Question

When studying acid-catalyzed nucleophilic attack of alcohol on carbonyl, I got puzzled by the first protonation step. In textbooks, they often show that the first step is to protonate the carbonyl oxygen by the acid to make the carbonyl carbon into a better electrophile, so that even a weak nucleophile such as the alcohol's oxygen could attack it. But why isn't that alcohol's oxygen getting protonaded by the acid instead? After all, it has a lone pair too, it is capable then of grabbing a proton if someone wants to get rid of it (and the acid certainly does). But if the alcohol's oxygen got protonated, it would get positively charged, which would undermine its ability to act as a nucleophile! So why is it that the acid protonates the carbonyl oxygen instead of the alcohol oxygen?

My guess is that this might have something to do with pKas, or perhaps with the fact that the alcohol's oxygen atom already has one proton on it. But I haven't seen any notions of pKa involved when these reaction mechanisms are described in textbooks. Am I on the right track?

Answer 1

In the acid-catalyzed nucleophilic attack of alcohol on carbonyl, the first step involves protonating the carbonyl oxygen by the acid to enhance the electrophilicity of the carbonyl carbon. Protonating the alcohol's oxygen would render it less effective as a nucleophile. Therefore, protonating the carbonyl oxygen ensures that the alcohol's oxygen remains a nucleophile.

Step-by-step explanation:

The first step in the acid-catalyzed nucleophilic attack of alcohol on carbonyl involves the protonation of the carbonyl oxygen by the acid. The purpose of this step is to make the carbonyl carbon a better electrophile, which allows a weaker nucleophile like the alcohol's oxygen to attack it.

The alcohol's oxygen is not protonated because it would become positively charged, which would reduce its ability to act as a nucleophile. Protonating the carbonyl oxygen instead ensures that the alcohol's oxygen remains a nucleophile.