ch.17 alcohols and phenols - yonsei...conversion of alcohols into alkyl halides ch3 ch3 oh ch3 o h h...
TRANSCRIPT
An alcohol A phenol An enol
OHOHC
OH
Ch.17 Alcohols and Phenols
CO + 2H2400oC
Zinc oxide/chromiaCH3OH
H3PO4CH3CH2OHH2C CH2 + H2O
250oC
- MeOH: wood alcohol: made from wood- industrial preparation of methanol:
- Ethanol: fermentation of grains and sugars- industrial preparation of ethanol:
t-But-Bu
CH3
OH
BHTantioxidantfood additive
OH
Phenol
OH
Methyl salicylate
CO2CH3
OH
Urushiols(R = different C15 alkyl
and alkenyl chains)
OH
R
allergenic constituents of poison oak and poison ivy
- Phenols
CH
R OHH
A primary alcohol(1o)
CR
R OHH
A secondary alcohol(2o)
CR
R OHR
A tertiary alcohol(3o)
17.1 Nomenclature
Alcohols
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
12
2-Methyl-2-pentanol
OH
OH
cis-1,4-Cyclohexanediol
12
3-Phenyl-2-butanol
OH
OH
OH HOOH HO OH
OH
Benzyl alcohol(Phenylmethalol)
tert-Butyl alcohol(2-Methyl-2-propanol)
Ethtylene glycol(1,2-Ethanediol)
Glycerol(1,2,3-Propanetriol)
OH
Allyl alcohol(2-Propen-1-ol)
common names;
H3C
OH
p-Methylphenol
O2N
OH
2,4-Dinitrophenol
NO2
Phenols: name as aromatic compounds, -phenol
H3CO
H
109o
H3CO
CH3
112o
17.2 Properties of Alcohols and Phenols: Hydrogen Bonding
alcohols, phenols, ethers are H2O derivatives
Hydrogen bonding: numbering: begin at the end nearer the OH
O
R
H HO
H
R
O
R
δ−δ− δ−
δ+δ+
δ+
H-bonding: 5-10 kcal/mol
- alcohols, phenols: high b.p., H-bonding must be destroyed to boil
Boiling points: alcohols > chloroalkanes > alkanes (with same molecular weight)
RO
H H X RO
H X-H
an oxonium ion
17.3 Properties of Alcohols and Phenols : Acidty and Basicity- weak acid, weak base
Alkoxide ion (RO-), phenoxide ion (PhO-)
HO
H H OR HO
H -OR
H
++
HO
H HO
H
H
++O
H
Y
O
Y
Alcohols are weakly acidicPhenols are much more acidic: resonance stabilization of phenoxide ion
AlcoholPhenol pKa
t-BuOHEtOHH2OCH3OHCF3CH2OHp-Aminophenolp-Methoxyphenolp-MethylphenolPhenolp-Chlorophenolp-Bromophenolp-Nitrophenol2,4,6-Trinitrophenol
18.0016.0015.7415.5412.4310.4610.2110.179.899.389.357.150.60
strongeracid
- 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 lesssolvated and less stabilized
O-CH
HH
sterically accessible;less hindered andmore easily solvated
pKa = 15.54 O-CC
CC
HHHH
HH
HH H
sterically less accessible;more hindered andless easily solvated
pKa = 18.00
Inductive effects;; electron withdrawing substituents stabilize alkoxide ions
O-C
H3C
H3C
H3C
pKa = 18
O-C
F3C
F3C
F3C
pKa = 5.4
- 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 + 2 K 2 t-BuOK + H2
Potassium tert-butoxide
- alkoxides are frequently used as reagent bases
+ NaH + H2CH3ONaCH3OH
+ NaNH2 + NH3RONaROH
+ CH3MgBr + CH4ROMgBrROH
- react with strong bases such as NaH, NaNH2, RMgX, RLi
OH + NaOH ONa + H2O
Sodium phenoxide
- phenols are deprotonated by aq.NaOH; phenols are soluble in dilute aq.NaOH solution
resonance stabilization of phenoxide ion
OO O O O
substituent effects of phenols
resonance stabilization of p-nitro phenoxide ion;
OO O O O
NO O
NO O N
O ON
O O NO O
O
NO O
OEWG
OEDG
more acidic less acidic
17.4 Preparation of Alcohols: A Review
ROR'
RCHO
R R'
OR
R
R
RR OH
O
R OR'
O
RXROH
Hydration of alkene:
CH3
CH3
HgOAc
H2O
Hg(OAc)2
CH3
OHNaBH4OH
CH3
BR2
BH3 CH3
OH
-OOH
Dihydroxylation of alkene:
CH3
H3COsO4
Pyridine
CH3OHNaHSO3O
OOs
O
OH
OHH2O
CH3
O
RCO3HOH
OH
H3O+ CH3
17.5 Alcohols from Reduction of Carbonyl Compounds
Hydride reduction:
CO [H-]
CH
OH [H-] is a generalizedreducing agent
[H-] = NaBH4, LiAlH4
Reduction of Aldehydes and Ketones
RC
H
O [H-]C
H
OH
HR
primary alcoholaldehyde
RC
R
OC
H
OH
RR
secondary alcoholketone
[H-]
Reduction of Aldehydes
H
O 1. NaBH4
2. H3O+EtOH OH
2. H3O+
OB-
4Na+
Reduction of KetonesO
1. NaBH4
2. H3O+EtOH
OH
Reduction with LiAlH4; much more reactive, reacts violently with water
1. LiAlH4
2. H3O+ether
O OH
1. H- 2. H3O+O
H
O
H
OH
Reduction of Esters and Carboxylic Acids: need strong hydride reagent ; LiAlH4; NaBH4 reduces esters very slowly and cannot reduce carboxylic acid at all
RC
OR'
O [H-]C
H
OH
HR
primary alcoholester
RC
OH
O
acid
or
OH
O1. LiAlH4
2. H3O+ether OH
OCH3
O1. LiAlH4
2. H3O+ether
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+ RMgX
O
R
MgX OH
R
H3O+
+ MgXOH
MgBrH H
OCH2OH1.
