John E.

McMurry

http://www.cengage.com/chemistry/mcmurry

Chapter 17
Alcohols and Phenols

Paul D. Adams • University of Arkansas

2016 Nobel Prize: Supramolecules
Jean-Pierre Sauvage

Praser Ben Feringa

StoFddart
Molecular Machines and Robots
 Alcohols and Phenols
 Alcohols contain an OH group connected to a saturated C (sp3)
 They are important solvents and synthesis intermediates
 Phenols contain an OH group connected to a carbon in a benzene
ring
 Methanol, CH3OH, called methyl alcohol, is a common solvent, a fuel
additive, produced in large quantities
 Ethanol, CH3CH2OH, called ethyl alcohol, is a solvent, fuel, beverage
 Phenol, C6H5OH (“phenyl alcohol”) has diverse uses - it gives its
name to the general class of compounds
 OH groups bonded to vinylic sp2-hybridized carbons are called enols
 Why this Chapter?
 To begin to study oxygen-containing functional
groups

 These groups lie at the heart of biological

chemistry
 17.1 Naming Alcohols and
Phenols
 General classifications of alcohols based on
substitution on C to which OH is attached
 Methyl (C has 3 H’s), Primary (1°) (C has two
H’s, one R), secondary (2°) (C has one H, two
R’s), tertiary (3°) (C has no H, 3 R’s)
 IUPAC Rules for Naming
Alcohols
 Select the longest carbon chain containing the hydroxyl group,
and derive the parent name by replacing the -e ending of the
corresponding alkane with -ol
 Number the chain from the end nearer the hydroxyl group
 Number substituents according to position on chain, listing the
substituents in alphabetical order
명명법 우선순위
 Naming Phenols
 Use “phenol” (the French name for benzene) as
the parent hydrocarbon name, not benzene
 Name substituents on aromatic ring by their
position from OH
 17.2 Properties of Alcohols and
Phenols
 The structure around O of the alcohol or phenol is similar to that in water, sp3 hybridized.
 Alcohols and phenols have much higher boiling points than similar alkanes and alkyl
halides.
 A positively polarized OH hydrogen atom from one molecule is attracted to a lone pair
of electrons on a negatively polarized oxygen atom of another molecule.
 This produces a force that holds the two molecules together
 These intermolecular attractions are present in solution but not in the gas phase, thus
elevating the boiling point of the solution.
 Properties of Alcohols and
Phenols: Acidity and Basicity
 Weakly basic and weakly acidic
 Alcohols are weak Brønsted bases
 Protonated by strong acids to yield oxonium ions, ROH2+
 Alcohols and Phenols are Weak
Brønsted Acids
 Can transfer a proton to water to a very small extent
 Produces H3O+ and an alkoxide ion, RO, or a phenoxide
ion, ArO
Acidity Measurements
 The acidity constant, Ka, measures the extent to which a
Brønsted acid transfers a proton to water
[A] [H3O+]
Ka = ————— and pKa = log Ka
[HA]
 Relative acidities are more conveniently presented on a
logarithmic scale, pKa, which is directly proportional to the
free energy of the equilibrium
 Differences in pKa correspond to differences in free energy
 Table 17.1 presents a range of acids and their pKa values
pKa Values for Typical OH
Compounds
Relative Acidities of Alcohols
 Simple alcohols are about as acidic as water
 Alkyl groups make an alcohol a weaker acid
 The more easily the alkoxide ion is solvated by water the
more its formation is energetically favored
 Steric effects are important
 Inductive Effects Also Important in
Determining Acidity of Alcohols
 Electron-withdrawing groups make an alcohol a stronger
acid by stabilizing the conjugate base (alkoxide)
Generating Alkoxides from
Alcohols
 Alcohols are weak acids – requires a strong base to form
an alkoxide such as NaH, sodium amide NaNH2, and
Grignard reagents (RMgX)
 Alkoxides are bases used as reagents in organic
chemistry
 Phenol Acidity
 Phenols (pKa ~10) are much more acidic than alcohols (pKa ~ 16)
because of resonance stabilization of the phenoxide ion
 Phenols react with NaOH solutions (but alcohols do not), forming salts
