Theoretical Study of The Reaction of Ketene with Methanimine Using DFT Method

  • Haydar Mohammad Salim Department of Chemistry, Faculty of Science, University of Zakho, Duhok 42001, Kurdistan Region, Iraq
Keywords: Stepwise mechanism; [2 2] cycloaddition; DFT; CDFT; Fukui Functions.


      The Density Functional Theory (DFT) method was used to investigate the stepwise mechanism of the [2+2] cycloaddition (22CA) reaction of ketene with methanimine at the B3LYP/6-311++G(d,p) level of theory. Two modes of attack between reactants were investigated, yielding Azetidin-2-one from path1 and Azetidin-2-one from path2 as two possible products passing through two different transition states. The geometry of transition states and products was analysed. The study of stationary points and energetic parameters shows that the reaction mechanism is stepwise and that Azetidin-2-one P1 is thermodynamically and kinetically more favoured than Azetidin-3-one P2. The analysis of the frontier molecular HOMO and LUMO orbitals shows that the Azetidin-2-one P1 is more stable due to its higher energy gab. The global electronic flux from the strong nucleophilic ketene R1 to the methanimine R2 is predicted using conceptual density functional theory (CDFT) indices. Reactant’s electrophilic and nucleophilic Fukui functions were also investigated.


Download data is not yet available.


Abbiche, K., Mohammad-Salim, H., Salah, M., Mazoir, N., Zeroual, A., El Alaoui El Abdallaoui, H., . . . Hochlaf, M. 2020. Insights into the mechanism and regiochemistry of the 1,3-dipolar cycloaddition reaction between benzaldehyde and diazomethane. Theoretical Chemistry Accounts, 139(9), 148. doi:

Acharjee, N., Mohammad-Salim, H. A., Chakraborty, M., Rao, M. P., & Ganesh, M. 2021. Unveiling the high regioselectivity and stereoselectivity within the synthesis of spirooxindolenitropyrrolidine: A molecular electron density theory perspective. Journal of Physical Organic Chemistry, n/a(n/a), e4189. doi:

Barber, J. S., Yamano, M. M., Ramirez, M., Darzi, E. R., Knapp, R. R., Liu, F., . . . Garg, N. K. 2018. Diels–Alder cycloadditions of strained azacyclic allenes. Nature chemistry, 10(9), 953.

Ditchfield, R., Hehre, W. J., & Pople, J. A. (1971). Self‐Consistent Molecular‐Orbital Methods. IX. An Extended Gaussian‐Type Basis for Molecular‐Orbital Studies of Organic Molecules. 54(2), 724-728. doi:10.1063/1.1674902

Domingo, L. R. 2016. Molecular electron density theory: a modern view of reactivity in organic chemistry. Molecules, 21(10), 1319.

Domingo, L. R., Acharjee, N., & Mohammad-Salim, H. A. 2020. Understanding the Reactivity of Trimethylsilyldiazoalkanes Participating in [3+2] Cycloaddition Reactions towards Diethylfumarate with a Molecular Electron Density Theory Perspective. Organics, 1(1), 3-18.

Domingo, L. R., Aurell, M. J., Pérez, P., & Contreras, R. 2002. Quantitative characterization of the global electrophilicity power of common diene/dienophile pairs in Diels–Alder reactions. Tetrahedron, 58(22), 4417-4423. doi:

Domingo, L. R., Pérez, P., & Sáez, J. A. 2013. Understanding the local reactivity in polar organic reactions through electrophilic and nucleophilic Parr functions. RSC Advances, 3(5), 1486-1494. doi:10.1039/C2RA22886F

Domingo, L. R., Ríos-Gutiérrez, M., & Pérez, P. 2018. A Molecular Electron Density Theory Study of the Reactivity and Selectivities in [3 + 2] Cycloaddition Reactions of C,N-Dialkyl Nitrones with Ethylene Derivatives. The Journal of Organic Chemistry, 83(4), 2182-2197. doi:10.1021/acs.joc.7b03093

Espinosa Ferao, A., & Streubel, R. 2020. 1, 2-Thiaphosphetanes: The Quest for Wittig-Type Ring Cleavage, Rearrangement, and Sulfur Atom Transfer. Inorganic Chemistry, 59(5), 3110-3117.

Flores, D. M., & Schmidt, V. A. 2019. Intermolecular 2 + 2 Carbonyl–Olefin Photocycloadditions Enabled by Cu(I)–Norbornene MLCT. Journal of the American Chemical Society, 141(22), 8741-8745. doi:10.1021/jacs.9b03775

Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., . . . Fox, D. J. 2009. Gaussian 09 B.01. Wallingford, CT.

