S5: Chemistry

    Key unit competency:

The learner should be able to relate the chemical nature of the amines and 

aminoacids to their properties, uses and reactivity.

Learning objectives

At the end of this unit, the students will be able to:
• Explain the zwitterion forms in the solution of different pH.
• Explain the isoelectric point in amino acids.
• Describe the physical properties and uses of amines.
• Describe the preparation methods of the amines.
• Describe the reactions of amino acids and amines with other substances.
• Classify amines as primary, secondary and tertiary amines.
• Compare and contrast the physical properties of the amino acids to those of 
carboxylic acids and amines.

• Test the presence of amines and amino acids in the solution. 

Introductory activity

Read the text below, observe the accompanying images and answer the 
questions.

The cell is the basic structural, functional, and biological unit of all known living 
organisms. A cell is the smallest unit of life. All cells are made up of Inorganic 
compounds and Organic compounds. Inorganic compounds are compounds 
that do not contain carbon atoms except carbonates ,carbides, carbon oxides 
,carbonic acid while organic compounds are compounds that mainly contain 
carbon (C) and hydrogen (H) atoms, and eventually other elements such as 
oxygen (O) and nitrogen (N) in biological macromolecules that include the 

carbohydrates, lipids, proteins and nucleic acids.

Proteins are macromolecules consisting of one or more long chains of amino 
acid residues. Proteins differ from one another primarily in their sequence of 
amino acids which is dictated by the nucleotide sequence of their genes, 
and which usually results in protein folding into a specific three-dimensional 
structure.
 
That determines its activity. Nucleic acids [Deoxyribonucleic acid (DNA) and 
ribonucleic acid (RNA)] alongside proteins, lipids and complex carbohydrates 
(polysaccharides), are one of the four major types of macromolecules that are 
essential for all known forms of life. They are a thread-like chain of nucleotides 
carrying the genetic instructions used in the growth, development, functioning 
and reproduction of all known living organisms and many viruses.
 
The image below shows the partial molecular structure of DNA (A) and of 

proteins (B, C).

       

1. Identify the common point between DNA and proteins. Explain your 
answer.
2. The terminology “amino acid” is found in the text and image above. 
     According to you, what is it, and what is its role in living organisms?
3. If protein molecules are made essentially of Carbon, Hydrogen, Oxygen, 
     Nitrogen and amino acid side chains (figure C),
    a. What kind of bonds do you expect to see in those structures?

    b. What kind of reactions do you expect in those molecules?

9.1. Nomenclature and classification of amines

      Activity 9.1 

Pentan-2-ol, butan-1-ol and 2-methylpropan-2-ol are alcohols.
1. For each one:
a. give its molecular formula 
b. give its structural formula 
c. give its displayed formula 
d. give its skeletal formula 
e. State whether it is a primary, secondary or tertiary alcohol. 
2. Give the general formula that is used to represent alcohols. 
3. Two of the alcohols in this question are isomers of each other. Identify 

   which two and identify the type of isomerism they show. 

4. Name the alcohol whose structural formula is 

Amines are one of organic compounds containing nitrogen. They are one of the 
most important classes of organic compounds which are obtained by replacing 
one or more hydrogen atoms by an alkyl or aryl group in a molecule of ammonia 
They are present in vitamins, proteins, hormones, etc. They are extensively 

used in the manufacturing of many drugs and detergents. 

 9.1.1 Classification of amines

As per VSEPR theory, nitrogen present in amines is sp3
 hybridized and due to the 
presence of lone pair, it is pyramidal in shape instead of tetrahedral shape which is a 
general structure for most  hybridized molecules. Each of the three 
 hybridized orbitals of nitrogen overlap with orbitals of hydrogen or carbon depending
upon the configuration of amines. Due to the presence of lone pair, the C-N-H angle in amines 
is less than 109 degrees which is characteristic angle of tetrahedral geometry. The 

angle in amines is near about 108 degrees.

The functional group of amines is  Depending upon the number of 
hydrogen atoms that are replaced by an alkyl or aryl group in ammonia, amines are 

classified as primary, secondary and tertiary (Table 9.1). 

