An amide, also known as an acid amide, is a compound with the functional group RnE(O)xNR'2.
Most common are "organic amides", but many other important types of amides are known
including phosphor amides and sulfonamides. The term amide refers both to classes of compounds
and to the functional groupxNR'2) within those compounds.
Amide can also refer to the conjugate base of ammonia or of an organic amine. For discussion
of these "anionic amides", see Metal amides#Alkali metal amides.
The remainder of this article is about the carbonyl-nitrogen sense of amide.
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wherein one hydrogen atom has been replaced by an acyl group.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 with the formula RC(O)NHR'. Amides are also commonly derived from secondary
amines 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acids in which the hydroxyl group has been replaced by an amine or ammonia.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%.
Laurenceamide Nomenclature
In the usual nomenclature, one adds the term "amide" to the stem of the parent acid's name.
For instance, the amide derived from acetic acid is named acetamide. 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.
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 relative 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. It is estimated
in silico that acetamide is represented by resonance structure A for 62% and by B for
28%. Resonance is largely prevented in the very strained quinuclidone.
Because of the greater electronegativity of oxygen, the carbonyl is a stronger dipole
than the N–C dipole. The presence of a C=O dipole and, to a lesser extent a N–C dipole,
allows amides to act as H-bond acceptors. In primary and secondary amides, the presence
of N–H dipoles allows amides to function as H-bond donors as well. Thus amides can
participate in hydrogen bonding with water and other protic solvents; the oxygen atom
can accept hydrogen bonds from water and the N–H hydrogen atoms can donate H-bonds. As
a result of interactions such as these, the water solubility of amides is greater than
that of corresponding hydrocarbons. The proton of a primary or secondary amide
does not dissociate readily under normal conditions; its pKa is usually well above 15. Conversely,
under extremely acidic conditions, the carbonyl oxygen can become protonated with a pKa of
roughly −1. Solubility
The solubilities of amides and esters are roughly comparable. Typically amides are less
soluble than comparable amines and carboxylic acids since these compounds can both donate
and accept hydrogen bonds. Tertiary amides, with the important exception of N,N-dimethylformamide,
exhibit low solubility in water. Characterization
The presence of the functional group is generally easily established, at least in small molecules.
They are the most common non-basic functional group. They can be distinguished from nitro
and cyano groups by their IR spectra. Amides exhibit a moderately intense νCO band near
1650 cm−1. By 1H NMR spectroscopy, CONHR signals occur at low fields. In X-ray crystallography,
the C(O)N center together with the three immediately adjacent atoms characteristically define a
plane. Applications and occurrence
Amides are pervasive in nature and technology as structural materials. The amide linkage
is easily formed, confers structural rigidity, and resists hydrolysis. Nylons are polyamides,
as are the very resilient materials Aramid, Twaron, and Kevlar. 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 linkages in a biochemical context
are called peptide bonds when they occur in the main chain of a protein and isopeptide
bonds when they occur to a side-chain of the protein. Proteins can have structural roles,
such as in hair or spider silk, but also nearly all enzymes are proteins. Low molecular weight
amides, such as dimethylformamideN(CH3)2), are common solvents. Many drugs are amides,
including penicillin and LSD. Moreover, plant N-alkylamides have a wide range of biological
functionalities. Amide synthesis
Amides are commonly formed via reactions of a carboxylic acid with an amine. Many methods
are known for driving the unfavorable equilibrium to the right:
RCO2H + R'R"NH RC(O)NR'R" + H2O For the most part, these reactions involve
"activating" the carboxylic acid and the best known method, the Schotten-Baumann reaction,
which involves conversion of the acid to the acid chlorides:
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. See also
Metal amides References
External links Amide synthesis – Synthetic protocols from
organic-reaction.com IUPAC Compendium of Chemical Terminology