Fuentes de Arriba, Á. L., Lenci, E., Sonawane, M., Formery, O., & Dixon, D. J. 2017. Iridium-Catalyzed Reductive Strecker Reaction for Late-Stage Amide and Lactam Cyanation. Angewandte Chemie International Edition, 56(13), 3655-3659. doi:10.1002/anie.201612367

Fukui, K. 1970. Formulation of the reaction coordinate. The Journal of Physical Chemistry, 74(23), 4161-4163. doi:10.1021/j100717a029

Glasnov, T. 2018. Photochemical Synthesis of Heterocycles: Merging Flow Processing and Metal-Catalyzed Visible Light Photoredox Transformations. In Flow Chemistry for the Synthesis of Heterocycles (pp. 103-132): Springer.

Gonzalez, C., & Schlegel, H. B. 1991. Improved algorithms for reaction path following: higher‐order implicit algorithms. The Journal of chemical physics, 95(8), 5853-5860.

King, T. A., Stewart, H. L., Mortensen, K. T., North, A. J. P., Sore, H. F., & Spring, D. R. 2019. Cycloaddition Strategies for the Synthesis of Diverse Heterocyclic Spirocycles for Fragment-Based Drug Discovery. European Journal of Organic Chemistry, 2019(31-32), 5219-5229. doi:10.1002/ejoc.201900847

Krylov, A., Windus, T. L., Barnes, T., Marin-Rimoldi, E., Nash, J. A., Pritchard, B., . . . Head-Gordon, T. 2018. Perspective: Computational chemistry software and its advancement as illustrated through three grand challenge cases for molecular science. The Journal of Chemical Physics, 149(18), 180901. doi:10.1063/1.5052551

Kyri, A., Gleim, F., Alcaraz, A. G., Schnakenburg, G., Ferao, A. E., & Streubel, R. 2018. “Low-coordinate” 1, 2-oxaphosphetanes–a new opportunity in coordination and main group chemistry. Chemical Communications, 54(52), 7123-7126.

Kyri, A. W., Gleim, F., Becker, D., Schnakenburg, G., Ferao, A. E., & Streubel, R. 2019. Synthesis of free and ligated 1, 2-thiaphosphetanes–expanding the pool of strained P-ligands. Chemical Communications, 55(11), 1615-1618.

Lee, C., Yang, W., & Parr, R. G. 1988. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Physical Review B, 37(2), 785-789. doi:10.1103/PhysRevB.37.785

Mathew, S., Yella, A., Gao, P., Humphry-Baker, R., Curchod, B. F., Ashari-Astani, N., . . . Grätzel, M. 2014. Dye-sensitized solar cells with 13% efficiency achieved through the molecular engineering of porphyrin sensitizers. Nature chemistry, 6(3), 242.

Mohammad-Salim, H., Hassan, R., Abdallah, H. H., & Oftadeh, M. 2020. The Theoretical Study on the Mechanism of [3+ 2] Cycloaddition Reactions between α, β-unsaturated Selenoaldehyde with Nitrone and with Nitrile Oxide. Journal of the Mexican Chemical Society, 64(2).

Mohammad-Salim, H. A. 2021. Understanding the Reactivity of C-Cyclopropyl-N-Methylnitrone Participating in [3+ 2] Cycloaddition Reactions Towards Styrene with a Molecular Electron Density Theory Perspective. Journal of the Mexican Chemical Society, 65(1).

Mohammad-Salim, H. A., & Abdallah, H. H. 2019a. Theoretical Study for the [2+ 2] Cycloaddition Reaction Mechanism of Ketenes and their Derivatives. Oriental Journal of Chemistry, 35(5), 1550-1556.

Mohammad-Salim, H. A., & Abdallah, H. H. 2019b. Theoretical Study of the [4+ 2] Cycloaddition Reaction of Trifluoroethylene with Five-membered Chalcogens Heterocyclic Compounds. ARO-THE SCIENTIFIC JOURNAL OF KOYA UNIVERSITY, 7(2), 69-77.

Mohammad-Salim, H. A., Abdallah, H. H., Maiyelvaganan, K. R., Prakash, M., & Hochlaf, M. 2020. Mechanistic study of the [2+2] cycloaddition reaction of cyclohexenone and its derivatives with vinyl acetate. Theoretical Chemistry Accounts, 139(2), 19. doi:10.1007/s00214-019-2542-y

Mohammad-Salim, H. A., Acharjee, N., & Abdallah, H. H. 2021. Insights into the mechanism and regioselectivity of the [3 + 2] cycloaddition reactions of cyclic nitrone to nitrile functions with a molecular electron density theory perspective. Theoretical Chemistry Accounts, 140(1), 1. doi:10.1007/s00214-020-02703-y

Mohammad-Salim, H. A., Acharjee, N., Domingo, L. R., & Abdallah, H. H. 2020. A molecular electron density theory study for [3 + 2] cycloaddition reactions of 1-pyrroline-1-oxide with disubstituted acetylenes leading to bicyclic 4-isoxazolines. International Journal of Quantum Chemistry, n/a(n/a), e26503. doi:

Mohammad-Salim, H. A., Basheer, H. A., Abdallah, H. H., Zeroual, A., & Jamil, L. A. 2021. A molecular electron density theory study for [3+2] cycloaddition reactions of N-benzylcyclohexylnitrone with methyl-3-butenoate. New Journal of Chemistry, 45(1), 262-267. doi:10.1039/D0NJ04049E

Pang, S., Yang, X., Cao, Z.-H., Zhang, Y.-L., Zhao, Y., & Huang, Y.-Y. 2018. Intermolecular [2 + 2] Cycloaddition/Isomerization of Allenyl Imides and Unactivated Imines for the Synthesis of 1-Azadienes Catalyzed by a Ni(ClO4)2·6H2O Lewis Acid. ACS Catalysis, 8(6), 5193-5199. doi:10.1021/acscatal.8b01454

Parr, R. G., & Pearson, R. G. 1983. Absolute hardness: companion parameter to absolute electronegativity. Journal of the American Chemical Society, 105(26), 7512-7516. doi:10.1021/ja00364a005

Parr, R. G., & Weitao, Y. 1989. Density-Functional Theory of Atoms and Molecules: Oxford University Press.

Parr, R. G., & Weitao, Y. 1994. Density-Functional Theory of Atoms and Molecules: Oxford University Press.

Pawlowski, R., Stanek, F., & Stodulski, M. 2019. Recent Advances on Metal-Free, Visible-Light- Induced Catalysis for Assembling Nitrogen- and Oxygen-Based Heterocyclic Scaffolds. Molecules, 24(8). doi:10.3390/molecules24081533

Ríos-Gutiérrez, M., & Domingo, L. R. 2019. Unravelling the Mysteries of the [3+2] Cycloaddition Reactions. European Journal of Organic Chemistry, 2019(2-3), 267-282. doi:10.1002/ejoc.201800916

Saha, R., Chatterjee, A., Mondal, S., Pal, P., Chakrabarty, K., & Das, G. K. 2019. Comparative DFT study on the platinum catalyzed [3+ 2] and [2+ 2] cycloaddition reactions between the derivatives of allene and alkene. Computational and Theoretical Chemistry, 1163, 112507.

Salim, H. A. M., Abdallah, H. H., & Ramasami, P. 2018. Stereoselectivity and Regioselectivity of the Cycloaddition Dimerization of allyl 3-(2-pyridyl) acrylate and allyl 3-(2-pyrryl) acrylate: DFT Calculations. Paper presented at the IOP Conference Series: Materials Science and Engineering.

Salim, H. M., Abdallah, H. H., & Ramasami, P. 2018. Mechanism and Thermodynamic Parameters of Paternὸ-Büchi Reaction of Benzene and Furan: DFT Study. Paper presented at the 2018 International Conference on Advanced Science and Engineering (ICOASE).

Sowmya, D. V., Lakshmi Teja, G., Padmaja, A., Kamala Prasad, V., & Padmavathi, V. 2018. Green approach for the synthesis of thiophenyl pyrazoles and isoxazoles by adopting 1,3-dipolar cycloaddition methodology and their antimicrobial activity. European Journal of Medicinal Chemistry, 143, 891-898. doi:

Svatunek, D., Pemberton, R. P., Mackey, J. L., Liu, P., & Houk, K. 2020. Concerted [4+ 2] and Stepwise (2+ 2) Cycloadditions of Tetrafluoroethylene with Butadiene: DFT and DLPNO-UCCSD (T) Explorations. The Journal of Organic Chemistry, 85(5), 3858-3864.

Tokunova, É. F., Tyurina, L. A., Nikitin, N. A., Nikitina, I. L., Klen, E. É., Khaliullin, F. A., . . . Kantor, E. A. 2001. Quantitative Structure - Activity Relationships for Microsomal Enzymatic System Modulants. Part I: Inhibitors. Pharmaceutical Chemistry Journal, 35(6), 322-327. doi:10.1023/A:1012345705162

Willenbring, D., & Tantillo, D. J. 2008. Mechanistic possibilities for oxetane formation in the biosynthesis of Taxol’s D ring. Russian Journal of General Chemistry, 78(4), 723-731. doi:10.1134/S1070363208040336

Xu, C., Zhang, L., & Luo, S. 2014. Merging Aerobic Oxidation and Enamine Catalysis in the Asymmetric α-Amination of β-Ketocarbonyls Using N-Hydroxycarbamates as Nitrogen Sources. Angewandte Chemie International Edition, 53(16), 4149-4153. doi:10.1002/anie.201400776

How to Cite
Mohammad Salim, H. (2021) “Theoretical Study of The Reaction of Ketene with Methanimine Using DFT Method”, Zanco Journal of Pure and Applied Sciences, 33(4), pp. 1-10. doi: 10.21271/ZJPAS.33.4.1.
Biology and Medical Researches