Download Dehydration of ROH

William H. Brown
Christopher S. Foote
Brent L. Iverson
Eric Anslyn
http://academic.cengage.com/chemistry/brown
Chapter 10
Alcohols
William H. Brown • Beloit College
10-1
Structure of Alcohols
 The
functional group of an alcohol is
an -OH group bonded to an sp3
hybridized carbon.
• Bond angles about the hydroxyl oxygen
atom are approximately 109.5°.
 Oxygen
is sp3 hybridized.
H
O
108.9°
C
H
H
H
• Two sp3 hybrid orbitals form sigma bonds
to a carbon and a hydrogen.
• The remaining two sp3 hybrid orbitals
each contain an unshared pair of
electrons.
10-2
Nomenclature of Alcohols
 IUPAC
names
• The parent chain is the longest chain that contains the
OH group.
• Number the parent chain to give the OH group the
lowest possible number.
• Change the suffix -e to -ol.
 Common
names
• Name the alkyl group bonded to oxygen followed by
the word alcohol.
10-3
Nomenclature of Alcohols
 Examples
OH
OH
OH
1-Propanol
(Propyl alcohol)
1-Bu tanol
(Bu tyl alcoh ol)
2-Propan ol
(Isoprop yl alcoh ol)
OH
OH
OH
2-Butanol
(s ec-Butyl alcohol)
3
2-Meth yl-1-p ropan ol
(Isobutyl alcohol)
10
2
1
4
2
9
3
OH
6
cis-3-Methylcyclohexan ol
OH
1
8
5
2-Meth yl-2-p ropan ol
(tert -Butyl alcohol)
7
6
4
5
Numbering of th e
bicyclic ring takes
preced ence over
the location of -OH
Bicyclo[4.4.0]decan -3-ol
10-4
Nomenclature of Alcohols
 Compounds
containing more than one OH group
are named diols, triols, etc.
CH2 CH2
OH OH
1,2-Ethanediol
(Ethylene glycol)
CH 3 CHCH2
HO OH
1,2-Propanediol
(Propylene glycol)
CH2 CHCH2
HO HO OH
1,2,3-Propanetriol
(Glycerol, Glycerine)
10-5
Nomenclature of Alcohols
 Unsaturated
alcohols
• Show the double bond by changing the infix from -anto -en-.
• Show the the OH group by the suffix -ol.
• Number the chain to give OH the lower number.
HO
1
2 3
6
4 5
(E)-2-Hexene-1-ol
(t rans-2-Hexen-1-ol)
10-6
Physical Properties
 Alcohols
are polar compounds.
• They interact with themselves and with other polar
compounds by dipole-dipole interactions.
 Dipole-dipole
interaction: The attraction between
the positive end of one dipole and the negative
10-7
end of another.
Physical Properties
 Hydrogen
bonding: When the positive end of one
dipole is an H bonded to F, O, or N (atoms of high
electronegativity) and the other end is F, O, or N.
• The strength of hydrogen bonding in water is
approximately 21 kJ (5 kcal)/mol.
• Hydrogen bonds are considerably weaker than
covalent bonds.
• Nonetheless, they can have a significant effect on
physical properties.
10-8
Hydrogen Bonding
 The
association of ethanol molecules in the
liquid state by hydrogen bonding.
10-9
Physical Properties
 Ethanol
and dimethyl ether are constitutional
isomers.
 Their boiling points are dramatically different
• Ethanol forms intermolecular hydrogen bonds, which
are attractive forces between its molecules, resulting
in a higher boiling point.
• There is no comparable attractive force between
molecules of dimethyl ether.
CH3 CH2 OH
CH3 OCH3
Ethanol
bp 78°C
Dimethyl ether
bp -24°C
10-10
Physical Properties
 In
relation to alkanes of comparable size and
molecular weight, alcohols
• have higher boiling points.
• are more soluble in water.
