Kinetic studies isotope effects

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 ... 

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. 

A positive iodinating species was postulated to account for the kinetics and isotope effect observed in the iodination of some amines by iodine in aqueous potassium iodide (in some cases in the presence of acetate, lactate, or phosphate ion). The isotope effects (kH/kD values in parenthesis) for these compounds studied were 2,4,6-trideutero-m-dimethylaminobenzenesulphonate ion, 25 °C (1.0) 2,4,6-trideutero-m-dimethyIbenzoate ion, 30 °C (1.4) 2,4,6-trideutero-dimethylaniline, 30 °C, lactate (3.0) 2,4,6-trideuteromethylaniline, 25 °C, acetate (3.2) 2,4,6-trideuteroaniline, 25 °C (3.5), phosphate (4.0) 2,4,6-trideutero-metanilate ion, 35 °C (2.0) 2,4,6-trideutero-m-aminobenzoate ion, 30 °C (4.8), phosphate (3.0) 2,6-dideutero-l-dimethylaminobenzene-4-sulphonate ion, 25 °C, phosphate (1.0) 4-deutero-l-dimethylaminobenzene-3-sulphonate ion, 25 °C, phosphate (1.0). The kinetics of these reactions was given by... 

Studies of the molar volumes of perdeuteriated organic compounds might be expected to be informative about non-bonded intermolecular forces and their manifestations, and such studies might be considered to obviate the necessity of investigating steric isotope effects in reacting systems. The results from non-reacting systems could then be simply applied to the initial and transition states in order to account for a kinetic steric isotope effect. 

These studies had therefore found the tunneling phenomenon, with coupled motion, as the explanation for failures of these systems to conform to the expectations that the kinetic secondary isotope effects would be bounded by unity and the equilibrium effect and that the primary and secondary effects would obey the Rule of the Geometric Mean (Chart 3), as well as being consistent with the unusual temperature dependences for isotope effects that were predicted by Bell for cases involving tunneling. 

Extensive studies of kinetics and isotope effects by Hartwig and coworkers support the mechanism shown in Scheme 5 for the lr(I)/dtbpy catalyzed borylation [81]. In particular, these studies indicate that the iridium(III) trisboryl bipyridine complex (10) is the species that activates the arene C-H bond this is in agreement with DFT calculations by Sakaki et al. predicting the key intermediacy of the trisboryl complex and the seven-coordinated Ir(V) species resulting from C-H addition [82]. C-H addition to Ir(III) was also proposed in the (Ind)Ir(COD)/ phosphine-catalyzed borylation by Smith et al. [76]. 

Kinetic studies of the reaction of Z-phenyl cyclopropanecarboxylates (1) with X-benzylamines (2) in acetonitrile at 55 °C have been carried out. The reaction proceeds by a stepwise mechanism in which the rate-determining step is the breakdown of the zwitterionic tetrahedral intermediate, T, with a hydrogen-bonded four-centre type transition state (3). The results of studies of the aminolysis reactions of ethyl Z-phenyl carbonates (4) with benzylamines (2) in acetonitrile at 25 °C were consistent with a four- (5) and a six-centred transition state (6) for the uncatalysed and catalysed path, respectively. The neutral hydrolysis of p-nitrophenyl trifluoroacetate in acetonitrile solvent has been studied by varying the molarities of water from 1.0 to 5.0 at 25 °C. The reaction was found to be third order in water. The kinetic solvent isotope effect was (A h2o/ D2o) = 2.90 0.12. Proton inventories at each molarity of water studied were consistent with an eight-membered cyclic transition state (7) model. 

Selection of the location of the radiolabel is also of importance. The position of the label within the compound should be such that no primary or secondary isotope effects perturb the kinetics of the system (unless, of course, the investigator is studying isotope effects). 

In 1998, Hasanayn and Streitwieser reported the kinetics and isotope effects of the Aldol-Tishchenko reaction . They studied the reaction between lithium enolates of isobu-tyrophenone and two molecule of beuzaldehyde, which results iu the formation of a 1,3-diol monoester after protonation (Figure 28). They analyzed several aspects of this mechanism experimentally. Ab initio molecular orbital calculatious ou models are used to study the equilibrium and transition state structures. The spectroscopic properties of the lithium enolate of p-(phenylsulfonyl) isobutyrophenone (LiSIBP) have allowed kinetic study of the reaction. The computed equilibrium and transition state structures for the compounds in the sequence of reactions in Figure 28 are given along with the computed reaction barriers and energy in Figure 29 and Table 6. 

Of the numerous nicotinamide model studies done since about 1970, the one that had perhaps the greatest impact on mechanistic thinking revealed a discrepancy between the kinetic deuterium isotope effect and the H/D ratio in the alcohol product formed upon reduction of trifluoroacetophenone by 4-protio- and 4-deuterio-A-alkyl-l,4-dihy-dronicotinamides (Scheme 2) (71JA6694). For example, while the reduction of... 

Recently, trans insertion of hexafluorobutyne into one of the M—H bonds in some metallocene hydrides, Cp2MH , was studied in some detail (47). Experiments carried out in the presence of various radical-sensitive reagents such as TV-phenyl-a-naphthylamine suggested that a free radical mechanism was unlikely. A stepwise ionic mechanism, involving a zwitter-ionic intermediate, Cp2(H2)M+—C(CF3)==CCF3, is improbable, since (i) the stereochemistry and the apparent rate are not influenced by the polarity of the solvents, (ii) no deuterium is incorporated in the reaction in EtOD, and (iii) the trend in reactivity (Mo > W) does not reflect the trend in v-basicity or M—C bond stability (W > Mo). An essentially concerted trans-insertion mechanism is inferred, which is supported inter alia by the low kinetic deuterium isotope effect (kH/k0 = 1). 

Flash photolysis of a substituted hexaarylbiimidazole and reactions of the imi-dazolyl radical. Coraor, G. R., Riem R. H. MacLachlan, A. Urban, E. J. (Exp. Stn., E. I. DuPont de Nemours, and Co., Wilmington, Del.). J. Org. Chem. 1971, 36 (16), 2272-5. (Eng). The rate of reaction of 2-(o-chlorophenyl)-4,5-diphenylimida-zolyl radicals (L with additives was studied in various solvents. Evidence based on measured rate consts., including kinetic D isotope effects, prove that the rate detg. step in the reaction L + aromatic amine is an electron change reaction at the amino N, while in the reaction L + hydroquinone the rate-detg. step is H abstraction. 

This study on the kinetic chlorine isotope effect in ethyl chloride50 was extended to secondary and tertiary alkyl halides pyrolyses51. The isotope effects on isopropyl chloride and terf-butyl chloride pyrolysis were found to be primary and exhibited a definite dependence on temperature. They increased with increasing methyl substitution on the central carbon atom. The pyrolysis results and model calculations implied that all alkyl chlorides involve the same type of activated complex. The C—Cl bond is not completely broken in the activated complex, yet the chlorine participation involves a combination of bending and stretching modes. 

The product 144 has 98.8% radiochemical purity after chromatography and recrystallization. No kinetic tritium isotope effect and tritium exchange with the solvent in the last two syntheses has been studied. 

Discussions and studies of reaction mechanisms attempt to analyse the way in which a compound A is transformed into a compound B. Varying degrees of sophistication are attached to the phrase reaction mechanism but the aim is generally to define the reaction in terms of elementary steps and stereochemistry. In solution chemistry, the structures of compounds A and B will be known and mechanistic information may be deduced from kinetic studies, solvent effects, stereochemistry, isotopic labelling, and other slight structural modifications. 

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