Secondary Isotope Effects in the Reactions of Methyl-d₃-pyridines with Boron Trifluoride. Consideration of the Secondary Isotope Effect as a Steric Phenomenon^1,2

Abstract

The introduction of methyl-^groups in the 3 or 4 position of pyridine results in no observable change in the heats of reaction of these bases with boron trifluoride over the normal derivatives. On the other hand, in the 2 position, there is observed a significant increase in the heat of reaction for the deuterium derivatives, corresponding to the smaller steric requirements of methyl-rf3 over methyl-^groups. Use of a reference acid of smaller steric requirements, BH3, causes the difference to disappear, consistent with the predictions of the steric interpretation, but contrary to the predictions of either of the two electronic interpretations, inductive or hyperconjugative, now under consideration. These results support the conclusion that the secondary isotope effects of deuterium arise predominantly from its smaller steric requirements. Deuterium labeling of the methyl groups in 3-and 4-picoline has no observable effect on the rates (1) Chemical Effects of Steric Strains. XX.(2) Based in part on theses submitted by John G. Koelling and Gerald J. McDonald in partial fulfillment of the requirements for the degree of

Acidity of hydrocarbons. XXV. Secondary isotope effects in the lithium cyclohexylamide catalyzed .alpha.-deuterium exchange of ring-deuterated toluenes

“…volume of deuterium that would allow greater conjugation.10 Indeed, Brown has taken the extreme position that steric effects are the cause of all secondary deuterium isotope effects. 18 In the present case such a steric effect increasing the conjugation to the exocyclic carbon of the developing benzyl anion would operate to increase the rate of the o-deuterated toluene and would result in a less negative or positive isotope effect in this position. Experimentally, an o-deuterium causes a larger decrease in rate than any other position.…”

Kinetic Isotope Effects in the Reduction of Methyl Iodide

“…The reactions with NaBH 4 and with LiAlH 4 (LAH) have low KIEs, confirming that these reagents react via an S N 2 transition state by direct hydride transfer. This is most obvious for the borohydride, for which the KIE is slightly inverse, corresponding to a slightly smaller steric bulk of the CD 3 group than of the CH 3 group . LAH likewise has a small, normal KIE and reacts as a nucleophile.…”

“…The ratio k H / k D for methane was 1.37 and for the methyl groups in ethane 1.03, which indicates that the nucleophilic attack of methylsodium on methyl iodide, (11), has a large inverse deuterium KIE. This is likely since CD 3 I is faster than CH 3 I by a factor 1.15 in nucleophilic hydrolysis and CD 3 Na is expected to be a better nucleophile than the protio analogue because it is less bulky …”

Conformational Equilibrium Isotope Effects in Glucose by 13C NMR Spectroscopy and Computational Studies

“…Latitudinally, conformational equilibrium isotope effects have been used to study molecular structure in a large number of compounds. Methylpyridines, , 1,3-dioxanes, 3-azabicyclo[3.2.2]nonanes, and cyclohexane derivates − can each serve as simple models for carbohydrates. In fact, hyperconjugation and steric interactions contribute to equilibrium isotope effects in these molecules in a well-understood way.…”