Chapter 11 Reactions of Alcohols

Introduction General
Organic, and
Biochemistry
Twelfth Edition
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or in part.
Chapter 11
Synthesis and Reactions of Alcohols,

Ethers, and Thiols
© 2020 Cengage. All Rights Reserved. May not be scanned, copied or duplicated, or posted to a publicly
accessible website, in whole or in part.
Video Introduction
Alcohols
Alcohol: A compound that containing an –OH (hydroxyl group)

bonded to a tetrahedral carbon: General formula of CnH2n+1OH
• Methanol, CH3OH, is the simplest alcohol.
Nomenclature
1. Select the longest carbon chain that contains the –OH group as the parent
alkane and number it from the end that gives the -OH the lower number.
2. Change the ending of the parent alkane from e to ol and use a number to
show the location of the –OH group; for cyclic alcohols, the carbon bearing
the –OH group is carbon-1.
3. Name and number substituents and list them in alphabetical order.
structural formula
• unambiguously shows how the atoms are bonded
together
• can use condensed structural formulas

• bonds are omitted, repeated groups put
together, side chains put in brackets
• CH3CH2CH2CH2CH2CH2OH
• or even CH3(CH2)4CH2OH
skeletal formula
• not accepted in the IB for answers but often used
in questions
• every “corner” represents a carbon
• hydrogens are implied
Nomenclature Activity
• Name and draw the first 10 alcohol
Nomenclature (1 of 4)
Example Problem: Write the IUPAC name for each

alcohol.
accessible website, in whole or in part. 1
Solution:
Classification of alcohols
• Alcohols are classified as
primary (1°), secondary
(2°), or tertiary (3°),
depending on the number
of carbon groups bonded to
the carbon bearing the –
OH group.
• In the IUPAC system, a compound containing two hydroxyl groups is named as a diol,
one containing three hydroxyl groups as a triol, and so forth.
• IUPAC names for diols, triols, and so on retain the final "-e" in the name of the parent
alkane.
• We commonly refer to compounds containing two hydroxyl groups on adjacent carbons
as glycols.
Physical Properties (1 of 3)
Figure 13.2 Alcohols are polar molecules.

• The C–O and O–H bonds are both polar covalent.
Figure 13.3
In the liquid state,
alcohols associate
by hydrogen
bonding.
Table 13.1 Boiling Points and Solubility in Water of Sets of

Alcohols, and Alkanes of Similar Molecular Weight. The solubility of some
simple alcohols in water. The water solubility decreases as the alkyl group becomes larger.
Alcohols with one-, two-, or three carbon alkyl groups are miscible with water.
Structural Formula Name Molecular Boiling Solubility

Weight (amu) Point (°C) in Water
CH3OH methanol 32 65 Unlimited
CH3CH3 ethane 30 89 Insoluble
CH3CH2OH ethanol 46 78 Infinite
CH3CH2CH3 propane 44 42 Insoluble
CH3CH2CH2OH 1-propanol 60 97 Infinite
CH3CH2CH2CH3 butane 58 0 Insoluble
CH3CH2CH2CH2OH 1-butanol 74 117 8 g/100 g
CH3CH 2CH2CH2CH3
© 2020 pentane
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Reserved. May not be insoluble
or posted to a publicly
Acidity of Alcohols
Alcohols have about the same pKa values as water.
• Aqueous solutions of alcohols have the same pH as that of pure water.
• Alcohols and phenols both contain an –OH group.
• Phenols are weak acids and react with NaOH and other strong bases to
form water-soluble salts.
• Alcohols are weaker acids than phenols and do not react in this manner.
• The acidity decreases as the substitution on the alkyl group increases, because a more highly substituted alkyl
group inhibits solvation of the alkoxide ion, decreasing the stability of the alkoxide ion and driving the dissociation
equilibrium toward the left
Physical Properties of Alcohols
• An alcohol’s potency as an anti-bacterial agent depends on the
size of the hydrophobic group
• The alcohol needs some water

solubility to travel through
aqueous media
• To kill a bacterium, the alcohol

should have a significant
hydrophobic region to penetrate
microbial membranes
1
Physical Properties of Alcohols
• Hexylresorcinol is used as an antibacterial and as an antifungal
agent
• It has a good combination of hydrophobic and hydrophilic regions
1
Practice Thiols
Synthesis of Alcohols and Phenols
2
Synthesis of Alcohols
• Alcohols can by synthesized from alkenes via addition reactions:
• Recall that acid-catalyzed hydration yield Markovnikov addition

