Download Alcohols

Organic Chemistry, 5th Edition
L. G. Wade, Jr.
Chapter 10
Structure and Synthesis
of Alcohols
Jo Blackburn
Richland College, Dallas, TX
Dallas County Community College District
2003, Prentice Hall
Structure of Alcohols
• Hydroxyl (OH) functional group
• Oxygen is sp3 hybridized.
=>
Chapter 10
2
Classification
• 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
Classify these:
CH3
CH3
CH3
CH CH2OH
CH3
C OH
CH3
OH
OH
CH3
Chapter 10
CH CH2CH3
=>
4
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, starting from the end
closest to the -OH group.
• Number and name all substituents. =>
Chapter 10
5
Name these:
CH3
CH3
CH CH2OH
2-methyl-1-propanol
OH
CH3
CH CH2CH3
2-butanol
CH3
CH3
OH
C OH
CH3
2-methyl-2-propanol
Br
CH3
3-bromo-3-methylcyclohexanol
=>
Chapter 10
6
Unsaturated Alcohols
• Hydroxyl group takes precedence. Assign
that carbon the lowest number.
• Use alkene or alkyne name.
OH
CH2
CHCH2CHCH3
4-penten-2-ol (old)
pent-4-ene-2-ol
(1997 revision of IUPAC rules)
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Chapter 10
7
Naming Priority
•
•
•
•
•
•
Acids
Esters
Aldehydes
Ketones
Alcohols
Amines
•
•
•
•
•
Alkenes
Alkynes
Alkanes
Ethers
Halides
=>
Chapter 10
8
Hydroxy Substituent
• When -OH is part of a higher priority class of
compound, it is named as hydroxy.
• Example:
OH
CH2CH2CH2COOH
also known as GHB
4-hydroxybutanoic acid
=>
Chapter 10
9
Common Names
• Alcohol can be named as alkyl alcohol.
• Useful only for small alkyl groups.
• Examples:
CH3
CH3
CH CH2OH
isobutyl alcohol
OH
CH3
CH CH2CH3
sec-butyl alcohol
=>
Chapter 10
10
Naming Diols
• Two numbers are needed to locate the two
-OH groups.
• Use -diol as suffix instead of -ol.
OH
HO
1,6-hexanediol
=>
Chapter 10
11
Glycols
• 1, 2 diols (vicinal diols) are called glycols.
• Common names for glycols use the name of
the alkene from which they were made.
CH2CH2
CH2CH2CH3
OH OH
OH OH
1,2-ethanediol
1,2-propanediol
ethylene glycol
propylene glycol
Chapter 10
=> 12
Naming Phenols
• -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.
OH
• Methyl phenols are cresols.
OH
H3C
4-methylphenol
para-cresol
Cl
3-chlorophenol
meta-chlorophenol
=>
Chapter 10
13
Physical Properties
• Unusually 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
14
Boiling Points
=>
Chapter 10
15
Solubility in Water
Solubility decreases as the size
of the alkyl group increases.
Chapter 10
=>
16
Methanol
•
•
•
•
“Wood alcohol”
Industrial production from synthesis gas
Common industrial solvent
Fuel at Indianapolis 500
Fire can be extinguished with water
High octane rating
Low emissions
But, lower energy content
Invisible flame
Chapter 10
=>
17
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 ethanol, 100 mL methanol
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Chapter 10
18
2-Propanol
• “Rubbing alcohol”
• Catalytic hydration of propene
CH2 CH CH2 + H2O
100-300 atm, 300°C
catalyst
CH3 CH CH3
OH
=>
Chapter 10
19
Acidity of Alcohols
• pKa range: 15.5-18.0 (water: 15.7)
• Acidity decreases as alkyl group
increases.
• Halogens increase the acidity.
• Phenol is 100 million times more acidic
than cyclohexanol!
