CH 13

Organic Chemistry
Second Edition
David Klein
Chapter 13
Alcohols and Phenols
Copyright 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e
13.1 Alcohols and Phenols

Alcohols possess a hydroxyl group (-OH)
Hydroxyl groups are extremely common in

natural compounds
Copyright 2015 John Wiley & Sons, Inc. All rights

reserved.
13-2

Hydroxyl groups in natural compounds

reserved.
13-3

Phenols possess a hydroxyl group directly
attached to an aromatic ring

reserved.
13-4
13.1 Alcohols Nomenclature
Alcohols are named using the same

procedure we used in Chapter 4 to name
alkanes with minor modifications
1. Identify the parent chain, which should include
the carbon that the OH is attached to
2. Identify and Name the substituents
3. Assign a locant (and prefix if necessary) to each
substituent. Give the carbon that the OH is
attached to the lowest number possible
4. List the numbered substituents before the parent
name in alphabetical order. Ignore prefixes
(except iso) when ordering alphabetically
5. The OH locant is placed either just before
Copyrightthe
2015 John
Wiley & Sons,
Inc. All rights
reserved.
parent
name
or
just before the
-olOrganic
suffix
13-5
Klein,
Chemistry 2e

1. Identify the parent chain

reserved.
13-6

3. Assign a locant (and prefix if necessary) to each
substituent. Give the carbon that the OH is
attached to the lowest number possible taking
precedence over C=C double bonds

reserved.
13-7

5. The OH locant is placed either just before the
parent name or just before the -ol suffix
R or S configurations should be shown at the

beginning of the name
reserved.
13-8
For cyclic alcohols, the OH group should be

on carbon 1, so often the locant is assumed
and omitted
Common names for some alcohols are also

frequently used

reserved.
13-9
Like halides, alcohols are often classified by

the type of carbon they are attached to
WHY do we use these classifications?

reserved.
13-10
When an OH group is attached to a benzene

ring, the parent name is phenol
Practice with SkillBuilder 13.1

reserved.
13-11
Name the following molecule
Draw the most stable chair conformation for

(cis)-1-isopropyl-1,2-cyclohexanediol

reserved.
13-12
13.1 Commercially Important

Alcohols
Methanol (CH3OH) is the simplest alcohol
Methanol is poisonous, but it has many uses
With a suitable catalyst, about 2 billion

gallons of methanol is made industrially from
CO2 and H2 every year
1. Solvent
2. Precursor for chemical syntheses
3. Fuel

reserved.
13-13

Alcohols
Ethanol (CH3CH2OH) has been produced by

fermentation for thousands of years. HOW?
About 5 billion gallons of ethanol is made
industrially from the acid-catalyzed
hydration of ethylene every year
Ethanol has many uses
1. Solvent, precursor for chemical syntheses, fuel

2. Human consumption ethanol suitable for
drinking is heavily taxed. Ethanol used for
purposes other than drinking is often denatured.
WHY?
Is it poisonous?
reserved.
13-14

Alcohols
Isopropanol is rubbing alcohol. Draw its

structure
Isopropanol is made industrially from the
acid-catalyzed hydration of propylene
Isopropanol is poisonous, but it has many
uses
1. Industrial solvent
2. Antiseptic
3. Gasoline additive

reserved.
13-15
13.1 Physical Properties of

Alcohols
The OH of an alcohol can have a big effect

on its physical properties
Compare the boiling points below
Explain the differences

reserved.
13-16

Alcohols
Because they can H-bond, hydroxyl groups

can attract water molecules strongly
Alcohols with small carbon chains are

miscible in water (they mix in any ratio).
WHY?
Alcohols with large carbon chains do not

readily mix with water
reserved.
13-17

Alcohols
Do hydrophobic groups repel or attract

water?
WHY are molecules with large hydrophobic

groups generally insoluble in water?
Alcohols with 3 or less carbons are generally
water miscible
Alcohols with more than 3 carbons are not
miscible, and their solubility decreases as

reserved.
13-18

Alcohols
An alcohols potency as an anti-bacterial

agent depends on the size of the
hydrophobic group
To kill a
bacterium, the
alcohol should
have some water
solubility. WHY?
To kill a
bacterium, the
alcohol should
have a significant
hydrophobic

reserved.
13-19

Alcohols
Hexylresorcinol is used as an antibacterial

and as an antifungal agent
It has a good combination of hydrophobic

and hydrophilic regions
It has significant water solubility

Its nonpolar region helps it to pass through cell
membranes
Practice with conceptual checkpoint 13.3

reserved.
13-20
13.2 Acidity of Alcohols and

Phenols
A strong base is usually necessary to

deprotonate an alcohol
A preferred choice to create an alkoxide is to

treat the alcohol with Na, K, or Li metal.
Show the mechanism for such a reaction

reserved.
13-21

Phenols
Recall from chapter 3 how ARIO is used to

qualitatively assess the strength of an acid
Lets apply these factors to alcohols and
phenols
Atom

reserved.
13-22

Phenols

phenols
Resonance
Explain why phenol is 100 million times more

acidic than cyclohexanol
Show all relevant resonance contributors

reserved.
13-23

Phenols
Given the relatively low pKa of phenols, will

NaOH be a strong enough base to
deprotonate a phenol?