• Hydroboration-oxidation yields anti Markovnikov addition
2
Prep. of Alcohols via Reduction
• A third method to prepare alcohols is by the
reduction of a carbonyl. What is a carbonyl?
• Reductions involve a change in oxidation state
• Oxidation state are a method of electron
bookkeeping
• Recall how we used formal charge as a method of
electron bookkeeping
• Each atom is assigned half of the electrons it is sharing
with another atom
• What is the formal charge on carbon in methanol?
2
• To determine the oxidation state of an atom, imagine the
electrons in a bond as a lone pair on the more electronegative
atom
2
• Oxidation states for carbon ranges from -4 to +4
• Oxidation Rxn – carbon’s oxidation state is increased

• Reduction Rxn – carbon’s oxidation state is decreased
2
• There are three reducing agents that can be used:
1. Catalytic Hydrogenation:
This method is rarely used; high temp and pressure is

required
2
2. Sodium Borohydride (NaBH4) – common reducing

agent for aldehydes and ketones
3
• There are three reducing agents that can be used
• NaBH4 is a source of hydride (H-) which does nucleophilic
addition to the carbonyl carbon, followed by proton transfer
from the solvent:
3
• There are three reducing agents that can be used
• When an unsymmetrical ketone is reduced, a new chiral
center is created and a pair of stereoisomers is obtained
Unsymmetrical ketone
has two different R groups
3
3. Lithium Aluminum Hydride (LiAlH4) – another

common reducing agent for reducing carbonyl
compounds
Lithium Aluminum Hydride is often abbreviated as LAH 3

Preparation of Alcohols
o Nucleophilic Substitution of Alkyl Halide
o Reduction of Ketones, and Aldehydes

Aldehydes and ketones are easily reduced to primary and secondary alcohols,
respectively.
3
Preparation of Alcohols
o Addition of Grignard’s Reagent to Aldehydes and Ketones
3
Prep of Alcohols – Grignard Reagents
• Grignard reagents are often used in the synthesis of alcohols
• To form a Grignard, an alkyl halide is treated with Mg metal
3
• The electronegativity difference between C (2.5) and Mg (1.3)
is great enough that the bond has significant ionic character
• The carbon atom behaves like a carbon anion, and is a

strong nucleophile, as well as a strong base
3
• Grignard reagents react like LAH, and will attack the carbonyl
group of a ketone or an aldehyde
• The key difference – Grignard reaction give a new C-C

bond!
3
• Because the Grignard is both a strong base and a strong
nucleophile, care must be taken to protect it from exposure
to water or alcohols
• Anhydrous ethers are usually used as solvents for Grignard

reactions
3
• Grignard examples
4
Examples cont…
4
4
Preparation of Diols
• Recall the methods we discussed in chapter 6 to convert an
alkene into a diol
4
Alcohols and Phenols
• Alcohols possess a hydroxyl group (-OH)
• Hydroxyl groups are extremely common in natural

compounds
4
• Phenols possess a hydroxyl group directly attached to a
benzene ring
4
• Hydroxyl groups in natural compounds
4
Alcohol and Phenols
• When an –OH group is attached to a benzene ring, the parent name
is phenol
Klein, Organic Chemistry 3e 4

Alcohol and Phenols
• For cyclic alcohols, the –OH group is always carbon 1
• Common names for some alcohols are also frequently

used
5
Cyclic Alcohols
Alcohols: Double and Triple Bonds
Phenols Nomenclature
• Because the phenol structure involves a benzene ring,

the terms ortho (1,2-disubstituted)
• meta (1,3-disubstituted), and
• para (1,4-disubstituted) are often used in the common
names. The following examples illustrate the
systematic names and the common names of some
simple phenols.
Ortho, Meta and Para Phenols
Phenols nomenclature
• The methylphenols are called cresols, whereas the names
of the benzenediols are based on their historical uses and
sources rather than their structures. We will generally use the
systematic names of phenolic compounds.
Preparation of Phenols
o The Alkali Fusion of Sulfonates

