Organic Chemistry, 7th Edition

L. G. Wade, Jr.

Chapter 10
Structure and Synthesis
of Alcohols

Dr.Abdulaziz Ajlouni

Structure of Water and Methanol

Oxygen is sp3 hybridized and tetrahedral.

The HOH angle in water is 104.5.
The COH angle in methyl alcohol is 108.9.
Chapter 10

Classification of Alcohols
Primary: carbon with OH is bonded to
one other carbon.
Secondary: carbon with OH is bonded
to two other carbons.
Tertiary: carbon with OH is bonded to
three other carbons.
Aromatic (phenol): OH is bonded to a
benzene ring.
Chapter 10

Examples of Classifications
OH

CH3

CH3

CH3

CH CH2OH
*

Primary alcohol

CH CH2CH3

Secondary alcohol

CH3

CH3

C* OH

Tertiary alcohol

CH3

Chapter 10

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.

Chapter 10

Examples of Nomenclature
OH

CH3
CH3
3

CH3

CH CH2OH
2

2-methyl-1-propanol
2-methylpropan-1-ol

2
CH3

CH3
1
C OH
CH3

CH CH2CH3
2

2-butanol
butan-2-ol

2-methyl-2-propanol
2-methylpropan-2-ol

Chapter 10

OH

Trans-2-Bromocyclohexanol

Br
OH
Cl

(Z)-4-chloro-3-buten-2-ol

Or
(Z)-4-chlorobut-3-en-2-ol

Enol:
End the name in ol, but also specify that there is a
double bond by using the ending ene before -ol
OH
CH2
5

CHCH2CHCH3
4

2 1

4-penten-2-ol
pent-4-ene-2-ol
Chapter 10

Naming Priority
Highest ranking

Lowest ranking

1. Acids
2. Esters
3. Aldehydes
4. Ketones
5. Alcohols
6. Amines
7. Alkenes
8. Alkynes
9. Alkanes
10. Ethers
11. Halides
Chapter 10

Hydroxy Substituent
When OH is part of a higher priority class of
compound, it is named as hydroxy.
carboxylic acid

OH
CH2CH2CH2COOH
4

4-hydroxybutanoic acid

also known as g-hydroxybutyric acid (GHB)

Chapter 10

Common Names
Alcohol can be named as alkyl alcohol.
Useful only for small alkyl groups.
OH

CH3
CH3

CH CH2OH

isobutyl alcohol

CH3

CH CH2CH3

sec-butyl alcohol

Chapter 10

10

Naming Diols
Two numbers are needed to locate the two
OH groups.
Use -diol as suffix instead of -ol.
1

hexane-1,6- diol
Chapter 10

11

Glycols
1, 2-diols (vicinal diols) are called glycols.
Common names for glycols use the name of the
alkene from which they were made.

ethane-1,2- diol

propane-1,2- diol

ethylene glycol

propylene glycol
Chapter 10

12

Solved Problem 1
Give the systematic (IUPAC) name for the following alcohol.

Solution
The longest chain contains six carbon atoms, but it does not contain the carbon bonded to the hydroxyl
group. The longest chain containing the carbon bonded to the OH group is the one outlined by the
green box, containing five carbon atoms. This chain is numbered from right to left in order to give the
hydroxyl-bearing carbon atom the lowest possible number.

The correct name for this compound is 3-(iodomethyl)-2-isopropylpentan-1-ol.

Chapter 10

13

Physical Properties
Most of the common alcohols, up to about 1112 carbons are liquids at R.T
Alcohols have high boiling points due to
hydrogen bonding between molecules.
Small alcohols are miscible in water, but
solubility decreases as the size of the alkyl
group increases.

Chapter 10

14

Boiling Points of alcohols

Alcohols have higher boiling points than ethers and

alkanes because alcohols can form hydrogen bonds.
The stronger interaction between alcohol molecules will
require more energy to break them resulting in a higher
boiling point.
Dipole-Dipole attraction also contributes to the relatively
high boiling points due to polarized C-O,O-H bonds and
the nonbonding electrons on oxygen.
Chapter 10

15

Solubility in Water

In chemistry, the hydroxyl group is

called hydrophilic, meaning water
loving and the alkyl group is called
hydrophobic, meaning water hating
Small alcohols are miscible in water, but
solubility decreases as the size of the
alkyl group increases.
Chapter 10

