Transcript Organic Chemistry - Rutgers University, Newark

Organic
Chemistry
William H. Brown
Christopher S. Foote
Brent L. Iverson
10-1
Alcohols
and Thiols
Chapter 10
10-2
Structure - 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°
H
 Oxygen
is sp3 hybridized
H
O
C
108.9°
H
H
• two sp3 hybrid orbitals form sigma bonds
to carbon and hydrogen
• the remaining two sp3 hybrid orbitals each
contain an unshared pair of electrons
10-3
Nomenclature-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
10-4
Nomenclature-Alcohols
 Examples
OH
OH
OH
1-Propanol
(Propyl alcohol)
1-Butanol
(Butyl alcohol)
2-Propanol
(Isopropyl alcohol)
OH
OH
OH
2-Butanol
(sec-Butyl alcohol)
3
10
2
1
4
5
2-Methyl-1-propanol
(Isobutyl alcohol)
OH
6
cis-3-Methylcyclohexanol
9
8
7
1
6
2-Methyl-2-propanol
(tert-Butyl alcohol)
2
OH
3
4
5
Numbering of the
bicyclic ring takes
precedence over
the location of -OH
Bicyclo[4.4.0]decan-3-ol
10-5
Nomenclature of Alcohols
 Compounds
containing more than one OH group
are named diols, triols, etc.
CH2 CH2
OH OH
1,2-Ethanediol
(Ethylene glycol)
CH3 CHCH2
HO OH
1,2-Propanediol
(Propylene glycol)
CH2 CHCH2
HO HO OH
1,2,3-Propanetriol
(Glycerol, Glycerine)
10-6
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
(trans-2-Hexen-1-ol)
10-7
Physical Properties
 Alcohols
O
are polar compounds
+
H
+C
H
H
H
• 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
end of another
10-8
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
10-9
Hydrogen Bonding
10-10
Physical Properties
 Ethanol
and dimethyl ether are constitutional
isomers.
 Their boiling points are dramatically different
• ethanol forms intermolecular hydrogen bonds which
increase attractive forces between its molecules
resulting in a higher boiling point
• there is no comparable attractive force between
molecules of dimethyl ether
CH 3 CH 2 OH
CH 3 OCH 3
Ethanol
bp 78°C
Dimethyl ether
bp -24°C
10-11
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
10-12
Physical Properties
MW
bp
(°C)
Solubility
in Water
Structural Formula
Name
CH3 OH
Methanol
Ethane
32
30
65
-89
Infinite
Insoluble
Ethanol
Propane
46
44
78
-42
Infinite
Insoluble
1-Propanol
Butane
60
58
97
0
Infinite
Insoluble
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 CH2 CH3
CH3 CH2 CH2 OH
CH3 CH2 CH2 CH3
CH3 ( CH 2 ) 2 CH 2 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
10-13
Acidity of Alcohols
 In
dilute aqueous solution, alcohols are weakly
acidic
CH3 O H +
:O H
H
CH3 O:
-
Ka =
–
+
+ H O H
H
+
[ CH3 O ] [H3 O ]
[ CH3 OH]
= 10
- 15 .5
pKa = 1 5 .5
10-14
Acidity of Alcohols
Compound
Structural
Formula
pKa
Hydrogen chloride
HCl
-7
Acetic acid
CH3 COOH
Methanol
CH3 OH
15.5
Water
H2 O
15.7
Ethanol
CH3 CH 2 OH
15.9
2-Propanol
( CH3 ) 2 CHOH
17
2-Methyl-2-propanol
( CH3 ) 3 COH
18
4.8
Stronger
acid
Weaker
acid
*Also given for comparison are pK a values for water,
acetic acid, and hydrogen chloride.
