Question

3. Consider the following reaction: (15 pts) ROOR H, H2O + 2 RÕH RO OR * * 150 2 ROH 20 A-S2) HH 767 a. If you radiolabeled the carbon and oxygens on the acetal: i. Describe their expected kinetic isotope effects as primary or secondary for each mechanism ii. Describe their expected kinetic isotope effects as normal or inverse for each mechanism. RO OR HO 2 ROH

Answer 1

(i) In reaction A-1 and A-2 in the rate determining step or the slow step there is a bond cleavage happening between the radiolabelled atom (which in both the cases of A-1 and A-2 is carbon) and R-OH. This direct cleavage of atoms from the radiolabelled atom is known as primary kinetic isotope effect. In reation mechanism A-Se2 again the radiolabelled oxygen atom is undergoing cleavage so as described above this is also primary kinetic isotope effect.

Therefore, all three reaction mechanisms undergo primary kinetic isotope effect.

(ii) kinetic isotopic effect can be written as the ratio between the reation rate constants for the reactions involving the light (kL) and the heavy (kH) isotopically substituted reactants

KIE= KH

In general, smaller force constants in the transition state are expected to yield a normal kinetic isotope effect, and larger force constants in the transition state are expected to yield an inverse kinetic isotope effect when stretching vibrational contributions dominate the kinetic isotope effect. what this statement means is that in the transition state (the one in the square box) the more "streaching arund of the radiolabelled atom is done higher the probability that the product will undergo the inverse kinetic isotope mechanism so in cases A-2 the carbon atom in the transition state has made 5 bonds which really changes its structure to something unusual (initially it is sp3 hybridysed but then it makes 5 bonds which is not stable) which means A-2 will produce inverse kinetic isotope product. For A-Se2 reaction mechanism in the transition state oxygen makes 3 bonds which is unstable therefore it will produce inverse kinetic isotope product. For A-1 reation mechanism in the transition state carbon(radiolabelled) remains in sp3 hybridysation which is stable and hence it undergoes normal kinetic isotope effect.