Chemical Reactions of Amines

Full Notes

Basic Character of Amines

Amines can behave as Lewis bases and accept a H⁺ ion because of the lone pair on nitrogen.

Basicity Equilibrium in Water:
R–NH₂ + H₂O ⇌ R–NH₃⁺ + OH⁻

This equilibrium allows us to define base strength in terms of an equilibrium constant, K_b:

Smaller pK_b = Stronger base

Key Observations

• pK_b of ammonia = 4.75
• Aliphatic amines are generally stronger bases than ammonia because:
  • Alkyl groups have a positive inductive, +I effect (electron donating), increasing electron density on nitrogen
  • This enhances the ability of nitrogen to donate a lone pair

Effect of Solvation (in Aqueous Solution)

In aqueous solution, solvation stabilizes substituted ammonium ions:

• Primary amines form more hydrogen bonds than secondary or tertiary
• Thus, order of stability by solvation: 1° > 2° > 3°
• Therefore, in aqueous solution: Greater solvation = More stable ammonium ion = Stronger base
• Order of stability due to solvation: Primary > Secondary > Tertiary

Trends in Basicity

In Gas Phase basicity is based only on the positive inductive effect (+I). Meaning the greater the positive inductive effect, the stronger the base.

Also, Tertiary amine > Secondary > Primary Ammonia

Note that in Aqueous Solution (based on positive inductive, +I effect and solvation) the order is different: Primary > Secondary > Tertiary > Ammonia

For Example:

• (C₂H₅)₃N is a stronger base than (C₂H₅)₂NH

Aromatic Amines vs Ammonia

In aromatic amines, the lone pair on nitrogen is delocalized into the aromatic ring via resonance.

• This makes the lone pair less available for protonation (as a result, phenylamine (aniline) is less basic than ammonia).

Substituent Effects on Basicity

• Electron-donating groups (EDGs) like –CH₃, –OCH₃ increase basicity
• Electron-withdrawing groups (EWGs) like –NO₂, –COOH, –SO₃H decrease basicity

Alkylation

Amines act as nucleophiles and react with alkyl halides in nucleophilic substitution reactions. Please see class 12 section 6 for more information.

Reaction: R–NH₂ + R′–X → R–NHR′ → R–NR′₂ → R₄N⁺X⁻ (quaternary salt)

Note: All types of amines can undergo successive alkylation leading to a mixture. Control is difficult.

Acylation

Aliphatic and aromatic primary and secondary amines react with acid chlorides, anhydrides, or esters via nucleophilic substitution. This reaction is called acylation.

• In acylation, the hydrogen atom of the amine group is replaced by an acyl group
• The resulting products are called amides
• A base (e.g. pyridine) is used in the reaction to neutralise HCl, pushing the reaction forward

Amines undergo a reaction with benzoyl chloride (C₆H₅COCl), a process known as benzoylation.

Note: Tertiary amines do not undergo acylation due to the absence of an N–H bond.

Carbylamine Reaction

When aliphatic and aromatic amines are heated with trichloromethane (chloroform) and potassium hydroxide (in ethanol), they form carbylamines (isocyanides).

This is a specific test for primary amines, with the carbylamines having a foul-smell.

Reaction: R–NH₂ + CHCl₃ + 3KOH → R–NC + 3KCl + 3H₂O

Reaction with Nitrous Acid

Amines react with nitrous acid (prepared in situ from NaNO₂ and an inorganic acid) differently, depending the class of amine.

Primary aliphatic amines:

• React with nitrous acid to form unstable diazonium salts.
• These decompose to release nitrogen gas and form alcohols.
• Quantitative nitrogen evolution is useful for amino acid and protein analysis.

General reaction: R–NH₂ + HNO₂ + HCl → [R–N₂]⁺Cl⁻ → ROH + N₂ + HCl

Aromatic amines:

• React at low temperature (273–278 K) to form stable diazonium salts.
• These are key intermediates in aromatic synthesis.

Example: C₆H₅–NH₂ + NaNO₂ + 2HCl → C₆H₅–N₂⁺Cl⁻ + NaCl + 2H₂O

Secondary and tertiary amines:

React in different ways to the above, often giving N-nitroso compounds or no reaction.

Reaction with Arylsulphonyl Chloride (Hinsberg Test)

Benzenesulphonyl chloride (C₆H₅SO₂Cl) reacts differently with primary, secondary, and tertiary amines. This enables us to determine the classification of an unknown amine.

With primary amines:

• Forms sulphonamides (e.g., N-ethylbenzenesulphonamide).
• Product is soluble in alkali due to acidic NH group.

C₆H₅SO₂Cl + H₂N–C₂H₅ → C₆H₅SO₂–NH–C₂H₅ + HCl

With secondary amines:

• Forms N,N-disubstituted sulphonamides.
• These are not soluble in alkali (no acidic H).

C₆H₅SO₂Cl + HN(C₂H₅)₂ → C₆H₅SO₂–N(C₂H₅)₂ + HCl

Tertiary amines:

Do not react with benzenesulphonyl chloride.

Electrophilic Substitution in Aromatic Amines

Aromatic amines can undergo electrophilic substitution.

Bromination:

C₆H₅NH₂ + 3Br₂ → C₆H₂Br₃NH₂ + 3HBr

The –NH₂ group activates the benzene ring, making it highly reactive towards electrophilic substitution, and directs incoming groups to the ortho (2) and para (4) positions.

To control this high reactivity the –NH₂ group can first be converted into the electron-withdrawing –NHCOCH₃ group (via acetylation). After the desired substitution, this protecting group can be hydrolysed back to regenerate the –NH₂ group.

NH₂–C₆H₅ → CH₃CONH–C₆H₅ → Br–CH₃CONH–C₆H₄ → Br–C₆H₄–NH₂

Nitration:

Direct nitration yields mainly para (4th position) and meta (3rd position) products due to formation of an anilinium ion which is meta directing.

To improve selectivity, we can:

• Protect –NH₂ as acetanilide.
• Nitrate and then hydrolyse to p-nitroaniline.

Sulphonation:

• Aniline + conc. H₂SO₄ forms anilinium hydrogen sulphate.
• On heating (453–473 K) this then forms sulphanilic acid (p-aminobenzenesulphonic acid)
• Sulphanilic acid exists as a zwitterion

Note: Aniline does not undergo Friedel–Crafts reactions due to salt formation with AlCl₃ catalyst.

Summary

• Amines are basic due to a nitrogen lone pair and their strength depends on structure and solvation.
• Primary amines show the carbylamine test and undergo diazotisation under appropriate conditions.
• Amines undergo alkylation and acylation while tertiary amines do not acylate.
• Primary aliphatic amines with nitrous acid give alcohols with nitrogen gas evolution.
• Aromatic amines form stable diazonium salts at low temperature.
• Aniline is ortho and para directing and often needs protection to control substitution.