 The
presence of additional -OH groups in a
molecule further increases solubility in water and
boiling point.
10-11
Physical Properties
MW
bp
(°C)
Solubility
in Water
Structural Formula
Name
CH3 OH
Methanol
Ethane
32
30
65
-89
Infinite
Insoluble
CH3 CH2 CH3
Ethanol
Propane
46
44
78
-42
Infinite
Insoluble
CH3 CH2 CH2 OH
CH3 CH2 CH2 CH3
1-Propanol
Butane
60
58
97
0
Infinite
Insoluble
CH3 ( CH 2 ) 2 CH 2 OH
1-Butanol
Pentane
74
72
117
36
8 g/100 g
Insoluble
90
88
86
230
138
69
Infinite
2.3 g/100 g
Insoluble
CH3 CH3
CH3 CH2 OH
CH3 ( CH 2 ) 3 CH3
HOCH2 ( CH2 ) 2 CH2 OH 1,4-Butanediol
CH3 ( CH 2 ) 3 CH2 OH
1-Pentanol
CH3 ( CH 2 ) 4 CH3
Hexane
10-12
Acidity of Alcohols
 In
dilute aqueous solution, alcohols are weakly
acidic.
CH3 O H + :O H
H
Ka =
+
CH3 O: + H O H
[ CH3 O-] [H3 O+ ]
[ CH3 OH]
–
H
= 1 0 - 15 .5
pKa = 1 5 .5
10-13
Acidity of Alcohols
Compound
Structural
Formula
pK a
Hydrogen chloride
HCl
-7
Acetic acid
CH 3 COO H
Methanol
CH 3 OH
15.5
Water
H2O
15.7
Ethanol
CH 3 CH 2 OH
15.9
2-Propanol
( CH 3 ) 2 CHO H
17
2-Methyl-2-propanol
( CH 3 ) 3 COH
18
4.8
Stronger
acid
Weaker
acid
Also given for comparison are p K a values for
water, acetic acid, and hydrogen chloride.
10-14
Acidity of Alcohols
 Acidity
depends primarily on the degree of
stabilization and solvation of the alkoxide ion.
• The negatively charged oxygens of methoxide and
ethoxide are about as accessible as the oxygen of
hydroxide ion for solvation; these alcohol are about as
acidic as water.
• As the bulk of the alkyl group increases, the ability of
water to solvate the alkoxide decreases, the acidity of
the alcohol decreases, and the basicity of the alkoxide
ion increases.
10-15
Reaction with Metals
 Alcohols
react with Li, Na, K, and other active
metals to liberate hydrogen gas and form metal
alkoxides.
2 CH3 O Na + + H2
2 CH3 OH + 2 Na
Sodium methoxide
(MeO Na +)
 Alcohols
are also converted to metal alkoxides
by reaction with bases stronger than the alkoxide
ion.
• One such base is sodium hydride.
CH3 CH2 OH
Ethanol
+
Na+ H
Sodium
hydride
CH3 CH2 O Na + + H2
Sodium ethoxide
10-16
Reaction with HX
• 3° alcohols react very rapidly with HCl, HBr, and HI.
OH + HCl
2-Methyl-2prop anol
25°C
Cl + H2 O
2-Chloro-2methylpropane
• Low-molecular-weight 1° and 2° alcohols are
unreactive under these conditions.
• 1° and 2° alcohols require concentrated HBr and HI to
form alkyl bromides and iodides.
OH +
1-Butanol
HBr
H2 O
reflux
Br
+
H2 O
1-Bromobutane
10-17
Reaction with HX
• With HBr and HI, 2° alcohols generally give some
rearranged product.
a product of
rearrangement
Br
OH
+ HBr
+ H2 O
+
heat
3-Pentanol
3-Bromopentane
(major product)
Br
2-Bromopentane
• 1° alcohols with extensive -branching give large
amounts of rearranged product.
