1. Chapter 15 Alcohols, Diols, and Thiols
Dr. Wolf's CHM 201 & 202
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2. Sources of Alcohols
Dr. Wolf's CHM 201 & 202
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3. Methanol is an industrial chemical end uses: solvent, antifreeze, fuel
principal use: preparation of formaldehyde
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4. Methanol is an industrial chemical end uses: solvent, antifreeze, fuel
principal use: preparation of formaldehyde
prepared by hydrogenation of carbon monoxide
CO + 2H2 ® CH3OH
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5. Ethanol is an industrial chemical Most ethanol comes from fermentation
Synthetic ethanol is produced by hydration of ethylene
Synthetic ethanol is denatured (made unfit for drinking) by adding methanol, benzene, pyridine, castor oil, gasoline, etc.
Dr. Wolf's CHM 201 & 202
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6. Isopropyl alcohol is prepared by hydration of propene.
Other alcohols
Isopropyl alcohol is prepared by hydration of propene.
All alcohols with four carbons or fewer are readily available.
Most alcohols with five or six carbons are readily available.
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7. Reactions discussed in earlier chapters (Table 15.1)
Sources of alcohols
Reactions discussed in earlier chapters (Table 15.1)
Hydration of alkenes
Hydroboration-oxidation of alkenes
Hydrolysis of alkyl halides
Syntheses using Grignard reagents organolithium reagents
Dr. Wolf's CHM 201 & 202
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8. Reduction of aldehydes and ketones Reduction of carboxylic acids
Sources of alcohols
New methods in Chapter 15
Reduction of aldehydes and ketones
Reduction of carboxylic acids
Reduction of esters
Reaction of Grignard reagents with epoxides
Diols by hydroxylation of alkenes
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9. Preparation of Alcohols by Reduction of Aldehydes and Ketones
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10. Reduction of Aldehydes Gives Primary Alcohols
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11. Example: Catalytic Hydrogenation
CH3O CH + H2
Pt, ethanol
CH3O
CH2OH
(92%)
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12. Reduction of Ketones Gives Secondary Alcohols
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13. Example: Catalytic HydrogenationOH O Pt + H2
ethanol
(93-95%)
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14. Retrosynthetic AnalysisOH C R H O
H:– C R H OH R' C R R' O
H:–
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15. Metal Hydride Reducing Agents– B H – Al H Na + Li +
Sodium borohydride
Lithium aluminum hydride
act as hydride donors
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16. Examples: Sodium Borohydride
Aldehyde O CH
O2N
O2N
NaBH4
CH2OH
methanol
(82%)
Ketone H OH O
NaBH4
ethanol
(84%)
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17. Lithium aluminum hydride
more reactive than sodium borohydride
cannot use water, ethanol, methanol etc. as solvents
diethyl ether is most commonly used solvent
Dr. Wolf's CHM 201 & 202
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18. Examples: Lithium Aluminum Hydride
Aldehyde
1. LiAlH4 diethyl ether O
CH3(CH2)5CH
CH3(CH2)5CH2OH
2. H2O
(86%)
Ketone O
1. LiAlH4 diethyl ether OH
(C6H5)2CHCHCH3
(C6H5)2CHCCH3
2. H2O
(84%)
Dr. Wolf's CHM 201 & 202
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19. neither NaBH4 or LiAlH4 reduces isolated double bonds
Selectivity O
neither NaBH4 or LiAlH4 reduces isolated double bonds
1. LiAlH4 diethyl ether
2. H2O H OH
(90%)
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20. Preparation of Alcohols By Reduction of Carboxylic Acids and Esters
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21. Reduction of Carboxylic Acids Gives Primary Alcohols
lithium aluminum hydride is only effective reducing agent
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22. Example: Reduction of a Carboxylic Acid
1. LiAlH4 diethyl ether O
COH
CH2OH
2. H2O
(78%)
Dr. Wolf's CHM 201 & 202
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23. Reduction of Esters Gives Primary Alcohols (Also Chapter 19)
Lithium aluminum hydride preferred for laboratory reductions
Sodium borohydride reduction is too slow to be useful
Catalytic hydrogenolysis used in industry but conditions difficult or dangerous to duplicate in the laboratory (special catalyst, high temperature, high pressure
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24. Example: Reduction of an Ester
1. LiAlH4 diethyl ether
2. H2O
(90%) O
COCH2CH3
CH3CH2OH
CH2OH +
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25. Preparation of Alcohols From Epoxides
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26. Reaction of Grignard Reagents with Epoxides
MgX R
H2C
CH2 O
CH2
CH2
OMgX
H3O+
RCH2CH2OH
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27. Example CH2 H2C CH3(CH2)4CH2MgBr + O 1. diethyl ether 2. H3O+
CH3(CH2)4CH2CH2CH2OH
(71%)
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28. Preparation of Diols
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29. reactions used to prepare alcohols hydroxylation of alkenes
Diols are prepared by...
