CHEMISTRY FORM 6

ORGANIC CHEMISTRY

CHAPTER 8 : AMINE

9.1 Introduction and nomenclature

� Amines are organic compounds with functioning group –NH2 (aminO)

� The naming of amine depends on the classification of amine. Table below shows different class of amine and their naming

Classificatio

nExample

Primary

amine

CH3CH2CH2NH2

propylamine 2-methylpropylamine3-ethyl-1-methylpentylamine

cyclopentylamine4,4-dimethyl

cyclohexylaminePhenylamineor Aniline

Secondary

amine

Tertiary

amine

Quaternary

salt

N-ethylpropylamineN-propylaniline

N-cyclopentylcyclohexylamine

N-ethyl-N-methyl propylamine

N,N-diphenylmethylamine

N,N-dipropylethylamine

Ammonium chloride Tetramethylammoniumbromide

Tetraethylammoniumhydroxide

9.1 Physical properties of amine

� Boiling point of increasing in homologous series

Amine CH3NH2 C2H5NH2 C3H7NH2 C4H9NH2 C5H11NH2

Boiling point oC 4 17 52 83 106

Boiling point

trend Boiling point increase

Explanation :

Classification of

aminePrimary amine Secondary amine Tertiary amine

Example (same

RMM)CH3CH2CH2NH2 CH3CH2NHCH3 (CH3)3N

Boiling point (oC) 52 34 2

Explanation :

When going down to homologous series, the boiling point increase. This is due to the increase in relative molecular mass, which increase the weak Van DerWaals forces causing boiling point increase.

Amine can form hydrogen bond between molecules. Straight chain molecule has a larger total surface area compare to a branched chain molecule. Hence, greater the total surface area exposed, greater the Van DerWaals forces, higher the boiling point. However, tertiary amine cannot form hydrogen bond, so their boiling point decrease significantly.

Organic CH3CH2CH2CH3 CH3CH2CH2NH2 CH3CH2CH2OH CH3COOH

RMM 58 57 60 60

Boiling point oC 4 52 78 118

•Boiling point of different organic compounds

Amine CH3NH2 C2H5NH2 C3H7NH2 C4H9NH2 C5H11NH2

Solubility trendSolubility DEcrease

Explanation

B) Solubility of amine

Ethanoic acid has 2 hydrogen bond within their molecules, so their hydrogen bond is the strongest. Both propylamine and propan1-ol has hydrogen bond, but propan-1-ol has a stronger hydrogen bond since O is more electronegative than N. Butane is a non-polar molecule, which is held by weak Van DerWaals forces

methylamine, ethylamine and propylamine are completely miscible in water as they can form hydrogen bond with water. However, the LONGER the ALKYL GROUPS ATTACHED, molecule become MORE HYDROPHOBIC. As a result, HYDROGEN BOND BECOME LESS SIGNIFICANT and cause the solubility decrease.

C) Basicity of amine

Amine is a weak base. When dissolve in water, it undergoes partial

dissociation where

The pKb of some amine is given in the table below

bbb KpKRNH

OHRNHK lg

][

]][[

2

3 −==−+

Amine CH3NH2 C2H5NH2 C3H7NH2 CH3CH2NHCH3

pKb 3.42 3.27 3.03 2.88

(CH3)3N

2.64 9.41 9.58

All alkyls are electron donating group, which donate electron

density to N in NH2, making N to be more readily to accept proton.

Hence, equilibrium shift more to right, increasing the basicity.

Longer the alkyl chain, greater the electron donating effect, greater

the basicity.

Basicity increase from 10 amine < 20 amine < 30 amine. This is due to, the more the

alkyl group surrounding N, greater the electron donating effect, where N has large

electron density and are more readily to accept proton, causing equilibrium to shift

more to right, increasing the basicity of amine.

