13.0 Nitrogen Compounds Notes 2021

1

Nitrogen Compounds

20 Nitrogen compounds

Many biological molecules contain nitrogen. This topic introduces the chemistry of a variety of organic compounds that contain nitrogen.

20.1 Primary Amines

20.2 Amides

Bilal Hameed Nitrogen Compounds

Nitrogen Compounds

2

Cambridge International AS and A Level Chemistry 9701 syllabus Syllabus content

43Back to contents page www.cie.org.uk/alevel

20 Nitrogen compounds

Many biological molecules contain nitrogen. This topic introduces the chemistry of a variety of organic compounds that contain nitrogen.

Learning outcomes Candidates should be able to:

20.1 Primary amines a) describe the formation of alkyl amines such as ethylamine (by the reaction of ammonia with halogenoalkanes; the reduction of amides with LiAlH4; the reduction of nitriles with LiAlH4 or H2/Ni) and of phenylamine (by the reduction of nitrobenzene with tin/concentrated HCl)

b) describe and explain the basicity of amines

c) explain the relative basicities of ammonia, ethylamine and phenylamine in terms of their structures

d) describe the reaction of phenylamine with:

(i) aqueous bromine

(ii) nitrous acid to give the diazonium salt and phenol

e) describe the coupling of benzenediazonium chloride and phenol and the use of similar reactions in the formation of dyestuff

20.2 Amides a) describe the formation of amides from the reaction between NH3 or RNH2 and R’COCl

b) recognise that amides are neutral

c) (i) describe amide hydrolysis on treatment with aqueous alkali or acid

(ii) describe the reduction of amides with LiAlH4

20.3 Amino acids a) describe the acid/base properties of amino acids and the formation of zwitterions

b) describe the formation of peptide bonds between amino acids to give di- and tri-peptides

c) describe simply the process of electrophoresis and the effect of pH, using peptides and amino acids as examples

Syllabus content

Nitrogen Compounds Bilal Hameed

31

13. AminesThe number of these groups determines whether the compound is a primary amine, a secondary amine or a tertiary amine.

2

4.1 Structures and namesAmines are nitrogen compounds in which one or more of the hydrogen atomsin ammonia, NH3, is replaced by an alkyl or an aryl group. The number ofthese groups determines whether the compound is a primary amine, asecondary amine or a tertiary amine. If one H atom in ammonia is replaced byan alkyl or aryl group, the compound is a primary amine; if two H atoms arereplaced, the compound is a secondary amine; and if all three H atoms inammonia are replaced, the compound is a tertiary amine.

Chemists have two systems for naming amines.

Simple aminesSimple amines are treated as a combination of the alkyl or aryl group followedby the ending –amine. So, CH3CH2NH2 is ethylamine, C6H5NH2 isphenylamine and CH3CH2NHCH3 is ethylmethylamine. The prefixes di- andtri- are used when there are two or three of the same alkyl or aryl group(Figure 4.3).

4 AminesAmines can be very smelly. Ethylamine, for example, has a fishy smell.However, the importance of the amine functional group is not itssmell, but the role it plays in biochemistry and medicine. The aminegroup is present in amino acids, the monomers for proteins (Topic 5).As a result of this, the amine group plays an important part inmetabolism and it appears in the structures of many medical drugs.In the chemical industry, aromatic amines have commercial valuebecause they are the basis of the manufacture of a wide range ofcolourful dyes.

40

Figure 4.1 !The active constituent of asthmainhalers is salbutamol, whichcontains the amine group.

Figure 4.2 "The smell of fish is partly due toethylamine.

Note

Notice that the terms primary,secondary and tertiary do not havethe same meaning with amines asthey do with alcohols.

Figure 4.3 "The structures and names of primary,secondary and tertiary amines containingthe methyl group.

CH3 N

H

H

CH3

CH3

N

H

CH3

CH3

CH3

N

methylamine(a primary amine)

dimethylamine(a secondary amine)

trimethylamine(a tertiary amine)

13. AminesAmines are nitrogen compounds in which one or more of the hydrogen atoms in ammonia, NH3, is replaced by an alkyl or an aryl group.

1

ORGANIC CHEMISTRY

450

Most alkaloids have a bitter taste, but are too involatile (that is, they produce too little vapour) to have an odour. Those amines that are volatile have distinctive smells. The short-chain amines have an astringent ammonia-like smell, but this is replaced by a strong fi shy odour in butylamine and longer-chain amines. Aryl amines such as phenylamine have a more ‘oily’ smell.

The amines can be derived from ammonia by replacing one or more of the hydrogen atoms in NH3 by organic groups; replacing the amine hydrogen atoms can often be carried out in the laboratory.

H N H

H

CH3 CH3

H H

ammonia dimethylamine phenylamine

NN

H

• • • •

• •

The carbon–nitrogen bond, although quite strongly polarised, is fairly inert and it is not so easily broken as the C¬O bond in alcohols (see Topic 16, page 282). There are few reactions in which the Cδ+ atom takes part. The key point of reactivity in the amines is the lone pair of electrons on the nitrogen atom, which is more readily donated than a lone pair on oxygen. This lone pair is nucleophilic towards Cδ+ and basic towards Hδ+. Amines form strong hydrogen bonds to hydrogen-donor molecules such as water. Those amines that contain N¬H bonds also form strong intermolecular hydrogen bonds (see Figure 27.2).

The short-chain amines are therefore water soluble and their boiling points are higher than those of the corresponding alkanes (see Table 27.1 and Figure 27.3). The effect of hydrogen bonding on boiling point is not so pronounced as it is in the alcohols, however (compare Table 27.1 with Table 16.1, page 282).

Number of electrons in the molecule

Alkane Amine Increase in boiling point/°C

Formula Boiling point/°C

Formula Boiling point/°C

18 C2H6 −88 CH3NH2 −8 80

26 C3H8 −42 C2H5NH2 17 59

34 C4H10 0 C3H7NH2 49 49

42 C5H12 36 C4H9NH2 78 42

50 C6H14 69 C5H11NH2 104 35

58 C7H16 98 C6H13NH2 130 32

27_02 Cam/Chem AS&A2

Barking Dog Art

R N

H

H

H

H

N R

H

H

N

RHR

N H

Figure 27.2 Intermolecular hydrogen bonding in amines

Table 27.1 Boiling points of some alkanes and corresponding amines


Barking Dog Art

N

N

N

NN

O

NH

HH

H

N

N

CH3

CH3

CH3

CH3CH3

CH3

CH3O

HO

OO

O

O

O

H

N

nicotine

cocaine caffeine

quinine

Figure 27.1 The structures of some naturally occurring alkaloids

Now try this1 Apart from the nitrogen atoms, what

functional groups are contained ina the quinine moleculeb the cocaine molecule?

2 Work out the molecular formula of:a quinineb caffeine

3 The molecule of nicotine is chiral. Draw out the structure, showing which atom is the chiral one.

181333_27_A_Chem_BP_449-468.indd 450 09/10/14 1:39 AM

13. Amines3

27 Amines, amides and amino acids

451

27.2 Isomerism and nomenclatureThe most important feature of the amine molecule is the nitrogen atom. This is refl ected in the nomenclature of amines. The simpler ones, such as dimethylamine and phenylamine shown opposite, are named as though they are derived from ammonia. Up to three hydrogen atoms in ammonia can be replaced by organic groups. Successive replacement forms primary, secondary and tertiary amines (see Table 27.2). Note that it is the branching that takes place at the nitrogen atom, rather than at the carbon atom attached to it, that determines whether an amine is primary, secondary or tertiary. This is not the same as in the case of the alcohols:

CH OH CHCH3CH2CH2

N HNH2

CH3CH2CH2

propan-2-ola secondary alcohol

2-aminopropanea primary amine

dipropylaminea secondary amine

CH3

CH3

CH3

CH3

Table 27.2 Some primary, secondary and tertiary amines

Primary amines Secondary amines Tertiary amine

CH3CH2NH2

ethylamine(CH3CH2)2NHdiethylamine

(CH3CH2)3Ntriethylamine

CH3 NH2

4-methylphenylamine

N

H

diphenylamine

CH3

CH3

N

N,N-dimethylphenylamine

NH2

cyclohexylamine

N H

piperidine

N

CH3N

nicotine


Barking Dog Art

–100

50

150

100

0

–50

60555045403530252015number of electrons

10

bo

ilin

g p

oin

t/°C

amines

alkanes

Figure 27.3 Boiling points of some alkanes and corresponding amines

181333_27_A_Chem_BP_449-468.indd 451 09/10/14 1:39 AM

Bilal Hameed MarginalizerBilal Hameed Nitrogen Compounds

4 2

13. Amines as Nucleophiles Amines are strong nucleophiles as well as strong bases, just like ammonia. As nucleophiles, their lone pair of electrons is attracted to any positive ion or positive centre in a molecule.

4Primary amides have the general formula

=

O

R − C − NH2, often written as RCONH2.

The simplest primary amide is ethanamide, CH3CONH2.

Primary amides are made by reacting acyl halides with ammonia (Section 19.5):

RCOCl(l) + NH3(aq) → RCONH2(aq) + HCl(aq)

A similar reaction occurs between acyl halides and primary amines. In this case, a secondary amide is formed. For example:

+ CH3COCl

−NHCOCH3

+ HCl

phenylamine N–phenylethanamide (m.pt. 114 °C)ethanoylchloride

−NH2

The general reaction can be written as:

RCOCl + R′NH2 → RCONHR′ + HCl

(R and R′ are alkyl or aryl groups)

Unlike the amines from which they are made, secondary amides are crystalline solids with sharp melting points. They are therefore useful in identifying (characterising) unknown amines. The amide is prepared and its melting point is taken. This is then checked against the melting points of known amides in published tables.

Amides are much weaker bases than amines, because the lone pair of electrons on the N atom is partly delocalised onto the neighbouring C = O group, making it less available for bonding to H+.

Hydrolysis of amides

When a primary amide is heated with a solution of aqueous alkali, such as NaOH(aq), or aqueous acid, such as HCl(aq), it splits up. The products are a carboxylic acid and ammonia. This is described as a hydrolysis reaction, because a molecule of H2O splits the amide apart. For example, with ethanamide:

ammoniaCH3− C − NH2 + H2O

=

O

CH3− C − OH + NH2H

=

O

This can also be written as:

CH3CONH2(aq) + H2O(l) → CH3COOH(aq) + NH3(aq)

ethanamide ethanoic acid

The hydrolysis reaction is catalysed by alkali or acid. In alkaline hydrolysis, if the alkali is present in excess, the carboxylic acid will react with the alkali to form a salt, for example CH3COO–Na+. In acid hydrolysis, if the acid is present in excess, the NH3 will react with the acid to form a salt, for example NH4

+Cl–.

515

Amides27.827.8 Amides

KEY POINTSPrimary amides have the formula RCONH2.

Secondary amides have the formula RCONHR′.

Primary amides are made by reacting RCOCl with NH3.Secondary amides are made by reacting RCOCl with R′NH2.

Amides are hydrolysed (split) by heating with aqueous acid or alkali. With acid, the products are a carboxylic acid and an ammonium salt. With alkali, the products are a carboxylic acid salt and ammonia.

In this section you will learn to:

• Give the general formula for an amide

• Distinguish between primary and secondary amides

• Describe the process of hydrolysis with an amide

Primary amides have the general formula

=

O






+ CH3COCl

−NHCOCH3

+ HCl


−NH2









=

O


=

O





+Cl–.

515










13. Amines as Nucleophiles When amines are reacted with acyl chlorides (at low temperature) N-substituted amides are formed.

