9.2 Basicity and Chemical Reactions of Amines

• Inductive effect. Alkyl groups release electrons ($+I$). They push electron density onto nitrogen, making the lone pair more available, and they stabilise the positive charge of the ammonium ion. On this count basicity should rise with the number of alkyl groups: $\mathrm{3°\gt2°\gt1°\gt NH_{3}}$. This is exactly the order found in the gas phase, where nothing else acts.
• Solvation. In water the ammonium ion is stabilised by hydrogen bonds from its N–H hydrogens to water. $\mathrm{RNH_{3}^{+}}$ has three such hydrogens, $\mathrm{R_{2}NH_{2}^{+}}$ two and $\mathrm{R_{3}NH^{+}}$ only one, so solvation favours $\mathrm{1°\gt2°\gt3°}$.
• Steric hindrance. Bulky groups crowd the nitrogen and hinder both the approach of the proton and the solvating water molecules.

The balance of these effects gives, in water: for methyl groups $\mathrm{(CH_{3})_{2}NH\gt CH_{3}NH_{2}\gt(CH_{3})_{3}N\gt NH_{3}}$; for ethyl groups $\mathrm{(C_{2}H_{5})_{2}NH\gt(C_{2}H_{5})_{3}N\gt C_{2}H_{5}NH_{2}\gt NH_{3}}$. Every alkylamine is a stronger base than ammonia.

In aniline the lone pair on nitrogen is in conjugation with the benzene ring and is delocalised over it: five resonance structures can be drawn, three of which put a negative charge on the ortho and para carbons and a positive charge on N. Protonation uses up the lone pair, so the anilinium ion, $\mathrm{C_{6}H_{5}NH_{3}^{+}}$, has only the two Kekulé structures. Aniline is therefore more stabilised by resonance than its cation, and gives up its lone pair reluctantly: $\mathrm{p}K_{b}=9.38$, against $4.75$ for ammonia. The $sp^{2}$ ring carbon also withdraws electrons ($-I$).

Substituents on the ring: electron-releasing groups such as $\mathrm{{-}CH_{3}}$ and $\mathrm{{-}OCH_{3}}$ increase the basic strength; electron-withdrawing groups such as $\mathrm{{-}NO_{2}}$, $\mathrm{{-}Cl}$, $\mathrm{{-}COOH}$ and $\mathrm{{-}SO_{3}H}$ decrease it, most strongly from the para (and ortho) positions, where $\mathrm{{-}NO_{2}}$ can take part in the resonance. A $\mathrm{CH_{2}}$ between the ring and N stops the conjugation: phenylmethanamine ($\mathrm{p}K_{b}=4.70$) is about as basic as ammonia.

Alkylation. Amines, like ammonia, attack haloalkanes (nucleophilic substitution), each step adding one alkyl group to N; with excess haloalkane the reaction runs on to the quaternary ammonium salt:

Acylation. Primary and secondary amines react with acid chlorides, acid anhydrides and esters: the H on nitrogen is replaced by an acyl group $\mathrm{RCO{-}}$, giving an amide. A base stronger than the amine, such as pyridine, is added to remove the HCl formed, which would otherwise protonate the unreacted amine and stop it reacting:

The products are $N$-ethylethanamide and $N$-phenylethanamide (acetanilide). Reaction with benzoyl chloride, $\mathrm{C_{6}H_{5}COCl}$, is called benzoylation: $\mathrm{CH_{3}NH_{2}}$ gives $N$-methylbenzamide, $\mathrm{C_{6}H_{5}CONHCH_{3}}$. Tertiary amines have no N–H and are not acylated.

Nitrous acid is unstable, so it is made in the reaction mixture from sodium nitrite and a mineral acid: $\mathrm{NaNO_{2}+HCl\rightarrow HNO_{2}+NaCl}$. The three classes of amine react with it in different ways. For primary amines:

(a) Primary aliphatic amines form aliphatic diazonium salts, which are unstable even in the cold: they decompose at once, giving an alcohol and a brisk effervescence of nitrogen.

The nitrogen is given off quantitatively, so measuring its volume is used to estimate amino acids and proteins.

(b) Primary aromatic amines react at low temperature ($273\text{–}278\ \mathrm{K}$) to give arenediazonium salts, which are stable enough to be used in solution (Section 9.3):

(a) Bromination. Aniline decolourises bromine water at room temperature and at once gives a white precipitate of 2,4,6-tribromoaniline: all three activated positions are substituted.

Protection by acetylation. To make a monosubstituted product, the activating effect is reduced by first converting $\mathrm{{-}NH_{2}}$ into the acetamido group, $\mathrm{{-}NHCOCH_{3}}$. Its nitrogen lone pair is shared with the neighbouring carbonyl oxygen as well as the ring, so it activates less; it is still ortho/para directing, and because it is bulky the para product dominates. Afterwards the amide is hydrolysed to give back $\mathrm{{-}NH_{2}}$:

(b) Nitration. Direct nitration of aniline is unsatisfactory: nitric acid oxidises much of it to tarry products, and in the strongly acidic mixture most of the aniline is protonated to the anilinium ion, $\mathrm{C_{6}H_{5}NH_{3}^{+}}$, which has no lone pair and is meta-directing and deactivating. A mixture results: roughly 51% 4-nitroaniline, 47% 3-nitroaniline and 2% 2-nitroaniline. Protecting the amino group as acetanilide first gives mainly 4-nitroacetanilide, which is hydrolysed to 4-nitroaniline.

(c) Sulphonation. Aniline with concentrated sulphuric acid forms anilinium hydrogensulphate; heated at $453\text{–}473\ \mathrm{K}$ this gives 4-aminobenzenesulphonic acid (sulphanilic acid) as the main product. It exists as a dipolar ion (zwitterion), $\mathrm{{}^{+}H_{3}N{-}C_{6}H_{4}{-}SO_{3}^{-}}$.

(d) No Friedel–Crafts reaction. Aniline is a Lewis base and forms a salt with the Lewis acid catalyst $\mathrm{AlCl_{3}}$. Nitrogen then carries a positive charge, which strongly deactivates the ring, so aniline does not undergo Friedel–Crafts alkylation or acylation.