Skip to content
Research Article Open access CC BY 4.0

Application of β-Phosphorylated Nitroethenes in [3+2] Cycloaddition Reactions Involving Benzonitrile N-Oxide in the Light of a DFT Computational Study

Karolina Zawadzińska, Karolina Kula

Organics · pp. 26–37 · Published 16 Feb 2021

10.3390/org2010003

Abstract

The regiochemistry of [3+2] cycloaddition (32CA) processes between benzonitrile N-oxide 1 and β-phosphorylated analogues of nitroethenes 2a–c has been studied using the Density Functional Theory (DFT) at the M062X/6-31+G(d) theory level. The obtained results of reactivity indices show that benzonitrile N-oxide 1 can be classified both as a moderate electrophile and moderate nucleophile, while β-phosphorylated analogues of nitroethenes 2a–c can be classified as strong electrophiles and marginal nucleophiles. Moreover, the analysis of CDFT shows that for [3+2] cycloadditions with the participation of β-phosphorylatednitroethene 2a and β-phosphorylated α-cyanonitroethene 2b, the more favored reaction path forms 4-nitro-substituted Δ2-isoxazolines 3a–b, while for a reaction with β-phosphorylated β-cyanonitroethene 2c, the more favored path forms 5-nitro-substituted Δ2-isoxazoline 4c. This is due to the presence of a cyano group in the alkene. The CDFT study correlates well with the analysis of the kinetic description of the considered reaction channels. Moreover, DFT calculations have proven the clearly polar nature of all analyzed [3+2] cycloaddition reactions according to the polar one-step mechanism.

Benzonitrile Cycloaddition Chemistry Nucleophile Electrophile Density functional theory Regioselectivity Reactivity (psychology)

References (55)

