Reactivity of activated versus nonactivated 2-(bromomethyl)aziridines with respect to sodium methoxide: a combined computational and experimental study
- Author
- Hannelore Goossens (UGent) , Karel Vervisch (UGent) , Saron Catak (UGent) , Sonja Stanković (UGent) , Matthias D'hooghe (UGent) , Frank De Proft, Paul Geerlings, Norbert De Kimpe (UGent) , Michel Waroquier (UGent) and Veronique Van Speybroeck (UGent)
- Organization
- Project
- Abstract
- The difference in reactivity between the activated 2-bromomethyl-1-tosylaziridine and the nonactivated 1-benzyl-2-(bromomethyl)aziridine with respect to sodium methoxide was analyzed by means of DFT calculations within the supermolecule approach, taking into account explicit solvent molecules. In addition, the reactivity of epibromohydrin with regard to sodium methoxide was assessed as well. The barriers for direct displacement of bromide by methoxide in methanol are comparable for all three heterocyclic species under study. However, ring opening was found to be only feasible for the epoxide and the activated aziridine, and not for the nonactivated aziridine. According to these computational analyses, the synthesis of chiral 2-substituted 1-tosylaziridines can take place with inversion (through ring opening/ring closure) or retention (through direct bromide displacement) of configuration upon treatment of the corresponding 2-(bromomethyl)aziridines with 1 equiv of a nucleophile, whereas chiral 2-substituted 1-benzylaziridines are selectively obtained with retention of configuration (via direct bromide displacement). Furthermore, the computational results showed that explicit accounting for solvent molecules is required to describe the free energy profile correctly. To verify the computational findings experimentally, chiral 1-benzyl-2-(bromomethyl)aziridines and 2-bromomethyl-1-tosylaziridines were treated with sodium methoxide in methanol. The presented work concerning the reactivity of 2-bromomethyl-1-tosylaziridine stands in contrast to the behavior of the corresponding 1-tosyl-2-(tosyloxymethyl)aziridine with respect to nucleophiles, which undergoes a clean ring-opening/ring-closure process with inversion of configuration at the asymmetric aziridine carbon atom.
- Keywords
- RING-OPENING REACTIONS, THEORETICAL RATIONALIZATION, NUCLEOPHILIC-SUBSTITUTION, DENSITY-FUNCTIONAL THEORY, CONTINUUM SOLVENT CALCULATIONS, THERMOCHEMICAL KINETICS, ASYMMETRIC-SYNTHESIS, CHEMICAL-REACTIONS, CHIRAL AZIRIDINES, FREE-ENERGY
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-1943629
- MLA
- Goossens, Hannelore, et al. “Reactivity of Activated versus Nonactivated 2-(Bromomethyl)Aziridines with Respect to Sodium Methoxide: A Combined Computational and Experimental Study.” JOURNAL OF ORGANIC CHEMISTRY, vol. 76, no. 21, 2011, pp. 8698–709, doi:10.1021/jo201255z.
- APA
- Goossens, H., Vervisch, K., Catak, S., Stanković, S., D’hooghe, M., De Proft, F., … Van Speybroeck, V. (2011). Reactivity of activated versus nonactivated 2-(bromomethyl)aziridines with respect to sodium methoxide: a combined computational and experimental study. JOURNAL OF ORGANIC CHEMISTRY, 76(21), 8698–8709. https://doi.org/10.1021/jo201255z
- Chicago author-date
- Goossens, Hannelore, Karel Vervisch, Saron Catak, Sonja Stanković, Matthias D’hooghe, Frank De Proft, Paul Geerlings, Norbert De Kimpe, Michel Waroquier, and Veronique Van Speybroeck. 2011. “Reactivity of Activated versus Nonactivated 2-(Bromomethyl)Aziridines with Respect to Sodium Methoxide: A Combined Computational and Experimental Study.” JOURNAL OF ORGANIC CHEMISTRY 76 (21): 8698–8709. https://doi.org/10.1021/jo201255z.
