Kinetic isotope effects chloride/nucleophile

The chlorine kinetic isotope effect in nucleophilic displacement at saturated carbon in para-substituted benzyl chlorides, with thiolate and analogous oxygen nucleophiles, has been examined . The reactions proceed via a concerted transition state. 

The haloalkane dehalogenase DhlA mechanism takes place in two consecutive Sn2 steps. In the first, the carboxylate moiety of the aspartate Aspl24, acting as a nucleophile on the carbon atom of DCE, displaces chloride anion which leads to formation of the enzyme-substrate intermediate (Equation 11.86). That intermediate is hydrolyzed by water in the subsequent step. The experimentally determined chlorine kinetic isotope effect for 1-chlorobutane, the slow substrate, is k(35Cl)/k(37Cl) = 1.0066 0.0004 and should correspond to the intrinsic isotope effect for the dehalogenation step. While the reported experimental value for DCE hydrolysis is smaller, it becomes practically the same when corrected for the intramolecular chlorine kinetic isotope effect (a consequence of the two identical chlorine labels in DCE). 

The competition between nucleophilic substitution and base-induced elimination in the gas phase has been studied using deuterium kinetic isotope effects (KIE).6 The overall reaction rate constants and KIE have been measured for the reactions of RC1 + CIO- (R = Me, Et, t -Pr, and r-Bu). As the extent of substitution in the alkyl chloride increases, the KIE effects become increasingly more normal. These results indicated that the E2 pathway becomes the dominant channel as the alkyl group becomes more sterically hindered. 

The kinetics and mechanism of the aminolysis of phenyl-substituted phenyl phosphonyl chlorides (136) with anilines (135) were investigated in MeCN at 55.0 °C. Very sensitive variation of /Oy(5/Oy2>0) with the change of substituent on the nucleophile Sax) led to a large negative cross-interaction constant, pxY = Spy)/ Sox) = —1.31. The secondary kinetic isotope effects observed with deuteriated aniline nucleophiles were of the inverse type (/th/ d = 0.61-0.87), and small A// (1.6-9.7kcalmor ) and large negative A5 (—43 to —65 e.u.) values were... 

Carbenoids deploy an exceptional reactivity toward nucleophiles (pp.89-90, 119). As selectivity tests and kinetic isotope effects have unveiled, 2-arylvinyl chlorides (P-styryl chlorides) react with organolithiums in two steps. Slow a-metalation is followed by a fast E2-dehalogenation of intermediates 253 (Scheme 1-199). The second step is fueled by the neutralization of one equivalent of organometallic base by the eliminated hydrogen chloride and, in addition, the accompanying partial neutralization due to the transformation of the 1-chloroalkenyllithium into a less basic alkynyllithium. 

A kinetic smdy of the acylation of ethylenediamine with benzoyl chloride (110) in water-dioxane mixtures at pH 5-7 showed that the reaction involves mainly benzoylation of the monoprotonated form of ethylenediamine. Stopped-flow FT-IR spectroscopy has been used to study the amine-catalysed reactions of benzoyl chloride (110) with either butanol or phenol in dichloromethane at 0 °C. A large isotope effect was observed for butanol versus butanol-O-d, which is consistent with a general-base-catalysed mechanism. An overall reaction order of three and a negligible isotope effect for phenol versus phenol- /6 were observed and are consistent with either a base- or nucleophilic-catalysed mechanism. Mechanistic studies of the aminolysis of substituted phenylacetyl chlorides (111) in acetonitrile at —15 °C have revealed that reactions with anilines point to an associative iSN2 pathway. ... 

Rates and product selectivities 5 = ([ester product]/[acid product]) x ([water]/ [alcohol solvent] were reported for solvolyses of chloroacetyl chloride at —10 °C and phenylacetyl chloride at 0 °C in EtOH- and MeOH-water mixtures. Additional kinetic data were reported for solvolyses in acetone-water, 2,2,2-trifluoroethanol (TFE)-water, and TFE-EtOH mixtures. Selectivities and solvent effects for chloroacetyl chloride, including the kinetic solvent isotope effect (KSIE) of 2.18 for MeOH, were similar to those for solvolyses of p-nilrobcnzoyl chloride rate constants in acetone-water were consistent with a third-order mechanism, and rates and products in EtOH-and MeOH-water mixtures could be explained quantitatively by competing third-order mechanisms in which one molecule of solvent (alcohol or water) acts as a nucleophile and another acts as a general base (an addition-elimination reaction channel) (29 R = Et, Me, H).23... 

Stabilization of cationic intermediates by conjugation with an aromatic ring, as in the 1-phenylethyl system, leads to nucleophilic substitution with diminished stereospecificity. A thorough analysis of stereochemical, kinetic, and isotope effect data on solvolysis reactions of 1-phenylethyl chloride has been carried out. For the ion-pair equilibria... 

Chlorine isotope effects (CP vs Cl ) have been determined for a series of SnI and Sn2 reactions of benzyl chloride and four p-substituted benzyl chlorides (Hill and Fry, 1962). The observed effects fall into two distinct groups, near 0.78% for the SnI reactions and near 0.58% for the Sn2 reactions, irrespective of the nature of the nucleophile or the p substituent. In hydrolysis, the nucleophile (H2O) is in large excess, and one cannot determine kinetically whether the SnI or Sn2 mechanism applies. Isotope effects in all the hydrolyses were 0.75-0.78%, strongly supporting the SnI mechanism. 

The kinetic study on tertiary-amine-catalyzed ester formation from benzoyl chloride (BC) and phenol in dichloromethane at 0°C showed the following (1) the lack of phenoxide in the UV-visible spectral study, which probably rules out specific base catalysis, (2) the presence of benzoylammonium salt (AAS) observed in low-temperature NMR experiments, (3) the presence of small or negligible deuterium isotope effect (i.e., kjj/ko 1), which rules out the general base catalysis, and (4) the rates of the reactions of BC with quinuclidine and triethyl amine (the most basic amines in pure aqueous solvent) differed by at least 3 orders of magnitude. These observations suggest the occurrence of nucleophilic catalysis for phenyl benzoate formation in the reaction of BC with phenol under the presence of tertiary amines. However, butyl benzoate formation... 

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