5

54718.2.3 The properties and reactions of amines

C4H9 N

H

CH3

CH3

+ CH3Br C4H9 N

CH3

CH3

H

++

+C4H9 N

CH3

CH3

H

+ C4H9

CH3

+ HBr

butyldimethylamine

N

Br–

Br–

Figure 18.2.11 Formation of the tertiary amine butyldimethylamine.

The tertiary amine similarly can react further to form a quaternary ammonium salt (Figure 18.2.12).

C4H9 + CH3CH3

CH3

Br C4H9 N

CH3

CH3

CH3

++

butyltrimethylammonium bromide

Br–N

Figure 18.2.12 Formation of the quaternary ammonium salt butyltrimethylammonium bromide.

It is possible to limit further reaction by using an excess of the primary amine so that there is a much greater chance of the primary amine rather than the secondary amine acting as nucleophile with the halogenoalkane molecules.

If an excess of the halogenoalkane is used, the quaternary ammonium salt is the main product.

Reaction with acyl chloridesAmines also react as nucleophiles with the δ+ carbon atoms in the C

O

Cl group of acyl chlorides such as ethanoyl chloride (Figure 18.2.13). The reaction forms an N-substituted amide (see also Section 17.3.4).

Key term

Quaternary ammonium salt is an ammonium salt where all four hydrogens are replaced by alkyl or aryl groups.

TipQuaternary ammonium salts where two of the alkyl groups are long chains, such as [(CH3(CH2)17]2N(CH3)2

+Cl−, are used in fabric softeners.

CH3 C

O

CI

+ CH CH23 CH2CH2NH2

CH3 C

O

NCH2CH2CH2CH3

H

+ HCI

N-butyl ethanamide

c+

c– Figure 18.2.13 The reaction of butylamine with ethanoyl chloride.

A reaction of this type is involved in the manufacture of paracetamol; this is discussed in the activity that follows.

469983_18.2_Chem_Y1-2_541-567.indd 547 13/04/19 9:59 PM

13. Amines as Nucleophiles 6Primary amides have the general formula

=

O






+ CH3COCl

−NHCOCH3

+ HCl


−NH2









=

O


=

O





+Cl–.

515










<��;JGI=:G�DG<6C>8�8=:B>HIGN '.8=:B>HIGN�;DG�I=:�>7�9>EADB6��86B7G>9<:�JC>K:GH>IN�EG:HH�'%&&

In all the reactions we will meet the acyl group will be added to the most electronegative atom of the nucleophile (N or O) and H (from the nucleophile) and Cl (from the acyl chloride) will be eliminated (Figure G36).

2 Reaction with alcohols Acyl chlorides react with alcohols to form esters.

;^\jgZ�<(+� GZVXi^dc�d[�Vc�VXna�X]adg^YZ�l^i]�lViZg#

8a= D

8a

=

88

=WjiVcdna�X]adg^YZ

=

8

=

=

=

=

=

8 =8

=

=

D

=

=

8

=

88

=Zi]na�WjiVcdViZ

=

8

=

=

= =

=

=

88

=

=

D

=

D

8

=A

8a

= D

8=

=

8=

VXna�\gdje�VYYZY�id�D

=8a�Za^b^cViZY

D =

This reaction is usually carried out in the presence of a base such as pyridine (C5H5N).An alkaline solution of phenol reacts with benzoyl chloride to form

phenyl benzoate:

8a=

8a D

D

8D= D

8

e]Zcna�WZcodViZ

8a=

=

=

8

=

=

8

=

8=D

8aC

==

egdeVcVb^YZ

=

=

8

=

=

8 8=D

C='

A more accurate way of writing this reaction would be as:

CH3CH2COCl + 2NH3 n CH3CH2CONH2 + NH4Cl

HCl would not be formed in the presence of a base such as ammonia but rather the salt ammonium chloride.

3 Reactions with ammoniaWhen concentrated ammonia solution is added to an acyl chloride at 0 °C a primary amide is formed.

4 Reactions with amines When acyl chlorides are reacted with amines (again at low

temperature) N-substituted amides are formed.

8a=

=

=

8

=

=

8 8=D

8a =

==

=

8

=

=

8 =C

=

=

=

8

=

=

8 =C

D"Zi]naegdeVcVb^YZ

Zi]naVb^cZ

=

=

8

=

=

8 8=D

Again, the balanced equation should, more correctly, be written as:

CH3CH2COCl + 2CH3CH2NH2 n CH3CH2CONHCH2CH3 + CH3CH2NH3Cl

Marginalizer Bilal HameedNitrogen Compounds Bilal Hameed

53

13. BasicityAmines are basic. They react with acids to form salts (just like ammonia):

8

13. Basicity of Alkyl AminesAlkyl amines are stronger bases than ammonia. Alkyl groups attached to the nitrogen atom increase the basicity of amines. Electron donation from an alkyl group will encourage dative bond formation.

9

39126 Organic nitrogen compounds

Ammonia is a stronger base than phenylamine because one of the p orbitals on the nitrogen atom in phenylamine overlaps with the π bonding system in the benzene ring. ! is causes the lone pair of the N atom in phenylamine to be delocalised into the benzene ring. ! is then makes the lone pair less available to form a co-ordinate bond with an H+ ion than it is in ammonia (Figure 26.5).

We can think of the amines as substituted ammonia (NH3) molecules. For example, a primary amine is an ammonia molecule with one of its H atoms replaced by an alkyl or aryl group. Ammonia and the amines act as bases because of the lone pair of electrons on the nitrogen atom. Remember that a base is a proton (H+ ion) acceptor. ! e nitrogen atom donates its lone pair to an H+ ion, forming a co-ordinate (dative) bond.

For ammonia:

NH3 + H+ → NH4+

For a primary amine:

RNH2 + H+ → RNH3+

Dilute hydrochloric acid reacts with ammonia and with amines to produce salts.

For ammonia:

NH3 + HCl → NH4+Cl−

ammonium chloride


CH3NH2 + HCl → CH3NH3+Cl−

methylammonium chloride

Ammonia and the amines have di# erent strengths as bases. ! eir strength as bases depends on the availability of the lone pair of electrons on the N atom to bond with an H+ ion.

Let us consider ammonia, ethylamine and phenylamine as examples. We $ nd that the strongest base of the three is ethylamine, followed by ammonia and, $ nally, phenylamine.

Ethylamine is a stronger base than ammonia because the ethyl group is electron-donating in nature (Figure 26.4). By releasing electrons to the N atom, the ethyl group makes the lone pair more readily available to bond with an H+ ion than it is in ammonia. Ammonia has three H atoms bonded to the N atom.

Some primary amines do not have the NH2 group at the end of an alkyl chain. We indicate the position of the NH2 group on the hydrocarbon chain by numbering from the nearest end of the molecule. In these cases we refer to the NH2 group as the ‘amino’ group, e.g. CH3CH2CHNH2CH2CH2CH3 is called 3-aminohexane.

Fact fi le

1 a Name the following compounds:i CH3CH2CH2CH2CH2NH2

ii (CH3CH2CH2)2NHiii C2H5NH3

+Cl−

b Predict whether diethylamine is a stronger or weaker base than ethylamine. Explain your reasoning.

Check-up

Making aminesPreparing ethylamine1 In Chapter 15 (page 233) you learned how

bromoethane undergoes nucleophilic substitution with ammonia to form a mixture of amines. In order to prepare ethylamine (whilst avoiding the formation of secondary and tertiary amines and ammonium salts) we use excess hot ethanolic ammonia:

CH3CH2Br + NH3 → CH3CH2NH2 + HBr ethylamine

Figure 26.4 Ethylamine is a stronger base than ammonia.

CH3CH2 NH2

alkyl groups areelectron-donating(or electron-releasing)

Figure 26.5 Phenylamine is a very weak base.

H N

H H Hnitrogen’s lone pair getsdrawn in to the delocalisedring of electrons

H H H

13. BasicityAmines are basic. They react with acids to form salts (just like ammonia):

7


6 4

13. Basicity of Phenyl AmineThe bonds around the nitrogen atom can take up a planar arrangement, with the nitrogen’s lone pair in a p orbital, so that extra stability can be gained by overlapping this p orbital with the delocalised ! bond of the benzene ring. This overlap causes the lone pair of the N atom in phenylamine to be delocalised into the benzene ring and results in the lone pair to be much less basic.

12

18.2 Amines, amides, amino acids and proteins544

Amines as basesPrimary amines, like ammonia, can act as Brønsted–Lowry bases. The lone pair of electrons on the nitrogen atom of ammonia and amines is a proton (H+ ion) acceptor.

Reaction with waterAmmonia acts as a Brønsted–Lowry base and a small proportion of the dissolved molecules react with water to form a weakly alkaline solution containing hydroxide ions.

NH3(aq) + H2O(l) ! NH4+(aq) + OH−(aq)

Butylamine and other amines act as Brønsted–Lowry bases in a similar manner by removing H+ ions from water molecules to form an alkaline solution containing hydroxide ions (Figure 18.2.6).

TipThe pKa values of their conjugate acids (see Section 12.2) give a measure of the strength of ammonia (pKa = 9.25), butylamine (pKa = 10.61) and phenylamine (pKa = 4.62) as bases. A higher pKa value corresponds to a stronger base.

TipNote that the shorthand C4H9 used here to represent the carbon chain in butylamine can also represent several other arrangements of the carbon chain.

N

H

H

Figure 18.2.7 Delocalisation of the lone pair into the ʌ cloud in phenylamine.

C4H9 N

H

H

+ H O H C4H9 N

H

H

H

+ O H

C4H9NH2(aq) + H2O(I) C4H9NH3+(aq) + OH– (aq)

butylamine butylammonium ion

–+

Figure 18.2.6 The reaction of butylamine with water.

As with ammonia, the reaction of amines with water is reversible so alkyl amines are also weak bases, although stronger than ammonia. This is because the alkyl group is electron releasing and increases the electron density on the lone pair on the nitrogen. This e"ect makes the lone pair more attractive to protons than the lone pair on the nitrogen in ammonia. The equilibrium in Figure 18.2.6 lies further to the right than the equilibrium involving ammonia.

By contrast, phenylamine is a much weaker base than ammonia because the lone pair in phenylamine is delocalised into the ʌ cloud of the benzene ring (Figure 18.2.7) and is less attractive to protons than the lone pair in ammonia. Therefore, the equilibrium for the reaction of phenylamine with water lies further to the left than that for ammonia.

C6H5NH2(l) + H2O(l) ! C6H5NH3+(aq) + OH−(aq)

Reaction with acids – formation of saltsAmines react even more readily with acids than they do with water. The lone pair on the nitrogen atom rapidly accepts an H+ ion from the acid to form a substituted ammonium salt.

C4H9NH2(g) + HCl(g) → C4H9NH3+Cl−(s)

butylamine butylammonium chloride

When the vapour of gaseous amines such as ethylamine reacts with hydrogen chloride gas, the product, ethylammonium chloride, forms as a white smoke. The smoke settles as a white solid (Figure 18.2.8).

CH3CH2NH2(g) + HCl(g) → CH3CH2NH3+Cl−(s)

ethylamine ethylammonium chloride

469983_18.2_Chem_Y1-2_541-567.indd 544 13/04/19 9:59 PM

13. Basicity of Phenyl AminePhenyl amine is a weaker base than ammonia.

This is because in phenylamine, the lone pair of electrons on the nitrogen atom is delocalised over the benzene ring.

