2024 Nitrogen Cpds Notes (Teacher)

Nitrogen Compounds 2024 Semester 1
CATHOLIC JUNIOR COLLEGE

H2 CHEMISTRY (Syllabus 9729)
NITROGEN COMPOUNDS
Syllabus content
• Amines (exemplified by ethylamine and • Amino acids (exemplified by
phenylamine) aminoethanoic acid)
(i) their formation (i) their acid and base properties
(ii) salt formation
(ii) zwitterion formation
(iii) other reactions of phenylamine
• Amides (exemplified by ethanamide) • Proteins
(i) formation from acyl chlorides (i) formation of proteins
(ii) neutrality of amides (ii) hydrolysis of proteins
(iii) hydrolysis (under acidic and under
basic conditions)
Learning Outcomes
Candidates should be able to:
(i) Amines
(a) describe the formation of amines as exemplified by ethylamine (through amide and
nitrile reduction) and by phenylamine (through the reduction of nitrobenzene)
(b) describe the reaction amine in the formation of salts
(c) describe and explain the basicity of primary, secondary and tertiary amines in the
gaseous phase (interpret as Lewis bases)
(d) explain the relative basicities of ammonia, ethylamine and phenylamine in terms of
their structures
(e) describe the reactions of phenylamine with aqueous bromine
(ii) Amides
(f) describe the formation of amides from the condensation reaction between RNH2 and
R’COCl
(g) explain why amide is neutral in terms of delocalisation of the lone pair of electrons on
nitrogen
(h) describe the chemistry of amides, exemplified by the following reactions:
i. hydrolysis on treatment with aqueous alkali or acid
ii. reduction to amines with lithium aluminium hydride
(iii) Amino acids
(i) describe the acid / base properties of amino acids and the formation of zwitterions
[knowledge of isoelectric points is not required]
(j) describe the formation of peptide (amide) bonds between α-amino acids, and hence,
explain protein formation
(iv) Proteins
(k) describe the hydrolysis of proteins
P a g e | 17-1
CONTENTS
NITROGEN COMPOUNDS
1. Introduction....................................................................................................................... 4
2. Amines .............................................................................................................................. 5
2.1 Nomenclature and Classification of Amines .................................................................. 5
2.2 Physical Properties of Amines ...................................................................................... 7
2.3 Preparation of Amines ................................................................................................ 10
2.4 Chemical Reactions of Amines ................................................................................... 12
2.4.1 Amines as bases .............................................................................................. 12
2.4.2 Amines as Nucleophiles ................................................................................... 18
2.4.3 Reactions of Amines with Aqueous Bromine .................................................... 19
3. Amides ............................................................................................................................... 21
3.1 Physical Properties of Amides.................................................................................... 21
3.2 Chemical Properties of Amides .................................................................................. 22
3.3 Preparation of Amides .............................................................................................. 23
3.4 Chemical Reactions of Amides .................................................................................. 24
3.4.1 Hydrolysis......................................................................................................... 24
3.4.2 Reduction ......................................................................................................... 25
3.5 Identification Test for Primary Amide.......................................................................... 26
4. Amino Acids .................................................................................................................... 26
4.1 Physical Properties of Amino Acids ............................................................................ 27
4.2 Reactions of Amino Acids .......................................................................................... 28
4.2.1 Acid/Base Properties of Amino Acids ................................................................ 28
4.2.2 Polymerisation – Formation of peptide (amide) bonds between amino acids.... 33
5. Proteins ........................................................................................................................... 35
5.1 Functions of Proteins ................................................................................................ 35
5.2 Formation of Proteins ................................................................................................ 36
5.3 Hydrolysis of Proteins ............................................................................................... 37
5.4 Partial Hydrolysis of proteins and peptide sequencing ............................................... 38
P a g e | 17-2
The history of amines
In the early days of organic chemistry, chemists discovered a group of compounds that were
insoluble in water, but dissolved in dilute acids. They are called the alkaloids (‘alkali-like’). Many
of the alkaloids extracted from plants are physiologically very active and often extremely
poisonous - they are the "bad guys" of the natural products world. Having said this, many find
applications in medicine when administered in small doses. These included hypnotics like
nicotine, caffeine and cocaine. All these contained at least one nitrogen atom, and all belonged
to the class of compounds we now called amines.
Most amines have a bitter taste, but are too non-volatile to have an odour. Those amines that are
volatile have distinctive smells. The lower members have an astringent ammonia-like smell, but
are rapidly replaced by a strong fishy odour in butylamine and higher amines.
Amines in fish
The fishy odour from fish is actually due to cadaverine, a foul smelling diamine (NH2(CH2)5NH2)
that is formed from the hydrolysis of proteins found in the fish due to decay. However, this
chemical is not entirely associated with decomposition. It is also produced by living bodies and is
partially responsible for the distinct odours of urine!
Since the fishy odour can be unbearable, have you ever wondered how to remove that fishy smell
from your hands after touching a raw fish, or make sure that your plate of fish and chips taste
great minus the fishy odour? The answer lies in the power of a lemon! Turn to page 17-16 to find
out more!
References:
(i) Cann, P. & Hughes, P. (2002) Chemistry for advanced level, John Murray (Publishers)
Ltd. Chapter 30
(ii) http://www.chemguide.co.uk/
P a g e | 17-3
1. Introduction
Nitrogen is found in a wide range of organic molecules and living organisms. The three main
types of organic nitrogen compounds that will be discussed in this chapter are: amines, amides
and amino acids. We will also be looking at proteins, which are polymeric molecules made up of
amino acids as well the different levels of structure found in them. The table below shows some
examples of the different nitrogen compounds.
Formula Type of compound Name
CH3CH2NH2 Amine Ethylamine
Aromatic amine Phenylamine
Ethanamide
Amide
Peptide
2-aminopropanoic acid
Amino acid
(alanine)
Nitro-compound Nitrobenzene
CH3CN Nitrile Ethanenitrile
P a g e | 17-4
2. Amines
2.1 Nomenclature and Classification of Amines
Amines are derivatives of ammonia, NH3, where one or more of the H atom(s) have been replaced
by alkyl or aryl groups.
They can be classified as primary (1), secondary (2) or tertiary (3) according to the number
of alkyl or aryl groups (-R) attached to the nitrogen atom.
Ammonia Primary Secondary Tertiary

No. of R groups
attached to N - 1 2 3
atom
A nitrogen atom can also have four groups bonded to it e.g. NH4+, in which the nitrogen atom
becomes part of a positive ion. If all the hydrogen atoms of NH4+ are replaced by alkyl or aryl
groups, we obtain what is known as quaternary ammonium ion, R4N+.
e.g.
compared with
tetramethylammonium chloride, ammonium chloride,

(CH3)4N+Cl− NH4+Cl−
Amines can also be classified into aliphatic and aromatic amines. Amines are named by specifying
the alkyl group(s) attached to the nitrogen atom, followed by –amine.
Aliphatic Amine Aromatic Amine
Phenylamine (1o amine)

