Normal kinetic isotope effect

This mechanism clearly implicated alkane complexes as precursors to C-H activation but the IR absorptions of [Cp Rh(CO)Kr] and [Cp Rh(CO)(C6Hi2)] were not resolved and were presumed to be coincident. The temperature dependent data gave values of AH = 18 (or 22) kj mol for the unimolecular C-H (or C-D) activation step representing a normal kinetic isotope effect, kn/fco 10- However, an inverse equilibrium isotope effect (K /Kq 0.1) was found for the slightly exothermic pre-equilibrium displacement of Kr by CoHn/C Dn implying that C6Dj2 binds more strongly to the rhodium center than does C Hn-... 

R and S isomers of HDT]acetic acid were synthesized by chemical and enzymatic methods that yield products of known stereochemistry.1819 The two isomers were then distinguished by using the following ingenious enzymatic assays. The acetic acid was first converted to acetyl-coenzyme A (by a reaction of the carboxyl group—and not the methyl—of acetic acid). The acetyl-coenzyme A was then condensed with glyoxylate to form malate in an essentially irreversible reaction catalyzed by malate synthase (equation 8.27). The crucial feature of this reaction is that it is subject to a normal kinetic isotope effect, so that more H than D... 

TABLE 8.4 Some Reactions Exhibiting Normal Kinetic Isotope Effects... 

The reaction was found to be first order with respect to amines and acrylamides and no base catalysis was observed. The reaction is believed to occur in a single step in which the addition of amine to Cp of acrylamide and proton transfer from amine to Ca of acrylamide take place concurrently with a four-membered cyclic transition-state structure. The Hammett (px) and Brpnsted (/3X) coefficients are rather small, suggesting an early transition state (TS). The sign and magnitude of the cross-interaction constant, pxy(= —0.26), is comparable to those found in the bond formation processes in the. S n2 and addition reactions. The normal kinetic isotope effect ( h/ d > 1.0) and relatively low A and large negative Avalues are also consistent with the mechanism proposed.192... 

A normal kinetic isotope effect has k /ko > 1. Deuterium Is often put into compounds by exchange with the cheapest source. D20, so reactions in D20 often go slower than reactions in H20. Reactions with k /ko < 1 have inverse deuterium isotope effects so a reaction that goes faster in D2Othan in H20 (even when that is the expected pattern) has an inverse solvent deuterium isotope effect. 

For another contrast between SAC and GAC we need only refer you back to the two Z/E isomer-izations earlier in the chapter. Isomerization of the diene is GAC—protonation at carbon is the slow step—and isomerization of the allylic alcohol is SAC. What we didn t tell you earlier was that the GAC reaction has a normal kinetic isotope effect of k(H)lk(D) = 2.5 and a negative entropy of activation AS = -36 J mol-1 K-1—just what we should expect for a bimolecular reaction involving rate-determining proton transfer from oxygen to carbon. Notice that the intermediate cation is tile same whichever the route only the ways of getting there, including the rate-determining steps, are different. 

Formation of tetrahydrofuran (THF) is also faster at higher pH but, by contrast, is also accelerated by various bases at constant pH. If anions of phenols (ArO ) are used as catalysts, a Hammett p value of -1-0.8 shows that electrons are flowing away from the aromatic ring. There is a small normal kinetic isotope effect 1ch/ D = 1-4- There is SBC and GBC in this reaction. Here is the mechanism with ArO as GBC. 

If we speed up the slow step by adding to the molecule some feature that stabilizes the cation intermediate, general acid catalysis may be found. One example is the aromatic cation formed in the hydrolysis of cycloheptatrienone acetals. The normal kinetic isotope effect proclaims GAC. 

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