Why Stale Fish Smells the Way It Does

The smell of stale fish, many medicines and the dyes in coloured clothes all involve amines — compounds formed when hydrogens of ammonia are replaced by carbon groups. Their nitrogen lone pair makes them bases and nucleophiles.

This part covers the structure and naming of amines, general preparation methods, selective routes to primary amines, and physical properties.

**Amines are derivatives of ammonia with a pyramidal nitrogen carrying a lone pair; replacing one, two or three hydrogens of NH${}_3$ gives primary, secondary and tertiary amines, which IUPAC names by replacing the final -e of the alkane with -amine.

Structure.** Nitrogen is $s{p}^3$ hybridised: three orbitals form bonds and the fourth holds the lone pair, which squeezes the bond angle in trimethylamine to about $108^{\circ }$.

Classification:

- Primary — RNH${}_2$
- Secondary — R${}_2$NH
- Tertiary — R${}_3$N
- Aryl amines — nitrogen bonded to a benzene ring, as in aniline

Naming:

- CH${}_3$NH${}_2$ — methylamine; IUPAC methanamine
- CH${}_3$CH${}_2$NHCH${}_3$ — ethylmethylamine; N-methylethanamine
- (CH${}_3$)${}_3$N — trimethylamine; N,N-dimethylmethanamine
- C${}_6$H${}_5$NH${}_2$ — aniline; benzenamine

Worked example. (CH${}_3$)${}_2$CHNH${}_2$ has one carbon group on nitrogen, so it is a primary amine even though that carbon is secondary. Its name is propan-2-amine.

An everyday example. The smell of fish that is no longer fresh comes largely from trimethylamine.

The substance. Amine classes count carbon groups on nitrogen — propan-2-amine is primary, while propan-2-ol is a secondary alcohol.

Reducing nitro compounds, nitriles or amides gives amines, while heating an alkyl halide with ammonia gives a mixture of primary, secondary and tertiary amines and a quaternary salt, because each amine formed is itself a nucleophile that attacks more alkyl halide.

Reduction routes:

- Nitro compounds — H${}_2$ with Ni, Pd or Pt, or iron scrap with HCl; nitrobenzene gives aniline. Iron with HCl is preferred, because the FeCl${}_2$ formed is hydrolysed and releases HCl, so little acid is needed
- Nitriles — LiAlH${}_4$ or H${}_2$/Ni gives RCH${}_2$NH${}_2$, adding one carbon to the chain
- Amides — LiAlH${}_4$ gives amines with the same number of carbons

Ammonolysis:

$$\text{RX}\stackrel{{\text{NH}}_3}{\to }{\text{RNH}}_2\stackrel{\text{RX}}{\to }{\text{R}}_2\text{NH}\stackrel{\text{RX}}{\to }{\text{R}}_3\text{N}\stackrel{\text{RX}}{\to }{\text{R}}_4{\text{N}}^{+}{\text{X}}^{-}$$

A large excess of ammonia favours the primary amine, but separating the mixture is still difficult.

Worked example. Reducing $12.3$ g of nitrobenzene ($M=123$ g mol${}^{-1}$) gives at most

$$\frac{12.3}{123}=0.100\text{ mol},0.100\times 93=9.3\text{ g of aniline}$$

An everyday example. Aniline made by reducing nitrobenzene is the starting point for many dyes used on cotton fabrics.

The substance. Nitrile reduction lengthens the chain by one carbon, while amide reduction keeps it the same — a handy way to plan a synthesis.

**Gabriel synthesis alkylates potassium phthalimide, whose nitrogen can take only one alkyl group, and then hydrolyses the product to release a pure primary amine; Hoffmann bromamide degradation treats an amide with Br${}_2$ and NaOH to give a primary amine with one carbon fewer.

Gabriel phthalimide synthesis:

- Phthalimide with ethanolic KOH gives potassium phthalimide
- Heating with an alkyl halide gives N-alkylphthalimide
- Alkaline hydrolysis releases the primary amine

Why it fails for aromatic amines. Aryl halides do not undergo nucleophilic substitution with the phthalimide anion, so aniline cannot be made this way.

Hoffmann bromamide degradation:**

$${\text{RCONH}}_2+{\text{Br}}_2+4\text{NaOH}\to {\text{RNH}}_2+{\text{Na}}_2{\text{CO}}_3+2\text{NaBr}+2{\text{H}}_2\text{O}$$

The R group migrates from the carbonyl carbon to nitrogen, and the carbonyl carbon leaves as carbonate.

Worked example. Hoffmann degradation of $12.1$ g of benzamide ($M=121$ g mol${}^{-1}$) gives aniline:

$$n=\frac{12.1}{121}=0.100\text{ mol},m=0.100\times 93=9.3\text{ g}$$

The product has six carbons against seven in benzamide.

An everyday example. Medicine manufacturers need one exact amine at a time, and routes such as Gabriel synthesis avoid the mixtures that ammonolysis produces.

The substance. Hoffmann degradation is one of the few reactions that shortens a carbon chain, making it useful for stepping down a homologous series.

Primary and secondary amines hydrogen-bond through N–H, so they boil higher than alkanes of similar mass but lower than alcohols, because nitrogen is less electronegative than oxygen and forms weaker hydrogen bonds; tertiary amines have no N–H and boil lowest.

Boiling points of isomeric amines: primary > secondary > tertiary.

Solubility:

- Lower aliphatic amines dissolve in water by hydrogen bonding with it
- Solubility falls as the hydrophobic alkyl part grows
- Higher amines and aniline are only slightly soluble

Colour. Pure amines are colourless, but aryl amines such as aniline darken on standing as air oxidises them.

Worked example. Compounds of similar molar mass:

- Butan-1-ol, $M=74$ — $390$ K
- Butan-1-amine, $M=73$ — $350.8$ K
- N-Ethylethanamine, $M=73$ — $329.3$ K
- N,N-Dimethylethanamine, $M=73$ — $310.5$ K
- Pentane, $M=72$ — $309$ K

The alcohol boils about $40$ K above the primary amine, while the tertiary amine barely beats pentane.

An everyday example. A bottle of aniline in a laboratory slowly turns from colourless to brown as it oxidises in air.

The substance. A tertiary amine boils almost like an alkane, because it cannot hydrogen-bond with its own molecules at all.