CHE 242
Unit V
CH
3
CH
2
CH
2
Br C O
H H
Structure and Reactions of
Alcohols, Ethers and
Epoxides; Basic Principles of
NMR Spectroscopy
H
H
CHAPTER ELEVEN
Terrence P. Sherlock
Burlington County College
2004

CH
3
CH
2
CH
2
Br
Types of Alcohol Reactions H
C
H
O
H
H
• Dehydration to alkene
• Oxidation to aldehyde, ketone
• Substitution to form alkyl halide
• Reduction to alkane
• Esterification
• Tosylation
• Williamson synthesis of ether
=>
Chapter 11 2

Summary Table
CH
3
CH
2
CH
2
Br C O
H H
H
H
Chapter 11 3
=>

1º, 2º, 3º Carbons
CH
3
CH
2
CH
2
Br C O
H H
H
H
Chapter 11 4
=>

Oxidation of 2 ° Alcohols
CH
3
CH
2
CH
2
Br C O
H H
H
H
• 2° alcohol becomes a ketone
• Reagent is Na
2
Cr
2
O
7
/H
2
SO
4
• Active reagent probably H
2
CrO
4
• Color change: orange to greenish-blue
OH
CH
3
CHCH
2
CH
3
Na
2
Cr
2
O
7
/ H
2
SO
4
Chapter 11
O
CH
3
CCH
2
CH
3
=>
5

CH
3
CH
2
CH
2
Oxidation of 1 ° Alcohols Br
H
C
H
O
• 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.
H
H
OH
CH
3
CH
2
CH
2
CH
2
N H CrO
3
Cl
O
CH
3
CH
2
CH
2
CH
=>
6 Chapter 11

3 ° Alcohols Don’t Oxidize
CH
3
CH
2
CH
2
Br
H
C
H
O
H
H
• Cannot lose 2 H’s
• Basis for chromic acid test
Chapter 11
=>
7

CH
3
CH
2
CH
2
Br C O
H H Alcohol as a Nucleophile
H
H
H
O
C R X
• ROH is weak nucleophile
• RO is strong nucleophile
• New O-C bond forms, O-H bond breaks.
Chapter 11
=>
8

CH
3
CH
2
CH
2
Alcohol as an Electrophile
Br
H
C
H
O
H
H
• 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)
=>
Chapter 11

+
C
O
H
C-Nuc bond forms,
C-O bond breaks
9

CH
3
CH
2
CH
2
Br C O
H H Formation of Tosylate Ester
H
C
O Cl
C
C
O S O N
H O O
O S O O S O
H
H
CH
3 p -toluenesulfonyl chloride
TsCl, “tosyl chloride”
CH
3
Chapter 11
CH
3
ROTs, a tosylate ester
=>
10

CH
3
CH
2
CH
2
Br C O
H H S
N
2 Reactions of Tosylates
H
H
• 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 LiAlH
4 produces alkane
=>
Chapter 11 11

Summary of Tosylate
CH
3
CH
2
CH
2
Br C O
H H
Reactions
H
H
Chapter 11
=>
12

Reduction of Alcohols
CH
3
CH
2
CH
2
Br C O
H H
H
H
• Dehydrate with conc. H
2
SO
4
, then add H
2
• Tosylate, then reduce with LiAlH
4
OH
CH
3
CHCH
3 alcohol
H
2
SO
4
CH
2
CHCH alkene
3
H
2
Pt
CH
3
CH
2
CH
3 alkane
OH
CH
3
CHCH
3 alcohol
TsCl
OTs
CH
3
CHCH
3 tosylate
LiAlH
4
CH
3
CH
2
CH
3 alkane
=>
Chapter 11 13

Reaction with HBr
CH
3
CH
2
CH
2
Br C O
H H
H
H
• -OH of alcohol is protonated
• -OH
2
+ is good leaving group
• 3° and 2° alcohols react with Br via S
N
1
• 1° alcohols react via S
N
2
R O H
H
3
O
+
H
R O H
Br
-
R Br =>
Chapter 11 14

Mechanism with PBr
3
CH
3
CH
2
CH
2
Br
H
C
H
O
H
H
• P bonds to -OH as Br -
• Br attacks backside (S leaves
N
2)
• HOPBr
2 leaves =>
Chapter 11 15