            

9.1.2 Nomenclature of amines

In organic chemistry, the names of the compounds are given according to the 
guidelines provided by IUPAC. In this regards, amines are named by ending with –
amine. The IUPAC system names amine functions as substituents on the largest alkyl 

group. 

         

If the amine is secondary and has two alkyl groups attached to the nitrogen, then 
each chain is named and the smaller alkyl group is preceded by an –N which plays 

the same role as a number in positioning a side alkyl chain.

           

 N-methylpropylamine is the common name and N-methyl-1-aminopropane
 is the IUPAC name.
If in the common naming the lengths of the chain are the same, an –N is not used 

as shown in the following example:

(Diethylamine is the common name which does not 
contain N because the chains have the same length and N-ethylethanamine is 

the IUPAC.

case of a tertiary amine, the use of N is applied at each alkyl side group.

                   

The following are examples of primary, secondary and tertiary amines (Table 9.2) 

with their corresponding names using IUPAC of common name.

             

      Aliphatic and Aromatic and heterocyclic amines are named after the groups 

     surrounding the nitrogen + amine.

         

 In case of heterocyclic amines, there is a systematic nomenclature of these 
compounds as indicated in the following examples. 
         
         

      Checking up 9.1

1. Classify the following as primary, secondary and tertiary amines.

           

2. For each compound below, provide the respective IUPAC name.

              

         3. Write IUPAC names of the following compounds and classify them into 

          primary, secondary and tertiary amines.

                  

   9.2 Physical properties, natural occurrences and uses of amines. 

    Activity 9.2 

Calculate the molecular mass of the given products and justify the difference 

between boiling points of amines, alkanes and alcohols

         

9.2.1 Physical properties of amines

Primary and secondary amines can form a hydrogen bond to each other (as shown 
in the Figure 9.1 below where two molecules of  are bonded together).

Because Nitrogen is less electronegative than oxygen, the N—H bond is not quite 
as polar as the O—H bond reason why hydrogen bonds in amines are not strong 
than these alcohol molecules. Therefore primary and secondary amines have lower 

boiling points than alcohols of similar molecular weight.

                    

Tertiary amines do not bond to each other by hydrogen bond and they have boiling 
points similar to those of hydrocarbons of the same molecular weight. However, 
primary, secondary and tertiary amines form hydrogen bond with water and amines 

with low-molecular weight are generally soluble in water.

               

Generally the boiling point of amines increases as the molecular weight increase 
and they boil at higher temperatures than alkanes but at lower temperatures than 
alcohols of comparable molar mass.
The amines are soluble in organic solvent and the solubility decreases as the 
molecular weight increases. The Table 9.3 summarizes some physical properties of 

some amines.

Table 9.3: Physical pproperties of some amines compared to some

 oxygen containing compounds.

             

Amines tend to be gases at low molecular weight (e.g. up to trimethylamine) 
and the heavier ones are liquids at room temperature. In fact, methyl, dimethyl, 
trimethyl, and ethyl -amines are gases under standard conditions. Most common 
alkyl amines are liquids, and high molecular weight amines are, quite naturally, solids
at standard temperatures. Additionally, gaseous amines possess a characteristic 
ammonia smell, while liquid amines have a distinctive “fishy” smell: higher molecular 
weight amines often smell like rotting fish, and are often found in decaying 
animal tissues. Cadaverine and putrescine are some 
of the examples. The lower molecular- weight amines with up to about five carbon 
atoms are soluble in water. The higher-molecular-weight amines that are insoluble 

in water will dissolve in acid to form ionic amine salts.

9.2.2 Natural occurrence of amines and their usage

Natural amines occur in proteins, vitamins, hormones, etc. and they are
 also prepared synthetically to make polymers, drugs and dyes.

Amines can be used as dyes (colorants) or as drugs: Primary aromatic amines are 
used as a starting material for the manufacture of azo dyes. They react with nitrous 
(II) acid to form diazonium salt which can undergo a coupling reaction in order to 
form an azo compound. As azo compounds are highly coloured, they are widely 

used in dyeing industries. Examples include Methyl orange and Direct brown 138.