11


453

Those amines that are soluble in water form weakly alkaline solutions, just as ammonia does, due to partial reaction with the solvent, producing OH− ions:

CH3CH2NH2 + H2O W CH3CH2NH3+ + OH−

Table 27.3 lists some amines, with values of their dissociation equilibrium constants, Kb, for the following equilibrium:

R3N + H2O W R3NH+ + OH−

Kb =

[R3NH+][OH−][R3N]

The larger Kb is, the stronger is the base. Ammonia is included for comparison.From Table 27.3 we can see that electron-donating alkyl groups attached to the

nitrogen atom increase the basicity of amines. This is expected, since the basicity depends on the availability of the lone pair of electrons on nitrogen to form a dative bond with a proton (see Figure 27.6). Electron donation from an alkyl group will encourage dative bond formation.

Table 27.3 The basicity of some amines

Amine Formula Kb/mol dm−3

phenylamine NH2 4.2 × 10−10

ammonia NH3 1.8 × 10−5

ethylamine CH3CH2NH2 5.1 × 10−4

diethylamine (CH3CH2)2NH 1.0 × 10−3

The most dramatic difference in basicities to be seen in Table 27.3 is between that of phenylamine (Kb ≈ 10−10) and the alkyl amines (Kb ≈ 10−3). Taking two compounds of about the same relative molecular mass and shape, we see that phenylamine is about a million times less basic than cyclohexylamine:

NH2 NH2

phenylamineKb = 4.2 × 10–10

cyclohexylamineKb = 3.3 × 10–4

This is because in phenylamine, the lone pair of electrons on the nitrogen atom is delocalised over the benzene ring. The bonds around the nitrogen atom can take up a planar arrangement, with the nitrogen’s lone pair in a p orbital, so that extra stability can be gained by overlapping this p orbital with the delocalised π bond of the benzene ring (see Figure 27.7).


Barking Dog Art

N H+R

R

R

N+R H

R

R

Figure 27.6 When an amine acts as a base, the nitrogen lone pair forms a dative bond with a proton.


Barking Dog Art

or

H

H

NH2 etc.+NH2–N

Figure 27.7 Delocalisation of the nitrogen lone pair in phenylamine

This overlap, causing a drift of electron density from nitrogen to the ring, has two effects on the reactivity of phenylamine.

O It causes the lone pair to be much less basic (see above) and also much less nucleophilic.

O It causes the ring to be more electron rich, and so to undergo electrophilic substitution reactions much more readily than benzene. The enhanced reactivity of phenylamine in this regard is similar to that of phenol (see Topic 25, page 434), an

181333_27_A_Chem_BP_449-468.indd 453 09/10/14 1:39 AM


RNH2 + H+ RNH3+


For ammonia:

NH3 + HCl NH4+Cl–

ammonium chloride


CH3NH2 + HCl CH3NH3+Cl–


Ammonia and the amines have di!erent strengths as bases.

The strength of ammonia and amines as bases depends on the availability of the lone pair of electrons on their N atom to bond with an H+ ion.

Let us consider ammonia, ethylamine and phenylamine as examples. We "nd that the strongest base of the three is ethylamine, followed by ammonia and, "nally, phenylamine.

ethylamine > ammonia > phenylamine STRONGEST WEAKEST BASE BASE

Ethylamine is a stronger base than ammonia because the ethyl group is electron-donating in nature (see Figure 27.4). By releasing electrons to the N atom, the ethyl group makes the lone pair more readily available to bond with an H+ ion than it is in ammonia. Ammonia has three H atoms bonded to the N atom.

CH3CH2 NH2



Ammonia is a stronger base than phenylamine because one of the p orbitals on the nitrogen atom in phenylamine overlaps with the π bonding system in the benzene ring. %is causes the lone pair of the N atom in phenylamine to be delocalised into the benzene ring. %is then makes the

lone pair less available to form a co-ordinate bond with an H+ ion than it is in ammonia (see Figure 27.5).

nitrogen’s lone pair getsdrawn in to the delocalisedring of electrons

H N

H H H

H H H

NNNNNNNNNNNNNNNNN

H H H

H H H


Formation of aminesMaking ethylamine1 In Chapter 16 (page 218) you learnt how bromoethane

undergoes nucleophilic substitution with ammonia to form a mixture of amines. In order to prepare ethylamine (while avoiding the formation of secondary and tertiary amines and ammonium salts) we use excess hot ethanolic ammonia:

CH3CH2Br + NH3 CH3CH2NH2 + HBr ethylamine

Hydrogen bromide, HBr, which could react with the ethylamine, is removed by the excess ammonia. It forms ammonium bromide, NH4Br. %e excess ammonia also reduces the chances of bromoethane being attacked by ethylamine; ethylamine is also a nucleophile.

2 We also learnt in Chapter 16 (pages 219–220) about the formation of nitriles by reacting a halogenoalkane with the CN– ion. To carry out the reaction, a solution of potassium cyanide, KCN, in ethanol is heated under re&ux with the halogenoalkane:

CH3Br + CN– CH3CN + Br–

bromomethane ethanenitrile

Note that we start with bromomethane, not bromoethane, as the cyanide group adds a carbon atom to the alkyl group. We can then reduce (add hydrogen to) the ethanenitrile to make ethylamine. %e nitrile

1 a Name the following compounds: i CH3CH2CH2CH2CH2NH2

ii (CH3CH2CH2)2NH iii C2H5NH3

+Cl–


QUESTION

402

Cambridge International A Level Chemistry

13. Basicity of alkyl aminesAlkyl groups are electron-releasing (positive inductive effect) and so will push electron density onto the N, making it more negative and therefore more likely to attract H+ and form a dative bond. E.g., Ethylamine, CH3CH2NH2, is a stronger base than ammonia.

10


Ammonia is a stronger base than phenylamine because one of the p orbitals on the nitrogen atom in phenylamine overlaps with the π bonding system in the benzene ring. ! is causes the lone pair of the N atom in phenylamine to be delocalised into the benzene ring. ! is then makes the lone pair less available to form a co-ordinate bond with an H+ ion than it is in ammonia (Figure 26.5).

We can think of the amines as substituted ammonia (NH3) molecules. For example, a primary amine is an ammonia molecule with one of its H atoms replaced by an alkyl or aryl group. Ammonia and the amines act as bases because of the lone pair of electrons on the nitrogen atom. Remember that a base is a proton (H+ ion) acceptor. ! e nitrogen atom donates its lone pair to an H+ ion, forming a co-ordinate (dative) bond.

For ammonia:

NH3 + H+ → NH4+


RNH2 + H+ → RNH3+


For ammonia:

NH3 + HCl → NH4+Cl−

ammonium chloride


CH3NH2 + HCl → CH3NH3+Cl−


Ammonia and the amines have di# erent strengths as bases. ! eir strength as bases depends on the availability of the lone pair of electrons on the N atom to bond with an H+ ion.

Let us consider ammonia, ethylamine and phenylamine as examples. We $ nd that the strongest base of the three is ethylamine, followed by ammonia and, $ nally, phenylamine.

Ethylamine is a stronger base than ammonia because the ethyl group is electron-donating in nature (Figure 26.4). By releasing electrons to the N atom, the ethyl group makes the lone pair more readily available to bond with an H+ ion than it is in ammonia. Ammonia has three H atoms bonded to the N atom.

Some primary amines do not have the NH2 group at the end of an alkyl chain. We indicate the position of the NH2 group on the hydrocarbon chain by numbering from the nearest end of the molecule. In these cases we refer to the NH2 group as the ‘amino’ group, e.g. CH3CH2CHNH2CH2CH2CH3 is called 3-aminohexane.

Fact fi le

1 a Name the following compounds:i CH3CH2CH2CH2CH2NH2

ii (CH3CH2CH2)2NHiii C2H5NH3

+Cl−


Check-up

Making aminesPreparing ethylamine1 In Chapter 15 (page 233) you learned how

bromoethane undergoes nucleophilic substitution with ammonia to form a mixture of amines. In order to prepare ethylamine (whilst avoiding the formation of secondary and tertiary amines and ammonium salts) we use excess hot ethanolic ammonia:

CH3CH2Br + NH3 → CH3CH2NH2 + HBr ethylamine


CH3CH2 NH2



H N

H H Hnitrogen’s lone pair getsdrawn in to the delocalisedring of electrons

H H H


75

13. Phenyl Amine With Bromine WaterLike phenol, phenylamine decolourises bromine water to give a white precipitate of 2,4,6-tribromophenylamine.

15

Reactions of the aromatic ring in phenylamine

The lone pair of electrons on the nitrogen atom in phenylamine tends to get partly delocalised round the ring. We have already seen how this reduces the basic strength of phenylamine relative to aliphatic amines. Another result is that the electron density round the ring in phenylamine is considerably increased. This allows it to undergo electrophilic substitution much more readily than benzene. For example, phenylamine reacts with bromine water even in the absence of a halogen carrier catalyst:

NH2

−

+ 3Br2(aq)

2,4,6-tribromophenylamine

+ 3HBr(aq)

NH2

−− −

−

Br Br

Br

Notice that the 2, 4 and 6 positions are preferentially substituted.

The high electron density in the phenylamine molecule also makes it very easy to oxidise. Pure phenylamine is colourless, but it quickly darkens owing to atmospheric oxidation. Chemical oxidising agents can convert it to a host of different products, including the pigment Aniline Black (Figure 27.5).

Fig 27.5 The pigment Aniline Black is a mixture of several substances. The structure of one of them is believed to be that shown here (the + and – charges are effectively delocalised over the molecule, which is electrically neutral overall)

N+

N

N– N+

N

N– N+

N

N– NH

NH2

Reaction with nitrous acid

Nitrous acid (HNO2) is rather unstable, so when it is used as a chemical reagent it is usually generated on the spot from sodium nitrite and hydrochloric acid.

When phenylamine is reacted with nitrous acid at low temperatures (below 10 °C), a clear solution is formed. When this solution is warmed, nitrogen is evolved and phenol is formed.

These observations are explained as follows. When amines react with nitrous acid, diazonium compounds are formed:

RNH2 + HNO2 → R − +N ≡ N + –OH + H2O

diazonium ion

The diazonium group, − +N ≡ N, is rather unstable. If it is attached to an alkyl

group, it decomposes at once, producing N2(g). But, if it is attached to an aromatic ring, the ion is stabilised to some extent by the delocalised electrons of the ring. Even so, the benzenediazonium ion decomposes at temperatures above 10 °C, giving phenol and nitrogen:

C6H5 − +N ≡ N(aq) + H2O(l) → C6H5 OH(aq) + N2(g) + H+(aq)

benzenediazonium ion


• Explain why electrophilic substitution can easily occur with phenylamine

• Describe the reaction of phenylamine with nitrous acid to give a diazonium compound

• Summarise reactions of phenylamine

512

Organic nitrogen compounds

Other reactions of phenylamine27.6

KEY POINTPhenylamine undergoes electrophilic substitution of the aromatic ring much more readily than benzene. The 2, 4 and 6 positions are preferentially substituted.

13. Reactivity of Phenyl Amine

The overlap that causes the lone pair of the N atom in phenylamine to be delocalised into the benzene ring increases the electron density of the ring. This results in the ring being more electron rich, and it undergoes electrophilic substitution reactions much more readily than benzene. The enhanced reactivity of phenylamine in this regard is similar to that of phenol, an example being the ease with which phenylamine decolorises bromine water.

14


Amines as basesPrimary amines, like ammonia, can act as Brønsted–Lowry bases. The lone pair of electrons on the nitrogen atom of ammonia and amines is a proton (H+ ion) acceptor.

Reaction with waterAmmonia acts as a Brønsted–Lowry base and a small proportion of the dissolved molecules react with water to form a weakly alkaline solution containing hydroxide ions.

