ch13 Alcoholes Klein PDF

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 Klein, Organic Chemistry 2e
• Hydroxyl groups in natural compounds
• Phenols possess a hydroxyl group directly attached to an
aromatic ring
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
the parent name or just before the -ol suffix
1. Identify the parent chain
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
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
• 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
• Like halides, alcohols are often classified by the type of
carbon they are attached to
• WHY do we use these classifications?
• When an –OH group is attached to a benzene ring, the
parent name is phenol
• Practice with SkillBuilder 13.1

• Name the following molecule
• Draw the most stable chair conformation for (cis)-1-

isopropyl-1,2-cyclohexanediol
13.1 Commercially Important Alcohols
• Methanol (CH3OH) is the simplest alcohol
• With a suitable catalyst, about 2 billion gallons of
methanol is made industrially from CO2 and H2 every
year
• Methanol is poisonous, but it has many uses
1. Solvent
2. Precursor for chemical syntheses
3. Fuel
• 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?
• 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
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
• 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
• 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 the size of the
hydrophobic group increases
• An alcohol’s 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 region.
WHY?
• 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
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

• 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
– Resonance
– Explain why phenol is 100 million times more acidic than

cyclohexanol
– Show all relevant resonance contributors
• Given the relatively low pKa of phenols, will NaOH be a
strong enough base to deprotonate a phenol?
– Induction: unless there is an electronegative group nearby,
induction won’t be very significant
– Orbital: in what type of orbital do the alkoxide electrons

reside? How does that effect acidity?
• 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
• Solvation explains the difference in acidity
• Draw partial charges on the solvent molecules to show

how solvation is a stabilizing effect
• Use ARIO and solvation to rank the following molecules
in order of increasing pKa
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
• The SN1 process generally uses a weak nucleophile

(H2O), which makes the process relatively slow
• Why isn’t a stronger nucleophile (-OH) used under SN1
conditions?
• 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?
• Practice with checkpoints 13.7 and 13.8
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?
• For oxidation states, we imagine the bonds breaking
heterolytically, and the electrons go to the more
electronegative atom
• 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?
• 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?
• 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)
• Reagents that can donate a hydride are generally good
reducing agents
2. Sodium borohydride
• Reagents that can donate a hydride are generally good
reducing agents
3. Lithium aluminum hydride (LAH)
• 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?
• Hydride delivery agents will somewhat selectively
reduce carbonyl compounds
• The reactivity of hydride delivery agents can be fine-
tuned by using derivatives with varying R-groups
– Alkoxides
– Cyano
– Sterically hindered groups
• LAH is strong enough to also reduce esters and
carboxylic acids, whereas NaBH4 is generally not
• To reduce an ester, 2 hydride equivalents are needed
• To reduce an ester, 2 hydride equivalents are needed
• Which steps in the mechanism are reversible?
• Predict the products for the following processes

13.5 Preparation of Diols
• Diols are named using the same method as alcohols,
except the suffix, “diol” is used
• If two carbonyl groups are present, and enough moles
of reducing agent are added, both can be reduced
• Recall the methods we discussed in chapter 9 to
convert an alkene into a diol
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?
• 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.?
• If the Grignard reagent reacts with a carbonyl
compound, an alcohol can result
• Note the similarities between the Grignard and LAH

mechanisms
• 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 can’t be used as the solvent, what solvent is

appropriate?
• What techniques are used to keep atmospheric
moisture out of the reaction?
• 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
• Design a synthesis for the following molecules starting
from an alkyl halide and a carbonyl, each having 5
carbons or less
13.7 Protection of Alcohols
• Consider the reaction below. WHY won’t 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
• A three-step process is required to achieve the desired
overall synthesis
• One such protecting group is trimethylsilyl (TMS)
• The TMS protection step requires the presence of a

base. Propose a mechanism
• 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
• The TMS group can later be removed with H3O+ or F-
• TBAF is often used to supply fluoride ions
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
– Food preservatives, etc.
13.9 Reactions of Alcohols
• Recall this SN1 reaction from section 7.5
• For primary alcohols, the reaction occurs by an SN2
• 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
• SOCl2 can also be used to convert an alcohol to an alkyl
chloride
• 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
• Fill in the necessary reagents for the conversions below
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
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
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
• 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
• Tertiary alcohols generally do not undergo oxidation.
WHY?
• There are two main methods to produce the most

