carey organic chemistry chapter 15 alcohols, diols, and thiols slides
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Carey Organic Chemistry Chapter 15Alcohols, Diols, and Thiols Slides by Dr,Kaafarani from AUB.TRANSCRIPT
Chem 212 B. R. Kaafarani 1
Chapter 15Alcohols, Diols, and Thiols
OH O
H
Chem 212 B. R. Kaafarani 2
15.1. Sources of Alcohols
Methanol
Methanol is an industrial chemical.- End uses: solvent, antifreeze, fuel.- Principal use: preparation of formaldehyde.- Prepared by hydrogenation of carbon monoxide.
CO + 2H2 CH3OH
Chem 212 B. R. Kaafarani 3
Ethanol is an industrial chemical. Most ethanol comes from fermentation.
Synthetic ethanol is produced by hydration ofethylene.
Synthetic ethanol is denatured (made unfit fordrinking) by adding methanol, benzene, pyridine,castor oil, gasoline, etc.
Ethanol
Chem 212 B. R. Kaafarani 4
Other Alcohols
Isopropyl alcohol is prepared by hydration ofpropene. Isopropyl alcohol evaporates quickly fromthe skin (bp. 82 oC) and has a cooling effect. It isused as rubbing alcohol and to sterilize medicalinstruments.
Most alcohols with five or six carbons are readilyavailable.
Chem 212 B. R. Kaafarani 5
Hydration of alkenes.
Hydroboration-oxidation of alkenes.
Hydrolysis of alkyl halides.
Syntheses using: - Grignard reagents.- Organolithium reagents.
Reactions discussed in earlier chapters (Table 15.1)
Sources of alcohols
Chem 212 B. R. Kaafarani 6
- Reduction of aldehydes and ketones.
- Reduction of carboxylic acids.
- Reduction of esters.
- Reaction of Grignard reagents with epoxides.
- Diols by hydroxylation of alkenes.
New methods in Chapter 15
Sources of alcohols
Chem 212 B. R. Kaafarani 7
C
R
H OH
H
C
R
H
O
Reduction of Aldehydes Gives Primary Alcohols
15.2. Preparation of Alcohols by Reduction of Aldehydes and Ketones
Chem 212 B. R. Kaafarani 8
Pt, ethanol
(92%)
CH3O CH2OH
O
CH3O CH + H2
Example: Catalytic Hydrogenation
Pt, Pd, Ni, or Ru as effective catalysts.
Chem 212 B. R. Kaafarani 9
C
R
H OH
R'
C
R
R'
O
Reduction of Ketones Gives Secondary Alcohols
(93-95%)
+ H2
O
Pt
ethanol
H OHExample: Catalytic Hydrogenation
Chem 212 B. R. Kaafarani 10
“H:–”
“H:–”
C
R
H OH
H
C
R
H
O
C
R
H OH
R'
C
R
R'
O
Retrosynthetic Analysis
Chem 212 B. R. Kaafarani 11
Sodiumborohydride
Lithiumaluminum hydride
Li+
Na+ –B
H
H
HH–
Al
H
H
HH
act as hydride donors
Metal Hydride Reducing Agents
Chem 212 B. R. Kaafarani 12
NaBH4
(82%)
CH2OH
O
CH
O2N
methanol
O2N
O H OH
(84%)
NaBH4
ethanol
Aldehyde
Ketone
Examples: Sodium Borohydride
Chem 212 B. R. Kaafarani 13
Lithium Aluminum Hydride
More reactive than sodium borohydride.
Cannot use water, ethanol, methanol etc. assolvents.
Diethyl ether is most commonly usedsolvent.
Chem 212 B. R. Kaafarani 14
(84%)
Aldehyde
Ketone
O
CH3(CH2)5CH CH3(CH2)5CH2OH
1. LiAlH4,diethyl ether
2. H2O
O
(C6H5)2CHCCH3
1. LiAlH4,diethyl ether
2. H2O
(86%)
OH
(C6H5)2CHCHCH3
Examples: Lithium Aluminum Hydride
Chem 212 B. R. Kaafarani 15
H OH
O
1. LiAlH4,diethyl ether2. H2O
(90%)
Selectivity
Neither NaBH4 or LiAlH4reduces isolated double bonds.
Chem 212 B. R. Kaafarani 16
Lithium aluminum hydride is the only effective reducing agent.
C
R
H OH
H
C
R
HO
O
Reduction of carboxylic acids gives primary alcohols:
15.3. Preparation of Alcohols By Reductionof Carboxylic Acids and Esters
Chem 212 B. R. Kaafarani 17
1. LiAlH4,diethyl ether2. H2OCOH
O
CH2OH
(78%)
Example: Reduction of a Carboxylic Acid
Chem 212 B. R. Kaafarani 18
Reduction of EstersGives Primary Alcohols
Lithium aluminum hydride preferred for laboratoryreductions.