reserved.
13-24

Phenols

phenols
Induction: unless there is an electronegative

group nearby, induction wont be very significant
Orbital: in what type of orbital do the alkoxide

electrons reside? How does that effect acidity?

reserved.
13-25

Phenols
Solvation is also an important factor that

affects acidity
Water is generally used as the solvent when
measuring pKa values
Which of the alcohols below is stronger?
ARIO cannot be used to explain the

difference
reserved.
13-26

Phenols
Solvation explains the difference in acidity
Draw partial charges on the solvent

molecules to show how solvation is a
stabilizing effect

reserved.
13-27

Phenols
Use ARIO and solvation to rank the following

molecules in order of increasing pKa

reserved.
13-28
13.3 Preparation of Alcohols
We saw in chapter 7 that substitution

reactions can yield an alcohol
What reagents did we use to accomplish this
transformation?
We saw that the substitution can occur by

SN1 or SN2

reserved.
13-29
The SN1 process generally uses a weak

nucleophile (H2O), which makes the process
relatively slow
Why isnt a stronger nucleophile (-OH) used
under SN1 conditions?

reserved.
13-30
In chapter 9, we learned how to make

alcohols from alkenes
Recall that acid-catalyzed hydration

proceeds through a carbocation intermediate
that can possibly rearrange
How do you avoid rearrangements?

reserved.
13-31
13.4 Alcohol Prep 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?

reserved.
13-32

Reduction
For oxidation states, we imagine the bonds

breaking heterolytically, and the electrons go
to the more electronegative atom

reserved.
13-33

Reduction
Each of the carbons below have zero formal

charge, but they have different oxidation
states
Calculate the oxidation number for each
Is the conversion from formic acid carbon

dioxide an oxidation or a reduction?
What about formaldehyde methanol?
reserved.
13-34

Reduction
The reduction of a carbonyl requires a

reducing agent
Is the reducing agent oxidized or reduced?

If you were to design a reducing agent, what
element(s) would be necessary?
Would an acid such as HCl be an appropriate
reducing agent? WHY or WHY NOT?

reserved.
13-35

Reduction
There are three reducing agents you should

know
1. We have already seen how catalyzed

hydrogenation can reduce alkenes. It can also
work for carbonyls
. Forceful conditions (high temperature and/or high

pressure)
reserved.
13-36

Reduction
Reagents that can donate a hydride are

generally good reducing agents
2. Sodium borohydride

reserved.
13-37

Reduction
Reagents that can donate a hydride are

generally good reducing agents
3. Lithium aluminum hydride (LAH)

reserved.
13-38

Reduction
Note that LAH is significantly more reactive

that NaBH4
LAH reacts violently with water. WHY?
How can LAH be used with water if it reacts

with water?
reserved.
13-39

Reduction
Hydride delivery agents will somewhat

selectively reduce carbonyl compounds

reserved.
13-40

Reduction
The reactivity of hydride delivery agents

can be fine-tuned by using derivatives with
varying R-groups
Alkoxides
Cyano
Sterically hindered groups

reserved.
13-41

Reduction
LAH is strong enough to also reduce esters

and carboxylic acids, whereas NaBH4 is
generally not

reserved.
13-42

Reduction
To reduce an ester, 2 hydride equivalents are

needed

reserved.
13-43

Reduction
To reduce an ester, 2 hydride equivalents are

needed
Which steps in the mechanism are reversible?

reserved.
13-44

Reduction
Predict the products for the following

processes

reserved.
13-45
13.5 Preparation of Diols
Diols are named using the same method as

alcohols, except the suffix, diol is used

reserved.
13-46
If two carbonyl groups are present, and

enough moles of reducing agent are added,
both can be reduced

reserved.
13-47
Recall the methods we discussed in chapter

9 to convert an alkene into a diol

reserved.
13-48
13.6 Grignard Reactions
Grignard reagents are often used in the

synthesis of alcohols
To form a Grignard, an alkyl halide is treated
with Mg metal
How does the oxidation state of the carbon

change upon forming the Grignard?
reserved.
13-49
The electronegativity difference between C

