Amide

An amide, also called an organic amide or carboxamide, has the general formula R−C(=O)−NR′R″, where R, R′, and R″ can be various groups, often organyl groups or hydrogen atoms. This functional group is essential in biology, where it forms peptide bonds that connect amino acids into proteins.

Amides can be thought of as derivatives of carboxylic acids, with the hydroxyl group (−OH) replaced by an amino group (−NR′R″), or as an acyl group (R−C(=O)−) bonded to an amino group. Common examples include formamide, acetamide, benzamide, and dimethylformamide. They are classified as primary, secondary, or tertiary based on how many acyl groups are attached to the nitrogen atom.

The core −C(=O)−(N) is called the amide group (specifically carboxamide). In standard naming, “amide” is added to the stem of the parent acid’s name—for instance, acetic acid gives acetamide (IUPAC name ethanamide, though rarely used). If derived from a primary or secondary amine, the nitrogen substituents are listed first, as in N,N-dimethylacetamide (often shortened to dimethylacetamide). Cyclic amides are called lactams and are always secondary or tertiary.

Amides are widespread in nature and technology. Proteins and plastics like nylons, aramids, Twaron, and Kevlar are polyamides—polymers linked by amide groups. These bonds are easy to form, provide structural rigidity, and resist hydrolysis. Many biological compounds and drugs, such as paracetamol, penicillin, and LSD, contain amides. Low-molecular-weight amides like dimethylformamide are common solvents.

Structurally, the lone pair on nitrogen delocalizes into the carbonyl group, creating a partial double bond between nitrogen and carbon. The oxygen, carbon, and nitrogen atoms form a conjugated system with delocalized electrons. This makes the nitrogen’s three bonds planar, not pyramidal as in amines. This planarity prevents rotation around the N linkage, affecting the mechanical properties of bulk materials and the configuration of macromolecules. The C-C(O)NR2 core is planar, with the C=O bond about 10% shorter than the C-N bond. The structure can be described as a resonance between a neutral form (A) and a zwitterionic form (B). For acetamide, structure A contributes about 62% and structure B about 28% (other minor forms account for the rest). In highly strained molecules like quinuclidone, resonance is largely prevented. In infrared spectra, amides show a moderately intense νCO band near 1650 cm⁻¹, about 60 cm⁻¹ lower than in esters and ketones, reflecting the zwitterionic contribution.

Amides are very weak bases compared to amines. The conjugate acid of an amide has a pKa around −0.5, while that of an amine is about 9.5, so amides show little acid–base behavior in water. This low basicity comes from the carbonyl withdrawing electrons from the amine. However, amides are much stronger bases than carboxylic acids, esters, aldehydes, and ketones (whose conjugate acids have pKas between −6 and −10). The proton of a primary or secondary amide does not dissociate easily, with a pKa usually above 15. Under very acidic conditions, the carbonyl oxygen can be protonated with a pKa around −1, due to both the positive charge on nitrogen and the negative charge on oxygen from resonance.

Because oxygen is more electronegative than nitrogen, the carbonyl (C=O) dipole is stronger than the N–C dipole. This allows amides to act as hydrogen-bond acceptors. Primary and secondary amides also have N–H dipoles, making them hydrogen-bond donors. Thus, amides can form hydrogen bonds with water and other protic solvents: oxygen accepts hydrogen bonds, and N–H hydrogens donate them. This makes amides more water-soluble than comparable hydrocarbons. These hydrogen bonds are also crucial for protein secondary structure. Amides and esters have roughly similar solubilities, but amides are generally less soluble than comparable amines and carboxylic acids, which can both donate and accept hydrogen bonds. Tertiary amides, except for N,N-dimethylformamide, have low water solubility.

Amides do not easily undergo nucleophilic substitution. They are stable in water and about 100 times more resistant to hydrolysis than esters. However, they can be hydrolyzed to carboxylic acids with acid or base. The stability of the amide bond has biological significance.