In medicine, amines can be used as drugs.

• Chlorpheniramine is an antihistamine that helps to relief allergic disorders 
   due to cold, hay fever, itchy skin, insect bites and stings.

• Diphenhydramine is the common antihistamine.

• Chlorpromazine is a tranquillizer that anaesthetizes without inducing sleep. 
   It is used to relieve anxiety, excitement, restlessness or even mental disorder.

• Acetaminophen is also known as paracetamol or p-acetaminophenol, it is 
an analgesic that relieves pains such as headaches. It is believed to be less 
corrosive to the stomach and is an alternative to aspirin.

Amines are widely encountered in biological and pharmacological studies. Some 
important examples are the 2-phenylethylamines, some vitamins, antihistamines, 
tranquilizers, and neurotransmitters (noradrenaline, dopamine and serotonin) 

which act at neuromuscular synapses.

Checking up 9.2

1. Which compound of each pair has the higher boiling point? Explain.

a. butylamine or pentane

    

 2. Between the two compounds  explain which 
is more soluble in water.
 

 9.3 Preparation of amines. 

Activity 9.3

Ammonia   molecules react with water molecules. Write the detailed 

chemical equation of that reaction.

The amines can be prepared based on the following reactions:

9.3.1 Alkylation of ammonia

Primary amines can be synthesized by alkylation of ammonia. The reaction involves 
nucleophilic substitution of an alkyl halide when ammonia is used as nucleophilic 

agent. The reaction is carried out in a sealed tube at 100 °C or 373 K. 

   

9.3.2. Gabriel phthalimide synthesis

This procedure is used for the preparation of primary amines. Phthalimide on 
treatment with ethanolic potassium hydroxide forms potassium salt of phthalimide 
which on heating with alkyl halide followed by alkaline hydrolysis produces the 
corresponding primary amine. However, primary aromatic amines cannot be 
prepared by Gabriel phthalimide synthesis because aryl halides do not undergo 

nucleophilic substitution with the anion formed by phthalimide.

               

9.3.3. Hoffmann bromamide degradation reaction

Hoffmann developed a method for the preparation of primary amines by treating an 
amide with bromine in an aqueous or ethanolic solution of sodium hydroxide. This 
is a degradation reaction with migration of an alkyl or aryl group taking place from 
carbonyl carbon of the amide to the nitrogen atom. 

The reaction is valid for the preparation of primary amines only, and it yields 

uncontaminated compound with other amines. 

      

9.3.4 Reduction of amides

Similarly to reduction of amides, lithium aluminium hydride reduces 

amides to amines. 

             

9.3.5 Reduction of nitriles

Nitriles are reduced to amines using hydrogen in the presence of a nickel catalyst, 
although acidic or alkaline conditions should not be used to avoid the possible 
hydrolysis of the -CN group. is more commonly employed for the reduction of 

nitriles on the laboratory scale.

                     

9.3.6 Reduction of nitro compounds

Nitro compounds are reduced to amines by passing hydrogen gas in the presence 
of finely divided nickel, palladium or platinum and also by reduction with metals 
in acidic medium. Nitroalkanes can also be similarly reduced to the corresponding 

alkanamines.

                   

Reduction with iron scrap and hydrochloric acid is preferred because 
 formed gets hydrolysed to release hydrochloric acid during the reaction.
Thus, only a small amount of hydrochloric acid is required to initiate the reaction.

Checking up 9.3

1. Give two reagents that could be used to synthesize the following 

    reaction.

       

2.Discuss the conditions for using each of the reagents of your choice.

3.Write chemical equations for the following reactions:

a. Reaction of ethanolic
b. Ammonolysis of benzoyl chloride and reaction of amine so formed with 

       two moles of 

9.4. Chemical properties of amines

      Activity 9.4

Experiment: In a solution of ethylamine at room temperature (A), add dilute 
hydrochloric acid (B). After a while (C), add excess of sodium hydroxide in the 
solution (D) to obtain the solution E.   
  

