CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11Reactions of Alcohols
Jo BlackburnRichland College, Dallas, TX
Dallas County Community College District2006,Prentice Hall
Organic Chemistry, 6th EditionL. G. Wade, Jr.
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 2
Types of Alcohol Reactions
• Dehydration to alkene
• Oxidation to aldehyde, ketone
• Substitution to form alkyl halide
• Reduction to alkane
• Esterification
• Tosylation• Williamson synthesis of ether =>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 3
Summary Table
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 4
Oxidation States• Easy for inorganic salts
CrO42- reduced to Cr2O3
KMnO4 reduced to MnO2
• Oxidation: loss of H2, gain of O, O2, or X2
• Reduction: gain of H2 or H-, loss of O, O2, or X2
• Neither: gain or loss of H+, H2O, HX =>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 5
1º, 2º, 3º Carbons
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 6
Oxidation of 2° Alcohols• 2° alcohol becomes a ketone
• Reagent is Na2Cr2O7/H2SO4
• Active reagent probably H2CrO4
• Color change: orange to greenish-blue
CH3CHCH2CH3
OHNa2Cr2O7 / H2SO4
CH3CCH2CH3
O
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 7
Oxidation of 1° Alcohols• 1° alcohol to aldehyde to carboxylic acid
• Difficult to stop at aldehyde
• Use pyridinium chlorochromate (PCC) to limit the oxidation.
• PCC can also be used to oxidize 2° alcohols to ketones.
CH3CH2CH2CH2
OH N H CrO3Cl
CH3CH2CH2CH
O
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 8
3° Alcohols Don’t Oxidize
• Cannot lose 2 H’s
• Basis for chromic acid test
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 9
Other Oxidation Reagents• Collins reagent: Cr2O3 in pyridine• Jones reagent: chromic acid in acetone• KMnO4 (strong oxidizer)• Nitric acid (strong oxidizer)• CuO, 300°C (industrial dehydrogenation)• Swern oxidation: dimethylsulfoxide, with
oxalyl chloride and hindered base, oxidizes 2 alcohols to ketones and 1 alcohols to aldehydes. =>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 10
Biological Oxidation
• Catalyzed by ADH, alcohol dehydrogenase.• Oxidizing agent is NAD+, nicotinamide
adenine dinucleotide.• Ethanol oxidizes to acetaldehyde, then acetic
acid, a normal metabolite.• Methanol oxidizes to formaldehyde, then
formic acid, more toxic than methanol.• Ethylene glycol oxidizes to oxalic acid, toxic.• Treatment for poisoning is excess ethanol.
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 11
Alcohol as a Nucleophile
• ROH is weak nucleophile• RO- is strong nucleophile• New O-C bond forms, O-H bond breaks.
=>
CO
H
R X
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 12
Alcohol as an Electrophile• OH- is not a good
leaving group unless it is protonated, but most nucleophiles are strong bases which would remove H+.
• Convert to tosylate (good leaving group) to react with strong nucleophile (base). =>
CO
H
+
C-Nuc bond forms, C-O bond breaks
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 13
Formation of Tosylate Ester
p-toluenesulfonyl chlorideTsCl, “tosyl chloride”
CO
H
CH3
S
Cl
OO N
CH3
S OO
OH
C
CH3
S
O
OO
C
ROTs,a tosylate ester
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 14
SN2 Reactions of Tosylates
• With hydroxide produces alcohol
• With cyanide produces nitrile
• With halide ion produces alkyl halide
• With alkoxide ion produces ether
• With ammonia produces amine salt
• With LiAlH4 produces alkane =>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 15
Summary of Tosylate Reactions
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 16
Reduction of Alcohols
• Dehydrate with conc. H2SO4, then add H2
• Tosylate, then reduce with LiAlH4
CH3CHCH3
OHH2SO4
CH2 CHCH3H2
PtCH3CH2CH3
alcohol alkene alkane
alcohol
CH3CHCH3
OHTsCl
CH3CHCH3
OTsLiAlH4
alkane
CH3CH2CH3
tosylate
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 17
Reaction with HBr
• -OH of alcohol is protonated
• -OH2+ is good leaving group
• 3° and 2° alcohols react with Br- via SN1
• 1° alcohols react via SN2
H3O+
Br-
R O H R O H
H
R Br =>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 18
Reaction with HCl• Chloride is a weaker nucleophile than
bromide.• Add ZnCl2, which bonds strongly with
-OH, to promote the reaction.• The chloride product is insoluble.• Lucas test: ZnCl2 in conc. HCl
1° alcohols react slowly or not at all.2 alcohols react in 1-5 minutes.3 alcohols react in less than 1 minute.