Ethylamine (1o amine) Trimethylamine (3o amine) (N atom is attached directly to
benzene ring.)
P a g e | 17-5
Amines with different alkyl groups substituted are named as N-substituted amines. The largest
alkyl group is chosen as the parent name, and the other alkyl groups are considered N-substituents
on the parent.
Amines with more than one functional group are named by considering the –NH2 as the amino
substituent on the parent molecule.
E.g.
N-ethyl-N-methylpropylamine 2-aminobutanoic acid

substituents parent chain (longest chain)
Worked Example 1
Naming Amines using IUPAC Nomenclature for Organic Compounds
by Leah4sci
https://youtu.be/STIamn93rds
Stop watching at 5 min 25s
This video explains the classification and naming of amines.
Name and classify the following amines.
(a) CH3CH2CH2NH2 propylamine (1o)

(b) (CH3)3N trimethylamine (3o)
(c) CH3CH2NHCH3 N-methylethylamine (2o)
(d) phenylmethylamine (1o)
Lecture Practice 1
1. Name and classify the following amines. 2. Draw the structure of the following:
(a) C6H5NHCH3 (a) 1-methylethylamine
N-methylphenylamine (2o)
(b) (b) N-methylethylamine
4-methylphenylamine (1o)
P a g e | 17-6
2.2 Physical Properties of Amines

Recap! Chemical Bonding
Type and strength of intermolecular forces
(a) Volatility (Depends on Boiling Point)
• For a given class of amines (i.e. 1o or 2o or 3o amines), the volatility decreases as the
number of carbon increases. (boiling point increases)
Reason: The relative molecular mass (Mr) or number of carbon atoms increases, the
number of electrons and thus the strength of instantaneous dipole-induced dipole
attractions increases. Hence, more energy is required to overcome these forces and
the boiling point increases leading to decreasing volatility.
• For compounds of similar molecular masses, amines have higher boiling points than
non-polar compounds.
Reason: Amines are polar and can form stronger hydrogen bonds (for 1o or 2o amine)
than the instantaneous dipole-induced dipole attractions in non-polar compounds. Hence,
more energy is required to overcome these forces and the boiling point is higher.
e.g.
δ-
Mr Boiling point / oC δ+ δ-
CH3CH2NH2 45 17
CH3CH2CH3 44 - 42
• For compounds of similar molecular masses, amines have lower boiling points than
alcohols.
Reason: The N−H bond in amine is less polar than O−H bond in alcohol as N atom is
less electronegative than the O atom. Hence, intermolecular hydrogen bonding in
amines is weaker than that in alcohols.
e.g.
Mr Boiling point / oC –
+ +
CH3CH2NH2 45 17
+
+ –
CH3CH2OH 46 78
P a g e | 17-7
• Boiling point of tertiary amines are lower than that of primary and secondary amines.
Reason: Tertiary amines cannot form intermolecular hydrogen bonds with each
other due to the absence of H atoms directly attached to the electronegative N atom
of the amine. They can only form weaker permanent dipole- permanent dipole
interaction (pd-pd) with each other.
Primary and secondary amines are capable of
forming intermolecular hydrogen bonds.
Since less energy is required to overcome the
weaker pd-pd, it thus has a lower boiling point.
pd - pd forces of
attraction
Lecture Practice 2
(a) Arrange the following compounds from the most volatile to the least volatile.
CH3CH2CH2NH2 , CH3CH2CH2CH3 , CH3CH2CH2OH
CH3CH2CH2CH3, CH3CH2CH2NH2, CH3CH2CH2OH
Mr 58 59 60
B.p. (oC) 0 49 97
CH3CH2CH2CH3 is non-polar and the molecules are held by weak id-id attractions.
Hence, least amount of energy required to overcome the forces of attraction and
thus the most volatile.
CH3CH2CH2OH and CH3CH2CH2NH2 are polar molecules. Hydrogen bonding in
CH3CH2CH2OH is stronger than that in CH3CH2CH2NH2 as O−H bond is more polar
than N−H bond. Hence, CH3CH2CH2OH is the least volatile.
(b) Explain why the boiling point of CH3CH2CH2NH2 (49C) is much higher than that of
(CH3)3N (3C)?
CH3CH2CH2NH2 is primary amine and are held by intermolecular hydrogen bonds.
(CH3)3N is a tertiary amine so its molecules cannot form hydrogen bonds with each
other, as they lack H atom that is bonded to the highly electronegative N, and are
only held by weaker pd-pd forces. Since more energy is required to overcome the
stronger H-bonds in CH3CH2CH2NH2 and thus higher b.p.
P a g e | 17-8
(b) Solubility
• Aliphatic amines are generally soluble in water δ-
Reason: Amines are soluble in water due to the formation

δ+
of hydrogen bonds with water molecules. Lower
members of aliphatic amines are very soluble in water. δ+ δ- δ-
δ+
• Primary and secondary amines are much more
δ+
soluble than the tertiary amines.
Reason: Primary/secondary amines are much more soluble due to the formation of more
extensive hydrogen bonds between molecules of primary (or secondary) amines
with water molecules.
Hydrogen bonds between primary amine and Hydrogen bonds between secondary
water molecules amine and water molecules
Hydrogen bonds between tertiary amine and water molecules
Only the lone pair of electrons on N atom of the tertiary amine forms hydrogen bonds with
water molecules.
• .The solubility of amines in water decreases as the number of carbon atoms increases
(especially above C6). Also, Phenylamines are insoluble in water.
Reason: The bulky, non-polar alkyl/aryl groups hinder the formation of hydrogen bonds
between the amine and water molecules. Instantaneous dipole-induced dipole forces of
attraction become the predominant solvent-solute interactions.
P a g e | 17-9
Learning outcome:
(a) describe the formation of amines as exemplified by ethylamine (through amide and nitrile
reduction) and by phenylamine (through the reduction of nitrobenzene)
2.3 Preparation of Amines

I. Nucleophilic
substitution of alcohol solvent
CH3Br + NH3 CH3NH2 + HBr
halogenoalkanes heat in sealed tube
with NH3 or
amines Further substitution occurs if there is excess bromomethane.
CH3Br + CH3NH2 (CH3)2NH + HBr

dimethylamine
CH3Br + (CH3)2NH (CH3)3N + HBr

trimethylamine
CH3Br + (CH3)3N (CH3)4N+Br–

tetramethylammonium bromide
II. Reduction of Reagent and condition: LiAlH4 in dry ether

nitriles or H2 over heated Ni catalyst
LiAlH4
CH3CN + 4[H] dry ether CH3CH2NH2
ethanenitrile ethylamine
Ni
CH3CH2CN + 2H2 CH3CH2CH2NH2
heat
III. Reduction of Reagent and condition: LiAlH4 in dry ether
amides e.g.
P a g e | 17-10
IV. Reduction of Reagent and condition: 1) Sn, conc. HCl, heat under reflux
nitrobenzene 2) NaOH(aq)
NO2 NH3+ NH2

