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Opposite regiospecific ring opening of 2-(cyanomethyl)aziridines by hydrogen bromide and benzyl bromide: experimental study and theoretical rationalization

Saron Catak UGent, Matthias D'hooghe UGent, Toon Verstraelen UGent, Karen Hemelsoet UGent, Andries Van Nieuwenhove, Hyun-Joon Ha, Michel Waroquier UGent, Norbert De Kimpe UGent and Veronique Van Speybroeck UGent (2010) JOURNAL OF ORGANIC CHEMISTRY. 75(13). p.4530-4541
abstract
Ring opening of 1-arylmethyl-2-(cyanomethyl)aziridines with HBr afforded 3-(arylmethyl)amino-4-bromobutyronitriles via regiospecific ring opening at the unsubstituted aziridine carbon. Previous experimental and theoretical reports show treatment of the same compounds with benzyl bromide to furnish 4-amino-3-bromobutanenitriles through ring opening at the substituted aziridine carbon. To gain insights into the regioselective preference with HBr, reaction paths have been analyzed with computational methods. The effect of solvation was taken into account by the use of explicit solvent molecules. Geometries were determined at the B3LYP/6-31++G(d,p) level of theory, and a Grimme-type correction term was included for long-range dispersion interactions; relative energies were refined with the meta-hybrid MPW1B95 functional. Activation barriers confirm preference for ring opening at the unsubstituted ring carbon for HBr. HBr versus benzyl bromide ring opening was analyzed through comparison of the electronic structure of corresponding aziridinium intermediates. Although the electrostatic picture fails to explain the opposite regiospecific nature of the reaction, frontier molecular orbital analysis of LUMOs and nucleophilic Fukui functions show a clear preference of attack for the substituted aziridine carbon in the benzyl bromide case and for the unsubstituted aziridine carbon in the HBr case, successfully rationalizing the experimentally observed regioselectivity.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
DENSITY-FUNCTIONAL THEORY, BETA-AMINO NITRILES, CHIRAL AZIRIDINES, GAS-PHASE, CHEMICAL-REACTIVITY, ASYMMETRIC-SYNTHESIS, CONTINUUM SOLVENT CALCULATIONS, INTERMEDIATE AZIRIDINIUM SALTS, SOLVATION MODELS, MOLECULAR ELECTROSTATIC POTENTIALS
journal title
JOURNAL OF ORGANIC CHEMISTRY
J. Org. Chem.
volume
75
issue
13
pages
4530 - 4541
Web of Science type
Article
Web of Science id
000279030900022
JCR category
CHEMISTRY, ORGANIC
JCR impact factor
4.002 (2010)
JCR rank
8/56 (2010)
JCR quartile
1 (2010)
ISSN
0022-3263
DOI
10.1021/jo100687q
project
HPC-UGent: the central High Performance Computing infrastructure of Ghent University
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1008706
handle
http://hdl.handle.net/1854/LU-1008706
date created
2010-07-12 08:16:04
date last changed
2013-09-17 10:47:01
@article{1008706,
  abstract     = {Ring opening of 1-arylmethyl-2-(cyanomethyl)aziridines with HBr afforded 3-(arylmethyl)amino-4-bromobutyronitriles via regiospecific ring opening at the unsubstituted aziridine carbon. Previous experimental and theoretical reports show treatment of the same compounds with benzyl bromide to furnish 4-amino-3-bromobutanenitriles through ring opening at the substituted aziridine carbon. To gain insights into the regioselective preference with HBr, reaction paths have been analyzed with computational methods. The effect of solvation was taken into account by the use of explicit solvent molecules. Geometries were determined at the B3LYP/6-31++G(d,p) level of theory, and a Grimme-type correction term was included for long-range dispersion interactions; relative energies were refined with the meta-hybrid MPW1B95 functional. Activation barriers confirm preference for ring opening at the unsubstituted ring carbon for HBr. HBr versus benzyl bromide ring opening was analyzed through comparison of the electronic structure of corresponding aziridinium intermediates. Although the electrostatic picture fails to explain the opposite regiospecific nature of the reaction, frontier molecular orbital analysis of LUMOs and nucleophilic Fukui functions show a clear preference of attack for the substituted aziridine carbon in the benzyl bromide case and for the unsubstituted aziridine carbon in the HBr case, successfully rationalizing the experimentally observed regioselectivity.},
  author       = {Catak, Saron and D'hooghe, Matthias and Verstraelen, Toon and Hemelsoet, Karen and Van Nieuwenhove, Andries and Ha, Hyun-Joon and Waroquier, Michel and De Kimpe, Norbert and Van Speybroeck, Veronique},
  issn         = {0022-3263},
  journal      = {JOURNAL OF ORGANIC CHEMISTRY},
  keyword      = {DENSITY-FUNCTIONAL THEORY,BETA-AMINO NITRILES,CHIRAL AZIRIDINES,GAS-PHASE,CHEMICAL-REACTIVITY,ASYMMETRIC-SYNTHESIS,CONTINUUM SOLVENT CALCULATIONS,INTERMEDIATE AZIRIDINIUM SALTS,SOLVATION MODELS,MOLECULAR ELECTROSTATIC POTENTIALS},
  language     = {eng},
  number       = {13},
  pages        = {4530--4541},
  title        = {Opposite regiospecific ring opening of 2-(cyanomethyl)aziridines by hydrogen bromide and benzyl bromide: experimental study and theoretical rationalization},
  url          = {http://dx.doi.org/10.1021/jo100687q},
  volume       = {75},
  year         = {2010},
}

Chicago
Catak, Saron, Matthias D’hooghe, Toon Verstraelen, Karen Hemelsoet, Andries Van Nieuwenhove, Hyun-Joon Ha, Michel Waroquier, Norbert De Kimpe, and Veronique Van Speybroeck. 2010. “Opposite Regiospecific Ring Opening of 2-(cyanomethyl)aziridines by Hydrogen Bromide and Benzyl Bromide: Experimental Study and Theoretical Rationalization.” Journal of Organic Chemistry 75 (13): 4530–4541.
APA
Catak, S., D’hooghe, M., Verstraelen, T., Hemelsoet, K., Van Nieuwenhove, A., Ha, H.-J., Waroquier, M., et al. (2010). Opposite regiospecific ring opening of 2-(cyanomethyl)aziridines by hydrogen bromide and benzyl bromide: experimental study and theoretical rationalization. JOURNAL OF ORGANIC CHEMISTRY, 75(13), 4530–4541.
Vancouver
1.
Catak S, D’hooghe M, Verstraelen T, Hemelsoet K, Van Nieuwenhove A, Ha H-J, et al. Opposite regiospecific ring opening of 2-(cyanomethyl)aziridines by hydrogen bromide and benzyl bromide: experimental study and theoretical rationalization. JOURNAL OF ORGANIC CHEMISTRY. 2010;75(13):4530–41.
MLA
Catak, Saron, Matthias D’hooghe, Toon Verstraelen, et al. “Opposite Regiospecific Ring Opening of 2-(cyanomethyl)aziridines by Hydrogen Bromide and Benzyl Bromide: Experimental Study and Theoretical Rationalization.” JOURNAL OF ORGANIC CHEMISTRY 75.13 (2010): 4530–4541. Print.