that are soluble in dilute aqueous solution
 A phenolic component can be separated from an organic solution by
extraction into basic aqueous solution and is isolated after acid is
added to the solution
Nitro-Phenols
 Phenols with nitro groups at the ortho and para positions
are much stronger acids
17.3 Preparation of Alcohols: A
Review
 Alcohols are derived from many types of compounds
 The alcohol hydroxyl can be converted to many other
functional groups
 This makes alcohols useful in synthesis
2021 Nobel prize
Review: Preparation of Alcohols by
Regiospecific Hydration of Alkenes
 Hydroboration/oxidation: syn, anti-Markovnikov hydration
 Oxymercuration/reduction: Markovnikov hydration
1,2-Diols
 Review: Cis-1,2-diols from hydroxylation of an alkene with
OsO4 followed by reduction with NaHSO3
 Trans-1,2-diols from acid-catalyzed hydrolysis of epoxides
17.4 Alcohols from Carbonyl
Compounds: Reduction
 Reduction of a carbonyl compound in general gives an
alcohol
 Note that organic reduction reactions add the equivalent
of H2 to a molecule
Reduction of Aldehydes and
Ketones
 Aldehydes gives primary alcohols
 Ketones gives secondary alcohols
Reduction Reagent: Sodium
Borohydride
 NaBH4 is not sensitive to moisture and it does not reduce
other common functional groups
 Lithium aluminum hydride (LiAlH4) is more powerful, less
specific, and very reactive with water
 Both add the equivalent of “H-”
Mechanism of Reduction
 The reagent adds the equivalent of hydride to the carbon
of C=O and polarizes the group as well
Reduction of Carboxylic Acids
and Esters
 Carboxylic acids and esters are reduced to give primary
alcohols
 LiAlH4 is used because NaBH4 is not effective
Summary
 1. Naming
 2. Properties – Hydrogen bonding,
 Relative Acidity-Basicity
 3. Preparation
- Hydroboration/oxidation – Syn, Anti-M
- Oxymerculation/reduction - Markovnikov
- Diol – OsO4, Cis 1,2 diol
RCOOOH, Trans 1,2 diol
 4. Reduction – NaBH4, Aldehyde & Ketone, H2O
 LiAlH4, All carbonyl-, acid & ester
17.5 Alcohols from Carbonyl
Compounds: Grignard Reagents
 Alkyl, aryl, and vinylic halides react with magnesium in
ether or tetrahydrofuran to generate Grignard reagents,
RMgX
 Grignard reagents react with carbonyl compounds to yield
alcohols
Reactions of Grignard Reagents
with Carbonyl Compounds
Reactions of Esters and
Grignard Reagents
 Yields tertiary alcohols in which two of the carbon
substituents come from the Grignard reagent
 Grignard reagents do not add to carboxylic acids – they
undergo an acid-base reaction, generating the
hydrocarbon of the Grignard reagent
Grignard Reagents and Other Functional
Groups in the Same Molecule: Limitations
 Cannot be prepared if there are reactive functional groups
in the same molecule, including proton donors
RMgX & RLi
Mechanism of the Addition of a
Grignard Reagent
 Grignard reagents act as nucleophilic carbon anions
(carbanions = : R) in adding to a carbonyl group
 The intermediate alkoxide is then protonated to produce
the alcohol
 17.6 Reactions of Alcohols
 Conversion of alcohols into alkyl halides:
- 3˚ alcohols react with HCl or HBr by SN1 through carbocation
intermediate
- 1˚ and 2˚ alcohols converted into halides by treatment with
SOCl2 or PBr3 via SN2 mechanism
Reactions of 1˚ and 2˚
alcohols
Conversion of Alcohols into
Tosylates
 Reaction with p-toluenesulfonyl chloride (tosyl chloride, p-
TosCl) in pyridine yields alkyl tosylates, ROTos
 Formation of the tosylate does not involve the C–O bond
so configuration at a chirality center is maintained
 Alkyl tosylates react like alkyl halides
Stereochemical Uses of
Tosylates
 The SN2 reaction of an alcohol via an alkyl halide
proceeds with two inversions, giving product with same
arrangement as starting alcohol
 The SN2 reaction of an alcohol via a tosylate, produces
inversion at the chirality center
Dehydration of Alcohols to Yield
Alkenes
 The general reaction: forming an alkene from an alcohol
through loss of O-H and H (hence dehydration) of the
