Amino acids, amides and chirality — OCR A-Level Chemistry

An amino acid carries both an amine group and a carboxylic acid group on the same molecule, so it shows the reactions of each functional group and some combined behaviour. The carboxylic acid group reacts with bases and carbonates to form salts, with alcohols in esterification, and with amines to form amides. The amine group behaves as a base, accepting a proton to form a salt with acids, and reacts with acyl chlorides to form amides. Because the two groups can react with each other, an amino acid exists mainly as a zwitterion, with a protonated ammonium group and a deprotonated carboxylate group. In acidic solution the carboxylate is protonated to give a cation; in alkaline solution the ammonium group is deprotonated to give an anion. A carbon bearing four different groups gives chirality, which matters for the α-carbon of most amino acids.

An α-amino acid carries two functional groups on the same carbon, the α-carbon: an amine group (NH₂) and a carboxylic acid group (COOH), with a side chain R and one hydrogen also attached. Its general formula is written RCH(NH₂)COOH, which shows the α-carbon bonded to R, H, NH₂ and COOH. The R group varies between amino acids, so glycine has R = H while other amino acids carry different side chains. Because the α-carbon has four different groups when R is not H, the molecule is chiral and can exist as two optical isomers. Recognise the formula in displayed and condensed forms, and identify the amine and carboxylic acid groups so you can predict reactions such as salt formation with acids and alkalis, ester formation and condensation polymerisation to peptides.

The COOH group of an amino acid behaves like any carboxylic acid. With an alkali such as sodium hydroxide it is neutralised to give a carboxylate salt and water: RCH(NH₂)COOH + NaOH → RCH(NH₂)COONa + H₂O. The amine group may also react with acid, so an amino acid can form salts with both acids and alkalis depending on conditions. With an alcohol and an acid catalyst the carboxylic acid group undergoes esterification to give an ester and water, for example RCH(NH₂)COOH + R'OH ⇌ RCH(NH₂)COOR' + H₂O. Recognise the reagents, the products and the balanced equation, and note that the ester link forms between the carboxyl carbon and the alcohol oxygen.

Amino acids contain both a basic amine group (–NH₂) and an acidic carboxyl group (–COOH). The lone pair on the nitrogen of the amine group accepts a proton from an acid, so the amine behaves as a Brønsted–Lowry base and is protonated to form an ammonium-type cation, –NH₃⁺. With a strong mineral acid such as HCl, the –NH₂ group becomes –NH₃⁺ and a chloride salt forms; the carboxyl group is left unchanged by this reaction. The product is described as the hydrochloride of the amino acid, and the reaction is a simple acid–base neutralisation. Recognise that the amine group, not the carboxyl group, is the site of protonation, and that the resulting species carries a positive charge on nitrogen.

An amide contains a carbonyl group (C=O) directly bonded to a nitrogen atom, giving the functional group –CONH₂ in a primary amide. The lone pair on the amide nitrogen is delocalised into the carbonyl group, so an amide is much less basic than an amine and does not readily accept a proton in the same way. Amides are formed when a carboxylic acid derivative such as an acyl chloride or acid anhydride reacts with ammonia or an amine, and they can be hydrolysed by heating with aqueous acid or alkali to release the carboxylic acid (or its salt) and ammonia or an amine. Recognise the –CONH– linkage, distinguish it from an amine, and link the structure to its lower basicity and its hydrolysis products.

An amide contains a carbonyl group, C=O, bonded directly to a nitrogen atom, giving the functional group –CONH–. In a primary amide the nitrogen is bonded to the carbonyl carbon, to two hydrogen atoms and to one carbon-containing group, written RCONH₂. In a secondary amide the nitrogen is bonded to the carbonyl carbon, to one hydrogen atom and to two carbon-containing groups, written RCONHR′. When classifying, count every group bonded to the nitrogen: the carbonyl carbon counts as one of those groups because it is directly attached to nitrogen. So RCONH₂ is primary and RCONHR′ is secondary. The R and R′ groups may be alkyl or aryl.

A chiral carbon is an sp³ carbon bonded to four different groups, so the molecule and its mirror image cannot be superimposed. In 2-hydroxypropanoic acid the central carbon carries –H, –CH₃, –OH and –COOH, four different groups, so it is chiral. In amino acids such as 2-aminopropanoic acid the alpha carbon carries –H, –NH₂, –CH₃ and –COOH, again four different groups. To test a candidate carbon, list all four substituents and check none repeats; a carbon with two identical groups, such as two hydrogens, is not chiral. Chiral molecules rotate plane-polarised light and exist as two enantiomers, but a 50:50 mixture is optically inactive.

Optical isomerism is one branch of stereoisomerism, the family of isomers that share the same structural formula but differ in the spatial arrangement of atoms. Two optical isomers, called enantiomers, are related as non-superimposable mirror images. The feature that produces them is a chiral centre: typically a carbon atom bonded to four different groups, so that reflection cannot be rotated onto the original. Take butan-2-ol, CH₃CH(OH)CH₂CH₃; the central carbon carries H, OH, CH₃ and C₂H₅, all different, so two enantiomers exist. Amino acids such as alanine show the same feature at the carbon bearing NH₂, COOH, H and CH₃. Enantiomers have identical physical properties except the direction they rotate plane-polarised light, and they differ in behaviour towards other chiral species.

To find a chiral centre, examine each carbon atom in turn and list the four groups attached to it. A chiral centre is a carbon bonded to four different groups; if any two groups match, that carbon is not chiral. Work through a molecule systematically: in 2-chlorobutane, CH₃CHClCH₂CH₃, the carbon bearing chlorine also carries H, CH₃ and C₂H₅, so it is chiral. In 2-chloropropane, CH₃CHClCH₃, the same carbon carries two identical CH₃ groups, so it is not chiral. Remember that carbon atoms in a C=C double bond or a C≡C triple bond cannot be chiral centres because they do not carry four separate groups. Apply the same test to any organic compound, including amino acids, alcohols and halogenoalkanes.