Advertisement

An investigation of the molecular mechanism, chemoselectivity and regioselectivity of cycloaddition reaction between acetonitrile N-Oxide and 2,5-dimethyl-2H-[1,2,3]diazaphosphole: a MEDT study

  • Abdellah ZeroualEmail author
  • Mar Ríos-Gutiérrez
  • Mohammed Salah
  • Habib El Alaoui El Abdallaoui
  • Luis Ramon Domingo
Regular Article

Abstract

The [3+2] cycloaddition (32CA) reactions of acetonitrile N-oxide with 2,5-dimethyl-2H-[1,2,3]diazaphosphole has been studied using the Molecular Electron Density Theory (MEDT) through DFT calculations at the B3LYP/6-31G(d,p) computational level. Analysis of the relative free energies associated with the competitive ortho and meta reaction paths shows high chemo- and regioselectivity for this 32CA reaction in clear agreement with the experimental outcomes. The topological analysis of the electron localization function (ELF) of the selected points of the IRC associated with the formation of the P-C and C-O single bonds indicates a zwitterionic type structure. The 32CA reaction takes place through a two-stage one-step mechanism initialized with the formation of the P-C single bond.

Graphic abstract

The mechanism, the chemo-, and regioselectivity of the [3+2] cycloaddition (32CA) reaction between ethylnitrile oxide and 2,5-dimethyl-2H-[1,2,3]diazaphosphole, have been theoretically studied at the DFT/ B3LYP/6-31(d,p) computational level. DFT calculations account for the total chemo- and regioselectivity in total conformity with the experimental results.

Keywords

Diazaphosphole acetonitrile N-oxide MEDT chemoselectivity regioselectivity 

Notes

Supplementary Information (SI)

ELF topological analysis of the P–C and C–O bond formation along with the 32CA reaction between 2,5-dimethyl-2H-[1,2,3]diazaphosphole 1 and acetonitrile N-oxide 2. Tables include B3LYP/6-31g(d,p) total and relative electronic energies, in the gas phase and in THF, and B3LYP/6-31G(d,p) thermodynamic data, computed at 25 °C and 1 atm in THF, for the stationary points involved in the 32CA reaction of 2,4-dimethyl-2H-phosphorus 1 with acetonitrile N-oxide 2. Supplementary information is available at www.ias.ac.in/chemsci.

Supplementary material

12039_2019_1656_MOESM1_ESM.pdf (616 kb)
Supplementary material 1 (PDF 616 kb)