           

           Explain: 

1. What evidence is there for a chemical reaction between ethylamine and 
   hydrochloric acid?
2. Why does the smell of ethylamine disappear when hydrochloric acid is added?
3. Why does the smell reappear when sodium hydroxide is added?

Difference in electronegativity between nitrogen and hydrogen atoms and the 

presence of unshared pair of electrons over the nitrogen atom makes amines 
reactive. The number of hydrogen atoms attached to nitrogen atom also is involved 
in the reaction of amines; that is why the reactivity of amines differ in many reactions. 
Amines behave as nucleophiles due to the presence of unshared electron pair.
 
The chemical properties of amines are summarized in the reactions below.

9.4.1 Reactions of amines diluted with acids
Amines, like ammonia, are bases. Being basic in nature, they react with acids to 

form salts.

               

Amine salts on treatment with a base like NaOH, regenerate the parent amine.

                  

             

 9.4.2 Reactions of amines (alkylation, acylation, and sulfonation)

Acyl chlorides and acid anhydrides react with primary and secondary amines to 
form amides. Tertiary amines cannot be acylated due to the absence of a replaceable 

hydrogen atom. 

                

              

9.4.3. Reaction with carboxylic acid

Because amines are basic, they neutralize carboxylic acids to form the corresponding 
ammonium carboxylate salts. Upon heating at 200°C, the primary and secondary 

amine salts dehydrate to form the corresponding amides.

             

9.4.4. Reaction with nitrous acid

Nitrous acid,  is unstable. It is produced indirectly using a mixture of 

 and a strong acid such as  in diluted solution. Primary aliphatic amines react 

with nitrous acid to produce a very unstable diazonium salts which spontaneously 

decomposes by losing to form a carbenium ion. Further, the carbonium ion is 

used to produce a mixture of alkenes, alkanols or alkyl halides, with alkanols as 

major product said above.

      

        

Primary aromatic amines, such as aniline (phenylamine) forms a more stable 
diazonium ion at  Above 5°C, it will decompose to give phenol and 
 Diazonium salts can be isolated in the crystalline form but are usually used in solution 

and immediately after preparation, due to its rapid decomposition.

                   

9.4.5. Reactions with ketones and aldehydes

Primary amines react with carbonyl compounds to form imines. Specifically, 
aldehydes become aldimines, and ketones become ketimines. In the case of 

formaldehyde (R’ = H), the imine products are typically cyclic trimers.

           

Secondary amines react with ketones and aldehydes to form enamines. An 
enamine contains a C=C double bond, where the second C is singly bonded to N as 

part of an amine ligand.

           

9.4.6. Neutralization reactions

Tertiary amines  react with strong acids such as hydroiodic acid (HI), hydrobromic 
acid (HBr) and hydrochloric acid (HCl) to give ammonium salts 

              

Checking up 9.4

1. Draw the structures of all amines of molecular formula . Classify 
    them as primary, secondary and tertiary amines
2. a. Write the equation for the reaction which happens when dimethylamine, 
 reacts with water.
b. Write the formula of the product of the reaction between trimethylamine 
     gas,  and hydrogen chloride gas, showing the essential details of 
      its structure.
3.Nitrous acid is unstable and has to be produced in the same test tube as the 
   reaction is happening in. If you were to test an amine with nitrous acid, how 

   would you do it?

4.This question is about the reactions between amines and halogenoalkanes 
(alkylhalides).
The reaction between bromoethane and ethylamine produces a complicated 
mixture of products, but the first to be formed are given by the equations 

below:

          

Describe in words what is happening.

These next three questions are deliberately made uncooperative so that you 
can only do them by understanding what you have read, and not just learning 
it. Take your time over them.

5. Write the formulae for the corresponding products of the reaction if you started 
    with methylamine rather than ethylamine, but still reacted it with bromoethane.

6. If you started with a secondary amine such as dimethylamine, you would 
     initially get a tertiary amine and its salt in the mixture. Write the formulae of 
    these products if you reacted dimethylamine with bromoethane.

