bond lengths and positions of the H atoms found by X-ray diffraction study indicate that in solid state the compound 3 exist as 3a (Fig. 2).In the crystal structure the molecules 3a form an infinite chain by N( 2

Theoretical calculations
Both tautomers of 3(5)-[(4-diphenylphosphinoyl)phenyl]pyrazole (3) have been fully optimized and characterized as minima (no imaginary frequencies) using different theoretical approaches (Table 1).All methods yield very similar results, including AM1, which gives confidence of the results obtained.At the highest level, the difference is 3.83 kJ mol -1 in favor of the 1H-3-substituted tautomer 3a.This difference in energy corresponds to K = 4.64, that is to 82% of 3a and 18% of 3b.Since in solution we have determined an 86/14 ratio, the agreement is excellent considering that the highest dipole moment of 3a would increase its stability in polar solvents.
The model for the secondary structure in crystals of NH-pyrazoles was established for NHpyrazoles lacking better hydrogen bond acceptors (HBA) than N-2. 1 In the case of 3 there is a strong HB between N1-H1 and O=P leading to catemers.It is well known that the phosphine oxides are excellent HBA. 25,26xperimental Section General Procedures.The starting material, 4-(diphenylphosphino)acetophenone, was prepared by the literature method. 27It was converted to 3( 5)-(4-diphenylphosphine)pyrazole by the method used for converting acetophenone to 3(5)-phenylpyrazole. 28 The crude product was characterized only by NMR [7.72 doublet (2H, 3-phenylene), 7.57 (1 H, d.H-5), 7.34 (12 H, phenyl groups plus phenylene doublet), 6.59 (1H, d, H-4) ppm], and was oxidized to 3( 5)-(4diphenylphinoylphenyl)pyrazole 3 by dissolving it in acetone, and treating this solution dropwise with an excess of 10% solution of hydrogen peroxide.Evaporation of the solution gave the product in over-all yield of 43 %, which was purified by recrystallization from anisole.M.

NMR measurements
NMR spectra were recorded on a Bruker DRX 400 (9.4 Tesla, 400.13 MHz for 1 H, 100.62 MHz for 13 C, for 31 P and 40.56 MHz for 15 N) spectrometer.Chemical shifts (δ in ppm) are given from internal solvent CDCl 3 7.26 for 1 H and 77.0 for 13 C, and for 31 P and 15 N NMR, 85% H 3 PO 4 and nitromethane were used as external standards.2D gs-COSY ( 1 H-1 H) and 2D inverse proton detected heteronuclear shift correlation spectra, gs-HMQC ( 1 H-13 C), gs-HMBC ( 1 H-13 C) and gs-HMBC ( 1 H-15 N), were obtained using the standard pulse sequences. 19olid state 13 C (100.73 MHz), 31 P (162.16MHz) and 15 N (40.60 MHz) CPMAS NMR spectra have been obtained on a Bruker WB 400 spectrometer at 300 K using a 4 mm DVT probehead.Samples were carefully packed in a 4-mm diameter cylindrical zirconia rotors with Kel-F endcaps and the standard CPMAS with the TPPM decoupling pulse sequence was used. 13C spectra were originally referenced to a glycine sample and then the chemical shifts were recalculated to the Me 4 Si (for the carbonyl atom δ (glycine) = 176.1 ppm), 31 P spectra to (NH 4 ) 2 HPO 4 and converted to solution 85% H 3 PO 4 using the relationship: δ 31 P(85% H 3 PO 4 ) = δ 31 P[(NH 4 ) 2 HPO 4 ] + 1.6 ppm and 15 N spectra to 15 NH 4 Cl and then converted to nitromethane scale using the relationship: δ 15 N(nitromethane) = δ 15 N(ammonium chloride) -338.1 ppm.
The typical acquisition parameters for 13 C CPMAS were: spectral width, 40 kHz, acquisition time, 30 ms; contact time, 2 ms; and spin rate, 12 kHz.To assign in the solid state the carbon signals we run the NQS (Non-Quaternary Suppression) experiments by conventional crosspolarization with the difference that before the acquisition the decoupler is switched off for a very short time of 25 µs 29 and by examination of short contact time, 200 µs (SCP CPMAS) 30 C-H subspectra (in this experiment only protonated carbon atoms are observed).
For 31 P CPMAS the acquisition conditions were: spectral width, 100 kHz, acquisition time, 40 ms; contact time, 2 ms; and spin rate, 10 kHz.For natural abundance 15 N were: spectral width, 40 kHz, acquisition time, 35 ms; spin rate 6 kHz, contact time for spin lock, 2 ms; and relaxation delay, 5 s.
All software is contained in the SHELXTL (5.1) library (G.M. Sheldrick, Bruker AXS, Madison, WI, USA).Crystallographic data for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as deposition No. CCDC-206683.Copies of the data can be obtained, free of charge, on application to the CCDC, 12 Union Road, Cambridge CB21EZ UK (fax: +44 (1223) 336033;e-mail: deposit@ccdc.cam.ac.uk).

Theoretical calculations
The optimization of the structures of the two tautomers was carried out at the different levels: semiempirical AM1, ab initio Hartree Fock (HF/6-31G* and HF/6-31G**) and density functional (B3LYP/6-31G**), as shown in Table 1, by using the Windows Titan 1.0.5 package from Wavefunction Inc.