Sodium borohydride reduction is too slow to beuseful.
Catalytic hydrogenation of esters used in industrybut conditions difficult or dangerous to duplicatein the laboratory (special catalyst, hightemperature, high pressure).
Chem 212 B. R. Kaafarani 19
1. LiAlH4,diethyl ether
2. H2O
(90%)
O
COCH2CH3
CH3CH2OHCH2OH +
Example: Reduction of an Ester
Chem 212 B. R. Kaafarani 20
CH2 CH2 OMgX
H3O+
H2C CH2
O
R MgX R
RCH2CH2OH
15.4. Reaction of Grignard Reagentswith Epoxides
Chem 212 B. R. Kaafarani 21
CH3(CH2)4CH2MgBr H2C CH2
O
+
1. Diethyl ether2. H3O+
CH3(CH2)4CH2CH2CH2OH
(71%)
Example
Hexylmagnesium bromide Ethylene oxide
1-Octanol
Chem 212 B. R. Kaafarani 22
Reactions used to prepare alcohols.
Hydroxylation of alkenes.
15.5. Preparation of Diols
Diols are prepared by...
Chem 212 B. R. Kaafarani 23
O O
HCCH2CHCH2CH
CH3
H2 (100 atm)
Ni, 125°C
HOCH2CH2CHCH2CH2OH
CH33-Methyl-1,5-pentanediol
(81-83%)
Example: reduction of a dialdehyde
3-Methylpentanedial
Chem 212 B. R. Kaafarani 24
Vicinal diols have hydroxyl groups onadjacent carbons.
Ethylene glycol (HOCH2CH2OH) is mostfamiliar example.
Hydroxylation of AlkenesGives Vicinal Diols
Chem 212 B. R. Kaafarani 25
syn addition of —OH groups to each carbonof double bond.
C CHO OH
C C
O OOs
OO
CC
Osmium Tetraoxide is Key Reagent
Oxidizing agent
OsO4Osmium tetroxide Cyclic
osmate ester
Chem 212 B. R. Kaafarani 26
(CH3)3COOH,OsO4 (cat),
tert-Butyl alcohol,HO–
(73%)
CH2CH3(CH2)7CH
CH3(CH2)7CHCH2OH
OH
Example
tert-Butyl hydroperoxide
OOH
Chem 212 B. R. Kaafarani 27
(CH3)3COOHOsO4 (cat)
tert-Butyl alcoholHO–
cis-1,2-cyclohexanediol
(62%)
H
H
H
H
OHHO
Example
cyclohexene
syn dihydroxylation of alkenes
Chem 212 B. R. Kaafarani 28
RCH2O
H
CH2R
OH
H+, heat
RCH2O CH2R H OH+
Acid-catalyzed. Referred to as a "condensation”. Equilibrium; most favorable for primary alcohols.
15.7. Conversion of Alcohols to Ethers
About this rxn:
Chem 212 B. R. Kaafarani 29
2 CH3CH2CH2CH2OH
H2SO4, 130°C
CH3CH2CH2CH2OCH2CH2CH2CH3
(60%)
Example
Chem 212 B. R. Kaafarani 30
Step 1:
CH3CH2O•• ••
H
H OSO2OH
Mechanism of Formation of Diethyl Ether
Ethanol Sulfuric acid
OSO2OH+ –CH3CH2O••
H
H+
Hydrogen sulfate ionEthyloxonium ion
Chem 212 B. R. Kaafarani 31
Step 2:
CH3CH2••
H
H
+O
CH3CH2O•• ••
H
Mechanism of Formation of Diethyl Ether
Ethanol
Ethyloxonium ion
++CH3CH2
CH3CH2O••
H
••
H
HO••
Diethyloxonium ion
Water
Chem 212 B. R. Kaafarani 32
Step 3:
+CH3CH2
CH3CH2O••
HHOCH2CH3••
••
Mechanism of Formation of Diethyl Ether
Diethyloxonium ion
Ethanol
+
H OCH2CH3••
CH3CH2
CH3CH2O••••
H
+
Diethyl ether
Ethyloxonium ion
Chem 212 B. R. Kaafarani 33
HOCH2CH2CH2CH2CH2OH
H2SO4 130°
O
(76%)
Intramolecular Analog
Reaction normally works wellonly for 5- and 6-memberedrings.
Chem 212 B. R. Kaafarani 34
HOCH2CH2CH2CH2CH2OH
H2SO4 130°
O
(76%)
via:
O
H
+O
H
H
••••••
Intramolecular Analog
+ H2O
Chem 212 B. R. Kaafarani 35
ROH H2O+H+
+R'COH
O
R'COR
O
15.8. Esterification
About this rxn: Called Fischer esterification. Acid catalyzed condensation reaction of an alcohol and
a carboxylic acid. Reversible. Drive reaction forward by removal of water (i.e.
azeotrop distillation using benzene).
