CHEM 159

FOUNDATION CHEMISTRY

DR.s MERCY BADU AND FRANCIS OPOKU

ORGANIC CHEMISTRY
INORGANIC CHEMISTRY
PHYSICAL CHEMISTRY

MON. 10:30 – 12:25

TUES. 8:00 – 10:00

www.knust.edu.gh
 IMPORTANT INFORMATION
• Lecture Attendance (100 %)
• Lecturer Assessment (At the end of the semester)
• Punctuality (Attend lectures on time)
• Respect
• Integrity
• Hard work
• Assistance

• Continuous Assessment (30 %)

– Quizzes
– Presentations
– Mid-Semester
• End of Semester Assessment (70 %)

www.knust.edu.gh
 RECOMMENDED BOOKS
• Organic Chemistry by Robert Thornton Morrison
and Robert Neilson Boyd. Published by Prentice Hall
Int. Inc., New York. 6th Edition or a later edition.

• Organic Chemistry by T.W. Graham Solomons.

Published by John Wiley and Sons, New York. 4th
Edition or later edition.

• Organic Chemistry by Francis Carey

www.knust.edu.gh
 ORGANIC CHEMISTRY

• Organic chemistry is the study of carbon compounds

• Carbon forms 4 strong bonds to other atoms including:
– Hydrogen, Oxygen, Nitrogen, Halogens etc
• Carbon has the ability to form a large number of possible compounds

• Different groups of compounds

– Hydrocarbons
– Carbonyls
– Alcohols
– Carboxylic acids
– Aromatics
– Heterocyclic compounds etc.

www.knust.edu.gh
 Carbon Types
• In an organic compound, carbon may be classified according to their
structural type in the molecule.

• The structural type is determined by the different kinds carbons

present

• Primary carbons (1°), are bonded to one other carbon.

• Secondary carbons (2°), are bonded to two carbons.

• Tertiary carbons (3°), are bonded to three others.

• Quaternary carbons (4°), are bonded to four others.

www.knust.edu.gh
 Organic Molecules
• Carbon form bonds by sharing electrons

• When atoms form bonds, their simple atomic orbitals often mix to form
new orbitals called hybrid orbitals.

• Orbitals are the spaces with highest probability of finding the electron

• The redistribution of the energy of orbitals of individual atoms to

give orbitals of equivalent energy is termed hybridization
 What is Hybridization?
Hybridization:
. • Mixing of two or more atomic orbitals to form new hybrid
orbitals
• In hybridization, mix at least 2 nonequivalent atomic orbitals
(e.g. s and p).
• Hybrid orbitals have very different shapes from original
atomic orbitals.
• Number of hybrid orbitals is equal to number of pure atomic
orbitals used in the hybridization process.

• Covalent bonds are formed by:

✓ Overlap of hybrid orbitals with atomic orbitals
✓ Overlap of hybrid orbitals with other hybrid orbitals

www.knust.edu.gh
 sp Hybridization
sp hybridization is observed when one s and one p orbital in the same main
shell of an atom mix to form two new equivalent orbitals.
The new orbitals formed are called sp hybridized orbitals.

It forms linear molecules with an angle of 180°

•.sp hybridization is also called diagonal hybridization.
•Each sp hybridized orbital has an equal amount of s and p character,
•i.e., 50% s and p character.

Examples of sp Hybridization:
All compounds of beryllium like BeF2,
BeH2, BeCl2
All compounds of carbon-containing triple
Bond like C2H2

www.knust.edu.gh
 sp2 Hybridization
sp2 hybridization is observed when one s and two p orbitals of the same shell of an
atom mix to form 3 equivalent orbital. The new orbitals formed are
called sp2 hybrid orbitals.
•The new orbitals are also called trigonal hybridization with an angle of 120° .

•All the three hybrid orbitals remain in one plane and make an angle of with one
120° another. Each of the hybrid orbitals formed has 33.33% s character and
66.66% ‘p’ character.

•The molecules in which the central atom is linked to 3 atoms and is sp2 hybridized
have a triangular planar shape.

Examples of sp2 Hybridization

•All the compounds of Boron i.e. BF3, BH3
•All the compounds of carbon containing a
carbon-carbon double bond, Ethylene
(C2H4)

www.knust.edu.gh
 sp3 Hybridization
When one ‘s’ orbital and 3 ‘p’ orbitals belonging to the same shell of an atom mix
together to form four new equivalent orbitals, the type of hybridization is called
a tetrahedral hybridization or sp3. The new orbitals formed are called sp3 hybrid
orbitals.

• The orbitals are directed towards the four corners of a regular tetrahedron and
make an angle of 109°28’ with one another.

•Each sp3 hybrid orbital has 25% s character and 75% p character.
•Example of sp3 hybridization: ethane (C2H6), methane.

www.knust.edu.gh
 FUNCTIONAL GROUPS
The bonding of carbon with other elements gives the unique property of
the molecule that result.
This unique features is referred to as functional group22

www.knust.edu.gh
HYDROCARBONS

www.knust.edu.gh
 HYDROCARBONS
Hydrocarbons

Aliphatic Aromatic

Alkanes Alkenes Alkynes Alicyclic

www.knust.edu.gh
 ALKANES

• They are hydrocarbons with a general

molecular formula CnH2n+2
where n = no. of carbon atoms
• They are made up of C – C bonds
• They are relatively unreactive
• The cycloalkanes have general formula CnH2n

www.knust.edu.gh
❖ Alkanes: CnH2n+2

5 3 1
e.g.
6 4 2
hexane (C6H14)

❖ Cycloalkanes: CnH2n

e.g.
cyclohexane (C6H12)
www.knust.edu.gh

Ch. 4 - 15
 Sources of Alkanes: Petroleum

❖ Petroleum is the primary source of

alkanes.
❖ Petroleum is a complex mixture of mostly
alkanes and aromatic hydrocarbons with
small amounts of oxygen-, nitrogen-, and
sulfur-containing compounds

www.knust.edu.gh

Ch. 4 - 16
 Typical Fractions Obtained by
Distillation of Petroleum
Boiling Range of # of Carbon Atoms Use
Fraction (oC) per Molecule

Below 20 C1 – C4 Natural gas, bottled

gas, petrochemicals

20 – 60 C5 – C6 Petroleum ether,
solvents

60 – 100 C6 – C7 Ligroin, solvents

40 – 200 C5 – C10 Gasoline (straight-run
gasoline)

175 – 325 C12 – C18 Kerosene and jet fuel

www.knust.edu.gh

Ch. 4 - 17
 Typical Fractions Obtained by
Distillation of Petroleum
(Cont’d)
Boiling Range of # of Carbon Atoms Use
Fraction (oC) per Molecule

250 – 400 C12 and higher Gas oil, fuel oil, and
diesel oil
Nonvolatile liquids C20 and higher Refined mineral oil,
lubricating oil, and
grease
Nonvolatile solids C20 and higher Paraffin wax,
asphalt, and tar
www.knust.edu.gh

Ch. 4 - 18
IUPAC Nomenclature of ALKANES
❖ One of the most commonly used nomenclature systems used
today is based on the system and rules developed by the
International Union of Pure and Applied Chemistry (IUPAC)

❖ Fundamental Principle: Each different compound shall have a

unique name

❖ Although the IUPAC naming system is now widely accepted

among chemists, common names (trivial names) of some
compounds are still widely used by chemists and in commerce.

❖ The common names of these chemicals and compounds are still

important

www.knust.edu.gh

Ch. 4 - 19
❖ Examples of some Unbranched alkanes and their
names

Name Structure Name Structure

Methane CH4 Hexane CH3(CH2)4CH3
Ethane CH3CH3 Heptane CH3(CH2)5CH3
Propane CH3CH2CH3 Octane CH3(CH2)6CH3
Butane CH3CH2CH2CH3 Nonane CH3(CH2)7CH3
Pentane CH3(CH2)3CH3 Decane CH3(CH2)8CH3

www.knust.edu.gh

Ch. 4 - 20
❖ Alkyl group
● For an unbranched alkane, the hydrogen
atom that is removed is a terminal hydrogen
atom
CH3 H CH3CH2 H CH3CH2CH2 H
Methane Ethane Propane

CH3 CH3CH2 CH3CH2CH2

Methyl Ethyl Propyl
(Me) (Et) (Pr)
www.knust.edu.gh

Ch. 4 - 21
 Nomenclature of Branched-Chain
Alkanes
❖ Rule
1. Use the longest continuous carbon chain as
parent name

7 6 5 4 3 6 5 4 3 2 1
CH3CH2CH2CH2CHCH3 CH3CH2CH2CH2CHCH3
2CH2 NOT CH2
1 CH3 CH3
(3-Methylheptane) (2-Ethylhexane)
www.knust.edu.gh

Ch. 4 - 22
❖ Rule (Cont’d)
2. Use the lowest number of the substituent
3. Use the number obtained by
Rule 2 to designate the location of the
substituent

7 6 5 4 3 1 2 3 4 5
CH3CH2CH2CH2CHCH3 CH3CH2CH2CH2CHCH3
2CH2 6 CH2
1 CH3 7 CH3
NOT
(3-Methylheptane) (5-Methylheptane)
www.knust.edu.gh

Ch. 4 - 23
 ❖ Rule
For two or more substituents, use the lowest possible individual
numbers of the parent chain

The substituents should be listed

alphabetically. In deciding alphabetical
order, disregard multiplying prefix, such
as “di”, “tri” etc.
7 5 3 1
8 6 4 2
2 4 6 8 (3-Ethyl-7-methyloctane)
1 3 5 7
(6-Ethyl-2-methyloctane)

2 4 6 8
1 3 5 7
(2-Methyl-6-ethyloctane)
www.knust.edu.gh

Ch. 4 - 24
5. When two substituents are present
on the same carbon, use that number
twice

2 4 6 8
1 3 5 7
(4-Ethyl-4-methyloctane)

www.knust.edu.gh

Ch. 4 - 25
 6. For identical substituents, use prefixes di-,
tri-, tetra- and so on
5 3 1
6 4 2 7 5 3 1
6 4 2

(2,4-Dimethylhexane) (2,4,5-Trimethylheptane)
NOT NOT
2 4 6
1 3 5 1 3 5 7
2 4 6

(3,5-Dimethylhexane) (3,4,6-Trimethylheptane)
www.knust.edu.gh

Ch. 4 - 26
 7. When two chains of equal length
compete for selection as parent
chain, choose the chain with the
greater number of substituents

7 1
6 4 2 1
5 3 4 2
3

5
NOT 6
7
(2,3,5-Trimethyl-
(only three substituents)
4-propylheptane)
www.knust.edu.gh

Ch. 4 - 27
 8. When branching first occurs at an
equal distance from either end of the
longest chain, choose the name that
gives the lower number at the first
point of difference
6 1 NOT
5 3 1 2 4 6
4 2 3 5

