A regio- and stereoselectivity and molecular mechanism study on the addition reactions of morpholine and m-CPBA to 9α-hydroxyparthenolide using DFT calculations

A regio- and stereoselectivity and molecular mechanism study on the addition reactions of morpholine and m-CPBA to 9α-hydroxyparthenolide using DFT calculations

Authors

  • Sanaa Elhamidi
  • Wafaa Boumya
  • Redouan Hammal
  • Mohamed Moumou
  • Asmaa Ben Naji
  • Sadiq Mhamed
  • Ahmed Chekroun
  • Ahmed Benharref
  • Noureddine Barka Sultan Moulay Slimane University of Beni-Mellal, Research Group in Environmental Sciences and Applied Materials (SEMA), FP Khouribga, B.P. 145, 25000 Khouribga, Morocco
  • Mohamed Abdennouri

DOI:

https://doi.org/10.13171/mjc10502005221429nb

Abstract

The chemoselectivity and stereospecificity of the addition of the morpholine and the meta-chloroperoxybenzoic acid (m-CPBA) onto 9α-hydroxyparthenolide were studied using Density Functional Theory (DFT) calculations with the B3LYP/6-311+G(d,p) computational level within the Molecular Electron Density Theory (MEDT), to demonstrate the key role of the Global Electron Density Transfer (GEDT) and to examine the polar character of these reactions. This work is divided into two parts; the first part concerns the reaction between the morpholine and the 9α-hydroxyparthenolide. The second part deals with the epoxidation of the 9α-hydroxyparthenolide by m-CPBA followed by the addition of the morpholine to the major product resulting from the epoxidation step. The obtained results show that the reaction between the morpholine and the 9α-hydroxyparthenolide takes place on the double bond C3=C4. On the other hand, when 9α-hydroxyparthenolide is attacked by m-CPBA, the epoxidation reaction is carried out on the double bond C1=C2.

References

- A. Ghantous, A. Sinjab, Z. Herceg, N. Darwiche, Parthenolide: from plant shoots to cancer roots, Drug discovery today, 2013,18, 894–905.

- M. Moumou, A. R. El Bouakher, H. Allouchi, A. El Hakmaoui, A. Benharref, V. Mathieu, G. Guillaumet, M. Akssira, Synthesis and biological evaluation of 9α- and 9β-hydroxyaminoparthenolides as novel anticancer agents, Bioorg. Med. Chem. Lett., 2014, 24, 4014-4018.

- H. Eyring, the energy of activation for bimolecular reactions involving hydrogen and the halogens, according to the quantum mechanics, J. Am. Chem. Soc., 1931, 53, 2537-2549.

- K. Fukui, T. Yonezawa, H. Shingu, A molecular orbital theory of reactivity in aromatic hydrocarbons, J. Chem. Phys., 1952, 20,

-725.

- G. Klopman, Chemical reactivity and the concept of charge-and frontier-controlled reactions, J. Am. Chem. Soc., 1968, 90, 223-234.

- R. G. Parr, R. G. Pearson, Absolute Hardness: Companion Parameter to Absolute Electronegativity, J. Am. Chem. Soc., 1983, 105, 7512-7516.

- S. El Hamidi, M. Khnifira, A. Elhalil, R. Hammal, N. Barka, M. Sadiq, A. Benharref, H. Lafridi, H. Zgou, M. Abdennouri, A theoretical study of regio and stereoselectivity nitration of thymol and carvacrol using DFT approach, Mor. J. Chem., 2019, 7, 363-372.

- L. R. Domingo, M. R. Gutiérrez, P. Pérez, A new model for C-C bond formation processes derived from the Molecular Electron-Density Theory in the study of the mechanism of [3+2] cycloaddition reactions of carbenoid nitrile ylides with electron-deficient ethylenes, Tetrahedron, 2016, 72, 1524-1532.

- R.G. Parr, L.V. Szentpaly, S. Liu, Electrophilicity index, J. Am. Chem. Soc., 1999, 121, 1922-1924.

- R. Hammal, M. Zoubir, A. Benharref, A. El Hajbi, Natural Bond Orbital Population Analysis of α-trans-himachalene, Research Journal of Pharmaceutical Biological and Chemical Sciences, 2017, 8(6), 423-432.

- L. R. Domingo, P. Pérez, The nucleophilicity N index in organic chemistry, J. Org. Biomol. Chem., 2011, 9, 7168-7175.

- L. R. Domingo, P. Pérez, J. A. Sáez, Understanding the local reactivity in polar organic reactions through electrophilic and nucleophilic Parr functions, RSC Advances, 2013, 3, 1486-1494.

- A. Zeroual, R. Hammal, A. Benharref, A. El Hajbi, The regio- and stereoselective addition of dibromocarbene and dichlorocarbene onto

β-himachalene, Mor. J. Chem., 2015, 3, 698-704.

- W. Yang, W.J. Mortier, The Use of Global and Local Molecular Parameters for the Analysis of the Gas-Phase Basicity of Amines, J. Am. Chem. Soc., 1986, 108, 5708-5711.

- R. K. Otmane, T. S. Ouk, R. Bahadi, A. Bouzina, S.D. Djouad, K. Bechlem, R. Zerrouki, T. Ben Hadda, F. Almalki, M. Berredjem, Synthesis, DFT and POM analyses of cytotoxicity activity of α-amidophosphonates derivatives: Identification of potential antiviral O, O-pharmacophore site, J. Mol. Struc., 2019, 1197, 196-203.

- P. Pérez, L. R. Domingo, M. Duque-Noreña, E. A. Chamorro, A condensed-to-atom nucleophilicity index. An application to the director effects on the electrophilic aromatic substitutions, J. Mol. Struc.Theochem., 2009, 895, 86-91.

- H. B. Schlegel, Optimization of equilibrium geometries and transition structure, J. Comput. Chern., 1982, 3, 214-218.

- R. Hammal, A. Benharref, A. El Hajbi, Exploitation of the mechanism and selectivity of [1+2] cycloaddition reaction between α– cis- himachalène and dibromocarbène using DFT- based reactivity indices, J. CMMDA, 2015, 5, 16-24.

- W. J. Hehre, L. Radom, P. R. Schleyer, Ab Initio Molecular Orbital Theory, Journal of Computational Chemistry, 1986, 7, 379-383.

- H. B. Schlegel, Geometry optimization on potential energy surfaces, Modern Electronic Structure Theory: Part I, 1995, 459-500.

- M. J. Frischet, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, Gaussian 09, Gaussian Inc., Wallingford CT, 2009.

Downloads

Additional Files

Published

22-05-2020

Issue

Vol. 10 No. 5 (2020)

Section

Computational Chemistry

License

Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal
    2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal
    3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).