Skip to main content
SpringerLink
Log in

Explaining the selectivities and the mechanism of [3+2] cycloloaddition reaction between isoalantolactone and diazocyclopropane

  • Original Paper
  • Published:
Journal of Molecular Modeling Aims and scope Submit manuscript

Abstract

Context

[3+2] cycloaddition processes between isoalantolactone (ISALL) and diazocyclopropane (DCYP), have been surveyed exercising the MEDT, reactivity indices, reactions, and activation energies, are computed. In an investigation of conceptual DFT indices, DCYP behaves as a nucleophile in this reaction, whereas ISALL acts as an electrophile. This cyclization is stereo-, chemo-, and regiospecific, as demonstrated by the activation and reaction energies, in clear agreement with the experiment’s results. The mechanism for this [3+2] cycloaddition is occurring in two steps, according to ELF analysis.

Methods

For the purposes of this investigation, all computations were performed using the Gaussian 09 program. The optimization was completed using Berny’s computational gradient optimization approach with the basis set 6-311G(d,p) and wB97XD functional. Frequency computations were utilized to characterize and locate stationary points where the transition phases have just one imaginary frequency and all frequencies for the reactants and products are positive. After evaluating the effect of dichloromethane (DCM) as a reaction solvent, the stationary point optimization was updated using the polarizable continuum model (PCM) developed by the Tomasi team. The electron localization function (ELF) has been examined within the context of topological investigations using Multiwfn software with a 0.05 grid step.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Scheme 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary material.

References

  1. Holota S, Derkach H, Demchuk IL et al (2019) Synthesis and In vivo evaluation of pyrazoline-thiazolidin-4-one hybrid Les-5581 as a potential non-steroidal anti-inflammatory agent. Biopolym Cell 35(6). https://doi.org/10.7124/bc.000A17

  2. Jasril THY, Aisyah N, Hendra R (2019) Microwave assisted synthesis and evaluation of toxicity and antioxidant activity of pyrazoline derivatives. Indones J Chem 19(3). https://doi.org/10.22146/ijc.34285

  3. Ahmad A, Husain A, Khan SA, Mujeeb M, Bhandari A (2016) Synthesis, antimicrobial and antitubercular activities of some novel pyrazoline derivatives antimicrobial and antitubercular activities of novel pyrazoline derivatives. J Saudi Chem Soc 20(5). https://doi.org/10.1016/j.jscs.2014.12.004

  4. Praceka MS, Megantara S, Maharani R, Muchtaridi M (2021) Comparison of various synthesis methods and synthesis parameters of pyrazoline derivates. J Adv Pharm Technol Res 12(4). https://doi.org/10.4103/japtr.JAPTR_252_21

  5. Castro Sánchez ME, Noriega L, Perez-Aguilar JM, Caballero-Concha NA, Merino-Montiel P, López AR, Melendez Bustamante FJ (2022) 8 - Green chemistry approaches to the synthesis of pyrazoline steroid derivatives and their theoretical DFT characterization. Green Chemistry and Computational Chemistry 193–214. https://doi.org/10.1016/B978-0-12-819879-7.00008-8

  6. Di M, Rein KS (2004) Aza analogs of kainoids by dipolar cycloaddition. Tetrahedron Lett 45(24). https://doi.org/10.1016/j.tetlet.2004.04.097

  7. Tomilov YV, Revunov EV, Shulishov EV, Semenov VV (2012) 1,3-Dipolar addition of diazocyclopropane to eudesmane-type methylidene lactones and thermolysis of the resulting spiro-fused pyrazolines. Russ Chem Bull 61(2). https://doi.org/10.1007/s11172-012-0039-0

  8. Domingo LR (2016) Molecular electron density theory: a modern view of reactivity in organic chemistry. Molecules 21(10). https://doi.org/10.3390/molecules21101319

  9. Salah M, Belghiti ME, Aitouna AO, Zeroual A, Jorio S, El Alaoui Abdellaoui H, El Hadki H, Marakchi K, Komiha N (2021) MEDT study of the 1,3-DC reaction of diazomethane with Psilostachyin and investigation about the interactions of some pyrazoline derivatives with protease (Mpro) of nCoV-2. J Mol Graph Model 102:107763. https://doi.org/10.1016/j.jmgm.2020.107763