=>
Chapter 10
20
Table of Ka Values
CH3
OH
=>
Chapter 10
21
Formation of Alkoxide
Ions
React methanol and ethanol with sodium
metal (redox reaction).
CH3CH2OH +
Na
CH3CH2O
Na
1
+ /2 H2
React less acidic alcohols with more
reactive potassium.
(CH3)3C OH +
(CH3)3CO
K
K
+ 1/2 H2
=>
Chapter 10
22
Formation of Phenoxide
Ion
Phenol reacts with hydroxide ions to form
phenoxide ions - no redox is necessary.
O
O H
+
OH
+
HOH
pKa = 15.7
pKa = 10
=>
Chapter 10
23
Synthesis (Review)
• Nucleophilic substitution of OH- on alkyl
halide
• Hydration of alkenes
water in acid solution (not very effective)
oxymercuration - demercuration
hydroboration - oxidation
=>
Chapter 10
24
Glycols (Review)
• Syn hydroxylation of alkenes
osmium tetroxide, hydrogen peroxide
cold, dilute, basic potassium
permanganate
• Anti hydroxylation of alkenes
peroxyacids, hydrolysis
=>
Chapter 10
25
Organometallic
Reagents
• Carbon is bonded to a metal (Mg or Li).
• Carbon is nucleophilic (partially
negative).
• It will attack a partially positive carbon.
C - X
C = O
• A new carbon-carbon bond forms.
=>
Chapter 10
26
Grignard Reagents
•
•
•
•
Formula R-Mg-X (reacts like R:- +MgX)
Stabilized by anhydrous ether
Iodides most reactive
May be formed from any halide
primary
secondary
tertiary
vinyl
aryl
=>
Chapter 10
27
Some Grignard
Reagents
Br
+
ether
Mg
Cl
CH3CHCH2CH3
+
Mg
CH3C CH2
Br
+
Mg
ether
ether
MgBr
MgCl
CH3CHCH2CH3
CH3C CH2
=>
MgBr
Chapter 10
28
Organolithium Reagents
• Formula R-Li (reacts like R:- +Li)
• Can be produced from alkyl, vinyl, or
aryl halides, just like Grignard reagents.
• Ether not necessary, wide variety of
solvents can be used.
=>
Chapter 10
29
Reaction with Carbonyl
• R:- attacks the partially positive carbon in the
carbonyl.
• The intermediate is an alkoxide ion.
• Addition of water or dilute acid protonates the
alkoxide to produce an alcohol.
R
C O
R C O
R C OH
HOH
Chapter 10
=>
30
OH
Synthesis of 1° Alcohols
Grignard + formaldehyde yields a primary
alcohol with one additional carbon.
CH3
H3C C CH2
C
H
H
CH3
H
H
MgBr
C O
CH3
CH CH2
H
CH2
H
MgBr
H
CH3
CH3
C O
CH CH2
H
CH2
HOH
C O H
H
=>
Chapter 10
31
Synthesis of 2º Alcohols
Grignard + aldehyde yields a secondary
alcohol.
CH3
H3C C CH2
C
H
H
CH3
H3C
H
MgBr
C O
CH3
CH CH2
CH3
CH2
H
MgBr
H
CH3
CH3
C O
CH CH2
CH3
CH2
HOH
C O H
H
=>
Chapter 10
32
Synthesis of 3º Alcohols
Grignard + ketone yields a tertiary alcohol.
CH3
H3C C CH2
C
H
H
CH3
H3C
H
MgBr
C O
CH3
CH CH2
CH3
CH2
H3C
MgBr
CH3
CH3
CH3
C O
CH CH2
CH3
CH2
HOH
C O H
CH3
=>
Chapter 10
33
How would you
synthesize…
OH
CH2OH
CH3CH2CHCH2CH2CH3
OH
OH
CH3
C CH3
CH2CH3
Chapter 10
=>
34
Grignard Reactions
with Acid Chlorides
and Esters
• Use two moles of Grignard reagent.