7. Draw the structure of the product that you would get if you reacted the tertiary 

    amine trimethylamine with bromoethane.

9.5. General structure of amino acids and some common 

         examples

     Activity 9.5

Amines are molecules that have as general formula,  while carboxylic 
acids have as general formula, R–COOH. Predict a general structure (skeletal 
formula) of a molecule that contains an amino group and a carboxyl group on 

an aliphatic chain.

9.5.1. General structure of amino acids

Amino acids are organic compounds containing amine  and carboxyl (-COOH) 
functional groups, along with a side chain (R group) specific to each amino acid. 
The key elements of an amino acid are carbon (C), hydrogen (H), oxygen (O), and 
nitrogen (N). About 500 naturally occurring amino acids are known. 

The general structure of amino acid is shown by the functional group  and 
a carboxylic acid group (-COOH) attached to the same carbon and they are called 

α-amino acids.

                                    

The R group is the part of the amino acid that can vary in different amino acids. It 
can be a hydrogen (in that case, the amino acid is called Glycine) or a 

 group (Alanine) or other radicals.

9.5.2. Common Amino Acids

Among the 500 known amino acids, there are 20 important α-amino acids, as shown 
in the Table 9.4 below. Each amino acid has a common name. You will notice that 
the names in common used for amino acids are not descriptive of their structural 
formulas; but at least they have the advantage of being shorter than the systematic 
names. The abbreviations (Gly, Glu, …) that are listed in table below, are particularly 
useful in designating the sequences of amino acids in proteins and peptides. 

Table 9.4: Common amino acids and their formulas [adapted from (Chang, 2005) and 

(Schmitz, 2018)]

         

                         

                           

                             

                               

The first amino acid to be isolated was asparagine in 1806. It was obtained from 
protein found in asparagus juice (hence the name). Glycine, the major amino acid 
found in gelatin, was named for its sweet taste (Greek glykys, meaning “sweet”). In 
some cases an amino acid found in a protein is actually a derivative of one of the 

common 20 amino acids.

Checking up 9.5

1. Write the side chain of each amino acid.
      a. serine
     b. arginine

     c. phenylalanine

2. Draw the structure for each amino acid.
    a. alanine
    b. cysteine
    c. histidine
3. Identify an amino acid whose side chain contains:
     a. amide functional group.
    b. aromatic ring.

    c. carboxyl group.

9.6. Comparison of physical properties of amino acids to 

       those of carboxylic acids and amines

   Activity 9.6 

By using examples, distinguish amines, carboxylic acids and amino acids (in 

different states: gas, liquid, solid) based on their characteristic odour. 

The amino acids, carboxylic acids and amines have different functional groups;
this is the base of their different physical properties as shown in the Table 9.5.

Table 9.5. Comparison of physical properties of amines, carboxylic acids and amino 

acids.

               

                 

                   

                            

      Checking up 9.6

Discuss the solubility of amino acids, referring on the solubility of amines and 

carboxylic acids

      9.7. Chemical properties of amino acids       

       Activity 9

A and B are organic products formed from the reactions in a) and b) 

respectively, propose a mechanism of those reactions and identify A and B.   

    

The reactivity of amino acids involves the reactions of both amines and carboxylic 

acids. Some of these reactions are given below.

9.7.1. Acid–base properties of amino acids

As the name suggests, amino acids are organic compounds that contain both a 
carboxylic acid group and an amine group. Amino acids are crystalline, high melting 
point (>200°C) solids. Such high melting points are unusual for a substance with 
molecules of this size — they are a result of internal ionisation. Even in the solid 
state, amino acids exist as zwitterions in which a proton has been lost from the 

carboxyl group and accepted by the nitrogen of the amine group:

                  

So instead of hydrogen bonds between the amino acid molecules there are stronger 
ionic (electrovalent) bonds. This is reflected in the relative lack of solubility of amino 
acids in non- aqueous solvents compared with their solubility in water.

