The alkoxide formed by addition of a Grignard reagent to an aldehyde or ketone is stable, last ing long enough to be protonated on work-up in acid to give an alcohol as product.

Tetrahedral intermediates are similarly formed by addition of a nucleophile, say ethanol in base, to the carbonyl group of acetyl chloride, but these tetrahedral intermediates are unstable. Why are they unstable? The answer is to do with leaving group ability. Once the nucleophile has added to the carbonyl compound, the stability of the product (or tetrahedral intermediate) depends on how good the groups attached to the new tetrahedral carbon atom are at leaving with the negative charge. In order for the tetrahedral intermediate to collapse (and therefore be just an intermediate and not the final product) one of the groups has to be able to leave and carry off the negative charge from the alkoxide anion formed in the addition.

The most stable anion will be the best leaving group. There were three choices for the leaving group: Cl⁻, EtO⁻, or Me⁻. We can make MeLi but not Me− because it is very unstable so Me− must be a very bad leaving group. EtO⁻ is not so bad—alkoxide salts are stable, but they are still strong, reactive bases. But Cl⁻ is the best leaving group: Cl⁻ ions are perfectly stable and quite unreactive, and happily carry off the negative charge from the oxygen atom.

You probably eat several grams of Cl− every day but you would be unwise to eat EtO− or MeLi.

So neither of these reactions occurs:

مواضيع ذات صلة

Strength of nucleophile and leaving group ability are related and pKa is a guide to both

Factors other than leaving group ability can be important

Using base strength to predict the outcome of substitution reactions of carboxylic acid derivatives

Amines react with acyl chlorides to give amides

pKa is a useful guide to leaving group ability

?How do we know that the tetrahedral intermediate exists

Acid chlorides and acid anhydrides react with alcohols to make esters

The product of nucleophilic addition to a carbonyl group is not always a stable compound

Oxidation of alcohols

?Secondary and tertiary alcohols: which organometallic, which aldehyde, which ketone

Making primary alcohols from organometallics and formaldehyde

Making carboxylic acids from organometallics and carbon dioxide