Br
OH + HBr
 
2,2-D imethyl-1propanol
+ H2 O
2-Bromo-2-meth ylb utane
(a product of rearrangement)
10-18
Reaction with HX
 Based
on
• the relative ease of reaction of alcohols with HX (3° >
2° > 1°) and
• the occurrence of rearrangements,
 Chemists
propose that reaction of 2° and 3°
alcohols with HX
• occurs by an SN1 mechanism, and
• involves a carbocation intermediate
10-19
Reaction with HX - SN1
Step 1: Proton transfer to the OH group gives an
oxonium ion.
CH 3
+
:
CH3 -C-OH
rapid and
reversib le
+
H O H
CH3
CH3 -C
H
CH 3
CH3
H
O
+
+
H
:O H
H
Step 2: Loss of H2O gives a carbocation intermediate.
CH3
CH3 -C
CH3
H
O
+
H
s low , rate
determin ing
SN 1
H
CH3
CH3 - C+
+
:O
CH3
H
A 3° carbocation
intermed iate
10-20
Reaction with HX - SN1
Step 3: Reaction of the carbocation intermediate (an
electrophile) with halide ion (a nucleophile) gives the
product.
CH3
CH3 - C+
CH3
+
:Cl
fast
CH3
CH3 - C- Cl
CH3
2-Chloro-2-methylprop ane
(t ert-Butyl ch loride)
10-21
Reaction with HX - SN2
 1°
alcohols react with HX by an SN2 mechanism.
Step 1: Rapid and reversible proton transfer.
RCH2 - O H
+
rapid and
reversible
+
H
O
H
H
+
RCH2 - O
H
+
O
H
H
H
Step 2: Displacement of HOH by halide ion.
Br:-
+
+ RCH2 -O
H
H
slow , rate
determining
SN2
H
RCH2 -Br
+ :O
H
10-22
Reaction with HX
 For
1° alcohols with extensive -branching
• SN1 is not possible because this pathway would
require a 1° carbocation.
• SN2 is not possible because of steric hindrance
created by the -branching.
 These
alcohols react by a concerted loss of HOH
and migration of an alkyl group.
10-23
Reaction with HX
• Step 1: Proton transfer gives an oxonium ion.
+
+ H O H
O
H
2,2-D imethyl-1prop anol
H
rapid and
revers ible
H
O+ +
H
An oxonium ion
O H
H
• Step 2: Concerted elimination of HOH and migration
of a methyl group gives a 3° carbocation.
H
O
H
H
s low an d
rate determining
+ O
(concerted)
H
A 3° carbocation
intermed iate
10-24
Reaction with HX
Step 3: Reaction of the carbocation intermediate (an
electrophile) with halide ion (a nucleophile) gives the
product.
Cl
-
+
fast
Cl
2-Ch loro-2-meth ylb utane
10-25
Reaction with PBr3
 An
alternative method for the synthesis of 1° and
2° bromoalkanes is reaction of an alcohol with
phosphorus tribromide.
• This method gives less rearrangement than with HBr.
OH
+
PBr 3
2-Meth yl-1-p ropan ol Phosph orus
(Isobutyl alcohol)
trib romide
0°
Br
1-Bromo-2-methylprop ane
(Is ob utyl bromide)
+
H3 PO 3
Phosp horous
acid
10-26
Reaction with PBr3
Step 1: Formation of a protonated dibromophosphite
converts H2O, a poor leaving group, to a good leaving
group.
a good leaving group
••
R-CH2 -O-H + Br P Br
R-CH2
+
O PBr2 +
Br
H
Br
Step 2: Displacement by bromide ion gives the alkyl
bromide.
+ R-CH2
+
O PBr2
SN 2
R-CH2 -Br + HO-PBr 2
•
•
•
•
Br
-
H
10-27
Reaction with SOCl2
 Thionyl
chloride is the most widely used reagent
for the conversion of 1° and 2° alcohols to alkyl
chlorides.