The alkali fusion of sulfonates involves the following steps;
1. Sulfonation of an aromatic ring.
2. Melting (fusion) of the aromatic sulfonic acid with sodium hydroxide to give a
phenoxide salt.
3. Acidification of the phenoxide with HCl to produce the phenol.
5
Preparation of Phenols
• 2 million tons of phenol is produced industrially yearly
• Acetone is a useful byproduct

• Phenol is a precursor in many chemical syntheses
• Pharmaceuticals
• Polymers
• Adhesives
• Food preservatives, etc.
5
Reactions of Alcohol and Phenols
5
Summary of Reactions of Alcohol
Dehydration (1 of 3)
Dehydration: Elimination of a molecule of water from

adjacent carbon atoms gives an alkene.
• Dehydration is most often brought about by heating an alcohol
with either 85% H3PO4 or concentrated H2SO4.
• 1°alcohols are the most difficult to dehydrate and require
temperatures as high as 180°C.
• 2°alcohols undergo acid-catalyzed dehydration at somewhat
lower temperatures.
• 3°alcohols generally undergo acid-catalyzed dehydration at
temperatures only slightly above room temperature.
When isomeric alkenes are obtained, the alkene having the

greater number of alkyl groups on the double bond generally
predominates.
• Examples:
Dehydration-Hydration
Acid-catalyzed hydration of alkenes to give alcohols (Chapter 12)

and acid-catalyzed dehydration of alcohols to give alkenes are
competing reactions.
• The following acid-catalyzed equilibrium exists.
• In accordance with Le Chatelier's principle, large amounts of water favor

alcohol formation, whereas removal of water from the equilibrium mixture
favors alkene formation.
Practice Problem
Oxidation of Alcohols
• Oxidation of alcohols leads to ketones, aldehydes, and

carboxylic acids. These functional groups, in turn,
undergo a wide variety of additional reactions. For these
reasons, alcohol oxidations are some of the most
common organic reactions.
Oxidation (1 of 2)
Oxidation of a 1° alcohol gives an aldehyde or a

carboxylic acid, depending on the experimental
conditions.
• Oxidation of a 1° alcohol to a carboxylic acid is commonly
carried out using potassium dichromate, K 2Cr2O7, in aqueous
sulfuric acid.
Oxidation (2 of 2)
• Oxidation of a 2° alcohol gives a ketone.
• Tertiary alcohols are resistant to oxidation. In the presence of

an acid catalyst they are prone to dehydration.
• There is a large number of oxidizing agents that can be used
to oxidize an alcohol
• The most common oxidizing agent is chromic acid; it is
formed from either CrO3 or Na2Cr2O7 in aqueous acid:
Chromic acid
is also
called the
Jones Reagent

• Oxidation of the alcohol with chromic acid involves (1) formation of
a chromate ester, and (2) elimination to form the p bond
6
• Chromic acid will oxidize a 1˚ alcohol to a carboxylic acid
• PCC (pyridinium chlorochromate) can be used as the

oxidant to produce an aldehyde
1˚ alcohol aldehyde
7
• Regardless of the oxidant used, either chromic acid or PCC
will convert a 2˚ alcohol to a ketone:
7
• Chromium reagents are toxic and horrible for the
environment.
• Alternatives have been developed, two of them are covered
here:
1. Swern oxidation – dimethyl sulfoxide (DMSO) and

oxalyl chloride form the active oxidant.
active
DMSO: Dimethyl Sulfoxide oxidant
7
• The chlorodimethyl sulfonium ion (active oxidant) is attacked
by the alcohol, and Et3N facilitates elimination to form the p bond
• 2˚ alcohols are oxidized to ketones