Zwitterions exhibit acid–base behaviour because they can accept and donate 
protons. In acids a proton is accepted by the carboxylic acid anion, forming a unit 

with an overall positive charge:

                        

  In alkalis the reverse occurs with the loss of a proton from the nitrogen atom:

             

       The species present in a given solution depends on the pH of the solution.

Carboxylic acids have acidic properties and react with bases. Amines have basic 
properties and react with acids. It therefore follows that amino acids have both 

acidic and basic properties.

      9.7.2. Isoelectric point in aminoacids (pI)

The isoelectric point (pI), is the pH at which a particular molecule carries no net 
electrical charge in the statistical mean. This means it is the pH at which the amino 
acid is neutral, i.e. the zwitterion form is dominant. The pI is given by the average of 

the pKa that involve the zwitterion, i.e. that give the boundaries to its existence

The table below shows the pKa values and the isoelectronic point, pI, are given 

below for the 20 α-amino acids (Table 9.6).

    

       Table 9.6. pKa and pI values for the 20 α-amino acids

              

           

             There are 3 cases to consider:

    1. Neutral side chains

These amino acids are characterised by two pKa values: and for the 
carboxylic acid and the amine respectively. The isoelectronic point will be halfway 
between, or the average of, these two pKa values . This is most readily appreciated 
when you realise that at very acidic pH (below pka1) the amino acid will have an 
overall positive charge and at very basic pH (above ) the amino acid will have 

an overall negative charge. 

                 

 The other two cases introduce other ionisable groups in the side chain “R” described 

by a third acid dissociation constant,

     2. Acidic side chains

The pI will be at a lower pH because the acidic side chain introduces an “extra” 
negative charge. So the neutral form exists under more acidic conditions when the 
extra -ve has been neutralised. For example, for aspartic acid shown below, the 
neutral form is dominant between pH 1.88 and 3.65, pI is halfway between these 

two values 

           

3. Basic side chains

The pI will be at a higher pH because the basic side chain introduces an “extra” 
positive charge. So the neutral form exists under more basic conditions when the 
extra positive has been neutralised. For example, for histidine, which has three acidic 
groups of pKa’s 1.82 (carboxylic acid), 6.04 (pyrrole NH) and 9.17 (ammonium NH), 
the neutral form is dominant between pH 6.04 and 9.17; pI is halfway between these 

two values, i.e. , so pI = 7.60. 

  9.7.3. Reaction with strong acids

In the following reaction, amino acids react with strong acids such as hydrochloric 

acid:

          

    9.7.4. Reaction with nitrous acid (deamination)

The amine function of α-amino acids and esters reacts with nitrous acid in a similar 
manner to that described for primary amines. The diazonium ion intermediate loses 
molecular nitrogen in the case of the acid, but the diazonium ester loses a proton 

and forms a relatively stable diazo compound known as ethyl diazo ethanoate:

                           

The diazo ester is formed because of the loss of from the diazonium ion which 

results in the formation of a quite unfavourable carbocation.

9.7.5. Reaction with sodium hydroxide
Amino acids react with strong bases such as sodium hydroxide:

9.7.5. Reaction with sodium hydroxide

Amino acids react with strong bases such as sodium hydroxide:

         

     In high pH, therefore, amino acids exist in anionic form:

                                           

9.7.6. Reaction of amino acids with sodium carbonate

Amino acids are instantly dissolved by strong hydrochloric acid but are in part 
recovered unchanged on dilution and evaporation. They are not decomposed by 
sodium carbonate but are easily decomposed by sodium hydroxide. (Dakin & West, 

1928).

Checking up 9.7

1. Draw the structure for the anion formed when glycine (at neutral pH) 
  reacts with a base.
2. Draw the structure for the cation formed when glycine (at neutral pH) 

reacts with an acid

3. Calculate the Isoelectric point of Glycine?

4. Calculate the Isoelectric point of Lysine?

9.8. Optical isomers of amino acids

Activity 9.8

The molecule CHBrClF exhibits optical isomerism. Draw the 3D displayed 

formulae of both optical isomers.

