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Ch.17 Alcohols and Phenols
OH
C
An alcohol
OH
A phenol
OH
An enol
- MeOH: wood alcohol: made from wood
- industrial preparation of methanol:
CO + 2H2
400oC
Zinc oxide/chromia
CH 3OH
- Ethanol: fermentation of grains and sugars
- industrial preparation of ethanol:
H2C CH 2
+ H 2O
250oC
H3PO 4
CH 3CH 2OH
- Phenols
OH
OH
t-Bu
t-Bu
OH
OH
CO 2CH 3
OH
R
Phenol
CH 3
BHT
antioxidant
food additive
Methyl salicylate
Urushiols
(R = different C15 alkyl
and alkenyl chains)
allergenic constituents of
poison oak and poison ivy
17.1 Nomenclature
Alcohols
H
R C OH
H
R
R C OH
H
A primary alcohol
(1o)
A secondary alcohol
(2o)
R
R C OH
R
A tertiary alcohol
(3o)
step 1. select the longest carbon chain containing the OH group
; -e to -ol
step 2. numbering: begin at the end nearer the OH
step 3. list alphabetically
OH
1
OH
2
OH
2
2-Methyl-2-pentanol
1
OH
cis-1,4-Cyclohexanediol
3-Phenyl-2-butanol
common names;
OH
HO
tert-Butyl alcohol
(2-Methyl-2-propanol)
OH
Benzyl alcohol
(Phenylmethalol)
OH
Ethtylene glycol
(1,2-Ethanediol)
OH
Allyl alcohol
(2-Propen-1-ol)
HO
OH
OH
Glycerol
(1,2,3-Propanetriol)
Phenols: name as aromatic compounds, -phenol
NO 2
OH
OH
H 3C
p-Methylphenol
O 2N
2,4-Dinitrophenol
17.2 Properties of Alcohols and Phenols: Hydrogen Bonding
alcohols, phenols, ethers are H2O derivatives
H 3C
O
109
H 3C
H
O
CH 3
112o
o
Hydrogen bonding: numbering: begin at the end nearer the OH
R
R
H
δ+
O
δ−
H
δ+
δ−
O
R
H
δ+
O
δ−
H-bonding: 5-10 kcal/mol
- alcohols, phenols: high b.p., Hbonding must be destroyed to boil
Boiling points: alcohols > chloroalkanes > alkanes (with same
molecular weight)
17.3 Properties of Alcohols and Phenols : Acidty and Basicity
- weak acid, weak base
R
O
H
H X
R
H
O
X-
H
an oxonium ion
Alkoxide ion (RO-), phenoxide ion (PhO-)
H
H
O
O
H +
H +
H OR
H
H
O
H
Y
H
O
H
O
-
+
H
OR
O
H
+
Y
Alcohols are weakly acidic
Phenols are much more acidic: resonance stabilization of phenoxide ion
Alcohol
Phenol
t-BuOH
EtOH
H2O
CH3OH
CF3CH2OH
p-Aminophenol
p-Methoxyphenol
p-Methylphenol
Phenol
p-Chlorophenol
p-Bromophenol
p-Nitrophenol
2,4,6-Trinitrophenol
pKa
18.00
16.00
15.74
15.54
12.43
10.46
10.21
10.17
9.89
9.38
9.35
7.15
0.60
stronger
acid
- The effects of alkyl substituents on alcohol acidity
; primarily solvation effects of alkoxide ion
(easily solvated ions by water are more stable, therefore, more
acidic)
; less hindered ions are easily solvated, hindered ions are less
solvated and less stabilized
sterically accessible;
H
less hindered and
C O- more easily solvated
H
H
H H
sterically less accessible;
pKa = 15.54
H C
H
C OH C
H C
H
H
H
pKa = 18.00
more hindered and
less easily solvated
Inductive effects;
; electron withdrawing substituents stabilize alkoxide ions
