We don’t expect you to be satisfi ed with the bland statement that tetrahedral intermediates are formed in these reactions: of course, you wonder how we know that this is true. The fi rst evidence for tetrahedral intermediates in the substitution reactions of carboxylic acid deriva-tives was provided by Bender in 1951. He made carboxylic acid derivatives RCOX that had been ‘labelled’ with an isotope of oxygen, 18O. This is a non-radioactive isotope that is detected by mass spectrometry. He then reacted these derivatives with water to make labelled carbox-ylic acids. By any reasonable mechanism, the products would have one 18O atom from the labelled starting material. Because the proton on a carboxylic acid migrates rapidly from one oxygen to another, both oxygens are labelled equally.

He then reacted these derivatives with insuffi cient water for complete consumption of the starting material. At the end of the reaction, he found that the proportion of labelled molecules in the remaining starting material had decreased significantly: in other words, it was no longer completely labelled with ¹⁸O; some contained ‘normal’ ¹⁶O. The formation of the tetrahedral intermediate would be as before but rapid proton transfer would also mean that the two oxygen atoms would be the same. Now you may see the next step in the argument.

This result cannot be explained by direct substitution of X by H₂O, but is consistent with the existence of an intermediate in which the unlabelled ¹⁶O and labelled ¹⁸O can ‘change places’. This intermediate is the tetrahedral intermediate for this reaction. Either isomer can lose X and, in each case, labelled carboxylic acid is formed.

But either tetrahedral intermediate could lose water instead. In one case (top line below) the original starting material is regenerated complete with label. But in the second case, labelled water is lost and unlabelled starting material is formed. This result would be difficult to explain without a tetrahedral intermediate with a lifetime long enough to allow for proton exchange. This ‘addition–elimination’ mechanism is now universally accepted.

مواضيع ذات صلة

Strength of nucleophile and leaving group ability are related and pKa is a guide to both

Factors other than leaving group ability can be important

Using base strength to predict the outcome of substitution reactions of carboxylic acid derivatives

Amines react with acyl chlorides to give amides

pKa is a useful guide to leaving group ability

?Why are the tetrahedral intermediates unstable

Acid chlorides and acid anhydrides react with alcohols to make esters

The product of nucleophilic addition to a carbonyl group is not always a stable compound

Oxidation of alcohols

?Secondary and tertiary alcohols: which organometallic, which aldehyde, which ketone

Making primary alcohols from organometallics and formaldehyde

Making carboxylic acids from organometallics and carbon dioxide