Simple substances which show optical isomerism exist as two isomers known as 
enantiomers. Where the atoms making up the various isomers are joined up in a 
different order, this is known as structural isomerism. Structural isomerism is not 
a form of stereoisomerism, which involve the atoms of the complex bonded in the 
same order, but in different spatial arrangements. Optical isomerism is one form of 

stereoisomerism; geometric isomers are a second type.

The general formula for an amino acid (apart from glycine, 2-aminoethanoic acid) 
is shown below.The carbon at the centre of the structure has four different groups 

attached. In glycine, the “R” group is another hydrogen atom.

                                                     

The lack of a plane of symmetry means that there will be two stereoisomers of an 
amino acid (apart from glycine) - one the non-superimposable mirror image of the 

other.

For a general 2-amino acid, the isomers are:

                               

The R group, usually referred to as a side chain, determines the properties of each 
amino acid. Scientists classify amino acids into different categories based on the 
nature of the side chain. A tetrahedral carbon atom with four distinct groups is 
called chiral. The ability of a molecule to rotate plane polarized light to the left, 
L (levorotary) or right, D (dextrorotary) gives it its optical and stereo chemical 

fingerprint.

 All the naturally occurring amino acids have the right-hand structure in the diagram 
above. This is known as the “L-” configuration. The other one is known as the “D-” 
configuration.

When asymmetric carbon atoms are present in a molecular compound, there are 
two ways in which the groups attached to that carbon can be arranged in the three 
dimensions, as we have just shown with the two models above. Chemically, optical 
isomers behave in the same way. Biologically, they do not. One will react properly, 

but the other will not.

Checking up 9.8

1. Write the optical isomers of 2-aminopropanoic and 

2. Using diagrams, explain why glycine is not chiral.

9.9. Peptides and polypeptides

Activity 9.9

Ethyne   is a compound which can undergo a polymerisation reaction. 
Deduce the reaction of polymerisation of ethyne, showing the mechanism of 

reaction.

9.9.1. Formation of peptide bonds

Amino acid molecules can also react with each other; the acidic –COOH group in one 
molecule reacts with the basic group in another molecule.
When two amino acids react together, the resulting molecule is called a dipeptide,
forming an amide linkage (peptide bond), with the elimination of a water molecule.

Each amino acid possesses a carboxylic acid group and an amine group. The 
possibilities for constructing polypeptides and proteins are enormous. Let us 
consider two simple amino acids, glycine (2-aminoethanoic acid) and alanine

(2-aminopropanoic acid). 

          The figures below show that these can be joined in two ways:

       

  Note: the amide link between the two amino acids. An amide link between two 
amino acid molecules is also called a peptide link. The reaction is a condensation 
reaction as a small molecule. The dipeptide product still has an 
 group at one end and a –COOH group at the other end.Therefore the reaction can continue,
to form a tripeptide initially, and then ever-longer chains of amino acids.
The longer molecules become known as polypeptides, and then proteins as they get even 
longer sequences of amino acids. A typical protein is formed from between 50 and 

200 amino acids joined in a variety of sequences. 

9.9.2. Structure of peptides and polypetides

A series of amino acids joined by peptide bonds form a polypeptide chain, and each 
amino acid unit in a polypeptide is called a residue. A polypeptide chain has polarity 
because its ends are different, with α-amino group at one end and α-carboxyl 
group at the other. By convention, the amino end is taken to be the beginning of 
a polypeptide chain, and so the sequence of amino acids in a polypeptide chain 
is written starting with the aminoterminal residue. Thus, in the pentapeptide
TyrGly-Gly-Phe-Leu (YGGFL), tyrosine is the amino-terminal (N-terminal) residue and 
leucine is the carboxyl-terminal (C-terminal)residue Leu-Phe-Gly-Gly-Tyr (LFGGY) is 

a different pentapeptide, with different chemical properties.

                  

This above illustration of the pentapeptide Tyr-Gly-Gly-Phe-Leu (YGGFL) shows 
the sequence from the amino terminus to the carboxyl terminus. This pentapeptide, 
Leu-enkephalin, is an opioid peptide that modulates the perception of pain. The 
reverse pentapeptide, Leu-Phe-Gly-Gly-Tyr (LFGGY), is a different molecule and 

shows no such effects.