7
• Like PCC, the Swern oxidation converts 1˚ alcohols to

aldehydes Oxalyl chloride
7
• Chromium reagents are toxic and horrible for the
environment.
• Alternatives have been developed, two of them are covered
here:
2. Dess-Martin periodane oxidation (DMP) – yields

analogous results as the Swern oxidation:
7
• Predict the product for the following reaction
7
• Predict the product for the following reaction
carboxylic
2˚ alcohol ketone acid
aldehyde
1˚ alcohol carboxylic
acid
7
Oxidation of Phenol
• Phenol oxidizes to form benzoquinone, which in turn can be
reduced to hydroquinone
• Quinones interconvert with hydroquinones, which is a key

process in cellular respiration
7
Oxidation of Phenol
• Ubiquinones act to catalyze the conversion of oxygen into
water, and are found in all cells in nature
7
Oxidation of Phenol
• Ubiquinone catalysis: Nicotinamide adenine dinucleotide

Reactions of Alcohols: Substitution
• 3˚ alcohols area converted to alkyl halides with HX (SN1 rxn)
• For 1˚ or 2˚ alcohols, the reaction occurs via SN2
8
Reactions of
Alcohols:
Substitution
Reactions of Alcohols; Substitution
• To make an alkyl chloride, ZnCl2 must be used with HCl
• The Zinc cation is required to make the –OH a better leaving

group
8
Reactions of Alcohols:Substitution
• Recall the –OH group can be converted into a good leaving group,
such as a tosyl group
• The tosylate can then undergo

SN2 substitution to obtain an
alkyl halide
8
• 1˚ and 2˚ alcohols can also be converted to alkyl halides

using SOCl2 or PBr3:
8
• SOCl2 mechanism:
8
Reactions of Alcohols: Esterification
• Replacing the -OH group of a carboxylic acid with the -OR
group of an alcohol gives a carboxylic ester. The following
condensation, called the Fischer esterification, shows the
relationship between the alcohol and the acid on the left and
the ester and water on the right
Reactions of Alcohols: Esterification
Practice Problem
Production of Alkoxide
• Some alcohols react sluggishly with both sodium and

potassium. In these cases, a useful alternative is sodium
hydride, usually in tetrahydrofuran solution. Sodium hydride
reacts quickly to form the alkoxide, even with difficult
compounds.
Alkoxide
• The alkoxide ion is a strong nucleophile as well as a

powerful base. Unlike the alcohol itself, the alkoxide ion
reacts with primary alkyl halides and tosylates to form
ethers. This general reaction, called the Williamson
ether synthesis, is an SN2 displacement. The alkyl
halide (or tosylate) must be primary so that a back-side
attack is not hindered. When the alkyl halide is not
primary, elimination usually results
Alkoxide Practice Problem
Reactions of Phenols
o Halogenation takes place without catalyst.
 The products depend on the solvent used.

 In aprotic solvents (solvents that do not release protons) (CCl4, CS2)-
bromination gives a mixture of o- and p-bromophenol.
 In protic solvents (solvents that can release protons) (H2O)-halogenation
gives a trisubstituted phenol is produced. 9
Ethers
The functional group of an ether is an oxygen atom

bonded to two carbon atoms.
• The simplest ether is dimethyl ether.
• The most common ether is diethyl ether.
Although ethers can be named according to the IUPAC system,
chemists almost invariably use common names for low-
molecular-weight ethers.
• Common names are derived by listing the alkyl groups bonded to oxygen
in alphabetical order and adding the word “ether.”
• Alternatively, name one of the groups on oxygen as an alkoxy group.
Cyclic ether: An ether in which one of the atoms in a ring is
oxygen.
• Cyclic ethers are also known by their common names.
• Ethylene oxide is an important building block for the organic chemical
industry. It is also used as a fumigant in foodstuffs and textiles, and in
hospitals to sterilize surgical instruments.
• Tetrahydrofuran is a useful laboratory and industrial solvent.
Figure 13.5 Ethers are polar molecules in which oxygen
bears a partial negative charge and each carbon bonded
to it bears a partial positive charge.
However, only weak forces of attraction exist between
ether molecules in the pure liquid.
• Consequently, boiling points of ethers are close to those of
hydrocarbons of similar molecular weight.
• Ethers have lower boiling points than alcohols of the same
molecular formula.
Thiols
Thiol: A compound containing an -SH (sulfhydryl
group).
• The most outstanding property of low-molecular-weight thiols is
their stench.
• They are responsible for smells such as those from rotten eggs
and sewage.
• The scent of skunks is due primarily to these two thiols.
Nomenclature
IUPAC names are derived in the same manner as are the names
of alcohols.
• To show that the compound is a thiol, the final -e of the parent alkane is
retained and the suffix -thiol added.
Common names for simple thiols are derived by naming the alkyl
group bonded to –SH and adding the word “mercaptan.”
Physical Properties
Because of the small difference in electronegativity between

