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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?

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    $\begingroup$ Bot the carbonyl and -OH [or -OR] are basic and will accept protons from a stronger acid. Both protonations are probably very rapid. The question is what can happen to the intermediate in either case. In this case either can give appropriate product from nucleophilic attack at the carbonyl carbon. The gem-diol intermediate is esthetically more pleasing and possibly of lower energy. $\endgroup$
    – jimchmst
    Jan 24 at 21:41

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I assume OP is wondering why always showing carbonyl carbon protonation instead hydroxyl carbon protonation in the mechanism of Fischer esterification. As I have mentioned this in another answer, those reactions are reversible and protonation happens in both oxygens. yet reaction would go through to give the thermodynamically most stable product, which in this case the final ester.

Then, why protonation go through carbonyl carbon? Carbonyl carbon of acid group is $\mathrm{sp^2}$ hybridized and hence, when oxygen is protonated, carbon is capable of stabilizing the positive charge on oxygen by resonance, although this act may migrate the positive charge to unfavorable carbon atom. Yet, since that same carbon (previously carbonyl carbon) already has another oxygen attached to it, which can stabilize the unfavorable positive charge on carbon by mesomeric effect (giving one of the lone pairs to make the third resonance). The higher the participation of the third resonance form (the higher the ability of $\ce{OH}$ group to release electrons), the more stable the protonated form of a carbonyl group (the larger the basicity of carbonyl group).

If the initial protonation has gone to the hydroxyl oxygen (instead of carbonyl oxygen), there is no way to stabilize the positive charge by any mesomeric effects (neither by first and second resonance). Thus, the protonated form is very unstable and reversed reaction (deprotonation) occurs very quickly. On the other hand, in a protonated carbonyl oxygen of a carboxylic acid, the first and third resonance forms are identical (both having $\ce{HO^+=C}$), which gives an extra stabilization ($\mathrm{p}K_\mathrm{a}$ of protonated acid is about $-6$).

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Your mentioned points are somewhat correct. Look in acidic medium electrophilicity of carbonyl increase, secondly nucleophile(like alcohol) get consume due to protonation. For the reaction to happen we maintain a particular particular pH(4.5-5) at which both factors are maintained so that not much consumption of electrophile takes place along with increase in electrophilicity of carbonyl.

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    $\begingroup$ This answer is poorly worded and not comprehensible. $\endgroup$
    – jimchmst
    Jan 24 at 21:27
  • $\begingroup$ I agree. All that I understood from it is that yes, the alcohol indeed gets protonated as well, just not in the same pH range, which is what I suspected. Still don't know the details. $\endgroup$ Jan 25 at 0:22

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