Amide

(CC) Image: Bob Mellish
two simple organic amides.

This article is about the acid derivatives. There are also ionic amides, which are very strong bases and the nitrogen equivalents of hydroxide, with the general formula R₂N^-(where R refers to hydrogen or any alkyl group). These are the conjugate bases of amines, and have pK_aHs around 35.

In general, an amide is derived from an oxoacid (an acid containing a central atom double bonded to at least one oxygen atom and singly bonded to at least one OH group) by replacing the OH group(s) with NR₂ - for instance, a sulfonic acid gives a sulfonamide. The most important amides are organic amides, derived from carboxylic acids. While these appear to contain a carbonyl bonded to an amine, their reactivity is very different from either of those two functional groups, due to resonance delocalisation of the nitrogen's lone pair into the carbonyl system. This makes the carbonyl less reactive than most carboxylic acid derivatives in electrophilic substitution reactions, and makes the nitrogen much less nucleophilic than it is in amines. In those reactions where amines do react as nucleophiles, they react through the oxygen instead of the nitrogen. It also lends partial double bond character to the carbonyl-nitrogen bond, limiting rotation around it. These reactivity patterns are true of amides derived from other acids as well.

Organic amides are important biologically, because proteins are made of amino acids held together by amide groups. An amide formed from two amino acids is the basis for the biochemical term, peptide bond. Sulfonamides are sometimes biologically active-many drug molecules (including the sulfa drugs, the first synthetic antibiotics), contain a sulfonamide group, and hexamethylphosphoramide (HMPA), the tri-amide of phosphoric acid, is sometimes used as an organic solvent.

Synthesis

• Reaction of most other carboxylic acid derivatives with ammonia, a primary amine, or a secondary amine will give an amide. By using derivatives of other acids [such as sulfuric], their amides can be obtained
• Organic amides may be formed by hydrolysing nitriles

Reactivity

• Concentrated acid or base will hydrolyse amides to their parent acids.
• Organic amides can be dehydrated to nitriles.
• Lithium aluminium hydride will reduce organic amides to amines
• The Hofmann rearrangement will convert an organic amide without alkyl groups on the nitrogen to an amine with one fewer carbon atom