    Article  CAS  PubMed  Google Scholar 

  10. Fukui K (1997) A simple quantum-theoretical interpretation of the chemical reactivity of organic compounds. Frontier Orbitals And Reaction Paths: Selected Papers of Kenichi Fukui. https://doi.org/10.1142/9789812795847_0014

    Chapter  Google Scholar 

  11. Domingo LR, Ríos-Gutiérrez M, Pérez P (2016) Applications of the conceptual density functional theory indices to organic chemistry reactivity. Molecules 21(6). https://doi.org/10.3390/molecules21060748

  12. Becke AD, Edgecombe KE (1990) A simple measure of electron localization in atomic and molecular systems. J Chem Phys 92(9). https://doi.org/10.1063/1.458517

  13. Thakkar AJ (2003) The momentum density perspective of the electronic structure of atoms and molecules. In: Rice SA (ed) Advances in chemical physics. https://doi.org/10.1002/0471484237.ch5

    Chapter  Google Scholar 

  14. Johnson ER, Keinan S, Mori-Sánchez P, Contreras-García J, Cohen AJ, Yang W (2010) Revealing noncovalent interactions. J Am Chem Soc 132(18). https://doi.org/10.1021/ja100936w

  15. Domingo LR, Ríos-Gutiérrez M, Emamian S (2017) Understanding the domino reaction between 1-diazopropan-2-one and 1,1-dinitroethylene. A molecular electron density theory study of the [3 + 2] cycloaddition reactions of diazoalkanes with electron-deficient ethylenes. RSC Adv 7(25). https://doi.org/10.1039/C7RA00544J

  16. El Idrissi M, El Ghozlani M, Eşme A, Ríos-Gutiérrez M, Ouled Aitouna A, Salah M, El Abdallaoui HE, Zeroual A, Mazoir N, Domingo LR (2021) Mpro-SARS-CoV-2 inhibitors and various chemical reactivity of 1-bromo- and 1-chloro-4-vinylbenzene in [3+2] cycloaddition reactions. Organics 2(1):1–16. https://doi.org/10.3390/org2010001

    Article  CAS  Google Scholar 

  17. Zeroual A, Ríos-Gutiérrez M, El Ghozlani M, El Idrissi M, Ouled Aitouna A, Salah M, El Abdallaoui HE (2020) Domingo LR (2020) A molecular electron density theory investigation of the molecular mechanism, regioselectivity, stereoselectivity and chemoselectivity of cycloaddition reaction between acetonitrile N-oxide and 2,5-dimethyl-2H-[1,2,3] diazarsole. Theor Chem Acc 139:37. https://doi.org/10.1007/s00214-020-2547-6

    Article  CAS  Google Scholar 

  18. Zeroual A, Ríos-Gutiérrez M, Salah M, El Abdallaoui HE, Domingo LR (2019) 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. J Chem Sci 131:75. https://doi.org/10.1007/s12039-019-1656-z

    Article  CAS  Google Scholar 

  19. El Idrissi M, Eşme A, Hakmaoui Y, Ríos-Gutiérrez M, Ouled Aitouna A, Salah M, Zeroual A (2021) Domingo LR (2021) Divulging the various chemical reactivity of trifluoromethyl-4-vinyl-benzene as well as methyl-4-vinyl-benzene in [3+2] cycloaddition reactions. J Mol Graph Model 102:107760. https://doi.org/10.1016/j.jmgm.2020.107760

    Article  CAS  PubMed  Google Scholar 

  20. Mohammad-Salim HA, Basheer HA, Abdallah HH, Zeroual A (2021) Abdi Jamila L (2021) A molecular electron density theory study for [3+2] cycloaddition reactions of N-benzylcyclohexylnitrone with methyl-3-butenoate. New J Chem 45:262–267. https://doi.org/10.1039/D0NJ04049E