reactions used to prepare alcohols
hydroxylation of alkenes
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30. Example: reduction of a dialdehyde
HCCH2CHCH2CH
CH3
H2 (100 atm)
Ni, 125°C
HOCH2CH2CHCH2CH2OH
CH3
3-Methyl-1,5-pentanediol
(81-83%)
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31. Hydroxylation of Alkenes Gives Vicinal Diols
vicinal diols have hydroxyl groups on adjacent carbons
ethylene glycol (HOCH2CH2OH) is most familiar example
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32. Osmium Tetraoxide is Key Reagent
syn addition of —OH groups to each carbon of double bond HO OH C C O Os C
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33. tert-Butyl alcohol HO–
Example
CH2
CH3(CH2)7CH
(CH3)3COOH OsO4 (cat)
tert-Butyl alcohol HO–
CH3(CH2)7CHCH2OH OH
(73%)
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34. tert-Butyl alcohol HO–
Example
(CH3)3COOH OsO4 (cat) H OH HO H
tert-Butyl alcohol HO–
(62%)
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35. Reactions of Alcohols: A Review and a Preview
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36. Table 15.2 Review of Reactions of Alcohols
reaction with hydrogen halides
reaction with thionyl chloride
reaction with phosphorous tribromide
acid-catalyzed dehydration
conversion to p-toluenesulfonate esters
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37. New Reactions of Alcohols in This Chapter
conversion to ethers
esterification
esters of inorganic acids
oxidation
cleavage of vicinal diols
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38. Conversion of Alcohols to Ethers
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39. Conversion of Alcohols to Ethers
RCH2O H
CH2R OH H+
RCH2O
CH2R + H OH
acid-catalyzed
referred to as a "condensation"
equilibrium; most favorable for primary alcohols
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40. Example H2SO4, 130°C 2CH3CH2CH2CH2OH CH3CH2CH2CH2OCH2CH2CH2CH3 (60%)
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41. Mechanism of Formation of Diethyl Ether
Step 1:
CH3CH2O ••
• • H
OSO2OH H H + – +
CH3CH2O
OSO2OH
• • H
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42. Mechanism of Formation of Diethyl Ether
Step 2:
CH3CH2
• • H + O
• • H O +
CH3CH2
CH3CH2O
• • H +
CH3CH2O ••
• • H
Dr. Wolf's CHM 201 & 202
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43. Mechanism of Formation of Diethyl Ether
Step 3: +
CH3CH2
CH3CH2O
• • H
CH3CH2
CH3CH2O
• • •• +
OSO2OH – ••
• • H
OSO2OH ••
Dr. Wolf's CHM 201 & 202
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44. Intramolecular Analog
HOCH2CH2CH2CH2CH2OH
H2SO4
130° O
reaction normally works well only for 5- and 6-membered rings
(76%)
Dr. Wolf's CHM 201 & 202
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45. Intramolecular Analog
HOCH2CH2CH2CH2CH2OH
via:
H2SO4
130° O H +
• • •• O
(76%)
Dr. Wolf's CHM 201 & 202
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46. Esterification (more on esters and other acid derivatives in later chapters)
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47. Esterification a condensation reaction called Fischer esterification
R'COH O
R'COR O H+
ROH + +
H2O
a condensation reaction
called Fischer esterification
acid catalyzed
reversible
Dr. Wolf's CHM 201 & 202
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48. Example of Fischer Esterification
CH3OH +
COH O
0.1 mol
0.6 mol (i.e. excess)
H2SO4
COCH3 O +
H2O
70% yield based on benzoic acid
Dr. Wolf's CHM 201 & 202
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49. Reaction of Alcohols with Acyl Chlorides
R'CCl O
R'COR O
ROH + +
HCl
high yields
not reversible when carried out in presence of pyridine
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50. Example CH3CH2 O + OH O2N CCl CH3 pyridine CH3CH2 O OC NO2 CH3 (63%)
