Download Organic Chemistry II Introduction

Organic Chemistry II
Alcohols, Phenols, Thiols, Ethers,
and Sulfides
Dr. Ralph C. Gatrone
Department of Chemistry and Physics
Virginia State University
Spring, 2011
1
Chapter Objectives
• Nomenclature
• Properties
• Preparation
• Reactions
• Spectroscopy
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2
Alcohols 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
• Ethanol, CH3CH2OH, common name is
ethyl alcohol, a solvent, fuel, beverage,
produced in large quantities
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Alcohols, Phenols, Thiols, Ethers
• Considered derivatives of water
alcohol
thiol
O
ether
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OH
SH
OH
phenol
SH
thiophenol
S
sulfide
4
Nomenclature 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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Examples
propanol
OH
OH
trans-1,2-cyclopentanediol
OH
OH
3-ethylheptan-3-ol
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Classification 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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Examples
OH
primary alcohol
secondary alcohol
OH
OH
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tertiary alcohol
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Common Names
OH
OH
OH
benzyl alcohol
OH
allyl alcohol
HO
HO
OH
OH
glycerol
ethylene glycol
t-butyl alcohol
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Phenols
• Common natural source – coal tar
• Found in many plants
OH
OH
CO2CH3
oil of wintergreen
OH
coal tar
OH
OH
CO2H
R
willow bark
bioactive ingredient
poison ivy and oak
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Phenols
OH
OH
OMe
OMe
eugenol (oil of clove)
isoeugenol (oil of nutmeg)
OH
OMe
O
OH
O
C5H11
tetrahydrocannabinol
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vanillin
11
Nomenclature 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
OH
H3C
p-methylphenol
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OH
Cl
OH
o-chlorophenol
O2N
NO2
2,4-dinitrophenol
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Common Names
• Many common names in use
OH
OH
OH
H3C
CH3
CH3
o-cresol
p-cresol
m-cresol
OH
OH
OH
HO
OH
OH
catechol
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resorcinol
hydroquinone
13
Nomenclature of Thiols
• Same naming system as alcohols
• Suffix is –thiol
• Sometimes named as mercaptans
SH
SH
CH3
isopropyl thiol
cis-2-methylcycloheptane thiol
OH
SH
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m-mercaptophenol
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Biosynthesis of Ethanol
(Fermentation)
O
OH
H3C
C6H12O6
O
glucose
pyruvate
O
OH
H3C
CH3CH2OH
O
pyruvate
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Properties
• 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 Constants
OH
pKa = 18
CH3CH2OH
pKa = 16
H2O
pKa = 15.7
CH3OH
pKa = 15.5
pKa = 10.3
CH3SH
OH
pKa = 10.2
H3C
OH
pKa = 9.9
OH
pKa = 7.2
decreasing acidity
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O2N
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Acidity 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 Bases
ROH + NH3
ROH + NaHCO3
No Reaction
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 Phenols
•
•
•
•
•
ArOH is more acidic than ROH
Soluble in dilute NaOH
Anion is resonance stabilized
EWG make phenols more acidic than phenol
EDG make phenols less acidic than phenol
O
OH
NaOH
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O
-
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Alcohols 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 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)
• 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 Ketones
OH
OH
NaBH4
O
+
OH
LAH
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Preparation of Alcohols
• From carboxylic acids
– Reduction with LiAlH4 is slow
– Reduction with NaBH4 doesn’t occur
– Reduction with BH3 is preferred method
LiAlH4
RCO2H
slow
NaBH4
RCO2H
RCH2OH
No Reaction
BH3
RCO2H
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RCH2OH
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Preparation of Alcohols
• From Alkyl Halides
• RX + Mg provides the Grignard reagent
• Grignard reagents react with carbonyls to
provide the alcohols
CH3Br + Mg
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CH3-Mg-Br
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Grignard Reactions
• with aldehydes or
O
1. CH3MgBr
ketones
2. H3O+
O
1. CH3MgBr
OH
CH3
OH
H
H
• with esters
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2. H3O+
1. CH3MgBr
O
CH3
OH
CH3
OMe
2. H3O+
CH3
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Grignard Reactions
• with carboxylic acids
• Grignards are strong bases
• React with the acidic proton
O
1. CH3MgBr
OH
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2.