neighboring C–H to give  bond
 Specific reagents are needed
Acid- Catalyzed Dehydration
 Tertiary alcohols are readily dehydrated with acid
 Secondary alcohols require severe conditions (75%
H2SO4, 100°C) - sensitive molecules do not survive
 Primary alcohols require very harsh conditions –
impractical
 Reactivity is the result of the nature of the carbocation
intermediate
Dehydration with POCl3
 Phosphorus oxychloride in the amine solvent
pyridine can lead to dehydration of secondary and
tertiary alcohols at low temperatures
 An E2 reaction via an intermediate ester of POCl 2
(see Figure 17.7)
Incorporation of Alcohols into
Esters
17.7 Oxidation of Alcohols
 Can be accomplished by inorganic reagents, such as
KMnO4, CrO3, and Na2Cr2O7 or by more selective,
expensive reagents
Oxidation of Primary Alcohols
 To aldehyde: pyridinium chlorochromate (PCC,
C5H6NCrO3Cl) in dichloromethane
 Other reagents produce carboxylic acids
Oxidation of Secondary
Alcohols
 Effective with inexpensive reagents such as Na2Cr2O7 in
acetic acid
 PCC is used for sensitive alcohols at lower temperatures
Mechanism of Chromic Acid
Oxidation
 Alcohol forms a chromate ester followed by
elimination with electron transfer to give ketone
 The mechanism was determined by observing
the effects of isotopes on rates
PCC(Pyridinium Chromate Chloride
17.8 Protection of Alcohols
 Hydroxyl groups can easily transfer their proton to a basic
reagent
 This can prevent desired reactions
 Converting the hydroxyl to a (removable) functional group
without an acidic proton protects the alcohol
Methods to Protect Alcohols
 Reaction with chlorotrimethylsilane in the presence of
base yields an unreactive trimethylsilyl (TMS) ether
 The ether can be cleaved with acid or with fluoride ion to
regenerate the alcohol
Protection-Deprotection
 An example of TMS-alcohol protection in a synthesis
Trialkyl Silyl Protecting Group
17.9 Phenols and Their Uses
 Industrial process from readily available cumene
 Forms cumene hydroperoxide with oxygen at
high temperature
 Converted into phenol and acetone by acid
Mechanism of Formation of
Phenol
17.10 Reactions of Phenols
 The hydroxyl group is a strongly activating, making
phenols substrates for electrophilic halogenation, nitration,
sulfonation, and Friedel–Crafts reactions
 Reaction of a phenol with strong oxidizing agents yields a
quinone
 Fremy's salt [(KSO3)2NO] works under mild conditions
through a radical mechanism
Quinones in Nature
 Ubiquinones mediate electron-transfer processes
involved in energy production through their redox
reactions
A Strong oxidizing agent
17.11 Spectroscopy of Alcohols
and Phenols
 Characteristic O–H stretching absorption at 3300 to 3600
cm1 in the infrared
 Sharp absorption near 3600 cm-1 except if H-bonded: then
broad absorption 3300 to 3400 cm1 range
 Strong C–O stretching absorption near 1050 cm1 (See
Figure 17.11)
 Phenol OH absorbs near 3500 cm-1
Nuclear Magnetic Resonance
Spectroscopy
 13
C NMR: C bonded to OH absorbs at a lower field, 
50 to 80
 1
H NMR: electron-withdrawing effect of the nearby
oxygen, absorbs at  3.5 to 4 (See Figure 17-13)
 Usually no spin-spin coupling between O–H proton and
neighboring protons on C because of exchange reactions
with moisture or acids
 Spin–spin splitting is observed between protons on the
oxygen-bearing carbon and other neighbors
 Phenol O–H protons absorb at  3 to 8
Mass Spectrometry
 Alcohols undergo alpha cleavage, a C–C bond nearest
the hydroxyl group is broken, yielding a neutral radical
plus a charged oxygen-containing fragment
 Radical cation alcohols undergo dehydration to yield an
alkene radical anion
Let’s Work a Problem

Predict the product from reaction of the following

substance with NaBH4; then H3O+.
Answer

There is no product formed with this series of

reagents because NaBH4 reduces esters very
slowly and does not reduce carboxylic acids at all.
 New Normal –Chemical Technology

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