D. N. Kursanov, a Russian chemist, proved that the bond that...

D. N. Kursanov, a Russian chemist, proved that the bond that is broken in the hydroxideion-promoted hydrolysis of an ester is the acyl $\mathrm{C}-\mathrm{O}$ bond, rather than the alkyl $\mathrm{C}-\mathrm{O}$ bond, by studying the reaction of the following ester with $\mathrm{HO}^{-} / \mathrm{H}_{2} \mathrm{O}$ : a. Which of the products contained the $^{18}$ O label? b. What product would have contained the $^{18} \mathrm{O}$ label if the alkyl $\mathrm{C}-$ O bond had broken?

D. N. Kursanov, a Russian chemist, proved that the bond that is broken in the hydroxideion-promoted hydrolysis of an ester is the acyl $\mathrm{C}-\mathrm{O}$ bond, rather than the alkyl $\mathrm{C}-\mathrm{O}$ bond, by studying the reaction of the following ester with $\mathrm{HO}^{-} / \mathrm{H}_{2} \mathrm{O}$ :
a. Which of the products contained the $^{18}$ O label?
b. What product would have contained the $^{18} \mathrm{O}$ label if the alkyl $\mathrm{C}-$ O bond had broken?

Key Concepts

Bond Cleavage in Ester Reactions

This concept focuses on the identity of the bond that breaks during the hydrolysis of an ester. In nucleophilic acyl substitution, whether the acyl C-O bond or the alkyl C-O bond is cleaved has significant implications for the reaction products. The determination of which bond is broken helps validate mechanistic hypotheses based on the distribution of isotopic labels in the resulting acid and alcohol components.

Isotopic Labeling

Isotopic labeling, such as the incorporation of 18O, is a technique used to trace the movement of atoms through a chemical reaction. By substituting a common atom with its heavier isotope, researchers can track which part of the molecule retains the label after bond cleavage, providing insight into the reaction mechanism, including the specific bond-breaking events.

Ester Hydrolysis Mechanism

This concept involves the transformation of an ester into a carboxylic acid and an alcohol, typically under nucleophilic conditions. The mechanism generally proceeds through nucleophilic acyl substitution, where a nucleophile (e.g., hydroxide ion) attacks the electrophilic carbonyl carbon, leading to the formation of a tetrahedral intermediate and subsequent departure of a leaving group.

Nucleophilic Acyl Substitution

This is the pivotal reaction mechanism for many carbonyl-containing compounds, including esters. The process involves a nucleophile attacking the acyl carbon of the carbonyl group, forming an unstable tetrahedral intermediate that eventually collapses by expelling a leaving group. The specific bond cleaved during this collapse (acyl C-O versus alkyl C-O) determines the distribution of atoms in the reaction products.

Transcript

00:02 Hi, so today we're going to be going over problem 24 out of chapter 17 in organic chemistry, fourth edition.

00:12 And this is going to be talking about the hydrolysis of esters.

00:17 So here i have this hydrolysis reaction set up.

00:24 So basically you have an ester in the presence of oh minus, and we're going to hydrolyze it and create carboxylic acid.

00:36 And there was some debate a while ago over which bond was broken.

00:41 So we either have our acil bond, acyl carbon oxygen bond that can be broken, or we can have this alcohol bond be broken.

00:56 And they didn't know which one.

00:58 There is one that we found out that is the one that is broken.

01:02 But we're going to try to figure out why.

01:07 And so this will create a carboxylic acid in its place.

01:18 And so if we wanted to figure out, so if we labeled this oxygen within the zester with oxygen 18, we need to figure out which product that would be in.

01:32 And that's probably how they answered this question.

01:37 But let's go through the mechanism.

01:39 So i'm going to label this oxygen in blue as oxygen.

01:45 18, it's radioactive, so kind of like a label to figure out which product it ends up in.

01:55 And we have our regular oxygen and our hydroxide.

01:58 The first step in carbonyl reactions, if you have an acid, we're going to go ahead and proteinate that carbonyl carbon, but we don't have an acid here.

02:09 And so we can go ahead and just attack that carbonyl carbon.

02:12 That carbonyl carbon is electrophilic, so that negative charge likes.

02:18 That partial positive charge.

02:22 And we'll make our tetrahedral intermediate, as we've seen in every other reaction so far, every other carbonyl reaction.

02:37 All right, and now we have this negative charge that we need to resolve.

02:41 And so we need to kick off a leaving group.

02:45 The thing is, it can kick off either of them...