A polypeptide chain consists of a regularly repeating part, called the main chain 
or backbone, and a variable part, comprising the distinctive side chains. The 
polypeptide backbone is rich in hydrogen-bonding potential. Each residue contains 
a carbonyl group, which is a good hydrogen-bond acceptor and, with the exception 
of proline, an NH group, which is a good hydrogen-bond donor. These groups 
interact with each other and with functional groups from side chains to stabilize 

particular structures, as will be discussed later.

              

A polypeptide chain consists of a constant backbone (shown in blue) and variable 

side chains (shown in green).

9.9.3. Uses of amino acids as building blocks of proteins

Like carbohydrates and lipids, proteins contain the elements carbon (C), hydrogen
(H) and oxygen (O), but in addition they also always contain nitrogen (N).sulphur(S) 
is often present as well as iron (Fe) and phosphorus (P). Before understanding how 

proteins are constructed, the structure of amino acids should be noted.

The process of construction of proteins begins by amino acids bonding together, as 
seen earlier, through peptide bonds. When many amino acids join together a long
chain polypeptide is produced. The linking of amino acids in this way takes place 
during protein synthesis.

 

The simplest level of protein structure, primary structure, is simply the sequence of 
amino acids in a polypeptide chain. The primary structure (Figure 9.2) of a protein 
refers to its linear sequence of amino de (–S–S–) bridges. One of those sequences is: 

–Gly–Ile–Val–Cyst–Glu–Gln–Ala–Ser–Leu–Asp–Arg–Asp–Arg–Cys–Val–Pro–

The primary structure is held together by peptide bonds that are made during the 
process of protein biosynthesis. The two ends of the polypeptide chain are referred 
to as the carboxyl terminus (C-terminus) and the amino terminus (N-terminus) based 

on the nature of the free group on each extremity.

                    

For example, the hormone insulin (Figure 9.3) has two polypeptide chains, A and B, 
shown in diagram below. Each chain has its own set of amino acids, assembled in a 
particular order. For instance, the sequence of the A chain starts with glycine at the 
N-terminus and ends with asparagine at the C-terminus, and is different from the 
sequence of the B chain. You may notice that the insulin chains are linked together 

by sulfur-containing bonds between cysteines.

             

Checking Up 9.9

1. Distinguish between the N– terminal amino acid and the C– terminal 
     amino acid of a peptide or protein.
2. Describe the difference between an amino acid and a peptide.
3. Amino acid units in a protein are connected by peptide bonds. What is 
     another name for the functional group linking the amino acids?
4. Draw the structure for each peptide.
a. gly-val
b. val-gly

5. Identify the C– and N– terminal amino acids for the peptide lys-val-phegly-arg-cys.

9.10. End Unit Assessment

1. Ethylamine and phenylamine are two organic compounds and both are basic.
    a. Draw the displayed formula of each compound, including lone pairs. 
     b. Write a balanced symbol equation for the reaction between one of these 
          compounds and an acid to form a salt. 
      c. Which structural feature of each compound accounts for the basicity?
2. The formulae of two amino acids, glycine (Gly) and alanine (Ala), are 

      given:

        

a. i. Give the systematic names of both amino acids. 
    ii. Draw their skeletal formulae. 
b. Alanine can exist as two stereoisomers.
    i. Draw these two stereoisomers, showing how they differ in their spatial 
       arrangements. 

   ii. Explain why glycine does not have stereoisomers.

3. The structure of a certain tripeptide is shown here:

          

 a. i. Draw the displayed formulae of the three amino acids that make up the 
          tripeptide. 
    ii. Which of these amino acids has two chiral carbon atoms? 
b. This tripeptide can be split up into the three amino acids by refluxing with 
      aqueous hydrochloric acid.
    i. Which bond is broken in this reaction? 
   ii. The reaction can be described as hydrolysis. Explain why, using a 

         diagram.