2. H3O+
Alcohol synthesis
CHO1.
2. H3O+
PhMgBr
OH
O 1.
2. H3O+
PhMgBrOH
Ph
1.
2. H3O+
excess PhMgBr
OO
OMe
OH
2
Carboxylic acid: no addition reaction
R
R'MgBrO
OH R
O
O-MgX + R'-H
acid salt
Limitations of Grignard reagents: good nucleophile, strong baseGrignard 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
FG = -OH, -NH, -SH, -COOH
FG = -CHO, COR, CONR2, CN, NO2, SO2R...
acidic groups
electrohilic groups
Br FGMolecule
17.7 Some Reactions of Alcohols
O
C
HO-H reactions
C-O reactions
Dehydration: 3o alcohol, strong acidic condition
OH+
major
H2SO4, H2O
CH3CH3
OHH2O
cat. H2SO4
50oC
CH
HR C
H
RR C
R
RR
reactivity
OH OH OH
Reactivity of dehydration:
SN1 reaction:
CH3CH3
OHH2O
cat. H2SO4
50oC
H3C
OH
H
CH3
H H2O
Dehydration under mild, basic condition
CH3CH3
OHPyridine
0oC
POCl3
OH PO
ClCl
Cl OPOCl2
H N
Conversion of Alcohols into Alkyl Halides
CH3CH3
OH
CH3
OH
H
CH3
Cl-
HCl
H Cl
Cl
3o alcohols: SN 1
RCH2 OHSOCl2
RCH2 O SO
Cl + HClCl-
RCH2 Cl
+ SO2 + HCl
SN2
1o and 2o alcohols: SOCl2, PBr3 by SN2 reaction
RCH2 OH RCH2 O P(OR')2+ 3 HBrBr-
RCH2 Br
+ P(OH)3
PBr33 3
SN2
Conversion of Alcohols into Tosylates
RCH2 OHp-TolSO2Cl
RCH2 O SO
Tol + HCl-PyridineOPyridine
Activation of C-O bond
S
H3C
O O
Clp-TsClorp-TolSO2Cl
OH H
(+)-1-Phenyl-2-propanol
HBrPBr3
OEtHEtO-
OH Ts
p-TsCl
pyridine
HEtO
EtO-
17.8 Oxidation of Alcohols
RC
R
OC
H
OH
RRoxidation
reduction
RC
H
O[O]C
H
OH
HR
primary alcohol aldehyde
RC
OH
O[O]
carboxylic acid
RC
R
OC
H
OH
RR
secondary alcohol ketone
[O]
CR
OH
RR
tertiary alcohol
[O]NO reaction
R CH2OHPCC
CH2Cl2R CHO
PCC
CH2Cl2
Na2Cr2O7
OH O
orH2O, CH3COOH
CrO3, H2Cr2O7, Na2Cr2O7Pyridinium chlorochromate (PCC): CrO3 + pyridine + HCl
R CH2OHCrO3
R COOHH3O+
CrO
O OOC
H
H CrO
OO
OC
H
HCr
O
OHO
OC
H
CO
CrO
HO O +
Cr(VI)
Cr(IV)
baseE2
Mechanism: chromate intermediate, E2
17.9 Protection of Alcohols
HO Br HO MgBrMg
ether
acidic proton not formed
HO Br
PO MgBr
Mg ether
PO Br
Protecting group:
ROH + H3C SiCH3
CH3
ClEt3N
R O Si + Et3N-HCl
R OTMS
Trimethylsilyl (TMS) ether: Et3N, ClSi(CH3)3
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
Cl C
CH3
CH3
CH3
C-C bond length: 154 pm
Cl Si
CH3
CH3
CH3
C-Si bond length: 195 pm
silicon is less hindered
OHOSiMe3 H3O+
or F-
+ (CH3)3SiOH
Deprotection of TMS ether: labile to acid and F- (strong F-Si bond)
TMS-protected alcohol in Grignard reaction
HO Br
TMSO MgBr
Mg
etherTMSO Br
(CH3)4SiCl
Et3N
1. RCHO
2. H3O+ ROTMS
OH F-
orH3O+
ROH
OH
17.10 Preparation and Uses of Phenols
Synthesis of phenol from cumene: produce phenol and acetone
