Nitrogen compounds: amines

A secondary amine has two alkyl groups linked to the nitrogen atom and one hydrogen left on it, so its general formula is \ce{R-NH-R}, written here as \ce{RNHR}.

\ce{RNH2} is the primary amine (only one alkyl group), \ce{NH3} is ammonia with no alkyl group, and \ce{RCONH2} is an amide, which is not an amine.

A nitrile contains the carbon-nitrogen triple bond, \ce{C#N}, attached to an alkyl or aryl group, so its general formula is \ce{R-C#N}, written \ce{RCN}.

\ce{RNH2} is the amine that a nitrile gives on reduction (\ce{RCN -> RCH2NH2}), not the nitrile itself. \ce{RNO3} is not a nitrile, and \ce{ROH} is an alcohol.

\ce{LiAlH4} is a reducing agent: it adds hydrogen (hydride ions) to the nitrogen-containing groups, which is how the book reduces nitriles, nitro compounds and amides to amines (Section 20.3).

\ce{KMnO4} and \ce{K2Cr2O7} are oxidizing agents, which remove electrons, so they are the opposite of reducing agents. \ce{NaOH} is a base and does not reduce these compounds.

An amine has a lone pair on the nitrogen atom that it can donate to an electron-deficient centre. This is why amines are nucleophiles (Key points, and Section 20.2).

In \ce{RX} the carbon is the electron-deficient site that is attacked, so it does not donate a pair. \ce{RCOR} and \ce{RCHO} are also attacked at their electron-deficient carbonyl carbon.

Amines are classified by the number of carbon atoms of alkyl groups that are attached directly to the nitrogen atom. A primary amine has one alkyl group, \ce{R-NH2} (for example methylamine, \ce{CH3NH2}). A secondary amine has two alkyl groups, \ce{R-NH-R} (for example dimethylamine, \ce{(CH3)2NH}).

A tertiary amine has three alkyl groups linked to the nitrogen, \ce{R3N} (for example triethylamine, \ce{(C2H5)3N}). Primary amines keep two hydrogen atoms on the nitrogen, secondary amines keep one, and tertiary amines have none.

All three types have the nitrogen atom with a lone pair, so the classes differ only in how many hydrogen atoms are replaced by alkyl groups.

A diazonium salt has the general formula \ce{R-N2+ X-}: an \ce{N2+} group, in which two nitrogen atoms are joined by a triple bond, is attached to an alkyl or aryl group and balanced by a halide ion such as \ce{Cl-}. The book's example is benzene diazonium chloride, \ce{C6H5N2+ Cl-}.

Alkyl diazonium salts are generally too unstable for practical use. In the benzene diazonium ion the delocalized electrons of the ring stabilize the positive charge to some extent, so it is far more stable than the aliphatic salts. Benzene diazonium chloride is a colourless crystalline solid that is stable below 10 °C and decomposes easily above 10 °C.

Diazonium salts are important because benzene diazonium chloride combines with phenol to form an orange-red azo dye (Section 20.5).

Basicity is the ability to accept a proton. Ammonia and methylamine both react with hydrochloric acid, \ce{NH3 + HCl -> NH4+ + Cl-} and \ce{CH3-NH2 + HCl -> CH3-NH3+ + Cl-}. The strength of a base is given by pK_b, and the smaller the pK_b, the stronger the base. Ammonia has pK_b = 4.76 and methylamine has pK_b = 3.38, so methylamine is the stronger base.

Alkyl groups are electron-donating: they push electron density towards the nitrogen atom. The lone pair on the nitrogen of an amine is therefore richer in electron density than the lone pair of ammonia and accepts a proton more readily. Each alkyl group adds to this effect, which is why secondary amines (two alkyl groups) are stronger bases than primary amines (Section 20.4).

Amines are organic compounds derived from ammonia, in which one or more hydrogen atoms of \ce{NH3} are replaced by alkyl or aryl groups. They contain nitrogen linked with alkyl or aryl groups and a lone pair on the nitrogen atom, so they are derivatives of ammonia.

The nitrogen atom in an amine is sp^3-hybridized and has a nearly tetrahedral shape. Three of its sp^3 orbitals form sigma bonds to the attached groups and the fourth holds the lone pair. Because the lone pair can be donated, amines act as bases and nucleophiles.

The N–H bond is polar, because nitrogen is more electronegative than hydrogen. The hydrogen atom of one amine molecule is therefore attracted to the nitrogen atom of a neighbouring molecule, and these hydrogen bonds hold amine molecules together.

An alkane of similar molar mass has no polar bond and no hydrogen bonding, so its molecules are held only by weak van der Waals forces. More energy is needed to separate amine molecules, so their melting and boiling points are higher.

The same hydrogen bonding with water makes amines highly soluble in water (Section 20.2).

Methylamine has pK_b = 3.38 and ammonia has pK_b = 4.76. A smaller pK_b means a stronger base, so methylamine is the stronger base. Both accept a proton from HCl:

The methyl group is electron-donating, so it pushes electron density towards the nitrogen atom. The lone pair on the nitrogen of methylamine is therefore richer in electron density than that of ammonia and binds the proton more strongly, which makes methylamine the stronger base.

A diazonium salt is prepared by treating a primary amine with nitrous acid in the presence of hydrochloric acid. The mixture must be kept below 10 °C.