References

  1. 1.
    Moriya O, Takenaka P H, lyoda M, Urataa Y and Endob T 1994 Generation of nitrite oxides via O-tributylstannylaldoximes; application to the synthesis of isoxazolines and isoxazoles J. Chem. Soc. Perkin. Trans. I 0 413CrossRefGoogle Scholar
  2. 2.
    Li X, Wang X, Wang Z, Yan X and Xu X 2019 TBHP-induced iodocyclization with I2: atom economic synthesis of iodinated isoxazolines in water under mild conditions ACS Sustain. Chem. Eng. 7 1875CrossRefGoogle Scholar
  3. 3.
    Woods D J, Vaillancourt V A, Wendt J A and Meeus P F 2011 Discovery and development of veterinary antiparasitic drugs: past, present and future Future Med. Chem. 3 887CrossRefGoogle Scholar
  4. 4.
    Zaki M, Oukhrib A, Akssira M and Berteina-Raboin S 2017 Synthesis of novel spiro-isoxazoline and spiro-isoxazolidine derivatives of tomentosin RSC Adv. 7 6523CrossRefGoogle Scholar
  5. 5.
    Zheng Y, Tice C M and Singh S B 2014 The use of spirocyclic scaffolds in drug discovery Bioorg. Med. Chem. Lett. 24 3673CrossRefGoogle Scholar
  6. 6.
    Yeung Lam KoY Y C, Tonnard F, Carrié R, De Sarlo F and Brandi A 1983 Cycloaddition d’oxydes de nitrile a des diazaphospholes et des composés apparentés. Réactivité comparée des doubles liaisons N=C, P=C et As=C. Tetrahedron 39 1507CrossRefGoogle Scholar
  7. 7.
    Domingo L R 2016 Molecular electron density theory: a modern view of reactivity in organic chemistry Molecules 21 1319CrossRefGoogle Scholar
  8. 8.
    Ríos-Gutiérrez M and Domingo L R 2019 Unravelling the mysteries of the [3+2] cycloaddition reactions Eur. J. Org. Chem. 267Google Scholar
  9. 9.
    Domingo L R, Aurell M J and Pérez P 2014 A DFT analysis of the participation of zwitterionic TACs in polar [3+2] cycloaddition reactions Tetrahedron 70 4519CrossRefGoogle Scholar
  10. 10.
    Ndassa I M, Adjieufack A I, Ketcha J M, Berski S, Ríos-Gutiérrez M and Domingo L R 2017 Understanding the reactivity and regioselectivity of [3 + 2] cycloaddition reactions between substituted nitrile oxides and methylacrylate. A molecular electron density theory study Int. J. Quantum Chem. 117 25451CrossRefGoogle Scholar
  11. 11.
    Lee C, Yang W and Parr R G 1988 Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density Phys. Rev. B 37 785CrossRefGoogle Scholar
  12. 12.
    Becke A D 1993 Density‐functional thermochemistry. III. The role of exact exchange J. Chem. Phys. 98 5648CrossRefGoogle Scholar
  13. 13.
    Hehre W J, Radom L, Schleyer P v R and Pople J A 1986 Ab initio Molecular Orbital Theory (New York: Wiley)Google Scholar
  14. 14.
    Schlegel H B 1982 Optimization of equilibrium geometries and transition structures J. Comput. Chem. 2 214CrossRefGoogle Scholar
  15. 15.
    Schlegel H B 1994 In Modern Electronic Structure Theory D R Yarkony (Ed.) (Singapore: World Scientific Publishing)Google Scholar
  16. 16.
    K Fukui 1970 Formulation of the reaction coordinate J. Phys. Chem. 74 4161CrossRefGoogle Scholar
  17. 17.
    González C and Schlegel H B 1990 Reaction path following in mass-weighted internal coordinates J. Phys. Chem. 94 5523CrossRefGoogle Scholar
  18. 18.
    González C and Schlegel H B 1991 Improved algorithms for reaction path following: higher‐order implicit algorithms J. Chem. Phys. 95 5853CrossRefGoogle Scholar
  19. 19.
    Tomasi J and Persico M 1994 Molecular interactions in solution: an overview of methods based on continuous distributions of the solvent Chem. Rev. 94 2027CrossRefGoogle Scholar
  20. 20.
    Cossi M, Barone V, Cammi R and Tomasi J 1996 Ab initio study of solvated molecules: a new implementation of the polarizable continuum model Chem. Phys. Lett. 255 327CrossRefGoogle Scholar
  21. 21.
    Cances E, Mennucci B and Tomasi J 1997 Evaluation of solvent effects in isotropic and anisotropic dielectrics and in ionic solutions with a unified integral equation method:  theoretical bases, computational implementation, and numerical applications J. Chem. Phys. 107 3032CrossRefGoogle Scholar
  22. 22.
    Barone V, Cossi M and Tomasi J 1998 Geometry optimization of molecular structures in solution by the polarizable continuum model J. Comput. Chem. 19 404CrossRefGoogle Scholar
  23. 23.
    Domingo L R 2014 A new C–C bond formation model based on the quantum chemical topology of electron density RSC Adv. 4 32415CrossRefGoogle Scholar
  24. 24.
    Reed A E, Weinstock R B and Weinhold F 1985 Natural population analysis J. Chem. Phys. 83 735CrossRefGoogle Scholar
  25. 25.
    Reed A E, Curtiss L A and Weinhold F 1988 Intermolecular interactions from a natural bond orbital, donor-acceptor viewpoint Chem. Rev. 88 899CrossRefGoogle Scholar
  26. 26.
    Parr R G, Szentpaly, L V and Liu S 1999 Electrophilicity Index J. Am. Chem. Soc. 121 1922CrossRefGoogle Scholar
  27. 27.
    Domingo L R, Chamorro E and Pérez P 2008 Understanding the reactivity of captodative ethylenes in polar cycloaddition reactions. A theoretical study J. Org. Chem. 73 4615CrossRefGoogle Scholar
  28. 28.
    Domingo L R, Pérez P and Sáez J A 2013 Understanding the local reactivity in polar organic reactions through electrophilic and nucleophilic Parr functions RSC Adv. 3 1486CrossRefGoogle Scholar
  29. 29.
    M J Frisch et al., Gaussian 09, Inc., Wallingford CT, 2009Google Scholar
  30. 30.
    Becke A D and Edgecombe K E 1990 A simple measure of electron localization in atomic and molecular systems J. Chem. Phys. 92 5397CrossRefGoogle Scholar
  31. 31.
    Noury S, Krokidis X, Fuster F and Silvi B 1999 Computational tools for the electron localization function topological analysis Comput. Chem. 23 597CrossRefGoogle Scholar
  32. 32.
    Domingo L R, Saez J A, Zaragoza R J and Arno M 2008 Understanding the participation of quadricyclane as nucleophile in polar [2 sigma+2 sigma+2 pi] cycloadditions toward electrophilic pi molecules J. Org. Chem. 73 8791CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  • Abdellah Zeroual
    • 1
    Email author
  • Mar Ríos-Gutiérrez
    • 2
  • Mohammed Salah
    • 1
  • Habib El Alaoui El Abdallaoui
    • 1
  • Luis Ramon Domingo
    • 2
  1. 1.Molecular Modeling and Spectroscopy Research Team, Faculty of ScienceChouaïb Doukkali UniversityEl JadidaMorocco
  2. 2.Department of Organic ChemistryUniversity of ValenciaBurjassot, ValenciaSpain

Personalised recommendations