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51. Reaction of Alcohols with Acid Anhydrides
R'COCR'
R'COR O
R'COH O
ROH + +
analogous to reaction with acyl chlorides
Dr. Wolf's CHM 201 & 202
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52. Example O + C6H5CH2CH2OH F3CCOCCF3 pyridine O C6H5CH2CH2OCCF3 (83%)
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53. Esters of Inorganic Acids
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54. Esters of Inorganic Acids
ROH + HOEWG
ROEWG + H2O
EWG is an electron-withdrawing group
(HO)3P O + –
HONO2
(HO)2SO2
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55. Esters of Inorganic Acids
ROH + HOEWG
ROEWG + H2O
EWG is an electron-withdrawing group
(HO)3P O + –
HONO2
(HO)2SO2
CH3OH HONO2
CH3ONO H2O
(66-80%)
Dr. Wolf's CHM 201 & 202
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56. Oxidation of Alcohols
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57. Oxidation of Alcohols Primary alcohols O O RCH2OH RCH RCOH
Secondary alcohols O
from H2O
RCHR' OH
RCR'
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58. Typical Oxidizing Agents
Aqueous solution
Mn(VII) Cr(VI)
KMnO4 H2CrO4
H2Cr2O7
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59. Aqueous Cr(VI) FCH2CH2CH2CH2OH H2SO4 K2Cr2O7 H2O O FCH2CH2CH2COH (74%)
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60. Aqueous Cr(VI) H OH FCH2CH2CH2CH2OH H2SO4 K2Cr2O7 H2SO4 H2O Na2Cr2O7
FCH2CH2CH2COH
(74%)
(85%)
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61. Nonaqueous Sources of Cr(VI)
All are used in CH2Cl2
Pyridinium dichromate (PDC)
(C5H5NH+)2 Cr2O72–
Pyridinium chlorochromate (PCC)
C5H5NH+ ClCrO3–
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62. Example: Oxidation of a primary alcohol with PCC (pyridinium chlorochromate)+
ClCrO3– O
CH3(CH2)5CH
PCC
CH3(CH2)5CH2OH
CH2Cl2
(78%)
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63. Example: Oxidation of a primary alcohol with PDC (pryidinium dichromate)
CH2OH
(CH3)3C
PDC
CH2Cl2 O CH
(CH3)3C
(94%)
Dr. Wolf's CHM 201 & 202
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64. Mechanism O H H O C HOCrOH C OH O CrOH
involves formation and elimination of a chromate ester
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65. Mechanism H O H O H H O C HOCrOH C OH O CrOH•• H
Mechanism O H H O C
HOCrOH C OH O
CrOH
involves formation and elimination of a chromate ester C O
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66. Biological Oxidation of Alcohols
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67. Enzyme-catalyzed NAD (a coenzyme) + CH3CH2OH + alcohol dehydrogenase +
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68. Figure 15.3 Structure of NAD+HO O N
NH2 P OH H C + _
nicotinamide adenine dinucleotide (oxidized form)
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69. Enzyme-catalyzed N H CNH2 O + R + H CH3CH2OH + + 15-69 34
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70. Enzyme-catalyzed CNH2 O H H CH3CH O N R •• 15-70 34
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71. Oxidative Cleavage of Vicinal Diols
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72. Cleavage of Vicinal Diols by Periodic AcidHO OH O O C
HIO4 C +
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73. Cleavage of Vicinal Diols by Periodic AcidCH
CCH3
CH3 OH HO
HIO4 CH O
CH3CCH3 O +
(83%)
Dr. Wolf's CHM 201 & 202
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74. Cyclic Diols are CleavedOH O
HCCH2CH2CH2CH
HIO4
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75. Preparation of Thiols
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76. Nomenclature of Thiols
1) analogous to alcohols, but suffix is -thiol rather than -ol