H3O+
O
OH
+ CH4
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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
tertiary alcohols
HCl
Cl
OH
HBr
Br
OH
primary or secondary alcohols
OH
OH
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SOCl2
PBr3
Cl
Cl
29
Alcohols to Alkenes
•
•
•
•
Dehydration
Acid catalyzed reaction
Excellent reaction for tertiary alcohols (E1)
Provides the Zaitsev product
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Alcohol 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
O
R
ROH/H+
OH
H3O+
O
R
OR
SOCl2
O
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R
O
ROH/pyridine
Cl
R
OR
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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 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 Oxidation
•
•
•
•
Chromium
Chromium
Chromium
Chromium
Starting Material
(VI) – yellow orange
Product
(III) – green
– Cr (VI)
Cr (IV)
– Cr (IV) + Cr (VI)
Cr (V)
– Cr(V)
Cr (III)
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Preparation and Uses of Phenols
• 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 Phenol
Cl
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NaOH/heat
OH
39
Laboratory Preparation of Phenols
• 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 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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Preparation of Thiols
• From alkyl halides by displacement with a sulfur
•
nucleophile such as SH
The alkylthiol product can undergo further
reaction
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Preparation of Thiols
• Thiourea (NH2(C=S)NH2) as a nucleophile
• Gives an intermediate alkylisothiourea salt
• Hydrolyzed cleanly to the alkyl thiourea
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Oxidation of Thiols to Disulfides
• Reaction of an alkyl thiol (RSH) with bromine or
•
iodine gives a disulfide (RSSR)
The thiol is oxidized in the process and the
halogen is reduced
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Ethers and Sulfides
• An ether has two organic groups (alkyl, aryl, or
•
•
•
•
•
vinyl) bonded to the an oxygen atom
General Formula is R–O–R
Diethyl ether is used industrially as a solvent
Tetrahydrofuran (THF) is a solvent that is a
cyclic ether
Stable and un-reactive
Sulfides (R–S–R) are sulfur analogs of ethers
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Nomenclature of Ethers
• Simple ethers are named by identifying the two
•
organic substituents and adding the word ether
If other functional groups are present, the ether
part is considered an alkoxy substituent
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Common Names
• Anisole
OMe
O
• Tetrahydrofuran
(THF)
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Nomenclature of Sulfides
• Sulfides (RSR), are sulfur analogs of ethers
– Named by rules used for ethers, with sulfide in
place of ether for simple compounds
– alkylthio in place of alkoxy
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Structure and Properties of Ethers
• R–O–R ~ tetrahedral bond angle (112° in dimethyl
•
•
ether)
Oxygen is sp3-hybridized
Oxygen atom gives ethers a slight dipole moment
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Preparation of Ethers
• Diethyl ether prepared industrially
• Sulfuric acid–catalyzed dehydration of ethanol
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Preparation of Ethers
The Williamson Ether Synthesis
• Reaction of metal alkoxides and primary alkyl halides
•
•
and tosylates
Best method for the preparation of ethers
Alkoxides prepared by reaction of an alcohol with a
strong base such as sodium hydride, NaH
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Preparation of Ethers
Silver Oxide-Catalyzed
• Reaction of alcohols with Ag2O directly with alkyl
•
halide forms ether in one step
Glucose reacts with excess iodomethane in the
presence of Ag2O to generate a pentaether in
85% yield
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Alkoxymercuration of Alkenes
• Alkene + alcohol and mercuric trifluoroacetate
• Remove Hg with NaBH4 yields an ether
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Reactions of Ethers
Cleavage
• Ethers are generally unreactive
• Strong acid will cleave an ether at elevated temperature
• HI, HBr produce an alkyl halide from less hindered
component by SN2 (tertiary ethers undergo SN1)
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Reactions of Ethers
Cleavage with Trimethylsilyl Iodide
• More mild reagent developed
OCH2CH2CH3
(CH3)3SiI/CCl4
OH
add water
• Iodide reacts with Less hindered side
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Allyl Aryl Ethers
The Claisen Rearrangement
• ArOCH2CH=CH2
• Heating to 200–250°C leads to an o-allylphenol
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Cyclic Ethers
• Cyclic ethers behave like acyclic ethers,
• Dioxane and tetrahydrofuran are used as
solvents
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Epoxides (Oxiranes)
• Three membered ring ether is called an oxirane (root “ir” from “tri”
for 3-membered; prefix “ox” for oxygen; “ane” for saturated)
• Also called epoxides
• Ethylene oxide (oxirane; 1,2-epoxyethane) is industrially important
as an intermediate
• Prepared by reaction of ethylene with oxygen at 300 °C and silver
oxide catalyst
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Laboratory Preparation of Epoxides
• Treat an alkene with a peroxyacid
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Epoxides from Halohydrins
• Addition of HO-X to an alkene gives a halohydrin
• Treatment of a halohydrin with base gives an
•
epoxide
Intramolecular Williamson ether synthesis
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Reactions of Epoxides
•
•
•
•
Treatment with dilute aqueous acid
Water adds to epoxides
Product is a 1,2-diol (on adjacent C’s: vicinal)
Trans product is observed
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Ethylene Glycol
• 1,2-ethanediol from acid catalyzed hydration of
•
ethylene
Widely used as automobile antifreeze (lowers
freezing point of water solutions)
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Halohydrins from Epoxides
• Anhydrous HF, HBr, HCl, or HI combines with an
•
epoxide
Gives trans product
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Reactions with Grignards
• Adds –CH2CH2OH to the Grignard reagent’s
•
hydrocarbon chain
Acyclic and other larger ring ethers do not react
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Preparation of Sulfides
• Thiolates (RS) are formed by the reaction of a thiol
•
•
with a base
Thiolates react with primary or secondary alkyl halide to
give sulfides (RSR’)
Thiolates are excellent nucleophiles and react with many
electrophiles
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Sulfides as Nucleophiles
• Sulfur compounds are more nucleophilic than
•
their oxygen-compound analogs
– 3p electrons valence electrons (on S) are less
tightly held than 2p electrons (on O)
Sulfides react with primary alkyl halides (SN2) to
give trialkylsulfonium salts (R3S+)
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Oxidation of Sulfides
• Sulfides are easily oxidized with H2O2 to the sulfoxide
•
•
(R2SO)
Oxidation of a sulfoxide with a peroxyacid yields a
sulfone (R2SO2)
Dimethyl sulfoxide (DMSO) is often used as a polar
aprotic solvent
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Spectroscopy
• Infrared Spectroscopy
• O-H stretches at 3400 cm-1
• Very broad absorption
• See examples
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cyclohexanol
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NMR Spectroscopy
• C atoms bonded to O are deshielded
• Resonate at lower field
• Protons on the O bearing carbon are
deshielded by the O atom
• Coupling between the O-H proton and
adjacent protons on carbon are rarely
observed
• O-H readily exchanges with D (add D2O)
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1-propanol
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Proton Deuteron Exchange
• D does not resonate in the NMR experiment
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Mass Spectroscopy
• Mass Spectrum
• Two primary cleavage patterns are observed
• Loss of water and Alpha cleavage
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1-butanol
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