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Organic Chemistry IIOrganic Chemistry II
Alcohols, Phenols, Thiols Alcohols, Phenols, Thiols
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Chapter ObjectivesChapter Objectives
• NomenclatureNomenclature
• PropertiesProperties
• PreparationPreparation
• ReactionReaction
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Alcohols and PhenolsAlcohols and Phenols
•Important solvents and intermediates•Phenols contain an OH group
connected to a carbon in a benzene ring
•Methanol, CH3OH, common name is methyl alcohol, a solvent, a fuel additive, produced in large quantities
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•Ethanol, CH3CH2OH, common name is ethyl alcohol, a solvent, fuel, beverage, produced in large quantities
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Alcohols, Phenols, Thiols, Alcohols, Phenols, Thiols, EthersEthers• Considered derivatives of waterConsidered derivatives of water
OH SH OH SH
O S
alcohol thiol phenol thiophenol
ether sulfide
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Nomenclature of AlcoholsNomenclature of Alcohols
•Derivatives of alkane with –ol suffix
•Name longest chain containing OH
•Number the chain starting nearest the carbon bearing the OH group
•Number substituents, name, and list alphabetically
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ExamplesExamples
OH
OH
OH
OH
propanol
trans-1,2-cyclopentanediol
3-ethylheptan-3-ol
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Classification of AlcoholsClassification of Alcohols•Primary – OH is attached to a carbon
bearing one carbon atom
•Secondary – OH is attached to a carbon bearing two carbon atoms
•Tertiary – OH is attached to a carbon bearing three carbon atoms
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ExamplesExamples
OH
OH
OH
primary alcohol
secondary alcohol
tertiary alcohol
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Common NamesCommon Names
OH
OH
OHOH OH
OH
OH
OH
benzyl alcohol allyl alcohol
t-butyl alcohol
ethylene glycol
glycerol
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PhenolsPhenols•Common natural source – coal tar•Found in many plants
OH
OH
CO2H
OH
CO2CH3
OH
R
OHcoal tar
willow bark
oil of wintergreen
bioactive ingredient poison ivy and oak
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PhenolsPhenolsOH
OMe
OH
OMe
OH
OMe
O O
OH
C5H11
eugenol (oil of clove) isoeugenol (oil of nutmeg)
vanillintetrahydrocannabinol
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Nomenclature of PhenolsNomenclature of 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
CH3
OH Cl
OH
OH
NO2O2N
p-methylphenol o-chlorophenol 2,4-dinitrophenol
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Common NamesCommon Names• Many common names in use
OH
CH3
OH
CH3
OH
CH3
OH
OH
OH
OH
OH
OH
o-cresol m-cresol p-cresol
catecholresorcinol
hydroquinone
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Nomenclature of ThiolsNomenclature of Thiols•Same naming system as alcohols
•Suffix is –thiol
•Sometimes named as mercaptans
SH
SH
CH3
OH
SH
isopropyl thiol cis-2-methylcycloheptane thiol
m-mercaptophenol
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Biosynthesis of EthanolBiosynthesis of Ethanol(Fermentation)(Fermentation)
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C6H12O6
glucose
CH3
O
O
OH
pyruvate
CH3
O
O
OH
pyruvate
CH3CH2OH
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PropertiesProperties
• Alcohols and phenols are similar to water form strong H-bonds
• Giving higher boiling points than the corresponding hydrocarbon
• Thiols do not form H-bonds (EN of S is low)
• Alcohols and phenols are weakly basic
• Alcohols and phenols are weakly acidic
• Phenols and Thiols are more acidic than water
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Acidity ConstantsAcidity ConstantsOH
OH
CH3
OH
O2N
OH
CH3CH2OH
H2O
CH3OH
CH3SH
pKa = 18
pKa = 16
pKa = 15.7
pKa = 15.5
pKa = 10.3
pKa = 10.2
pKa = 9.9
pKa = 7.2decreasing acidity
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Acidity of AlcoholsAcidity of Alcohols•Do not react with amines or
NaHCO3
•Limited reactivity with NaOH
•React with alkali metals Na, K
•React with strong bases like NaH or NaNH2 or RLi and RMgBr
•Forms the alkoxide (RO-1)
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Reactions with BasesReactions with BasesROH + NH3 No Reaction
ROH + NaHCO3 No Reaction
ROH + NaOH RO- + H2O
ROH + NaH RO- + H2
ROH + Na RO- + H2
ROH + RLi RO- + RH
ROH + RMgX RO- + RH
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Acidity of PhenolsAcidity of Phenols
• ArOH is more acidic than ROHArOH is more acidic than ROH• Soluble in dilute NaOHSoluble in dilute NaOH• Anion is resonance stabilizedAnion is resonance stabilized• EWG make phenols more acidic than phenolEWG make phenols more acidic than phenol• EDG make phenols less acidic than phenolEDG make phenols less acidic than phenol
OH O O
NaOH -
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Alcohols an OverviewAlcohols an Overview• Alcohols are derived from many types of
compounds
• Alkenes, alkyl halides, ketones, esters, aldehydes, and carboxylic acids can provide the alcohol