sulfur and hydrogen (2.5 – 2.1 = 0.4), an S–H bond is nonpolar
covalent.
• Thiols show little association by hydrogen bonding.
• Thiols have lower boiling points and are less soluble in water and other
polar solvents than alcohols of similar molecular weight.
TABLE 13.2 Boiling Points of Three Sets of Thiols and Alcohols with the Same Number of Carbon Atoms
Thiol Boiling Point (°C) Alcohol Boiling Point (°C)

methanethiol 6 methanol 65
ethanethiol 35 ethanol 78
1-butanethiol 98 1-butanol 117
Acidity of Thiols
Thiols are weak acids (pKa 10) and are comparable in

strength to phenols (pKa 10).
• Thiols react with strong bases such as NaOH to form water-
soluble thiolate salts.
Oxidation of Thiols
The most common reaction of thiols in biological systems is their

oxidation to disulfides, the functional group of which is a
disulfide (–S–S–) bond.
• Thiols are readily oxidized to disulfides by O2.
• They are so susceptible to oxidation that they must be protected from
contact with air during storage.
• Disulfides, in turn, are easily reduced to thiols by several reducing agents
including H2 in the presence of a transition metal catalyst.
Preparation of Ethers
1) Dehydration of Alcohols
o It takes place in the presence of acid catalysts (H2SO4, H3PO4) (intermolecular reaction)
o Example;
The most important commercial ether is diethyl ether. It is prepared from ethanol and sulfuric acid.
o When ethyl alcohol is dehydrated by sulfuric acid at 180° C, the dominant product is ethylene.
11
2) Williamson
Synthesis
• This method has two steps;
1) An alcohol is converted to its alkoxide by treatment with a reactive metal
(sodium or potassium).
2) Displacement is carried out between the alkoxide and an alkyl halide.
• To obtain the best yields of mixed dialkyl ethers, we select a 1 rather than
a 2or 3alkyl halide and react it with a sodium alkoxide
• To prepare an alkyl aryl ether, we must be careful not to pick a combination
in which one of the reagents has a halogen directly attached to an aromatic
ring.
11
o Example 1; Preparation of t-butyl methyl ether, (CH3)3C-O-
CH
 In3. theory, this could be done by either of two
reactions.
1. You could react sodium methoxide, CH3O-Na+, with t-butyl chloride, (CH3)3C-Cl.
This combination leads to dehydrohalogenation to an alkene, an elimination
reaction.
2. You could react sodium t-butoxide, (CH3)3C-O Na , with methyl chloride, CH3Cl.
- +
This route gives the desired ether by substitution.
11
Example 2; Assume you need to synthesize methyl phenyl ether

(anisole), CH3-O-C6H5, by the Williamson method.
 In theory, you could obtain anisole in either of two ways.
11
Reactions of Ethers
oCleavage of Ethers by Hot Concentrated Acids

 When ethers are heated in concentrated acid solutions, the ether linkage is broken.
 The acids most often used in this reaction are HI, HBr, and HCl.
 If an excess of acid is present, the alcohol initially produced is converted into an alkyl
halide by the reaction.
11
Important Alcohols (1 of 2)
Important Alcohols (2 of 2)
• Propene is the raw material base for the manufacture

of these important compounds.
Uses of Alcohols and Phenols
o Drinks – The “alcohol” in alcoholic drinks is simply ethanol.