NH3(aq) + H2O(l) ! NH4+(aq) + OH−(aq)

Butylamine and other amines act as Brønsted–Lowry bases in a similar manner by removing H+ ions from water molecules to form an alkaline solution containing hydroxide ions (Figure 18.2.6).

TipThe pKa values of their conjugate acids (see Section 12.2) give a measure of the strength of ammonia (pKa = 9.25), butylamine (pKa = 10.61) and phenylamine (pKa = 4.62) as bases. A higher pKa value corresponds to a stronger base.

TipNote that the shorthand C4H9 used here to represent the carbon chain in butylamine can also represent several other arrangements of the carbon chain.

N

H

H

Figure 18.2.7 Delocalisation of the lone pair into the ʌ cloud in phenylamine.

C4H9 N

H

H

+ H O H C4H9 N

H

H

H

+ O H

C4H9NH2(aq) + H2O(I) C4H9NH3+(aq) + OH– (aq)

butylamine butylammonium ion

–+

Figure 18.2.6 The reaction of butylamine with water.

As with ammonia, the reaction of amines with water is reversible so alkyl amines are also weak bases, although stronger than ammonia. This is because the alkyl group is electron releasing and increases the electron density on the lone pair on the nitrogen. This e"ect makes the lone pair more attractive to protons than the lone pair on the nitrogen in ammonia. The equilibrium in Figure 18.2.6 lies further to the right than the equilibrium involving ammonia.

By contrast, phenylamine is a much weaker base than ammonia because the lone pair in phenylamine is delocalised into the ʌ cloud of the benzene ring (Figure 18.2.7) and is less attractive to protons than the lone pair in ammonia. Therefore, the equilibrium for the reaction of phenylamine with water lies further to the left than that for ammonia.

C6H5NH2(l) + H2O(l) ! C6H5NH3+(aq) + OH−(aq)

Reaction with acids – formation of saltsAmines react even more readily with acids than they do with water. The lone pair on the nitrogen atom rapidly accepts an H+ ion from the acid to form a substituted ammonium salt.

C4H9NH2(g) + HCl(g) → C4H9NH3+Cl−(s)

butylamine butylammonium chloride

When the vapour of gaseous amines such as ethylamine reacts with hydrogen chloride gas, the product, ethylammonium chloride, forms as a white smoke. The smoke settles as a white solid (Figure 18.2.8).

CH3CH2NH2(g) + HCl(g) → CH3CH2NH3+Cl−(s)

ethylamine ethylammonium chloride

469983_18.2_Chem_Y1-2_541-567.indd 544 13/04/19 9:59 PM

13. Basicity of phenyl amineThe overlap of the lone pair on the N with the benzene delocalised system makes the lone pair less available for donation to H+ (to form a co-ordinate bond).

13

453

Learning objectives:➔ Explain why amines behave

as Brønsted–Lowry bases.➔ Explain why the base

strengths of amines di!er from each other and from ammonia.

Speci!cation reference: 3.3.11

28.2

Amines as basesAmines can accept a proton (an H+ ion) so they are Brønsted–Lowry bases.

—

— N

H

H

——

+ H+ + Cl–

H

— N — H + Cl–—

H

phenylamine

+

phenylammonium chloridea water-soluble, ionic salt

Reaction as basesAmines react with acids to form salts. For example, ethylamine, a soluble alkylamine, reacts with dilute hydrochloric acid:

C2H5NH2 + H+ + Cl

–

ethylamine

C2H5NH3+ + Cl

–

ethylammonium chloride

The products are ionic compounds that will crystallise as the water evaporates.

Phenylamine, an arylamine, is relatively insoluble, but it will dissolve in excess hydrochloric acid because it forms the soluble ionic salt.

— NH2 + H+ + Cl–

— NH3+ + Cl

–

phenylamine phenylammonium chloridea water-soluble, ionic salt

If a strong base like sodium hydroxide is added, it removes the proton from the salt and regenerates the insoluble amine.

— NH3+ + Cl

– + OH

– — NH2 + H2O + Cl

–

phenylamine

Comparing base strengthsThe strength of a base depends on how readily it will accept a proton, H+. Both ammonia and amines have a lone pair of electrons that attract a proton. So amines are weak bases.

Alkyl groups release electrons away from the alkyl group and towards the nitrogen atom. This is called the inductive effect and is shown by an arrow (Figure 1).

The inductive effect of the alkyl group increases the electron density on the nitrogen atom and therefore makes it a better electron pair donor (i.e., more attractive to protons). So, primary alkylamines are stronger bases than ammonia.

The properties of amines as bases

HintThe salts of amines are sometimes named as the hydrochloride of the parent amine. So ethylammorium chloride is also called ethylamine hydrochloride.

HintThe smell of a solution of an amine disappears when an acid is added due to the formation of the ionic (and therefore involatile) salt. The smell returns if a strong base is then added.

R — N

H2

⟨

▲ Figure 1 A primary amine. The arrow shows that R releases electrons. This is called the inductive e"ect


8 6

13. Diazonium SaltsAlkyl and aryl amines react with nitrous acid, HNO2, below 10 °C to produce diazonium salts containing the diazo group, N!N+. The diazonium salts of aryl amines are important intermediates in the manufacture of azo dyes.

16


26.2 AmidesMaking an amideAn amide group is represented in structural formulae by CONH2. For example, ethanamide can be shown as CH3CONH2. Its displayed formula is:

ethanamide

CH C

H

H NH2

O

Ethanamide can be made by reacting ethanoyl chloride with concentrated ammonia solution:

CH3COCl + NH3 → CH3CONH2 + HCl

On page 387 we saw how a primary amine reacts with an acyl chloride to produce a substituted amide.

C3H7COCl + C2H5NH2 → C3H7CONHC2H5 + HCl butanoyl chloride ethylamine N-ethylbutanamide

! e " rst step is the production of benzenediazonium chloride:

NH2 + HNO2 + HCl

benzenediazoniumchloride

N NCl– + 2H2O+

! is reaction is called diazotisation. Note that the positive charge on the diazonium ion is on the nitrogen atom with four bonds.

! e reaction mixture must be kept below 10 °C by using ice. ! is is because the diazonium salt is unstable and will decompose easily, giving o# nitrogen gas, N2, at higher temperatures.

In the second step, the diazonium ion reacts with an alkaline solution of phenol in a coupling reaction:

N2+

+ OH + H+

OH NN

! e positively charged diazonium ion acts as an electrophile. It substitutes into the benzene ring of phenol at the 4 position. An orange dye is formed, called an azo dye. ! e delocalised π bonding system extends between the two benzene rings through the N N group which acts like a ‘bridge’. ! is makes the azo dye, called 4-hydroxyphenylazobenzene, very stable (an important characteristic of a good dye). ! e azo dye forms immediately on addition of the phenol to the solution containing the diazonium ion (Figure 26.7).

By using alternative aryl compounds to phenol, we can make a range of brightly coloured dyes. For example, Figure 26.8 shows a molecule of a compound used as a yellow dye.

Figure 26.7 The azo dye (also called a diazonium dye) forms in a coupling reaction between the diazonium ion and an alkaline solution of phenol.

3 a i Which would be more readily attacked by an electrophile – benzene or phenylamine? Explain your answer.

ii Write a general equation to show the equation for the reaction of phenylamine with excess of an electrophile, represented as X+.

b i Why is the reaction of phenylamine to make the diazonium ion carried out below 10 °C?

ii Write a balanced equation to show how nitrous acid is made for the reaction in part b i to take place.

iii Show the two steps that would be used to make the yellow dye shown in Figure 26.8, starting from phenylamine.

Check-up

Figure 26.8 A molecule of a yellow azo dye.

N N N(CH3)2

diazonium salt



ethanamide

CH C

H

H NH2

O






NH2 + HNO2 + HCl


N NCl– + 2H2O+




N2+

+ OH + H+

OH NN









Check-up


N N N(CH3)2



ethanamide

CH C

H

H NH2

O






NH2 + HNO2 + HCl


N NCl– + 2H2O+




N2+

+ OH + H+

OH NN









Check-up


N N N(CH3)2

13. Diazonium SaltsThe reaction mixture must be kept below 10 °C by using ice. This is because the diazonium salt is unstable and will decompose easily, giving off nitrogen gas, N2, and phenols at room temperature.

18



ethanamide

CH C

H

H NH2

O






NH2 + HNO2 + HCl


N NCl– + 2H2O+




N2+

+ OH + H+

OH NN









Check-up


N N N(CH3)2



ethanamide

CH C

H

H NH2

O






NH2 + HNO2 + HCl


N NCl– + 2H2O+




N2+

+ OH + H+

OH NN









Check-up


N N N(CH3)2

380 24 Benzene and its compounds

Phenol also reacts vigorously with sodium metal, giving off hydrogen gas and again forming sodium phenoxide:

OH + 2Na 2 O–Na+ + H22 ⎯→

Substitution into the benzene ring of phenolCompared with benzene, phenol reacts more readily with electrophiles. " e overlap of one of the lone pairs of electrons on the oxygen atom in the OH group with the π bonding system increases the electron density of the benzene ring in phenol. " is makes the benzene ring more open to attack from electron-defi cient electrophiles. It ‘activates’ the benzene ring, especially at positions 2, 4 and 6.

Phenol therefore undergoes similar reactions to benzene, but phenol does so under milder conditions. For example, bromine water will not react with benzene at room temperature. To produce bromobenzene we need pure bromine (not a solution) and an iron(III) bromide catalyst. However, bromine water reacts readily with phenol, decolorising the orange solution and forming a white precipitate of 2,4,6-tribromophenol (Figure 24.6). Similar reactions happen between phenol and chlorine or iodine.

+ 3HBr+ 3Br2

OHOH

BrBr

Br

→

hydroxide or ethoxide ions, making phenoxide ions less likely to re-form the undissociated molecules.

Alternatively, we can explain the greater acidity of phenol by saying that phenol ionises to form a more stable negative ion, so the ionisation of phenol is more likely. " is results in the position of equilibrium in the phenol equation in Table 24.3 lying further to the right-hand side (i.e. more molecules donating H+ ion) than the other equations.

Ethanol is a weaker acid than water due to the electron-donating alkyl (ethyl) group attached to the oxygen atom in the ethoxide ion. " is has the eff ect of concentrating more negative charge on this oxygen atom, which more readily accepts an H+ ion. " is explains why the position of equilibrium lies further to the left-hand side, favouring the undissociated ethanol molecules.

5 a Place the following molecules in order of their acidity, starting with the most acidic:

CH3COOH C6H5OH HCl C3H7OH H2O

b Would you expect methanol to be more or less acidic than phenol? Explain your answer.

Check-up

24.4 Reactions of phenolWe can divide the reactions of phenol into those involving the hydroxyl group, OH, and those involving substitution into the benzene ring.

Breaking of the O H bond in phenolAlthough phenol is sparingly soluble in water, it dissolves well in an alkaline solution. As you have just learned, phenol is a weak acid so it will react with an alkali to give a salt plus water:

+ H2OOH + NaOH O–Na+

" e salt formed, sodium phenoxide, is soluble in water.

Figure 24.6 Bromine water is added to aqueous phenol.

" is activation of the benzene ring is also shown in the nitration of phenol. With benzene, we need a mixture of concentrated nitric and sulfuric acids to refl ux with

13. Diazonium SaltsBenzenediazonium chloride is prepared by adding a cold solution of sodium nitrite, NaNO2, to a solution of phenylamine in concentrated hydrochloric acid at 5 °C.

Initially, the sodium nitrite reacts with the hydrochloric acid to form nitrous acid. This then reacts with the phenylamine and more conc. HCl to produce benzenediazonium chloride.

