Chemical Reactions: Alkylation, Acylation & Tests

Alkylation and Acylation

The amine nitrogen's lone pair makes it a good nucleophile, so amines react with electrophiles.

Alkylation: an amine reacts with an alkyl halide to give a higher amine, and with excess can go all the way to a quaternary ammonium salt (R$_4$N$^+$X$^-$). This is the same stepwise process as ammonolysis.

Acylation: 1° and 2° amines (which still have an N-H bond) react with acyl chlorides or anhydrides to give amides (the N-H is replaced by N-COR). The reaction is usually done in the presence of a base such as pyridine to remove the HCl formed.

C$_6$H$_5$NH$_2$ + CH$_3$COCl → C$_6$H$_5$NHCOCH$_3$ (acetanilide) + HCl

3° amines do NOT acylate because they have no N-H bond.

Key Point: amines are nucleophiles — they alkylate (→ higher amines/quaternary salts) and acylate (1°/2° + acyl chloride → amide). 3° amines can't acylate because they have no N-H bond.

Carbylamine and Hinsberg Tests

Carbylamine (isocyanide) test — for 1° amines only: a primary amine (aliphatic or aromatic) heated with chloroform (CHCl$_3$) and alcoholic KOH gives an isocyanide (carbylamine) with a very foul, offensive smell. 2° and 3° amines do not respond, so this is a clean test for a primary amine.

R-NH$_2$ + CHCl$_3$ + 3 KOH → R-N≡C (carbylamine, foul smell) + 3 KCl + 3 H$_2$O

Hinsberg test — distinguishes 1°, 2°, 3°: the amine is shaken with Hinsberg's reagent (benzenesulphonyl chloride, C$_6$H$_5$SO$_2$Cl) and then aqueous KOH:

• 1° amine → forms an N-substituted sulphonamide with an acidic N-H → soluble in KOH (clear solution).
• 2° amine → forms a sulphonamide with no N-H → insoluble (precipitate).
• 3° amine → has no N-H to react → no reaction (the amine stays as is).

Key Point: carbylamine (CHCl$_3$ + KOH, foul smell) → only 1° amines. Hinsberg (C$_6$H$_5$SO$_2$Cl): 1° → soluble, 2° → insoluble precipitate, 3° → no reaction.

Reaction with Nitrous Acid (HNO$_2$)

Nitrous acid (HNO$_2$, made in situ from NaNO$_2$ + dilute HCl) reacts differently with each class — a key way to tell amines apart:

• 1° aliphatic amine → forms an unstable diazonium salt that decomposes immediately, giving an alcohol + N$_2$ gas (brisk effervescence of nitrogen). R-NH$_2$ + HNO$_2$ → R-OH + N$_2$↑ + H$_2$O
• 1° aromatic amine → forms a stable at 0-5 °C diazonium salt at 273-278 K (the basis of all diazonium chemistry — next section). Ar-NH$_2$ + HNO$_2$ + HCl → Ar-N$_2^+$Cl$^-$ (at 0-5 °C)
• 2° amine (aliphatic or aromatic) → gives a yellow oily N-nitrosamine (R$_2$N-N=O).
• 3° amine → no useful reaction of this type (it has no N-H).

Key Point: with HNO$_2$ — 1° aliphatic → alcohol + N$_2$; 1° aromatic → cold-stable diazonium salt; 2° → N-nitrosamine; 3° → no characteristic reaction.

Solved Examples

Example 1: Acylation of aniline

Give the product when aniline reacts with acetyl chloride.

Solution: Acylation of the N-H gives the amide acetanilide (C$_6$H$_5$NHCOCH$_3$) + HCl.

Example 2: Carbylamine test

How would you confirm that an unknown is a primary amine?

Solution: Heat it with CHCl$_3$ and alcoholic KOH (carbylamine test). A foul, offensive smell of the isocyanide confirms a primary amine; 2° and 3° amines give no such smell.

Example 3: Hinsberg test results

In the Hinsberg test, what is observed for a 1°, a 2° and a 3° amine?

Solution: 1° → sulphonamide with an acidic N-H, soluble in KOH (clear solution); 2° → sulphonamide with no N-H, insoluble precipitate; 3° → no reaction (no N-H).

Example 4: 1° aliphatic amine + HNO$_2$

What happens when ethylamine is treated with nitrous acid?

Solution: It forms an unstable diazonium salt that decomposes to give ethanol + N$_2$ gas (brisk effervescence): C$_2$H$_5$NH$_2$ + HNO$_2$ → C$_2$H$_5$OH + N$_2$ + H$_2$O.

Example 5: 1° aromatic amine + HNO$_2$

What is formed when aniline is treated with NaNO$_2$/HCl at 273-278 K?

Solution: A cold-stable benzene diazonium chloride (C$_6$H$_5$N$_2^+$Cl$^-$) — the key intermediate for diazonium reactions.

Example 6: 2° amine + HNO$_2$

Give the product of dimethylamine with nitrous acid.

Solution: An N-nitrosamine: (CH$_3$)$_2$N-N=O (N-nitrosodimethylamine), a yellow oily liquid.

Example 7: Why 3° amines don't acylate

Why does trimethylamine not form an amide with acetyl chloride?

Solution: Acylation replaces an N-H bond with N-COR. A 3° amine has no N-H bond, so there is nothing to replace and no amide forms.

Example 8: Quaternary salt

What forms when trimethylamine reacts with excess methyl iodide?

Solution: A quaternary ammonium salt, tetramethylammonium iodide (CH$_3$)$_4$N$^+$I$^-$ (the lone pair is fully alkylated).

Example 9: Distinguish a 1° from a 3° amine

Which single test distinguishes a primary amine from a tertiary amine?

Solution: The carbylamine test — the primary amine gives a foul-smelling isocyanide with CHCl$_3$/KOH; the tertiary amine does not react. The Hinsberg test also distinguishes them.

Example 10: Identify by HNO$_2$ behaviour

An aliphatic amine gives brisk effervescence of N$_2$ with nitrous acid. What class is it?

Solution: A primary aliphatic amine — only it forms the unstable diazonium salt that decomposes to an alcohol and releases N$_2$ gas.