含氮化合物

An amine 胺 has an $\text{–NH}_2$ (primary) or $\text{–NH}$ (secondary) group.

Making amines

• a halogenoalkane 卤代烷 with $\text{NH}_3$ in ethanol, heated under pressure → a primary amine.
• a halogenoalkane with a primary amine, heated under pressure → a secondary amine.
• reduction 还原 of an amide 酰胺 with $\text{LiAlH}_4$.
• reduction of a nitrile 腈 with $\text{LiAlH}_4$ or $\text{H}_2/\text{Ni}$.

An amine (or ammonia 氨) reacts with an acyl chloride in a condensation 缩合 reaction to give an amide. The reagent is an acyl chloride 酰氯.

Basicity of amines

The basicity 碱性 of an amine comes from the lone pair on its nitrogen, which can accept an $\text{H}^+$ from water.

Making phenylamine

Make phenylamine 苯胺 from benzene in two steps: nitrate benzene to nitrobenzene, then reduce it with hot $\text{Sn}$ and concentrated $\text{HCl}$, followed by $\text{NaOH(aq)}$.

Reactions

• with bromine water at room temperature → 2,4,6-tribromophenylamine (a white precipitate). The ring is activated, like phenol.
• with $\text{HNO}_2$ (from $\text{NaNO}_2$ and dilute acid) below $10\,°\text{C}$ → a diazonium salt; warming this with water gives phenol.

Relative basicity

Ethylamine is the strongest base: its alkyl group pushes electron density onto the nitrogen, making the lone pair more available. Phenylamine is the weakest, because its lone pair is delocalised 离域 into the benzene ring, so it is less available to accept an $\text{H}^+$.

Azo compounds

A diazonium salt 重氮盐 (benzenediazonium chloride) couples with phenol 苯酚 in $\text{NaOH(aq)}$ to form an azo compound 偶氮化合物. The azo group is $\text{–N=N–}$. Azo compounds are brightly coloured and are often used as dyes 染料; many other azo dyes are made the same way.

Worked example. An amino acid has an isoelectric point of pH 6.0. Give its charge, and the electrode it moves towards in electrophoresis, at pH 2, at pH 6.0 and at pH 11. Compare the solution's pH with the isoelectric point each time. At pH 2, well below it, the solution is acidic, so the $\text{–NH}_2$ gains an $\text{H}^{+}$: the amino acid is positive and moves to the cathode (negative electrode). At pH 6.0, exactly its isoelectric point, it is the zwitterion with no net charge, so it does not move. At pH 11, well above it, the $\text{–COOH}$ loses its $\text{H}^{+}$: the amino acid is negative and moves to the anode. Compare the pH with the isoelectric point, never with 7 - and note the zwitterion still carries both charges, it simply has no net charge.

An amide is made from ammonia or a primary amine with an acyl chloride at room temperature.

Its reactions:

• hydrolysis with aqueous acid or alkali, giving the carboxylic acid (or its salt) and the amine (or ammonium).
• reduction of the C=O group with $\text{LiAlH}_4$ to give an amine.

An amide is a much weaker base than an amine, because the nitrogen lone pair is delocalised onto the neighbouring C=O group, so it is not available to accept an $\text{H}^+$.

An amino acid 氨基酸 has both a basic $\text{–NH}_2$ group and an acidic $\text{–COOH}$ group.

Zwitterions and the isoelectric point

The $\text{–COOH}$ can give its $\text{H}^+$ to the $\text{–NH}_2$ in the same molecule, forming a zwitterion 两性离子 ($\text{H}_3\text{N}^+\text{–CHR–COO}^-$) — an ion with both a positive and a negative end but no overall charge.

• in acid (low pH), the amino acid gains $\text{H}^+$ and becomes positive.
• in alkali (high pH), it loses $\text{H}^+$ and becomes negative.
• at one special pH, the isoelectric point 等电点, it is mostly the zwitterion with no net charge.

Peptide bonds

Two amino acids join in a condensation reaction: the $\text{–COOH}$ of one and the $\text{–NH}_2$ of the other react, losing water and forming a peptide bond 肽键 (an amide link). Two amino acids give a dipeptide 二肽, three give a tripeptide.

Electrophoresis

In electrophoresis 电泳, a mixture is placed in an electric field at a chosen pH:

• above its isoelectric point, an amino acid is negative and moves to the positive electrode.
• below its isoelectric point, it is positive and moves to the negative electrode.
• at its isoelectric point, it does not move. So different amino acids separate.

Common mistakes.

• Saying phenylamine is a stronger base than ethylamine because "the ring donates electrons". The opposite is true: the nitrogen lone pair is delocalised into the ring, so it is less available for $\text{H}^+$, and phenylamine is the weakest of the three.
• Calling an amide basic like an amine. In an amide the lone pair is delocalised onto the C=O group, so amides are essentially neutral.
• Making the diazonium salt above $10\,°\text{C}$. The diazonium ion decomposes on warming, giving phenol and nitrogen gas, so keep it below $10\,°\text{C}$ until it is coupled.
• Coupling with phenol in acid. The coupling is done in alkaline solution ($\text{NaOH(aq)}$), where the phenoxide ion is more strongly activated.
• Using ammonia alone to make a pure primary amine. The primary amine formed is itself a nucleophile and reacts further, so a large excess of ammonia is needed to favour the primary amine.
• Sending an amino acid the wrong way in electrophoresis. Below its isoelectric point it is positive and moves to the cathode; above it, negative, it moves to the anode.
• Drawing a zwitterion as an uncharged amino acid. The zwitterion is $\text{H}_3\text{N}^+\text{–CHR–COO}^-$: both groups are ionised, but the overall charge is zero.

• Phenylamine is a weaker base than aliphatic amines because the N lone pair delocalises into the ring.
• Diazotisation ($\text{NaNO}_2$/HCl, below $10\ ^\circ\text{C}$) then coupling gives azo dyes — learn the conditions and the coloured product.
• Amino acids are zwitterions (both $-\text{NH}_2$ and $-\text{COOH}$), so they are amphoteric; describe behaviour either side of the isoelectric point.