(2,3,5-Trimethylhexane) (2,4,5-Trimethylhexane)
www.knust.edu.gh

Ch. 4 - 28
● Use the lowest numbering for
substituents
4 6 4 2
5 7 3 1
instead of
3 1 5 7
2 6

● Substituents: two methyl groups

⧫ dimethyl
4 6
5 7

3 1
2
www.knust.edu.gh

Ch. 4 - 29
● Substituents in alphabetical order
⧫ Ethyl before dimethyl
(recall Rule 4 – disregard “di”)
● Complete name 8
7
9
6
5
2
3
4
1

(4-Ethyl-3,7-dimethylnonane)
www.knust.edu.gh

Ch. 4 - 30
Nomenclature of Branched Alkyl Groups

❖ For alkanes with more than two carbon atoms, more

than one derived alkyl group is possible
❖ Three-carbon groups

Propyl Isopropyl
(or 1-methylethyl)

www.knust.edu.gh

Ch. 4 - 31
❖ Other-carbon groups

Butyl Isobutyl

sec-butyl tert-butyl
(1-methylpropyl) (or 1,1-dimethylethyl)

neopentyl
(2,2,-dimethylpropyl)
www.knust.edu.gh

Ch. 4 - 32
 Classification of Hydrogen Atoms

1o hydrogen atoms
CH3
CH3 CH CH2 CH3

3o hydrogen atoms 2o hydrogen atoms

www.knust.edu.gh

Ch. 4 - 33
 Naming Cycloalkanes
Monocyclic Compounds
H2C CH2 =
Use prefix cyclo-
C
H2C CH2 = H2
Cyclopropane
H2C CH2
C
H2
Cyclopentane
Isopropylcyclopropane

tert-Butylcyclopentane Methylcyclobutane
www.knust.edu.gh

Ch. 4 - 34
❖ Example 1

4 3 2
1-Ethyl-3-methyl-
1
cyclopentane
5

NOT NOT
3 4 5 5 1 2

2 1 4 3

1-Ethyl-4-methyl- 3-Ethyl-1-methyl-
cyclopentane cyclopentane
www.knust.edu.gh

Ch. 4 - 35
 Cycloalkylalkanes
● When a single ring system is attached to a single chain
with a greater number of carbon atoms

1-Cyclobutylpentane

When more than one ring system is attached to a single chain

1,3-Dicyclohexylpropane
www.knust.edu.gh

Ch. 4 - 36
 Bicyclic Alkanes
❖ Bicycloalkanes
● Alkanes containing two fused or bridged rings

❖ Total # of carbons = 7
● Bicycloheptane

❖ Bridgehead
www.knust.edu.gh

Ch. 4 - 37
❖ Example (Cont’d)

❖ Between the two bridgeheads

● Two-carbon bridge on the left
● Two-carbon bridge on the right
● One-carbon bridge in the middle
❖ Complete name
● Bicyclo[2.2.1]heptane
www.knust.edu.gh

Ch. 4 - 38
❖ Other examples
9 2
1
3
8
7 4
6
5

7-Methylbicyclo[4.3.0]nonane
8

7
4
5 3
1

6 2

1-Isopropylbicyclo[2.2.2]octane
www.knust.edu.gh

Ch. 4 - 39
 Bicyclic & Polycyclic Alkanes

Decalin
(Bicyclo[4.4.0]decane)

H H

H H
cis-Decalin trans-Decalin
H H
H

H
www.knust.edu.gh

Ch. 4 - 40
 ISOMERISM

❖ Butane and isobutane have the same molecular

formula (C4H10) but different bond connectivities. Such
compounds are called constitutional isomers

Butane Isobutane

www.knust.edu.gh

Ch. 4 - 41
❖ C4 and higher alkanes exist as constitutional isomers. The number of constitutional
isomers increases rapidly with the carbon number

Molecular # of Possible Molecular # of Possible

Formula Const. Isomers Formula Const. Isomers
C4H10 2 C9H20 35

C5H12 3 C10H22 75

C6H14 5 C20H42 366,319

C7H16 9 C40H82 62,481,801,147,341

C8H18 18

www.knust.edu.gh

Ch. 4 - 42
❖ Constitutional isomers usually have different physical properties
Hexane Isomers (C6H14)
Formula M.P. B.P. Density Refractive
(oC) (oC) (g/mL) Index
-95 68.7 0.6594 1.3748

-153.7 60.3 0.6532 1.3714

-118 63.3 0.6643 1.3765

-128.8 58 0.6616 1.3750

-98 49.7 0.6492 1.3688

www.knust.edu.gh

Ch. 4 - 43
CONFORMATIONS OF ALKANES
❖ Two groups bonded by a single bond can undergo
rotation about that bond with respect to each other
● Conformations – temporary molecular shapes
result from a rotation about a single bond
● Conformer – each possible structure of
conformation
● Conformational analysis – analysis of energy
changes that occur as a molecule undergoes
rotations about single bonds

www.knust.edu.gh

Ch. 4 - 44
Newman Projections
Me
H H Sawhorse formula

Cl OH
Et
Look from this
direction
H Me H H
combine Me H
Cl Et OH Cl Et
front carbon back carbon OH
Newman Projection

www.knust.edu.gh

Ch. 4 - 45
How to Do a Conformational Analysis

Look from this

direction
a f1 = 60o
H
H b
H staggered
f2 = 180o
confirmation
H H of ethane
Hc
www.knust.edu.gh

Ch. 4 - 46
 60o 0o
CH3
CH3 CH3 CH3
CH3
180o

CH3
anti gauche eclipsed

www.knust.edu.gh

Ch. 4 - 47
Physical Properties of Alkanes and Cycloalkanes

Non-nonbonding intermolecular attractive forces

(van der Waals forces)
1. Dipole – Dipole
2. Dipole – Induced-dipole
3. Induced-dipole – Induced-dipole : small instantaneous
dipoles
that result from a distortion of the electron clouds. There
is an attraction between molecules as result of these
temporary dipoles

www.knust.edu.gh

Ch. 4 - 48
Alkanes show: regular increase in bp and mp as the
molecular
weight increase. Branching lowers the bp or alkanes
n-pentane bp= 36.1 °C
iso-pentane bp= 27.9 °C
neo-pentane bp= 9.5°C

Alkanes have low polarity and are hydrophobic (low water

solubility). Solubility deceases are the number of carbons
increase

www.knust.edu.gh

Ch. 4 - 49
 Preparation of Alkanes
Hydrogenation of Alkenes & Alkynes (Addition Rxn)
H2
H H
Pt, Pd or Ni
C C
solvent
heat and pressure

2H2
H H
Pt, Pd or Ni
C C
solvent
heat and pressure H H
www.knust.edu.gh

Ch. 4 - 50
 Preparation of Alkanes

• Reduction of Alkylhalide
a) Hydrolysis of Grignard reagents
R-X + Mg dry ether R-MgX H2O R-H

b) Reduction by metal and acid

R-X + Zn + H+ R-H + Zn2+ + X-

www.knust.edu.gh
 Preparation of Alkanes
3. Coupling of alkylhalides with organometallic
compounds. R
R-X Li R-Li CuX R – CuLi
1°,2° or 3° lithium dialkylcopper R – R’
R’-X

www.knust.edu.gh
 REACTIONS OF ALKANES
1. HALOGENATION
• Proceeds via free radical mechanism.
• Three steps are involved:
- Initiation step
- Propagation step
- Termination step

www.knust.edu.gh
 REACTIONS OF ALKANES
Eg. Cl2 hv Cl . + Cl .
Chlorine radicals
H H
abstr. of H
H C H + Cl* H C* + HCl

H
H methyl radical
Methane

H
H
H C Cl + Cl*
H C * + Cl2

H H chlorine radical
methyl radical Chloromethane
www.knust.edu.gh
• Termination Step: two radicals combine to
produce neutral molecules:

Eg.
H H H H

H C* + H C* H C CH
H H H H
methyl radical methyl radical Ethane

Cl* + Cl* Cl2

www.knust.edu.gh
2. Combustion or oxidation
• Here the alkanes are burnt or combusted in air to
yield CO2, H2O and heat.

www.knust.edu.gh
 REACTIONS OF ALKANES
3. Pyrolysis (Thermal Cracking): this is the
decomposition of a compound by heat alone.

400-600°C
Alkane H2 + Smaller alkane + Alkene

www.knust.edu.gh
 Kwame Nkrumah University of
Science & Technology, Kumasi, Ghana

ALKENES
Introduction
❖ Alkenes
● Hydrocarbons containing C=C
● Old name: olefins

CH2OH

Vitamin A H3C

H3C

H H
Cholesterol
HO
www.knust.edu.gh

Ch. 7 - 59
 NOMENCLATURE

2-butene 2-hexene
3-methyl-2-hexene

Br

Cl
3-bromo-2,4-dimethyl-1-heptene 2-chloro-2,4-dimethyl-3-octene

www.knust.edu.gh
❖ The Cahn-Ingold-Prelog (E) - (Z)
Convention

● The system is based on the atomic

number of the attached atom

● The higher the atomic number, the

higher the priority

www.knust.edu.gh

Ch. 7 - 61
❖ The Cahn-Ingold-Prelog (E) - (Z) Convention
● (E) configuration – the highest priority
groups are on the opposite side of the
double bond
⧫ “E ” stands for “entgegen”; it means
“opposite” in German
● (Z) configuration – the highest priority
groups are on the same side of the double
bond
⧫ “Z ” stands for “zusammer”; it means
“together” in German
www.knust.edu.gh

Ch. 7 - 62
● Examples
CH3
Cl 1
2 Br
H

On carbon 2: Priority of Br > C

On carbon 1: Priority of Cl > H
 highest priority groups
are Br (on carbon 2)
and Cl (on carbon 1)

www.knust.edu.gh

Ch. 7 - 63
● Examples
CH3
Cl
Br
H
 (E )-2-Bromo-1-chloropropene
Br
Cl
CH3
H
 (Z )-2-Bromo-1-chloropropene
www.knust.edu.gh

Ch. 7 - 64
 ● Other examples

H (E )-1,2-Dichloroethene
(1) Cl [or trans-1,2-Dichloroethene]
2
1 Cl
H C1: Cl > H
C2: Cl > H

Cl
2 (Z )-1-Bromo-1,2-dichloroethene
(2) 1 Cl
Br C1: Br > Cl
C2: Cl > H
www.knust.edu.gh

Ch. 7 - 65
 ● Other examples

Br
3 1
4
(3) 2
7 5
8 6 (Z )-3-Bromo-4-tert-butyl-3-octene

C3: Br > C
C4: tBu > nBu

www.knust.edu.gh

Ch. 7 - 66
 Relative Stabilities of Alkenes
❖ Cis and trans alkenes do not have the same stability

crowding

R R H R
C C C C
H H R H
Less stable More stable

www.knust.edu.gh

Ch. 7 - 67
 Overall Relative Stabilities of
Alkenes

❖ The greater the number of attached alkyl groups (i.e.,

the more highly substituted the carbon atoms of the
double bond), the greater the alkene’s stability.