16

Methanol1
Wood alcohol
Industrial production from synthesis gas
High Temp
3C + 4 H2O
CO

+ H2

400 C, 300 atm H2

CO2 + 2CO + 4H2

CH3OH

CuO-ZnO

Common industrial solvent

Toxic Dose: 100 mL methanol
Used as fuel engine at Indianapolis 500 (1965-2006)
Fire can be extinguished with water
High octane rating
Low emissions
Lower energy content
Invisible flame
Can damage the optic nerve
Chapter 10

17

Ethanol
Fermentation of sugar and starches in grains such as
corn, wheat and barley resulting in grain alcohol.
C6H12O6

yeast enzyme

2 CH3OH + 2 CO2

1215% alcohol result, then yeast cells die

Distillation increase the alcohol concentration and
produces hard liquors.
Azeotrope: 95% ethanol at lower temp (78.3) by
constant boiling
Denatured alcohol is ethanol that contain impurites,
therefore can be used as solvent only
Gasahol: 10% ethanol in gasoline and used since 2006
Methanol is about twice toxic as ethanol,Toxic dose:
200 mL
Chapter 10

18

Acidity of Alcohols
pKa range: 15.518.0 (water: 15.7)
Acidity decreases as the number of carbons increase
bcs alkyl group inhibits solvation of alkoxide ion and
therefore decrease the stability of the alkoxide ion
Halogens and other electron withdrawing groups
increase the acidity, it helps stabilize the alkoxide ion.

ROH

RO

alcohol

alkoxide ion

Chapter 10

19

Table of Ka Values

Chapter 10

20

Formation of Alkoxide Ions

Since alcohols are weak acids, therefore NaOH is not

strong enough to for alkoxide ion
Ethanol reacts with sodium or potassium metal to form
sodium ethoxide (NaOCH2CH3), a strong base commonly
used for elimination reactions.
Oxidation-Reduction reaction.
More hindered alcohols like 2-propanol or tert-butanol
react faster with potassium(more reactive) than with
sodium.
Alternative reagents is sodium hydride (NaH).
Chapter 10

21

Formation of Phenoxide Ion

The aromatic alcohol phenol is more acidic than

aliphatic alcohols by around 100 million times due to
the ability of aromatic rings to delocalize the negative
charge of the oxygen within the carbons of the ring.
Chapter 10

22

Charge Delocalization on the

Phenoxide Ion

The negative charge of the oxygen can be delocalized over four

atoms of the phenoxide ion.
There are three other resonance structures that can localize the
charge in three different carbons of the ring.
The true structure is a hybrid between the four resonance forms.
Chapter 10

23

Synthesis of Alcohols (Review)

1.Alcohols can be synthesized by nucleophilic
substitution of alkyl halide.(Ch.6)
H3CH2C

HO

KOH

Br

CH2CH3

SN2

H CH3

H CH3

2. from Alkene
1.Hydration of alkenes also produce alcohols(Ch.8)
Acid-catalyzed hydration
R

H2O,
H

Markonikove

Chapter 10

R OH

24

Indirect Hydration

2. Oxymercuration-Demercuration
Markovnikov product formed
Anti addition of H-OH
No rearrangements

3.Hydroboration
Anti-Markovnikov product formed
Syn addition of H-OH
CH3

CH3
BH3 THF

H
BH2

CH3
H2O2
NaOH

H
OH
25

Synthesis of Vicinal Diols

4. Vicinal diols can be synthesized by two different
methods:
A)Syn hydroxylation of alkenes
Osmium tetroxide,
hydrogen peroxide
Cold, dilute, basic
potassium permanganate
B) Anti Dihydroxylation: Peroxy acid
O

OH

CH3COOH

H
H

Chapter 10

OH

26

3. Nucleophilic Addition to Carbonyl

Compounds

Nucleophiles can attack the carbonyl carbon

forming an alkoxide ion which on protonation
will form an alcohol.

Chapter 9

27

Organometallic Reagents
Carbon is negatively charged so it is
bonded to a metal (usually Mg or Li).
It will attack a partially positive carbon.
CX
CO

Good for forming carboncarbon bonds.

Chapter 10

28

Grignard Reagents

Formula RMgX (reacts like R:- +MgX).

