Acid Halides

Acid halides are the most reactive acyl derivatives, and can be readily converted into carboxylic acids, esters and amides, by simple reaction with the appropriate nucleophile. The reaction involves an addition-elimination mechanism, as shown below:

Reaction of acid halides with Grignard reagents, or reduction with LiAlH₄, leads to the incorporation of two moles of Grignard (or hydride), in a mechanism which involves an intermediate aldehyde or ketone, as shown below for hydride reduction.

When a bulky reducing agent, such as lithium tri-tert-butoxylaluminum hydride is utilized, the reduction or acyl halides can be stopped at the intermediate aldehyde.

Partial alkylation can be achieved with acyl halides by reaction with a dialkylcopper lithium reagent, at low temperatures. This reaction is also useful for a-b-unsaturated aldehydes and ketones since conjugate addition of the alkyl group does not occur at the low temperatures utilized.

Acid Anhydrides

Acid halides are the next most reactive acyl derivatives, and can be readily converted into carboxylic acids, esters and amides, by simple reaction with the appropriate nucleophile. The reaction involves an addition-elimination mechanism, as shown below:

As with acid halides, reduction of anhydrides with LiAlH₄ results in the addition of two moles of hydride, forming the primary alcohol.

Carboxylic Esters

Carboxylate esters can be readily converted into carboxylic acids and amides, by simple reaction with the appropriate nucleophile. The reaction involves an addition-elimination mechanism, as shown below:

Reaction of esters with Grignard reagents, or reduction with LiAlH₄, leads to the incorporation of two moles of Grignard (or hydride), in a mechanism which involves an intermediate aldehyde or ketone, as shown below for hydride reduction.

Amides

Amides are relatively unreactive in acyl transfer reactions, largely because the electrons from the adjacent nitrogen participate in resonance delocalization with the adjacent carbonyl, making the carbonyl carbon significantly less electropositive.

Amides undergo acid-catalyzed hydrolysis to give carboxylic acids by the addition-elimination mechanism shown below:

Unsubstituted amides also undergo dehydration in the presence of SOCl₂ to give the corresponding nitrile.

Nitriles

Nitriles can be hydrolyzed carboxylic acids, converted into ketones by reaction with Grignard reagents, reduced to primary amines with LiAlH₄ and partially reduced to aldehydes using DIBAH (diisobutylaluminum hydride). The reaction with Grignard reagent is typical of these latter reactions and involves nucleophilic attack on the nitrile carbon to give an anionic intermediate which is resistant to further attack, and undergoes hydrolysis to give a ketone, as shown below.