Acid hydrolysis of lactones?

Question

What is the mechanism for the acid hydrolysis of lactones?

Answer 1

Acid hydrolysis of lactones is essentially the same as acid hydrolysis of a normal ester (and most carboxylic acid derivatives):

1) acid (H₃O⁺) comes and protonates the carbonyl oxygen,

2) an H₂O molecule attacks the carbonyl carbon, and the electrons from the C=O double bond move onto the (positively charged) oxygen,

3) another H₂O molecule comes in to deprotonate the H₂O attached to the carbon,

[now we have the same lactone as before, but the carbonyl turned into two OH groups; if you've heard someone talk about/say "tetrahedral intermediate", this is what they're referring to]

4) now acid comes again to protonate the oxygen that's in the ring,

5) a lone pair from one of the OH groups comes down and reforms the C=O double bond and the oxygen from step 4 leaves,

[now the ring is broken and we're one step away from the final product]

finally 6) H₂O comes in and removes the H from the carbonyl oxygen.

Ta-da! You've broken the lactone ring and turned it into an alcohol and a carboxylic acid!

Answer 2

Hi Kayley C.,

In general, it's Aac2, with simultaneous attack on the acyl oxygen by one water molecule and donation of a H+ to the leaving ester oxygen by another, linked water molecule. But there may be simultaneous contribution by the Aac1 pathway, for hindered, or highly strained sites, and so on. If you have ACS journal access, you may read more at https://pubs.acs.org/doi/full/10.1021/jo4002596 . Incidentally, reaction-order-kinetic studies help to show how many molecules are involved in the transition state, a very useful thing to know!

-- Cheers, -- Mr. d.