Saponification (ester hydrolysis)

                                                                                                                                                                                     (general reaction)

We saw esters can be handled quite easily in acid environment. It is indeed simple to turn one ester to another (transesterification) with an acid catalyst , or else have an acid-hydrolysis which gives back the constituents of the ester (carboxylic acid and alcohol).

While as soon as we get to a basic environment things change . When an ester face a strong base such as an hydroxyde , we're not going to get the products we would expect from an hydrolysis reaction.

Let's have a look to the step by step mechanism of this important reaction:


       (reaction mechanism)




First of all, as we expect, the hydroxyl ion(OH-) act as a nucleophile, the lone pair on oxygen through an addition reaction goes on the sp2 carbon of the esters, the acyl carbon. The reaction proceeds through a tetrahedral intermediate (N.B: the attack of a nucleophile over a carbonyl carbon (sp2)is never gonna give a nucleophilic substitution)


        (reaction mechanism)




The tetrahedral intermediate will then collapse to give again a carbonyl and the choice is between two leaving groups: the hydroxyl ion, OH- or the alkoxyde (isopropoxyde in the present example).

The alkoxyde  (RO-) and hydroxyl (OH-) ions are leaving groups who differs very slightly. This means that this two groups have more or less equally likely to be lost. If the hydroxyl is lost from the intermediate we're just getting back to the starting molecule. What is more interesting and what actually the overall direction of the generale reaction is the loss of the alkoxyde ion, as shown in the image above.

Here's what happens when the intermediate eject the alkoxyde:




          (reaction mechanism)







As you surely can see the reaction proceeds as a really simple acid-base reaction! Considered the product of the addition-elimination mechanism are an acid (carboxylic acid) and a base (isopropoxide, by the way very strong) the most logical development of the reaction is the exchange of a single proton from the acid to the base.

The reaction is irreversible because we just got a carboxylate (salt of a carboxylic acid), a very unreactive species, especially towards nucleophiles, and that is what moves the general reaction to the right, to the products.

That's why the carboxylate anion is stabilized by:

1. The negative charge (that makes the carbonyl not electrophilic)

2. Two resonance structures

Actually the molecule we took for this specific example is exceptionally stable given the conjugation at the same time with the arylic system.

Esters base-promoted hydrolysis can therefore be rather usefull to distill alcohols constituents ( in the present example isopropilic alcohol).