    Article  CAS  Google Scholar 

  21. Salah M, Zeroual A, Jorio S, El Hadki H, Kabbaj O, Marakchi K, Komiha N (2020) Theoretical study of the 1,3-DC reaction between fluorinated alkynes and azides: reactivity indices, Transition structures, IGM and ELF analysis. J Mol Graph Model 94:107458. https://doi.org/10.1016/j.jmgm.2019.107458

    Article  CAS  PubMed  Google Scholar 

  22. Zeroual A, Benharref A, El Hajbi A (2015) Theoretical study of stereoselectivity of the [1+2] cycloaddition reaction between (1S,3R,8S)-2,2-dichloro-3,7,7,10-tetramethyltricyclo[6,4,0,01.3]dodec-9-ene and dibromocarbene using density functional theory (DFT) B3LYP/6-31G*(d). J Mol Model 21:44. https://doi.org/10.1007/s00894-015-2594-4

    Article  CAS  PubMed  Google Scholar 

  23. Barhoumi A, El Idrissi M, Zeroual A et al (2021) Theoretical study of the chemical reactivity of a class of trivalent phosphorus derivatives towards polyhaloalkanes: DFT study. J Mol Model 27:197. https://doi.org/10.1007/s00894-021-04814-0

    Article  CAS  PubMed  Google Scholar 

  24. El Ghozlani M, Barhoumi A, Elkacmi R, Ouled Aitouna A, Zeroual A, El Idrissi M (2020) Mechanistic study of hetero-Diels–Alder [4 + 2] cycloaddition reactions between 2-nitro-1H-pyrrole and isoprene. Chem Afr 3:901–909. https://doi.org/10.1007/s42250-020-00187-8

    Article  CAS  Google Scholar 

  25. Barhoumi A, Ourhriss N, Elalaoui Belghiti M, Chafi M, Syed A, Eswaramoorthy R-M, Verma M, Zeroual A, Zawadzińska K, Jasiński R (2023) 3-Difluormethyl-5-carbomethoxy-2,4-pyrazole: Molecular mechanism of the formation and molecular docking study. Current Chemistry Letters 12:477–488. https://doi.org/10.5267/j.ccl.2023.3.008

    Article  Google Scholar 

  26. Abdoul-Hakim M, El Idrissi K, Zeroual A, Garmes H (2023) Investigation of the solvent effect, regioselectivity, and the mechanism of the cycloaddition reaction between 2-chlorobenzimidazole and benzonitrile oxide. Chem Heterocycl Compd 59(3):155–164

    Article  CAS  Google Scholar 

  27. Raji H, Ouled Aitouna A, Barhoumi A, Hammal R, Chekroun A, Zeroual A, Benharref A, Mazoir N (2023) [2+1] Cycloaddition reaction of α-atlantone with m-CPBA in the light of experimental and MEDT quantum-chemical study. Chem Heterocycl Compd 59(3):112–117

    Article  CAS  Google Scholar 

  28. Ameur S, Barhoumi A, Ríos-Gutiérrez M, Ouled Aitouna A (2023) El Alaoui El Abdallaoui H, Mazoir N, Elalaoui Belghiti M, Syed A, Zeroual A, Domingo L R, A MEDT study of the mechanism and selectivity of the hetero-Diels–Alder reaction between 3-benzoylpyrrolo[1,2-c][1,4]-benzoxazine-1,2,4-trione and vinyl acetate. Chem Heterocycl Compd 59(3):165–170

    Article  CAS  Google Scholar 

  29. Zeroual A, Ríos-Gutiérrez M, Amiri O, El Idrissi M, Domingo LR (2019) An MEDT study of the mechanism, chemo- and stereoselectivity of the epoxidation reaction of R-carvone with peracetic acid. RSC Adv-R Soc Chem 9:28500–28509

    Article  CAS  Google Scholar 

  30. Zeroual A, Ríos-Gutiérrez M, El Idrissi M, Abdallaoui El Alaoui El, H, Domingo LR, (2019) An MEDT study of the mechanism and selectivities of the [3+2] cycloaddition reaction of tomentosin with benzonitrile oxide. Int J Quantum Chem 119:e25980. https://doi.org/10.1002/qua.25980

