In
organic chemistry, an amide, also known as an organic amide or a carboxamide, is a
compound with the general formula , where R, R', and R″ represent
organic
Organic may refer to:
* Organic, of or relating to an organism, a living entity
* Organic, of or relating to an anatomical organ
Chemistry
* Organic matter, matter that has come from a once-living organism, is capable of decay or is the product ...
groups
A group is a number of persons or things that are located, gathered, or classed together.
Groups of people
* Cultural group, a group whose members share the same cultural identity
* Ethnic group, a group whose members share the same ethnic ide ...
or
hydrogen
Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-to ...
atoms. The amide group is called a
peptide bond when it is part of the
main chain of a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
, and an
isopeptide bond when it occurs in a
side chain, such as in the
amino acids asparagine
Asparagine (symbol Asn or N) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the depro ...
and
glutamine. It can be viewed as a
derivative of a
carboxylic acid () with the
hydroxyl group () replaced by an
amine group (); or, equivalently, an
acyl (alkanoyl) group () joined to an amine group.
Common examples of amides are
acetamide (),
benzamide (), and
dimethylformamide ().
Amides are qualified as primary, secondary, and tertiary according to whether the amine subgroup has the form , , or , where R and R' are groups other than hydrogen.
The core of amides is called the amide group (specifically, carboxamide group).
Amides are pervasive in nature and technology.
Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s and important
plastic
Plastics are a wide range of synthetic or semi-synthetic materials that use polymers as a main ingredient. Their plasticity makes it possible for plastics to be moulded, extruded or pressed into solid objects of various shapes. This adapta ...
s like
Nylons,
Aramid,
Twaron, and
Kevlar are
polymers whose units are connected by amide groups (
polyamides); these linkages are easily formed, confer structural rigidity, and resist
hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolysi ...
. Amides include many other important biological compounds, as well as many
drugs like
paracetamol,
penicillin and
LSD. Low-molecular-weight amides, such as dimethylformamide, are common solvents.
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 (CH
3CONH
2). IUPAC recommends
ethanamide, but this and related formal names are rarely encountered. When the amide is derived from a primary or secondary amine, the substituents on nitrogen are indicated first in the name. Thus, the amide formed from
dimethylamine
Dimethylamine is an organic compound with the formula (CH3)2NH. This secondary amine is a colorless, flammable gas with an ammonia-like odor. Dimethylamine is commonly encountered commercially as a solution in water at concentrations up to arou ...
and
acetic acid is ''N'',''N''-dimethylacetamide (CH
3CONMe
2, where Me = CH
3). Usually even this name is simplified to
dimethylacetamide. Cyclic amides are called
lactams; they are necessarily secondary or tertiary amides.
Applications
Amides are prevalent throughout the natural and engineered world. Most biological macromolecules consist of
peptides linked together through amide bonds; some man-made polymers adopt the same strategy.
Properties
Bonding
The lone pair of
electrons on the nitrogen atom is delocalized into the carbonyl group, thus forming a partial
double bond between nitrogen and carbon. In fact the O, C and N atoms have
molecular orbital
In chemistry, a molecular orbital is a mathematical function describing the location and wave-like behavior of an electron in a molecule. This function can be used to calculate chemical and physical properties such as the probability of find ...
s occupied by
delocalized electrons, forming a
conjugated system. Consequently, the three bonds of the nitrogen in amides is not pyramidal (as in the amines) but planar. This planar restriction prevents rotations about the N linkage and thus has important consequences for the mechanical properties of bulk material of such molecules, and also for the configurational properties of macromolecules built by such bonds. The inability to rotate distinguishes amide groups from ester groups which allow rotation and thus create more flexible bulk material.
The structure of an amide can be described also as a
resonance between two alternative structures:
:
It is estimated that for
acetamide, structure A makes a 62% contribution to the structure, while structure B makes a 28% contribution. (These figures do not sum to 100% because there are additional less-important resonance forms that are not depicted above). There is also a hydrogen bond present between the active groups hydrogen and nitrogen atoms.
Resonance is largely prevented in the very strained
quinuclidone.