R R R R R H R H R R R H H H
> > > > > >
R R R H R H H R H H H H H H
tetra- tri- di- mono- un-
substituted substituted substituted substituted substituted

www.knust.edu.gh

Ch. 7 - 68
Cycloalkenes
❖ Cycloalkenes containing 5 carbon atoms or fewer exist
only in the cis form

cyclopropene cyclobutene cyclopentene

www.knust.edu.gh

Ch. 7 - 69
Synthesis of Alkenes via
Elimination Reactions
❖ Dehydrohalogenation of Alkyl Halides
H
H H H H
base
C C
H -HX
X H H
H
❖ Dehydration of Alcohols
H
H H H+, heat H H
C C
H OH -HOH H H
H
www.knust.edu.gh

Ch. 7 - 70
Dehydrohalogenation of Alkyl
Halides
❖ The best reaction conditions to use when
synthesizing an alkene by dehydrohalogenation
are those that promote an E2 mechanism

H
B: C C E2
C C + B:H + X
X
www.knust.edu.gh

Ch. 7 - 71
 Zaitsev’s Rule
❖ Examples of dehydrohalogenations where only a single
elimination product is possible
EtONa
(1) o
(79%)
Br EtOH, 55 C

EtONa
(2) o
(91%)
Br EtOH, 55 C

t -BuOK
(3) ( )
Br ( ) (85%)
n o
t -BuOH, 40 C n

www.knust.edu.gh

Ch. 7 - 72
❖ Zaitsev’s Rule
● In elimination reactions, the more highly
substituted alkene product predominates
❖ Stability of alkenes

Me Me Me Me Me H
C C > C C > C C
Me Me Me H H Me

Me Me Me H
> C C > C C
H H H H
www.knust.edu.gh

Ch. 7 - 73
Mechanism for an E2 Reaction

Et O Et O
H CH3 H CH3
α − H3C CH3
C C CH3 C C CH3 C C
H3C β H3C − H CH3
H Br H Br +

Et OH + Br
EtO removes a
⊖
Partial bonds in
b proton; C−H the transition C=C is fully
breaks; new p state: C−H and formed and the
bond forms and C−Br bonds break, other products
Br begins to new p C−C bond are EtOH and
depart forms Br⊖
www.knust.edu.gh

Ch. 7 - 74
Formation of the Less Substituted
Alkene Using a Bulky Base

❖ Hofmann’s Rule
● Most elimination reactions follow Zaitsev’s
rule in which the most stable alkenes are
the major products. However, under some
circumstances, the major elimination
product is the less substituted, less stable
alkene

www.knust.edu.gh

Ch. 7 - 75
 ● Case 1: using a bulky base

EtO CH3CH CHCH3 (80%)

+
(small) CH3CH2CH CH2 (20%)

CH3CH2CHCH3
Br t CH3CH CHCH3 (30%)
BuO
+
⊖
(bulky) CH3CH2CH CH2 (70%)
EtO
(small base) H H H H
tBuO⊖
H C C C C H
H H Br H (bulky base)
www.knust.edu.gh

Ch. 7 - 76
 ● Case 2: with a bulky group next
to the leaving halide

less crowded β-H

Me H Br H Me H
EtO
H3C C C C C H H3C C C C CH2
Me H Me H Me H Me

(mainly)
more crowded β-H

www.knust.edu.gh

Ch. 7 - 77
 Acid-Catalyzed Dehydration of
Alcohols

❖ Most alcohols undergo dehydration (lose a

molecule of water) to form an alkene when
heated with a strong acid

HA
C C C C + H2O
heat
H OH

www.knust.edu.gh

Ch. 7 - 78
 ● Primary alcohols are the most difficult to
dehydrate. Dehydration of ethanol, for
example, requires concentrated sulfuric acid
and a temperature of 180°C

H H conc. H2SO4 H H
H C C H C C + H2O
180oC H H
H OH
Ethanol (a 1o alcohol)
www.knust.edu.gh

Ch. 7 - 79
 ● Secondary alcohols usually dehydrate under
milder conditions. Cyclohexanol, for
example, dehydrates in 85% phosphoric
acid at 165–170°C
OH
85% H3PO4
+ H2O
165-170oC

Cyclohexanol Cyclohexene
(80%)

www.knust.edu.gh

Ch. 7 - 80
 ● Tertiary alcohols are usually so easily
dehydrated that extremely mild conditions
can be used. tert-Butyl alcohol, for
example, dehydrates in 20% aqueous
sulfuric acid at a temperature of 85°C
CH3 CH2
20% H2SO4
H3C C OH + H2O
CH3 85oC H3C CH3

tert-Butyl alcohol 2-Methylpropene

(84%)
www.knust.edu.gh

Ch. 7 - 81
 ● The relative ease with which alcohols will
undergo dehydration is in the following
order:

R R H
R C OH > R C OH > R C OH
R H H

3o alcohol 2o alcohol 1o alcohol

www.knust.edu.gh

Ch. 7 - 82
 ❖ Some primary and secondary alcohols also
undergo rearrangements of their carbon
skeletons during dehydration
CH3
H3C C CH CH3
CH3OH 85% H3PO4
3,3-Dimethyl-2-butanol 80oC

H3C CH3 H3C CH3

C C + C CHCH3
H3C CH3 H2C
2,3-Dimethyl-2-butene 2,3-Dimethyl-1-butene
(80%) (20%)
www.knust.edu.gh

Ch. 7 - 83
 Summary of Methods for the Preparation of
Alkenes
(Dehydrohalogenation
of alkyl halides) C C
C C
base, heat H+ H OH
H X
heat
H2, Ni2B (P-2) (Dehydration
C C of alcohols)
or Lindlar's catalyst
(give (Z)-alkenes) Li, liq. NH3
(give (E)-alkenes)
C C (Semi- (Dissolving
hydrogenation metal reduction C C
of alkynes) of alkynes)
www.knust.edu.gh

Ch. 7 - 84
REACTIONS OF ALKENE

Addition Reactions of Alkenes

E
C C + E Nu C C
Nu

www.knust.edu.gh

Ch. 8 - 85
 Additions to Alkenes
❖ This is an addition reaction: E–Nu added across the
double bond
E
C C + E Nu C C
Nu
p-bond s-bond 2 s-bonds

Bonds broken Bonds formed

www.knust.edu.gh

Ch. 8 - 86
❖ Electrophilic
● electron seeking
● C=C and C≡C p bonds are particularly susceptible to
electrophilic reagents (electrophiles)

❖ Common electrophile
● H+, X+ (X = Cl, Br, I), Hg2+, etc.
❖ In an electrophilic addition, the p electrons seek an
electrophile, breaking the p bond, forming a s bond and
leaving a positive charge on the vacant p orbital on the
–
adjacent carbon. Addition of B to form a s bond
provides an addition product
www.knust.edu.gh

Ch. 8 - 87
Electrophilic Addition of Hydrogen
Halides to Alkenes:
Mechanism and Markovnikov’s Rule

❖ Mechanism

+ − A Nu E
E Nu Nu
C C C C C C

www.knust.edu.gh

Ch. 8 - 88
❖ Markovnikov’s Rule
● For symmetrical substrates

H H E E
E Nu same
C C H C C H as H C C H
H H H H H H

Nu

E Nu Nu E
same
H C C H as H C C H
H H H H
www.knust.edu.gh

Ch. 8 - 89
 ❖ Markovnikov’s Rule
● For unsymmetrical substrates

H3C H E E
E Nu
C C CH3 C C H or CH3 C C H
H H H H H H

Nu Nu

E Nu different Nu E
CH3 C C H from CH3 C C H
H H H H

www.knust.edu.gh

Ch. 8 - 90
❖ Addition of Hydrogen Halides
● Addition of HCl, HBr and HI across a C=C bond
+
● H is the electrophile

+ − Br
  slow Br
+ H Br
r.d.s fast

Br
NO

www.knust.edu.gh

Ch. 8 - 91
Addition of Sulfuric Acid to Alkenes
OSO3H
conc. H2SO4
cold
H
O
− + OSO3H
HO S O H
O
H
more stable H
o
3 cation
less stable
❖ Addition of H–OSO3H across a C=C o
1 cation
bond
www.knust.edu.gh

Ch. 8 - 92
 Alcohols from Alkyl Hydrogen
Sulfates (Hydrolysis)

OSO3H OH
conc. H2SO4 H2O
cold heat
H H

❖ The overall result of the addition of sulfuric acid to an

alkene followed by hydrolysis is the Markovnikov
addition of H– and –OH

www.knust.edu.gh

Ch. 8 - 93
 Addition of Water to Alkenes:
Acid-Catalyzed Hydration
❖ Overall process
● Addition of H–OH across a C=C bond
+
● H is the electrophile
● Follow Markovnikov’s rule
OH H
H2O
dilute H3O+
(e.g. dilute H2SO4, H3PO4)

www.knust.edu.gh

Ch. 8 - 94
 Rearrangements
❖ Rearrangement can occur with certain
carbocations
H2O
H
H2SO4
1,2-alkyl shift
NOT OH
H2O
OH

(major product)

www.knust.edu.gh

Ch. 8 - 95
Oxymercuration–Demercuration:
Markovnikov Addition

❖ Step 1: Oxymercuration
Hg(OAc)2
C C C C
THF-H2O
HO HgOAc
❖ Step 2: Demercuration

NaBH4
C C C C
−
OH
HO HgOAc HO H
www.knust.edu.gh

Ch. 8 - 96
 Hydroboration–Oxidation:

Alcohols from Alkenes through Anti-Markovnikov Syn Hydration

"BH3"
C C C C
H BH2
❖ Addition of H–BH2 across a C=C bond

www.knust.edu.gh

Ch. 8 - 97
❖ BH3 exists as dimer B2H6 or complex with coordinative
solvent
H H
H B B H
H H

H H Me
H B O H B S
H H Me

(BH3-THF) (BH3-DMS)
www.knust.edu.gh

Ch. 8 - 98
6. Hydroboration: Synthesis of
Alkylboranes

hydroboration
C C +H B C C
H B
alkene boron alkylborane
hydride

www.knust.edu.gh

Ch. 8 - 99
7. Electrophilic Addition of Bromine and Chlorine to Alkenes

❖ Addition of X–X (X = Cl, Br) across a C=C bond

Br
Br2
C C C C
CCl4
Br
(vicinal
dibromide)

www.knust.edu.gh

Ch. 8 - 100
 8. Halohydrin Formation

X2 OH
C C C C
H2O
X

❖ Addition of –OH and –X (X = Cl, Br) across a C=C

bond
+
❖ X is the electrophile
❖ Follow Markovnikov’s rule

www.knust.edu.gh

Ch. 8 - 101
9. Oxidation of Alkenes:
Syn 1,2-Dihydroxylation
❖ Overall: addition of 2 OH groups across a C=C bond

