Inversion secondary

The calculations were performed at the semiempirical level using AMI parametrization. The results for the methyl chloride reaction (Table 8) supported Williams earlier findings for the methylammonium ion-ammonia reaction (p. 147) and the results by Wolfe and Kim in that the inverse secondary a-deuterium KIE arose from an increase in the C —H stretching force constants which accompanied the change from sp3 hybridization at the a-carbon in the reactant to the spMike hybridization in the transition state. More important, however, were the observations that (i) the total KIE is dominated by the vibrational (ZPE) component of the KIE with which it correlates linearly, and (ii) that the inverse contribution from the C —H(D) stretching vibrations is almost constant for all the reactions. Ibis suggests that the contribution from the other vibrations, i.e. the rest in Table 8, determines the magnitude of the KIE. In fact, Barnes and Williams stated that the... 

While it is difficult to rule out an inductive contribution to the secondary a-deuterium KIEs in these Menshutkin SN2 reactions, the steric origin of these KIEs is clearly indicated by the inverse secondary a-deuterium KIEs found in an extensive study of the SN2 Menshutkin reactions between substituted... 

Kaplan and Thornton (1967) also concluded that the secondary deuterium KIEs found in these SN2 reactions were not inductive in origin. Although the large inverse secondary deuterium KIE (kH/kD = 0.883 0.008) found in the... 

A large inverse secondary deuterium KIE of 0.64 was observed in acetic acid at 25°C when the perdeutero (d2o) compound was the deuterated substrate. This large inverse deuterium KIE was attributed to the KIE for the rate-determining formation of the bromonium ion (62). Although a portion of this KIE is undoubtedly due to the inductive effect (deuterium is more electron-donating than hydrogen and the deuterated bromonium ion would... 

Scheme 3) a large inverse secondary deuterium KIE is observed both in the presence, and in the absence, of added bromide ion. However, in acetic acid, the KIE becomes even more inverse as the concentration of bromide ion increases, i.e. it decreases from kH/kD = 0.64 to a minimum of 0.55 as the bromide ion concentration increases from zero to 0.04 mol dm-3 (Table 44). In methanol, on the other hand, the inverse secondary deuterium KIE of 0.56 0.04 is effectively independent of bromide ion concentration. 

Subsequent work confirmed this apparently abnormal behaviour. Deuteriation at remote sites (the S- or e-position) induces small inverse secondary isotope effects in a-cleavages occurring in the ion source, but normal isotope effects in the decomposition of metastable ions in the field-free regions94,95. The time dependence of the isotope effect was also studied by field ionization kinetics, which permit the analysis of fragmentations occurring after lifetimes as short as 10 12 s-1. It was found that the inverse isotope effect favouring loss of the deuteriated radical operates at times shorter than 10 9 s95. 

Finally, it is worth noting that the substituent effects are different on the two types of Menshutkin reactions as well. For the benzyl substrates, changing to a better nucleophile, i.e. changing the substituent on the nucleophile from the meta-nitro to a para-methoxy substituent, leads to a later, more product-like transition state with more inverse secondary incoming nucleophile deuterium kinetic isotope effects. Flowever, the same change in nucleophile in the reactions with the methyl and ethyl substrates leads to an earlier transition state and less inverse secondary incoming nucleophile deuterium kinetic isotope effects. 

Schneider, F.W. and Rabinovitch, B. S., The unimolecular isomerization of methyl-d3 isocyanide. Statistical-weight inverse secondary intermolecular kinetic isotope effects in nonequilibrium thermal systems. J. Am. Chem. Soc. 85, 2365 (1963). 

Veith, H.J. Gross, J.H. Alkene Loss From Metastable Methyleneinunonium Ions Unusual Inverse Secondary Isotope Effect in Ion-Neutral Complex Intermediate Fragmentations. Org. Mass Spectrom. 1991,26, 1097-1105. 

A corollary of this argument is that a change from sp to sp hybridization should result in an inverse secondary isotope effect (i.e., C/ko < 1). 

Figure 15.3 Secondary KIEs are associated with normal modes other than the reaction coordinate, one of which is shown in this diagram. The heavy and light vibrational frequencies both change on going from the reactant (R) to the TS structure ( ) because in this example the mode is tighter in the TS structure, the difference between the heavy and light ZPVEs increases, and this causes the potential energy of activation to be larger for the light isotopomer than the heavy one (an example of an inverse secondary KIE). In a real many-atom system there are potentially a large number of modes that will contribute to the secondary KIE. some in a normal fashion and some in an inverse fashion...

Deuterium substitution on the four carbon atoms changing from trigonal to tetrahedral as the reaction proceeds, gives rise to inverse secondary kinetic isotope effects, small but measurable, both for the diene and the dienophile 3.1. If both bonds are forming at the same time, the isotope effect when both ends are deuterated is geometrically related to the isotope effects at each end. If the bonds are being formed one at a time, the isotope effects are arithmetically related. It is a close call, but the experimental results, both for cycloadditions and for cycloreversions, suggest that they are concerted. 

The inductive effect of the donating C—D bonds to the observed large inverse secondary deuterium isotope effect has not been given proper consideration but treated as a rather minor component superimposed on the important steric component caused by larger amplitudes of vibrations of C—H bonds than those of the C—D bonds. 14C KIE have not been studied in this reaction. The C2, C V. C3 , C3, endo hydrogens are separated only by 2.11 A, substantially less than van der Waals radii (2 x 1.2 A)404. 

An unusually large inverse secondary deuterium kinetic isotope effect (1.53-2.75, depending on the reaction conditions) has been reported for bromination of the sterically congested olefin 74. This behaviour can be rationalized by decreased steric hindrance due, in particular, to the ewrfo-placement of the deuterium atoms relative to the double bond135. 

Zirconium imido complexes have been used to carry out S 2 reactions of allylic chloride, bromide, iodide, and alkyl, aryl, and trimethylsilyl ethers in high yields at room temperature.12 The syn stereochemistry, an inverse secondary (k /k Oy = 0.88 obtained using the ( )-l-(r-butyldimethylsilyloxy)-3-deuterioprop-2-ene and the rate expression led the authors to suggest the reactions occurred via the mechanism in Scheme 4 with transition state (9). 

Experimental and computational studies of the pericyclic Meisenheimer rearrangement and a competitive rearrangement of A-propargyl morphol i nc N-oxide revealed a novel inverse secondary kinetic isotope effect (kn/kD 0.8) for the rate-determining cyclization step, probably occurring because of a C(sp) to C(sp2) change in hybridization at the reaction center (Scheme 3).5... 

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