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Alcohols and Phenols
Alcohols contain an OH group connected to a 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
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Why this Chapter?
To begin to study oxygen-containing
functional groups
These groups lie at the heart of biological
chemistry
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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),
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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
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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
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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
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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
+
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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
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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
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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
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Inductive Effects
Electron-withdrawing groups make an alcohol a
stronger acid by stabilizing the conjugate base
(alkoxide)
(alcohol) (alcohol)
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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
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Phenol Acidity
Phenols (pKa ~10) are much more acidic than alcohols (pKa ~ 16) due to 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
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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
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Review: Preparation of Alcohols by
Regiospecific Hydration of Alkenes
Hydroboration/oxidation: syn, non-Markovnikov hydration
Oxymercuration/reduction: Markovnikov hydration
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MARKOVNIKOV’S RULE
Named for Vladimir W. Markovnikov (1838–1904),
this rule originally stated that the addition of HX (Xhalogen) to an
unsymmetrically substituted alkene occurs with attachment of the hydrogen
to the carbon atom of the double bond having more hydrogens.
Markovnikov addition: (a) Markovnikov product via a tertiary carbocation and
(b) anti-Markovnikov product (minor product) via a much less stable primary
carbocation.
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Addition of non-symmetrical reagent to a non-symmetrical
alkene, then two isomeric products that are constitutional
isomers can be obtained.
For example,
the reaction of HCl with propene gives 1-chloropropane and
2-chloropropane.
Normally, 2-chloropropane is the major product.
Since one product is favoured over the other, the reaction is
said to be regioselective.
If 2-chloropropane were the only product then the reaction is
said to be regiospecific
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1,2-Diols
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
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17.4 Alcohols from Reduction of
Carbonyl Compounds
Reduction of a carbonyl compound in general gives an alcohol
Note that organic reduction reactions add the equivalent of H2 to a molecule
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Reduction of Aldehydes and
Ketones
Aldehydes gives primary alcohols
Ketones gives secondary alcohols
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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-” (+1H)
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Mechanism of Reduction
The reagent adds the equivalent of hydride to the carbon of C=O and polarizes the group as well
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Reduction of Carboxylic Acids
and Esters
Carboxylic acids and esters are reduced to give
primary alcohols (+2H)
LiAlH4 is used because NaBH4 is not effective
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17.5 Alcohols from Reaction of Carbonyl
Compounds with 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
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Reactions of Esters and
Grignard Reagents
Yields tertiary alcohols in which two of the substituents carbon 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
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Grignard Reagents and Other Functional
Groups in the Same Molecule
Can't be prepared if there are reactive functional
groups in the same molecule, including proton donors
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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
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- 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
Conversion of alcohols into
alkyl halides:
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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
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Stereochemical Uses of Tosylates
The SN2 reaction of an alcohol via a tosylate,
produces inversion at the chirality center
The SN2 reaction of an alcohol via an alkyl halide
proceeds with two inversions, giving product with
same arrangement as starting alcohol
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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
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Acid- Catalyzed Dehydration
Tertiary alcohols are readily dehydrated with acid
Secondary alcohols require severe conditions (75% H2SO4, 100°C) - sensitive molecules don't survive
Primary alcohols require very harsh conditions – impractical
Reactivity is the result of the nature of the carbocation intermediate
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Figure 17.6
Mechanism of the acid-
catalyzed dehydration of
an alcohol to yield an
alkene.
The process is an E1
reaction and involves a
carbocation intermediate.
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Dehydration with POCl3
Phosphorus oxychloride in the amine solvent pyridine
can lead to dehydration of secondary and tertiary
alcohols at low temperatures
An E2 via an intermediate ester of POCl2 (see Figure
17.7)
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Fjgure 17.7
Mechanism of the dehydration
of secondary and tertiary
alcohols by reaction with
POCI3 in pyridine.
The reaction is an E2 process.
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17.7 Oxidation of Alcohols
Can be accomplished by inorganic reagents, such as KMnO4, CrO3, and Na2Cr2O7 or by more selective,
expensive reagents
Pyridinium ChloroChromate
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Oxidation of Primary Alcohols
To aldehyde: pyridinium chlorochromate (PCC,
C5H6NCrO3Cl) in dichloromethane
Other reagents produce carboxylic acids
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Oxidation of Secondary Alcohols
Effective with inexpensive reagents such as Na2Cr2O7 in acetic acid
PCC is used for sensitive alcohols at lower temperatures
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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
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How Alcohol Is Metabolized in
the Human Body
Alcohol dehydrogenase converts methanol into
formaldehyde (H2CO)
and aldehyde dehydrogenase turns this formaldehyde into a
formic acid radical.
Both formaldehyde and formic acid are highly poisonous and
quickly dead to blindness and death.
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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
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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
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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
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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
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Quinones in Nature
Ubiquinones mediate electron-transfer processes
involved in energy production through their redox
reactions
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17.11 Spectroscopy of Alcohols
and Phenols Characteristic O–H stretching absorption at 3300 to
3600 cm1 in the infrared
Sharp absorption near 3600 cm-1 except if H-bonded:
then broad absorption 3300 to 3400 cm1 range
Strong C–O stretching absorption near 1050 cm1
(See Figure 17.11)
Phenol OH absorbs near 3500 cm-1
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Nuclear Magnetic Resonance
Spectroscopy
13C NMR: C bonded to OH absorbs at a lower field, 50 to 80
1H 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 due to 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
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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
Alcohols undergo dehydration to yield an alkene radical anion