C C
OH OH
⊖
❖ Reagents: dilute KMnO4 / OH / H2O / cold or OsO4,
pyridine then NaHSO3, H2O
www.knust.edu.gh

Ch. 8 - 102
 10. Oxidative Cleavage of Alkenes
a) Cleavage with Hot Basic Potassium Permanganate
O
a KMnO4, OH−, H2O
b b 2 a O
a  b
or H3O+
a a
O
b b
2 a OH
b
www.knust.edu.gh

Ch. 8 - 103
b) Cleavage with Ozone

R R" 1. O3 R R"
O + O
2. Zn, AcOH
R' H R' H
or Me2S

www.knust.edu.gh

Ch. 8 - 104
11. CATALYTIC HYDROGENATION
H2
H H
Pt, Pd or Ni
C C C C
solvent
heat and pressure

H2
H H
Pt, Pd or Ni
C C C C
solvent
heat and pressure H H

www.knust.edu.gh
Syn and Anti Additions

❖ An addition that places the parts of the reagent on the same

side (or face) of the reactant is called syn addition

syn
C C + X Y C C
addition
X Y

Pt
C C + H H C C
H H

Catalytic hydrogenation is a syn addition.

www.knust.edu.gh

Ch. 7 - 106
❖ An anti addition places parts of the adding
reagent on opposite faces of the reactant

Y
anti
C C + X Y C C
addition
X

www.knust.edu.gh

Ch. 7 - 107
 Kwame Nkrumah University of
Science & Technology, Kumasi, Ghana

ALKYNES
 WHAT ARE ALKYNES?
• They are compounds containing a carbon-carbon triple bond resulted from sp
orbital on each C.
• The carbons form a sigma bond and unhybridized px and py orbitals forming a π
bonds

• Alkynes have a general formula of CnH2n-2

• Some reactions are like alkenes: addition and oxidation.
• Some reactions are specific to alkynes.

• They are Nonpolar, insoluble in water and Soluble in most organic solvents,
• Their boiling points are similar to alkane of the same size,
• They are less dense than water,
• Up to 4 carbons are gases at room temperature.

www.knust.edu.gh
 NOMENCLATURE
• The “-yne” is used as a suffix indicating an alkyne:
• Number from the end closest to the triple bond
• For a tie between the ends to two triple bonds, use branching
• Double bonds take priority over triple bonds when they are equal distance to
the end of a chain.
• Triple bonds are linear so there is no cis/trans or E/Z, although any double
bonds in the molecule can still have stereochemical designators

www.knust.edu.gh
 Preparation of alkynes

Alkynes from Calcium Carbide Elimination Reactions of Dihalides

Calcium carbide undergoes • 1,2 dihaloalkane with KOH or
treatment with water to form NaOH produces a two-fold
ethyne. elimination of HX
 Reactions of Alkynes
Acidic nature

Alkynes are slightly electronegative due to the triply bonded carbon atoms
The triple bond makes it easier for the carbon to attract the shared electron
pair of the C-H bond.
In the presence of a strong base like NaNH2, H2 gas is liberated.

Hence the hydrogen atoms attached to the carbon-carbon triple bond in

alkynes are easily released.

HC ≡ CH + Na → HC ≡ C– Na+ + 1/2H2

Addition Reactions

Under suitable conditions alkynes react with water, halogens, hydrogen and
other elements to give a saturated compound as products

www.knust.edu.gh
 Addition of Dihydrogen
The reaction occurs in the presence of a catalyst such as Nickel or Platinum or
Palladium.
The addition of hydrogen to the alkyne gives an alkene and subsequently to
an alkane.

C3H4(g) + 2H2(g) C3H8(g)

Addition of Halogens
Alkynes react with halogens, halogen
substituted alkenes, further treatment
of the halogen gives a tetra-substituted
alkane.

www.knust.edu.gh
 Addition of Water
Alkynes do not react with water molecules. This is called immiscibility.

In dilute sulphuric acid (about 40%) and a catalyst, mercuric Sulphate,

the alkyne reacts water. To form a carbonyl compounds, and such a
reaction can be called a hydration reaction

www.knust.edu.gh
 Addition of HX and X2
• Addition reactions of alkynes may exhibit regiospecificity according to Markovnikov

www.knust.edu.gh
Hydroboration/Oxidation of Alkynes
• BH3 (borane) adds to alkynes to give a vinylic borane
• Oxidation with H2O2 produces an enol that converts to the ketone or aldehyde
• Process converts alkyne to ketone or aldehyde with orientation opposite to
mercuric ion catalyzed hydration

www.knust.edu.gh
 Reduction of Alkynes
• Addition of H2 over a metal catalyst (such as palladium on carbon, Pd/C)
converts alkynes to alkanes (complete reduction)
• The addition of the first equivalent of H2 produces an alkene, which is
more reactive than the alkyne so the alkene is not observed

www.knust.edu.gh
 Hydrogenation of Alkynes

Treatment of an alkyne with hydrogen in the presence of a transition

metal catalyst, most commonly Pd, Pt, or Ni, converts the alkyne to an
alkane

• Addition of H2 using chemically deactivated palladium on calcium carbonate as a

catalyst (the Lindlar catalyst)
produces a cis alkene
• The two hydrogens add syn (from the same side of the triple bond

www.knust.edu.gh
 Hydrogenation of Alkynes
• Anhydrous ammonia (NH3) is a liquid below -33ºC
• Alkali metals dissolve in liquid ammonia and function as reducing agents
• Alkynes are reduced to trans alkenes with sodium or lithium in liquid
ammonia

www.knust.edu.gh
 Oxidative Cleavage of Alkynes
• Strong oxidizing reagents (O3 or KMnO4) cleave internal alkynes,
producing two carboxylic acids
• Terminal alkynes are oxidized to a carboxylic acid and carbon dioxide

www.knust.edu.gh
 Alkyl halides
❖ Alkyl halides are organic compounds containing a halogen
atom bonded to an sp3 hybridized carbon atom

❖ Halogens are more electronegative than carbon hence pull

electrons more to itself resulting in the charge distribution

+ −
 
C X X = Cl, Br, I

www.knust.edu.gh
 Classification of alkyl halides
• Primary
• Secondary
• Tertiary
Depending on the number of carbons bonded to the carbon with the
halogen atom.

www.knust.edu.gh
Other important halide organic compounds

❖ Vinyl halides (Alkenyl • Vinyl halides have a

halides) 2
halogen atom (X) bonded
sp to a C—C double bond.
• Aryl halides have a
X halogen atom bonded to a
❖ Aryl halides benzene ring.
sp2 • Allylic halides have X
X bonded to the carbon atom
adjacent to a C—C double
benzene or aromatic ring bond.
❖ Acetylenic halides
• Benzylic halides have X
(Alkynyl halides) bonded to the carbon atom
sp adjacent to a benzene ring.
X

www.knust.edu.gh
Nomenclature

www.knust.edu.gh
 Using the common name system
▪ Common names are often used for simple alkyl halides.

To assign a common name:

Name all the carbon atoms of the molecule as a single alkyl group.
Name the halogen bonded to the alkyl group as a halide.
Combine the names of the alkyl group and halide, separating the words
with a space.

www.knust.edu.gh
 Physical Properties
• Alkyl halides are weak polar molecules. They exhibit dipole-dipole interactions because
of their polar C—X bond, but because the rest of the molecule contains only C—C and
C—H bonds, they are incapable of intermolecular hydrogen bonding.

www.knust.edu.gh
 Carbon-Halogen Bond Lengths
and Bond Strength

H H H H
H C F H C Cl H C Br H C I
H H H H

C–X Bond
Length (Å)
1.39 1.78 1.93 2.14

increase
C–X Bond
Strength 472 350 293 239
(kJ/mol)

decrease

www.knust.edu.gh
 Preparation of Alkyl Halides

25°C (CH3)3CCl + H2O

(CH3)3COH + HCl
78-88%

OH + HBr 80-100°C
Br + H2O

73%

CH3(CH2)5CH2OH + HBr 120°C CH3(CH2)5CH2Br + H2O

87-90%

www.knust.edu.gh
 Preparation of Alkyl Halides

2. Using a mixture of a salt and acid

NaBr
H2SO4
CH3CH2CH2CH2OH CH3CH2CH2CH2Br
heat 70-83%

3. Thionyl chloride
SOCl2 + ROH → RCl + HCl + SO2
4. Phosphorus tribromide
PBr3 + 3ROH → 3RBr + H3PO3

www.knust.edu.gh
 Reactions of alkyl halides
• Prone to undergo Nucleophilic Substitutions
(SN) and Elimination Reactions (E)

sp3

+ C −
X

Alkyl halides

www.knust.edu.gh
General features of the substitution Rxn
• Three components are necessary in any substitution reaction.

www.knust.edu.gh

131
 General Features of Nucleophilic Substitution
• Negatively charged nucleophiles like HO¯ and HS¯ are used as salts with Li+,
Na+, or K+ counterions to balance the charge. Since the identity of the
counterion is usually inconsequential, it is often omitted from the chemical
equation.

• When a neutral nucleophile is used, the substitution product bears a positive

charge.

www.knust.edu.gh

132
 The Leaving Group

• There are periodic trends in leaving group ability:

www.knust.edu.gh

133
 Mechanisms of Nucleophilic Substitution

In a nucleophilic substitution:

But what is the order of bond making and bond breaking? In theory,
there are three possibilities.

www.knust.edu.gh

134
 Mechanisms of Nucleophilic Substitution

[1] Bond making and bond breaking occur at the same time.

In this scenario, the mechanism is comprised of one step. In such a

bimolecular reaction, the rate depends upon the concentration of both
reactants, that is, the rate equation is second order.

www.knust.edu.gh

135
 Mechanisms of Nucleophilic Substitution

[2] Bond breaking occurs before bond making.

In this scenario, the mechanism has two steps and a

carbocation is formed as an intermediate. Because the first
step is rate-determining, the rate depends on the
concentration of RX only; that is, the rate equation is first
order.

www.knust.edu.gh

136
 Mechanisms of Nucleophilic Substitution

[3] Bond making occurs before bond breaking.