  31. Zeroual A, Zoubir M, Hammal R, Benharref A, El Hajbi A (2015) Understanding the regioselectivity and reactivity of FriedeleCraftsbenzoylation using Parr function. Mor J Chem 3:356–360. https://doi.org/10.48317/IMIST.PRSM/morjchem-v3i4.3050

    Article  CAS  Google Scholar 

  32. Ouahdi Z, Ourhriss N, Aitouna AO et al (2022) Exploration of the mechanism, chemospecificity, regiospecificity and stereoselectivity of the cycloaddition reaction between 9α-hydroxyparthenolide and nitrilimine: MEDT study. Theor Chem Acc 141:50. https://doi.org/10.1007/s00214-022-02913-6

    Article  CAS  Google Scholar 

  33. Frisch MJ, Trucks GW, Schlegel HB et al (2016) Gaussian 09, Rev. D.01. Gaussian Inc, Wallingford, CT

    Google Scholar 

  34. Da CJ, Head-Gordon M (2008) Long-range corrected hybrid density functionals with damped atom-atom dispersion corrections. Phys Chem Chem Phys 10(44). https://doi.org/10.1039/b810189b

  35. Pople JA, Schleyer P V., Hehre WJ, Radom L. AB INITIO molecular orbital theory.; 1986. 10.1016/s0022-328x(00)99651-7

  36. Schlegel HB (1982) Optimization of equilibrium geometries and transition structures. J Comput Chem 3(2). https://doi.org/10.1002/jcc.540030212

  37. Gonzalez C, Schlegel HB (1990) Reaction path following in mass-weighted internal coordinates. J Phys Chem 94(14). https://doi.org/10.1021/j100377a021

  38. Tomasi J, Persico M (1994) Molecular interactions in solution: an overview of methods based on continuous distributions of the solvent. Chem Rev 94(7). https://doi.org/10.1021/cr00031a013

  39. Domingo LR (2014) A new C-C bond formation model based on the quantum chemical topology of electron density. RSC Adv 4(61). https://doi.org/10.1039/c4ra04280h

  40. Domingo LR, Pérez P, Sáez JA (2013) Understanding the local reactivity in polar organic reactions through electrophilic and nucleophilic Parr functions. RSC Adv 3(5). https://doi.org/10.1039/c2ra22886f

  41. Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 98(7). https://doi.org/10.1063/1.464913

  42. Lu T, Chen F (2012) Multiwfn: A multifunctional wavefunction analyzer. J Comput Chem 33(5). https://doi.org/10.1002/jcc.22885

  43. Parr RG, Szentpály LV, Liu S (1999) Electrophilicity index. J Am Chem Soc 121:9. https://doi.org/10.1021/ja983494x

    Article  Google Scholar 

  44. Jaramillo P, Domingo LR, Chamorro E, Pérez P (2008) A further exploration of a nucleophilicity index based on the gas-phase ionization potentials. J Mol Struct Theochem:865(1-3). https://doi.org/10.1016/j.theochem.2008.06.022

  45. Adjieufack AI, Ndassa IM, Ketcha Mbadcam J, Ríos-Gutiérrez M, Domingo LR (2017) Steric interactions controlling the syn diastereofacial selectivity in the [3 + 2] cycloaddition reaction between acetonitrile oxide and 7-oxanorborn-5-en-2-ones: a molecular electron density theory study. J Phys Org Chem 30(12). https://doi.org/10.1002/poc.3710

  46. Raji H, Ouled Aitouna A, Barhoumi A, Chekroun A, Zeroual A, Syed A, Elgorban AM, Verma M, Benharref A, Varma RS (2023) Antiviral docking analysis, semisynthesis and mechanistic studies on the origin of stereo- and chemoselectivity in epoxidation reaction of α′-trans-Himachalene. J Mol Liq 385:122204. https://doi.org/10.1016/j.molliq.2023.122204