phenylamine is a weaker base compare to alkyl amine, due to the

benzene ring is an electron withdrawing group. As a result, N in

amine has lesser electron density and is less readily to accept

proton (conversely more readily to donate proton) which caused

equilibrium shift more to left. This results the basicity of

phenylamine is lesser than alkyl amine. When a ring activator is

bonded to phenylamine, ita activate further the ring and caused

the ring to be more readily to accept proton, hence increase the

basicity. Conversely, if a ring deactivator is bonded to

phenylamine, it deacticate the ring and caused benzene to be

less readily to accept proton, decreasing the basicity

9.2 Preparation of amine

Name of

reaction

Reagent used

and conditionEquation

Alkylation

of

haloalkane

Concentrated

NH3 1-bromopropane conc. propylamine

Ammonia

Reduction

of nitrile

Lithium

aluminium

tetrahydride

LiAlH4

2-methylbutylnitrile 2-methylbutylamine

Reduction

of amide

Lithium

tetrahydrido-

aluminate,

LiAlH4

propanamide propylamine

9.2.1 Chemical reaction of amine

Name of

reaction

Reagent used

and conditionEquation

Reaction with

mineral acid

Mineral acid

such as HCl ;

H2SO4

Nitrosation of

amine

HNO2 under

certain

condition

Reaction with

acyl chloride,

R–COCl

R–COCl,

acyl chloride

(A) Reaction with mineral acids : Formation of salts

� Amine dissolves in aqueous solution of mineral acid to form salt of ammonium. Example

� The amine salt form is white crystalline solid dissolve readily in water

� When dissolve in alkaline solution, amine is form back

� CH3CH2NH3+Cl– (aq) + OH– (aq) � CH3CH2NH2 (aq) + H2O (l) + Cl

–

(aq)

Class of amine Example Mineral acid Salt

CH3CH2NH2 HCl CH3CH2NH3+Cl–

(CH3CH2)2NH HCl

(CH3CH2)3N HCl

Primary amine

Secondary amine

Tertiary amine

(CH3CH2)2NH2+Cl–

(CH3CH2)3NH+Cl–

(B) Reaction of amine with nitrous acid

� Nitrous acid (or nitric (III) acid) is unstable. It can be prepared by reaction of sodium nitrite and hydrochloric acid

� Equation : NaNO2 (s) + HCl (aq) � NaCl (aq) + O=N–OH (aq)

� The organic products formed from the reaction between nitrous acid and amine depend on 2 factors

� Class of amine used � Condition of the reaction

� When aliphatic primary amine reacts with nitrous acid, nitrogen is evolved rapidly and alcohol is produce as major product along with some side product such as alkene and in some case, ether.

� The reaction of nitrous acid follows the mechanism below

Primary amine :

� Amine act as nucleophile and attack nitrosyl cation, the following mechanism of reaction take place.

diazonium ion

� The reaction after the formation of diazonium ion is complex. Depend on the condition of the reaction, it form various organic compound such as alcohol or alkene. Example :

Secondary amine

� Secondary amine reacts with nitrous acid (nitrosyl cation) under room condition to form nitrosoamine. Unlike primary amine, there’s no nitrogen gas evolve. Example

N–nitrosoamine

Tertiary amine

� Tertiary amine dissolve readily in acidic solution of nitrous acid to form salt according to the equation

(C) Reaction with acyl chloride (refer Chap 8.4)

� When acyl chloride reacts with primary amine, it will form a secondary amide

� When react acyl chloride with a secondary amine, it will form a tertiary amide

� Acyl chloride will not be acylated as it does not has a hydrogen atom to be substituted.

9.3 Aromatic amine

� The simplest form of aromatic amine is phenylamine, which is better known as aniline

� Some of the common naming of aromatic amines are shown below

aniline p-nitroaniline o-methylaniline N-methylaniline

diphenylamineN-ethyl-N-methylaniline

N,N-diethylaniline phenylmethylamine

9.3.1 Preparation of aniline

� Aniline can be prepare by using nitrobenzene. Reagent : conc. HCl catalysed by tin, Sn.

9.3.2 Chemical reaction of aniline

1. Reaction with acid : the basic properties of aniline

� Aniline is considerably weak acid as the pKb = 9.3

� This is due to the electron withdrawing effect of the benzene, causes the electron density of nitrogen decrease. When this occur, nitrogen are more readily to donate proton rather than accept and equilibrium shift more to the left (Kb decrease)

� Though, aniline is able to react with acid by accepting the H+ from acid and form salt

Aniline Acid Salt

HCl

H2SO4

in excess

H2SO4

HNO3

• Salts of aniline are colourless, crystalline solid and mostly are soluble in water. When react with alkali, it give back the phenyl amine with salt and water

2. Reaction of aniline with haloalkane

� If aniline is reacted with iodomethane (CH3I) under ethanolic, a secondary amine is first formed and eventually turns out to become salt

� If excess haloalkane is used, the reaction will further to form a tertiary amine and quaternary salt.