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 19
Limitations of HX Reactions
• HI does not react• Poor yields of 1° and 2° chlorides• May get alkene instead of alkyl halide• Carbocation intermediate may rearrange.
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 20
Reactions with Phosphorus Halides
• Good yields with 1° and 2° alcohols
• PCl3 for alkyl chloride (but SOCl2 better)
• PBr3 for alkyl bromide
• P and I2 for alkyl iodide (PI3 not stable)
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 21
Mechanism with PBr3
• P bonds to -OH as Br- leaves
• Br- attacks backside (SN2)
• HOPBr2 leaves =>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 22
Reaction with Thionyl Chloride
• Produces alkyl chloride, SO2, HCl
• S bonds to -OH, Cl- leaves• Cl- abstracts H+ from OH
• C-O bond breaks as Cl- transferred to C =>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 23
Dehydration Reactions
• Conc. H2SO4 produces alkene
• Carbocation intermediate
• Zaitsev product
• Bimolecular dehydration produces ether
• Low temp, 140°C and below, favors ether• High temp, 180°C and above, favors
alkene =>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 24
Dehydration Mechanisms
CH3CHCH3
OHH2SO4
alcoholCH3CHCH3
OH
H
CH3CHCH3
CH2 CHCH3H2O
CH3OH
H3O+
CH3OH CH3 OH2 CH3 O
H
CH3
H2OCH3OCH3
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 25
Energy Diagram, E1
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 26
Unique Reactions of Diols
• Pinacol rearrangement• Periodic acid cleavage
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 27
Pinacol Rearrangement• Pinacol: 2,3-dimethyl-2,3-butanediol
• Dehydration with sulfuric acid
CH3 C
CH3
OH OH
CH3
C CH3H
+
CH3 C
CH3
OH OH
CH3
C CH3
H
CH3 C
CH3
OH
CCH3
CH3
CH3 C
CH3
OH
CCH3
CH3CH3 C
OH
CH3
C CH3
CH3
CH3 C
OH
CH3
C CH3
CH3
CH3 C
O
CH3
C CH3
CH3
pinacolone
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 28
Periodic Cleavage of Glycols
Same products formed as from ozonolysis of the corresponding alkene.
CH3 C
H
OH OH
CH3
C CH3
HIO4CH3 C
H
O+ C
OCH3
CH3
C CH3C
H CH3
CH3
OsO4
H2O2
O3
(CH3)2S
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 29
Esterification
• Fischer: alcohol + carboxylic acid
• Tosylate esters
• Sulfate esters
• Nitrate esters• Phosphate esters
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 30
Fischer Esterification• Acid + Alcohol yields Ester + Water
• Sulfuric acid is a catalyst.
• Each step is reversible.
CH3 C OH
O
+ CH2CH2CHCH3
CH3
OHH
+
CH3C
O
OCH2CH2CHCH3
CH3
+ HOH
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 31
Tosylate Esters• Alcohol + p-Toluenesulfonic acid, TsOH
• Acid chloride is actually used, TsCl
CH3CH2 O H + HO S
O
O
CH3
CH3CH2 O S
O
O
CH3
HOH+
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 32
Sulfate Esters
Alcohol + Sulfuric Acid
+HO S
O
O
OH H O CH2CH3H
+
OCH2CH3
O
O
SHO
CH3CH2O H + OCH2CH3
O
O
SHOH
+
CH3CH2O S
O
O
OCH2CH3
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 33
Nitrate Esters
+ H O CH2CH3H
+
N OH
O
OOCH2CH3N
O
O
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 34
Phosphate Esters
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 35
Phosphate Esters in DNA
=>
OCH2
HH
H
base
OP
O
O O
OCH2
HH
H
base
OP
O
O O
OCH2
HH
H
base
OP
O
O O
O
OCH2
HH
H
base
OP
O
O O
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 36
Alkoxide Ions
• ROH + Na (or NaH) yields sodium alkoxide• RO- + 1° alkyl halide yields ether (Williamson
ether synthesis)
CH3CH2CHCH3
O
CH3CH2 Br+ CH2CH2CH
CH3
O CH2CH3
=>
CH3CH2CH2
C
HH
Br OH
H
_
+
Chapter 11 37
End of Chapter 11