Useful for preparing
aromatic amines 1) Sn, conc. HCl, 2) NaOH(aq)
+ 6 [H] + 2 H2O
heat under reflux
where the –NH2 group
is directly bonded to nitrobenzene phenylamine
the benzene ring.
1. In the acidic solution, the amine is obtained as a salt, C6H5NH3+Cl-
2. Excess NaOH is thus added to liberate the free amine.
Note: LiAlH4 cannot be used as nitrobenzene will be reduced to form
C6H5–N=N–C6H5, an azo compound.
Worked Example 2
How would you make the following conversions which may involve more than one step?
(a) CH3CH2Br → CH3CH2NH2
excess NH3 (alc)

CH3CH2Br CH3CH2NH2
heat in sealed tube
(b) CH3CH2Br → CH3CH2CH2NH2
alc. KCN LiAlH4 in ether

CH3CH2Br CH3CH2CN CH3CH2CH2NH2
heat under reflux
Lecture Practice 3
How would you make the following conversion which may involve more than one step?
benzene → phenylamine
conc. HNO3
conc. H2SO4 1) Sn, conc. HCl, reflux
benzene
55 °C – 60 °C 2) NaOH (aq)
Self-Practice 1
After the reduction of nitrobenzene to phenylamine using tin and concentrated hydrochloric
acid, an excess of sodium hydroxide is added. What is the purpose of sodium hydroxide?
A. To dry the product

B. To liberate the phenylamine
C. To lower the boiling point of subsequent distillation
D. To precipitate tin(II) hydroxide N2012/P1/28
P a g e | 17-11
2.4 Chemical Reactions of Amines
Big Idea
The chemical reactivity of amines is mainly due to the tendency for nitrogen to share
/donate the electron pair with electron deficient reagents.
The lone pair of electrons accounts for:

a) the basicity of amines
b) the behaviour of amines as nucleophiles
c) the increased reactivity of amino-substituted aromatic rings compared to benzene.
In general,
Electron-donating groups (EDG) increase the availability of the lone pair of electrons on N
atom to accept proton.
Electron-withdrawing groups (EWG) decrease the availability of the lone pair of electrons
on N atom to accept proton.
Learning outcome:
(c) describe and explain the basicity of primary, secondary and tertiary amines in the
gaseous phase (interpret as Lewis bases)
2.4.1 Amines as bases

Recap!
Theories of
Like ammonia, amines are Lewis bases (nucleophile). The lone pair of electrons
acids and
on the nitrogen atom can be donated to a Lewis acid forming a covalent bond. bases
Lewis Base
The strength of amines as Lewis bases can be explained by is an
• the availability of the lone pair on nitrogen for donation electron
o the more available the lone pair, the stronger it is as a base. pair donor.
Alkyl groups are electron-donating; thus basicity of amines increases from primary to
secondary to tertiary in gaseous phase (as Lewis Base)
E.g.
In gaseous phase, basicity increases from CH3NH2 to (CH3)2NH to (CH3)3N [2018/P3/Q3]
Methyl (alkyl) group is an electron-donating group and it increases the availability of the lone
pair of electrons on the N atom to be donated to a Lewis acid.
Therefore, the higher the number of methyl groups bonded to N, the more basic the amine is.
Hence, trimethylamine is the strongest base as is has the highest number of methyl group.
P a g e | 17-12
In addition, amines like ammonia are also weak Brønsted-Lowry base, as it can accept
proton. In addition to availability of the lone pair of electrons, the strength of Brønsted-
Lowry base can be explained by stability of the conjugate acid ion:
o The same factors that increase the availability of the lone pair will disperse the positive
charge on the corresponding conjugate acid ion, making it more stable.
Recap!
o The more stable the conjugate acid ion, the stronger the base.
The stronger
the base, the
weaker the
conjugate
acid.
Amine Formula Kb at 25oC / moldm-3 pKb

Recap!
Ammonia NH3 1.8 x 10-5 4.75 The higher
Ethylamine CH3CH2NH2 5.0 x 10-4 3.30 the Kb value
Diethylamine (CH3CH2)2NH 1.0 x 10 -3
2.98 or the
smaller the
Triethylamine* (CH3CH2)3N 5.6 x 10-4 3.25
pKb value,
Phenylamine 4.2 x 10-10 9.38 the stronger
the base.
*Note: Triethylamine(tertiary amine) is weaker Brønsted-Lowry base than
diethyalamine (secondary amine). This will be explained in the next page.
Learning outcome:
(d) explain the relative basicities of ammonia, ethylamine and phenylamine in terms of
their structures
i) Relative Basicities of Ammonia, Ethylamine & Phenylamine
From the table,

Order of base strength of ammonia, ethylamine & phenylamine is:
CH3CH2NH2 > NH3 >>

Ethylamine > ammonia >> phenylamine
• Ethylamine is a stronger base than ammonia
The electron donating ethyl group increases the electron density on the N atom,
making the lone pair on N more available to accept proton than ammonia.
OR The electron donating alkyl group disperses the positive charge on

CH3CH2NH3+, making it more stable than NH4+.
P a g e | 17-13
• Phenylamine is a weaker base than ammonia.
The p–p orbital overlap results in the

delocalisation of the lone pair of electrons on N
atom of phenylamine into the  electron system
of benzene ring, making the lone pair less
available to accept proton.
OR The electron withdrawing phenyl group intensifies the positive charge on

C6H5NH3+, making it less stable than NH4+.
Summary on Basicity of Amines:
Electron–donating Electron–withdrawing N atom of amine directly attached to

substituent (e.g. –CH3) substituent (e.g. –Cl, –NO2) benzene ring
p–p orbital overlap results in the

delocalisation of the lone pair of
lone pair of electrons on N lone pair of electrons on N atom electrons on N atom of
atom MORE available to LESS available to accept phenylamine into the  electron
accept proton proton system of benzene ring, making
the lone pair less available to
accept proton
stronger base compared to

weaker base compared to NH3 weaker base compared to NH3
NH3
NOTE:
Based on the above reasoning, tertiary amines are expected to be the strongest bases,
followed by secondary then primary amines.
However, from Kb data, it is noted that tertiary amines are not as basic as expected.
Base NH3 CH3NH2 (CH3)2NH (CH3)3N

–5 –4 –4
Kb 1.8 x 10 4.4 x 10 5.4 x 10 5.9 x 10–5
Thus, in aqueous solution, the order of increasing basic strength:

NH3 <(CH3)3N <CH3NH2 < (CH3)2NH
Reason:
Tertiary amines are less soluble (due to steric hinderance and lack of hydrogen in tertiary
amine for hydrogen bonding) than the secondary and primary amines, thus tertiary amines
ionise in water to a smaller extent, giving less OH– in the aqueous solution and forming
weaker bases as compared to secondary and primary amines.
P a g e | 17-14
Worked Example 3
Why is phenylamine, C6H5NH2, a weaker base than methylamine, CH3NH2?
C6H5NH2is a weaker base than CH3NH2 due to the delocalisation of the lone pair of
electrons on N atom of phenylamine into the  electron system of benzene ring, making
the lone pair less available to accept proton.
Alternatively, the electron withdrawing phenyl group intensifies the positive charge on
C6H5NH3+, making it less stable than CH3NH3+.
Lecture Practice 4
Arrange the following in decreasing order of base strength. Explain your answer.
Least basic Most basic
CH3 group is electron-donating. Thus, the lone pair of electron on N atom is more
OR The conjugate acid ion is more stable as the positive charge is dispersed.
Thus, 4-methylphenylamine is more basic than phenylamine.
Cl atom is electron-withdrawing. Thus, the lone pair of electron on N is less

OR The conjugate acid ion is less stable as the positive charge is intensified.
Thus, 4-chlorophenylamine is less basic than phenylamine.
Self-Practice 2
Arrange the following compounds in order of increasing pKb.
1.
2.
Answers: 1. A < C < B

2. D < B < A < C
P a g e | 17-15
Learning outcome:
(b) describe the reaction amine in the formation of salts
ii) Formation of Salt

• Amines, which are bases, can dissolve in acids to form salt. Both aliphatic and
aromatic amines form stable salts with mineral acids.
R–NH2 + HCl (aq) ⎯→ (RNH3)+Cl- where R = alkyl or aryl groups
E.g.
ethylammonium chloride
phenylammonium chloride
Note: Phenylamine is only slightly soluble in water, but it dissolves readily in hydrochloric
acid because a salt is formed. The salt is an ionic compound and dissolves due to
ion-dipole attraction formed with water molecules. Evaporation of the salt
solution gives a white solid.
• The free amine is liberated from its salt by adding a strong alkali such as sodium
hydroxide.
Addition of alkali to this salt solution causes phenylamine to be released.
Behold the power of lemons!

You may be familiar with the sour taste of lemons; this taste comes from
citric acid (which contains three carboxylic acid groups). When we wash
our hands with water containing lemon juice or squeeze that lemon over
our fish platter, the citric acid in lemon juice neutralises the amines in the
fish to form a salt. Since the salt formed is an ionic compound, it is no longer volatile and hence
the fishy odour is thus effectively removed.
Make sure you remember this to impress your mum during a trip to the market, or when you’re
out eating with your friends!
P a g e | 17-16
Worked Example 4
What is the general method used to separate an organic amine from a mixture of benzene and
amine?
A extracting the benzene with ethoxyethane, CH3CH2OCH2CH3.
B extracting the amine with ethanol
C shaking the mixture with dilute aqueous acid
D shaking the mixture with dilute aqueous alkaline
Organic amine is basic. It dissolved readily in dilute aq acid and forms an immiscible
layer with benzene which can then be separated using a separating funnel.
Lecture Practice 5
Which reagent could be used to separate a mixture of phenylamine, C6H5NH2, and
methylbenzene, C6H5CH3?
A dilute aqueous sodium hydrogen carbonate
B dilute aqueous sodium hydroxide
C dilute hydrochloric acid
D propanone N04/I/29
C6H5NH2 + HCl → C6H5NH3+ Cl-
The salt formed is an ionic compound and dissolves in aqueous solution to be
separated from methylbenzene.
Self-Practice 3
1. A liquid P is sparingly soluble in water but dissolves readily in cold hydrochloric acid.
Evaporation of this solution yields a crystalline solid.
Which of the following could be P?
A C6H5COCH3 B C6H5CN C C6H5NH2 D C6H5OH N06/I/29
2. Which method is able to separate benzene from a mixture of benzene and an amine?
A extracting the amine with ethanol
B nitrating the benzene with a nitrating mixture
C shaking the mixture with dilute aqueous acid
D shaking the mixture with dilute aqueous alkali N09/I/28
P a g e | 17-17
2.4.2 Amines as Nucleophiles

Recap!
i) Reaction with acid chlorides to form amides Carboxylic acids
Type of reaction: Nucleophilic substitution / addition-elimination / Reaction of acyl

condensation chloride.
Reagents and condition: Room temperature Amide functional group
rt
amide where R, R’ = aryl

or alkyl groups
e.g.
rt
Note:
1. To make amides, carboxylic acids cannot be used instead of acid chlorides

as the acids will simply protonate the amine and form a salt.
2. Tertiary amines do not contain a replaceable H atom on the N, so they cannot
form amides. This reaction only occurs with primary and secondary amines.
ii) Reaction with halogenoalkanes

Type of reaction: Nucleophilic substitution Recap!
Halogen
Reagents and condition: alcohol solvent, heat in sealed tube derivatives
alcohol solvent
(CH3CH2)2NH + CH3Br (CH3CH2)2NCH3 + HBr
heat in sealed tube
P a g e | 17-18
Learning
2.4.3 outcome:
Reactions of Amines with Aqueous Bromine
(e) describe theamines
aliphatic − of no
reactions phenylamine
reaction with aqueous bromine
aromatic amines − electrophilic substitution of the benzene ring with
aqueous bromine at room temperature
Observations: 1. orange bromine solution decolourised

2. white precipitate of 2,4,6-tribromophenylamine is formed
Thinking Time 1:
Phenylamine undergoes electrophilic aromatic substitution but not nucleophilic
substitution readily. Why?
The lone pair of electrons on nitrogen is delocalized into the benzene ring, thus the C-N has a partial
double bond character, making it stronger and harder to break. Hence, phenylamine is unable to undergo
nucleophilic substitution readily. However, this delocalization will increase the electron density of the
benzene ring to make it more susceptible to electrophilic attack by electrophiles.
Why does the reaction occur readily in the cold and in the absence of a halogen carrier?
This is because the –NH2 group is electron donating (lone pair from N atom is delocalised into the ring).
The ring becomes more electron rich and is more reactive than benzene towards electrophiles.
Substitution occurs at 2-, 4- and 6- positions.
Recap!
What is another compound that reacts in a similar way with aqueous
Hydroxy
bromine as phenylamine? compounds
Phenol –
electrophilic
substitution
Phenylamine undergoes polysubstitution in both Br2(aq) and Br2/hexane of phenol
while phenol undergoes monosubstitution in Br2/hexane. Why?
The −NH2 group is more electron-donating than –OH group, hence it activates the
benzene ring to a larger extent. At the same time, in non-polar solvent, phenol can’t dissociate to form
phenoxide. (Phenoxide is formed in the aqueous solution. Phenoxide has more lone pairs of electrons on
the oxygen atom and activates the benzene ring to greater extent.)
P a g e | 17-19
Worked Example 5
1. When 2-methylphenylamine reacts with an excess of Br2(aq), one of the intermediates is
cation Z.
What is the final product of this reaction?
Answer: A N2012/ I/30
Lecture Practice 6
1. When aqueous bromine is added to a solution of phenylamine, the colour of bromine
disappears. Which of the following statement is true?
A The solution gets more acidic

B The mechanism is electrophilic addition
C The –NH2 group of phenylamine is substituted by Br.
D Bromine forms a colourless complex with phenylamine. TJC Prelim 07/I/30
2. Consider the aromatic amine, phenylamine. Which of the following statement is true?
A It is more basic than ethylamine.

