Small Kinetic Isotope Effect Research Articles

Direct spectrophotometric measurement of small kinetic isotope effects

Direct spectrophotometric measurement of small kinetic isotope effects

S N2 Reactions in Dipolar Aprotic Solvents. VII. Kinetic and Equilibrium Secondary α-Deuterium Isotope Effects in Chlorine Isotopic Exchange Reactions of Substituted Chloromethanes in Acetonitrile

Abstract Secondary α-deuterium isotope effects were studied in the symmetrical nucleophilic substitution of the substituted chloromethanes in acetonitrile. The apparent second order rate coefficients show a significant isotope effect for chloromethyl aryl ethers and sulfides (1.11–1.14 per D), and an intermediate value of 1.05 for cinnamyl chlorides. 2-Arylethyl chlorides were shown to give an appreciable isotope effect of 1.03–1.04, and arylchloromethanes to give varying amount of the isotope effect from 1.006 to 1.050 depending upon the ring substituent. The deuterium label also gave rise to a significant equilibrium isotope effect on the substrate-nucleophile association in the reaction mixture. The observation of an equilibrium isotope effect suggested a possibility that an apparent isotope effect was a composite of the thermodynamic and the kinetic isotope effects. Thus the dissection resulted in a uniform and a fairly large kinetic isotope effect for all the activated substrates studied and in a small kinetic isotope effect for 2-arylethyl chloride. The results are explained in a framework of loose–tight transition state.

Deuterium isotope effect and base catalysis in σ-complex formation between 1,3,5-trinitrobenzene and aniline

The diazabicyclo-octane-catalysed σ-complex formation between 1,3,5-trinitrobenzene and aniline in dimethy sulphoxide involves rate-limiting proton transfer from nitrogen and is subject to a small kinetic isotope effect.

Reaction of o-carboxyphenyl sulfoxides with acetic anhydride : Kinetic studies on the neighboring group effect of ortho-carboxyl group in the oxygen exchange and Pummerer reactions

Kinetic studies on the concurrent oxygen exchange and racemization reactions and Pummerer reaction of o-carboxyphenyl sulfoxides with acetic anhydride were carried out. In the reaction of o-carboxyphenyl phenyl sulfoxide, ortho-carboxyl group was found to enhance the rates of both oxygen exchange and racemization about 180 times, and the rate of racemization was nearly twice that of oxygen exchange. In the reaction of alkyl o-carboxyphenyl sulfoxides, an intramolecular Pummerer reaction took place to give 3,1-benzoxathian-4-one derivatives, and the Pummerer reaction was accelerated about 140 times that of the usual unassisted Pummerer reaction of aryl methyl sulfoxide. A very small deuterium kinetic isotope effect (k H/k D = 1.07 with trideuterated-methyl o-carboxyphenyl sulfoxide) and the rate-enhancing effect of α-alkyl group were also noticed. The markedly large rate-enhancement of both oxygen exchange and the Pummerer reactions is undoubtedly caused by the neighboring group participation of carboxyl group in the rate-determining intramolecular acylation of sulfinyl O atom.

The addition of bisulfite to 5-fluorouracil. Evidence for a change in rate determining step

The kinetics of bisulfite addition to 5-fluorouracil were studied as a function of increasing concentrations of potential general acids. Values of k obsd [ SO 3 =] measured at 25°C and ionic strength 1.0 M increased linearly and then became invariant with increasing concentrations of either HSO 3 − or (OHCH 2CH 2) 2N +C(CH 2OH) 3 HCl (BisTris +HCl). A small kinetic hydrogen-deuterium isotope effect ( k HS k DS = 1.10 ) was observed for the general acid catalysed portion of the addition reaction. The kinetics of bisulfite elimination from 5-fluoro-5,6-dihydrouracil-6-sulfonate were studied in ethanolamine buffers. As previously observed with 1,3-dimethyl-5,6-dihydrouracil-6-sulfonate, this reaction is subject to general base catalysis and exhibits a large kinetic hydrogen-deuterium isotope effect ( k 2 H 2O k 2 D 2O = 3.8 ). The kinetic results for the addition reaction are consistent with a multistep reaction pathway involving the initial formation of an oxyanion sulfite addition intermediate (II) which subsequently adds a proton and undergoes tautomerization to yield the final 5-fluoro-5,6-dihydrouracil-6-sulfonate product. Thus the elimination of bisulfite from 5-fluoro-5,6-dihydrouracil-6-sulfonate probably proceeds by an ElcB mechanism which involves, at relatively low concentrations of general base, rate determining general base catalyzed proton abstraction from carbon 5 to yield intermediate II followed by the rapid elimination of sulfite to yield 5-fluorouracil. These results may be related to both the enzymatically catalyzed dehalogenation of bromoand iodouracil and the methylation of deoxyuridylate by thymidylate synthetase.

