Isotope effects, and reactions

Carbon isotope fractionation effects of individual compounds were observed in living organisms and also as a result of enzymatic isotope effects and reaction kinetics in biological systems. Such fractionation effects have to be examined by isotope ratio mass spectrometry in order to understand specific processes in life sciences or in environment.75... 

Most of the chemical properties of tritium are common to those of the other hydrogen isotopes. However, notable deviations in chemical behavior result from isotope effects and from enhanced reaction kinetics induced by the ( -emission in tritium systems. Isotope exchange between tritium and other hydrogen isotopes is an interesting manifestation of the special chemical properties of tritium. 

For E2 eliminations in 2-phenylethyl systems with several different leaving groups, both the primary isotope effect and Hammett p values for the reactions are known. Deduce from these data the relationship between the location on the E2 transition state spectrum and the nature of the leaving group i.e., deduce which system has the most El-like transition state and which has the most Elcb-like. Explain your reasoning. 

In analyzing the behavior of these types of tetrahedral intermediates, it should be kept in mind that proton-transfer reactions are usually fast relative to other steps. This circumstance permits the possibility that a minor species in equilibrium with the major species may be the major intermediate. Detailed studies of kinetics, solvent isotope effects, and the nature of catalysis are the best tools for investigating the various possibilities. 

At this point, attention can be given to specific electrophilic substitution reactions. The kinds of data that have been especially useful for determining mechanistic details include linear ffee-energy relationships, kinetic studies, isotope effects, and selectivity patterns. In general, the basic questions that need to be asked about each mechanism are (1) What is the active electrophile (2) Which step in the general mechanism for electrophilic aromatic substitution is rate-determining (3) What are the orientation and selectivity patterns ... 

A substantial body of data, including reaction kinetics, isotope effects, and structure-reactivity relationships, has permitted a thorough understanding of the steps in aromatic nitration. As anticipated from the general mechanism for electrophilic substitution, there are three distinct steps ... 

When one of the ortho hydrogens is replaced by deuterium, the rate drops from 1.53 X 10 " s to 1.38 X lO s. What is the kinetic isotope effect The product from such a reaction contains 60% of the original deuterium. Give a mechanism for this reaction that is consistent with both the kinetic isotope effect and the deuterium retention data. 

In the El reaction, C-X bond-breaking occurs first. The substrate dissociates to yield a carbocation in the slow rate-limiting step before losing H+ from an adjacent carbon in a second step. The reaction shows first-order kinetics and no deuterium isotope effect and occurs when a tertiary substrate reacts in polar, nonbasic solution. 

SECOND-ORDER RATE COEFFICIENTS (Ar2) AND KINETIC ISOTOPE EFFECTS FOR REACTION... 

RATE COEFFICIENTS, SOLVENT AND SUBSTRATE ISOTOPE EFFECTS FOR REACTION OF... 

RATE COEFFICIENTS AND SOLVENT ISOTOPE EFFECT FOR REACTION OF 4-ClC6H4SiMe3 WITH AQUEOUS TRIFLUOROACETIC ACID AT 25 "C471... 

If one limits the consideration to only that limited number of reactions which clearly belong to the category of nucleophilic aromatic substitutions presently under discussion, only a few experimental observations are pertinent. Bunnett and Bernasconi30 and Hart and Bourns40 have studied the deuterium solvent isotope effect and its dependence on hydroxide ion concentration for the reaction of 2,4-dinitrophenyl phenyl ether with piperidine in dioxan-water. In both studies it was found that the solvent isotope effect decreased with increasing concentration of hydroxide ion, and Hart and Bourns were able to estimate that fc 1/ for conversion of intermediate to product was approximately 1.8. Also, Pietra and Vitali41 have reported that in the reaction of piperidine with cyclohexyl 2,4-dinitrophenyl ether in benzene, the reaction becomes 1.5 times slower on substitution of the N-deuteriated amine at the highest amine concentration studied. 