Ethers are used as solvents to stabilize the complex.
RI > RBr > RCl > > RF
May be formed from any halide.
Chapter 10

29

Reactions with Grignards

Br
+

Mg

ether

Cl
CH3CHCH2CH3

Mg

ether

Chapter 10

MgBr

MgCl
CH3CHCH2CH3

30

Organolithium Reagents
Formula RLi (reacts like R:- +Li)
Can be produced from alkyl, vinyl, or aryl halides, just
like Grignard reagents.
Ether not necessary, wide variety of solvents can be
used.
Li X

RX
+ 2Li
X = Cl, Br, I

+ RLi

Reactivity: alkyl > aryl, Cl < Br < I etc

Commercial synthesis: mostly from chlorides
In laboratory: usually from alkyl bromides/iodides
(easier to start)
In apolar or weakly polar solvents
Chapter 10

31

Limitations of Grignard
Grignards are good nucleophiles but in
the presence of acidic protons it will
acts as a strong base.
No water or other acidic protons like
OH, NH, SH, or terminal alkynes.
No other electrophilic multiple bonds,
like CN, CN, SO, or NO.
Chapter 10

32

Organolithium and Organomagnesium Compounds

as Brnsted Bases - Grignard reagents (M = MgX) and
organolithium reagents (M = Li) are very strong bases.
R-M + H2O

R-H + M-OH

Hydrocarbons are very weak acids; their conjugate bases are

very strong bases.
R C C H

H3C-H2C-H2C-H2C-Li

terminal
acetylene
(pKa ~ 26)
R C C H

THF

butyllithium

H3C-H2C-MgBr

ethylmagnesium
bromide

R C C Li + H3C-H2C-H2C-H2C-H

lithium
acetylide
THF

pKa > 60

R C C MgBr + H3C-H2C-H

magnesium
acetylide
33

Reaction with Carbonyl

Chapter 10

34

Formation of Primary Alcohols

Using Grignard Reagents

Reaction of a Grignard with formaldehyde will

produce a primary alcohol after protonation.

Chapter 10

35

Synthesis of 2 Alcohols

Addition of a Grignard reagent to an aldehyde

followed by protonation will produce a
secondary alcohol.
Chapter 10

36

Synthesis of 3 Alcohols

Tertiary alcohols can be easily obtained by

addition of a Grignard to a ketone followed by
protonation with dilute acid.

Chapter 10

37

Solved Problem 2

Show how you would synthesize the following alcohol from compounds containing no more than five
carbon atoms.

Solution

Chapter 10

38

Grignard Reactions with

Acid Chlorides and Esters
Use two moles of Grignard reagent.
The product is a tertiary alcohol with
two identical alkyl groups.
Reaction with one mole of Grignard
reagent produces a ketone
intermediate, which reacts with the
second mole of Grignard reagent.
Chapter 10

39

Reaction of Grignards with

Carboxylic Acid Derivatives

Chapter 10

40

Mechanism
Step 1: Grignard attacks the carbonyl forming the tetrahedral
intermediate.

CH3

H3C
R

MgBr

C O

R C O

Cl

MgBr

Cl

Step 2: The tetrahedral intermediate will reform the carbonyl and form
a ketone intermediate.

CH3
R C O

CH3
R C

MgBr

Cl
Chapter 10

MgBrCl

O
41

Mechanism continued
Step 3: A second molecule of Grignard attacks the carbonyl of the
ketone.
CH3
CH3
R MgBr

R C

R C O
O

MgBr

Step 4: Protonation of the alkoxide to form the alcohol as the product.

CH3
R C O

CH3

HOH

MgBr

R C OH

R
Chapter 10

42

Addition to Ethylene Oxide

Grignard and lithium reagents will attack epoxides (also called

oxiranes) and open them to form alcohols.
This reaction is favored because the ring strain present in the
epoxide is relieved by the opening.
The reaction is commonly used to extend the length of the
carbon chain by two carbons.
Chapter 10

43

Limitations of Grignard
Grignards are good nucleophiles but in
the presence of acidic protons it will
acts as a strong base.
No water or other acidic protons like
OH, NH, SH, or terminal alkynes.
No other electrophilic multiple bonds,
like CN, CN, SO, or NO.
Chapter 10

44

Organolithium and Organomagnesium Compounds

as Brnsted Bases - Grignard reagents (M = MgX) and
organolithium reagents (M = Li) are very strong bases.
R-M + H2O

