[Lo.Lee.Ta.]

How do I know if the nucleophile would attack the carbonyl carbon or deprotonate the alpha carbon?

Someone else has tried to ask this question on a different website, but I don't think the answer was satisfactory... :/
I would like to intuitively understand why something else is not the product instead.

It doesn't much sense to say that forming a hydrate, for instance, is not synthetically useful- and that's why it doesn't happen.


This is where the question was originally asked:
http://www.coursesaver.com/showthread.php?3890-How-do-I-know-if-the-nucleophile-would-attack-the-carbonyl-carbon-or-the-alpha-hydrogen


If I have a ketone + an OH-, it seems like either a hydrate or an enolate could result.

If I have a ketone + -OCH3, it seems like either an acetal or an enolate could result.

How am I supposed to know what happens in these situations...?

Thanks SO much!

[Dan]

It doesn't much sense to say that forming a hydrate, for instance, is not synthetically useful- and that's why it doesn't happen.

It's not that it doesn't happen, it does, the thing to understand is that it is reversible. If hydration is not a step in a pathway that leads to a stable product, then it is unproductive.

If you were to treat a ketone with Na¹⁸OD in D₂¹⁸O - i.e. aqueous sodium hydroxide with isotopically labelled O and H, you would see incorporation of ¹⁸O in the carbonyl (via hydration-dehydration) and D incorporation at the α-position (via deprotonation/deuteration).

If I have a ketone + an OH-, it seems like either a hydrate or an enolate could result.

Both occur, and both are reversible. The result of each will usually only be apparent if they are steps in productive pathways.

If I have a ketone + -OCH3, it seems like either an acetal or an enolate could result.

A hemiacetal, not an acetal. Again reversible. Non-cyclic hemiacetals are usually not stable enough to be isolated.

[sjb]

How do I know if the nucleophile would attack the carbonyl carbon or deprotonate the alpha carbon?

Also, somewhat linked, is there not a confusion here?

Deprotonation is related to acid-base behaviour, rather than nucleophilic behaviour. In many cases nucleophilicity is  linked to basic behaviour but not always.