This mechanism has an inherent problem. The intermediate generated in the

first step has 10 electrons around carbon, violating the octet rule. Because two
other mechanistic possibilities do not violate a fundamental rule, this last
possibility can be disregarded.

www.knust.edu.gh

137
 Mechanisms of Nucleophilic Substitution

Kinetic data show that the rate of reaction depends on the

concentration of both reactants, which suggests a bimolecular
reaction with a one-step mechanism. This is an example of an SN2
(substitution nucleophilic bimolecular) mechanism.

www.knust.edu.gh

138
 Mechanisms of Nucleophilic Substitution

Kinetic data show that the rate of reaction depends on the

concentration of only the alkyl halide. This suggests a two-
step mechanism in which the rate-determining step involves
the alkyl halide only. This is an example of an SN1 (substitution
nucleophilic unimolecular) mechanism.

www.knust.edu.gh

139
 Mechanisms of Nucleophilic Substitution

An energy diagram for the SN2 reaction:

www.knust.edu.gh

140
 Mechanisms of Nucleophilic Substitution—Stereochemistry

• All SN2 reactions proceed with backside attack of the nucleophile, resulting in
inversion of configuration at a stereogenic center.

www.knust.edu.gh

141
 Mechanisms of Nucleophilic Substitution—Stereochemistry

• Two examples of inversion of

configuration in the SN2 reaction

www.knust.edu.gh

142
 Mechanisms of Nucleophilic Substitution

• Methyl and 1° alkyl halides undergo SN2 reactions with ease.

• 2° Alkyl halides react more slowly.
• 3° Alkyl halides do not undergo SN2 reactions.

• This order of reactivity can be explained by steric effects. Steric hindrance

caused by bulky R groups makes nucleophilic attack from the backside more
difficult, slowing the reaction rate.

www.knust.edu.gh

143
 Mechanisms of Nucleophilic Substitution

Mechanisms of Nucleophilic Substitution

• Increasing the number of R groups on the carbon with the

leaving group increases crowding in the transition state,
thereby decreasing the reaction rate.
• The SN2 reaction is fastest with unhindered halides.

www.knust.edu.gh

144
 Mechanisms of Nucleophilic Substitution

The mechanism of an SN1 reaction would be drawn as follows:

Note the curved arrow formalism that is used to show the flow of
electrons.

Key features of the SN1 mechanism are that it has two steps, and
carbocations are formed as reactive intermediates.

www.knust.edu.gh

145
Mechanisms of Nucleophilic Substitution

An energy diagram
for the SN1 reaction:

www.knust.edu.gh

146
Mechanisms of Nucleophilic Substitution—Stereochemistry

To understand the stereochemistry of the SN1 reaction, we must

examine the geometry of the carbocation intermediate.

www.knust.edu.gh

147
Mechanisms of Nucleophilic Substitution—Stereochemistry

• Loss of the leaving group in Step [1] generates a planar carbocation

that is achiral. In Step [2], attack of the nucleophile can occur on
either side to afford two products which are a pair of enantiomers.
• Because there is no preference for nucleophilic attack from either
direction, an equal amount of the two enantiomers is formed—a
racemic mixture. We say that racemization has occurred.

www.knust.edu.gh

148
 Mechanisms of Nucleophilic Substitution—Stereochemistry

Two examples of racemization

in the SN1 reaction

www.knust.edu.gh

149
 Mechanisms for Nucleophilic Substitution

• The rate of an SN1 reaction is affected by the type of alkyl halide

involved.

• This trend is exactly opposite to that observed in SN2 reactions.

www.knust.edu.gh

150
 Carbocation Stability

• The effect of the type of alkyl halide on SN1 reaction rates

can be explained by considering carbocation stability.
• Carbocations are classified as primary (1°), secondary
(2°), or tertiary (3°), based on the number of R groups
bonded to the charged carbon atom. As the number of R
groups increases, carbocation stability increases.

www.knust.edu.gh

151
 Carbocation Stability

• The order of carbocation stability can be rationalized

through inductive effects and hyperconjugation.
• Inductive effects are electronic effects that occur through s
bonds. Specifically, the inductive effect is the pull of
electron density through s bonds caused by
electronegativity differences between atoms.
• Alkyl groups are electron donating groups that stabilize a
positive charge. Since an alkyl group has several s bonds,
each containing electron density, it is more polarizable than
a hydrogen atom, and better able to donate electron
density.
• In general, the greater the number of alkyl groups attached
to a carbon with a positive charge, the more stable will be
the cation.

www.knust.edu.gh

152
Carbocation Stability

Electrostatic
potential maps
for differerent
carbocations

www.knust.edu.gh

153
 Predicting the Likely Mechanism of a Substitution Reaction

• Four factors are relevant in predicting whether a given reaction is

likely to proceed by an SN1 or an SN2 reaction—The most important
is the identity of the alkyl halide.

www.knust.edu.gh

154
 Predicting the Likely Mechanism of a Substitution Reaction

• The nature of the nucleophile is another factor.

• Strong nucleophiles (which usually bear a negative charge) present
in high concentrations favor SN2 reactions.
• Weak nucleophiles, such as H2O and ROH favor SN1 reactions by
decreasing the rate of any competing SN2 reaction.
• Let us compare the substitution products formed when the 2° alkyl
halide A is treated with either the strong nucleophile HO¯ or the
weak nucleophile H2O. Because a 2° alkyl halide can react by
either mechanism, the strength of the nucleophile determines which
mechanism takes place.

www.knust.edu.gh

155
 Predicting the Likely Mechanism of a Substitution Reaction

• The strong nucleophile favors an SN2 mechanism.

• The weak nucleophile favors an SN1 mechanism.

www.knust.edu.gh

156
 Predicting the Likely Mechanism of a Substitution Reaction

• A better leaving group increases the rate of both SN1 and SN2
reactions.

www.knust.edu.gh

157
 Predicting the Likely Mechanism of a Substitution Reaction

• The nature of the solvent is a fourth factor.

• Polar protic solvents like H2O and ROH favor SN1 reactions
because the ionic intermediates (both cations and anions)
are stabilized by solvation.
• Polar aprotic solvents favor SN2 reactions because
nucleophiles are not well solvated, and therefore, are more
nucleophilic.

www.knust.edu.gh

158
Predicting the Likely Mechanism of a Substitution Reaction

www.knust.edu.gh

159
 Elimination Reactions
• Elimination reactions involve the loss of elements from the starting
material to form a new p bond in the product.

www.knust.edu.gh

160
• Equations [1] and [2] illustrate examples of elimination reactions. In both
reactions a base removes the elements of an acid, HX, from the organic
starting material.

www.knust.edu.gh

161
• Removal of the elements HX is called dehydrohalogenation.
• Dehydrohalogenation is an example of b elimination.
• The curved arrow formalism shown below illustrates how four bonds are
broken or formed in the process.

• The most common bases used in elimination reactions are

negatively charged oxygen compounds, such as HO¯ and its alkyl
derivatives, RO¯, called alkoxides.

www.knust.edu.gh

162
 Mechanisms of Elimination
• There are two mechanisms of elimination—E2 and E1, just
as there are two mechanisms of substitution, SN2 and SN1.
• E2 mechanism—bimolecular elimination
• E1 mechanism—unimolecular elimination
• The E2 and E1 mechanisms differ in the timing of bond
cleavage and bond formation, analogous to the SN2 and
SN1 mechanisms.
• E2 and SN2 reactions have some features in common, as do
E1 and SN1 reactions.

www.knust.edu.gh

163
 E2 mechanism—bimolecular elimination
• The most common mechanism for dehydrohalogenation is the E2 mechanism.
• It exhibits second-order kinetics, and both the alkyl halide and the base appear
in the rate equation, i.e.,
rate = k[(CH3)3CBr][¯OH]

• The reaction is concerted—all bonds are broken and formed in a single step.

www.knust.edu.gh

164
Energy diagram for an E2 reaction:

www.knust.edu.gh

165
 The Zaitsev rule
• The major product in b elimination has the more substituted double bond.
• A reaction is regioselective when it yields predominantly or exclusively one
constitutional isomer when more than one is possible. Thus, the E2 reaction is
regioselective.

www.knust.edu.gh

166
 Mechanisms of Elimination—E1
• The dehydrohalogenation of (CH3)3CCI with H2O to form (CH3)2C=CH2
can be used to illustrate the second general mechanism of elimination,
the E1 mechanism.
• An E1 reaction exhibits first-order kinetics:
rate = k[(CH3)3CCI]

• The E1 reaction proceeds via a two-step mechanism: the bond to the

leaving group breaks first before the p bond is formed.
• The slow step is unimolecular, involving only the alkyl halide.

www.knust.edu.gh

167
www.knust.edu.gh

168
Energy diagram for an E1 reaction:

www.knust.edu.gh

169
• The rate of an E1 reaction increases as the number of R groups on the
carbon with the leaving group increases.

• The strength of the base usually

determines whether a reaction
follows the E1 or E2
mechanism.

• Strong bases like ¯OH and ¯OR

favor E2 reactions, whereas
weaker bases like H2O and
ROH favor E1 reactions.

• E1 reactions are regioselective, favoring formation of the more substituted, more

stable alkene.
• Zaitsev’s rule applies to E1 reactions also.

www.knust.edu.gh

170
Predicting the Mechanism from the Reactants—SN1, SN2,
E1 or E2.

• Good nucleophiles that are weak bases favor substitution

over elimination—Certain anions generally give products of
substitution because they are good nucleophiles but weak
bases. These include I¯, Br¯, HS¯, ¯CN, and CH3COO¯.

www.knust.edu.gh

171
• Bulky nonnucleophilic bases favor elimination over
substitution—KOC(CH3)3, DBU, and DBN are too sterically
hindered to attack tetravalent carbon, but are able to
remove a small proton, favoring elimination over
substitution.

www.knust.edu.gh

172
Determining whether an alkyl halide reacts by an SN1, SN2, E1, or E2 mechanism

www.knust.edu.gh

173
www.knust.edu.gh

174
www.knust.edu.gh

175
Overall Summary

SN1 SN2 E1 E2
CH3X ─ Very fast ─ ─

Hindered bases give

RCH2X ─ Mostly ─ mostly alkenes;
e.g. with tBuO⊖

R' Very little;

Solvolysis possible;
Mostly SN2 with
weak bases; Very little
Strong bases
promote E2;
RCHX
e.g. with H2O;
e.g. with CH3COO⊖ e.g. with RO⊖, HO⊖
MeOH

R' Very favorable

Strong bases
RCX with weak bases;
e.g. with H2O;
─
Always competes
with SN1
promote E2;
e.g. with RO⊖, HO⊖
MeOH
R"
www.knust.edu.gh
ALCOHOLS, PHENOLS,ETHERS AND THIOLS

www.knust.edu.gh
 Introduction
• Alcohol – organic compound that contains a hydroxyl (-OH) group attached to an
alkyl group

• Phenol – organic compound that contains a hydroxyl (-OH) group attached to an

aryl group

• Ether – organic compound that has two alkyl or aryl groups attached to the oxygen
atom; can be thought of as a substituted alcohol.

• Thiols-

www.knust.edu.gh
www.knust.edu.gh
 Structure and Properties
• R-O-H portion of alcohol is similar to the structure of water.
– The oxygen and two atoms bonded to it lie in the same plane.
– The bond angle is 104°

• Hydroxyl groups are very polar due to different electronegativities.

