Substantial kinetic isotope effect

In confirmation, when acetone-dg was studied, a very substantial kinetic isotope effect was observed, being about 7 to 12 depending upon the base catalyst. 

A further investigation of the ortholithiation of anisole has taken advantage of previous spectroscopic evidence of the exclusive formation of disolvated dimers of n-BuLi in TMEDA, combined with rate studies which demonstrate that this combination promotes ortholithiation via [(n-BuLi)2((TMEDA)2(anisole)] in pentane. The substantial kinetic isotope effect fcbs(H)/ obs(D) = 20 3] found on comparison of anisole with anisole- fg is indicative of rate-determining proton transfer but the unusually high value has not been explained satisfactorily. 

The same type of ring cleavage occurs in the benz[d]isoxazole series. Thus, benz[d]isoxazole is cleaved by aqueous alkali to give the anion of 2-hydroxybenzonitrile (27) (73JOC2294). As for the monocyclic systems, the reaction can be represented as a concerted E2 elimination since there is a substantial kinetic isotope effect. Salts of benz[d]isoxazole-3-carboxylic adds are also cleaved, with loss of carbon dioxide, in a concerted manner (72JOC2498 75JA7305). 

From the temperature dependence of the substantial kinetic isotope effect (KIE) observed in the oxidation of diols to hydroxycarbonyl compounds by 2,2/-bipyridinium chlorochromate (BPCC), it is proposed that hydride transfer occurs in a chromate ester intermediate, involving a six-electron Hiickel-type transition state.9 A similar conclusion is drawn for the oxidation of substituted benzyl alcohols by quinolinium chlorochromate.10... 

The oxidation of a-hydroxy acids by benzyltrimethylammonium tribromide (BTMAB) to the corresponding carbonyl compounds shows a substantial solvent isotope effect, A (H20)/A (D20) = 3.57, but no KIE for a-deuteromandelic acid.133 The oxidation of glucose by hypobromous acid is first order in glucose and the acid.134 [l,l-2H2]Ethanol shows a substantial kinetic isotope effect when oxidized by hexamethylenetetramine-bromine (HABR) in acetic acid to aldehyde.135 Kinetics of the oxidation of aliphatic aldehydes by hexamethylenetetramine-bromine have been studied by the same group.136 Dioxoane dibromide oxidizes y-tocopherol to 5-bromomethyl-y-tocopherylquinone, which spontaneously cyclizes to 5-formyl-y-tocopherol.137... 

Several reports deal with the action of heterocycle-chromate agents such as quinolin-ium dichromate on five-membered heteroaldehydes340 and quinolinium bromochromate on benzaldehydes,341,342 all in acetic acid solution. The latter studies show a second-order dependence on proton concentration, acceleration by electron-withdrawing para-substituents, and a substantial kinetic isotope effect for the deuterated aldehyde. 

A second-order dependence on both the reductant and acidity was observed in the oxidation of alcohols with butyltriphenylphosphonium dichromate study of MeCD2OH and Me2CDOH indicated the presence of a substantial kinetic isotope effect. The reaction was studied in 19 organic solvents and the rates were correlated with mul-tiparametric equations. The reaction is susceptible to both electronic and steric effects of the substituents. A mechanism involving the formation of a dichromate ester and an a-C-H cleavage has been proposed.4... 

This principal reaction mechanism is widely believed to apply to most S Ar reactions irrespective of the electrophilic reagent. There are however a number of experimental observations that indicate exceptions to this mechanism. There are examples of thermodynamically controlled Friedel-Crafts reactions, when using reaction conditions like polyphosphoric acid and elevated temperatures [27,28]. In iodination and some cases of Friedel-Crafts acylation, the last step of the reaction, the proton abstraction, has been shown to have a substantial kinetic isotope effect, which indicates that this step is at least partially rate limiting [29-31]. There are also still open questions regarding the exact nature of the reaction intermediates, and we will focus on these issues in the remaining part of the chapter. 

Holt and co-workers ° demonstrated that aluminium chloride readily dissolved in dichloromethane and they successfully sulfonylated several aromatic compounds by treatment with this homogeneous reagent. Studies of the />-toluene-sulfonylation of benzene and bromobenzene using /7-toluenesulfonyl chloride and aluminium chloride in dichloromethane showed that the reaction followed third order kinetics with substantial kinetic isotope effects ( h 2.0-2.8). The IR... 

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