R-H + M-OH

Hydrocarbons are very weak acids; their conjugate bases are

very strong bases.
R C C H

H3C-H2C-H2C-H2C-Li

terminal
acetylene
(pKa ~ 26)
R C C H

THF

butyllithium

H3C-H2C-MgBr

ethylmagnesium
bromide

R C C Li + H3C-H2C-H2C-H2C-H

lithium
acetylide
THF

pKa > 60

R C C MgBr + H3C-H2C-H

magnesium
acetylide
45

Reduction of Carbonyl
Reduction of aldehyde yields 1 alcohol.
Reduction of ketone yields 2 alcohol.
Reagents:
Sodium borohydride, NaBH4
Lithium aluminum hydride, LiAlH4
Raney nickel

Chapter 10

46

Sodium Borohydride
NaBH4 is a source of hydrides (H-)
Hydride attacks the carbonyl carbon, forming
an alkoxide ion.
Then the alkoxide ion is protonated by dilute
acid.
Only reacts with carbonyl of aldehyde or
ketone, not with carbonyls of esters or
carboxylic acids.
Takes place with wide variety of solvents:
alcohol, ether, water
Chapter 10

47

Mechanism of Hydride Reduction

The hydride attacks the carbonyl of the aldehyde or

the ketone.
A tetrahedral intermediate forms.
Protonation of the intermediate forms the alcohols.
Chapter 10

48

Lithium Aluminum Hydride

LiAlH4 (LAH) is source of hydrides (H-)
Stronger reducing agent than sodium
borohydride, but dangerous to work with.
Reduces ketones and aldehydes into the
corresponding alcohol.
Converts esters and carboxylic acids to 1
alcohols.
LAH and water are incompatibile. An explosion
and fire would result from the process
Chapter 10

49

Reduction with LiAlH4

The LiAlH4 (or LAH) will add two hydrides to

the ester to form the primary alkyl halide.
The mechanism is similar to the attack of
Grignards on esters.
Chapter 10

50

Reducing Agents
NaBH4 can reduce
aldehydes and
ketones but not
esters and
carboxylic acids.
LiAlH4 is a stronger
reducing agent and
will reduce all
carbonyls.
Chapter 10

51

Catalytic Hydrogenation

Raney nickel is a hydrogen rich nickel powder that is

more reactive than Pd or Pt catalysts.
This reaction is not commonly used because it will
also reduce double and triple bonds that may be
present in the molecule.
Hydride reagents are more selective so they are used
more frequently for carbonyl reductions.
Chapter 10

52

SELECTIVE HYDROGENATIONS
H

OH

20O C
1 atm
Pd/C

easy
H

Hydride
reagents
Conditions will vary
with the specific
compound.

+ H2

Ni 40O C
2 atm

PtO2
100o C
5 atm

OH

more
difficult
OH

most
difficult

Thiols (Mercaptans)
Sulfur analogues of alcohols are called thiols.
The SH group is called a mercapto group.
Named by adding the suffix -thiol to the
alkane name.
They are commonly made by an SN2 reaction
so primary alkyl halides work better.
The odor of thiols is their strongest
characterstics. Shunk scent is 3methylbutane-1-thiol. Ethanethiol added to
natural gas to give it gassy odor
Chapter 10

54

Thiols - Nomenclature

IUPAC names are derived in the same manner

as are the names of alcohols
Retain the final -e of the parent alkane and add the
suffix -thiol
Common names for simple thiols are derived by
naming the alkyl group bonded to -SH and adding
the word "mercaptan"
CH3
CH3 CH 2 SH
Ethaneth iol
(Ethyl mercap tan)

CH3 CHCH2 SH
2-Methyl-1-propan ethiol
(Isobu tyl mercaptan)

Synthesis of Thiols

The thiolate will attack the carbon displacing

the halide.
This is an SN2 reaction so methyl halides will
react faster than primary alkyl halides.
To prevent dialylation use a large excess of
sodium hydrosulfide with the alkyl halide.
Chapter 10

56

Reactions of Thiols
Thiols are weak acids (pKa~10), and are
comparable in strength to phenols
thiols react with strong bases such as
NaOH to form water-soluble thiolate salts
CH3 CH2 SH + NaOH
Ethan ethiol
(pKa 10)

H2 O

CH3 CH2 S Na + H2 O
S od ium
ethaneth iolate

Thiol Oxidation

Thiols can be oxidized (by Zn/HCl) to form disulfides. The

disulfide bond
can be reduced back to the thiols with a reducing agent.
Chapter 10

58