amide n : any organic compound containing the group -CONH2

English

Noun

1. Any derivative of an oxoacid in which the hydroxyl group has been replaced with an amino or substituted amino group; especially such derivatives of a carboxylic acid, the carboxamides.
2. Any ionic derivative of ammonia in which a hydrogen atom has been replaced with a metal cation.

Translations

In chemistry, an amide is one of three kinds of compounds:

• (sometimes called acid amide) the organic functional group characterized by a carbonyl group (C=O) linked to a nitrogen atom (N), or a compound that contains this functional group (pictured to the right); or
• a particular kind of nitrogen anion.
• any organic compound derived by the replacement of a hydroxyl group by an amino group.

Amides are the most stable of all the carbonyl functional groups.

Many chemists make a pronunciation distinction between the two, saying ( for the carbonyl-nitrogen compound and /ˈæmɑɪd/ for the anion. Others substitute one of these pronunciations with /ˈæmɨd/, while still others pronounce both /ˈæmɨd/, making them homonyms.

In the first sense referred to above, an amide is an amine where one of the nitrogen substituents is an acyl group; it is generally represented by the formula: R1(CO)NR2R3 , where either or both R2 and R3 may be hydrogen. Specifically, an amide can also be regarded as a derivative of a carboxylic acid in which the hydroxyl group has been replaced by an amine or ammonia. Compounds in which a hydrogen atom on nitrogen from ammonia or an amine is replaced by a metal cation are also known as amides or azanides.

The second sense of the word amide is the amide anion, which is a deprotonated form of ammonia (NH3) or an amine. It is generally represented by the formula: [R1NR2]-, and is an extremely strong base, due to the extreme weakness of ammonia and its analogues as Brønsted acids.

The remainder of this article is about the carbonyl-nitrogen sense of amide. For examples of the anionic amide, see the articles Sodium amide and Lithium diisopropylamide.

Amide synthesis

• Amides are commonly formed from the reaction of a carboxylic acid with an amine. This is the reaction that forms peptide bonds between amino acids. These amides can participate in hydrogen bonding as hydrogen bond acceptors and donors, but do not ionize in aqueous solution, whereas their parent acids and amines are almost completely ionized in solution at neutral pH. Amide formation plays a role in the synthesis of some condensation polymers, such as nylon and Aramid (Twaron / Kevlar). In biochemistry peptides are synthesized in solid phase peptide synthesis. The Schotten-Baumann reaction describes the formation of amides from amines and acid chlorides.

• Cyclic amides are synthesized in the Beckmann rearrangement from oximes.

• Amides also form from ketones and hydrazoic acid in the Schmidt reaction
• Amides can be prepared from aryl alkyl ketones, sulfur and morpholine in the Willgerodt-Kindler reaction
• Other amide-forming multicomponent reactions are the Passerini reaction and the Ugi reaction

• In the Bodroux reaction an amide RNHCOR' is synthesized from a carboxylic acid R-COOH and the adduct of a Grignard reagent with an aniline derivative ArNHR'
• In the Chapman rearrangement (first reported in 1925) an aryl imino ether is converted to a N,N-diaryl amide:

The reaction mechanism is based on a nucleophilic aromatic substitution.

• The seemingly simple direct reaction between an alcohol and an amine to an amide was not tried until 2007 when a special ruthenium-based catalyst was reported be effective in a so-called dehydrogenative acylation :

The generation of hydrogen gas compensates for unfavorable the thermodynamics. The reaction is believed to proceed by one dehydrogenation of the alcohol to the aldehyde followed by formation of a hemiaminal and the after a second dehydrogenation to the amide. Elimination of water in the hemiaminal to the imine is not observed.

Amide reactions

• Amide breakdown is possible via amide hydrolysis. Such hydrolysis can occur under basic or acidic conditions. Acidic conditions yield the carboxylic acid and the ammonium ion while basic hydrolysis yield the carboxylate ion and ammonia.
• In the Vilsmeier-Haack reaction an amide is converted into an imine.
• Hofmann rearrangement of primary amides to primary amines.

Owing to their resonance stabilization, amides are relatively unreactive under physiological conditions, even less than similar compounds such as esters. Nevertheless, amides can undergo chemical reactions, usually through an attack of an electronegative atom on the carbonyl carbon, breaking the carbonyl double bond and forming a tetrahedral intermediate. When the functional group attacking the amide is a thiol, hydroxyl or amine, the resulting molecule may be called a cyclol or, more specifically, a thiacyclol, an oxacyclol or an azacyclol, respectively.

The proton of an amide does not dissociate readily under normal conditions; its pKa is usually well above 15. However, under extremely acidic conditions, the carbonyl oxygen can become protonated with a pKa of roughly -1.

Amides will react with nitrous acid (HONO) forming the carboxylic acid and yielding nitrogen. Nitrous acid is formed by addition of a strong acid to a nitrate (III) salt in solution at temperatures of between 0 and 10 degrees.

Amides undergo the Hofmann rearrangement in which an amine with one less carbon atom is produced upon reaction with bromine and sodium hydroxide. On the other hand, reacting the amide with the strong reducing agent lithium aluminium hydride yields an amine with the same number of carbon atoms.

Amides are dehydrated with phosphorus (V) oxide forming the nitrile. Care should be taken when performing such a reaction since phosphorus (V) oxide smoulders when in contact with organic matter.

Amide linkage (peptide bond)

An amide linkage is kinetically stable to hydrolysis. However, it can be hydrolysed in boiling alkali, as well as in strong acidic conditions. Amide linkages in a biochemical context are called peptide linkages. Amide linkages constitute a defining molecular feature of proteins, the secondary structure of which is due in part to the hydrogen bonding abilities of amides.

Amide properties

• Other examples: propan-1-amide, N,N-dimethylpropanamide, acrylamide
• For more detail see IUPAC nomenclature of organic chemistry - Amines and Amides

References

External links

• IUPAC Compendium of Chemical Terminology