• A base, most commonly pyridine or triethylamine, is
added to catalyze the reaction and to neutralize the
HCl.
OH +
1-Heptanol
SOCl 2
pyridine
Thionyl
chloride
Cl + SO + HCl
2
1-Chloroheptane
10-28
Reaction with SOCl2
 Reaction
of an alcohol with SOCl2 in the
presence of a 3° amine is stereoselective.
• It occurs with inversion of configuration.
Cl
OH
(S)-2-Octanol
+ SOCl2
Thionyl
chloride
3° amine
+ SO2 + HCl
(R)-2-Chlorooctane
10-29
Reaction with SOCl2
Step 1: Formation of an alkyl chlorosulfite.
R1
R1
O
C O H + Cl-S-Cl
O
C
O S
H-Cl
Cl
H
R2
H
R2
+
An al ky l
chl orosul fi te
Step 2: Nucleophilic displacement of this leaving group
by chloride ion gives the chloroalkane.
R1
Cl
+
O
C O S
H
R2
Cl
SN 2
R1
Cl
+
C
R2
O
O S + Cl
H
10-30
Alkyl Sulfonates
 Sulfonyl
chlorides are derived from sulfonic
acids.
• Sulfonic acids, like sulfuric acid, are strong acids.
O
R- S- Cl
O
A sulfonyl
chloride
O
R- S- OH
O
A s ulfonic acid
(a very s trong acid)
O
R- S- OO
A s ulfonate anion
(a very weak base and
stable anion; a very
good leaving group
10-31
Alkyl Sulfonates
A
commonly used sulfonyl chloride is ptoluenesulfonyl chloride (Ts-Cl).
O
CH3 CH2 OH + Cl-S
CH 3
O
p-Toluenesulfonyl
Ethanol
chloride
pyridine
O
CH 3 CH 2 O-S
CH3 + HCl
O
Ethyl p- toluenesulfonate
(Ethyl tosylate)
10-32
Alkyl Sulfonates
 Another
commonly used sulfonyl chloride is
methanesulfonyl chloride (Ms-Cl).
OH
+
O
Cl-S- CH3
pyridine
O
Cyclohexanol
Methanesulfonyl
chloride
O
O-S-CH3 + HCl
O
Cyclohexyl
methanesulfonate
(Cyclohexyl mes ylate)
10-33
Alkyl Sulfonates
 Sulfonate
anions are very weak bases (the
conjugate bases of strong acids) and are very
good leaving groups for SN2 reactions.
 Conversion of an alcohol to a sulfonate ester
converts HOH, a very poor leaving group, into a
sulfonic ester, a very good leaving group.
10-34
Alkyl Sulfonates
 This
two-step procedure converts (S)-2-octanol
to (R)-2-octyl acetate.
Step 1: Formation of a p-toluenesulfonate (Ts) ester.
OTs
OH
+ TsCl
(S)-2-Octanol
pyridine
+ HCl
(S)-2-Octyl tosylate
Tosyl
chloride
Step 2: Nucleophilic displacement of tosylate.
O
O
OTs
-
+
O Na
S od ium
acetate
O
SN 2
+
(S)-2-Octyl tos ylate
ethanol
+
+ Na OTs
(R)-2-Octyl acetate
10-35
Dehydration of ROH
 An
alcohol can be converted to an alkene by
acid-catalyzed dehydration (a type of elimination).
• 1° alcohols must be heated at high temperature in the
presence of an acid catalyst, such as H2SO4 or H3PO4.
2° alcohols undergo dehydration at somewhat lower
temperatures.
• 3° alcohols often require temperatures at or only
slightly above room temperature.