B It undergoes electrophilic addition.
C It gives no reaction with ethanoyl chloride
D It reacts with aqueous bromine to give a white precipitate. YJC Prelim 07/I/29
P a g e | 17-20
3. Amides
Amides have the general structure:
where R, R’ and R’’ can be H, alkyl or aryl.

They can be classified as primary (1), secondary (2) or tertiary (3) according to the
number of alkyl or aryl groups (-R) attached to the nitrogen atom
Primary Secondary Tertiary

No. of R groups
0 1 2
attached to N atom
3.1 Physical Properties of Amides

(a) Volatility Type and strength of intermolecular forces
• Amides have relatively high melting points due to

δ+
intermolecular hydrogen bonding. All 1 amides, except δ-
methanamide are crystalline solids due to fairly strong

δ-
intermolecular hydrogen bonding. δ+
Thinking Time 2:
Explain the boiling point of 3o amides compare with that of 1 and 2 amides.
(same explanation as for amines) 1 and 2 amides are capable of forming intermolecular
hydrogen bonds. 3o amides cannot form intermolecular hydrogen bonds with each other
due to the absence of H atoms directly attached to the electronegative N atom of the
amine. They can only form weaker dipole-dipole attractions with each other. Since less
energy is required to overcome the weaker permanent dipole – permanent dipole attractions,
it thus has a lower boiling point.
(b) Solubility
• Amides are soluble in water as they form hydrogen bonds with water molecules. Solubility
decreases with increasing molecular mass as the non-polar groups are unable to form
hydrogen bonds with water.
P a g e | 17-21
Learning outcome:
(g) explain why amide is neutral in terms of delocalisation of the lone pair of electrons on
nitrogen
3.2 Chemical Properties of Amides

Unlike amines, amides DO NOT function as a base and/or nucleophile.
• The lone pair of electrons on the nitrogen atom is NOT available for PROTONATION.
 Amides do NOT function as a base and are NEUTRAL to litmus in aqueous
solution.
Reason: The p–p orbital overlap results in the delocalisation of the lone pair of
electrons on N atom into the electron system of C=O, making the lone pair of
electrons on N atom NOT available for protonation.
Video: Amine vs Amide

https://youtu.be/fsUsw_m2RU4
Duration: 2 min 19 s
• The lone pair is NOT available for NUCLEOPHILIC ATTACK.
 Amides do NOT function as a nucleophile.
Reason: The p–p orbital overlap results in the delocalisation of the lone pair of
electrons on N atom into the electron system of C=O, making the lone pair of
electrons on N atom NOT available for nucleophilic attack.
Thinking Time 3: What is the hybridisation of the N atom on an amide?

sp2 – due to delocalization of electrons, shape around N atom is trigonal planar.
Self-Practice 4
Why are amides, RCONH2, less basic than amines, RNH2?
A Amides form a zwitterion in which the nitrogen atom carries a positive charge.
B Amides have a resonance structure involving the movement of a pair of electrons from
the nitrogen atom to the oxygen atom.
C Electrons on the nitrogen atom move on to the C-N bond giving it some double bond
character so that it is more difficult to break.
D The amide carbonyl group withdraws electrons from the NH2 group to make the hydrogen
atoms acidic. N2012/ I/29
P a g e | 17-22
Learning outcome:
(f) describe the formation of amides from the reaction between RNH2 and R’COCl
3.3 Preparation of Amides (Recall: Section 2.4.2 amines)

Type of reaction: Nucleophilic substitution / addition-elimination / condensation
Reagents and condition: Room temperature
Amides are prepared by reacting an acyl chloride with ammonia or an amine.
e.g.
Recap!
Carboxylic
Acids -
propanoyl chloride propanamide Reactions of
Acyl Chlorides
Thinking Time 4:
Why can’t amides be prepared by reacting carboxylic acids with amines?
The carboxylic acids will protonate/ react with the amines which are bases to form a
salt instead.
P a g e | 17-23
Learning outcome:
(h) (i) describe amide hydrolysis on treatment with aqueous alkali or acid
3.4 Chemical Reactions of Amides

3.4.1 Hydrolysis
Amides are hydrolysed by heating under reflux with aqueous acid or alkalis.
Acid Hydrolysis:
Reagent/condition: Heat under reflux with dilute H2SO4 (or dilute HCl)
Product: Carboxylic acid and ammonium salt
Alkaline Hydrolysis:
Reagent/condition: Heat under reflux with aqueous NaOH
Product: Salt of the carboxylic acid and ammonia
Worked Example 6
Mepivacaine is a local anaesthetic.
What are the products when mepivacaine is hydrolysed by heating with NaOH(aq)?
[N2018/1/29]
P a g e | 17-24
Lecture Practice 7
Aspartame is another artificial sweetening agent, used in soft drinks and other foodstuffs.
Draw the structural formulae of the organic compounds formed when aspartame is treated with
(i) hot NaOH (aq)
(ii) cold HCI (aq) N08/III/5(e)
(i) hot NaOH(aq) (ii) cold HCl (aq)
(i) Alcohols are neutral and will not be deprotonated in this case.
(ii) Since cold HCl is used, this is an acid-base reaction and not hydrolysis. The amide
nitrogen will not be protonated as amides are neutral.
Learning outcome:
(h) (ii) describe amide reduction to amines with lithium aluminium hydride
3.4.2 Reduction
(Refer to Section 2.3 preparation of amines)
Reagent/condition: LiAlH4 in dry ether
e.g.
P a g e | 17-25
3.5 Identification Test for Primary Amide
Test: Add NaOH (aq) to the unknown and heat. Then test with moist red litmus paper.
Observation: NH3(g) turns moist red litmus paper blue.
Note:
There are no distinguishing test for amides. Hydrolysis of the amides should be carried out
first before distinguishing test can be done on the hydrolysed products.
4. Amino Acids
All amino acids have
i. a basic amine group (-NH2),

ii. an acidic carboxylic acid group (-CO2H),
iii. an R group (diagram on the right)
The R group can be polar, nonpolar or electrically charged .
Naturally occurring amino acids are α-amino acids. −amino acids have both the -NH2 and
–CO2H groups attached to the −carbon atom (the carbon that is adjacent to the –COOH
group).
NH2
e.g.
H C H
R = H, CO2H aminoethanoic acid (glycine)
NH2
CH3 C H
R = CH3, 2-aminopropanoic acid (alanine)
CO2H
All −amino acids, except glycine, contain a chiral carbon atom and so, exhibit
enantiomerism. The two enantiomers are
P a g e | 17-26
Learning outcome:
(i) describe the acid / base properties of amino acids and the formation of zwitterions
[knowledge of isoelectric points is not required]
4.1 Physical Properties of Amino Acids

