In Chapter 18 we introduced the enolates of aldehydes and ketones (review) and looked at their reactions as C nucleophiles (review).  These enolates were formed by treating the aldehyde or ketone with a suitable base :

Now we will investigate another group of carbonyl containing compounds, the esters, which behave in a very similar fashion.....

This avoids problems caused by transesterification (conversion of one ester into another)......

Note that in both cases the problem arises because the base reacts as a "nucleophile"

• The most common bases for preparing enolates are shown below:

• General points to remember:
• Hydroxide will cause hydrolysis of esters
• Alkoxide basses should match the alcohol part of an ester to avoid transesterification
• NaH and LDA are usually used in tetrahydrofuran (THF) as the solvent (like many organometallic reagents)
• NaH and LDA are strong bases.
• Important things about LDA:
• Strong base but poor nucleophile (too sterically hindered)
• LDA is very good for making enolates of esters, aldehydes and ketones since it can give essentially 100% (quantitative conversion) to the enolate
• This allows the enolate to be alkylated or acylated with less chance of self-condensation reactions.

• In some molecules there are H atoms that are adjacent to 2 carbonyl groups (which are electron withdrawing).
• Extra resonance stabilization of the enolate anion makes these H more acidic (i.e. lower pKa) than hydrogens adjacent to a single carbonyl group.
• These type of compounds are sometimes called "active methylenes"  (recall a methylene group is a CH₂)

Highlight acidic H	Highlight acidic H	Highlight acidic H

As we will see later is this Chapter, these compounds are useful synthetic intermediates.
Their enolates can be formed readily and can be alkylated, then further manipulated.

Acidity of a-Hydrogens

• In the following table, the acidity of the H for various enolate systems and other closely related systems are given.
• You should be able to justify the trends in this data !

Why are the protons adjacent to carbonyl groups acidic?
As we have advocated before, look at the stabilization of the conjugate base.
Notice the proximity of the adjacent p system, and hence the possibility for RESONANCE stabilization by delocalization of the negative charge to the more electronegative oxygen atom.

The more effective the resonance stabilization of the negative charge, the more stable the conjugate base is and therefore the more acidic the parent system.

Let's compare pKa of the common systems: aldehyde pKa = 17, ketone pKa = 19 and an ester pKa = 25, and try to justify the trend.

H atoms are regarded as having no electronic effect : they don't withdraw or donate electrons.

Alkyl groups are weakly electron donating, they tend to destabilize anions (you should recall that they stabilize carbocations).
This is because they will be "pushing" electrons towards a negative system which is unfavorable electrostatically.
Hence, the anion of a ketone where there are extra alkyl groups is less stable than that of an aldehyde, and so, a ketone is less acidic.