17



ethanamide

CH C

H

H NH2

O






NH2 + HNO2 + HCl


N NCl– + 2H2O+




N2+

+ OH + H+

OH NN









Check-up


N N N(CH3)2

diazonium salt



ethanamide

CH C

H

H NH2

O






NH2 + HNO2 + HCl


N NCl– + 2H2O+




N2+

+ OH + H+

OH NN









Check-up


N N N(CH3)2



ethanamide

CH C

H

H NH2

O






NH2 + HNO2 + HCl


N NCl– + 2H2O+




N2+

+ OH + H+

OH NN









Check-up


N N N(CH3)2

dil HCl & NaNO2

at 5 oC

ORGANIC CHEMISTRY

456

Reaction with nitrous acid (nitric(III) acid)Nitrous acid, HNO2, is unstable, and has to be made as required by reacting together sodium nitrite and hydrochloric acid:

NaNO2 + HCl → NaCl + HNO2

Aromatic and aliphatic amines differ markedly in their reactions with nitrous acid.Primary aliphatic amines react in warm aqueous acidic solution to give nitrogen gas

and alcohols:

R NH2 ! HNO2 R OH ! N2 ! H2ONaNO2 ! HCl30 °C in water

Aryl amines, however, form fairly stable diazonium salts at low temperatures. Under these conditions nitrogen is not evolved, but a solution of the diazonium salt is formed:

NH2 HNO2 H

phenyldiazonium chloride

N N Cl 2H2ONaNO2 + HCl

Aryl diazonium salts are unstable and explosive when dry, but can be kept for several days in solution in a refrigerator.

Reactions of diazonium salts1 Adding a solution of a diazonium salt to hot water causes decomposition, and

produces phenol:

OH ! N2 ! HCladd to water

phenol

at T > 60°CN N Cl H2O

This is the analogous product to the alcohol produced when an aliphatic primary

amine reacts with nitrous acid.

2 The most important reactions of diazonium salts are their use in the formation of azo dyes (see panel opposite). When a solution of a diazonium salt is added to an alkaline solution of a phenol, an electrophilic substitution reaction (known as a coupling reaction) takes place:

NaOH(aq)

T < 5°CN N N OH

an azo compound

OH OH O H2O

N O

27.4 Preparing aminesThe two main methods of preparing alkyl amines both start with halogenoalkanes.

O By nucleophilic substitution with ammonia (see Topic 15, page 273):

heat in ethanolCH3CH2Br + 2NH3 CH3CH2NH2 + NH4Br under pressure

As long as an excess of ammonia is used, further substitutions giving secondary and tertiary amines can be avoided (see page 444).

181333_27_A_Chem_BP_449-468.indd 456 09/10/14 1:40 AM


97

13. Diazonium Salts Reaction With PhenolThe most important reactions of diazonium salts are their use in the formation of azo dyes. When a solution of a diazonium salt is added to an alkaline solution of a phenol, a coupling reaction takes place:

21

Coupling reactions

The positive charge on the − +N ≡ N group of the benzenediazonium ion means

that this group is itself a strong electrophile. Thus we might expect it to attack another benzene ring, particularly one that has an electron-donating group such as − OH attached to it:

N ≡ N + − +OH− OH + H+−N = N − −

(4-hydroxyphenyl)azobenzene

This is an example of a coupling reaction. If a cold solution of benzenediazonium chloride is added to a cold solution of phenol in sodium hydroxide, a bright orange precipitate is immediately formed. This is (4-hydroxyphenyl)azobenzene – a typical azo compound. Many different azo compounds can be formed by coupling reactions between diazonium compounds and activated aromatic rings. They are all brightly coloured. Their colour results from the extensive delocalised electron systems they possess, which extends from one ring through the —N——N— group to the next ring.

Fig 27.7 Many of the dyes used for clothes and fabrics are azo dyes

Fig 27.8 Structures of some azo dyes

‘Acid Orange 7’ (bright reddish-orange)

NaO3S−

−

N = N − −

HO

‘Direct Red 39’ (bluish-red)

OC2H5−N = N − −−N = N − −

− − −

−

CH3CH3

NaO3S

SO3Na

OH−N = N − −−N = N − −

−

−

−

NH2

−

N = N

H2N

−

OHHOOC

SO3Na

‘Direct Brown 57’ (reddish-brown) −

−

Coupling reactions are important in the dyestuffs industry for making azo dyes. Many different colours can be obtained by adjusting the structure of the azo compound. These can be quite complex as Figure 27.8 shows.

Unlike diazonium compounds, azo compounds are quite stable. Azo dyes do not fade or lose their colour, unlike many natural dyes.

514

Organic nitrogen compounds

9 Write the structures of the products you would expect to be formed at each stage when:

a phenylamine is dissolved in excess concentrated hydrochloric acid,

b sodium nitrite solution is added to the cooled solution from part a,

c the product from part b is added to a fresh solution of phenylamine.

Q U E S T I O N

13. Reactions of Diazonium Salts Adding a solution of a diazonium salt to hot water causes decomposition, and produces phenol.

19



ethanamide

CH C

H

H NH2

O






NH2 + HNO2 + HCl


N NCl– + 2H2O+




N2+

+ OH + H+

OH NN









Check-up


N N N(CH3)2



ethanamide

CH C

H

H NH2

O






NH2 + HNO2 + HCl


N NCl– + 2H2O+




N2+

+ OH + H+

OH NN









Check-up


N N N(CH3)2

380 24 Benzene and its compounds

Phenol also reacts vigorously with sodium metal, giving off hydrogen gas and again forming sodium phenoxide:

OH + 2Na 2 O–Na+ + H22 ⎯→

Substitution into the benzene ring of phenolCompared with benzene, phenol reacts more readily with electrophiles. " e overlap of one of the lone pairs of electrons on the oxygen atom in the OH group with the π bonding system increases the electron density of the benzene ring in phenol. " is makes the benzene ring more open to attack from electron-defi cient electrophiles. It ‘activates’ the benzene ring, especially at positions 2, 4 and 6.

Phenol therefore undergoes similar reactions to benzene, but phenol does so under milder conditions. For example, bromine water will not react with benzene at room temperature. To produce bromobenzene we need pure bromine (not a solution) and an iron(III) bromide catalyst. However, bromine water reacts readily with phenol, decolorising the orange solution and forming a white precipitate of 2,4,6-tribromophenol (Figure 24.6). Similar reactions happen between phenol and chlorine or iodine.

+ 3HBr+ 3Br2

OHOH

BrBr

Br

→

hydroxide or ethoxide ions, making phenoxide ions less likely to re-form the undissociated molecules.

Alternatively, we can explain the greater acidity of phenol by saying that phenol ionises to form a more stable negative ion, so the ionisation of phenol is more likely. " is results in the position of equilibrium in the phenol equation in Table 24.3 lying further to the right-hand side (i.e. more molecules donating H+ ion) than the other equations.

Ethanol is a weaker acid than water due to the electron-donating alkyl (ethyl) group attached to the oxygen atom in the ethoxide ion. " is has the eff ect of concentrating more negative charge on this oxygen atom, which more readily accepts an H+ ion. " is explains why the position of equilibrium lies further to the left-hand side, favouring the undissociated ethanol molecules.

5 a Place the following molecules in order of their acidity, starting with the most acidic:

CH3COOH C6H5OH HCl C3H7OH H2O

b Would you expect methanol to be more or less acidic than phenol? Explain your answer.

Check-up

24.4 Reactions of phenolWe can divide the reactions of phenol into those involving the hydroxyl group, OH, and those involving substitution into the benzene ring.

Breaking of the O H bond in phenolAlthough phenol is sparingly soluble in water, it dissolves well in an alkaline solution. As you have just learned, phenol is a weak acid so it will react with an alkali to give a salt plus water:

+ H2OOH + NaOH O–Na+

" e salt formed, sodium phenoxide, is soluble in water.

Figure 24.6 Bromine water is added to aqueous phenol.

" is activation of the benzene ring is also shown in the nitration of phenol. With benzene, we need a mixture of concentrated nitric and sulfuric acids to refl ux with

13. Phenyl Amine Reactions: Summary20Aromatic diazonium ions are important in the manufacture of dyes (Section 27.7).

Figure 27.6 summarises some important reactions of phenylamine.

Fig 27.6 Some important reactions of phenylamine

−NH2

HNO 2

below 10 °C

C6H5NH3+ Cl–

−− Br

−NH2

Br

Br

−

H+

OH–

Br2 (aq)

RCO Cl

RCONHC6H5

C6H5N ≡ N

C6H5OH + N2(g)

H 2O

above 10 °C

secondary amide

phenylammoniumchloride

benzenediazonium ion

2,4,6-tribromophenylaminephenol

+

The only stable diazonium salts are aromatic ones (Section 27.6), and even these are not particularly stable. Benzenediazonium chloride decomposes in aqueous solution above about 10 °C, and the compound is explosive when solid. However, the fact that it is reactive makes it useful in synthesis.

Benzenediazonium chloride is prepared by adding a cold solution of sodium nitrite to a solution of phenylamine in concentrated hydrochloric acid below 5 °C:

C6H5NH2(aq) + HNO2(aq) + HCl (aq) → C6H5 +N2Cl–(aq) + 2H2O (l)

phenylamine benzenediazonium chloride

Owing to the explosive nature of the solid, the compound is always used in solution.

The benzenediazonium ion reacts readily with nucleophiles. With a general nucleophile X−:

N2+−

+ N2

+ X−X–

The introduction of the diazonium group is therefore a way of making the aromatic ring susceptible to nucleophilic substitution. (Remember the characteristic reaction of an aromatic ring is normally electrophilic substitution.) This makes diazonium compounds useful in synthesis. For example:

C6H5N2+ + I– → C6H5I + N2

iodobenzene (warm benzenediazonium chloride with KI solution)

C6H6N2+ + H2O → C6H5OH + N2 + H+

phenol (warm the aqueous solution)

C6H5N2+ + Cl– → C6H5Cl + N2

chlorobenzene (warm benzenediazonium chloride with CuCl catalyst)

513

Diazonium salts27.7

27.7 Diazonium salts

8 Predict the structures of the products when phenylamine reacts with:

a dilute nitric acid, to give two monosubstituted products,

b concentrated nitric acid, to give a tri-substituted product.

Q U E S T I O N


• Describe the reaction to form diazonium salts

• Describe nucleophilic substitution and coupling reactions of diazonium salts


10 8

13. Diazonium Salts Reaction With Phenyl AmineBenzenediazonium chloride reacts with phenylamine it produces a yellow dye 4-aminoazobenzene

22

The nitrogen dioxide is very soluble in water, but the nitrogen monoxideescapes into the air and turns brown as it reacts with oxygen to form nitrogendioxide:

2NO(g) + O2(g) → 2NO2(g)

As the nitrous acid is unstable, it is usually prepared as and when needed byadding hydrochloric acid to sodium nitrite. The nitrous acid is said to begenerated in situ.

4.5 Azo dyesThe positive charge on the N≡N+− group means that diazonium ions arestrong electrophiles. So, we would expect them to attack aryl compounds withdelocalised π electrons, particularly those that have an electron-donatinggroup, such as −OH in phenols (Figure 4.13) and −NH2 in aromatic amines.

Reactions like this between diazonium ions and phenols or aromatic amines arecalled coupling reactions. If a cold solution of benzenediazonium chloride isadded to a cold solution of phenol in sodium hydroxide, an orange precipitateforms. The precipitate is 4-hydroxyazobenzene, which is an azo dye.