– Hydrogen bonding can form between alcohol molecules.

• Alcohols boil at much higher temperatures than
+ hydrocarbons of similar molecular weight.
O
+ H
−
H
H • Alcohols with fewer than five carbons are very
O
− soluble in water.
R O
R
+ H • Alcohols with five to eight carbons are moderately
soluble in water.
− O

H
H • As the nonpolar (R) portion of the alcohol gets
larger, the water solubility decreases.
www.knust.edu.gh
 Solubility of Alcohols
• Very large alcohols are not soluble in water.
• Hydrophobic – “water fearing”; used to describe nonpolar region of molecule
• Hydrophilic – “water loving”; used to describe polar region of molecule

CH3CH2CH2CH2CH2CH2CH2CH2CH2OH

Hydrophobic Hydrophilic

• An increase in the number of hydroxyl groups will increase the influence of the
polar hydroxyl group.
– Diols and triols are more water soluble than alcohols with only a single hydroxyl
group.

www.knust.edu.gh
 IUPAC Nomenclature
• Find the longest carbon chain containing the carbon with the —OH group.
• Drop the -e from the alkane name; add -ol.
• Number the chain, giving the —OH group the lowest number possible.
• Number and name all substituents and write them in alphabetical order.

CH4 methane
CH3OH methanol (methyl alcohol)
CH3CH3 ethane
CH3CH2OH ethanol (ethyl alcohol)

www.knust.edu.gh
 Alcohol Nomenclature
OH
2
5
3 6
3-heptanol 5-methyl-6-hepten-2-ol OH

2 OH
OH
1 1

CH3
3
CH3 CH3 5 CH3
3,3-dimethylcyclohexanol 5,5-dimethylcyclohex-2-enol

• Alcohols containing two hydroxyl groups are named –diols.

• Alcohols containing three hydroxyl groups are named –triols.
• A number giving the position of each of the hydroxyl groups is needed in
these cases.

www.knust.edu.gh
Examples of Classifications

CH3 OH
CH3 CH CH2OH CH3 CH CH2CH3
* *
Primary alcohol Secondary alcohol

CH3
OH
CH3 C* OH
CH3
Tertiary alcohol Phenol

www.knust.edu.gh
 Preparation of Alcohols
• Reduction of ketones and aldehydes
• Reduction of esters and carboxylic acids
• Hydration of Alkenes
• Nucleophilic addition
– Grignard reaction
– Acetylide addition
• Substitution
• Epoxide opening

www.knust.edu.gh
 Reduction
O OH O O OH O
1) NaBH4
1) LiAlH4, THF +
+ OH 2) H3O OH
2) H3O

OH
LiAlH4 will reduce: 1) LiAlH4
o
ketones to 2 alcohols + OH
o
2) H3O
aldehydes to 1 alcohols
o
carboxylic acids and esters to 1 alcohols

1) LiAlH 4
O OH
+
2) H3O
O + CH3OH

1) NaBH4
no reaction
+
2) H3O

www.knust.edu.gh
 Reducing Agents
• NaBH4 can reduce aldehydes
and ketones but not esters and
carboxylic acids.

• They are very selective hence

yields a targeted product

• LiAlH4 is a stronger reducing

agent and will reduce all
carbonyls.

www.knust.edu.gh
 Hydration of Alkenes
Oxymercuration (Markovnikov)

1) Hg(OAc) 2 in
THF/H2O OH

2) NaBH4
H

Hydroboration Hydration
Anti-Markovnikov

1) BH3-THF H OH
3 3
2) H2O2, NaOH

www.knust.edu.gh
 Organometallic Reagents
Grignard Reaction
− +
CH3 Br + Mg CH3 MgBr Br
MgBr
Grignard Reagent ether
+ Mg

"CH3 MgBr "

excellent nucleophile
very strong base
Cl MgCl
ether
CH3CHCH2CH3 + Mg CH3CHCH2CH3

www.knust.edu.gh
Reactions of the G. Reagent

www.knust.edu.gh
Reactions of Alcohols

www.knust.edu.gh
Oxidation - Reduction

www.knust.edu.gh
Oxidation Summary
CH2CO2H
Na2Cr2O7
H2SO4

NH
CH2CH2OH CH2CHO
CrO3Cl

OO
CH2CHO
DMSO, ClCCCl
(CH3CH2)3N, in CH 2Cl2

www.knust.edu.gh
Reduction Summary

1) LiAlH 4 CH2CO2H
+
2) H3O

CH2CH2OH 1) NaBH CH2CHO

4
+
2) H3O
or
CH2CHO
H2, Raney Ni

www.knust.edu.gh
 Dehydration of Alcohols
• Alcohols undergo dehydration (lose water) when heating with concentrated
sulfuric or phosphoric acid.
• Dehydration is an example of an elimination reaction.
• Elimination reaction – a reaction in which a molecule loses atoms or ions from
its structure.
• Dehydration is opposite of hydration!

www.knust.edu.gh
• Alcohol dehydration generally takes place through the E1 mechanism.
• Rearrangements are possible.
• The rate of the reaction follows the same rate as the ease of formation of carbocations:
3o > 2o > 1o.
• Primary alcohols rearrange, so this is not a good reaction for converting 1° alcohols into
alkenes.

www.knust.edu.gh
 Esterification
• Fischer: Alcohol + carboxylic acid
• Tosylate esters
• Sulfate esters
• Nitrate esters
• Phosphate esters

www.knust.edu.gh
 • Phenols – compounds in which the hydroxyl group is attached to a benzene
ring
• They are polar compounds because of the polar hydroxyl group.
• Smaller phenols are somewhat soluble in water.
• They are found in fragrances and flavorings and are also used as
preservatives and germicides.

• Flammable, like alcohols

• Phenols cannot be dehydrated.
• Oxidation occurs only with strong oxidizing agents.
• Halogenation
• Weak acids in solution (Ka~10-10)

www.knust.edu.gh
 Nomenclature of Phenols

• Phenol = “phenyl” + “alcohol”

• IUPAC rules are same as for benzene
derivatives. Parent ring is “phenol”.

• Ex.:

www.knust.edu.gh
 Occurance & Uses of

spoilage.
BHT to help prevent
antioxidants BHA and
baked goods contain the
Many commercially
Phenols
• Antiseptics (but phenol derivatives are much safer than
phenol itself).
– Mouthwashes, Lysol, etc.
• Antioxidant - several phenols are preferentially oxidized
– Food additives
– Vit. E
• Flavoring agents
• Irritants: poison ivy & poison oak

Nutmeg tree fruit. A phenolic compound,

isoeugenol, is responsible for the odor associated
with nutmeg.

www.knust.edu.gh
 Ethers
• Structural Characteristics
– Functional group = -C-O-C-
– Remember ascorbic acid?
• R-O-R
• Similar structure to alcohols
• R-O-R’
• R-O-Ar Alcohols: R-OH
• Ar-O-Ar –OH is “hydroxy” group

Ethers: R-OR
–OR is “alkoxy” group

www.knust.edu.gh
 Nomenclature of Ethers
• IUPAC
– Select longest C chain = base name. • Common
– Change -yl ending of other group to -
oxy. (ie. Methyl becomes methoxy) – Name the two alkyl
– Place alkoxy name (w/ locator #) in
front of base chain name groups (alpha order)
• Ex.: C-C-O-C-C-C-C attached to the O
and add the word
“ether”.

www.knust.edu.gh
 Preparation of Ethers
• Ethers are formed from alcohols
R-OH + R’-OH → R-O-R’ +H2O
– R and R’ can be the same or different
– Called a dehydration reaction

Common Uses of Ethers

• Ethers as anesthetics:
– Penthrane
– Enthrane

• Ethers as additives in gasoline

– MTBE – methyl tert-butyl ether

www.knust.edu.gh
 Isomerism
• Consitutional • Functional Group
Isomers
– Partitioning of
(1st time we encounter
this possibility)

C atoms (by O) – Consitutional

- positional! isomers with
different
– Isomers of functional
individual alkyl groups
groups • Ex.: C3 ether and
• Ex.: C4 ethers C3 alcohol

www.knust.edu.gh
 Physical & Chemical
Properties
1. Find the root name of the smaller “R” group Ex: meth-,
eth-, prop-
2. Add –oxy
Ex: methoxy, ethoxy, propoxy
3. Add the full name of the larger “R” group
EXAMPLE:

• The root names are used with –oxy to name that portion of the
ether:
– meth- + -oxy
– eth- + -oxy O
– prop- + -oxy
methoxypropane

www.knust.edu.gh
 Thiols
• Compounds that contain the sulfhydryl
group (-SH)
• Similar to alcohols in structure, but the
sulfur atom replaces the oxygen atom
• Have nauseating aromas – defense spray
of North American striped skunk
H CH3

Trans-2-butene-1-thiol H2C H

SH
www.knust.edu.gh
 Naming Thiols
• Use the same rules as for alcohols except that the full name of the alkane is
retained.
• Add the suffix –thiol.

CH3CH2SH
CH3

CH3CHCH2CH2 ethanethiol
SH

HSCH2CH2SH 3-methyl-1-butanethiol

1,2-ethanedithiol
www.knust.edu.gh
 Naming Thiols
• Use the same rules as for alcohols except
that the full name of the alkane is retained.
• Add the suffix –thiol.
CH3CH2SH ethanethiol
CH3

CH3CHCH2CH2 3-methyl-1-butanethiol
SH

HSCH2CH2SH 1,2-ethanedithiol
 Uses of Thiols
• Thiols are involved in protein structure and
conformation.
• Cysteine is an amino acid that contains a
sulfhydryl group.
• Coenzyme A serves as a carrier of acetyl
groups in biochemical reactions.
 ARYL HALIDES
• Aryl halides are compounds in which a halogen
substituent is attached directly to an aromatic
ring.
• Halogen-containing compounds in which the
halogen is not directly bonded to an aromatic
ring, even though an aromatic ring may be
present, are not aryl halides. Benzyl chloride
(C6H5CH2Cl) is not an aryl halide.
• The strength of their carbon-halogen bonds
causes aryl halides to react very slowly in
reactions in which carbon-halogen bond cleavage
is rate-determining step as in nucleophilic
substitution

www.knust.edu.gh
Physical properties of aryl halide
• Aryl halides resemble alkyl halides in many of
their physical properties. All are practically
insoluble in water and most are denser than
water.
• They are polar molecules but they are less polar
than alkyl halides.
• Since carbon is sp2-hybridised in chlorobenzene,
it is more electtronegative than the sp3-
hybridised carbon of chlorocyclohexane.
• Withdrawal of electron density away from carbon
by chlorine is less pronounced in aryl halides than
in alkyl halides.