F 3C
H 3C
H 3C
C
H 3C
pKa = 18
O
-
C
F 3C
F 3C
pKa = 5.4
O-
- alcohols are unreactive to weak bases such as amine, bicarbonate ion
- react to only a limited extent with RONa and NaOH
- react with alkali metals
2 CH3OH
+ 2 Na
2 CH3ONa
+ H2
2 t-BuOH
+ 2K
2 t-BuOK
+ H2
Potassium tert-butoxide
- alkoxides are frequently used as reagent bases
- react with strong bases such as NaH, NaNH2, RMgX, RLi
CH 3OH + NaH
ROH
+ NaNH 2
ROH + CH 3MgBr
CH 3ONa
+ H2
RONa
+ NH 3
ROMgBr
+ CH 4
- phenols are deprotonated by aq.NaOH
; phenols are soluble in dilute aq.NaOH solution
OH
+
NaOH
ONa
+
H 2O
Sodium phenoxide
resonance stabilization of phenoxide ion
O
O
O
O
O
substituent effects of phenols
O
O
EDG
EWG
less acidic
more acidic
resonance stabilization of p-nitro phenoxide ion;
O
O
O
N
O
O
N
O
O
N
O
O
O
O
O
N
O
O
N
O
O
O
N
O
17.4 Preparation of Alcohols: A Review
O
R
R
R
R
R
O
R
OH
R'
O
R
RX
RCHO
OR'
ROH
ROR'
Hydration of alkene:
H2O
Hg(OAc)2
CH3
OH
NaBH4
CH3
OH
HgOAc
CH3
BH3
CH3
BR2
-
OOH
CH3
OH
Dihydroxylation of alkene:
H3C
O O
Os
O O
OsO4
Pyridine
NaHSO3
H2O
H
CH3
RCO3H
CH3
H3O
+
CH3
OH
OH
CH3
OH
O
OH
17.5 Alcohols from Reduction of Carbonyl Compounds
Hydride reduction:
O
C
[H-]
[H-] = NaBH4, LiAlH4
OH
C
H
[H-] is a generalized
reducing agent
Reduction of Aldehydes and Ketones
R
O
C
[H-]
H
aldehyde
R
O
C
primary alcohol
[H-]
R
ketone
OH
R C H
H
OH
R C H
R
secondary alcohol
Reduction of Aldehydes
O
1. NaBH4
H
OH
EtOH
2. H3O+
4
O
2. H3O+
B- Na+
Reduction of Ketones
O
OH
1. NaBH4
EtOH
2. H3O+
Reduction with LiAlH4; much more reactive, reacts
violently with water
OH
O
1. LiAlH4
ether
2. H3O+
O
-
1. H
O
+
2. H3O
H
OH
H
Reduction of Esters and Carboxylic Acids: need strong hydride reagent
; LiAlH4
; NaBH4 reduces esters very slowly and cannot reduce carboxylic acid
at all
R
O
C
OR'
ester
or
R
O
C
acid
[H-]
OH
OH
R C H
H
primary alcohol
O
1. LiAlH4
OH
O
OH
ether
2. H3O+
1. LiAlH4
OCH3
ether
2. H3O+
OH
+ CH3OH
17.6 Alcohols from Reaction of Carbonyl Compounds with
Grignard Reagents
Grignard reagent:
R-X +
Mg
R-Mg-X
R = 1o, 2o, 3o alkyl, aryl, alkenyl
X = Cl, Br, I
O MgX
O
+ RMgX
R
H3O+
OH
R
+ MgXOH
Alcohol synthesis
O
MgBr
1.
H
CH2OH
H
2. H3O+
OH
CHO
1. PhMgBr
2. H3O+
O
OH
1. PhMgBr
2. H3O+
Ph
O
OMe
1. excess
PhMgBr
O
2. H3O+
OH
2
Carboxylic acid: no addition reaction
O
R
O
R'MgBr
OH
R
O-MgX
acid salt
+ R'-H
Limitations of Grignard reagents: good nucleophile, strong base
Grignard reagents can't be prepared from an organohalide that has
other reactive functional groups in the same molecule.
- acidic protons are deprotonated
- electrophilic functional groups react
Br
Molecule
acidic groups
FG
FG = -OH, -NH, -SH, -COOH
electrohilic groups
FG = -CHO, COR, CONR2, CN, NO2, SO2R...