(2.5) and Mg (1.3) is great enough that the
bond has significant ionic character
The carbon atom is not able to effectively

stabilize the negative charge it carries
Will it act as an acid, base, electrophile,
nucleophile, etc.?

reserved.
13-50
If the Grignard reagent reacts with a

carbonyl compound, an alcohol can result
Note the similarities between the Grignard

and LAH mechanisms

reserved.
13-51
Because the Grignard is both a strong base

and a strong nucleophile, care must be taken
to protect it from exposure to water
If water cant be used as the solvent, what

solvent is appropriate?
What techniques are used to keep
atmospheric moisture out of the reaction?

reserved.
13-52
Grignard examples
With an ester substrate, excess Grignard

reagent is required. WHY? Propose a
mechanism
List some functional groups that are NOT
compatible with the Grignard

reserved.
13-53
Design a synthesis for the following

molecules starting from an alkyl halide and a
carbonyl, each having 5 carbons or less

reserved.
13-54
13.7 Protection of Alcohols
Consider the reaction below. WHY wont it

work?
The alcohol can act as an acid, especially in

the presence of reactive reagents like the
Grignard reagent
The alcohol can be protected to prevent it
from reacting

reserved.
13-55
A three-step process is required to achieve

the desired overall synthesis

reserved.
13-56
One such protecting group is trimethylsilyl

(TMS)
The TMS protection step requires the

presence of a base. Propose a mechanism

reserved.
13-57
Evidence suggests that substitution at the Si

atom occurs by an SN2 mechanism
Because Si is much larger than C, it is more

open to backside attack

reserved.
13-58
The TMS group can later be removed with

H3O+ or F-
TBAF is often used to supply fluoride ions

reserved.
13-59

reserved.
13-60
13.8 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
Copyright
2015 John Wiley & Sons, Inc. All rights
reserved.
13-61
13.9 Reactions of Alcohols
Recall this SN1 reaction from section 7.5
For primary alcohols, the reaction occurs by

an SN2

reserved.
13-62
The SN2 reaction also occurs with ZnCl2 as

the reagent
Recall from section 7.8 that the OH group

can be converted into a better leaving
groups such as a tosyl group

reserved.
13-63
SOCl2 can also be used to convert an alcohol

to an alkyl chloride

reserved.
13-64
PBr3 can also be used to convert an alcohol

to an alkyl bromide
Note that the last step of the SOCl2 and PBr3

mechanisms are SN2

reserved.
13-65
Fill in the necessary reagents for the

conversions below

reserved.
13-66
13.9 E1 and E2 Reactions of

Alcohols
In section 8.9, we saw that an acid (with a

non-nucleophilic conjugate base) can
promote E1
Why is E2 unlikely?
Recall that the reaction generally produces
the more substituted alkene product

reserved.
13-67
13.9 E1 and E2 Reactions of

Alcohols
If the alcohol is converted into a better

leaving group, then a strong base can be
used to promote E2
E2 reactions do not involve rearrangements.

WHY?
When applicable, E2 reactions also produce
the more substituted product

reserved.
13-68
13.10 Oxidation of Alcohols
We saw how alcohols can be formed by the

reduction of a carbonyl
The reverse process is also possible with the
right reagents

reserved.
13-69
Oxidation of primary alcohols proceed to an

aldehyde and subsequently to the carboxylic
acid
Very few oxidizing reagents will stop at the

aldehyde
Oxidation of secondary alcohols produces a

ketone
Very few agents are capable of oxidizing the

ketone

reserved.
13-70
Tertiary alcohols generally do not undergo

oxidation. WHY?
There are two main methods to produce the

most common oxidizing agent, chromic acid

reserved.
13-71
When chromic acid reacts with an alcohol,

there are two main steps

reserved.
13-72
Chromic acid will generally oxidize a primary

alcohol to a carboxylic acid
PCC (pyridinium chlorochromate) can be

used to stop at the aldehyde

reserved.
13-73
PCC (pyridinium
chlorochromate) is
generally used
with methylene
chloride as the
solvent
Both oxidizing
agents will work
with secondary
alcohols

reserved.
13-74
Predict the product for the following reaction

reserved.
13-75
13.11 Biological Redox

Reactions
Nature employs reducing and oxidizing

agents
They are generally complex and selective.
WHY?
NADH is one such reducing agent

reserved.
13-76

Reactions
The reactive site of NADH acts as a hydride

delivery agent
This is one way nature

converts carbonyls into
alcohols
Why is an enzyme required?