Chem 212 B. R. Kaafarani 36
H2O+
CH3OH+COH
O
COCH3
O
H2SO4
0.1 mol 0.6 mol (i.e. excess)
70% yield based on benzoic acid
Example of Fischer Esterification
Chem 212 B. R. Kaafarani 37
ROH HCl+ +R'CCl
O
R'COR
O
Reaction of Alcohols with Acyl Chlorides
About this rxn:
- High yields.- Not reversible when carried out in presence of pyridine.
Chem 212 B. R. Kaafarani 38
pyridine
+ CClO2N
O
(63%)CH3
NO2
CH3CH2
OC
O
Example: Note the configuration on the alcohol!
(R)-(+)-2-phenyl-2-butanol
(R)-(-)-1-Methyl-1-phenylpropyl-p-nitrobenzoate
CH3
CH3CH2
OH
Chem 212 B. R. Kaafarani 39
ROH + +R'COR
OO
R'COCR'
O
R'COH
O
Reaction of Alcohols with Acid Anhydrides
analogous to reaction with acyl chlorides
Chem 212 B. R. Kaafarani 40
Pyridine
(83%)
+C6H5CH2CH2OH
O
F3CCOCCF3
O
C6H5CH2CH2OCCF3
O
Example
2-Phenylethanol Trifluoroacetic anhydride
2-Phenylethyl trifluoroacetate
O
F3CCOH+Trifluoroacetic acid
Chem 212 B. R. Kaafarani 41
Primary alcohols
Secondary alcohols
from H2O
RCH2OH
O
RCH
O
RCOH
O
RCR'RCHR'
OH
15.9. Oxidation of Alcohols
Chem 212 B. R. Kaafarani 42
Aqueous solution
Mn(VII) Cr(VI)
KMnO4 H2CrO4
H2Cr2O7
Typical Oxidizing Agents
Potassium permanganate
Chromic acid (H2CrO4):Prepared by acidification of solutions of chromate and
dichromate
chromate: CrO42-
dichromate: Cr2O72-
Chem 212 B. R. Kaafarani 43
FCH2CH2CH2CH2OH
K2Cr2O7H2SO4,H2O
FCH2CH2CH2COH
(74%)
O
Na2Cr2O7H2SO4,H2O
(85%)
H
OH
O
Aqueous Cr(VI)
3-fluoropropanoic acid
3-fluoro-1-propanol
Chem 212 B. R. Kaafarani 44
Nonaqueous Sources of Cr(VI)
Allows easy isolation of aldehydes in good yield by oxidation of primary alcohols.
All are used in CH2Cl2:
- Pyridinium dichromate (PDC)
(C5H5NH+)2 Cr2O72–
- Pyridinium chlorochromate (PCC)
C5H5NH+ ClCrO3–
Chem 212 B. R. Kaafarani 45
CH3(CH2)5CH2OHPCC
CH2Cl2
O
CH3(CH2)5CH
(78%)
ClCrO3–
N
H
+
Example: Oxidation of aprimary alcohol with PCC(pyridinium chlorochromate)
Chem 212 B. R. Kaafarani 46
PDC CH2Cl2
O
(94%)
CH2OH(CH3)3C
CH(CH3)3C
Example: Oxidation of a primary alcohol with PDC(pyridinium dichromate)
Chem 212 B. R. Kaafarani 47
MechanismStep 1:
Step 2:
Step 3:A series of redox reactions converts chromium from the 4+ oxidation state in HCrO3
– to the 3+ oxidation state.
Chem 212 B. R. Kaafarani 48
alcohol dehydrogenase
CH3CH2OH + NAD (a coenzyme)+
+ + +HNAD HCH3CH O
Enzyme-catalyzed
15.10. Biological Oxidation of Alcohols
Reduced form of NAD coenzymeacetaldehyde
Nicotinamide adenine dinucleotide
Chem 212 B. R. Kaafarani 49
Nicotinamide adenine dinucleotide (oxidized form)
HO
HO
OO
NN
NH2
PO
PO
O
HOOH
H
C
O
NH2N
O O O O
+
__
Figure 15.2. Structure of NAD+
Chem 212 B. R. Kaafarani 50
CH3CH2OH +N
H
CNH2
O
+
R
Enzyme-catalyzed
CH3CH
O
N
H
CNH2
O
R
H
••
NAD+
NADH
Chem 212 B. R. Kaafarani 51
CC
HO OH
HIO4 C O O C+
15.11. Oxidative Cleavage of Vicinal Diols
HIO4: Periodic Acid
Chem 212 B. R. Kaafarani 52
HIO4
CH CCH3
CH3
OHHO
CH3CCH3
O
CH
O
+
(83%)
Cleavage of Vicinal Diols by Periodic Acid
benzaldehydeacetone
2-Methyl-1-phenyl-1,2-pentanediol
Chem 212 B. R. Kaafarani 53
HIO4
OH
OH
O
HCCH2CH2CH2CH
O
Cyclic Diols are Cleaved
1,2-Cyclopentanediol Pentane-1,5-dial
* Both stereoisomers react* cis faster than trans
Chem 212 B. R. Kaafarani 54
1) Analogous to alcohols, but suffix is -thiol rather than –ol.
