Amines, Amides and Amino Acids

Amines are organic compounds derived from ammonia, NH3, in which one or more of the hydrogen atoms have been replaced by an alkyl or aryl group. Because the nitrogen atom keeps a lone pair of electrons, amines share some of ammonia's chemistry, but the attached carbon groups change how basic and how reactive the compound is.

Amines are classified by how many carbon groups are attached to the nitrogen atom, not by the carbon skeleton itself:

• Primary amine: one carbon group attached to nitrogen, general formula R-NH2
• Secondary amine: two carbon groups attached to nitrogen, general formula R2NH
• Tertiary amine: three carbon groups attached to nitrogen, general formula R3N

The lone pair on the nitrogen atom can accept a proton, so amines behave as Brønsted–Lowry bases, forming an ammonium ion such as R-NH3+ when they react with an acid. Aliphatic amines are generally more basic than ammonia itself, because alkyl groups push electron density towards nitrogen through the inductive effect, making the lone pair more available to accept a proton.

Aromatic amines such as phenylamine are noticeably weaker bases than aliphatic amines. In phenylamine, the nitrogen lone pair overlaps with the delocalised electron system of the benzene ring, so it is less available for protonation. This delocalisation effect connects directly to the bonding you meet when studying the structure, bonding and reactions of benzene.

Several reaction types come up repeatedly when amine reactions are examined at A Level:

• Reaction with acids: the amine acts as a base and forms an ammonium salt, for example R-NH2 plus HCl gives R-NH3+Cl-.
• Reaction with haloalkanes: the amine acts as a nucleophile, attacking the carbon bonded to the halogen and displacing the halide ion to give a more highly substituted amine salt.
• Reaction with acyl chlorides: the amine's nitrogen attacks the carbonyl carbon of the acyl chloride, releasing HCl and forming an amide. This condensation reaction links amines directly to the chemistry of carboxylic acids, acyl chlorides and esters.

An amide contains the functional group -CO-NH-, where a carbonyl carbon is bonded directly to a nitrogen atom. Amides can be hydrolysed by breaking the carbon to nitrogen bond:

• Acid hydrolysis (heating with dilute aqueous acid) breaks the amide into a carboxylic acid and an ammonium salt.
• Base hydrolysis (heating with aqueous sodium hydroxide) breaks the amide into a carboxylate salt and an amine.

Because amines are the products of amide hydrolysis and the reactants that form amides with acyl chlorides, it helps to picture the amide link as a two-way relationship: amine plus acyl chloride forms the amide going one way, and water plus acid or base breaks it apart going the other way.

An alpha amino acid has both an amine group, NH2, and a carboxylic acid group, COOH, attached to the same carbon atom. Because one part of the molecule is basic and the other is acidic, an amino acid does not exist as a simple neutral molecule in solution. Instead, the carboxylic acid group loses a proton and the amine group gains one, producing a zwitterion, an ion that carries both a positive and a negative charge overall while remaining neutral.

Whether an amino acid exists mainly as the zwitterion, the fully protonated cation, or the fully deprotonated anion depends on the pH of the solution. The pH at which the zwitterion form dominates and the molecule carries no net charge is called the isoelectric point.

Most amino acids, other than glycine, have four different groups attached to the central carbon, which makes that carbon a chiral centre. This is exactly the situation explored in chirality and optical isomers, where you meet the two mirror-image forms an amino acid can take.

Two amino acids can join in a condensation reaction: the amine group of one molecule reacts with the carboxylic acid group of another, releasing a molecule of water and forming an amide link between them. This particular carbon to nitrogen amide bond, when it joins amino acids together, is called a peptide bond.

Repeating this condensation along a chain of amino acids builds up proteins, and the same amide-forming chemistry underlies the synthetic condensation polymers covered in polyesters and polyamides, where repeating amide links hold a polymer chain together instead of a biological chain.

Consider a primary amine, R-NH2, reacting first with an acyl chloride, and separately with dilute hydrochloric acid.

• With the acyl chloride R'-COCl, the nitrogen lone pair attacks the carbonyl carbon, HCl is eliminated, and the product is the amide R'-CO-NH-R.
• With dilute HCl, no bond to carbon is broken. The lone pair simply accepts a proton, giving the ammonium salt R-NH3+Cl-.

Spotting whether a reagent supplies a proton (acid-base behaviour) or a reactive carbonyl carbon (nucleophilic attack forming an amide) is the key skill for working through amine reaction questions.

Related lessons

• Uk A Level Chemistry