3. Reaction of aniline with acyl chloride (Chapter 8.4)

� This is one of the method use to prepare amide as discussed earlier. When acyl chloride react with amine, a secondary amide is formed

� When a secondary amine reacts with acyl chloride, it will form a tertiary amide.

� Tertiary amine will not react with acyl chloride as there’s no H substitute out

4. Reaction of aniline with nitrous acid

� Similar to the reaction of nitrous acid with alkyl amine, aniline react with the electrophilenitrosyl cation where the formation of ion follow the mechanism below

� When aniline attacks the electrophilic nitrosyl cation, it form benzenediazonium ion.

� Benzenediazonium chloride formed is unstable and tends to react with other substances. Diagram below shows the type of reaction that the benzenediazonium can undergoes

5. Formation of dyes by coupling reaction

� The reaction of forming azo dye is via coupling reaction. Diazonium ion react with benzene attached with strong ring activate group, under alkaline condition, to give bright colouration of azo dye. Strong ring activate group direct at ortho-para position.

Benzenediazonium chloride phenol 4-hydroxyphenylazobenzene

� When react with 1-naphthol, it form a bright scarlet azo dye

� When react with another aniline, it form an orange-red precipitate dye.

9.4 Chemical tests for aniline

(1) Reaction with bromine

� Similar to phenol, aniline is a strong ring activate group. So, when aniline is reacted with aqueous bromine solution, it forms a white precipitate.

(2) Reaction with sodium chlorate (I), NaClO

� When aniline is added to NaClO, a purple colouration is obtained

(3) Reaction with phenol under alkaline solution

� As discuss earlier, when aniline is react phenol under NaOH, a yellow precipitate is observed.

10.1 Introduction

� Amino acid has the general formula of NH2 – CHR –COOH.

� From the general above, we can tell that there are 2 functioning groups of –NH2 (amine) and –COOH (carboxylic acid).

� There are 22 types of amino acids and almost all naturally occurring amino acids are α-amino acid

� The terms α- mean both NH2 and COOH are attached at the same C. Considering –COOH act as the functioning group, α-amino acid has the general naming as 2-aminocarboxylic acid

� The simplest form of amino acid is called glycine (2-aminoethanoic acid)

� All amino acids are optical active (except glycine) as they have 4 different functioning groups (chiral carbon atom).

Acidic amino acid Neutral amino acid Basic amino acid

The number of COOH is

more than NH2

The number of COOH is

equal to the number of NH2

The number of COOH is less

than NH2

� Since amino acid has both acidic (–COOH) and basic (–NH2) fuctional group, hence amino acid undergoes 3 types of chemical reaction :

� reactions characteristic of the amino group

� reactions characteristic of the carboxylic group

� reaction due to the presence of both group

� Because of both (–COOH) and (–NH2) group, it makes amino acid very soluble in water. Neutral amino acid such as alanine and glycine are slightly miscible on ethanol and epoxyethan.

� This is due to amino acid exist as polar ion.amino acid exist as a zwitterions, which carries both positive and negative charge in its molecule. A zwitterions is formed when –COOH donated its proton to –NH2, according to

Condition Equation Charge

AcidicPositive

charge

Neutral Zwitterions

BasicNegative

charge

� Isoelectric point – the pH at which amino acid has a net charge of zero.

� Amino acids with one –COOH and one –NH2 have isoelectric points in the pH range 5.5 – 6.5

� Acidic amino acid (eg : aspartic acid and glutamic acid) has lower isoelectric point (lower pH value) while basic amino acids (eg : lysine and arginine) have higher isoelectric point (higher pH value)

10.2 Chemical Properties of Amino acid

10.2.1 Preparation of amino acid

Name of

reaction

Reagent used

and conditionEquation

Reaction of

ammonia with

α-halo

carboxylic acid

Concentrated

ammonia

10.2.2 Formation of peptide lingkage

� The reaction which link 2 amino acids together is a condensation reaction where water is given off and formed a dipeptide. Peptide link is a secondary amide group where the C-from one amino acid is linked to the –N of another amino acid.

� If 3 amino acids joined together, the product is ………………….. When a lot of amino acids join together, the product is a …………….. When the many chain of peptide formed …………..…....