10-36
Dehydration of ROH
CH3 CH2 OH
OH
H2 SO 4
180°C
CH2 = CH2
H2 SO 4
+
+
H2 O
H2 O
140°C
Cyclohexanol
Cyclohexene
CH3
CH3 COH
CH3
CH3
2-Methyl-2-propanol
(tert- Butyl alcohol)
H2 SO 4
50°C
CH3 C= CH2 + H2 O
2-Methylpropene
(Is obutylene)
10-37
Dehydration of ROH
• Where isomeric alkenes are possible, the alkene
having the greater number of substituents on the
double bond (the more stable alkene) usually
predominates (Zaitsev rule).
OH
CH3 CH2 CHCH3
2-Butanol
8 5 % H3 PO 4
heat
CH3 CH= CH CH 3 + CH3 CH2 CH= CH2 + H2 O
2-Butene
1-Butene
(80%)
(20%)
10-38
Dehydration of ROH
 Dehydration
of 1° and 2° alcohols is often
accompanied by rearrangement.
H2 SO 4
OH
+
140 - 170°C
3,3-Dimethyl2-butanol
2,3-Dimethyl2-butene
(80%)
2,3-Dimethyl1-butene
(20%)
• Acid-catalyzed dehydration of 1-butanol gives a
mixture of three alkenes.
OH
1-Butanol
H2 SO 4
+
+
140 - 170°C
trans- 2-butene
(56%)
cis- 2-butene
(32%)
1-Butene
(12%)
10-39
Dehydration of ROH
 Based
on evidence of
• ease of dehydration (3° > 2° > 1°) and
• prevalence of rearrangements
 Chemists
propose a three-step mechanism for
the dehydration of 2° and 3° alcohols.
• Because this mechanism involves formation of a
carbocation intermediate in the rate-determining step,
it is classified as E1.
10-40
Dehydration of ROH
Step 1: Proton transfer to the -OH group gives an
oxonium ion.
H
H
rapid and
O
+
+
H
O
+
H
O
reversible
H
+
O
H
H
H
Step 2: Loss of H2O gives a carbocation intermediate.
H
+ H
O
slow, rate
determining
+
H2 O
A 2° carbocation
intermediate
10-41
Dehydration of ROH
Step 3: Proton transfer from a carbon adjacent to the
positively charged carbon to water. The sigma
electrons of the C-H bond become the pi electrons of
the carbon-carbon double bond.
H O
H
rap id and
reversible
+
H H
+
+
+ H O H
H
10-42
•Dehydration of ROH
alcohols with little -branching give terminal
alkenes and rearranged alkenes.
 1°
• Step 1: Proton transfer to OH gives an oxonium ion.
O-H +
1-Butanol
+
H O H
H
rapid and
reversible
+
O-H +
H
O-H
H
• Step 2: Loss of H from the -carbon and H2O from the
-carbon gives the terminal alkene.
H O
H
+
+
O-H
H H
H
+
E2
+ H O H+
1-Bu tene
H
O H
H
10-43
Dehydration of ROH
Step 3: Shift of a hydride ion from -carbon and loss of
H2O from the -carbon gives a carbocation.
+
O-H
H H
1,2-s hift of a
hydride ion
+
+
H
O-H
H
A 2° carb ocation
Step 4: Proton transfer to solvent gives the alkene.
H
H O +
H
+
E1
+
+
+H O H
H
t rans-2-Butene cis-2-Butene
10-44
Dehydration of ROH
 Dehydration
with rearrangement occurs by a
carbocation rearrangement.
H+
OH
3,3-D imethyl2-butan ol
-H2 O
+
H2 O
A 2° carbocation
intermed iate
+
+ H3 O+
2,3-D imethyl2-bu tene
A 3° carbocation
intermed iate
H2 O
+ H3 O+
2,3-D imethyl1-bu tene
10-45
Dehydration of ROH
 Acid-catalyzed
alcohol dehydration and alkene
hydration are competing processes.
C
C
An alkene
 Principle
+ H2 O
acid
catalyst
C
C
H OH
An alcohol
of microscopic reversibility: The
sequence of transition states and reactive intermediates
in the mechanism of a reversible reaction must be the
same, but in reverse order, for the reverse reaction as for
the forward reaction.