    Article  CAS  Google Scholar 

  47. Asserne F, Ouahdi Z, Hakmaoui Y et al (2023) Molecular docking, regio, chemo and stereoselectivity study of the [3 + 2] cycloaddition reaction between pyridazi-3-one and nitrilimine. Chem Afr. https://doi.org/10.1007/s42250-023-00735-y

  48. Ouahdi Z, Oueld Aitouna A, Barhoumi A, Belghiti ME, El Idrissi M, El Alaoui Abdellaoui H, Syed A, Zeroual A, Benharref A (2023) Elucidating the selectivities and the mechanism of [3+2] cycloloaddition reaction between 9α-hydroxyparthenolide and 4-methylbenzene-nitrile-oxide. Comput Theor Chem 1226:114212. https://doi.org/10.1016/j.comptc.2023.114212

    Article  CAS  Google Scholar 

  49. Aitouna AO, Barhoumi A, Zeroual A (2023) A mechanism study and an investigation of the reason for the stereoselectivity in the [4+2] cycloaddition reaction between cyclopentadiene and gem-substituted ethylene electrophiles. Sci Rad 2(3):217–228. https://doi.org/10.58332/scirad2023v2i3a01

    Article  Google Scholar 

Download references

Funding

The authors extend their appreciation to the Researchers Supporting Project number (RSP2023R15), King Saud University, Riyadh, Saudi Arabia.

Author information

Authors and Affiliations

  1. Molecular Modeling and Spectroscopy Research Team, Faculty of Science, Chouaïb Doukkali University, P.O. Box 20, 24000, El Jadida, Morocco

    Anas Ouled Aitouna, Ali Barhoumi, Habib El Alaoui El Abdallaoui & Abdellah Zeroual

  2. Laboratory of Bioorganic Chemistry, Department of Chemistry, Faculty of Sciences, Chouaïb Doukkali University, P.O. Box 20, 24000, El Jadida, Morocco

    Anas Ouled Aitouna & Noureddine Mazoir

  3. Laboratory of Physical Chemistry of Materials, Ben M’Sick Faculty of Sciences, Hassan II University, P.O. Box 7955, Casablanca, Morocco

    Mohammed Elalaoui Belghiti

  4. Laboratory of Nernest Technology, 163 Willington Street, Sherbrooke, QC, J1H5C7, Canada

    Mohammed Elalaoui Belghiti

  5. Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    Asad Syed & Ali H. Bahkali

  6. University Centre for Research & Development, Department of Chemistry, Chandigarh University, Gharuan, Mohali, India

    Meenakshi Verma

Authors
  1. Anas Ouled Aitouna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ali Barhoumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Habib El Alaoui El Abdallaoui
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Noureddine Mazoir
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammed Elalaoui Belghiti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Asad Syed
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ali H. Bahkali
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Meenakshi Verma
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Abdellah Zeroual
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Anas Ouled Aitouna, Ali Barhoumi, and Mohammed Elalaoui Belghiti: article writing. Abdellah Zeroual, Habib El Alaoui El Abdallaoui, and Noureddine Mazoir: numerical calculations and acquisition of data. Ali H. Bahkali and Meenakshi Verma: revising and editing language. Mohammed Elalaoui Belghiti Abdellah Zeroual and Asad Syed: final review and editing. All authors: analysis and interpretation of data and drafting the article.

Corresponding author

Correspondence to Abdellah Zeroual.

Ethics declarations

Ethics approval

The manuscript is prepared in compliance with the Ethics in Publishing Policy as described in the Guide for Authors.

Consent to participate

The manuscript is approved by all authors for publication.

Consent for publication

The consent for publication was obtained from all participants.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

ESM 1

(PDF 1847 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ouled Aitouna, A., Barhoumi, A., El Alaoui El Abdallaoui, H. et al. Explaining the selectivities and the mechanism of [3+2] cycloloaddition reaction between isoalantolactone and diazocyclopropane. J Mol Model 29, 280 (2023). https://doi.org/10.1007/s00894-023-05688-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00894-023-05688-0

Keywords

Search

Navigation