• Alcohols are among most common natural materials
• The alcohol hydroxyl can be converted to many other functional groups
• This makes alcohols useful in synthetic planning
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Preparation
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Preparation of AlcoholsPreparation of Alcohols
•Hydration of Alkenes•BH3/THF followed by H2O2 in
NaOH•Hg(OAc)2 followed by NaBH4
•OsO4 followed by NaHSO3 (cis-1,2-diols)
•RCO3H followed by aqueous acid (trans-1,2-diols)
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• From Aldehydes and Ketones• Reduction with NaBH4
– Reduces alpha beta unsaturated carbonyls as well
Reduction with LiAlH4
– Doesn’t touch alpha beta unsaturated carbonyls
• From Esters– Reduction with LiAlH4 (LAH)– No reaction with NaBH4
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Reduction of KetonesReduction of Ketones
O
OH
OH
OH
LAH
NaBH4
+
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Preparation of AlcoholsPreparation of Alcohols• From carboxylic acids
– Reduction with LiAlH4 is slow
– Reduction with NaBH4 doesn’t occur
– Reduction with BH3 is preferred method
RCO2HLiAlH4
RCH2OHslow
RCO2HNaBH4
No Reaction
RCO2H RCH2OHBH3
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From Alkyl halides•RX + Mg provides the Grignard
reagent
•Grignard reagents react with carbonyls to provide the alcohols
CH3Br + Mg CH3-Mg-Br
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Grignard Reactions
•With aldehydes or ketones
•With esters
O OH
CH3
O
H
OH
H
CH3
1. CH3MgBr
2. H3O+
1. CH3MgBr
2. H3O+
O
OMe
OH
CH3
CH3
1. CH3MgBr
2. H3O+
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Grignard Reactions
•With carboxylic acids•Grignard's are strong bases
•React with the acidic proton
O
OH
O
OH
1. CH3MgBr
2. H3O+
+ CH4
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Reactions
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Reactions of Alcohols
•Alcohols react at– the O-H bond– the C-O bond
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Alcohols to Alkyl Halides
OH Cl
OH Br
OH Cl
OH Cl
HCl
HBr
tertiary alcohols
primary or secondary alcohols
SOCl2
PBr3
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Alcohols to Alkenes
• Dehydration
• Acid catalyzed reaction
• Excellent reaction for tertiary alcohols (E1)
• Provides the Zaitsev product
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•When the substrate is asymmetric, regioselectivity is determined by Zaitsev’s rule
• The one -step mechanisms is E2 reaction and two step reaction mechanism is called E1 reaction, respectively.
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•It is the preference of one direction of chemical bond making or breaking over all other possible directions
What is regioselectivity
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•In chemistry, Zaitsev's rule, Saytzeff's rule or Saytsev's rule is a rule that states
“that if more than one alkene can be
formed during dehalogenation by an
elimination reaction the more stable
alkene is the major product”
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What is Zaitsev’s ruleWhat is Zaitsev’s rule
•In general, the compound that has a more highly substituted C=C double bond is more stable.
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Who is then stable
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Alcohol to AlkeneAlcohol to Alkene
• Milder reaction developed
• E2 process
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Alcohols to Esters• Alcohols react with carboxylic acids
• Reaction is acid catalyzed
• Alcohols react with acid chlorides
• Reaction is base catalyzed
R
O
OH R
O
OR
R
O
Cl R
O
OR
ROH/H+
H3O+
SOCl2
ROH/pyridine
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Alcohols to Tosylate Esters • 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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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 Oxidation of Primary AlcoholsAlcohols•To aldehyde: pyridinium chlorochromate
(PCC = C5H6NCrO3Cl) in dichloromethane•Other reagents produce carboxylic acids
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Oxidation of Secondary Oxidation of Secondary AlcoholsAlcohols• Effective with inexpensive reagents such as
Na2Cr2O7 in acetic acid• PCC is used for sensitive alcohols at lower
temperatures
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Preparation and Uses of Preparation and Uses of PhenolsPhenols • 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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Industrial Preparation of Industrial Preparation of PhenolPhenol
Cl OHNaOH/heat
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Laboratory Preparation of Laboratory Preparation of PhenolsPhenols• From aromatic sulfonic acids by melting
with NaOH at high temperature• Limited to the preparation of alkyl-
substituted phenols
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Reactions of PhenolsReactions 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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