• In the solid phase or in aqueous solutions, amino acids exist predominantly as
dipolar ions known as zwitterions (German for ‘double ion’).
zwitterion
• An internal acid-base reaction between the basic –NH2 group and acidic –CO2H
group results in the formation of an ion with an overall electrical charge of zero.
• Zwitterion has both the positively and negatively charged groups with no overall
electrical charge.
• Hence, the dipolar nature of amino acids account for these unique physical properties
that resemble that of ionic compounds:
(1) Crystalline solids with high meting points Type and strength of
intermolecular forces
Reason: Large amount of energy is required to
overcome the strong electrostatic attraction between oppositely charged
groups of the zwitterions.
H H
+ +
H3N C COO− H3N C COO−
R R
strong electrostatic
attraction
(2) Soluble in water (polar solvent) but insoluble in non-polar solvents.

Reason: Both charged groups (–NH3+ and –COO−) of the zwitterions can form
ion-dipole attractions with water molecules.
Ion-dipole attractions
P a g e | 17-27
4.2 Reactions of Amino Acids

4.2.1 Acid/Base Properties of Amino Acids
(a) Amphoteric Nature

• Amino acids are amphoteric (i.e. they are able to react with both acids and bases to
form ionic salts).
• In an acidic solution (low pH), the amino acid behaves as a base and accepts a
proton (H+) from the acid to form a cation.
The cation will migrate towards the negative electrode (cathode) if the acidic solution
is electrolysed.
• In a basic solution (high pH), the amino acid behaves as an acid and donates a
proton (H+) to the base to form an anion.
The anion will migrate towards the positive electrode (anode) if the basic solution is
electrolysed.
Add H+ Add OH—

Cation Zwitterion Anions
pH decrease pH increase
(b) Buffering Action

Recap! Chemistry
Amino acids can act as buffers by resisting changes in pH when small of Aqueous
amounts of acids/alkali is added to it. Solutions -
When a small amount of acid is added:: Buffer solutions
(any H+ added
is removed)
When a small amount of alkali is added::
(any OH- added

is removed)
Note: -NH3+ is acting as the weak acid and –CO2- the weak base
P a g e | 17-28
Thinking Time 5:
How is a buffer solution of amino acid different from a salt buffer solution?
A salt buffer solution contains large amount of a weak acid and large amounts of its
conjugate base or vice versa.
A solution of amino acid contains a weak acid and a weak base which are not conjugate of
one another. The weak acid and weak base are part of the same molecule as the amino
acid is amphoteric
(c) Isoelectric Points (pI)

(This section on pI is NOT in the syllabus and presented here for your information only)
• There is a particular pH at which an amino acid exists solely in its zwitterionic form
with a net charge of zero on the species and thus will NOT migrate under the influence
of an electric field. This pH value is known as the isoelectric point (pI) of that amino
acid.
• Every amino acid has a characteristic isoelectric point, dependent on the type of side-
chain R group of the amino acid.
Neutral R group Acidic R group Basic R group

pI  7 pI < 7 pI > 7
Video Title: Isoelectric Point and Zwitterions
https://youtu.be/WxNYfc98Iqw
P a g e | 17-29
• The difference in isoelectric points can be used to separate amino acids by a technique
called electrophoresis, in which an amino acid will move towards the cathode or
anode depending on the pH of the solution in which the amino acids are dissolved in.
➢ At a pH well below its isoelectric point (i.e. pH << pI), the amino acid exists
predominantly as cations and migrate towards the negative electrode
(cathode).
➢ At a pH well above its isoelectric point (i.e. pH >> pI), the amino acid exist
predominantly as anions and migrate towards the positive electrode (anode).
For e.g. pI of glycine (Gly) = 5.97

+ve plate (anode) +ve plate (anode) +ve plate (anode)
Gly −
Gly
Gly+
pH = 3.0 (<<pI) pH = 6.0 (pI*) pH = 10.0 (>>pI)

−ve plate (cathode) −ve plate (cathode) −ve plate (cathode)
In summary, all amino acids can exist as 3 forms, depending on the pH of the solution.
pH of solution Structure of molecule Overall charge Migration in the
presence of
electric field
pH < pI H3N+ —CH(R) —COOH Positive Negative electrode
pH = pI H3N+ —CH(R) —COO— Neutral No migration
pH > pI H2N —CH(R) —COO— Negative Positive electrode
P a g e | 17-30
(d) How do we assign the pKa to the various acidic groups in amino acids?
• Amino acids will always exist in their most protonated form before that are
subjected to neutralisation .
–carbon
• The –CO2H group is in close proximity to the electron-withdrawing N atom (or -
NH3+) group. Thus, the conjugate base anion (-CO2-) is stabilized to a greater
extent. As a result, the dissociation of –CO2H to form H+ is more favoured.
➔ Assigned the lowest pKa (most acidic)
• The –NH3+ group is a conjugate acid derived from a basic amine group and
there is stronger attractive force between the lone pair of electrons on N atom
and the H+ ion. As a result, the dissociation of –NH3+ to form H+ is less favoured.
➔ Assigned the highest pKa (most basic)
Worked Example 8
There are three pKa values associated with glutamic acid: 2.1, 4.1 and 9.5.
With the use of these pKa values, suggest the major species present in solutions of glutamic
acid with the following pH values: pH 1, 3, 7, 11
[N2010//2a(ii)]
Solution:
Protonated form of glutamic acid
P a g e | 17-31
(e) Titration curve of the protonated form of amino acids
Example: Titration curve of amino acids with neutral R group (e.g. glycine).
Protonated form of glycine:
pKa1 pKa2
2.34 9.60
R Group
• Since pKa1 (–COOH) < pKa2 (–NH3+), the –COOH group is a stronger acid than –NH3+ group.
Thus, as we add the base, OH– to A, the stronger acidic –COOH group will be neutralised
first, followed by weaker acidic –NH3+ group.
pKa2 = 9.60
pKa1 = 2.34
• Sketch of the titration curve (pH against volume of OH– added) when NaOH is added to 10.0
cm3 of the protonated form of glycine of the same concentration.
C
pH = pKa2
[B]=[C] max. buffering capacity
B zwitterion
pH = pKa1
[A]=[B] max. buffering capacity