The commercial importance of diazonium salts is based on their couplingreactions with phenols and aromatic amines to form azo dyes. Most of thesedyes are red, orange or yellow. As we have already seen, benzenediazoniumchloride reacts with phenol to give an orange dye. With phenylamine itproduces a yellow dye 4-aminoazobenzene (Figure 4.14).

Unlike diazonium compounds, azo compounds are very stable and unreactive.The bright colours of azo compounds result from the extended delocalised

electron systems that spread across the whole molecule through the azo group,−N=N−. These delocalised azo systems absorb light in the blue region of thespectrum which results in the yellow, orange and red dyes. 45

10 a) Write an equation for the formation of nitrous acid, HNO2, in situ fromsodium nitrite solution and hydrochloric acid.

b) Write an ionic equation for the formation of nitrous acid, excluding spectatorions and showing only the ions involved.

c) The structural formula of nitrous acid is H−O−N=O. Draw a ‘dot-and-cross’diagram for nitrous acid showing outer shell electrons only.

11 When nitrous acid decomposes, it disproportionates (gets oxidised and reducedat the same time).a) Write an equation for the decomposition of nitrous acid.b) Calculate the oxidation numbers of the different atoms before and after

decomposition and explain why disproportionation has occurred.12 A solution of benzenediazonium chloride decomposes forming phenol above 10 °C.

a) What are the other products of the decomposition?b) Write a balanced equation, with state symbols, for the decomposition.

13 What kind of reactants would you expect diazonium ions with the diazo group,N≡N+−, to be?

Test yourself

Azo dyes

Figure 4.13 !The reaction between benzenediazoniumions and phenol.

N N OH OH + H+cold

solutions

+N N+

in NaOH(aq) 4-hydroxyazobenzene

Figure 4.14 !The reaction of benzenediazoniumchloride with phenylamine to form theyellow dye 4-aminoazobenzene.

NH2

4-aminoazobenzene

N N Cl– NH2 + HCl+

N N+

13. Diazonium Salts Reaction With Phenyl AmineThe following is a molecule of a yellow azo dye. Instead of phenol, C6H5OH, the reactant used in the coupling reaction is C6H5N(CH3)2.

23


N2+

+ OH + H+

OH NN

!e positively charged diazonium ion acts as an electrophile. It substitutes into the benzene ring of phenol at the 4 position. An orange dye is formed, called an azo dye, or diazonium dye. !e delocalised π bonding system extends between the two benzene rings through the NN group, which acts like a ‘bridge’. !is makes the azo dye, called 4-hydroxyphenylazobenzene, very stable (an important characteristic of a good dye). !e azo dye forms immediately on addition of the phenol to the solution containing the diazonium ion (Figure 27.7).



N N N(CH3)2

Figure 27.8 A molecule of a yellow azo dye. Instead of phenol, C6H5OH, the reactant used in the coupling reaction is C6H5N(CH3)2.

Amino acidsAmino acids are an important group of compounds that all contain the amino group ( NH2) and the carboxylic acid group ( COOH). One type of amino acid has the

NH2 group bonded to the C atom next to the COOH group. !ese 2-amino-carboxylic acids are the ‘building blocks’ that make up proteins.

!e general structure of a 2-amino-carboxylic acid molecule is shown in Figure 27.9.

R C

NH2

COOH

H

Figure 27.9 The general structure of a 2-amino-carboxylic acid.

!e general structural formula of a 2-amino-carboxylic acid is RCH(NH2)COOH.

!e R group is the part of the amino acid that can vary in di$erent amino acids. !e simplest amino acid is glycine (systematic name aminoethanoic acid) in which R is an H atom:

CH2N COOH

H

H

glycine (aminoethanoic acid)

Alanine (systematic name 2-aminopropanoic acid) is an amino acid in which the R group is the methyl group, CH3.

!e R group can be acidic (e.g. it contains another carboxylic acid group, COOH group), basic (e.g. it






QUESTION

404

Cambridge International A Level Chemistry

13. Skill CheckWrite an equation for the coupling reaction between benzenediazonium chloride and naphthalen-2-ol to form an azo dye.

24

When azo dyes were first discovered in the late nineteenth century, theyheralded a new regime for the dyeing of different fabrics. Vegetable dyes,which had been used in the past, faded easily. Azo dyes fade much moreslowly as a result of atmospheric oxidation and are not removed by water,soap or other cleaning agents because they attach themselves more stronglyto fabrics.

Azo dyes are also used in some foods (Figure 4.18) in spite of their toxicity.Fortunately, azo dyes are so strongly coloured that the quantities used amountto only milligrams per kilogram of food. Even so, some azo dyes have beenbanned from use in food (see the Activity on page 96). The toxicity arises notfrom the azo dyes themselves, but when they are metabolised and brokendown in the body. Their breakdown produces aromatic amines, some of whichare carcinogenic.

Some azo dyes were once thought to increase, or possibly cause,hyperactivity in children. Since the late 1970s, there have been several studiesinto the effects of azo dyes on hyperactivity, but most have provedinconclusive.

However, there is more substantial evidence to suggest that certain azodyes, especially tartrazine (Figure 4.19), increase the allergic reactions to somedrugs and cause increased breathing problems in people with asthma.

46

Figure 4.18 !Azo dyes are used to colour foods suchas sweets and fruit drinks.

Figure 4.19 "Tartrazine. Na+ –O NC

O

C S O– Na+

N

N OH

C

O S

O– Na+

O

C O

O

N

Amines

Figure 4.15 !This shirt is dyed with azo dyes.

14 a) Write an equation for the coupling reactionbetween benzenediazonium chloride andnaphthalen-2-ol (Figure 4.16) to form an azo dye.

b) Why is the reaction usually carried out with thenaphthalen-2-ol dissolved in sodium hydroxidesolution?

15 a) Draw the structures of the diazonium compound and the amine which couldbe used to make the red form of the acid–base indicator, methyl orange, inFigure 4.17.

b) Draw the structure of the amine used to make the diazonium compound inpart a).

c) Draw the structure of the yellow form of methyl orange which is produced inan alkaline solution such as NaOH(aq).

Test yourself

Figure 4.16 !

OH

Figure 4.17 !The red form of methyl orange.

H3C

H3C

OH

O

O

SN NN

naphthalen-2-ol


119

13. Preparing Amines Alkyl amines can be made: • By nucleophilic substitution of a halogenoalkane with ammonia • By reduction of nitriles using either LiAlH4 (lithium aluminium hydride) or

hydrogen over a nickel catalyst. • By nucleophilic substitution of a halogenoalkane with sodium cyanide,

followed by reduction using either LiAlH4 (lithium aluminium hydride) or hydrogen over a nickel catalyst.

• By the the reduction of amides with LiAlH4. Phenylamine can be prepared by the reduction of nitrobenzene with tin/concentrated HCl.

27

13. Skill checkWhat are the structures of the two compounds that couple to form the following dye?

26


457

Azo dyesThe azo group, ¬N“N¬, is called a chromophore. Compounds containing this group are highly coloured. Their colours range from yellow and orange to red, blue and green, depending on what other groups are attached to the benzene rings.

The common acid–base indicator methyl orange is an azo compound, made by the coupling reaction shown in Figure 27.12.

Many dye molecules used for dyeing clothes do not easily stick to the fi bres of the material by themselves. This is especially the case if their main method of intermolecular bonding (for example, van der Waals’, hydrogen bonding, ionic forces) does not match that of the molecules that make up the material. Mordants are often used to help the dye molecules stick. A mordant is a polyvalent metal ion, such as Al3+ or Fe3+, which can form co-ordination complexes both with the dye molecule and with ¬OH, ¬CO or ¬NH groups on the molecules that make up the fi bres of the material. By this means the dye molecule and the fi bre molecule are permanently held together by the metal ion. A great number of dyes for clothes, colour printing and food colouring (Figure 27.13) are azo dyes. Figure 27.14 shows two examples.

A chromophore is a group which, especially when joined to other unsaturated groups, causes a compound to absorb visible light, and so become coloured.


Barking Dog Art

Na+ –O3S NH2

Na+ –O3S N N N+(CH3)2

H

Na+ –O3S

+H+

+OH–

HNO2/HCl

T < 5°CN2Cl–

N(CH3)2+

Na+ –O3S N N N(CH3)2

(red, acid form) (orange, base form)methyl orange

+Figure 27.12 Methyl orange is an azo compound formed by a coupling reaction.


Barking Dog Art

NaO3S

Sunset Yellow Carmoisine (red)

SO3Na

N

N

HONaO3S

SO3Na

N

N

HOFigure 27.14 Some azo dyes used commercially

Figure 27.13 Food colours often contain azo dyes.

Now try this1 Draw the structures of the two compounds from which Sunset Yellow can be made by

a coupling reaction.2 What are the structures of the two compounds that couple to form Carmoisine?

181333_27_AS_Chem_BP_449-468.indd 457 06/11/14 5:42 PM

13. Skill checkDraw the structures of the two compounds from which Sunset Yellow can be made by a coupling reaction.

25


457

Azo dyesThe azo group, ¬N“N¬, is called a chromophore. Compounds containing this group are highly coloured. Their colours range from yellow and orange to red, blue and green, depending on what other groups are attached to the benzene rings.

The common acid–base indicator methyl orange is an azo compound, made by the coupling reaction shown in Figure 27.12.

Many dye molecules used for dyeing clothes do not easily stick to the fi bres of the material by themselves. This is especially the case if their main method of intermolecular bonding (for example, van der Waals’, hydrogen bonding, ionic forces) does not match that of the molecules that make up the material. Mordants are often used to help the dye molecules stick. A mordant is a polyvalent metal ion, such as Al3+ or Fe3+, which can form co-ordination complexes both with the dye molecule and with ¬OH, ¬CO or ¬NH groups on the molecules that make up the fi bres of the material. By this means the dye molecule and the fi bre molecule are permanently held together by the metal ion. A great number of dyes for clothes, colour printing and food colouring (Figure 27.13) are azo dyes. Figure 27.14 shows two examples.

A chromophore is a group which, especially when joined to other unsaturated groups, causes a compound to absorb visible light, and so become coloured.


Barking Dog Art

Na+ –O3S NH2

Na+ –O3S N N N+(CH3)2

H

Na+ –O3S

+H+

+OH–

HNO2/HCl

T < 5°CN2Cl–

N(CH3)2+

Na+ –O3S N N N(CH3)2

(red, acid form) (orange, base form)methyl orange

+Figure 27.12 Methyl orange is an azo compound formed by a coupling reaction.


Barking Dog Art

NaO3S

Sunset Yellow Carmoisine (red)

SO3Na

N

N

HONaO3S

SO3Na

N

N

HOFigure 27.14 Some azo dyes used commercially

Figure 27.13 Food colours often contain azo dyes.

Now try this1 Draw the structures of the two compounds from which Sunset Yellow can be made by

a coupling reaction.2 What are the structures of the two compounds that couple to form Carmoisine?

181333_27_AS_Chem_BP_449-468.indd 457 06/11/14 5:42 PM


12 10

13. Preparingamines: Halogenoalkane and Ammonia28Reagent Ammonia, NH3 (conc. or dissolved in ethanol)Condition heat under refluxProduct AmineType nucleophilic substitution

CHZCHZCN + 2h20 -7 CHZCHZCOZH t NHZ

H H H H"C-C- CN -> A -

C-C- Coat"t H A

CHZCHZCN + 2h20 + Ht 7 CHBCHZCOZH + NHK

CHZCHZCN + to OH -

-7 Cttsutzcoz+NHZ

CH3CHzBr + Ntb -

CH3CHzNHz+ HBN

H H H HI I I I

It -

C-C - H - H -

C-C-H"

3r H NHZ

13. Preparing Amines: Reduction of NitrilesNitriles can be reduced to amines by using either LiAlH4 in ether (lithium aluminium hydride) or or heating with H2 and Ni catalyst.

