Amines

The One Thing

Amines act as bases because the nitrogen lone pair accepts a proton; their basicity depends on how available that lone pair is, which is influenced by inductive, resonance, solvation and steric effects. Gabriel phthalimide synthesis prepares primary aliphatic amines, while diazotization converts primary aromatic amines into versatile diazonium intermediates.

Reactions, Processes and Experiments

Key Terms

• Amine: An organic compound derived from ammonia by replacing one or more hydrogen atoms with alkyl or aryl groups.
• Primary amine: An amine in which nitrogen is attached to one carbon-containing group, represented as RNH2.
• Secondary amine: An amine in which nitrogen is attached to two carbon-containing groups, represented as R2NH.
• Tertiary amine: An amine in which nitrogen is attached to three carbon-containing groups, represented as R3N.
• Basicity of amines: The ability of an amine to accept a proton using the lone pair of electrons on nitrogen.
• Lewis base: A species that donates an electron pair; amines act as Lewis bases because nitrogen has a lone pair.
• Brønsted base: A species that accepts a proton; amines form substituted ammonium ions on protonation.
• Aliphatic amine: An amine in which nitrogen is attached to an alkyl group, such as methylamine or ethylamine.
• Aromatic amine: An amine in which nitrogen is directly attached to an aromatic ring, such as aniline.
• Aniline: The aromatic primary amine C6H5NH2; it is less basic than ammonia because the nitrogen lone pair is delocalized into the benzene ring.
• Inductive effect: Electron-releasing alkyl groups increase electron density on nitrogen and generally increase amine basicity, whereas electron-withdrawing groups decrease it.
• Resonance effect: Delocalisation of the nitrogen lone pair reduces its availability for protonation, as observed in aniline and amides.
• Solvation effect: In aqueous solution, stronger solvation of the protonated amine can increase its apparent basicity.
• Gabriel phthalimide synthesis: A method for preparing primary aliphatic amines by reacting potassium phthalimide with an alkyl halide followed by hydrolysis or hydrazinolysis.
• Potassium phthalimide: The nucleophilic reagent formed by treating phthalimide with potassium hydroxide; it attacks suitable alkyl halides by an SN2 mechanism.
• Diazotization: The conversion of a primary aromatic amine into an aromatic diazonium salt using sodium nitrite and a mineral acid at 273–278 K.
• Diazonium salt: A compound containing the functional group Ar-N2+, usually isolated as a salt such as benzenediazonium chloride.
• Azo coupling: A reaction in which a diazonium salt couples with an activated aromatic compound to form a brightly coloured azo compound.

Easily Confused

• Primary, secondary and tertiary amines: These are classified by whether nitrogen is attached to one, two or three carbon-containing groups: RNH2, R2NH and R3N, respectively.
• Gas-phase and aqueous basicity: In the gas phase, basicity generally follows (CH3)3N > (CH3)2NH > CH3NH2 > NH3; in aqueous solution, the usual order for simple methylamines is (CH3)2NH > CH3NH2 > (CH3)3N > NH3 because solvation and steric effects also affect protonated-ion stability.
• Aniline and aliphatic amines: Aniline is less basic than ammonia because its nitrogen lone pair is delocalized into the benzene ring; aliphatic amines are affected mainly by inductive and solvation effects.
• Amines and amides: Amides are much less basic than amines because the nitrogen lone pair is strongly delocalized toward the carbonyl group.
• Gabriel synthesis and aryl-amine preparation: Gabriel synthesis is suitable for primary aliphatic amines but generally does not prepare primary aryl amines because aryl halides do not readily undergo the required SN2 substitution.
• Sandmeyer and Gattermann reactions: Sandmeyer reactions use copper(I) salts such as CuCl, CuBr or CuCN, whereas the Gattermann reaction uses copper powder and the corresponding hydrogen halide.
• Diazotization and azo coupling: Diazotization forms a diazonium salt from a primary aromatic amine; azo coupling uses that diazonium salt to form a brightly coloured azo compound.
• Carbylamine and Hinsberg tests: The carbylamine test is positive only for primary amines and produces an unpleasant-smelling isocyanide, whereas the Hinsberg test distinguishes primary, secondary and tertiary amines using benzenesulfonyl chloride and alkali.

What Gets Asked

• Questions may require the general formulas of primary, secondary and tertiary amines: RNH2, R2NH and R3N. A common mark-losing error is assigning the classes according to the number of hydrogen atoms rather than the number of carbon-containing groups attached to nitrogen.
• Basicity-order questions may distinguish the gas phase from aqueous solution. The gas-phase order is (CH3)3N > (CH3)2NH > CH3NH2 > NH3, whereas the usual aqueous order is (CH3)2NH > CH3NH2 > (CH3)3N > NH3; omitting solvation and steric effects loses the relevant explanation.
• Explanations of aniline’s lower basicity must state that the nitrogen lone pair is delocalized into the benzene ring. Merely stating that aniline contains an aromatic ring is insufficient.
• Gabriel synthesis questions may require the sequence phthalimide + KOH → potassium phthalimide, reaction with R-X by SN2 substitution, and subsequent hydrolysis or hydrazinolysis to give RNH2. The key limitation is that the method is generally unsuitable for primary aryl amines and for substrates that do not undergo the required SN2 reaction.
• Diazotization questions may require the equation ArNH2 + NaNO2 + 2HCl → ArN2+Cl− + NaCl + 2H2O, the in situ formation of nitrous acid through NaNO2 + HCl → HNO2 + NaCl, and the temperature range 273–278 K. Failure to specify the ice-cold acidic conditions is a significant omission.
• Reaction-identification questions may test diazonium-salt transformations, including Sandmeyer, Gattermann, Balz–Schiemann, hydrolysis, reduction and azo coupling. The reagent or medium must be matched to the product: for example, copper(I) salts in Sandmeyer reactions, copper powder with hydrogen halide in the Gattermann reaction, warm water for phenol formation, and mildly alkaline or mildly acidic conditions for azo coupling with phenol or aniline, respectively.