12.5 Amines: Basicity, Synthesis, Reactions, and Arenediazonium Chemistry

12.5 Amines: Basicity, Synthesis, Reactions, and Arenediazonium Chemistry

Quick Answer: Amines are one of the functional groups the TOS names explicitly under Organic area C, the largest Organic area at 25 items. Expect basicity rankings, the best way to make a primary amine, the Hinsberg and nitrous-acid tests, Hofmann elimination regiochemistry, and multi-step aromatic syntheses that run through arenediazonium salts.

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Classification, Naming, and Structure

Amines are classified by the number of carbon groups on nitrogen: primary ($RNH_2$), secondary ($R_2NH$), tertiary ($R_3N$), and quaternary ammonium salts ($R_4N^+X^-$). This differs from alcohols, where classification follows the carbon bearing the OH group: tert-butylamine is a primary amine.

IUPAC names use the suffix -amine (propan-1-amine, $N$-methylethanamine, $N,N$-dimethylaniline). When a higher-priority group is present, use the prefix amino- (4-aminobenzoic acid).

Nitrogen is roughly $sp^3$ and pyramidal, with C-N-C angles near 108 degrees. Amines with three different groups are chiral in principle, but nitrogen inversion (barrier about 25 kJ/mol) interconverts the enantiomers rapidly at room temperature, so they cannot be resolved. Quaternary ammonium salts with four different groups have no lone pair to invert and can be resolved.

Primary and secondary amines hydrogen-bond, so they boil higher than tertiary amines of similar mass but lower than alcohols, because N-H bonds are less polar than O-H.

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Basicity

Compare amines by the $pK_a$ of the conjugate acid ($pK_{aH}$): a higher $pK_{aH}$ means a stronger base.

Rules of thumb:

• In the gas phase basicity is $3^\circ > 2^\circ > 1^\circ > NH_3$; in water, solvation reorders the methylamines to $2^\circ > 1^\circ > 3^\circ > NH_3$.
• Electron-donating ring substituents (4-methyl, 4-methoxy) raise aniline's basicity; withdrawing groups (4-nitro, 4-cyano) lower it.
• Quaternary ammonium hydroxides such as $(CH_3)_4N^+OH^-$ are strong bases, as strong as NaOH.

Basicity enables acid-base extraction: shaking an ether solution with dilute HCl moves an amine into water as its ammonium salt, and adding NaOH frees it again.

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Synthesis of Amines

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Reactions of Amines

• Acylation: primary and secondary amines react with acid chlorides or anhydrides to give amides. Acetylating aniline to acetanilide tames its very strong ring activation, which allows clean para monobromination; hydrolysis then frees the amine.
• Hinsberg test with benzenesulfonyl chloride and aqueous KOH:
  • Primary amine: the sulfonamide $RNHSO_2Ph$ still has an acidic N-H, so it dissolves in base and precipitates on acidification.
  • Secondary amine: $R_2NSO_2Ph$ has no N-H and precipitates from the basic solution.
  • Tertiary amine: no stable sulfonamide forms; the amine stays insoluble in base but dissolves in acid.
• Carbylamine (isocyanide) test: only primary amines react with $CHCl_3$ and KOH, giving foul-smelling isocyanides.
• Hofmann elimination: exhaustive methylation with excess $CH_3I$, then $Ag_2O$/$H_2O$ and heat, eliminates $(CH_3)_3N$. The bulky leaving group gives the less substituted alkene (Hofmann product): the 2-butyltrimethylammonium ion gives mainly but-1-ene. Section 12.1 contrasts this with Zaitsev elimination.

Nitrous Acid ($NaNO_2$ + HCl, 0-5 C)

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Arenediazonium Chemistry

The $N_2$ group is an excellent leaving group, so arenediazonium salts give access to substitution patterns that electrophilic aromatic substitution cannot make directly.

Worked synthesis: 1,3,5-tribromobenzene from aniline.

1. $Br_2$/$H_2O$ adds three bromines ortho and para to the strongly activating $NH_2$, giving 2,4,6-tribromoaniline.
2. $NaNO_2$/HCl at 0-5 C converts the amine to the diazonium salt.
3. $H_3PO_2$ replaces $N_2^+$ with H, leaving the three bromines in a meta relationship that direct bromination of benzene could never produce.