Chapter 5
Alcohols Thiols
Ethers
Structure of Water and Methanol
• Oxygen is sp3 hybridized and tetrahedral.
• The H—O—H angle in water is 104.5°.
• The C—O—H angle in methyl alcohol is 108.9°.
Chapter 10
2
Classification of Alcohols
• Primary: carbon with —OH is bonded to one
other carbon.
• Secondary: carbon with —OH is bonded to
two other carbons.
• Tertiary: carbon with —OH is bonded to
three other carbons.
• Aromatic (phenol): —OH is bonded to a
benzene ring.
Chapter 10
3
Examples of Classifications
OH
CH3
CH3
CH3
CH CH2OH
*
CH CH2CH3
*
CH3
CH3
C* OH
CH3
Chapter 10
4
Examples of Classifications
OH
CH3
CH3
CH3
CH CH2OH
*
CH CH2CH3
*
Primary alcohol
CH3
CH3
C* OH
CH3
Chapter 10
5
Examples of Classifications
OH
CH3
CH3
CH3
CH CH2OH
*
Primary alcohol
CH CH2CH3
*
Secondary alcohol
CH3
CH3
C* OH
CH3
Chapter 10
6
Examples of Classifications
OH
CH3
CH3
CH3
CH CH2OH
*
Primary alcohol
CH CH2CH3
*
Secondary alcohol
CH3
CH3
C* OH
Tertiary alcohol
CH3
Chapter 10
7
IUPAC Nomenclature
• Find the longest carbon chain containing the carbon
with the —OH group.
• Drop the -e from the alkane name, add -ol.
• Number the chain giving the —OH group the lowest
number possible.
• Number and name all substituents and write them in
alphabetical order.
Chapter 10
8
Examples of Nomenclature
OH
CH3
CH3
3
CH3
CH CH2OH
2
1
1
2-methyl-1-propanol
2-methylpropan-1-ol
2
CH3
CH3
1
C OH
CH3
CH CH2CH3
2
3
4
2-butanol
butan-2-ol
2-methyl-2-propanol
2-methylpropan-2-ol
Chapter 10
9
Alkenols (Enols)
• Hydroxyl group takes precedence. Assign the carbon
with the —OH the lowest number.
• End the name in –ol, but also specify that there is a
double bond by using the ending –ene before -ol
OH
CH2
5
CHCH2CHCH3
4
3
2 1
4-penten-2-ol
pent-4-ene-2-ol
Chapter 10
10
Naming Priority
Highest ranking
Lowest ranking
1. Acids
2. Esters
3. Aldehydes
4. Ketones
5. Alcohols
6. Amines
7. Alkenes
8. Alkynes
9. Alkanes
10. Ethers
11. Halides
Chapter 10
11
Hydroxy Substituent
• When —OH is part of a higher priority class of
compound, it is named as hydroxy.
carboxylic acid
OH
CH2CH2CH2COOH
4
3
2
1
4-hydroxybutanoic acid
also known as g-hydroxybutyric acid (GHB)
Chapter 10
12
Common Names
• Alcohol can be named as alkyl alcohol.
• Useful only for small alkyl groups.
OH
CH3
CH3
CH CH2OH
isobutyl alcohol
CH3
CH CH2CH3
sec-butyl alcohol
Chapter 10
13
Naming Diols
• Two numbers are needed to locate the two
—OH groups.
• Use -diol as suffix instead of -ol.
1
2
3
4
5
6
hexane-1,6- diol
Chapter 10
14
Glycols
• 1, 2-diols (vicinal diols) are called glycols.
• Common names for glycols use the name of the alkene
from which they were made.
ethane-1,2- diol
ethylene glycol
propane-1,2- diol
propylene glycol
Chapter 10
15
Phenol Nomenclature
• —OH group is assumed to be on carbon 1.
• For common names of disubstituted phenols, use
ortho- for 1,2; meta- for 1,3; and para- for 1,4.
• Methyl phenols are cresols.
OH
OH
H3C
Cl
3-chlorophenol
(meta-chlorophenol)
4-methylphenol
(para-cresol)
Chapter 10
16
Solved Problem 1
Give the systematic (IUPAC) name for the following alcohol.