- Chicago author-date (all authors)
- Goossens, Hannelore, Karel Vervisch, Saron Catak, Sonja Stanković, Matthias D’hooghe, Frank De Proft, Paul Geerlings, Norbert De Kimpe, Michel Waroquier, and Veronique Van Speybroeck. 2011. “Reactivity of Activated versus Nonactivated 2-(Bromomethyl)Aziridines with Respect to Sodium Methoxide: A Combined Computational and Experimental Study.” JOURNAL OF ORGANIC CHEMISTRY 76 (21): 8698–8709. doi:10.1021/jo201255z.
- Vancouver
- 1.Goossens H, Vervisch K, Catak S, Stanković S, D’hooghe M, De Proft F, et al. Reactivity of activated versus nonactivated 2-(bromomethyl)aziridines with respect to sodium methoxide: a combined computational and experimental study. JOURNAL OF ORGANIC CHEMISTRY. 2011;76(21):8698–709.
- IEEE
- [1]H. Goossens et al., “Reactivity of activated versus nonactivated 2-(bromomethyl)aziridines with respect to sodium methoxide: a combined computational and experimental study,” JOURNAL OF ORGANIC CHEMISTRY, vol. 76, no. 21, pp. 8698–8709, 2011.
@article{1943629, abstract = {{The difference in reactivity between the activated 2-bromomethyl-1-tosylaziridine and the nonactivated 1-benzyl-2-(bromomethyl)aziridine with respect to sodium methoxide was analyzed by means of DFT calculations within the supermolecule approach, taking into account explicit solvent molecules. In addition, the reactivity of epibromohydrin with regard to sodium methoxide was assessed as well. The barriers for direct displacement of bromide by methoxide in methanol are comparable for all three heterocyclic species under study. However, ring opening was found to be only feasible for the epoxide and the activated aziridine, and not for the nonactivated aziridine. According to these computational analyses, the synthesis of chiral 2-substituted 1-tosylaziridines can take place with inversion (through ring opening/ring closure) or retention (through direct bromide displacement) of configuration upon treatment of the corresponding 2-(bromomethyl)aziridines with 1 equiv of a nucleophile, whereas chiral 2-substituted 1-benzylaziridines are selectively obtained with retention of configuration (via direct bromide displacement). Furthermore, the computational results showed that explicit accounting for solvent molecules is required to describe the free energy profile correctly. To verify the computational findings experimentally, chiral 1-benzyl-2-(bromomethyl)aziridines and 2-bromomethyl-1-tosylaziridines were treated with sodium methoxide in methanol. The presented work concerning the reactivity of 2-bromomethyl-1-tosylaziridine stands in contrast to the behavior of the corresponding 1-tosyl-2-(tosyloxymethyl)aziridine with respect to nucleophiles, which undergoes a clean ring-opening/ring-closure process with inversion of configuration at the asymmetric aziridine carbon atom.}}, author = {{Goossens, Hannelore and Vervisch, Karel and Catak, Saron and Stanković, Sonja and D'hooghe, Matthias and De Proft, Frank and Geerlings, Paul and De Kimpe, Norbert and Waroquier, Michel and Van Speybroeck, Veronique}}, issn = {{0022-3263}}, journal = {{JOURNAL OF ORGANIC CHEMISTRY}}, keywords = {{RING-OPENING REACTIONS,THEORETICAL RATIONALIZATION,NUCLEOPHILIC-SUBSTITUTION,DENSITY-FUNCTIONAL THEORY,CONTINUUM SOLVENT CALCULATIONS,THERMOCHEMICAL KINETICS,ASYMMETRIC-SYNTHESIS,CHEMICAL-REACTIONS,CHIRAL AZIRIDINES,FREE-ENERGY}}, language = {{eng}}, number = {{21}}, pages = {{8698--8709}}, title = {{Reactivity of activated versus nonactivated 2-(bromomethyl)aziridines with respect to sodium methoxide: a combined computational and experimental study}}, url = {{http://doi.org/10.1021/jo201255z}}, volume = {{76}}, year = {{2011}}, }
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