Basicity
Compared to
amines, amides are very weak
bases. While the
conjugate acid of an
amine has a
p''K''a of about 9.5, the
conjugate acid of an amide has a p''K''
a around −0.5. Therefore, amides don't have as clearly noticeable
acid–base properties in
water
Water (chemical formula ) is an inorganic, transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living organisms (in which it acts as ...
. This relative lack of basicity is explained by the withdrawing of electrons from the amine by the carbonyl. On the other hand, amides are much stronger
bases than
carboxylic acids,
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...
s,
aldehydes, and
ketones (their conjugate acids' p''K''
as are between −6 and −10).
The proton of a primary or secondary amide does not dissociate readily under normal conditions; its p''K''
a is usually well above 15. Conversely, under extremely acidic conditions, the carbonyl
oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements ...
can become protonated with a p''K''
a of roughly −1. It is not only because of the positive charge on the nitrogen, but also because of the negative charge on the oxygen gained through resonance.
Hydrogen bonding and solubility
Because of the greater electronegativity of oxygen, the carbonyl (C=O) 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. These hydrogen bonds are also have an important role in the
secondary structure of proteins.
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 amide group –C(=O)N– is generally easily established, at least in small molecules. It can be distinguished from nitro and cyano groups in
IR spectra. Amides exhibit a moderately intense ''ν''
CO 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.
Reactions
:
Amides undergo many chemical reactions, although they are less reactive than esters. Amides hydrolyse 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. The protonation of the initially generated amine under acidic conditions and the deprotonation of the initially generated carboxylic acid under basic conditions render these processes non-catalytic and irreversible. Amides are also versatile precursors to many other
functional groups. Electrophiles react with the
carbonyl oxygen. This step often precedes hydrolysis, which is catalyzed by both
Brønsted acids and
Lewis acids. Enzymes, e.g.
peptidases and artificial catalysts, are known to accelerate the hydrolysis reactions.
Synthesis
Many methods exist in amide synthesis.
Amides can be prepared by coupling
carboxylic acid with an
amine. The direct reaction generally requires high temperatures to drive off the water:
:
R^1 CO2H + R^2 R^3 NH -> R^2 R^3 NH2+R^1 CO2-
:
R^2 R^3 NH2+R^1 CO2- -> R^1 C(O)NR^2 R^3 + H2O
Many methods involve "activating" the carboxylic acid by converting it to a better
electrophile; such as
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...
s,
acid chlorides (
Schotten-Baumann reaction), or
anhydrides (
Lumière–Barbier method).
Conventional methods in
peptide synthesis use coupling agents such as
HATU,
HOBt
Hydroxybenzotriazole (abbreviated HOBt) is an organic compound that is a derivative of benzotriazole. It is a white crystalline powder, which as a commercial product contains some water (~11.7% wt as the HOBt monohydrate crystal). Anhydrous HOBt ...
, or
PyBOP.
A variety of reagents, e.g.
Tris(2,2,2-trifluoroethyl) borate have been developed for specialized applications.
Other methods
Dehydrogenative acylation of amines is catalyzed by
organoruthenium compound Organoruthenium chemistry is the chemistry of organometallic compounds containing a carbon to ruthenium chemical bond. Several organoruthenium catalysts are of commercial interest and organoruthenium compounds have been considered for cancer therapy ...
s:
:
The reaction proceed by one dehydrogenation of the alcohol to the
aldehyde followed by formation of a
hemiaminal
In organic chemistry, a hemiaminal (also carbinolamine) is a functional group or type of chemical compound that has a hydroxyl group and an amine attached to the same carbon atom: . R can be hydrogen or an alkyl group. Hemiaminals are interm ...
, which undergoes a second dehydrogenation to the amide. Elimination of water in the hemiaminal to the imine is not observed.
Transamidation is typically very slow, but it is accelerated with
Lewis acid and
organometallic catalysts:
:
RC(O)NR'_2 + HNR''_2 -> RC(O)NR''_2 + HNR'_2
Primary amides () are more amenable to this reaction.
See also
*
Amidogen
*
Amino radical
*
Amidicity
*
Metal amides
References
External links
IUPAC Compendium of Chemical Terminology
{{Authority control
Functional groups