A
5.0 10.0 15.0 20.0
Volume of NaOH added/cm3 Predominant species in solution

0 cm3 A
Between 0 cm3 and 5 cm3 Buffer mixture of A and B
5 cm3 Equal conc of A and B
10 cm3 B
Between 10 cm3 and 15 cm3 Buffer mixture of B and C
15 cm3 Equal conc of B and C
20 cm3 C
P a g e | 17-32
Learning outcome:
(j) describe the formation of peptide (amide) bonds between amino acids and, hence, explain
protein formation
4.2.2 Polymerisation – Formation of peptide (amide) bonds between amino acids
The most important reaction of amino acids is polymerisation. It occurs through
linking of the –CO2H group of one amino acid and the –NH2 group of another
amino acid, with the loss of one water molecule. This process is known as
condensation polymerisation.
Peptide linkage
+ H2O
Title: Peptide Bonds

https://youtu.be/cgf1l3YQPXo
The –CONH– group is called an amide linkage, or specifically, a peptide linkage if it occurs
between amino acids.
The product formed is a dipeptide since it is formed from two amino acids.
If three amino acids forms the product, it is a tripeptide. Similarly, many amino acids can
react, to form polypeptides.
Proteins are naturally occurring polypeptides and may contain over 105 amino acids.
P a g e | 17-33
Thinking Time 6:
Are the dipeptides below the same?
No. There is directionality in polypeptides. In the dipeptide on the left, the R group is
connected to a carbon that is connected to –NH2 group while in the dipeptide on the
right, the R group is connected to a carbon that is connected to a –COOH group.
Lecture Practice 8
An anti-HIV drug is made by combining A, which is an amino acid, with the amino acid, glycine,
H2NCH2COOH. Draw the structures of two different compounds that could be formed when
one molecule of A reacts with one molecule of glycine. [N2006/II/4(f)]
P a g e | 17-34
5. Proteins
5.1 Functions of Proteins
Proteins are polymers built up from amino acid monomers. Many proteins contain several
thousands of amino acid units, arranged in different ways, which enable them to perform
different functions in living organisms.
The table below shows some of the functions of proteins in the body.
(This is NOT in the syllabus and presented here for your information only.)
Type of Protein Function Examples
Support –
Keratin in hair, horns, feathers and horns.
Provides the framework
Structural proteins Collagen in connective tissue and tendon.
which defines the size
Elastin in ligament.
and shape of cells.
Transport metabolites
Haemoglobin, the iron-containing protein,
around the cell or
Transport proteins transports oxygen from the lungs to other
around the whole
parts of the body.
mechanism.
Coordination of Insulin, a hormone secreted by the
Hormonal
activities in the body. pancreas, helps regulate the
proteins
concentration of sugar in the blood.
Defensive
Protection against Antibodies combat bacteria and viruses.
proteins
diseases.
(antibodies)
Selective acceleration of Digestive enzymes catalyse the
Enzymes
chemical reactions. hydrolysis of polymers in food.
P a g e | 17-35
5.2 Formation of Proteins

Proteins are formed when about 100 or more amino acids undergo condensation polymerization.
*Refer to section 4.2.2 – Formation of peptide bonds
The twenty amino acids that make up all the proteins in the body are all -amino acids with
the general formula RCH(NH2)CO2H.
The structures of amino acids (not required to recall) are classified according to the nature
of the R group:
(a) non-polar (or hydrophobic) R groups
(b) polar uncharged (or hydrophilic) R groups
(c) negatively charged (at pH 6-7) R groups
(d) positively charged (at pH 6-7) R groups
-amino acid
Polar uncharged R
Amino acid Abbreviation Non-polar R group Amino acid Abbreviation
group
glycine Gly serine Ser
alanine Ala cysteine Cys
valine Val threonine Thr
leucine Leu asparagine Asn
isoleucine Ile glutamine Gln
methionine Met
tyrosine Tyr
phenylalanine Phe
Positively charged R
tryptophan Trp
group
proline* Pro lysine Lys
Negatively
charged R group
arginine Arg
aspartic acid Asp
glutamic acid Glu histidine His
*the full structure of proline is shown as it is the only amino acid that has a secondary amine.
*this table is for your information, it is not required to recall this knowledge.
P a g e | 17-36
Learning outcome:
(l) describe the hydrolysis of proteins
5.3 Hydrolysis of Proteins
Proteins can be broken into its constituent amino acids by
(a) heating under reflux (for 6+ hours) with 6 mol dm-3 NaOH or 6 mol dm-3 sulfuric acid
(b) Using specific enzymes, e.g. trypsin
The peptide bond is broken during the reaction to give the amino acids.
e.g.
Recap!
Carboxylic
Acids
Hydrolysis of
ester
Worked Example 9
The following shows a tripeptide.
Give the structure of the product(s) when the tripeptide is (a) placed in a cold aqueous solution
of pH 2, and (b) boiled with sodium hydroxide.
(a)
(b)
P a g e | 17-37
Lecture Practice 8
Upon hydrolysis, a tripeptide X forms the constituent amino acids according to the equation:
What is the Mr of X?
A tripeptide has 2 peptide bonds. (n amino acid residue has (n-1) peptide bonds)
When peptide bonds are formed, a water molecule (Mr = 18) is lost.
Mr of X = 75 + 103 + 105 – (2 x 18)
= 247
5.4 Partial Hydrolysis of proteins and peptide sequencing
• Partial hydrolysis of protein gives different fragments which still retain amino acid
sequence information
• When these fragment are separated and identified, the overall amino acid sequence of
the protein may be deduced from the overlaps to the peptide sequences.
Worked Example 10
Upon partial hydrolysis of a tetrapeptide, a mixture of the following 3 dipeptides fragments
were obtained.
Ala-Trp
Ala-Ala
Trp-Glu
Using the same 3-letter abbreviations as above, write out the formula of the tetrapeptide.
The 3 dipeptides overlap in the following way

Ala-Ala
Ala-Trp
Trp-Glu
Hence the sequence is Ala-Ala-Trp-Glu
P a g e | 17-38
SUMMARY
Amines
Amines dissolve in water to form base e.g.CH3CH2NH2 + H2O CH3CH2NH3+ + OH–
Amines dissolve in acids to form salt e.g. CH3CH2NH2 + HCl →_ CH3CH2NH3+Cl–_

Strength of the amines as bases depends on:
a. Availability of the lone pair of electrons on nitrogen
i.e. The more available the electrons, the stronger it is as a base.
b. Stability of the conjugate ion
i.e. The more stable the conjugate ion is, the stronger it is as a base.
* Test for phenylamine: A white ppt of 2,4,6-tribromophenylamine

is obtained and the orange Br2(aq) is decolourised.
P a g e | 17-39
Amino acids
Zwitterion
Amino acids usually exist as zwitterions. Zwitterions, being dipolar and therefore having no
net charge, there is no migration to cathode or anode when a potential difference is applied.
+
NH3-CH2-CO2-
Zwitterion (dipolar ion)
pH=4 H+ pH=10 OH–
+NH
3-CH2-CO2H NH2-CH2-CO2–
Cationic species, migrates to Anionic species, migrates to