common oxidizing agent, chromic acid
• When chromic acid reacts with an alcohol, there are
two main steps
• Chromic acid will generally oxidize a primary alcohol to
a carboxylic acid
• PCC (pyridinium chlorochromate) can be used to stop

at the aldehyde
• PCC (pyridinium
chlorochromate) is
generally used with
methylene chloride as
the solvent
• Both oxidizing agents

will work with
secondary alcohols

• Predict the product for the following reaction
13.11 Biological Redox Reactions
• Nature employs reducing and oxidizing agents
• They are generally complex and selective. WHY?
• NADH is one such reducing agent
• 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?
• NAD+ can undergo the reverse process
• The NADH / NAD+

interconversion plays a
big role in metabolism
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
• Phenol oxidizes to form benzoquinone, which in turn
can be reduced to hydroquinone
• Quinones are found everywhere in nature

• They are ubiquitous
• 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?
• Ubiquinone catalysis:
13.13 Synthetic Strategies
• Recall some functional group conversions we learned
• Classify the functional groups based on oxidation state
• Give necessary reagents for the following conversions
• Recall the C-C bond forming reactions we learned
• What if you want to convert an aldehyde into a ketone?
• What reagents are needed for the following

conversion?
• Practice with conceptual checkpoint 13.27 and

SkillBuilder 13.9
Additional Practice Problems
• Name the following molecule
• Draw (1R,2R)-1-(3,3-dimethylbutyl)-3,5-cyclohexadien-
1,2-diol
• Use ARIO and solvation to rank the following molecules
in order of increasing pKa
• Predict the products for the following processes
• Design a synthesis for the following molecule starting
from an alkyl halide and a carbonyl, each having 5
carbons or less
• Give necessary reagents for the multi-step synthesis
below

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Organic Chemistry

• Hydroxyl groups are extremely common in natural

• R or S configurations should be shown at the beginning

• Common names for some alcohols are also frequently

• WHY do we use these classifications?

• Practice with SkillBuilder 13.1

• Draw the most stable chair conformation for (cis)-1-

• Explain the differences

• Alcohols with small carbon chains are miscible in water

• Alcohols with large carbon chains do not readily mix

• WHY are molecules with large hydrophobic groups

• It has a good combination of hydrophobic and

• A preferred choice to create an alkoxide is to treat the

• Practice with conceptual checkpoint 13.4

– Explain why phenol is 100 million times more acidic than

– Orbital: in what type of orbital do the alkoxide electrons

• ARIO cannot be used to explain the difference

• Draw partial charges on the solvent molecules to show

• We saw that the substitution can occur by SN1 or SN2

• The SN1 process generally uses a weak nucleophile

• Recall that acid-catalyzed hydration proceeds through a

• Is the conversion from formic acid  carbon dioxide an

• Is the reducing agent oxidized or reduced?

– Forceful conditions (high temperature and/or high pressure)

• How can LAH be used with water if it reacts with water?

• Which steps in the mechanism are reversible?

• Practice with SkillBuilder 13.4

• How does the oxidation state of the carbon change

• The carbon atom is not able to effectively stabilize the

• Note the similarities between the Grignard and LAH

• If water can’t be used as the solvent, what solvent is

• With an ester substrate, excess Grignard reagent is

• The alcohol can act as an acid, especially in the

• The TMS protection step requires the presence of a

• Practice with conceptual checkpoint 13.18

• Acetone is a useful byproduct

• For primary alcohols, the reaction occurs by an SN2

• Recall from section 7.8 that the –OH group can be

• Note that the last step of the SOCl2 and PBr3

• E2 reactions do not involve rearrangements. WHY?

• Oxidation of secondary alcohols produces a ketone

• There are two main methods to produce the most

• PCC (pyridinium chlorochromate) can be used to stop

• Both oxidizing agents

• Practice with SkillBuilder 13.7

• This is one way nature

• The NADH / NAD+

• Yet, phenol is even more readily oxidized than primary

• Quinones are found everywhere in nature

• Where in a cell do you think unbiquinones are most

• Practice with SkillBuilder 13.8

• What reagents are needed for the following

• Practice with conceptual checkpoint 13.27 and

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