Kinetic isotope effects observed

A. Alkaline Hydrolysis. -The low kinetic isotope effect observed in the protonation of carbanions formed in phosphonium salt hydrolysis leads to the idea that there is little breaking of the phosphorus-carbon bond and correspondingly little transfer of a proton to the incipient carbanion in the transition state (87) of the rate-determining step. ... 

Jacobs, G., Patterson, P.M., Graham, U.M., Sparks, D.E., and Davis, B.H. 2004. Low temperature water-gas shift Kinetic isotope effect observed for decomposition of surface formates for Pt/ceria catalysts. Appl. Catal. A Gen. 269 63-73. 

An enantioselective imino-ene reaction was developed by Lectka to provide ct-amino acid derivatives.27 Aryl alkenes (cr-methyl styrene, tetralene), aliphatic alkenes (methylene cyclohexane), and heteroatom-containing enes, all gave high yields and high ee s of the homoallylic amides (Equation (17)). The mechanism of this reaction has been proposed to proceed through a concerted pathway. This mechanism is evidenced by a large kinetic isotope effect observed in the transfer of H(D). 

According to isotope studies the rate-determining step of this sequence is the reductive elimination, and all other reactions (C-H activation, insertion of alkene) are reversible. The first indication of this behaviour was the H/D exchange of the ortho proton of acetophenone. Secondly, and perhaps useful for many other systems, was the kinetic isotope effect observed for 13C natural... 

Recently, some attempts were nndertaken to uncover the intimate mechanism of cation-radical deprotonation. Thns, the reaction of the 9-methyl-lO-phenylanthracene cation-radical with 2,6-Intidine (a base) was stndied (Ln et al. 2001). The reaction proceeds through two steps that involve the intermediary formation of a cation-radical/base complex before unimolecular proton transfer and separation of prodncts. Based on the value of the kinetic isotope effect observed, it was concluded that extensive proton tnnneling is involved in the proton-transfer reaction. The assumed structure of the intermediate complex involves n bonding between the unshared electron pair on nitrogen of the Intidine base with the electron-deficient n system of the cation-radical. Nonclassical cation-radicals wonld also be interesting reactants for snch a reaction. The cation-radical of the nonclassical natnre are known see Ikeda et al. (2005) and references cited therein. 

In the study of isotope effects, the isotope partitioning factor at a particular site is independent of the isotopic composition at any other site. Thus, an isotope effect for a diisotopically substituted species should be the product of the kinetic isotope effects observed for each of the monoisotopically substituted compounds. 

A kinetic isotope effect observed by a single reactant, having isotopic atoms at equivalent reactive positions, which reacts to produce isotopomeric products with a nonstatistical distribution. The pathway favored will be the one having lower force constants for the displacement of the isotopic nuclei in the transition state. 

For acid-catalyzed hydrolysis of methyl glucosides53 the kinetic isotope effect observed for the oxygen of the leaving group was /c,6()//c18() = 1.024-1.026. Observation of similar effects for enzymes supports the participation of an acidic group of the protein (Glu 35 of lysozyme) in catalysis but does not eliminate the possibility of concerted involvement of a nucleophilic group, e.g., Asp 52 in lysozyme.81 82... 

The kinetic isotope effect observed for the FTT synthesis by Lancet and Anders71) on C02, CH4, C2 + (which means ethane and heavier hydrocarbons) and a wax fraction recovered from the catalyst, is not in disagreement with the experimental values (comparison between Fig. 2,1 and II A). The same group 1 have pointed out that in the case of FTT in the presence of NH3, the amino acid data (813C as high as +44%0) would not be inconsistent with the experimental values either (see Fig. 1). 

The nonconcerted diradical pathway was still considered viable in the thermal decomposition of 1,2-diazetines assuming that the loss of nitrogen from the intermediate was rapid relative to the C-C bond rotation. Olsen using mono- and dideuterated diazetines provided mechanistic evidence for this process <1982JA6836>. The kinetic isotope effect observed suggested that the transition state was unsymmetrical and should be proceeding via a diradical like pathway (Scheme 3). 

Significant characteristics of the porphyrin iron monoxide are seen in the chemical reactivity. Naphthalene is converted initially to the corresponding arene oxide on treatment with P 450 (19), consistent with a molecular mechanism of oxygen transfer from an iron monoxide to the aromatic nucleus. Retention of stereochemistry in the P-450 catalyzed hydroxylation of d ethylbenzene also supports the molecular mechanism. The unusually large kinetic isotope effect observed for the P-450 oxidation of dideutero 1,3-diphenylpropane, kJkD = 11, demonstrates that C—H cleavage is involved in the rate determining step (20), probably in a very unusual environment, not incompatible with a molecular mechanism. 

Many arguments are against this mechanism. As shown by Bar-Eli and Klein (1), the hydride ion from LiH is not a catalyst for this reaction. In the similar case of water, Schindewolf (16) has shown that the hydride ion does not appear in a solution of potassium hydroxide in water. The kinetic isotopic effect observed is also in contradiction to a dissociative mechanism (1). The largely negative value of the entropy of activation is an argument for a highly organized activated complex. 

For acid-catalyzed hydrolysis of methyl gluco-sides the kinetic isotope effect observed for the oxygen of the leaving group was = 1.024-1.026. 

Sialosides have a distinct mechanism of hydrolysis for its unusual sugar structure of sialic acid. For example, the large 8-dideuterium and small primary kinetic isotope effects observed at the anomeric carhon and the large secondary kinetic isotope effect observed at the carboxylate carbon in the acid-catalyzed solvolysis of CMP-Af-acetyl neuraminate 24 support an oxocarbenium ion-like transition state 25 having the 5S conformation without nucleophilic participation of carboxylate and with the carboxylate anion in a looser environment than in the ground state [15] (O Fig. 3). Such a zwitterion structure is consistent with the results from calculations using the COSMO-AMI method for aqueous solutions [16]. 

The concentration and the pH determines the form of Cr in aqueous solutions in dilute solution the monomoeric form (HCr04 ) dominates while in concentrated solution the dimeric form (HCr207 ) is prevalent. The alcohol substrate is first converted to the corresponding chromate ester, which suffers a rate-determining deprotonation by a base to release the Cr species. This mechanism is supported by a large kinetic isotope effect observed during the oxidation of an a-deuterated alcohol substrate. 

The large primary kinetic isotope effects observed for propane and propylene oxidation over these catalysts suggest homolytic C-H bond breaking as the rate limiting step, and a relatively symmetric transition state. Propane and propylene compete with similar effectiveness for the metal oxide catalytic sites, with propylene favored by a factor of 2.3. 

SCHEME 11.14 Qualitative energy diagram that explains kinetic isotope effects observed for benzene C—H activation by Cp Rh(PMe3). 

Isotope effect and relative rate studies also suggest an early TS for benzylic chlorination and bromination. The benzylic position is only moderately activated toward uncomplexed chlorine atoms. Relative to ethane, toluene reactivity is increased only by a factor of 3.3. The kinetic isotope effect observed for bromination and chlorination of toluene suggest little rehybridization at the TS. 

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