  1. 1 Huisgen, 1963, 1,3-Dipolare Cycloadditionen Rückschau und Ausblick [DOI]
  2. 2 Dresler, 2017, A full regio- and stereoselective synthesis of 4-nitroisoxazolidines via stepwise [3+2] cycloaddition reactions between (Z)-C-(9-anthryl)-N-arylnitrones and (E)-3,3,3-trichloro-1-nitroprop-1-ene: Comprehensive experimental and theoretical study [DOI]
  3. 3 Kula, 2019, Recent progress in the field of cycloaddition reactions involving conjugated nitroalkenes
  4. 4 Fryzlewicz, 2020, Regio- and stereoselective synthesis of nitro-functionalized analogs of nicotine [DOI]
  5. 5 Martina, 2019, Green Protocols in Heterocycle Syntheses via 1,3-Dipolar Cycloadditions [DOI]
  6. 6 Zhang, 2007, The synthesis and biological activity of novel spiro-isoxazoline C-disaccharides based on 1,3-dipolar cycloaddition of exo-glycals and sugar nitrile oxides [DOI]
  7. 7 Jasinski, R., and Dresler, E. (2020). On the Question of Zwitterionic Intermediates in the [3+2] Cycloaddition Reactions: A Critical Review. Organics, 7. [DOI]
  8. 8 Kula, 2018, A DFT computational study on the [3+2] cycloaddition between parent thionitrone and nitroethene [DOI]
  9. 9 Kula, 2020, [3+2] Cycloaddition of diaryldiazomethanes with (E)-3,3,3-trichloro-1-nitroprop-1-ene: An experimental, theoretical and structural study [DOI]
  10. 10 Huisgen, 1963, 1,3-Dipolar Cycloadditions. Past and Future [DOI]
  11. 11 Jeddeloh, 2007, A Library of 3-aryl-4,5- dihydroisoxazole-5-carboxamides [DOI]
  12. 12 Quadrelli, 2014, Syntheses of Isoxazoline-Carbocyclic Nucleosides and Their Antiviral Evaluation: A Standard Protocol [DOI]
  13. 13 Znati, 2018, Synthesis of new anticancer and anti-inflammatory isoxazolines and aziridines from the natural (-)-deltoin [DOI]
  14. 14 Filial, 2014, Synthesis of new isoxazoline derivatives from harmine and evaluation of their anti-Alzheimer, anti-cancer and anti-inflammatory activities [DOI]
  15. 15 Saravanan, G., Alagarsamy, V., and Dineshkumar, P. (2013). Synthesis, analgesic, anti-inflammatory and in vitro antimicrobial activities of some novel isoxazole coupled quinazolin-4(3H)-one derivatives. Arch. Pharm. Res. [DOI]
  16. 16 Sharifi, 2012, Side effects of risperidone
  17. 17 Masaguer, 2007, Synthesis and binding affinity of new pyrazole and isoxazole derivatives as potential atypical antipsychotics [DOI]
  18. 18 2005, Recent Advances on the Synthesis and Reactivity of Isoxazoles [DOI]
  19. 19 Kanemasa, 1990, Recent advances in synthetic applications of nitrile oxide cycloaddition [DOI]
  20. 20 Sewald, 2003, Synthetic Routes towards Enantiomerically Pure β-Amino Acids [DOI]
  21. 21 Harada, 1997, Ring Transformation of 2-Isoxazoline 2-Oxides by Lewis Acids
  22. 22 Ono, N. (2001). The Nitro Group in Organic Synthesis, Wiley-VSH. [DOI]
  23. 23 Padwa, A., and Pearson, W.H. (2002). Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products, John Wiley & Sons. [DOI]
  24. 24 Kula, 2019, Novel functionalized β-nitrostyrenes: Promising candidates for new antibacterial drugs [DOI]
  25. 25 1992, Phosphoryl group participation leads to peptide formation from N-phosphorylamino acids [DOI]
  26. 26 Nalwa, H.S. (2001). Handbook of Surfaces and Interfaces of Materials, Academic Press. [DOI]
  27. 27 Ram, V.J., Sethi, A., Nath, M., and Pratap, R. (2019). The Chemistry of Heterocycles, Elsevier.
  28. 28 Mersbergen, 1998, 1,3-Dipolar Cycloadditions of Benzonitrile Oxide with Various Dipolarophiles in Aqueous Solutions. A Kinetic Study [DOI]
  29. 29 Dresler, 2017, A DFT computational study of the molecular mechanism of [3+2] cycloaddition reactions between nitroethene and benzonitrile N-oxides [DOI]
  30. 30 Domingo, 2016, Understanding the molecular mechanism of the [3+2] cycloaddition reaction of benzonitrile oxide toward electron-rich N-vinylpyrrole: A DFT study [DOI]
  31. 31 Domingo, L.R., Ríos Gutiérrez, M., and Castellanos Soriano, J. (2020). Understanding the Origin of the Regioselectivity in Non-Polar [3+2] Cycloaddition Reactions through the Molecular Electron Density Theory. Organics, 1. [DOI]
  32. 32 Demchuk, 2014, Regio- and stereoselectivity of polar [2+3] cycloaddition reactions between (Z)-C-(3,4,5-trimethoxyphenyl)-N-methylnitrone and selected (E)-2-substituted nitroethenes
  33. 33 2018, Competition between one-step and two-step mechanism in polar [3+2] cycloadditions of (Z)-C-(3,4,5-trimethoxyphenyl)-N-methyl-nitrone with (Z)-2-EWG-1-bromo-1-nitroethenes [DOI]
  34. 34 Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Petersson, G.A., and Nakatsuji, H. (2016). Gaussian 09 Rev. A.02, Gaussian, Inc.
  35. 35 2020, A new insight on the molecular mechanism of the reaction between (Z)-C,N-diphenylnitrone and 1,2-bismethylene-3,3,4,4,5,5-hexamethylcyclopentane [DOI]
  36. 36 Kącka-Zych, A. (2020). Participation of Phosphorylated Analogues of Nitroethene in Diels–Alder Reactions with Anthracene: A Molecular Electron Density Theory Study and Mechanistic Aspect. Organics, 1. [DOI]
  37. 37 Kula, 2021, Local nucleophile-electrophile interactions in [3+2] cycloaddition reactions between benzonitrile N-oxide and selected conjugated nitroalkenes in the light of MEDT computational study [DOI]
  38. 38 Stephens, 1994, Ab Initio Calculation of Vibrational Absorption and Circular Dichroism Spectra Using Density Functional Force Fields [DOI]
  39. 39 Domingo, L.R., Kula, K., and Ríos-Gutiérrez, M. (2020). Unveiling the Reactivity of Cyclic Azomethine Ylides in [3+2] Cycloaddition Reactions within the Molecular Electron Density Theory. Eur. J. Org. Chem., 5938–5948. [DOI]
  40. 40 Schlegel, 1982, Optimization of equilibrium geometries and transition structures [DOI]
  41. 41 Yarkony, D.R. (1994). Modern Electronic Structure Theory, World Scientific Publishing. [DOI]
  42. 42 Fukui, 1970, Formulation of the reaction coordinate [DOI]
  43. 43 Tapia, 1992, Solvent Effect Theories: Quantum and Classical Formalism and their Applications in Chemistry and Biochemistry [DOI]
  44. 44 Tomasi, 1994, Molecular Interactions in Solution: An Overview of Methods Based on Continuous Distributions of the Solvent [DOI]
  45. 45 Cossi, 1996, Ab initio study of solvated molecules: A new implementation of the polarizable continuum model
  46. 46 Domingo, 2014, A New C-C bond formation model based on the quantum chemical topology of electron density [DOI]
  47. 47 Mloston, G., Jasiński, R., Kula, K., and Heimgartner, H. (2020). A DFT Study on the Barton-Kellogg Reaction—The Molecular Mechanism of the Formation of Thiiranes in the Reaction between Diphenyldiazomethane and Diaryl Thioketones. Eur. J. Org. Chem., 176–182. [DOI]
  48. 48 Parr, 1999, Electrophilicity Index [DOI]
  49. 49 Domingo, L.R., Ríos-Gutiérrez, M., and Pérez, P. (2016). Applications of the Conceptual Density Functional Theory Indices to Organic Chemistry Reactivity. Molecules, 21. [DOI]
  50. 50 Domingo, 2009, A condensed-to-atom nucleophilicity index. An application to the director effects on the electrophilic aromatic substitutions [DOI]
  51. 51 Greelings, 2003, Conceptual Density Functional Theory [DOI]
  52. 52 Domingo, 2003, Quantitative characterization of the global electrophilicity pattern of some reagents involved in 1,3-dipolar cycloaddition reactions [DOI]
  53. 53 Domingo, 2013, Understanding the local reactivity in polar organic reactions through electrophilic and nucleophilic Parr functions [DOI]
  54. 54 Domingo, 2009, Understanding the mechanism of polar Diels-Alder reactions [DOI]
  55. 55 Domingo, 2019, On the nature of organic electron density transfer complexes within molecular electron density theory [DOI]