2) final -e of alkane name is retained, not dropped as with alcohols
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77. Nomenclature of Thiols
1) analogous to alcohols, but suffix is -thiol rather than -ol
2) final -e of alkane name is retained, not dropped as with alcohols
CH3CHCH2CH2SH
CH3
3-Methyl-1-butanethiol
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78. Properties of Thiols 1. low molecular weight thiols have foul odors
2. hydrogen bonding is much weaker in thiols than in alcohols
3. thiols are stronger acids than alcohols
4. thiols are more easily oxidized than alcohols; oxidation takes place at sulfur
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79. Thiols are less polar than alcohols
Methanol
Methanethiol
bp: 65°C
bp: 6°C 6

80. Thiols are stronger acids than alcohols
have pKas of about 10; can be deprotonated in aqueous base – •• OH
• • – H RS •• •• H •• OH + RS +
• •
stronger acid (pKa = 10)
weaker acid (pKa = 15.7)
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81. RS– and HS – are weakly basic and good nucleophiles
C6H5S
C6H5SNa
SN2
(75%)
KSH
SN2
(67%) Br SH 2

82. Oxidation of thiols take place at sulfurRS •• H RS •• SR
thiol (reduced)
disulfide (oxidized)
thiol-disulfide redox pair is important in biochemistry
other oxidative processes place 1, 2, or 3 oxygen atoms on sulfur
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83. Oxidation of thiols take place at sulfurRS •• H RS •• SR
thiol
disulfide RS •• OH O
• • – + •• – O
• •
• • RS •• OH 2+ RS OH O
• •
• • •• –
sulfenic acid
sulfinic acid
sulfonic acid
Dr. Wolf's CHM 201 & 202
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84. Example: sulfide-disulfide redox pairSH O
HSCH2CH2CH(CH2)4COH
O2, FeCl3 S O S
a-Lipoic acid (78%)
(CH2)4COH
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85. Spectroscopic Analysis of Alcohols
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86. Infrared Spectroscopy
O—H stretching: cm–1 (broad)
C—O stretching: cm–1 (broad)
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87. Figure 15.4: Infrared Spectrum of Cyclohexanol
C—H
O—H
C—O
2000
3500
3000
2500
1000
1500
500
Wave number, cm-1
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88. 1H NMR
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) H C O H
d ppm
d ppm
Dr. Wolf's CHM 201 & 202
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89. Figure 15.5 (page 607) CH2CH2OH Chemical shift (d, ppm) 1 15-91 1.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
10.0
Chemical shift (d, ppm)
Dr. Wolf's CHM 201 & 202
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90. 13C NMR chemical shift of C—OH is d 60-75 ppm
C—O is about ppm less shielded than C—H
CH3CH2CH2CH3
CH3CH2CH2CH2OH
d 13 ppm
d 61.4 ppm
Dr. Wolf's CHM 201 & 202
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91. UV-VIS
Unless there are other chromophores in the molecule, alcohols are transparent above about 200 nm;
lmax for methanol, for example, is 177 nm.
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92. Mass Spectrometry of Alcohols
molecular ion peak is usually small
a peak corresponding to loss of H2O from the molecular ion (M - 18) is usually present
peak corresponding to loss of an alkyl group to give an oxygen- stabilized carbocation is usually prominent
Dr. Wolf's CHM 201 & 202
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93. Mass Spectrometry of Alcohols
molecular ion peak is usually small
a peak corresponding to loss of H2O from the molecular ion (M - 18) is usually present
peak corresponding to loss of an alkyl group to give an oxygen- stabilized carbocation is usually prominent
CH2 R OH ••
CH2 R OH •+ •• + R •
CH2 OH ••
Dr. Wolf's CHM 201 & 202
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94. End of Chapter 15