- Steric effect in alkylation reactions by N-alkyl-N-nitrosoureas: A kinetic approach
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The alkylation reactions of 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to DNA base 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
- Manso,Perez-Prior,Garcia-Santos,Calle,Casado
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experimental part
p. 932 - 938
(2009/10/26)
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- Kinetic study of the nitrosation of N-alkylureas in dioxane-acetic acid mixtures
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The rate constants were determined for the nitrosation reactions of the following substrates: Methyl (MU), Ethyl (EU), Propyl (PU)Butyl (BU), and Allylurea (AU). The rate equation found at a constant pH was: v = k[HNO2] [Urea]. The reactions were carried out in predominantly organic media(dioxane-acetic acid-water) with differing polarities. The proposed reaction mechanism involves the proton transfer from the protonated N-alkyl-N-nitrosourea to the acetate anion. As the polarity of the medium decreased, an approximation of the rate constants of the nitrosation of the different substrates was observed. This approximation can be interpreted as a function of the impediment generated by the R alkyl radical in the rate controlling step. Accordingly, the substrate reactivity will be associated with the ease in which the protonated N-alkyl-N nitrosurea can transfer the proton to the acetate anion. The results achieved in this study are in accordance with there activities observed in the nitrosation of these substrates in aqueous media MU ? (EU ≈ PU ≈ BU) > AU.
- Alatorre,Zapiain,Quintana,Martinez
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p. 145 - 150
(2007/10/03)
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- The nitrosation of N-alkylureas: Evidence for a proton transfer mechanism
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The kinetics of the nitrosation of methyl, ethyl, propyl, butyl, and allyl urea were studied by conventional and stopped-flow spectrophotometry in the presence or absence of acetate or mono-, di-, or trichloroacetate anions In the presence of a large excess of urea, the observed rate equation was chemical equations presented where Ka is the acidity constant of nitrous acid and KR that of the carboxylic acid The ureas exhibited the reactivity order methylurea ? (ethylurea ≈ propylurea ≈ butylureal ? allylurea. Experiments in D2O afforded values of kH2O/kD2O in general agreement with the values 4.1-5 5 predicted by a semiclassical transition state theory of kinetic isotope effects [i.e., kH2O/kD2O = exp(0.130hv/kT)]where v is the frequency of R3N - H stretching (2700-2250 cm-1) in the protonated urea. This result, the observed catalysis by carboxylate ions and the value of the Bronsted parameter β(0.45) show the rate-controlling step of these reactions to be the transfer of a proton from the protonated N-alkyl-N-nitrosourea to the solvent or to the organic anion. if present. The observed order of substrate reactivities is explicable in terms of the capacity of the protonated N-alkyl-N-nitrosourea for forming a hydrogen bond with the water molecule to which the proton will be transferred, and the degree to which the formation of such bonds is hindered by the hydrophobic alkyl chain of the nitrosourea.
- Casado, Iulio,Gonzalez-Alatorre, Guillermo,Izquierdo, Carmen,Brunner, Christian
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p. 307 - 313
(2007/10/03)
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