ch h br o c h h h types of alcohol reactions organica ii... · ch3ch2ch2 c h h br o h types of...
TRANSCRIPT
Chapter 11 1
CH3CH2CH2
CHH
Br OH
H
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 =>
Chapter 11 3
CH3CH2CH2
CHH
Br OH
H
Oxidation States• Easy for inorganic saltsCrO4
2- 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=>
Chapter 11 5
CH3CH2CH2
CHH
Br OH
H
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
=>
Chapter 11 6
CH3CH2CH2
CHH
Br OH
HOxidation 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
=>
Chapter 11 7
CH3CH2CH2
CHH
Br OH
H3° Alcohols Don’t Oxidize• Cannot lose 2 H’s• Basis for chromic acid test
=>
Chapter 11 8
CH3CH2CH2
CHH
Br OH
H
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 1alcohols to aldehydes. =>
Chapter 11 9
CH3CH2CH2
CHH
Br OH
HBiological 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.
=>
Chapter 11 10
CH3CH2CH2
CHH
Br OH
H
Alcohol as a Nucleophile
• ROH is weak nucleophile• RO- is strong nucleophile• New O-C bond forms, O-H bond breaks.
=>
COH
R X
Chapter 11 11
CH3CH2CH2
CHH
Br OH
HAlcohol 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)
=>
COH
+
C-Nuc bond forms, C-O bond breaks
Chapter 11 12
CH3CH2CH2
CHH
Br OH
H
Formation of Tosylate Ester
p-toluenesulfonyl chlorideTsCl, “tosyl chloride”
COH
CH3
S
Cl
OO N
CH3
S OO
OH
C
CH3
S
O
OO
C
ROTs,a tosylate ester
=>
Chapter 11 13
CH3CH2CH2
CHH
Br OH
H
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
=>
Chapter 11 15
CH3CH2CH2
CHH
Br OH
HReduction of Alcohols• Dehydrate with conc. H2SO4, then add H2
• Tosylate, then reduce with LiAlH4
CH3CHCH3
OHH2SO4
CH2 CHCH3H2
PtCH3CH2CH3
alcohol alkene alkane
alcoholCH3CHCH3
OHTsCl
CH3CHCH3
OTsLiAlH4
alkaneCH3CH2CH3
tosylate=>
Chapter 11 16
CH3CH2CH2
CHH
Br OH
HReaction 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
HR Br =>
Chapter 11 17
CH3CH2CH2
CHH
Br OH
HReaction 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. HCl1° alcohols react slowly or not at all.2 alcohols react in 1-5 minutes.3 alcohols react in less than 1 minute.
=>
Chapter 11 18
CH3CH2CH2
CHH
Br OH
H
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.
=>
Chapter 11 19
CH3CH2CH2
CHH
Br OH
HReactions 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)
=>
Chapter 11 20
CH3CH2CH2
CHH
Br OH
HMechanism with PBr3
• P bonds to -OH as Br- leaves• Br- attacks backside (SN2)• HOPBr2 leaves =>
Chapter 11 21
CH3CH2CH2
CHH
Br OH
HReaction 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
=>
Chapter 11 22
CH3CH2CH2
CHH
Br OH
H
Dehydration Reactions
• Conc. H2SO4 produces alkene• Carbocation intermediate• Saytzeff product• Bimolecular dehydration produces ether• Low temp, 140°C and below, favors ether• High temp, 180°C and above, favors
alkene =>
Chapter 11 23
CH3CH2CH2
CHH
Br OH
H
Dehydration Mechanisms
CH3CHCH3
OHH2SO4
alcoholCH3CHCH3
OHH
CH3CHCH3
CH2 CHCH3H2O
CH3OH
H3O+
CH3OH CH3 OH2 CH3 O
H
CH3
H2OCH3OCH3
=>
Chapter 11 25
CH3CH2CH2
CHH
Br OH
H
Unique Reactions of Diols
• Pinacol rearrangement• Periodic acid cleavage
=>
Chapter 11 26
CH3CH2CH2
CHH
Br OH
HPinacol 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
=>
Chapter 11 27
CH3CH2CH2
CHH
Br OH
HPeriodic Cleavage of Glycols
Same products formed as from ozonolysisof the corresponding alkene.
CH3 C
H
OH OH
CH3
C CH3HIO4
CH3 CH
O+ C
OCH3
CH3
C CH3C
H CH3
CH3
OsO4H2O2
O3(CH3)2S
=>
Chapter 11 28
CH3CH2CH2
CHH
Br OH
H
Esterification
• Fischer: alcohol + carboxylic acid• Tosylate esters• Sulfate esters• Nitrate esters• Phosphate esters
=>
Chapter 11 29
CH3CH2CH2
CHH
Br OH
H
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
=>
Chapter 11 30
CH3CH2CH2
CHH
Br OH
H
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+
=>
Chapter 11 31
CH3CH2CH2
CHH
Br OH
H
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
=>
Chapter 11 32
CH3CH2CH2
CHH
Br OH
H
Nitrate Esters
+ H O CH2CH3H+
N OHO
OOCH2CH3N
O
O
CH2
CH2
CH2
O H
O H
O H
+ 3 HO NO2
CH2
CH2
CH2
O NO2
O NO2
O NO2
nitroglycerineglycerine =>
Chapter 11 33
CH3CH2CH2
CHH
Br OH
H
Phosphate Esters
P
O
OH
OH
HO CH3OHP
O
OH
OH
CH3OCH3OH
P
O
OCH3
OH
CH3O
P
O
OCH3
OCH3
CH3O
CH3OH
=>
Chapter 11 34
CH3CH2CH2
CHH
Br OH
HPhosphate 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