Reaction with
Thionyl Chloride
CH
3
CH
2
CH
2
Br C O
H H
H
H
• Produces alkyl chloride, SO
2
, HCl
• S bonds to -OH, Cl leaves
• Cl abstracts H + from OH
• C-O bond breaks as Cl transferred to C
Chapter 11 16
=>

CH
3
CH
2
CH
2
Periodic Cleavage
Br C
H H of Glycols
Same products formed as from ozonolysis of the corresponding alkene.
O
H
H
CH
3
H
C
CH
3
C CH
3
OH OH
HIO
4
CH
3
OsO
4
H
2
O
2
O
3
(CH
3
)
2
S
H
3
H
C
CH
3
C C
CH
3
Chapter 11
H
C
O
=>
+
O
CH
3
C CH
3
17

CH
3
Fischer Esterification
CH
3
CH
2
CH
2
Br C O
H H
H
H
• Acid + Alcohol yields Ester + Water
• Sulfuric acid is a catalyst.
• Each step is reversible.
O
C OH + H O
CH
3
CH
2
CH
2
CHCH
3
H
+
O
CH
3
C
CH
3
OCH
2
CH
2
CHCH
3
+ HOH
=>
Chapter 11 18

CH
3
CH
2
CH
2
Br C O
H H
H
H
Tosylate Esters
• Alcohol + p -Toluenesulfonic acid, TsOH
• Acid chloride is actually used, TsCl
CH
3
CH
2
O
O H + HO S
O
CH
3
CH
3
CH
2
O
O S
O
Chapter 11
CH
3
=>
+ HOH
19

CH
3
CH
2
CH
2
Br C O
H H
H
H
Sulfate Esters
Alcohol + Sulfuric Acid
O
HO S
O
OH + H O CH
2
CH
3
H
+
HO
O
S
O
OCH
2
CH
3
CH
3
CH
2
O H + HO
O
S
O
OCH
2
CH
3
Chapter 11
H
+
O
CH
3
CH
2
O S
O
OCH
2
CH
3
=>
20

CH
3
CH
2
CH
2
Br C O
H H
H
H
Nitrate Esters
O
O
N OH + H O CH
2
CH
3
H
+
O
N
O
OCH
2
CH
3
CH
2
CH
2
CH
2
O
O
O glycerine
H
H
H
+ 3 HO NO
2
CH
2
CH
2
CH
2
O
O
O
NO
NO
NO nitroglycerine
2
2
2
=>
Chapter 11 21

CH
3
CH
2
CH
2
Br C O
H H
H
H
Phosphate Esters
HO
O
P
OH
OH
CH
3
OH
CH
3
O
O
P
OH
OH
CH
3
OH
CH
3
O
O
P
OH
OCH
3
CH
3
O
O
P OCH
3
OCH
3
CH
3
OH
=>
Chapter 11 22

Phosphate Esters in DNA
CH
3
CH
2
CH
2
Br C O
H H
H
H
O CH
2
O base
H
H
O O
P
O O
H
CH
2
O base
H
H
O O
P
O O
H
CH
2
O base
H
H
O O
P
O O
H
CH
2
O base
H
H
O O
P
O O
H
Chapter 11
=>
23

CH
3
CH
2
CH
2
Br C O
H H
H
H
Alkoxide Ions
• ROH + Na (or NaH) yields sodium alkoxide
• RO + 1 ° alkyl halide yields ether (Williamson ether synthesis)
CH
3
CH
2
CHCH
3
O
+ CH
3
CH
2
Br
Chapter 11
CH
3
CH
2
CH
2
CH O CH
2
CH
3
=>
24

CH
3
CH
2
CH
2
Br C O
H H
H
H
Chapter 11 25

POWER POINT IMAGES FROM
“ORGANIC CHEMISTRY, 5 TH EDITION”
L.G. WADE
ALL MATERIALS USED WITH PERMISSION OF AUTHOR
PRESENTATION ADAPTED FOR BURLINGTON COUNTY COLLEGE
ORGANIC CHEMISTRY COURSE
BY:
ANNALICIA POEHLER STEFANIE LAYMAN CALY MARTIN
CH
3
CH
2
CH
2
Br C O
H H
H
H
Chapter 11 26