10-46
Pinacol Rearrangement
 The
products of acid-catalyzed dehydration of a
glycol are different from those of an alcohol.
HO
OH
2,3-D imethyl-2,3-bu taned iol
(Pinacol)
O
H2 SO4
+ H2 O
3,3-D imethyl-2-bu tanone
(Pinacolone)
10-47
Pinacol Rearrangement
Step 1: Proton transfer to OH gives an oxonium ion.
HO
OH
+
rapid and
reversible
+ H O H
H
HO
H
O H
+
An oxoniu m ion
O H
H
Step 2: Loss of water gives a carbocation intermediate.
HO
H
O H
HO
+ H2 O
A 3o carb ocation
intermediate
10-48
Pinacol Rearrangement
Step 3: A 1,2- shift (in this example a methyl group) gives
a more stable carbocation.
H
H
H
O
O
+
+
O
+
A resonance-stabilized cation intermediate
Step 4: Proton transfer to solvent completes the
reaction.
H2 O
+
H O
H3 O
+
+
O
10-49
Oxidation: 1° ROH
 Oxidation
of a primary alcohol gives an aldehyde
or a carboxylic acid, depending on the
experimental conditions.
OH
CH3 -C H
H
A primary
alcohol
[O]
O
CH3 -C- H
An aldehyde
[O]
O
CH3 -C- OH
A carboxylic
acid
• oxidation to an aldehyde is a two-electron oxidation.
• oxidation to a carboxylic acid is a four-electron
oxidation.
10-50
Oxidation of ROH
A
common oxidizing agent for this purpose is
chromic acid, prepared by dissolving
chromium(VI) oxide or potassium dichromate in
aqueous sulfuric acid.
CrO 3
+ H2 O
H2 SO 4
Chromium(VI)
oxide
K2 Cr 2 O 7
Potassium
dichromate
H2 SO 4
H2 Cr O 4
Chromic acid
H2 Cr 2 O 7
H2 O
2 H2 Cr O 4
Chromic acid
10-51
Oxidation: 1° ROH
 Oxidation
of 1-octanol gives octanoic acid.
• The aldehyde intermediate is not isolated.
O
OH
1-Hexan ol
H2 CrO4
H 2O, aceton e
H
Hexan al
(not isolated)
O
OH
Hexan oic acid
10-52
Oxidation: 2° ROH
A
2° alcohol is oxidized by chromic acid to a
ketone.
OH
+ H2 CrO4
2-Isoprop yl-5-methylcycloh exanol
(Men thol)
O
aceton e
+ Cr
3+
2-Is op ropyl-5-methylcycloh exanone
(Men thone)
10-53
Chromic Acid Oxidation of ROH
• Step 1: Formation of a chromate ester.
OH
O
fas t and
revers ible
O
O-Cr-OH
+ HO-Cr-OH
H
Cycloh exanol
O
+ H2 O
H
An alkyl chromate
O
• Step 2: Reaction of the chromate ester with a base,
here shown as H2O.
chromiu m(V I)
chromiu m(IV)
O
O
H
H
slow , rate
Cr-OH determining
O
H
O + O+ H +
H
Cyclohexan on e
OCr-OH
O
O
H
10-54
Chromic Acid Oxidation of RCHO
• Chromic acid oxidizes a 1° alcohol first to an aldehyde
and then to a carboxylic acid.
• In the second step, it is not the aldehyde per se that is
oxidized but rather the aldehyde hydrate.