2) Final -e of alkane name is retained, not dropped as with alcohols.
15.12. Preparation of Thiols
Nomenclature of Thiols
CH3CHCH2CH2SH
CH3
3-Methyl-1-butanethiol
HOCH2CH2SH
2-Mercaptoethanolor
2-Sulfanylethanol
Chem 212 B. R. Kaafarani 55
Properties of Thiols
1. Low molecular weight thiols have foul odors.
2. Hydrogen bonding is much weaker in thiols thanin alcohols.
3. Thiols are stronger acids than alcohols.
4. Thiols are more easily oxidized than alcohols;oxidation takes place at sulfur.
Chem 212 B. R. Kaafarani 56
Thiols are less polar than alcohols
Methanol Methanethiol
bp: 65°C bp: 6°C
Chem 212 B. R. Kaafarani 57
stronger acid(pKa = 10)
waterweaker acid(pKa = 15.7)
HRS••
••
••
••OH••
–RS
••
••H
••
••OH••
–++
Thiols have pKas of about 10; can be deprotonated in aqueous base.
Thiols are stronger acids than alcohols
Hydroxide ion(stronger base)
Alkanethiolate ion (weaker base)
Thiols dissolve in aqueous base.
Chem 212 B. R. Kaafarani 58
RS– and HS– are weakly basic and good nucleophiles
H Cl HC6H5SC6H5SNa
SN2(75%)
KSH
SN2(67%)
Br SH
(S)-3-Chlorocyclopentene (R)-2-Cyclopentyl phenyl sulfide
Chem 212 B. R. Kaafarani 59
thiol (reduced)
disulfide (oxidized)
RS••
••H RS
••
••SR••
••
Oxidation of thiols takes place at sulfur
- Thiol-disulfide redox pair is important in biochemistry.
- Other oxidative processes place 1, 2, or 3 oxygenatoms on sulfur.
Chem 212 B. R. Kaafarani 60
thiol disulfide
sulfinic acid sulfonic acid
RS••
••H RS
••
••SR••
••
sulfenic acid
RS••
••OH RS
••
••OH
O•• ••–
+RS
••
OH
O•• ••–
2+
••O•• ••–
Oxidation of thiols takes place at sulfur
Chem 212 B. R. Kaafarani 61
O2, FeCl3
(CH2)4COH -Lipoic acid (78%)
HSCH2CH2CH(CH2)4COH
SH O
OS S
Example: sulfide-disulfide redox pair
Chem 212 B. R. Kaafarani 62
O—H stretching: 3200-3650 cm–1 (broad)
C—O stretching: 1025-1200 cm–1 (broad)
15.13. Spectroscopic Analysis of Alcohols
Infrared Spectroscopy
Chem 212 B. R. Kaafarani 63
Figure 15.4: Infrared Spectrum of Cyclohexanol
Chem 212 B. R. Kaafarani 64
Chemical shift of O—H proton is variable; depends on temperature and concentration
O—H proton can be identified by adding D2O; signal for O—H disappears (converted to O—D)
As S has a lower electronegativity than oxygen, sulfur shields neighboring Hs more.
C OH H 3.3-4 ppm 0.5-5 ppm
1H NMR
CH3CH2CH2CH2-OH CH3CH2CH2CH2SH 3.6 ppm 2.5 ppm
Chem 212 B. R. Kaafarani 65
Figure 15.5 (page 674)
Chem 212 B. R. Kaafarani 66
CH3CH2CH2CH3 CH3CH2CH2CH2OH
13 ppm 61.4 ppm
13C NMR
Chemical shift of C—OH is 60-75 ppm C—O is about 35-50 ppm less shielded than C—H.
Chem 212 B. R. Kaafarani 67
Unless there are other chromophores in themolecule, alcohols are transparent above about 200nm; max for methanol, for example, is 177 nm.
UV-VIS
Chem 212 B. R. Kaafarani 68
CH2R OH••
••
CH2R OH•+
••
CH2 OHR•••
+
Molecular ion peak is usuallysmall.
A peak corresponding to lossof H2O from the molecular ion(M - 18) is usually present.
Peak corresponding to lossof an alkyl group to give anoxygen-stabilized carbocation isusually prominent.
Mass Spectrometry of Alcohols