17.7 Some Reactions of Alcohols
H
O
C
O-H reactions
C-O reactions
Dehydration: 3o alcohol, strong acidic condition
CH3
OH
CH3
cat. H2SO4
H2O
50oC
H2SO4, H2O
+
OH
major
Reactivity of dehydration:
H
R C OH
H
H
R C OH
R
reactivity
R
R C OH
R
SN1 reaction:
CH3
OH
cat. H2SO4
CH3
H2O
50oC
CH3
H3C
O H
H
H H O
2
Dehydration under mild, basic condition
CH3
OH
CH3
POCl3
Pyridine
0oC
OH
O
Cl P Cl
Cl
OPOCl2
H
N
Conversion of Alcohols into Alkyl Halides
3o alcohols: SN 1
CH3
OH
HCl
CH3
Cl
H Cl
CH3
O H
H
CH3
Cl-
1o and 2o alcohols: SOCl2, PBr3 by SN2 reaction
RCH2 OH
3 RCH2 OH
SOCl2
RCH2
PBr3
O
O S Cl
+ HCl
SN2
Cl-
RCH2 O P(OR')2 + 3 HBr
SN2
Br-
RCH2 Cl
+ SO2 + HCl
3 RCH2 Br
+ P(OH)3
Conversion of Alcohols into Tosylates
Activation of C-O bond
RCH2 OH
p-TolSO 2Cl
RCH2
Pyridine
p-TsCl
or
p-TolSO2Cl
O
O S Tol + HCl-Pyridine
O
O
O
S
H3C
Cl
EtO
-
H OEt
PBr3
Br
H
H O H
(+)-1-Phenyl-2-propanol
p-TsCl
pyridine
H O Ts
EtOEtO H
17.8 Oxidation of Alcohols
OH
R C H
R
OH
R C H
H
primary alcohol
oxidation
reduction
[O]
R
O
C
R
O
C
R
[O]
H
aldehyde
R
O
C
OH
carboxylic acid
OH
R C H
R
[O]
R
secondary alcohol
OH
R C R
R
tertiary alcohol
O
C
R
ketone
[O]
NO reaction
CrO3, H2Cr2O7, Na2Cr2O7
Pyridinium chlorochromate (PCC): CrO3 + pyridine + HCl
PCC
R CH2OH
R CH2OH
CH2Cl2
R CHO
CrO3
H3O
+
OH
R COOH
O
PCC
CH2Cl2
or Na2Cr2O7
H2O, CH3COOH
Mechanism: chromate intermediate, E2
H
O
C
O
O
Cr
O
O
H Cr(VI)
H
HO
O
Cr
O
C
O
Cr
O
O
O
C
H
H
E2
O
HO Cr O
Cr(IV)
+
O
C
base
17.9 Protection of Alcohols
Mg
HO
Br
ether
HO
MgBr
not formed
acidic proton
Protecting group:
HO
Br
PO
Mg
PO
Br
ether
MgBr
Trimethylsilyl (TMS) ether: Et3N, ClSi(CH3)3
ROH
+
CH3
H3C Si Cl
CH3
Et3N
R O Si
+
Et3N-HCl
R OTMS
OH
TMSCl
Et3N
OSiMe3
OTMS
Silyl ether can be formed with tertiary Si-Cl: SN2 at tertiary center
- silicon is 3rd -row atom, larger than C, form longer Si-C bond
- sterically less hindered
CH3
Cl
C
CH3
CH3
C-C bond length: 154 pm
CH3
Cl
Si
CH3
silicon is
less hindered
CH3
C-Si bond length: 195 pm
Deprotection of TMS ether: labile to acid and F- (strong F-Si bond)
OSiMe3
H3O+
OH
or F+ (CH3)3SiOH
TMS-protected alcohol in Grignard reaction
(CH3)4SiCl
HO
Br
Mg
TMSO
Et3N
MgBr
OH
R
OH
2. H3O
+
ether
OH
1. RCHO
TMSO
Br
R
OTMS
For
H3O+
17.10 Preparation and Uses of Phenols
Used as: raw material for picric acid (2,4,6-trinitrophenl),
Bakelite resin, adhesives for binding plywood
Dow process: chlorobenzene + NaOH at high temperature