O
R-C-H + H2 O
An ald ehyde
fas t and
revers ible
OH
R-C-OH
H2 CrO4
H
An ald ehyde
hydrate
O-CrO3 H
R-C-OH
H2 O
H
O
R-C-OH + HCrO3 - + H3 O+
A carb oxylic
acid
10-55
Oxidation: 1° ROH to RCHO
 Pyridinium
chlorochromate (PCC): A form of
Cr(VI) prepared by dissolving CrO3 in aqueous
HCl and adding pyridine to precipitate PCC as a
solid.
pyrid inium ion
chlorochromate ion
CrO3 + HCl
ClCrO3 -
+
N
Pyrid ine
N
H
Pyrid inium ch lorochromate
(PCC)
• PCC is selective for the oxidation of 1° alcohols to
aldehydes; it does not oxidize aldehydes further to
carboxylic acids.
10-56
Oxidation: 1° ROH
• PCC oxidizes a 1° alcohol to an aldehyde.
O
PCC
OH
H
Geraniol
Geranial
• PCC oxidizes a 2° alcohol to a ketone.
OH
Men thol
PCC
O
Men thone
10-57
Oxidation of Alcohols by NAD+
• Biological systems do not use chromic acid or the
oxides of other transition metals to oxidize 1° alcohols
to aldehydes or 2° alcohols to ketones.
• What they use instead is NAD+.
A p yridine
ring
The b usines s
+
end of N AD
O
OH
N
N icotinic acid
(N iacin; Vitamin B6)
O
An amid e grou p
NH2
N
Ad
N icotinamide aden ine
d inucleotide (N AD + )
The p lus sign in N AD +
represents th is ch arge
on nitrogen
• The Ad part of NAD+ is composed of a unit of the sugar
D-ribose (Chapter 25) and one of adenosine
diphosphate (ADP, Chapter 28).
10-58
Oxidation of Alcohols by NAD+
• When NAD+ functions as an oxidizing agent, it is
reduced to NADH.
• In the process, NAD+ gains one H and two electrons;
NAD+ is a two-electron oxidizing agent.
O
CNH2
reduction
H H O
CNH2
+ H+ + 2 e-
N+
Ad
N AD +
(oxid ized form)
oxid ation
N
Ad
N AD H
(red uced form)
10-59
Oxidation of Alcohols by NAD+
• NAD+ is the oxidizing agent in a wide variety of
enzyme-catalyzed reactions, two of which are
CH3 CH2 OH + NAD+
Eth anol
OH
+
CH3 CHCOO + NAD
Lactate
alcohol
d ehydrogenase
O
CH3 CH + NADH + H+
Eth anal
(A cetaldehyde)
lactate
d ehydrogenase
O
CH3 CCOO + NADH + H+
Pyru vate
10-60
Oxidation of Alcohols by NAD+
• The mechanism of NAD+ oxidation of an alcohol.
• Hydride ion transfer to NAD+ is stereoselective; some
enzymes catalyze delivery of hydride ion to the top
face of the pyridine ring, others to the bottom face.
10-61
Oxidation of Glycols
 Glycols
are cleaved by oxidation with periodic
acid, HIO4.
OH
+
OH
cis- 1,2-Cyclohexanediol
HIO 4
Periodic
acid
CHO
CHO
Hexanedial
+ HIO 3
Iodic
acid
10-62
Oxidation of Glycols
 The
mechanism of periodic acid oxidation of a
glycol is divided into two steps.
Step 1: Formation of a cyclic periodate.
O
O
C OH
+ O
C OH
I
O
C
O
OH
I
C
OH + H2 O
O
O
A cyclic period ate
Step 2: Redistribution of electrons within the fivemembered ring.
O
O
C
O
C
I
C
O
OH
+
I
OH
C O
O
O
O
10-63
Oxidation of Glycols
• This mechanism is consistent with the fact that HIO4
oxidations are restricted to glycols that can form a
five-membered cyclic periodate.
• Glycols that cannot form a cyclic periodate are not
oxidized by HIO4.
OH
OH
HO
OH
The t rans is omer is
un reactive tow ard
periodic acid
O
HIO4
O
Th e cis is omer forms
a cyclic periodate and
is cleaved
10-64
Thiols: Structure
 The
functional group of a thiol is an
SH (sulfhydryl) group bonded to an
sp3 hybridized carbon.