The isotope effects of reactions of HD + ions with He, Ne, Ar, and Kr over an energy range from 3 to 20 e.v. are discussed. The results are interpreted in terms of a stripping model for ion-molecule reactions. The technique of wave vector analysis, which has been successful in nuclear stripping reactions, is used. The method is primarily classical, but it incorporates the vibrational and rotational properties of molecule-ions which may be important. Preliminary calculations indicate that this model is relatively insensitive to the vibrational factors of the molecule-ion but depends strongly on rotational parameters. 

Various factors involved in both steps have been considered explicitly by Friedman and colleagues (29, 47, 49, 54, 67) to rationalize isotope effects in these reactions. Their treatment involves orientation effects, displacement isotope effects, and dissociation isotope effects in order to account for observed results. Stevenson and Schachtschneider (59) have also presented a treatment of decomposition isotope effects. 

Brown and McDonald (1966) provided another type of kinetic evidence for these size relationships by determining secondary kinetic isotope effects in reactions of pyridine-4-pyridines with alkyl iodides. For example, the isotopic rate ratio in the reaction between 4-(methyl-d3)-pyridine and methyl iodide at 25-0 C in nitrobenzene solution was determined to be kjyfk = l-OOl, while that in the corresponding reaction with 2,6-(dimethyl-d6)-pyridine was 1-095. (Brown and McDonald (1966) estimate an uncertainty of 1% in the k jk values.) Furthermore, the isotopic rate ratio in the case of the 2-(methyl-d3)-compound increased from 1 030 to 1-073 as the alkyl group in the alkyl iodide was changed from methyl to isopropyl, i.e. the isotope effect increased with increasing steric requirements of the alkyl iodide. 

The first step, as we have already seen (12-3), actually consists of two steps. The second step is very similar to the first step in electrophilic addition to double bonds (p. 970). There is a great deal of evidence for this mechanism (1) the rate is first order in substrate (2) bromine does not appear in the rate expression at all, ° a fact consistent with a rate-determining first step (3) the reaction rate is the same for bromination, chlorination, and iodination under the same conditions (4) the reaction shows an isotope effect and (5) the rate of the step 2-step 3 sequence has been independently measured (by starting with the enol) and found to be very fast. With basic catalysts the mechanism may be the same as that given above (since bases also catalyze formation of the enol), or the reaction may go directly through the enolate ion without formation of the enol ... 

For reviews, see L. Melander, Isotope Effects on Reaction Rates, Ronald Press, New York, 1960 F.W. Westheimer, Chem. Rev., 61, 265 (1961) Streitwieser, A., Jr., Solvolytic Displacement Reactions, McGraw-Hill, New York, 1962 E. H. Halevi,Prog Phys. Org. Chem., 1, 109 (1963) C. J. Collins and N. S. Bowman, eis.. Isotope Effects in Chemical Reactions, Van Nostrand Reinhold Co., New York, 1970. 

One-step hydroxylation of aromatic nucleus with nitrous oxide (N2O) is among recently discovered organic reactions. A high eflSciency of FeZSM-5 zeolites in this reaction relates to a pronounced biomimetic-type activity of iron complexes stabilized in ZSM-5 matrix. N2O decomposition on these complexes produces particular atomic oj gen form (a-oxygen), whose chemistry is similar to that performed by the active oxygen of enzyme monooxygenases. Room temperature oxidation reactions of a-oxygen as well as the data on the kinetic isotope effect and Moessbauer spectroscopy show FeZSM-5 zeolite to be a successfiil biomimetic model. 

Mechanistic studies have been designed to determine if the concerted cyclic TS provides a good representation of the reaction. A systematic study of all the E- and Z-decene isomers with maleic anhydride showed that the stereochemistry of the reaction could be accounted for by a concerted cyclic mechanism.19 The reaction is only moderately sensitive to electronic effects or solvent polarity. The p value for reaction of diethyl oxomalonate with a series of 1-arylcyclopentenes is —1.2, which would indicate that there is little charge development in the TS.20 The reaction shows a primary kinetic isotope effect indicative of C—H bond breaking in the rate-determining step.21 There is good agreement between measured isotope effects and those calculated on the basis of TS structure.22 These observations are consistent with a concerted process. 

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