amide bond

Amide can also refer to a conjugate base of ammonia and an organic amine, represented as anions R₂N^–. For discussion of these "anionic amides," see the articles sodium amide and lithium diisopropilamide.

The simplest amides are derivatives of ammonia wherein one hydrogen atom has been replaced by an acyl group.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 amides (R'RNH) with the formula RC(O)NR'R. Amide are usually regarded as derivatives of carboxylic acid in which the hydroxil group has been replaced by an amine or ammonia.

Properties

Basicity

Compared to amines, amides are very weak bases. While the conjugate acid of an amines 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, esters, aldehyde, 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%. Resonance is largely prevented in the very strained quinuclidone.

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.

The proton of a primary or secondary amide does not dissociate readily under normal conditions; its pK_a is usually well above 15. Conversely, under extremely acidic conditions, the carbonyl oxygen can become protonated with a pK_a 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 specta. 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.

Applications and occurrence

Amides are pervasive in nature and technology as structural materials. The amide linkage is easily formed, confers structural rigidity, and resists hydrolisis. Nylons are polyamides as are the very resilient materials Aramid, Twaron, and Kevlar. Amide linkages in a biochemical context are called peptide linkage. 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. Low molecular weight amides, such as dimethylformamide (HC(O)N(CH₃)₂), are common solvents. Many drugs are amides, including penicilin and LSD.

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-bouman reaction, which involves conversion of the acid to the acid chlorides.