For aniline (phenylamine) the reaction is \ce{C6H5NH2 + HNO2 + HCl -> C6H5N2+ Cl- + 2H2O}, giving benzene diazonium chloride. The cold is essential, because the product decomposes easily above 10 °C.

Overview

The book describes three groups of methods: the reaction of alkyl halides with ammonia, the reduction of nitrogen-containing functional groups (nitriles, nitro compounds and amides), and the Hoffmann degradation of amides. The figure below summarizes the routes.

1. From alkyl halides and ammonia

When an alcoholic solution of ammonia is heated with an alkyl halide in a sealed tube at 100^\circ\mathrm{C}, the ammonia lone pair attacks the alkyl halide. Each amine formed still has a lone pair, so it can react again. The sequence with ethyl iodide is:

The product is a mixture of primary, secondary and tertiary amines and a quaternary salt. Adding a strong alkali such as KOH liberates the free amines from their salts, but the quaternary salt is unaffected. The three amines are then separated by fractional distillation.

2. By reduction of nitrogen-containing functional groups

Nitriles, nitro compounds and amides are reduced to the amino group by suitable reducing agents. In each case the nitrogen is already in the molecule; reduction adds hydrogen, shown as [\mathrm{H}].

a. Reduction of nitriles

Alkyl or aryl nitriles give primary amines on reduction, with \ce{LiAlH4} or with sodium in ethanol. Hydrogen gas over the catalysts Rh–Al₂O₃, Pt or Raney nickel also works.

Examples from the book: ethanenitrile is reduced by catalytic hydrogenation to aminoethane, and benzyl cyanide gives phenylethylamine.

b. Reduction of nitro compounds

Nitro compounds give primary amines. Nitrobenzene is reduced to aniline (phenylamine) by tin and concentrated HCl, or by hydrogen with a palladium catalyst (H₂/Pd). The book also reduces 4-nitroaniline to 1,4-diaminobenzene with iron and \ce{H2SO4}.

c. Reduction of amides

Amides are reduced by \ce{LiAlH4}. The \ce{-CO-} group of the amide is reduced to \ce{-CH2-}, the carbon chain stays intact and a primary amine is formed.

d. Hoffmann degradation

Treating an amide with bromine in KOH removes one carbon atom from the chain, and the product is a primary amine with one carbon fewer (Hoffmann degradation).

Summary

Nitriles

Nitriles are organic compounds that contain the cyano group, \ce{-C#N}, attached to an alkyl or aryl group. Their general formula is \ce{R-C#N}, written \ce{RCN}. Ethanenitrile (\ce{CH3CN}) and benzyl cyanide (\ce{C6H5CH2CN}) are examples.

Reduction of nitriles

Reduction converts the \ce{C#N} group into a \ce{CH2-NH2} group, so alkyl or aryl nitriles give primary amines. The carbon of the nitrile group becomes the \ce{CH2} carbon of the amine, so the number of carbon atoms is unchanged. Three methods are given in the book:

1. Lithium aluminium hydride, \ce{LiAlH4}, as the reducing agent: \ce{R-C#N ->[LiAlH4] R-CH2-NH2}.
2. Sodium in ethanol as the reducing agent.
3. Catalytic hydrogenation: hydrogen gas with the catalysts Rh–Al₂O₃, Pt or Raney nickel.

Worked examples

Structure

The types differ in how many alkyl groups are attached to the nitrogen atom, and so in how many hydrogen atoms remain on it. In all three the nitrogen is sp^3-hybridized, has a nearly tetrahedral shape and carries one lone pair.

Chemical properties

A primary amine has two N–H bonds and so can be alkylated twice before it becomes quaternary. A secondary amine has one N–H bond, so it gives a tertiary amine on alkylation. A tertiary amine has no N–H bond and can only form the quaternary salt.

Formation and stability

Diazonium salts form when amines react with nitrous acid in the presence of hydrochloric acid, below 10 °C. Alkyl diazonium salts are too unstable for practical use, so the useful salts are aromatic. The benzene diazonium ion is stabilized by the delocalized electrons of the ring, and benzene diazonium chloride is a colourless crystalline solid that is stable below 10 °C.

Uses

• Dyes and pigments. Benzene diazonium chloride combines with phenol to give an orange-red dye. Phenyl azo compounds are used as dyes and pigments in the textile, cosmetics, paint and leather industries.
• Antibacterial and antifungal properties. Phenyl azo dyes have antibacterial and antifungal properties, which adds to their value beyond colour.

Limitations

• The reaction mixture must be kept below 10 °C, because benzene diazonium chloride decomposes easily above 10 °C.
• Alkyl diazonium salts are generally too unstable to be used in practice, so their use is limited to the aromatic salts.

Evaluation

The importance of diazonium salts rests on the azo dyes and pigments they make, which colour many everyday products such as textiles, cosmetics, paints and leather goods, and on the antibacterial and antifungal properties of those dyes. The main practical limit is their low-temperature stability: they must be made cold, but this does not prevent their use.

Comparison

Summary

Both classes have the same nitrogen centre with a lone pair, so both are bases and nucleophiles. The difference lies in the number of N–H bonds. The primary amine has two, so it can react with more alkyl groups and gives the diazonium salt with nitrous acid. The secondary amine has one N–H bond and is the stronger base, because its two alkyl groups push more electron density onto the nitrogen.