which of the following works best as a base to quantitatively convert ethyl acetate, CH3CO2CH2CH3, to its enol

Question

which of the following works best as a base to quantitatively convert ethyl acetate, CH3CO2CH2CH3, to its enolate?

1) NaOH
2) KOC(CH3)3
3) CH3Li
4) [ (CH3)2CH]2NLi

Answer 1

The pKa of an alpha hydrogen to an ester is around 25, so you need something more basic (higher pka) to deprotonate it.

1) NaOH = pKa of 16
2) tert-butoxide = pka of 18
3) Methyl lithium = pka of 60
4) Lithium Diisopropylamine (LDA) = pka of 36

I like to use Robert Grossman's "Rule of 5", which is that something will deprotonate something if it's 5 pKa units less. This is from "The Art of Writing Reasonable Organic Reaction Mechanisms". Based on that, 1 and 2 cannot be expected to deprotonate the ester.

3 and 4 will both quantitatively convert the ester to an enolate. I'd probably use 4 in the lab

Answer 2

Ethyl Acetate Pka

Answer 3

No 2 is most effective. It's a very strong base.