www.knust.edu.gh
 Sources of aryl halides
• Halogenation of arenes: Aryl chlorides and bromides
are conveniently prepared by electrophilic aromatic
substitution. The rreaction is limited to chlorination
and bromiination. Fluorination is difficult to control
and iodation is too slow to be useful
• The Sandmeyer reaction: Diazotization of a primary
arylamine followed by treatment of the diazonium
salt with copper(I) bromide or copper (I) chloride
yields thee corresponding aryl bromide or aryl
chloride.

www.knust.edu.gh
• The Schiemann reaction: Diazotisation of an
arylamine followed by treatment with
fluoroboric acid gives an aryl diazonium
fluoroborate salt. Heating this salt converts it to
an aryl fluoride.
• Reaction of diazonium salts with iodide ion:
Adding potassium iodide to a solution of an aryl
diazonium ion leads to the formation of an aryl
iodide.

www.knust.edu.gh
 REACTIONS OF ARYL HALIDES
• Electrophilic aromatic substitution:
halogen substituents are slightly
deactivating and ortho, para –
directing.
• Formation of aryl Grignard
reagents: Aryl halides react with
magnesium to form the
corresponding arylmagnesium
halide

www.knust.edu.gh
 Kwame Nkrumah University of
Science & Technology, Kumasi, Ghana

Carboxylic acids and

Derivatives
Introduction
• The functional group of carboxylic acids consists of a
C=O with -OH bonded to the same carbon.
• Carboxyl group is usually written -COOH.
• Aliphatic acids have an alkyl group bonded to -
COOH.
• Aromatic acids have an aryl group.
• Fatty acids are long-chain aliphatic acids.

www.knust.edu.gh
 IUPAC Names
• Remove -e from alkane (or alkene) name, add -oic
acid.
• The carbon of the carboxyl group is 1.

Ph H
Cl O
C C
CH3CH2CHC OH H COOH

2-chlorobutanoic acid
trans-3-phenyl-2-propenoic
acid

www.knust.edu.gh
 Naming Cyclic Acids
• Cycloalkanes bonded to -COOH are named as
cycloalkanecarboxylic acids.
• Aromatic acids are named as benzoic acids.
COOH

CH(CH3)2
COOH
2-isopropylcyclopentanecarboxylic acid
OH

o-hydroxybenzoic acid (salicylic acid)

www.knust.edu.gh
 Common Names
• Many aliphatic acids have historical names.
• Positions of substituents on the chain are labeled with
Greek letters.

Cl O Ph
CH3CH2CHC OH CH3CH2CH2CHCH2COOH

-chlorobutyric acid b-phenylcaproic acid

www.knust.edu.gh
 Dicarboxylic Acids
• Aliphatic diacids are usually called by their common
names.
• For IUPAC name, number the chain from the end
closest to a substituent.
• Two carboxyl groups on a benzene ring indicate a
phthalic acid.
Br
HOOCCH2CHCH2CH2COOH

3-bromohexanedioic acid
b-bromoadipic acid
www.knust.edu.gh
 Structure of Carboxyl
• Carbon is sp2 hybridized.
• Bond angles are close to 120.
• O-H eclipsed with C=O, to get overlap of p orbital with
orbital of lone pair on oxygen.

www.knust.edu.gh
 Boiling Points
Higher boiling points than similar alcohols, due
to dimer formation.

Acetic acid, b.p. 118C

www.knust.edu.gh
 Melting Points
• Aliphatic acids with more than 8 carbons are
solids at room temperature.
• Double bonds (especially cis) lower the melting
point.
Example (C-18 cpds)
– Stearic acid (saturated): 72C
– Oleic acid (one cis double bond): 16C
– Linoleic acid (two cis double bonds): -5C

www.knust.edu.gh
 Solubility

• Water solubility decreases with the length of the

carbon chain.
• Up to 4 carbons, acid is miscible in water.
• More soluble in alcohol.
• Also soluble in relatively nonpolar solvents like
chloroform because it dissolves as a dimer.

www.knust.edu.gh
 Salts of Carboxylic Acids

• Sodium hydroxide removes a proton to form the

salt.
• Adding a strong acid, like HCl, regenerates the
carboxylic acid.

O O
NaOH _ +
CH3 C OH HCl CH3 C O Na

www.knust.edu.gh
 Naming Acid Salts
• Name the cation.
• Then name the anion by replacing the
-ic acid with -ate.

Cl
- +
CH3CH2CHCH2COO K

potassium b-chlorovalerate
potassium 3-chloropentanoate

www.knust.edu.gh
 Properties of Acid Salts

• Usually solids with no odor.

• Carboxylate salts of Na+, K+, Li+, and NH4+ are
soluble in water.
• Salts can be formed by the reaction of an acid
with NaHCO3, releasing CO2.

www.knust.edu.gh
 Some Important Acids
• Acetic acid is used in vinegar and other foods,
used industrially as solvent, catalyst, and reagent
for synthesis.
• Fatty acids are found in fats and oils.
• Benzoic acid in drugs, preservatives.
• Adipic acid used in the production of nylon 66.
• Phthalic acid used in polyesters.

www.knust.edu.gh
 Carboxylic acids, syntheses
1. oxidation of primary alcohols
RCH2OH + K2Cr2O7 → RCOOH
2. oxidation of arenes
ArR + KMnO4, heat → ArCOOH
3. carbonation of Grignard reagents
RMgX + CO2 → RCO2MgX + H+ →
RCOOH
4. hydrolysis of nitriles
RCN + H2O, H+, heat → RCOOH

www.knust.edu.gh
1. oxidation of 1o alcohols:

CH3CH2CH2CH2-OH + CrO3 → CH3CH2CH2CO2H

n-butyl alcohol butyric acid
1-butanol butanoic acid

CH3 CH3
CH3CHCH2-OH + KMnO4 → CH3CHCOOH
isobutyl alcohol isobutyric acid
2-methyl-1-propanol` 2-methylpropanoic acid

www.knust.edu.gh
2. oxidation of arenes:
KMnO4, heat
CH3 COOH

toluene benzoic acid

CH3 COOH
KMnO4, heat

H3C HOOC

p-xylene terephthalic acid

KMnO4, heat
CH2CH3 COOH + CO2

ethylbenzene benzoic acid

www.knust.edu.gh
3. carbonation of Grignard reagent:
Mg CO2 H+
R-X RMgX RCO2MgX RCOOH
Increases the carbon chain by one carbon.

Mg CO2 H+
CH3CH2CH2-Br CH3CH2CH2MgBr CH3CH2CH2COOH
n-propyl bromide butyric acid

www.knust.edu.gh
4. Hydrolysis of a nitrile:

H2O, H+
R-CN R-CO2H
heat

H2O, OH-
R-CN R-CO2- + H+ → R-CO2H
heat

R-X + NaCN → R-CN + H+, H2O, heat → RCOOH

1o alkyl halide

www.knust.edu.gh
 Br2, hv NaCN
CH3 CH2Br CH2 CN

toluene
H2O, H+, heat

CH2 COOH

phenylacetic acid

KCN
CH3CH2CH2CH2CH2CH2-Br CH3CH2CH2CH2CH2CH2-CN
1-bromohexane
H2O, H+, heat

CH3CH2CH2CH2CH2CH2-COOH
heptanoic acid

www.knust.edu.gh
carboxylic acids, reactions:

1. as acids
2. conversion into functional derivatives
a) → acid chlorides
b) → esters
c) → amides
3. reduction
4. alpha-halogenation
5. EAS

www.knust.edu.gh
Carboxylic acids, reactions:
1. as acids
2. conversion into functional derivatives
a) → acid chlorides
b) → esters
c) → amides
3. reduction
4. alpha-halogenation
5. EAS

www.knust.edu.gh
Carboxylic Acid Derivatives

www.knust.edu.gh

237
Structure and Reactivity of Carboxylic Acid Derivatives
Increasing reactivity

acid chloride

All acyl derivatives are prepared acid anhydride ester amide

directly from the carboxylic acid.
acid anhydride
Acyl derivative such as amides and
carboxylic
esters can be readily prepared from
acid ester amide
more reactive derivatives (acid
chlorides and anhydrides) ester

amide

amide

www.knust.edu.gh

238
The reactivity of the acid derivative is related to it resonance
stabilization.

The C-N bond of amides is significantly stabilized

through resonance and is consequently, the least reactive acid
derivative.

The C-Cl bond of acid chlorides is the least stabilized

by resonance and is the most reactive acid derivative

www.knust.edu.gh

239
 Chemistry of Acid Halides
• Acid chlorides are prepared from carboxylic acids
by reaction with SOCl2, PCl3, PCl5 etc

• Reaction of a carboxylic acid with PBr3 yields the

acid bromide

www.knust.edu.gh

240
Naming Carboxylic Acid Derivatives
• Acid Halides, RCOX
– Derived from the carboxylic acid name by
replacing the -ic acid ending with -yl or the -
carboxylic acid ending with –carbonyl and
specifying the halide

www.knust.edu.gh
Reactions of Acid Halides

www.knust.edu.gh

242
 Mechanism Hydrolysis
Conversion of Acid Halides into Acids’
Acid chlorides react with water to yield carboxylic acids

www.knust.edu.gh

243
Conversion of Acid Halides to Esters
• Esters are produced in the reaction of acid chlorides with alcohols in the
presence of pyridine or NaOH. This is called Alcoholysis

• The reaction is better with less steric bulk

www.knust.edu.gh

244
Aminolysis: Conversion of Acid Halides
into Amides
• Amides result from the reaction of acid
chlorides with NH3, primary (RNH2) and
secondary amines (R2NH)

• The reaction with tertiary amines (R3N) gives an

unstable species that cannot be isolated

• HCl is neutralized by the amine or an added

base
www.knust.edu.gh

245
Aminolysis

www.knust.edu.gh

246
Reduction: Conversion of Acid
Chlorides into Alcohols
• LiAlH4 reduces acid chlorides to yield
aldehydes and then primary alcohols

www.knust.edu.gh

247
 Reaction of Acid Chlorides with
Organometallic Reagents
• Grignard reagents react with acid chlorides to yield
tertiary alcohols in which two of the substituents
are the same

www.knust.edu.gh
Formation of Ketones from Acid
Chlorides
• Reaction of an acid chloride with a lithium
diorganocopper (Gilman) reagent, Li+ R2Cu−

• Addition produces an acyl diorganocopper

intermediate, followed by loss of RCu and
formation of the ketone

www.knust.edu.gh

249
 Carboxylic Acid Anhydrides
Synthesis of Carboxylic Acid Anhydrides
O O
+ +
R OH R' Cl N

O O
+ Cl
R O R'
N
H
www.knust.edu.gh
 • Prepared by nucleophilic acyl substitution
of a carboxylate with an acid chloride
O O O O
+ + Na Cl
R O Na R' Cl R O R'

www.knust.edu.gh

251
A dicarboxylic acid may undergo cyclisation
at elevated temperature to give an acid anhydride
O O

OH 300oC
O + H2O
OH
Succinic O Succinic
O acid anhydride
O O

OH 230oC
O + H2O
OH
Phthalic Phthalic anhydride O
acid O (~100%)
www.knust.edu.gh
Naming Acid Anhydrides, RCO2COR'
• If the compound formed is symmetrical,
replace “acid” with “anhydride” based on
the related carboxylic acid
• Unsymmetrical anhydrides— cite the two
acids alphabetically

www.knust.edu.gh
www.knust.edu.gh

254
A mixed or unsymmetrical anhydride is a carboxylic acid anhydride that has the following
general structural formula.

where R1≠R2, but are hydrogen atoms, alkyl groups, aryl groups. When naming
unsymmetrical acid anhydrides, name both using alkanoic general method and then put
the two names alphabetically. Hence, first name each component and alphabetically
arranged them followed by spaces and then the word anhydride.

propanoic anhydride

ethanoic propanoic anhydride

www.knust.edu.gh

255
 Reactivity of Acid Anhydrides

Anhydride reactions are facilitated by acid or base catalysts

www.knust.edu.gh

256
Reactions of Carboxylic Acid Anhydrides

Reactions of acid anhydrides

Acid anhydrides are slightly less reactive than acid
chlorides; however, the overall reactions are nearly identical and
they can often be used interchangeably.