cathode when a potential anode when a potential difference
difference is applied is applied
Amino acids can act as buffer solutions as they are amphoteric in nature (reacts with both
acids and bases).
P a g e | 17-40
Proteins
Formation and hydrolysis of proteins
P a g e | 17-41
Answers to Self-Practice Questions
1 B In the acidic solution, the amine is obtained as a salt, C6H5NH3+Cl-. Thus NaOH is
added to liberate the free amine.
2 Increasing pKb  decreasing Kb  decreasing basic strength
1. A < C < B
Cl atom is the most electron-withdrawing group among the Cl, Br and I. Thus, the lone
pair on N in B is the least available to accept proton. Br atom is the less electron-
withdrawing than Cl. Thus, the lone pair on N in C is the more available to accept proton.
I atom is the least electron-withdrawing. Thus, the lone pair on N in A is the most
available to accept proton. Therefore, A is the strongest base, followed by C and D.
2. D < B < A < C
Aliphatic amines are stronger bases than aromatic amines, Thus B and D are stronger
bases than A and C. B is a primary amine while D is a secondary amine, thus D
experiences a greater electron-donating effect from the alkyl groups compared to B,
making the lone pair of electron on N in D more available to accept proton compare to
B.
C is a weaker base than A as C has an electron-withdrawing CN group attached to the
benzene, thus decreasing the availability of the lone pair of electron on N to accept
proton. Therefore, D is the strongest base, followed by B, then A and weakest base is
C.
3 1. C P reacts with cold HCl (acid-base reaction), thus P must be a basic compound.
2. C Using acid, amine undergoes acid-base reaction to form salt which will be found in
the aqueous layer, while benzene will remain in the organic layer. Amine salt and
benzene can then be separated using a separating funnel. Amine is obtained when
the added acid is neutralized.
4 Ans: B
The p–p orbital overlap results in the delocalisation of the lone pair of electrons on N atom
into the electron system of C=O, making the lone pair of electrons on N atom NOT available
for protonation. Thus, amides have a resonance structure involving the movement of a pair
of electrons from the nitrogen atom to the oxygen atom.
P a g e | 17-42
Answers to Thinking Questions
1. (a) The lone pair of electrons on nitrogen is delocalized into the benzene ring, decreasing
availability of lone pair for donation. Hence, phenylamine is unable to undergo nucleophilic
substitution readily. However, the lone pair of electrons on nitrogen that delocalized into
the benzene ring will increase the electron density of the benzene ring to make it more
susceptible to electrophilic attack by electrophiles.
(b) This is because the –NH2 group is electron donating (lone pair from N atom is
delocalised into the ring). The ring becomes more electron rich and is more reactive
than benzene towards electrophiles.
Substitution occurs at 2-, 4- and 6- positions.
(c) Phenol
(d) The −NH2 group is more electron-donating than –OH group, hence it activates the
benzene ring to a larger extent. At the same time, in non-polar solvent, phenol can’t
dissociate to form phenoxide (which is formed in the aqueous solution, and has more lone
pair of electrons on the oxygen atom, and activates the benzene ring to greater extent).
2. 1 and 2 amides are capable of forming intermolecular hydrogen bonds. 3o amides
cannot form intermolecular hydrogen bonds with each other due to the absence of H
atoms directly attached to the electronegative N atom of the amine. They can only
form weaker dipole-dipole attractions with each other. Since less energy is required to
overcome the weaker permanent dipole – permanent dipole attractions, it thus has a lower
boiling point.
3. sp2 – due to delocalization of electrons, shape around N atom is trigonal planar.
4. The carboxylic acids will protonate/react with the amines which are bases to form a salt
instead.
5. A salt buffer solution contains large amount of a weak acid and large amounts of its
conjugate base or vice versa.
A solution of amino acid contains a weak acid and a weak base which are not conjugate
of one another. The weak acid and weak base are part of the same molecule as the
amino acid is amphoteric.
6. No. There is directionality in polypeptides. In the dipeptide on the left, the R group is
connected to a carbon that is connected to –NH2 group while in the dipeptide on the right,
the R group is connected to a carbon that is connected to a –COOH group.
P a g e | 17-43

2024 Nitrogen Cpds Notes (Teacher)

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Nitrogen Compounds 2024 Semester 1

CATHOLIC JUNIOR COLLEGE

The history of amines

Formula Type of compound Name

CH3CH2NH2 Amine Ethylamine

Aromatic amine Phenylamine

CH3CN Nitrile Ethanenitrile

Ammonia Primary Secondary Tertiary

tetramethylammonium chloride, ammonium chloride,

Aliphatic Amine Aromatic Amine

Phenylamine (1o amine)

N-ethyl-N-methylpropylamine 2-aminobutanoic acid

Name and classify the following amines.

(a) CH3CH2CH2NH2 propylamine (1o)

(b) (b) N-methylethylamine

2.2 Physical Properties of Amines

• Aliphatic amines are generally soluble in water δ-

Reason: Amines are soluble in water due to the formation

Hydrogen bonds between tertiary amine and water molecules

2.3 Preparation of Amines

CH3Br + CH3NH2 (CH3)2NH + HBr

CH3Br + (CH3)2NH (CH3)3N + HBr

CH3Br + (CH3)3N (CH3)4N+Br–

II. Reduction of Reagent and condition: LiAlH4 in dry ether

NO2 NH3+ NH2

excess NH3 (alc)

(b) CH3CH2Br → CH3CH2CH2NH2

alc. KCN LiAlH4 in ether

A. To dry the product

2.4 Chemical Reactions of Amines

The lone pair of electrons accounts for:

2.4.1 Amines as bases

In gaseous phase, basicity increases from CH3NH2 to (CH3)2NH to (CH3)3N [2018/P3/Q3]

Amine Formula Kb at 25oC / moldm-3 pKb

i) Relative Basicities of Ammonia, Ethylamine & Phenylamine

From the table,

CH3CH2NH2 > NH3 >>

• Ethylamine is a stronger base than ammonia

OR The electron donating alkyl group disperses the positive charge on

• Phenylamine is a weaker base than ammonia.

The p–p orbital overlap results in the

OR The electron withdrawing phenyl group intensifies the positive charge on

Summary on Basicity of Amines:

Electron–donating Electron–withdrawing N atom of amine directly attached to

p–p orbital overlap results in the

stronger base compared to

Base NH3 CH3NH2 (CH3)2NH (CH3)3N

Thus, in aqueous solution, the order of increasing basic strength:

Least basic Most basic

Cl atom is electron-withdrawing. Thus, the lone pair of electron on N is less

Answers: 1. A < C < B

ii) Formation of Salt

Addition of alkali to this salt solution causes phenylamine to be released.

Behold the power of lemons!

2.4.2 Amines as Nucleophiles

Type of reaction: Nucleophilic substitution / addition-elimination / Reaction of acyl

Reagents and condition: Room temperature Amide functional group

amide where R, R’ = aryl

1. To make amides, carboxylic acids cannot be used instead of acid chlorides

ii) Reaction with halogenoalkanes

Observations: 1. orange bromine solution decolourised

What is the final product of this reaction?

Answer: A N2012/ I/30

A The solution gets more acidic