Kinetics of the Reaction of O(3P) Atoms with Benzene

The kinetics of the gas phase reaction of O(3P) atoms with benzene was investigated using fast flow techniques. Specific rate constants were obtained using two separate systems, one with ESR detection to monitor the decrease in O(3P) atoms and the other with mass spectrometry to follow the change in benzene concentration. The rate constant computed with respect to O(3P) removal is much larger than that obtained in the mass spectrometer studies and this is believed to result from further reactions of oxygen atoms with radical species produced in the initial O(3P)+C6H6 interaction. On the basis of the mass spectrometric studies a specific rate constant for the reaction O(3P)+C6H6→ [C6H6O]of (3.8± 1.5) × 1013 exp(−4,400± 500/RT) cm3 mole−1· sec−1 was obtained over the temperature range of 255–305°K. A negligibly small kinetic isotope effect was observed in competitive experiments with C6H6 and C6D6. The results obtained are interpreted in terms of a rate determining step involving the addition of oxygen atoms to the benzene ring followed by subsequent isomerization and/or decomposition reactions.

Kinetic hydrogen isotope effect in the fluorination of H2, CH4 and CHCl3

Kinetic isotope effects for the hydrogen abstraction reactions of fluorine atoms with H2, CH4 and CHCl3 have been measured by indirect competitive methods. The relative rate constants are given by k(CHCl3)/k(CDCl3)= 0.81 ± 0.25 exp[(620 ± 50)/RT], k(H2)/k(D2)= 1.5 ± 0.4 exp[(130 ± 300)/RT], k(CH4)/k(CD4)= 1.0 ± 0.3 exp[(230 ± 200)/RT]. The result for k(H2)/k(D2) agrees with that previously measured. These relatively small kinetic isotope effects are compared with rate parameters calculated from activated complex theory and classical trajectory analysis. Hydrogen atom transfer by quantum mechanical tunnelling is apparently unimportant.

Rearrangement of tertiary amine N-oxides—XXVII : Mechanism of the reaction of isoquinoline N-oxide with substituted benzenesulfonyl chlorides

Kinetic experiments have been carried out on the reactions of isoquinoline N-oxide with p-toluenesulfonyl and other substituted benzenesulfonyl chlorides, varying solvent and salt compositions. The rate was correlated by the second-order equation, i.e., v = [N → O] × [ArSO 2Cl], and was found to be accelerated in polar media. The addition of chloride ion was found to increase the rate considerably, while the rates of the over-all reaction became greater with arenesulfonyl chlorides bearing stronger electron-withdrawing substituents (ϱ = +2·0). By the use of 1-deuterated isoquinoline N-oxide a small kinetic isotope effect ( k H/ k D = 1·2) was observed for this reaction. Based on these kinetic observations the rate-determining step of this reaction is considered to be the cleavage of NO bond. Meanwhile, from the 18O-tracer experiments in several solvents using uniformly 18O-labelled p-toluenesulfonyl or p-bromobenzenesulfonyl chloride the migration of arenesulfonate was found to proceed mainly via oxygen-bridged ion pair pathway.

Implication of small hydrogen-deuterium kinetic isotope effect in the reaction of quinaldine and 1-methylisoquinoline N-oxides with acetic anhydride

Implication of small hydrogen-deuterium kinetic isotope effect in the reaction of quinaldine and 1-methylisoquinoline N-oxides with acetic anhydride