1. Alcoholysis to give esters

2. Aminolysis to give amides

3. Hydrolysis to give carboxylic acids

www.knust.edu.gh

257
Reactions of Acid Anhydrides
• Similar to acid chlorides in reactivity

www.knust.edu.gh

258
www.knust.edu.gh

259
www.knust.edu.gh

260
www.knust.edu.gh

261
www.knust.edu.gh

262
 Esters
• Esters are carboxylic acid derivatives with the -OH portion replaced by an -
OR group.
– R-COOR
– Ex.

– Methyl ethanoate Ethyl ethanoate

www.knust.edu.gh
 Chemistry of Esters
• Many esters are pleasant-smelling liquids:
fragrant odors of fruits and flowers

• Esters are present in fats and vegetable oils

www.knust.edu.gh

264
 Preparation of Esters
• Esters are usually prepared from carboxylic acids

www.knust.edu.gh

265
 Ester Nomenclature
• IUPAC
– Name the alcohol part 1st & acid part 2nd.
– Alcohol part name = name of R group (alkyl) in the -OR portion of the ester.
– Acid part name = drop “ic acid” ending of acid name and add suffix “ate”.
– Alkyl alkanoate
• Common: same as for IUPAC, except change the common acid name to end in
“ate”.

www.knust.edu.gh
www.knust.edu.gh
Lactones

❖ Carboxylic acids whose molecules have a

hydroxyl group on a g or  carbon undergo an
intramolecular esterification to give cyclic esters
known as g- or -lactones

www.knust.edu.gh
 O H O H
H
g 
R  b OH O H O
O H O H
HO O H A
a -hydroxyacid R R

O H
A + H O H + O
H O + O H
R
a -lactone H
R
www.knust.edu.gh
❖ Lactones are hydrolyzed by aqueous base just as other
esters are
O
O
H+/H2O
O C6H5
O
HA, slight excess
OH
C6H5
o
0 C
O HA, exactly
1 equiv.
C6H5
OH
OH
www.knust.edu.gh
 Common Esters
• Flavors/Fragrances
• Pheromones
– Alarm
– Trail
– Sex
– Deception
– Releaser
– Primer

• Medications
– Benzocaine
• Amino ester
– Salicylic Acid Esters
• Aspirin (acid rxn)

www.knust.edu.gh
 Reactions of Esters

• Less reactive toward nucleophiles than are

acid chlorides or anhydrides

• Cyclic esters are called lactones and react

similarly to acyclic esters

www.knust.edu.gh

272
Hydrolysis: Conversion of Esters
into Carboxylic Acids
• An ester is hydrolyzed by aqueous base or
aqueous acid to yield a carboxylic acid plus
an alcohol

www.knust.edu.gh

273
 Aminolysis of Esters
• Ammonia reacts with esters to form amides

www.knust.edu.gh

274
Reduction: Conversion of Esters into
Alcohols
• Reaction with LiAlH4 yields primary alcohols

www.knust.edu.gh

275
 Reduction of Esters
• Hydride ion adds to the carbonyl group,
followed by elimination of alkoxide ion to yield
an aldehyde
• Reduction of the aldehyde gives the primary
alcohol

www.knust.edu.gh

276
Reaction of Esters with Grignard
Reagents
• React with 2 equivalents of a Grignard
reagent to yield a tertiary alcohol

www.knust.edu.gh

277
 Amides
• Amides are carboxylic acid derivatives
– OH group is replaced by an amino or substituted amino group
• 1˚ amide RCONH2
• 2˚ amide RCONHR
• 3˚ amide RCONR2

• Aromatic amide
• Cyclic amides = “lactams”
– (similar to cyclic esters = “lactones”)

www.knust.edu.gh
 Chemistry of Amides
• Amides are abundant in all living organisms. As
proteins, nucleic acids, and pharmaceuticals

www.knust.edu.gh

279
 Amide Nomenclature
• Naming system (IUPAC vs. Common) is similar
to that for carboxylic acids
Primary amides are named by changing the name of the acid by
dropping the -oic acid or -ic acid endings and adding -amide.

www.knust.edu.gh
 Nomenclature
Secondary amides are named by using an upper case N to
designate that the alkyl group is on the nitrogen atom.

Alkyl groups attached to the nitrogen are named as

substituents. The letter N is used to indicate they are attached
to the nitrogen.

N-methylpropanamide

www.knust.edu.gh

281
 Nomenclature
Tertiary amides are named in the same way as
secondary amides, but with two N's

www.knust.edu.gh

282
 Physical Properties of Amides

• Not basic - due to polarity of adjacent carbonyl

group
• BP - related to the degree of hydrogen bonding
(note the difference between 1˚, 2˚, & 3˚)
• Water solubility
– Low MW = soluble
– High MW = less soluble

www.knust.edu.gh
• The lower members of the series are soluble in water
• The amides generally have high boiling points and melting points.
• These characteristics and their solubility in water result from the
• Polar nature of the amide group and hydrogen bonding

www.knust.edu.gh

284
 Preparation of Amides
• Prepared by reaction of an acid chloride with
ammonia, monosubstituted amines, or disubstituted
amines

www.knust.edu.gh
Amides from Acyl Chlorides
O
O
R Cl
R Cl
:NHR'R" H N R"
R' O
R"
O :Cl:
R N R'
Cl + R'R"NH2 + R"
R N H
R' R"R'HN:
www.knust.edu.gh
Amides from Carboxylic Anhydrides

O O H R'
+ 2 N
R O R R"

O O H

R' + H N R'
R N R O R"
R"
R', R" can be H, alkyl, or aryl.
www.knust.edu.gh
 O O

H2O NH2
O + 2 NH3
warm O NH4

O O Ammonium
Phthalamic O
anhydride phthalamate
(94%)
NH2 H3O+
OH (- NH4+)

Phthalamic acid
O
(81%)

www.knust.edu.gh
 O O

NH2 150-160oC
N H
OH

+ H2O O
O
Phthalamic acid Phthalimide
(~ 100%)

www.knust.edu.gh
Amides from Esters
O
O H R' R'
+ N R N + R'"OH
R OR'" R" R"

R' and/or R" may be H.

e.g. O O
Me
OMe MeNH2 N
heat H
+ MeOH
www.knust.edu.gh
Amides from Carboxylic Acids and
Ammonium Carboxylates

O O
+ NH3
R OH R O NH4

heat

O
H2O +
R NH2

www.knust.edu.gh
 Polyamides
• Polyamide = condensation polymer of diamines + dicarboxylic acids

– Natural: wool, silk (proteins)

– Synthetic: Nylon,

Kevlar

Nomex

www.knust.edu.gh
 Polyurethanes

• Polyurethanes are polymers that contain

portions of both ester & amide functional
groups

www.knust.edu.gh
 Reactions of Amides
• Heating in either aqueous acid or aqueous
base produces a carboxylic acid and amine
• Acidic hydrolysis by nucleophilic addition of
water to the protonated amide, followed by
loss of ammonia

www.knust.edu.gh
 Basic Hydrolysis of Amides
• Addition of hydroxide and loss of amide ion

www.knust.edu.gh

295
Reduction: Conversion of Amides
into Amines
• Reduced by LiAlH4 to an amine rather than
an alcohol
• Converts C=O → CH2

www.knust.edu.gh

296
 Reduction of Amides
• Addition of hydride to carbonyl group
• Loss of the oxygen as an aluminate anion to give an
iminium ion intermediate which is reduced to the amine

www.knust.edu.gh

297
Uses of Reduction of Amides
• Works with cyclic and acyclic
• Good route to cyclic amines

www.knust.edu.gh

298
 Hydrolysis of Amides

❖ Acid hydrolysis of amides

O + O
H
+ NH4
R NH2 H2O, heat R OH

www.knust.edu.gh
❖ Mechanism

H
:O : H+ O OH

:
H2O

R NH2 R NH2 R NH2

:
H O
H

H
:O : O : OH
:
+ NH3
R OH R OH R NH3
HO
www.knust.edu.gh
❖ Basic hydrolysis of amides

O − O
OH
+ NH3
R NH2 H2O, heat R O

www.knust.edu.gh
❖ Mechanism

O OH O O
H + NH2
R NH2 R NH2 R O
HO

O
NH3 +
R O
www.knust.edu.gh
 Nitriles from the Dehydration of
Amides

:O : P4O10 or (CH3CO)2O
R C N: + H3PO4
heat
:

R NH2 (a nitrile) (or CH3CO2H)

(−H2O)

❖ This is a useful synthetic method for

preparing nitriles that are not available by
nucleophilic substitution reactions between
alkyl halides and cyanide ions

www.knust.edu.gh
❖ e.g.

O
C N
NH2 P4O10

dehydration

www.knust.edu.gh
Hydrolysis of Nitriles

O
base or acid
R C N
H2O, heat R OH

❖ Catalyzed by both acid and base

www.knust.edu.gh
❖ Examples

H2SO4 OH
CN
H2O, 
O
(82%)

OH
CN
1. NaOH, H2O,  O
2. H3O+ (68%)

www.knust.edu.gh
Lactams O
O
O 
 NH
 NH
b 
b NH b g g
a b-lactam a g-lactam a -lactam
R = C6H5CH2 Penicillin G
H
R N S CH3 R = C6H5CH Ampicillin

O N CH3 NH2
O
CO2H Penicillin V
R = C6H5OCH2
www.knust.edu.gh
Lactams.

b-lactams (4-membered ring lactams) are important acti-bacterial

agents.

Penicillin G Amoxicillin Cephalexin

www.knust.edu.gh

308