o As a fuel – Ethanol burns to give carbon dioxide and water and can be used as a fuel
in its own right, or in mixtures with petrol (gasoline).
o As a solvent – Ethanol is widely used as a solvent. It is relatively safe, and can be
used to dissolve many organic compounds which are insoluble in water. It is used, for
example, in many perfumes and cosmetics.
o Isopropanol; rubbing alcohol, rapid evaporation, Antiseptic, more toxic than ethanol,
but induces vomiting and used for manufacture of acetone.
o Phenol is used for resins, and pharmacuticals.
11
Uses of Ethers
o Ether is used as a mild anesthetic and as a solvent in industries

o It is used as an antiseptic to prevent infection when an injection is administered.
o Dimethyl ether is used as refrigerant and as solvent at low temperature.
o Diethyl ether is a common ingredient as an aesthesia in surgery.
o Diethyl ether is common solvent for oils, gums, resins etc.
o We use phenyl ether as a heat transfer medium because of its high boiling point.
11
Chapter 13 Alcohols, Ethers, and Thiols
End
Chapter 11

Chapter 11 Reactions of Alcohols

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Chapter 11 Reactions of Alcohols

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Introduction General

Synthesis and Reactions of Alcohols,

Alcohol: A compound that containing an –OH (hydroxyl group)

• can use condensed structural formulas

• Name and draw the first 10 alcohol

Example Problem: Write the IUPAC name for each

Figure 13.2 Alcohols are polar molecules.

Table 13.1 Boiling Points and Solubility in Water of Sets of

Structural Formula Name Molecular Boiling Solubility

• The alcohol needs some water

• To kill a bacterium, the alcohol

• It has a good combination of hydrophobic and hydrophilic regions

• Recall that acid-catalyzed hydration yield Markovnikov addition

• Oxidation Rxn – carbon’s oxidation state is increased

This method is rarely used; high temp and pressure is

2. Sodium Borohydride (NaBH4) – common reducing

3. Lithium Aluminum Hydride (LiAlH4) – another

Lithium Aluminum Hydride is often abbreviated as LAH 3

o Nucleophilic Substitution of Alkyl Halide

o Reduction of Ketones, and Aldehydes

o Addition of Grignard’s Reagent to Aldehydes and Ketones

• The carbon atom behaves like a carbon anion, and is a

• The key difference – Grignard reaction give a new C-C

• Anhydrous ethers are usually used as solvents for Grignard

• Hydroxyl groups are extremely common in natural

Klein, Organic Chemistry 3e 4

• Common names for some alcohols are also frequently

• Because the phenol structure involves a benzene ring,

o The Alkali Fusion of Sulfonates

3. Acidification of the phenoxide with HCl to produce the phenol.

• Acetone is a useful byproduct

Dehydration: Elimination of a molecule of water from

When isomeric alkenes are obtained, the alkene having the

Acid-catalyzed hydration of alkenes to give alcohols (Chapter 12)

• In accordance with Le Chatelier's principle, large amounts of water favor

• Oxidation of alcohols leads to ketones, aldehydes, and

Oxidation of a 1° alcohol gives an aldehyde or a

• Oxidation of a 2° alcohol gives a ketone.

• Tertiary alcohols are resistant to oxidation. In the presence of

Klein, Organic Chemistry 3e 6

• PCC (pyridinium chlorochromate) can be used as the

1. Swern oxidation – dimethyl sulfoxide (DMSO) and

• 2˚ alcohols are oxidized to ketones

• Like PCC, the Swern oxidation converts 1˚ alcohols to

2. Dess-Martin periodane oxidation (DMP) – yields

• Predict the product for the following reaction

• Quinones interconvert with hydroquinones, which is a key

Klein, Organic Chemistry 3e 8

• For 1˚ or 2˚ alcohols, the reaction occurs via SN2

• The Zinc cation is required to make the –OH a better leaving

• The tosylate can then undergo

• 1˚ and 2˚ alcohols can also be converted to alkyl halides

• Some alcohols react sluggishly with both sodium and

• The alkoxide ion is a strong nucleophile as well as a

o Halogenation takes place without catalyst.

 The products depend on the solvent used.

The functional group of an ether is an oxygen atom

Because of the small difference in electronegativity between

Thiol Boiling Point (°C) Alcohol Boiling Point (°C)

Thiols are weak acids (pKa 10) and are comparable in

The most common reaction of thiols in biological systems is their

2) Displacement is carried out between the alkoxide and an alkyl halide.

This route gives the desired ether by substitution.

Example 2; Assume you need to synthesize methyl phenyl ether