 The bond angle about sulfur in
methanethiol is 100.3°, which
indicates that there is considerably
more p character to the bonding
orbitals of divalent sulfur than there
is to the bonding orbitals of divalent
oxygen.
10-65
Nomenclature
 IUPAC
names
• The parent is the longest chain that contains the -SH
group.
• Change the suffix -e to -thiol.
• When -SH is a substituent, it is named as a sulfanyl
group.
 Common
names:
• Name the alkyl group bonded to sulfur followed by the
word mercaptan.
SH
SH
1-Butaneth iol
2-Methyl-1-prop anethiol
(Butyl mercaptan)
(Isobutyl mercaptan)
OH
HS
2-Sulfanylethan ol
(2-Mercap toeth anol)
10-66
Thiols: Physical Properties
 Because
of the low polarity of the S-H bond,
thiols show little association by hydrogen
bonding.
• They have lower boiling points and are less soluble in
water than alcohols of comparable MW.
Thiol
bp (°C)
Methanethiol
6
Ethanethiol
35
1-Butanethiol 98
Alcohol
Methanol
Ethanol
1-Butanol
bp (°C)
65
78
117
• The boiling points of ethanethiol and its constitutional
isomer dimethyl sulfide are almost identical.
CH3 CH2 SH
Ethaneth iol
(bp 35°C)
CH3 SCH3
D imeth yl s ulfide
(b p 37°C)
10-67
Thiols: Physical Properties
 Low-molecular-weight
thiols = STENCH
• The scent of skunks is due primarily to these two
thiols.
SH
SH
2-Buten e-1-th iol 3-Meth yl-1-b utanethiol
(Isopen tyl mercaptan)
• A blend of low-molecular weight thiols is added to
natural gas as an odorant. The two most common of
these are
SH
SH
2-Methyl-2-propan ethiol
2-Propan eth iol
(t ert -Bu tyl mercaptan) (Isoprop yl mercaptan)
10-68
Thiols: preparation
 The
most common preparation of thiols depends
on the very high nucleophilicity of hydrosulfide
ion, HS-.
SN 2
+
+
CH3 (CH2 ) 8 CH2 I
Na SH
ethan ol
S od ium
1-Iod od ecane
h yd rosu lfid e
O
+
-
-
+
Na SH + ICH2 CO Na
Sodium
Sodiu m
hydros ulfide iod oacetate
SN 2
+ -
CH3 (CH2 ) 8 CH2 SH + Na I
1-D ecan ethiol
O
-
+
+ -
HSCH2 CO Na + Na I
Sodiu m mercaptoacetate
(Sodiu m th ioglycolate)
10-69
Thiols: acidity
 Thiols
are stronger acids than alcohols.
CH3 CH2 OH + H2 O
CH3 CH2 O + H3 O
-
+
pK a = 15.9
CH3 CH2 SH + H2 O
CH3 CH2 S
-
+ H3 O+
pK a = 8.5
• When dissolved an aqueous NaOH, they are converted
completely to alkylsulfide salts.
+
CH3 CH2 SH + Na OH
pK a 8.5
(Strong er aci d)
CH3 CH2 S- Na+ +
H2 O
p Ka 15.7
(Weak er acid )
10-70
Thiols: oxidation
 The
sulfur atom of a thiol can be oxidized to
several higher oxidation states.
[O]
R-S-H
A th iol
[O]
R-S-S-R
A disu lfid e
O
R-S-OH
A s ulfinic
acid
[O]
O
R-S-OH
O
A s ulfon ic
acid
• The most common reaction of thiols in biological
systems in interconversion between thiols and
disulfides, -S-S-.
2 RSH +
A thiol
1 O
2 2
RSSR + H2 O
A dis ulfide
10-71
Alcohols
and
Thiols
End of Chapter 10
10-72