Solution
The longest chain contains six carbon atoms, but it does not contain the carbon bonded to the hydroxyl
group. The longest chain containing the carbon bonded to the —OH group is the one outlined by the
green box, containing five carbon atoms. This chain is numbered from right to left in order to give the
hydroxyl-bearing carbon atom the lowest possible number.
The correct name for this compound is 3-(iodomethyl)-2-isopropylpentan-1-ol.
Chapter 10
17
Physical Properties
• Alcohols have high boiling points due to
hydrogen bonding between molecules.
• Small alcohols are miscible in water, but
solubility decreases as the size of the alkyl
group increases.
Chapter 10
18
Boiling Points of alcohols
• Alcohols have higher boiling points than ethers and
alkanes because alcohols can form hydrogen bonds.
• The stronger interaction between alcohol molecules will
require more energy to break them resulting in a higher
boiling point.
Chapter 10
19
Solubility in Water
Small alcohols are miscible in
water, but solubility decreases as
the size of the alkyl group
increases.
Chapter 10
20
Methanol
•
•
•
•
•
“Wood alcohol”
Industrial production from synthesis gas
Common industrial solvent
Toxic Dose: 100 mL methanol
Used as fuel at Indianapolis 500
–
–
–
–
–
Fire can be extinguished with water
High octane rating
Low emissions
Lower energy content
Invisible flame
Chapter 10
21
Ethanol
•
•
•
•
•
•
•
Fermentation of sugar and starches in grains
12–15% alcohol, then yeast cells die
Distillation produces “hard” liquors
Azeotrope: 95% ethanol, constant boiling
Denatured alcohol used as solvent
Gasahol: 10% ethanol in gasoline
Toxic dose: 200 mL
Chapter 10
22
Acidity of Alcohols
• pKa range: 15.5–18.0 (water: 15.7)
• Acidity decreases as the number of carbons
increase.
• Halogens and other electron withdrawing
groups increase the acidity.
• Phenol is 100 million times more acidic than
cyclohexanol!
Chapter 10
23
Table of Ka Values
Chapter 10
24
Formation of Alkoxide Ions
• Ethanol reacts with sodium metal to form sodium ethoxide
(NaOCH2CH3), a strong base commonly used for elimination
reactions.
• More hindered alcohols like 2-propanol or tert-butanol react
faster with potassium than with sodium.
Chapter 10
25
Formation of Phenoxide Ion
The aromatic alcohol phenol is more acidic than aliphatic
alcohols due to the ability of aromatic rings to delocalize
the negative charge of the oxygen within the carbons of
the ring.
Chapter 10
26
Charge Delocalization on the Phenoxide Ion
• The negative charge of the oxygen can be delocalized over four atoms
of the phenoxide ion.
• There are three other resonance structures that can localize the
charge in three different carbons of the ring.
• The true structure is a hybrid between the four resonance forms.
Chapter 10
27
Synthesis of Alcohols (Review)
• Alcohols can be synthesized by nucleophilic
substitution of alkyl halide.
• Hydration of alkenes also produce alcohols:
Chapter 10
28
Synthesis of Vicinal Diols
Vicinal diols can be synthesized by two
different methods:
• Syn hydroxylation of alkenes
– Cold, dilute, basic potassium permanganate
Chapter 10
29
Reduction of Carbonyl
• Reduction of aldehyde yields 1º alcohol.
• Reduction of ketone yields 2º alcohol.
• Reagents:
– Sodium borohydride, NaBH4
– Lithium aluminum hydride, LiAlH4
– Raney nickel
Chapter 10
30
Sodium Borohydride
• NaBH4 is a source of hydrides (H-)
• Hydride attacks the carbonyl carbon,
forming an alkoxide ion.
• Then the alkoxide ion is protonated by
dilute acid.
• Only reacts with carbonyl of aldehyde or
ketone, not with carbonyls of esters or
carboxylic acids.
Chapter 10
31
Lithium Aluminum Hydride
• LiAlH4 is source of hydrides (H-)
• Stronger reducing agent than sodium
borohydride, but dangerous to work with.
• Reduces ketones and aldehydes into the
corresponding alcohol.
• Converts esters and carboxylic acids to 1º
alcohols.
