Amide

spread over the O, C and N atoms, consisting of molecular orbitals occupied by delocalized electrons. One of the π molecular orbitals in formamide is shown above.]] In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group (R-C=O) linked to a nitrogen atom (N). The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia (NH₃) or an amine, often represented as anions R₂N^-. The remainder of this article is about the carbonyl-nitrogen sense of amide. For discussion of these "anionic amides," see the articles sodium amide and lithium diisopropylamide.

Structure and Bonding

The simplest amides are derivatives of ammonia wherein one hydrogen atom has been replaced by an acyl group. The ensemble is generally represented as RC(O)NH₂. Closely related and even more numerous are amides derived from primary amines (R'NH₂) with the formula RC(O)NHR'. Amides are also commonly derived from secondary amines (R'RNH) with the formula RC(O)NR'R. Amide are usually regarded as derivatives of carboxylic acids in which the hydroxyl group has been replaced by an amine or ammonia. : The lone pair of electrons on the nitrogen is delocalized into the carbonyl, thus forming a partial double bond between N and the carbonyl carbon. Consequently the nitrogen in amides is not pyramidal. It is estimated that acetamide is described by resonance structure A for 62% and by B for 28%

Nomenclature

In the usual nomenclature, one adds the term "amide" to the stem of the parent acid's name. Thus, the simplest amide derived from acetic acid is named acetamide (CH₃CONH₂). IUPAC recommends ethanamide, but this and related formal names are rarely encountered. When the amide is derived from a primary or secondary amine, the substitutents on nitrogen are indicated first in the name. Thus the amide formed from dimethylamine and acetic acid is N,N-dimethylacetamide (CH₃CONMe₂, where Me = CH₃). Usually even this name is simplified to dimethylacetamide. Cyclic amides are called lactams; they are necessarily secondary or tertiary amides. Functional groups consisting of -P(O)NR₂ and -SO₂NR₂ are phosphonamides and sulfonamides, respectively.

Pronunciation

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

Properties

Basicity

Compared to amines, amides are very weak bases. While the conjugate acid of an amine has a pKa of about 9.5, the conjugate acid of an amide has a pKa around -0.5. Therefore amides don't have as clearly noticeable acid-base properties in water. This lack of basicity is explained by the electron-withdrawing nature of the carbonyl group where the lone pair of electrons on the nitrogen is delocalized by resonance. On the other hand, amides are much stronger bases than carboxylic acids, esters, aldehydes, and ketones (conjugated acid pKa between -6 and -10). It is estimated in silico that acetamide is represented by resonance structure A for 62% and by B for 28%. |carboxylic acid, Grignard reagent with an aniline derivative ArNHR' | |- |Chapman rearrangement |aryl imino ether |for N,N-diaryl amides. The reaction mechanism is based on a nucleophilic aromatic substitution. |- | Leuckart amide synthesis | isocyanate | Reaction of arene with isocyanate catalysed by aluminium trichloride, formation of aromatic amide. |- |}

Other methods

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 to be effective in a so-called dehydrogenative acylation: : :The generation of hydrogen gas compensates for unfavorable 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 == Amides undergo many chemical reactions, usually through an attack on the carbonyl breaking the carbonyl double bond and forming a tetrahedral intermediate. Thiols, hydroxyls and amines are all known to serve as nucleophiles. Owing to their resonance stabilization, amides are less reactive under physiological conditions than esters. Enzymes, e.g. peptidases or artificial catalysts, are known to accelerate the hydrolysis reactions. They can be hydrolysed in hot alkali, as well as in strong acidic conditions. Acidic conditions yield the carboxylic acid and the ammonium ion while basic hydrolysis yield the carboxylate ion and ammonia. Amides are also versatile precursors to many other functional groups.

{| class="wikitable sortable" style="background-color:white;float: center; border-collapse: collapse; margin: 0em 1em;" border="1" cellpadding="2" cellspacing="0"

! width=200px|Reaction name !! Product !! class="unsortable" | Comment |- |valign=top | dehydration |valign=top|nitrile | reagent: phosphorus pentoxide |- |valign=top| Hofmann rearrangement |valign=top|amine with one fewer carbon atoms |reagents: bromine and sodium hydroxide |- |valign=top| amide reduction |valign=top| amine |reagent: lithium aluminium hydride |- |Vilsmeier-Haack reaction |imine | POCl₃, aromatic substrate, formamide |- |}

References

External links

Amide synthesis (coupling reaction) - Synthetic protocols from organic-reaction.com

IUPAC Compendium of Chemical Terminology

Category:Functional groups