Synthesis of E-Isomer of α-Hydrazone Phosphonates via Nucleophilic Addition of Trialkyl Phosphite to Nitrile Imines (NIs) and DFT Calculations

Year 2024, Volume: 10 Issue: 2, 415 - 425, 25.06.2024

Sıdıka Polat Çakır Sinem Altınışık

https://doi.org/10.28979/jarnas.1418948

Abstract

Nitrile imines (NIs) belong to the nitrilium betaine family of 1,3-dipoles. Due to their high reactivity, NI compounds cannot be isolated and must be generated in situ before undergoing the desired transformation. NI derivatives were prepared by the utilization of N-phenyl hydrazine chloride precursors in the presence of a base. The title compounds α-hydrazone phosphonates have the potential to be biologically active and may serve as a precursor compound for other biologically active substances like amino phosphonic acids. Shortly, they are highly significant compounds in medicinal and synthetic chemistry. The derivatives of α-hydrazone phosphonate are synthesized by the nucleophilic addition of trialkyl phosphite to in situ generated NI derivatives and obtained in 44-95% isolated chemical yields. It is worth noting that only the E-isomer of the α-hydrazone phosphonates was obtained. Structural analyses of the α-hydrazone phosphonates were conducted by using proton and carbon NMR analysis along with FTIR. The researchers also performed DFT calculations including structural parameters (bond length, bond angle, and dihedral angle), HOMO and LUMO energy levels, and the zero-point vibrational energy (ZPE) for both E and Z geometric isomers of unsubstituted phenyl α-hydrazone phosphonate.

Keywords

Nitrile imines, nucleophilic addition, trialkyl phosphite, 1, 3-dipole, α-hydrazone phosphonates

References

• C. Jamieson, K. Livingstone, The nitrile imine 1,3-dipole: Properties, reactivity, and applications, 1st Edition, Springer, Cham, 2020.
• R. Huisgen, M. Seidel, J. Sauer, J. McFarland, G. Wallbillich, The formation of nitrile imines in the thermal breakdown of 2,5-disubstituted tetrazoles, Journal of Organic Chemistry 24 (1959) 892–893.
• S. Ningaiah, S.D. Doddaramappa, Chandra, M. Madegowda, S. Keshavamurthy, U. K. Bhadraiah, One-pot tandem synthesis of tetrasubstituted pyrazoles via 1,3-dipolar cycloaddition between aryl hydrazones and ethyl but-2-ynoate, Synthetic Communication 44 (2014) 2222–2231.
• A. S. Shawali, M. A. N. Mosselhi, Hydrazonoyl halides: useful building blocks for the synthesis of arylazoheterocycles, Journal of Heterocyclic Chemistry 40 (2003) 725–746.
• R. Huisgen, H. J. Sturm, M. Seidel, Ringöffnungen der Azole, V. Weitere Reaktionen der Tetrazole mit elektrophilen Agenzien, Chemische Berichte 94 (1961) 1555–1562.
• R. Huisgen, R. Grashey, M. Seidel, H. Knupfer, R. Schmidt, 1.3-Dipolare additionen, III. umsetzungen des diphenylnitrilimins mit carbonyl und thiocarbonyl-verbindungen, Justus Liebigs Annalen der Chemie 658 (1962) 169–180.
• R. Huisgen, M. Seidel, G. Wallbillich, H. Knupfer, Diphenyl-nitrilimin und seine 1.3-dipolaren additionen an alkene und alkine, Tetrahedron 17 (1962) 3–29.
• Y. Zhang, W. Liu, Z. Zhao, Nucleophilic trapping nitrilimine generated by photolysis of diaryltetrazole in aqueous phase, Molecules 19 (2013) 306–315.
• C. Csongár, L. Grubert, G. Tomaschewski, Photochemistry of Aryl-Substituted Sydnone IV. and 2H-Tetrazole VIII. Reaction of nitrilimines with phenols, Zeitschrift für Chemie 28 (1988) 24–25.
• Z. Li, L. Qian, L. Li, J.C. Bernhammer, H. V. Huynh, J. S. Lee, S. Q. Yao, Tetrazole photo click chemistry: reinvestigating its suitability as a bioorthogonal reaction and potential applications, Angewandte Chemie International Edition 55 (2016) 2002–2006.
• P. D. Croce, P. Del Buttero, E. Licandro, S. Maiorana, Synthesis of Arylazomethylenetriphenylphosphoranes from Arylhydrazonoyl chlorides (via Nitrilimines in situ) and Triphenylphosphine, Synthesis 4 (1979) 299–300.
• M. P. Kaushik, B. Lal, C. D. Raghuveeran, R. Vaidyanathaswamy, Stereochemistry of aroylphosphonate phenylhydrazones and their conversion to 1H-indazole-3-phosphonates, The Journal of Organic Chemistry 47 (18) (1982) 3503-3505.
• G. Baccolini, M. Faggiano, P. E. Todesco, Reactions of Diphenyl nitrilimine with Phosphites and Diazaphospholenes, Journal of the Chemical Society, Perkin Transactions 1 0 (1979) 2329–2333.
• K. Paulvannan, T. Chen, R. Hale, An improved synthesis of 1,2,4-triazoles using Ag2CO3, Tetrahedron 56 (2000) 8071–8076.
• M.J.Frisch, G.W.Trucks, H.B.Schlegel, G.E.Scuseria, M.A.Robb, J.R.Cheeseman, G.Scalmani, V.Barone, G.A.Petersson, H.Nakatsuji, X.Li, M.Caricato, A.Marenich, J.Bloino, B.G.Janesko, R.Gomperts, B.Mennucci, H.P.Hratchian, J.V.Ortiz, A.F.Izmaylov, J.L.Sonnenberg, D.Williams-Young, F.Ding, F.Lipparini, F.Egidi, J.Goings, B.Peng, A.Petrone, T.Henderson, D.Ranasinghe, V.G.Zakrzewski, J.Gao, N.Rega, G.Zheng, W.Liang, M.Hada, M.Ehara, K.Toyota, R.Fukuda, J.Hasegawa, M.Ishida, T.Nakajima, Y.Honda, O.Kitao, H.Nakai, T.Vreven, K.Throssell, J.A.Montgomery, Jr., J.E.Peralta, F.Ogliaro, M.Bearpark, J.J.Heyd, E.Brothers, K.N.Kudin, V.N.Staroverov, T.Keith, R.Kobayashi, J.Normand, K.Raghavachari, A.Rendell, J.C.Burant, S.S.Iyengar, J.Tomasi, M.Cossi, J.M.Millam, M.Klene, C.Adamo, R.Cammi, J.W.Ochterski, R.L.Martin, K.Morokuma, O.Farkas, J.B.Foresman, D.J.Fox, Gaussian 09 – Revision A.02 (2016), https://gaussian.com/g09citation/, Accessed 1 Jan 2024.
• M. Ríos-Gutiérrez, A. S. Sousa, L. R. Domingo, Electrophilicity and nucleophilicity scales at different DFT computational levels, The Journal of Physical Organic Chemistry 36 (7) (2023) e4503 14 pages.