Chapter 10
32
Reduction with LiAlH4
• The LiAlH4 (or LAH) will add two hydrides to the ester
to form the primary alkyl halide.
• The mechanism is similar to the attack of Grignards
on esters.
Chapter 10
33
Reducing Agents
• NaBH4 can reduce
aldehydes and ketones
but not esters and
carboxylic acids.
• LiAlH4 is a stronger
reducing agent and will
reduce all carbonyls.
Chapter 10
34
Catalytic Hydrogenation
• Raney nickel is a hydrogen rich nickel powder that is more
reactive than Pd or Pt catalysts.
• This reaction is not commonly used because it will also
reduce double and triple bonds that may be present in the
molecule.
• Hydride reagents are more selective so they are used
more frequently for carbonyl reductions.
Chapter 10
35
Thiols (Mercaptans)
• Sulfur analogues of alcohols are called thiols.
• The —SH group is called a mercapto group.
• Named by adding the suffix -thiol to the alkane
name.
• They are commonly made by a substitution.
• Primary alkyl halides work better.
Chapter 10
36
Synthesis of Thiols
• The thiolate will attack the carbon displacing the
halide.
• This is a substitution reaction
• methyl halides will react faster than primary alkyl
halides.
• To prevent dialylation use a large excess of sodium
hydrosulfide with the alkyl halide.
Chapter 10
37
Alcohol Reactions
•
•
•
•
•
•
Dehydration to alkene
Oxidation to aldehyde, ketone
Substitution to form alkyl halide
Reduction to alkane
Esterification
Williamson synthesis of ether
Chapter 11
38
Summary Table
Chapter 11
39
Oxidation States
• Easy for inorganic salts (reduced, organic oxidized)
– CrO42- 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
40
Oxidation States
• Easy for inorganic salts (reduced, organic oxidized)
– CrO42- 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
41
1º, 2º, 3º Carbons
Chapter 11
42
Oxidation of 2° Alcohols
•
•
•
•
2° alcohol becomes a ketone
Reagent is Na2Cr2O7/H2SO4 = H2CrO4
Active reagent probably H2CrO4
Color change: orange to greenish-blue
OH
CH3CHCH2CH3
Na2Cr2O7 / H2SO4
O
CH3CCH2CH3
=>
Chapter 11
43
Oxidation 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.
OH
N H CrO3Cl
CH3CH2CH2CH2
O
CH3CH2CH2CH
Chapter 11
44
3° Alcohols Don’t Oxidize
• Cannot lose 2 H’s
• Basis for chromic acid test
Chapter 11
45
Alcohol as a Nucleophile
H
C
O
R
X
• ROH is weak nucleophile
• RO- is strong nucleophile
• New O-C bond forms, O-H bond breaks.
Chapter 11
46
Alcohol 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).
H
+
C
O
C-Nuc bond forms,
C-O bond breaks
Chapter 11
47
Reduction of Alcohols
• Dehydrate with conc. H2SO4, then add H2
OH
CH3CHCH3
alcohol
H2SO4
CH2
CHCH3
alkene
Chapter 11
H2
Pt
CH3CH2CH3
alkane
48
Reaction 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
R O H
H3O
+
H
R O H
Chapter 11
-
Br
R Br
49
Reaction 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. HCl
– 1° alcohols react slowly or not at all.
– 2 alcohols react in 1-5 minutes.
– 3 alcohols react in less than 1 minute.
Chapter 11
50
Limitations of HX Reactions
• Poor yields of 1° and 2° chlorides
• May get alkene instead of alkyl halide
Chapter 11
51
Reactions with Phosphorus Halides
• Good yields with 1° and 2° alcohols
• PCl3 for alkyl chloride (but SOCl2 better)
• PBr3 for alkyl bromide
Chapter 11
52
Dehydration Reactions
•
•
•
•
•
•
Conc. H2SO4 (or H3PO4) produces alkene
Carbocation intermediate
Zaitsev product
Bimolecular dehydration produces ether
Low temp, 140°C and below, favors ether
High temp, 180°C and above, favors alkene
Chapter 11
53
Ethers
H
O
O
O
H
Hydrogen Oxide
Aka Water
R
H
Alcohol
R
R
Ether
• Ethers contain an sp3 hybridized oxygen atom
• Ethers do not hydrogen bond between each
other, but will hydrogen bond with water and
alcohols.
