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Steric effect in alkylation reactions by N ‐alkyl‐ N ‐nitrosoureas: a kinetic approach
Author(s) -
Manso J. A.,
PérezPrior M. T.,
GarcíaSantos M. P.,
Calle E.,
Casado J.
Publication year - 2008
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.1402
Subject(s) - chemistry , alkylation , steric effects , adduct , nucleophile , medicinal chemistry , alkyl , pyridine , yield (engineering) , reaction rate constant , stereochemistry , organic chemistry , kinetics , catalysis , materials science , physics , quantum mechanics , metallurgy
The alkylation reactions of 4‐( p ‐nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to DNA bases, by five N ‐alkyl‐ N ‐nitrosoureas (methyl‐, ethyl‐, propyl‐, butyl‐, and allylnitrosourea) were investigated in 7:3 (v/v) water/dioxane medium in the 5.0–6.5 pH range. Decomposition of alkylnitrosoureas (ANU) gives rise to alkyldiazonium ions that yield NBP‐R adducts directly or through carbocations in certain instances. The NBP alkylation rate constants by these species were determined. The following sequence of alkylating potential was found: methyl‐ > ethyl‐ > allyl‐ > propyl‐ > butyl group. Application of Ingold–Taft correlation analysis to the kinetic results revealed that the NBP alkylation reactions occur mainly through steric control. The values of the molar absorption coefficients of the NBP‐R adducts also reveal the determinant influence of a steric effect in the formation of alkylation adducts. The kinetic results are consistent with the biological activity of ANU. Copyright © 2008 John Wiley & Sons, Ltd.