Primary kinetic hydrogen isotope effects

The first unequivocal evidence for the AE + DE mechanism came in three papers by Zollinger (1955 a-c) dealing with general base catalysis and primary kinetic hydrogen isotope effects in azo coupling reactions of various types. Three classes of reactions were identified i) reactions with no isotope effects (ArH/A D - 1.0) and no general base catalysis, ii) others with large isotope effects (k /k — 6.5) and (practically) linear base catalysis, and iii) intermediate cases with isotope effects of around 3.0 and less-than-linear base catalysis. 

Primary Kinetic Hydrogen Isotope Effects in the Base-Cataeyzed Exchange of Varioxts Heterocyclic Compounds... 

Primary kinetic hydrogen isotope effects in the reductions of triarylmethyl cations by formate in aqueous trifluoroacetic acid have been determined (Stewart and Toone, 1978). For 16 cations with pK + ranging from —2.25 (4-methoxy-4 -methyl) to — 7.63 (4,4 -dichloro), plots of log kH and log kD against pA"R+ show poor linear fits with the best straight lines (least squares) having slopes of 0.473 (r = 0.973) for the H-data and 0."491(r = 0.983) for the D-data. Both plots show downward curvature, with the effect being more emphatic for the H-data. Least squares fit to quadratics better... 

H Kwart. Temperatme Dependence of the Primary Kinetic Hydrogen Isotope Effect as a Mechanistic Criterion. Acc Chem Res 15 401 408, 1982. 

In view of the complications imposed on interpretation of kinetic isotope effects by quantum mechanical tunnelling and a variable profile of isotope effect with proton transfer to different bases, a more certain prediction would seem most probable if comparisons are restricted to reactions of a series of similar substrates within a given reaction medium. Within this framework it is possible to make reasonable predictions of the effect of substrate structure on the nature of the transition state for elimination using only primary kinetic hydrogen isotope effects. 

The observation of primary kinetic hydrogen isotope effects for elimination from /3-bromostyrenes in alkoxide-alcohol media suggests these substrates follow an E2 rather than an E1 cB mechanism - . Certainly greater carbanion character is associated with the transition states than those of the corresponding saturated halides. The magnitude of the isotope effect (Table 27) decreases... 

The Eco2 reaction of 9-fluorenyl toluene-p-sulphonate with sodium hydroxide in 90% methanolic acetone has a primary kinetic hydrogen isotope effect of only 2.3 at 25°C . It is difficult to compare this result with that for the corresponding nitrate but if a transition state with considerable carbanion character is involved, then the indications are that nitrite is a better leaving group than toluene-p-sulphinate. It would be worth while to investigate the sulphur isotope effect for this latter reaction. 

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