Transcript Alcohols and Phenols

CH 17: Alcohols and Phenols
Renee Y. Becker
CHM 2211
Valencia Community College
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Alcohols and Phenols
• Alcohols contain an OH group connected to a saturated
C (sp3)
– They are important solvents and synthesis
intermediates
• Enols also contain an OH group connected to an
unsaturated C (sp2)
• Phenols contain an OH group connected to a carbon in a
benzene ring
OH
an enol
2
Alcohols and Phenols
• 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
3
Naming Alcohols
• General classifications of alcohols based on
substitution on C to which OH is attached
4
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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Many Alcohols Have Common Names
• These are accepted by IUPAC
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Example 1: Give the IUPAC names for these compounds
OH OH
3
1
HO
2
OH
OH
4
H3C
CH3
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Example 2: Draw the following structures
• 2-Ethyl-2-buten-1-ol
• 3-Cyclohexen-1-ol
• 1,4-Pentanediol
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Naming Phenols
• Use “phene” (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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Properties of Alcohols and Phenols: Hydrogen Bonding
• 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
11
Alcohols Form Hydrogen Bonds
• 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
12
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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Alchols 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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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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Stronger acid
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Inductive Effects
• Electron-withdrawing groups make an alcohol a
stronger acid by stabilizing the conjugate base
(alkoxide)
Stronger acid
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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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1
2
3
Example 3:
+
CH3OH
NaH
+
CH3CH2OH
NaNH2
OH
+
4
CH3Li
OH
+
CH3MgBr
5
2
OH
+
2K
20
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 soluble salts that are soluble in dilute aqueous
• 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
21
Substituted Phenols
• Can be more or less acidic than phenol itself
• An electron-withdrawing substituent makes a
phenol more acidic by delocalizing the negative
charge
• Phenols with an electron-donating substituent
are less acidic because these substituents
concentrate the charge
22
Example 4:
p-Nitrobenzyl alcohol is more acidic than
benzyl alcohol. Explain.
OH
OH
O2N
23
Nitro-Phenols
• Phenols with nitro groups at the ortho and para
positions are much stronger acids
• The pKa of 2,4,6-trinitrophenol is 0.6, a very
strong acid
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Preparation of Alchols: an Overview
• 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
25
Review: Preparation of Alcohols by Regiospecific Hydration of Alkenes
• Hydroboration/oxidation: syn, non-Markovnikov hydration
• Oxymercuration/reduction: Markovnikov hydration
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Preparation of 1,2-Diols
• Review: Cis 1,2-diols from hydroxylation of an alkene
with OsO4 followed by reduction with NaHSO3
• In Chapter 18: Trans-1,2-diols from acid-catalyzed
hydrolysis of epoxides
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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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Catalytic Hydrogenation:
O
RCH
aldehyde
+
H2
Pt, Pd or Ni
RCH2OH
primary alcohol
O
Pt, Pd or Ni
RCR' + H2
ketone
OH
RCHR'
secondary alcohol
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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-”
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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
Not a complete mechanism!!!
33
Reduction of Carboxylic Acids and Esters
• Carboxylic acids and esters are reduced to give
primary alcohols
• LiAlH4 is used because NaBH4 is not effective
34
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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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
37
Examples of Reactions of Grignard Reagents with Carbonyl
Compounds
• Formaldehyde reacts with Grignard
reagents to yield primary alcohols.
• Aldehydes react with Grignard reagents to
yield secondary alcohols.
• Ketones yield tertiary alcohols.
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Examples of Reactions of Grignard Reagents with Carbonyl
Compounds
39
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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Synthesis of Diols
Catalytic hydrogenation:
O
O
HCCH2CHCH2CH
OH
H2
Ni, 125oC
OH
CH2CH2CHCH2CH2
CH3
CH3
3-Methylpentanedial
3-Methyl-1,5-pentanediol
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Some Reactions of Alcohols
• Two general classes of reaction
– At the carbon of the C–O bond
– At the proton of the O–H bond
45
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
46
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 (See Figure 17-5)
• Note that Zaitsev’s rule is followed!
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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 17.6)
N
pyridine
Follows an E2 mechanism
49
Mechanism 1: Dehydration of Alcohol (2 or 3 )
N
H
O+
OH
O
+
POCl2
+
Cl–
P
Cl
Cl
Cl
H
OPOCl2
N
+
OPOCl2
+
+
HCl
H
N
50
Conversion of Alcohols into Alkyl Halides
• 3° alcohols are converted by HCl or HBr at low
temperature (Figure 17.7)
• 1° and alcohols are resistant to acid – use SOCl2
or PBr3 by an SN2 mechanism (ether solvent)
51
Mechanism 2:
52
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
53
Stereochemical Uses of Tosylates
• The SN2 reaction of an alcohol via a tosylate,
produces inversion at the chiral 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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Oxidation of Alcohols
• Can be accomplished by inorganic
reagents, such as KMnO4, CrO3, and
Na2Cr2O7 or by more selective, expensive
reagents
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Oxidation of Primary Alcohols
• To aldehyde: pyridinium chlorochromate
(PCC, C5H6NCrO3Cl) in dichloromethane
– Other reagents produce carboxylic acids
• Converts secondary alcohol to ketone
59
Oxidation of Primary Alcohols
• Jones’ Reagent: CrO3 in aqueous sulfuric
acid.
– Oxidizes primary alcohols to carboxylic acids:
All of the oxidations occur via an E2 mechanism.
60
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
61
Oxidation of Secondary Alcohols
• Na2Cr2O7 in aqueous acetic acid is an
inexpensive oxidizing agent:
CH3
OH
Na2Cr2O7
acetic acid
4-tert-Methylcyclohexanol
CH3
O
4-tert-Methylcyclohexanone
62
Example 5: Predict the major organic product
OH
Cl
K2Cr2O7
acetic acid
OH
PCC
CH2Cl2
63
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
64
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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Protection-Deprotection
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Preparation and Uses of Phenols
• Industrial process from readily available cumene
• Forms cumene hydroperoxide with oxygen at
high temperature
68
Laboratory Preparation of Phenols
• From aromatic sulfonic acids by melting with
NaOH at high temperature
• Limited to the preparation of alkyl-substituted
phenols
69
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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