H3C CH3H
O2
heat
H3C CH3
OOH
H3O+OH
+H3C CH3
O
Dow process: chlorobenzene + NaOH at high temperature
Used as: raw material for picric acid (2,4,6-trinitrophenl), Bakelite resin, adhesives for binding plywood
Radical mechanism
H3C CH3 H3C CH3
OOH
H3O+
OH
+H3C CH3
O
H3CCH3
OO
HH
OH2O
OOH2
OO
HH
H2O
O O
H
Synthesis of phenols from sulfonic acid
CH3
SO3
H2SO4
CH3
SO3H
1. NaOH
300oC2. H3O+
CH3
OH
72%
other use of phenolOH
Pentachlorophenol
Cl Cl
ClCl
Cl
wood presertive
OCH2COOH
2,4-Dichlorophenoxyacetic acid
Cl
Cl
2,4-D (herbicide)
OHCl
ClCl
OHCl
ClCl
Hexachlorophene
antiseptic
t-But-Bu
CH3
OH
BHTantioxidantfood additive
CH3
OH
H+
t-Bu
OCH3
OH
OCH3
OH
t-Bu
BHA
17.11 Reactions of PhenolsElectrophilic Aromatic Substitution Reactions
OH
OH
Br
Br2, FeBr3
OH
NO2
HNO3, H2SO4
OH
SO3H
SO3, H2SO4
Alcohol-like reactions of phenols:no dehydration, no reaction with HCl, H2SO4
acetone
OH
NO2
K2CO3
n-BuBr
On-Bu
NO2
Oxidation of Phenols
OH O
O
H2O
Benzoquinone
SnCl2
Fremy's salt
OH
OHHydroquinone
(KSO3)2NO
- Na2Cr2O7, Fremy's salt [potassium nitrosodisulfonate, (KSO3)2NO)]- quinones are reduced to hydroquinone by NaBH4 or SnCl2.
- hydroquinone is used as photographic developer: reduces Ag+
on film to metallic silver
Ubiquinone: coenzyme Qbiological oxidizing agent
O
O
Ubiquinones (n = 1 - 10)
CH3MeO
MeO n H
O
OCH3MeO
MeO RNADH + H+ +
OH
OHCH3MeO
MeO R+ NAD+
OH
OHCH3MeO
MeO R+ O2
12
O
OCH3MeO
MeO R+ H2O
reducedform
oxidizedform
17.12 Spectroscopy of Alcohols and Phenols
IR Spectroscopy
- hydrogen bonded alcohol3300-3400 cm-1
1050 cm-1C-O stretching
- non hydrogen bonded alcohol3600 cm-1O-H stretching
OH
NMR Spectroscopy
- 50-80 ppm- no coupling with nearby C-H- 3.5-4.5 ppm
O-HC-OH13C NMR
C-H-(OH)1H NMR
C O HH
HAC O HH
+ HA
no coupling
C O HH
D2OC O DH
+ HDO
Deuterium exchange: O-H proton signal disappears rapidly
O-H proton signal: unpredictable chemical shift, often not observed
MS Spectrometry
Alchols: fragment in two pathways
CRH2C OH RCH2+
alpha (α) cleavage
C OH
OHCC +
dehydration
HC C H2O
C6H12O6
A carbohydrate
Yeast2 EtOH + 2 CO2
Fermentation: alcoholic beverage
Ethyl Alcohol: Chemical, Drug, and Poison
Chemistry @ Work
acidH2C CH2 + H2O
catalystEtOH
Hydration of ethylene: industrial production
CH3CH2OH CH3CHO CH3COOH
Acetaldehyde Acetic acid
toxic
Metabolism
- test of blood alcohol concentration: oxidation test with K2Cr2O7
Ethyl Alcohol: Chemical, Drug, and Poison
Chemistry @ Work
Chapter 17
Problem Sets
26, 31, 36, 44, 52, 57, 64