• Ethers are polar and water soluble
Ether Nomenclature
Common System
Give alkyl names to the carbon groups (alkyl groups)
bonded to the oxygen, followed by ether.
Examples
Ether Nomenclature
Common System
Give alkyl names to the carbon groups (alkyl groups)
bonded to the oxygen, followed by ether.
Examples
Dimethyl ether
Ether Nomenclature
Common System
Give alkyl names to the carbon groups (alkyl groups)
bonded to the oxygen, followed by ether.
Examples
Dimethyl ether
Ethylmethyl ether
Ether Nomenclature
Common System
Give alkyl names to the carbon groups (alkyl groups)
bonded to the oxygen, followed by ether.
Examples
Dimethyl ether
Ethylmethyl ether
Isopropylmethyl ether
Ether Nomenclature
Common System
Give alkyl names to the carbon groups (alkyl groups)
bonded to the oxygen, followed by ether.
Examples
Dimethyl ether
Ethylmethyl ether
Isopropylmethyl ether
Sec-butylcyclopropyl
ether
Ether Nomenclature
IUPAC System
Name the longest chain of carbons in the normal
fashion. The oxygen containing group is named by
giving the carbon portion the Latin root followed by
oxy.
Examples
Methoxymethane
Ether Nomenclature
IUPAC System
Name the longest chain of carbons in the normal
fashion. The oxygen containing group is named by
giving the carbon portion the Latin root followed by
oxy.
Examples
Methoxymethane
Methoxyethane
Ether Nomenclature
IUPAC System
Name the longest chain of carbons in the normal
fashion. The oxygen containing group is named by
giving the carbon portion the Latin root followed by
oxy.
Examples
Methoxymethane
Methoxyethane
2-Methoxypropane
Ether Nomenclature
IUPAC System
Name the longest chain of carbons in the normal
fashion. The oxygen containing group is named by
giving the carbon portion the Latin root followed by
oxy.
Examples
Methoxymethane
Methoxyethane
2-Methoxypropane
2-Cyclopropoxybutane
Ether Formation
• Primary alcohols can dehydrate to ethers
• This reaction occurs at lower temperature than the competing dehydration to an alkene
•This method generally does not work with secondary or tertiary alcohols because elimination
competes strongly
The mechanism is an SN2 reaction:
Williamson Ether Synthesis
• Good for unsymmetrical ethers
Dehydration Mechanisms
H
OH
CH3CHCH3
H2SO4
OH
CH3CHCH3
CH3CHCH3
alcohol
H2O
CH2
CHCH3
+
CH3OH
H3O
CH3
CH3
OH2
O CH3
H
CH3OH
H2O
Chapter 11
CH3OCH3
66
Esterification
• Fischer: alcohol + carboxylic acid
• Nitrate esters
• Phosphate esters
Chapter 11
67
Fischer Esterification
• Acid + Alcohol yields Ester + Water
• Sulfuric acid is a catalyst.
• Each step is reversible.
O
CH3
C OH
CH3
+ H O CH2CH2CHCH3
+
H
O
CH3
CH3C OCH2CH2CHCH3
+ HOH
Chapter 11
68
Sulfate Esters
Alcohol + Sulfuric Acid
O
HO
S OH
H
+ H O CH2CH3
O
HO
S OCH2CH3
O
O
CH3CH2O H + HO
O
+
S
O
+
OCH2CH3
O
Chapter 11
H
CH3CH2O
S
OCH2CH3
O
=>
69
Nitrate Esters
O
O
+
N OH
+
H O CH2CH3
H
O
N OCH2CH3
O
Chapter 11
70
Phosphate Esters
=>
Chapter 11
71
Phosphate Esters in DNA
O CH2
base
O
H
H
H
O
O
CH2
O
H
P
O
base
O
H
H
O
O
CH2
O
H
P
O
base
O
H
H
O
O
CH2
O
H
P
O
base
O
H
H
O
O
P
O
Chapter 11
O
=>
72
End of Chapter 5
Chapter 11
73