CH3CH2CN ⟶ CH3CH2CH2NH2

30

13. Halogenoalkane With CN—29Reagent potassium cyanide, KCN, (or sodium cyanide, NaCN) dissolved in

ethanolCondition heat under reflux in ethanolic solutionProduct NitrileType nucleophilic substitution

A A H H

it -

d-d-d-d- # Nat ,it It for! heatunawrpuxCHZCHZCHBRCHZ

It CH3 it H H

I I 1 I 1 NaottlaqlH - C - C -

C- c- C - H ->I I I I I hlatunderrthnH H Br

BNH(

CHDZCHCHIWCHBNC

'tZCHZBR + the7 CH3CHzOH+ HBN

H H H H1 1 1 1

It -

C-C - H - It -

C-C-H⇒

3r H OH

CH3CHzB✓ + CN.

7

CH3CHzCN+ Bt

H H H HI I I I

It -

C-C - H - It -

C-C-H"

Br H CN

A A H H

H -

d-[ -[ -d- H

Nauvdissdredinethanolh

.

It

for! heatunawrtmxCHZCHZCHBRCHZ

It CH3 it H H

1 1 I 1 I

Nacndissdredinethanolit

. c-c- c-Ctt 't heatundwrthn¥A Br H CI

(

CHDZCHCHIWCHZCHZU

A A H H

it -

d-d-d-d- # Nat ,it It for! heatunawrpuxCHZCHZCHBRCHZ

It CH3 it H H

I I 1 I 1 NaottlaqlH - C - C -

C- c- C - H ->I I I I I hlatunderrthnH H Br

BNH(

CHDZCHCHIWCHBNC

'tZCHZBR + the7 CH3CHzOH+ HBN

H H H H1 1 1 1

It -

C-C - H - It -

C-C-H⇒

3r H OH

CH3CHzB✓ + CN.

7

CH3CHzCN+ Bt

H H H HI I I I

It -

C-C - H - It -

C-C-H"

Br H CN

A A H H

H -

d-[ -[ -d- H

Nauvdissdredinethanolh

.

It

for! heatunawrtmxCHZCHZCHBRCHZ

It CH3 it H H

1 1 I 1 I

Nacndissdredinethanolit

. c-c- c-Ctt 't heatundwrthn¥A Br H CI

(

CHDZCHCHIWCHZCHZU

Importance of the reaction with CN҆ is that it extends the carbon chain by one carbon atom.


1311

13. Preparing Amines: Reduction of AmidesAmines are produced when amides are reduced. This allows amines to be synthesised from carboxylic acids:

32

13. Preparing Amines: ExampleThe ‘good feeling’ factor in chocolate has been identified as 2-phenylethylamine, C6H5CH2CH2NH2. Suggest a synthesis of this compound from chloromethylbenzene, C6H5CH2Cl.

33

ORGANIC CHEMISTRY

458

O By nucleophilic substitution with sodium cyanide, followed by reduction using either lithium tetrahydridoaluminate(III) (lithium aluminium hydride) or hydrogen over a nickel catalyst (see Topic 15, page 274):

heat in ethanol H2 + NiCH3CH2Br + NaCN CH3CH2CN CH3CH2CH2NH2

Notice that during this reaction the carbon chain length has been extended by one carbon atom.

Amines are also produced when amides are reduced by lithium tetrahydridoaluminate(III) (catalytic hydrogenation only succeeds under conditions of high pressure and temperature). This allows amines to be synthesised from carboxylic acids:

CO2H COCl CONH2SOCl2 NH3

CH2NH2LiAlH4

in dry ether

phenylmethylaminebenzoic acid

Aryl amines are most commonly prepared by the reduction of aromatic nitro compounds (see Topic 25, page 424):

NO2 NH2

Sn + conc. HCl

T <55 °C heat

3conc. HNO + conc. H2SO4

To produce the free amine, excess sodium hydroxide must be added after the reduction is completed.

Worked exampleThe ‘good feeling’ factor in chocolate has been identified as 2-phenylethylamine, C6H5CH2CH2NH2. Suggest a synthesis of this compound from chloromethylbenzene, C6H5CH2Cl.

AnswerThe target amine has one more carbon atom than the suggested starting material, so the cyanide route is required:

CH2Cl CH2CN CH2CH2NH2

NaCN in ethanol

heat

H2 + Ni

27.5 AmidesProperties of amidesAmides have the functional group:

C

NHR!

OR

δ–

δ+

δ–

R and R′ can be alkyl, aryl or hydrogen.Amides are extensively hydrogen bonded, having both Hδ+ atoms (on nitrogen) and

lone pairs of electrons (on oxygen and nitrogen). Most amides are solids at room temperature, and quite a number are soluble in water.

Unlike amines, amides form neutral solutions in water, and can be protonated only by strong acids. The site of protonation is unusual, and explains why amides are such weak bases.

Now try thisSuggest two ways of making butylamine (CH3CH2CH2CH2NH2), each method starting from a compound containing a different number of carbon atoms.

Now try thisDraw diagrams to show the hydrogen bonding between

a two molecules of ethanamide, CH3CONH2

b a molecule of ethanamide and two molecules of water.

181333_27_A_Chem_BP_449-468.indd 458 09/10/14 1:40 AM

13. Preparing Amines: Reduction of AmidesAmines are also produced when amides are reduced by heating with LiAlH4 (lithium aluminium hydride) dissolved in ether.

CH3CH2CONH2 ⟶ CH3CH2CH2NH2

31


14 12

13. Skill checkSuggest two-stage syntheses of the following compounds, from the stated starting materials.

36


461

Worked exampleSuggest products of the following reactions.

CH3CH2

a

X Y Z

b

A B

SOCl2 LiAlH4

PCl5 CH3CH2NH2

OH

C

O

OH

C

ONH3

Answera X is CH3CH2COCl Y is CH3CH2CONH2 Z is CH3CH2CH2NH2

b A is COCI B is CONHC2H5

Now try thisSuggest two-stage syntheses of the following compounds, from the stated starting materials.

1 CH2NH2 COClfrom

2 (CH3)2CH¬CH2NH2 from (CH3)CH¬Br

27.6 Amino acidsAmino acids have two functional groups:

H

H C

O

C

O

HH C

O

CN H

H

H O2

HN1

HH

The 2-amino acids (α-amino acids) form an interesting class of compounds, apart from their great importance as the building blocks of proteins. In many compounds containing two or more functional groups, the reactions of one group can be considered independently of those of the other group. They are often widely separated, and dissimilar to each other. In 2-amino acids, however, the two groups are near to each other. What is more, they are of opposite chemical types: the ¬NH2 group is basic, whilst the ¬CO2H group is acidic. Interaction between the two is inevitable.

Physical and chemical propertiesWhilst alkyl amines and the small-chain aliphatic carboxylic acids are liquids, the amino acids are all solids. They have high melting points (often decomposing before they can be heated to a suffi ciently high temperature to melt them), and are soluble in water. In another contrast to amines and carboxylic acids, they are insoluble in organic solvents such as methylbenzene.

181333_27_A_Chem_BP_449-468.indd 461 09/10/14 1:40 AM


461


CH3CH2

a

X Y Z

b

A B

SOCl2 LiAlH4

PCl5 CH3CH2NH2

OH

C

O

OH

C

ONH3




1 CH2NH2 COClfrom



H

H C

O

C

O

HH C

O

CN H

H

H O2

HN1

HH



181333_27_A_Chem_BP_449-468.indd 461 09/10/14 1:40 AM

13. Skill checkSuggest products of the following reaction:

34


461


CH3CH2

a

X Y Z

b

A B

SOCl2 LiAlH4

PCl5 CH3CH2NH2

OH

C

O

OH

C

ONH3




1 CH2NH2 COClfrom



H

H C

O

C

O

HH C

O

CN H

H

H O2

HN1

HH



181333_27_A_Chem_BP_449-468.indd 461 09/10/14 1:40 AM

13. Preparing Phenyl Amine: Reduction of NitrobenzeneAryl amines are prepared by the reduction of aromatic nitro compounds by heating with Sn and conc HCl.

35


Preparing aromatic aminesThe usual laboratory method for introducing an amine group into an aromatic compound is a two-step process – !rst nitration to make a nitro compound and then reduction (Figure 18.2.16). The reduction of the aromatic nitro-compound is achieved by boiling under re"ux with tin and concentrated hydrochloric acid (Figure 18.2.17). The aromatic amine dissolves in excess concentrated hydrochloric acid, forming a salt. The free amine can be liberated from the solution by adding sodium hydroxide solution. It is then separated from the mixture by steam distillation.

Equations for the reduction of nitrocompounds are usually simpli!ed by using [H] to represent the reducing agent.

C6H5NO2 + 6[H] ĺ C6H5NH2 + 2H2O

18.2.5 The preparation of amidesAmides form rapidly at room temperature when acyl chlorides, such as ethanoyl chloride, react with ammonia or with amines. For example, when ethanoyl chloride is carefully added to a concentrated aqueous solution of ammonia, a vigorous reaction takes place producing fumes of hydrogen chloride and ammonium chloride plus a residue of ethanamide.

CH3COCl(l) + NH3(aq) → CH3CONH2(s) + HCl(g) ethanamide

HCl(g) + NH3(g) → NH4Cl(s) ammonium chloride

The preparation of paracetamol discussed in the Activity in Section 18.2.3 involves the synthesis of an N-substituted amide.

TipReduction of nitrobenzene to phenylamine is an important reaction in industry notably in the preparation of dyes. Tin is an expensive metal so in industry the cheaper metal iron is used.

Figure 18.2.16 The two-step preparation of phenylamine from benzene.

benzene nitrobenzene phenylamine

NO2 NH2conc. HNO3

conc. H2SO450–60 °C

Sn metal

+ conc. HClheat

Figure 18.2.17 Reducing nitrobenzene to phenylamine by re!uxing with tin and hot concentrated hydrochloric acid.

water out

water in

concentrated hydrochloric acid

nitrobenzene

tin

cold water while adding the acid, then boiling to complete the reaction

TipThe reaction of a carboxylic acid with ammonia or an amine forms a salt, so in the laboratory, reactions using acyl chlorides are preferred for making amides. However, industrial methods to make polyamides use acids (see Section 18.2.9) rather than acyl chlorides because of the dif"culty of storing acyl chlorides and using them on a large scale (see Section 17.3.4).

469983_18.2_Chem_Y1-2_541-567.indd 550 13/04/19 9:59 PM


Preparing aromatic aminesThe usual laboratory method for introducing an amine group into an aromatic compound is a two-step process – !rst nitration to make a nitro compound and then reduction (Figure 18.2.16). The reduction of the aromatic nitro-compound is achieved by boiling under re"ux with tin and concentrated hydrochloric acid (Figure 18.2.17). The aromatic amine dissolves in excess concentrated hydrochloric acid, forming a salt. The free amine can be liberated from the solution by adding sodium hydroxide solution. It is then separated from the mixture by steam distillation.

Equations for the reduction of nitrocompounds are usually simpli!ed by using [H] to represent the reducing agent.

C6H5NO2 + 6[H] ĺ C6H5NH2 + 2H2O

18.2.5 The preparation of amidesAmides form rapidly at room temperature when acyl chlorides, such as ethanoyl chloride, react with ammonia or with amines. For example, when ethanoyl chloride is carefully added to a concentrated aqueous solution of ammonia, a vigorous reaction takes place producing fumes of hydrogen chloride and ammonium chloride plus a residue of ethanamide.