• The product is a tertiary alcohol with
two identical alkyl groups.
• Reaction with one mole of Grignard
reagent produces a ketone
intermediate, which reacts with the
second mole of Grignard reagent.
=>
Chapter 10
35
Grignard + Acid
Chloride (1)
• Grignard attacks the carbonyl.
• Chloride ion leaves.
CH3
H3C
R
MgBr
C O
Cl
CH3
R C O
R C O
MgBr
Cl
CH3
MgBr
R C
Cl
+
MgBrCl
O
Ketone intermediate
Chapter 10
=>
36
Grignard and Ester (1)
• Grignard attacks the carbonyl.
• Alkoxide ion leaves! ? !
CH3
H3C
R
MgBr
C O
R C O
CH3O
OCH3
CH3
R C O
OCH3
MgBr
CH3
MgBr
R C
+
O
MgBrOCH3
Ketone intermediate
Chapter 10
=>
37
Second step of reaction
• Second mole of Grignard reacts with the
ketone intermediate to form an alkoxide ion.
• Alkoxide ion is protonated with dilute acid.
CH3
CH3
R
MgBr
+
R C
R C O
O
MgBr
R
HOH
CH3
R C OH
R
Chapter 10
=>
38
How would you
synthesize...
Using an acid chloride or ester.
OH
CH3
CH3CH2CCH3
C
CH3
OH
OH
CH3CH2CHCH2CH3
Chapter 10
=>
39
Grignard Reagent +
Ethylene Oxide
• Epoxides are unusually reactive ethers.
• Product is a 1º alcohol with 2 additional
carbons.
O
O
MgBr
+
CH2
MgBr
CH2CH2
CH2
HOH
O H
CH2CH2
Chapter 10
=>
40
Limitations of Grignard
• No water or other acidic protons like
O-H, N-H, S-H, or -C—C-H. Grignard
reagent is destroyed, becomes an
alkane.
• No other electrophilic multiple bonds,
like C=N, C—N, S=O, or N=O.
=>
Chapter 10
41
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
42
Sodium Borohydride
• Hydride ion, H , 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.
O
C
H
H
C
H
H
O
+
H
H3O
O H
C
H
=>
Chapter 10
43
Lithium Aluminum Hydride
• Stronger reducing agent than sodium
borohydride, but dangerous to work with.
• Converts esters and acids to 1º alcohols.
O
C
OCH3
H
LAH
H3O+
Chapter 10
C
O H
H
=>
44
Comparison of
Reducing Agents
• LiAlH4 is stronger.
• LiAlH4 reduces more
stable compounds
which are resistant
to reduction.
=>
Chapter 10
45
Catalytic Hydrogenation
• Add H2 with Raney nickel catalyst.
• Also reduces any C=C bonds.
OH
O
OH
H2, Raney Ni
NaBH4
=>
Chapter 10
46
Thiols (Mercaptans)
•
•
•
•
•
Sulfur analogues of alcohols, -SH.
Named by adding -thiol to alkane name.
The -SH group is called mercapto.
Complex with heavy metals: Hg, As, Au.
More acidic than alcohols, react with
NaOH to form thiolate ion.
• Stinks!
=>
Chapter 10
47
Thiol Synthesis
Use a large excess of sodium
hydrosulfide with unhindered alkyl
halide to prevent dialkylation to R-S-R.
_
H S
_
R X
R
SH
+ X
=>
Chapter 10
48
Thiol Oxidation
• Easily oxidized to disulfides, an
important feature of protein structure.
Br2
R
SH
+ HS
R
R
S
S
R +
2 HBr
Zn, HCl
Vigorous oxidation with KMnO4,
HNO3, or NaOCl, produces sulfonic acids.
•
SH
HNO3
boil
O
S
O
Chapter 10
OH
=>
49
End of Chapter 10
Chapter 10
50