10.2.3 Hydrolysis of Protein

� Protein could be broken into its constituent amino acids by heating under reflux with aqueous NaOH or dilute H2SO4 via hydrolysis reaction.

� Hydrolysis of protein can be completely or partially hydrolyse.

� Complete hydrolysis of protein gives the number and relative amount of amino acids, but does not provide the information of the order of how they joined together (the sequence of R)

� Partially hydrolysis give fragments which still retain sequence information. When these fragments are separated and identified, the overall protein structure can be deduced. Example

10.3 Chemical Test for amino acid

� Aminoethanoic acid (NH2CH2COOH) gives the following reactions :

� It liberates CO2 when treated with Na2CO3 and NaHCO3.

� Form dark red solution when treated with neutral iron (III) chloride solution.

� It gives a deep blue solution when treated with copper (II) solution due to the copper (II) complex.

10.4 Function of Proteins

� All proteins are made up of long chains of amino acids.

� Each protein is determined by its amino acid sequence (which ranges from 44 amino acids in the hormone insulin to giant molecules with more than 50,000 amino acids).

� Proteins are essential in living systems - animals, plants and micro-organisms.

� Proteins are responsible for growth, repair and maintenance of the body.

Types of proteins Function

structural proteins

• provide the framework which defines the size and shape of cells

• e.g. elastin (in ligament)

a -keratins (in skin, hair, nails)

collagen (in connective tissue, tendon, cartilage)

muscle fibres• produces mechanical force and movement,

• e.g. actin and myosin

transport proteins• move metabolites around the cell or around the whole

organism

• e.g. haemoglobin which transports oxygen in blood

Some hormones• control the level and type of cell activity,

• e.g. insulin which regulates glucose metabolism

Enzymes• catalyse metabolic processes which produce energy, build

up new cell structures and destroy old ones

10.5 Protein Structures

� The structure of proteins are categorised into four levels of complexity:

> primary (1°) structure > secondary (2°) structure

> tertiary (3°) structure > quaternary (4°) structure

10.5.1 Primary (1°) structure

� The primary (1°) structure of a protein shows the order (or sequence) of amino acids in a protein chain

� By convention, amino acid sequence is written with free –NH2 on left & free –COOH on right.

� The primary structure includes any covalent cross-linkages, e.g. –S–S– bonds.

� The primary structure determines -what the protein is, how it folds, and its function.

� The sequence of R groups determines whether the protein chain will

1. coil with hydrogen bonding between N-H and C=O groups within each chain (α–helix), or

2. fold with hydrogen bonds formed between two protein chains (β–pleated sheet).

Conc. HNO3 catalysed by H2SO4 under reflux

Conc. HCl under tin

C6H5NH2 + HCl � C6H5NH3Cl

Phenylamine is a weaker base than ammonia

Phenyl is an electron withdrawing group, which decrease the electron density of N

Making –N more readily to donate proton

Sodium nitrite, NaNO2 + hydrochloric acid, HCl

0 – 5 0C

Sodium hydroxide

Iodine in Sodium hydroxide

Yellow precipitate is formed

No changes occur

CH3CH(OH)COOH + I2 + OH- � -OOC–COO- + CHI3 + 3 HI

J (chloropropanoic acid) is stronger acid than propanoic acid

Due to the inductive effect caused by –Cl in the carboxylic acid

CH3CH(NH2)COOH + NaOH � CH3CH(NH2)COONa + H2O

peptide linkage / peptide bond / amide

C6H5COCl

HCl or H2SO4 or NaOH (aq) + heat/reflux

Electrophilic aromatic substitution reaction

Conc. HNO3 catalysed by conc. H2SO4 under reflux

NO2+ H+

reduction

Conc. HCl under tin

PCl5 under room temperature

amide

amide

2 Ag+ + HO–Ph–NH2 + 2 OH- � O=<>=O + H2O + NH3 + 2 Ag

Rodinol is a weaker base than ammonia, since rodinol has an electron withdrawing

benzene ring to reduce the basicity.

Conc. HNO3 in conc. H2SO4 under reflux

reduction

Conc. HCl in tin

Phenol and amide

CH3COCl

Bromine water

amide

NaNO2 in HCl under 0-50C

To increase its solubility in water or to increase binding to food components (1)

due to ionic solvation or more oxygen atoms to H-bond to H2O/glucose etc (1)