CH3COCl(l) + NH3(aq) → CH3CONH2(s) + HCl(g) ethanamide

HCl(g) + NH3(g) → NH4Cl(s) ammonium chloride

The preparation of paracetamol discussed in the Activity in Section 18.2.3 involves the synthesis of an N-substituted amide.

TipReduction of nitrobenzene to phenylamine is an important reaction in industry notably in the preparation of dyes. Tin is an expensive metal so in industry the cheaper metal iron is used.

Figure 18.2.16 The two-step preparation of phenylamine from benzene.

benzene nitrobenzene phenylamine

NO2 NH2conc. HNO3

conc. H2SO450–60 °C

Sn metal

+ conc. HClheat

Figure 18.2.17 Reducing nitrobenzene to phenylamine by re!uxing with tin and hot concentrated hydrochloric acid.

water out

water in

concentrated hydrochloric acid

nitrobenzene

tin

cold water while adding the acid, then boiling to complete the reaction

TipThe reaction of a carboxylic acid with ammonia or an amine forms a salt, so in the laboratory, reactions using acyl chlorides are preferred for making amides. However, industrial methods to make polyamides use acids (see Section 18.2.9) rather than acyl chlorides because of the dif"culty of storing acyl chlorides and using them on a large scale (see Section 17.3.4).

469983_18.2_Chem_Y1-2_541-567.indd 550 13/04/19 9:59 PM


1513

13. AmidesAmides have the following functional group, where R and R′ can be alkyl, aryl or hydrogen. Most amides are solids at room temperature, and quite a number are soluble in water. Unlike amines, amides form neutral solutions in water.

37

13. Formation of Amides: Acyl Chlorides With AmmoniaWhen concentrated ammonia solution is added to an acyl chloride a primary amide is formed.

39





8a= D

8a

=

88


=

8

=

=

=

=

=

8 =8

=

=

D

=

=

8

=

88

=Zi]na�WjiVcdViZ

=

8

=

=

= =

=

=

88

=

=

D

=

D

8

=A

8a

= D

8=

=

8=


=8a�Za^b^cViZY

D =


phenyl benzoate:

8a=

8a D

D

8D= D

8

e]Zcna�WZcodViZ

8a=

=

=

8

=

=

8

=

8=D

8aC

==

egdeVcVb^YZ

=

=

8

=

=

8 8=D

C='







8a=

=

=

8

=

=

8 8=D

8a =

==

=

8

=

=

8 =C

=

=

=

8

=

=

8 =C

D"Zi]naegdeVcVb^YZ

Zi]naVb^cZ

=

=

8

=

=

8 8=D



13. AmidesAmides are most readily prepared by reacting acyl chlorides with ammonia or amines.

38

ORGANIC CHEMISTRY

458

O By nucleophilic substitution with sodium cyanide, followed by reduction using either lithium tetrahydridoaluminate(III) (lithium aluminium hydride) or hydrogen over a nickel catalyst (see Topic 15, page 274):

heat in ethanol H2 + NiCH3CH2Br + NaCN CH3CH2CN CH3CH2CH2NH2

Notice that during this reaction the carbon chain length has been extended by one carbon atom.

Amines are also produced when amides are reduced by lithium tetrahydridoaluminate(III) (catalytic hydrogenation only succeeds under conditions of high pressure and temperature). This allows amines to be synthesised from carboxylic acids:

CO2H COCl CONH2SOCl2 NH3

CH2NH2LiAlH4

in dry ether

phenylmethylaminebenzoic acid

Aryl amines are most commonly prepared by the reduction of aromatic nitro compounds (see Topic 25, page 424):

NO2 NH2

Sn + conc. HCl

T <55 °C heat

3conc. HNO + conc. H2SO4

To produce the free amine, excess sodium hydroxide must be added after the reduction is completed.

Worked exampleThe ‘good feeling’ factor in chocolate has been identified as 2-phenylethylamine, C6H5CH2CH2NH2. Suggest a synthesis of this compound from chloromethylbenzene, C6H5CH2Cl.

AnswerThe target amine has one more carbon atom than the suggested starting material, so the cyanide route is required:

CH2Cl CH2CN CH2CH2NH2

NaCN in ethanol

heat

H2 + Ni

27.5 AmidesProperties of amidesAmides have the functional group:

C

NHR!

OR

δ–

δ+

δ–

R and R′ can be alkyl, aryl or hydrogen.Amides are extensively hydrogen bonded, having both Hδ+ atoms (on nitrogen) and

lone pairs of electrons (on oxygen and nitrogen). Most amides are solids at room temperature, and quite a number are soluble in water.

Unlike amines, amides form neutral solutions in water, and can be protonated only by strong acids. The site of protonation is unusual, and explains why amides are such weak bases.

Now try thisSuggest two ways of making butylamine (CH3CH2CH2CH2NH2), each method starting from a compound containing a different number of carbon atoms.

Now try thisDraw diagrams to show the hydrogen bonding between

a two molecules of ethanamide, CH3CONH2

b a molecule of ethanamide and two molecules of water.

181333_27_A_Chem_BP_449-468.indd 458 09/10/14 1:40 AM


16 14

13. Formation of Amides: Acyl Chlorides With AminesWhen acyl chlorides are reacted with amines N-substituted amides are formed.

40

54718.2.3 The properties and reactions of amines

C4H9 N

H

CH3

CH3

+ CH3Br C4H9 N

CH3

CH3

H

++

+C4H9 N

CH3

CH3

H

+ C4H9

CH3

+ HBr

butyldimethylamine

N

Br–

Br–

Figure 18.2.11 Formation of the tertiary amine butyldimethylamine.

The tertiary amine similarly can react further to form a quaternary ammonium salt (Figure 18.2.12).

C4H9 + CH3CH3

CH3

Br C4H9 N

CH3

CH3

CH3

++

butyltrimethylammonium bromide

Br–N

Figure 18.2.12 Formation of the quaternary ammonium salt butyltrimethylammonium bromide.

It is possible to limit further reaction by using an excess of the primary amine so that there is a much greater chance of the primary amine rather than the secondary amine acting as nucleophile with the halogenoalkane molecules.

If an excess of the halogenoalkane is used, the quaternary ammonium salt is the main product.

Reaction with acyl chloridesAmines also react as nucleophiles with the δ+ carbon atoms in the C

O

Cl group of acyl chlorides such as ethanoyl chloride (Figure 18.2.13). The reaction forms an N-substituted amide (see also Section 17.3.4).

Key term

Quaternary ammonium salt is an ammonium salt where all four hydrogens are replaced by alkyl or aryl groups.

TipQuaternary ammonium salts where two of the alkyl groups are long chains, such as [(CH3(CH2)17]2N(CH3)2

+Cl−, are used in fabric softeners.

CH3 C

O

CI

+ CH CH23 CH2CH2NH2

CH3 C

O

NCH2CH2CH2CH3

H

+ HCI

N-butyl ethanamide

c+

c– Figure 18.2.13 The reaction of butylamine with ethanoyl chloride.

A reaction of this type is involved in the manufacture of paracetamol; this is discussed in the activity that follows.

469983_18.2_Chem_Y1-2_541-567.indd 547 13/04/19 9:59 PM

13. Skill checkSuggest products of the following reaction:

42


461


CH3CH2

a

X Y Z

b

A B

SOCl2 LiAlH4

PCl5 CH3CH2NH2

OH

C

O

OH

C

ONH3




1 CH2NH2 COClfrom



H

H C

O

C

O

HH C

O

CN H

H

H O2

HN1

HH



181333_27_A_Chem_BP_449-468.indd 461 09/10/14 1:40 AM

13. Formation of Amides: Acyl Chlorides With Amines41





8a= D

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phenyl benzoate:

8a=

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phenyl benzoate:

8a=

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8a=

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1715

13. Amide HydrolysisHydrolysis of primary amides produces a carboxylic acid and ammonia. The amide is heated under reflux with hydrochloric acid or sodium hydroxide solution, to hydrolyse it.

43

RCONH2 + H2O ⟶ RCO2H + NH3

RCONHR’ + H2O ⟶ RCO2H + R’NH2

carboxylic acid

Primary amides have the general formula

=

O






+ CH3COCl

−NHCOCH3

+ HCl


−NH2









=

O


=

O





+Cl–.

515










13. Amide HydrolysisHydrolysis of secondary amides produces a carboxylic acid and an amine

44

RCONHR’ + H2O ⟶ RCO2H + R’NH2

394 26 Organic nitrogen compounds

With an alkali, the products are the salt of the carboxylic acid and ammonia.

Both these reactions occur at room temperature, releasing white fumes of hydrogen chloride immediately as the reactants are added together. If there is an excess of the amine, it will react with the HCl formed to make its salt. For example, in the previous reaction ethylamine will form ethylammonium chloride, C2H5NH3

+Cl−.

The italic letter N is used in naming substituted amides to denote which alkyl or aryl group or groups are bonded to the nitrogen atom. For example, in N-ethylbutanamide, C3H7CONHC2H5, the ethyl (C2H5–) group has replaced an H atom in the amide group. If the H atom on the nitrogen in this molecule is replaced by another alkyl or aryl group, two N’s are used in the name, e.g. C3H7CON(C2H5)2 is called N,N-diethylbutanamide.

Fact fi le

Hydrolysis of amides" e characteristic CONH group in substituted amides links the two hydrocarbon sections of their molecules together. " is link can be broken by hydrolysis with an acid or an alkali. " e amide is re# uxed with, for example, hydrochloric acid or sodium hydroxide solution, to hydrolyse it:

R1 C

NHR2

Ohydrolysis

R1COOH

R1COO–Na+

H+

acid

OH–

alkaliR2NH2+

R2NH2

R2NH3+

excess H++

" e products of hydrolysis of a substituted amide with acid are a carboxylic acid (R1COOH) and a primary amine (R2NH2). " e amine formed will react with excess acid in the reaction vessel to make its ammonium salt, e.g. R2NH3

+Cl− with excess hydrochloric acid.With an alkali, such as aqueous sodium hydroxide,

the products are the sodium salt of the carboxylic acid (R1COO−Na+) and the primary amine (R2NH2).

If we re# ux an unsubstituted amide (RCONH2) with acid, the products are the corresponding carboxylic acid and ammonia. " e ammonia in solution reacts with excess acid to make an ammonium salt.

4 a Write an equation to show the formation of the following compounds using an acid chloride:i propanamideii N-ethylpropanamide.

b Write an equation to show the hydrolysis of:i butanamide by re# uxing with dilute

hydrochloric acidii N-ethylbutanamide by re# uxing with

aqueous sodium hydroxide.

Check-up

26.3 Amino acidsAmino acids are an important group of compounds that all contain the amino group ( NH2) and the carboxylic acid group ( COOH). One type of amino acid has the

NH2 group bonded to the C atom next to the COOH group. " ese 2-amino-carboxylic acids are the

‘building blocks’ that make up proteins." e general structure of a 2-amino-carboxylic acid

molecule is shown in Figure 26.9.

" e general structural formula of a 2-amino-carboxylic acid is RCH(NH2)COOH.

" e R group is the part of the amino acid which can vary in di$ erent amino acids. " e simplest amino acid is glycine, aminoethanoic acid, in which R is an H atom:

Figure 26.9 The general structure of an amino acid.

R C

NH2

COOH

H

13. Reduction of Amides45Amines are also produced when Amides undergo reduction by heating with LiAlH4 (lithium aluminium hydride) or H2 and Ni to produce amines.

CH3CH2CONH2 ⟶ CH3CH2CH2NH2


18

Nitrogen Compounds Bilal Hameed

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