Synthesis of phenol from cumene: produce phenol and acetone
H3C
H
OOH
CH3
H3C
CH3
O2
heat
+
H3O
OH
O
+
H3C
CH3
Radical mechanism
H3C
H
H
CH3 O H
O
H3C
OOH
H3C
CH3
CH3
H3O+
O O
O
H2O
H2O
H
OH
O
+
H3C
CH3
OH2
O H
O
O
Synthesis of phenols from sulfonic acid
SO3H
CH3
OH
SO3
1. NaOH
H2SO4
300oC
CH3
2. H3O+
CH3
72%
other use of phenol
OH
Cl
Cl
Cl
Cl
OCH 2COOH
Cl
OH
Cl
Cl
Cl
Pentachlorophenol
wood presertive
Cl
Cl
2,4-Dichlorophenoxyacetic acid
OH
t-Bu
t-Bu
ClCl
Cl
Hexachlorophene
2,4-D (herbicide)
OH
OH
antiseptic
OH
OH
t-Bu
H+
CH 3
t-Bu
CH 3
BHT
antioxidant
food additive
OCH3
OCH3
BHA
17.11 Reactions of Phenols
Electrophilic Aromatic Substitution Reactions
Br2, FeBr3
OH
Br
OH
HNO3, H2SO4
OH
NO2
SO3, H2SO4
OH
SO3H
Alcohol-like reactions of phenols:
no dehydration, no reaction with HCl, H2SO4
OH
K2CO3
On-Bu
NO2
acetone
n-BuBr
NO2
Oxidation of Phenols
- Na2Cr2O7, Fremy's salt [potassium nitrosodisulfonate, (KSO3)2NO)]
- quinones are reduced to hydroquinone by NaBH4 or SnCl2.
O
OH
OH
(KSO3)2NO
SnCl2
H2O
Fremy's salt
O
Benzoquinone
OH
Hydroquinone
- hydroquinone is used as photographic developer: reduces Ag+
on film to metallic silver
O
CH3
MeO
Ubiquinone: coenzyme Q
biological oxidizing agent
MeO
n H
O
Ubiquinones (n = 1 - 10)
OH
O
MeO
CH3
MeO
MeO
R
MeO
CH3
+
NADH + H +
reduced
form
OH
O
OH
MeO
O
CH3
+
MeO
R
OH
R
+ NAD+
oxidized
form
1
2
MeO
CH3
O2
+ H2O
MeO
R
O
17.12 Spectroscopy of Alcohols and Phenols
IR Spectroscopy
O-H stretching
C-O stretching
3600 cm-1
- non hydrogen bonded alcohol
3300-3400 cm-1 - hydrogen bonded alcohol
1050 cm-1
OH
NMR Spectroscopy
1H
NMR
13C
NMR
C-H-(OH)
O-H
C-OH
- 3.5-4.5 ppm
- no coupling with nearby C-H
- 50-80 ppm
O-H proton signal: unpredictable chemical shift, often not observed
HA
C O H
H
C O H
H
+ HA
no coupling
Deuterium exchange: O-H proton signal disappears rapidly
C O H
H
D2O
C O D
H
+ HDO
MS Spectrometry
Alchols: fragment in two pathways
alpha (α) cleavage
RH2C
C OH
C OH
+
RCH2
dehydration
OH
H
C C
C C
+
H2O
Chemistry @ Work
Ethyl Alcohol: Chemical, Drug, and Poison
Fermentation: alcoholic beverage
C6H12O6
Yeast
2 EtOH + 2 CO2
A carbohydrate
Hydration of ethylene: industrial production
H2C CH2 + H2O
acid
catalyst
EtOH
Chemistry @ Work
Ethyl Alcohol: Chemical, Drug, and Poison
Metabolism
CH3CH2OH
CH3CHO
CH3COOH
Acetaldehyde
Acetic acid
toxic
- test of blood alcohol concentration: oxidation test with K2Cr2O7
Problem Sets
Chapter 17
26, 31, 36, 44, 52, 57, 64