Cited by 75

Analysis of the possibility and molecular mechanism of carbon dioxide consumption in the Diels-Alder processes

Karolina Kula, Agnieszka Kącka‐Zych, Agnieszka Łapczuk-Krygier · Pure and Applied Chemistry · 2021

Green, one-pot synthesis of 1,2-oxazine-type herbicides via non-catalyzed Hetero Diels-Alder reactions comprising (2E)-3-aryl-2-nitroprop-2-enenitriles

Przemysław Woliński, Agnieszka Kącka‐Zych, Barbara Mirosław · Journal of Cleaner Production · 2022

Preparation of conjugated nitroalkenes: short review

Karolina Zawadzińska, Gajendra Kumar Gaurav, Radomir Jasiński · Scientiae Radices · 2022

Modeling of the General Trends of Reactivity and Regioselectivity in Cyclopentadiene–Nitroalkene Diels–Alder Reactions

Adrianna Fałowska, Stanisław Grzybowski, Daniel Kapuściński · Molecules · 2025

Computational model of the formation of novel nitronorbornene analogs via Diels–Alder process

Aleksandra Karaś, Agnieszka Łapczuk-Krygier · Reaction Kinetics Mechanisms and Catalysis · 2025

In Silico Study About Substituent Effects, Electronic Properties, and the Biological Potential of 1,3-Butadiene Analogues

Karolina Kula, Emilia Kuś · International Journal of Molecular Sciences · 2025

Showing 42 of 75 known citations — external sources report more than can currently be individually listed.

Article metrics

Real usage data collected on this platform.

0

Page views

0

PDF downloads

0

Outbound clicks

75

Citations

Views by country

Approximate, from request IP at view time — not citizenship or institution. Countries with fewer than 5 views are grouped as "Other".

No views recorded yet.

Traffic sources

Referring site, by host.

No traffic recorded yet.

Views and downloads exclude known bots/crawlers. Citations combines this platform's own DOI-resolved index with each external source's own reported total — see Cited by above for individually listed citing works. Last refreshed 0 seconds ago.