reserved.
13-77

Reactions
NAD+ can undergo the reverse process
The NADH / NAD+

interconversion plays a
big role in metabolism

reserved.
13-78
13.12 Oxidation of Phenol
Recall that tertiary alcohols do not undergo

oxidation, because they lack an alpha proton
You might expect phenol to be similarly
unreactive
Yet, phenol is even more readily oxidized

than primary or secondary alcohols
reserved.
13-79
Phenol oxidizes to form benzoquinone, which

in turn can be reduced to hydroquinone
Quinones are found everywhere in nature

They are ubiquitous

reserved.
13-80
Ubiquinones act to catalyze the conversion

of oxygen into water, a key step in cellular
respiration
Where in a cell do you think unbiquinones

are most likely found?
reserved.
13-81
Ubiquinone catalysis:

reserved.
13-82
13.13 Synthetic Strategies
Recall some functional group conversions we

learned

reserved.
13-83
Classify the functional groups based on

oxidation state

reserved.
13-84

reserved.
13-85
Give necessary reagents for the following

conversions

reserved.
13-86
Recall the C-C bond forming reactions we

learned

reserved.
13-87
What if you want to convert an aldehyde

into a ketone?
What reagents are needed for the following

conversion?

and SkillBuilder 13-88
13.9
Copyright 2015 John Wiley & Sons, Inc. All rights reserved.
Additional Practice Problems
Name the following molecule
Draw (1R,2R)-1-(3,3-dimethylbutyl)-3,5cyclohexadien-1,2-diol

reserved.
13-89
Use ARIO and solvation to rank the following

molecules in order of increasing pKa

reserved.
13-90
Predict the products for the following

processes

reserved.
13-91
Design a synthesis for the following molecule

starting from an alkyl halide and a carbonyl,
each having 5 carbons or less

reserved.
13-92
Give necessary reagents for the multi-step

synthesis below

reserved.
13-93

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Organic Chemistry

Klein, Organic Chemistry 2e

13.1 Alcohols and Phenols

Hydroxyl groups are extremely common in

Copyright 2015 John Wiley & Sons, Inc. All rights

Klein, Organic Chemistry 2e

13.1 Alcohols and Phenols

Copyright 2015 John Wiley & Sons, Inc. All rights

Klein, Organic Chemistry 2e

13.1 Alcohols and Phenols

Copyright 2015 John Wiley & Sons, Inc. All rights

Klein, Organic Chemistry 2e

13.1 Alcohols Nomenclature

Alcohols are named using the same

13.1 Alcohols Nomenclature

Alcohols are named using the same

Copyright 2015 John Wiley & Sons, Inc. All rights

Klein, Organic Chemistry 2e

13.1 Alcohols Nomenclature

Alcohols are named using the same

Copyright 2015 John Wiley & Sons, Inc. All rights

Klein, Organic Chemistry 2e

13.1 Alcohols Nomenclature

Alcohols are named using the same

R or S configurations should be shown at the

Klein, Organic Chemistry 2e

13.1 Alcohols Nomenclature

For cyclic alcohols, the OH group should be

Common names for some alcohols are also

Copyright 2015 John Wiley & Sons, Inc. All rights

Klein, Organic Chemistry 2e

13.1 Alcohols Nomenclature

Like halides, alcohols are often classified by

WHY do we use these classifications?

Copyright 2015 John Wiley & Sons, Inc. All rights

Klein, Organic Chemistry 2e

13.1 Alcohols Nomenclature

When an OH group is attached to a benzene

Practice with SkillBuilder 13.1

Klein, Organic Chemistry 2e

13.1 Alcohols Nomenclature

Name the following molecule

Draw the most stable chair conformation for

Copyright 2015 John Wiley & Sons, Inc. All rights

Klein, Organic Chemistry 2e

13.1 Commercially Important

Methanol (CH3OH) is the simplest alcohol

Methanol is poisonous, but it has many uses

With a suitable catalyst, about 2 billion

Copyright 2015 John Wiley & Sons, Inc. All rights

Klein, Organic Chemistry 2e

13.1 Commercially Important

Ethanol (CH3CH2OH) has been produced by

Ethanol has many uses

1. Solvent, precursor for chemical syntheses, fuel

Klein, Organic Chemistry 2e

13.1 Commercially Important

Isopropanol is rubbing alcohol. Draw its

Copyright 2015 John Wiley & Sons, Inc. All rights

Klein, Organic Chemistry 2e

13.1 Physical Properties of

The OH of an alcohol can have a big effect

Explain the differences