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An MNDO molecular orbital study of the reactions of protonated oxirane derivatives (XCHCH 2 OH + , X = CN, Cl, CH 3 , Ph) with simple nucleophiles. Implications for regioselectivity in the reactions of electrophiles with nucleic acid bases
Author(s) -
Ford George P.,
Smith Christopher T.
Publication year - 1989
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.540100413
Subject(s) - nucleophile , chemistry , mndo , protonation , electrophile , computational chemistry , leaving group , substituent , transition state , carbenium ion , molecular orbital , mindo , stereochemistry , medicinal chemistry , ion , molecule , organic chemistry , catalysis
Abstract The gas‐phase analogs of the classical S N 1 and S N 2 reactions of nucleophiles with a series of protonated oxiranes bearing the substituents CN, Cl, Me, and Ph were studied using MNDO semiempirical molecular orbital theory. The transition states for nucleophilic attack on the intact rings are calculated to become progressively more “S N 1‐like,” as the ability of the substituent group to stabilize the corresponding ring opened carbenium ion increases. At the same time the activation barriers become progressively smaller and their relative values for different nucleophiles approach the order expected on the basis of a purely electrostatic attraction between the reacting moieties. Exactly the opposite trends are calculated for the transition states for nucleophilic attack on the intermediate carbenium ions. As the stabilities of the latter increase the extent of bond formation, and transfer of charge to the incoming nucleophile also increase. Here, the relative barriers for attack by different nucleophiles approach the order expected on the basis of a superposition of both covalent and electrostatic interactions in which the former dominate. These results support a previously suggested rationalization for the enhanced reactivities of certain alkylating agents towards the exocyclic oxygen atoms, rather than the ring nitrogens, of the nucleic acid bases. They also suggest a new explanation for the tendencies of aralkylating electrophiles to modify the exocyclic amino groups of the nucleic acid bases: sites which are unreactive towards simple alkylating agents.