10-15
Acidity of Alcohols
 Acidity
depends primarily on the degree of
stabilization and solvation of the alkoxide ion
• the negatively charged oxygens of methanol and
ethanol are about as accessible as 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
10-16
Reaction with Metals
 Alcohols
react with Li, Na, K, and other active
metals to liberate hydrogen gas and form metal
alkoxides
2CH3 OH + 2Na
-
+
2CH3 O Na + H2
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 + Na+ HEthanol
Sodium
hydride
CH3 CH2 O- Na+ + H2
Sodium ethoxide
10-17
Reaction with HX
• 3° alcohols react very rapidly with HCl, HBr, and HI
OH + HCl
2-Methyl-2propanol
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
r eflux
Br
+
1-Br omobutane
H2 O
10-18
Reaction with HX
• with HBr and HI, 2° alcohols generally give some
rearranged product
a pr oduct of
Br
OH
+ HBr
3-Pentanol
r ear r angement
heat
+ H2 O
+
Br
3-Br omopentane 2-Br omopentane
(major pr oduct)
• 1° alcohols with extensive -branching give large
amounts of rearranged product
Br
OH + HBr
 
2,2-Dimethyl-1propanol
+ H2 O
2-Bromo-2-methylbutane
(a product of rearrangement)
10-19
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
10-20
Reaction with HX - SN1
Step 1: proton transfer to the OH group gives an
oxonium ion
CH 3
+
:
CH3 -C-OH
rapid and
reversible
+
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
slow, rate
determining
SN 1
H
CH3
CH3 - C+
CH3
+
:O
H
A 3° carbocation
intermediate
10-21
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-methylpropane
(tert-Butyl chloride)
10-22
Reaction with HX - SN2
 1°
alcohols react with HX by an SN2 mechanism
Step 1: rapid and reversible proton transfer
:
+
RCH2 -OH + H O H
rapid and
reversible
+
RCH2 - O
H
+
H
H
:O H
H
Step 2: displacement of HOH by halide ion
Br:-
+
+ RCH2 -O
H
H
slow, rate
determining
SN2
H
RCH2 -Br
+ :O
H
10-23
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
10-24
Reaction with HX
• Step 1: proton transfer gives an oxonium ion
+
+ H O H
O
H
2,2-Dimethyl-1propanol
H
rapid and
reversible
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
slow and
rate determining
+ O
(concerted)
H
A 3° carbocation
intermediate
10-25
Reaction with HX
Step 3: reaction of the carbocation intermediate (an
electrophile) with halide ion (a nucleophile) gives the
product
Cl
-
+
fast
Cl
2-Chloro-2-methylbutane
10-26
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-Methyl-1-propanol Phosphorus
(Isobutyl alcohol)
tribromide
0°
Br
1-Bromo-2-methylpropane
(Isobutyl bromide)
+
H3 PO 3
Phosphorous
acid
10-27
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
10-28
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
Thionyl
chlor ide
pyridine
Cl + SO + HCl
2
1-Chloroheptane
10-29
Reaction with SOCl2
 Reaction
of an alcohol with SOCl2 in the
presence of a 3° amine is stereoselective
• it occurs with inversion of configuration
OH
(S)-2-Octanol
+ SOCl2
Thionyl
chloride
3° amine
Cl
(R)-2-Chlorooctane
+ SO2 + HCl
10-30
Reaction with SOCl2
Step 1: formation of an alkyl chlorosulfite
R1
R1
O
C O H + Cl-S-Cl
O
C
H-Cl
Cl
H
R2
H
R2
+
O S
An alkyl
chlorosulfite
Step 2: nucleophilic displacement of this leaving group
by chloride ion gives the chloroalkane
R1
Cl
+
O
C O S
H
R2
Cl
SN2
R1
Cl
+
C
R2
O
O S + Cl
H
10-31
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
O
R- S- OH
R- S- OO
O
A sulfonate anion
A sulfonic acid
(a very strong acid) (a very weak base and
stable anion; a very
good leaving group
10-32
Alkyl Sulfonates
A
commonly used sulfonyl chloride is ptoluenesulfonyl chloride (Ts-Cl)
O
CH 3 CH 2 OH + Cl-S
CH 3
O
Ethanol p-Toluenesulfonyl
chlor ide
pyridine
O
CH 3 CH 2 O-S
CH 3 + HCl
O
Ethyl p-toluenesulfonate
(Ethyl tosylate)
10-33
Alkyl Sulfonates
 Another
commonly used sulfonyl chloride is
methanesulfonyl chloride (Ms-Cl)
OH
+
O
Cl-S- CH3
O
pyridine
Cyclohexanol Methanesulfonyl
chlor ide
O
O-S-CH3 + HCl
O
Cyclohexyl
methanesulfonate
(Cyclohexyl mesylate)
10-34
Alkyl Sulfonates
 Sulfonate
anions are very weak bases (the
conjugate base of a strong acid) 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
10-35
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
Sodium
acetate
+
(S)-2-Octyl tosylate
SN 2
ethanol
O
+
Na
OTs
+
(R)-2-Octyl acetate
10-36
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 slightly
above room temperature
10-37
Dehydration of ROH
CH 3 CH 2 OH
OH
H2 SO 4
180°C
CH 2 = CH 2
H2 SO 4
+
H2 O
+ H2 O
140°C
Cyclohexanol
CH 3
CH 3 COH
Cyclohexene
H2 SO 4
CH 3
2-Methyl-2-propanol
(tert- Butyl alcohol)
50°C
CH 3
CH 3 C= CH 2 +
H2 O
2-Methylpropene
(Isobutylene)
10-38
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%)
10-39
Dehydration of ROH
 Dehydration
of 1° and 2° alcohols is often
accompanied by rearrangement
H2 SO4
OH
140 - 170°C
3,3-Dimethyl2,3-Dimethyl2-butanol
2-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% )
10-40
Dehydration of ROH
 Based
on evidence of
• ease of dehydration (3° > 2° > 1°)
• 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
10-41
Dehydration of ROH
Step 1: proton transfer to the -OH group gives an
oxonium ion
H
O
+
+ H O H
rapid and
reversible
H
H + H
O
+
O H
H
Step 2: loss of H2O gives a carbocation intermediate
H +H
O
slow, rate
determining
+ H2 O
A 2° carbocation
intermediate
10-42
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
rapid and
reversible
+
H H
+
+
+ H O H
H
10-43
•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
+
+
H H
O-H
H
+
E2
+ H O H+ O H
1-Butene
H
H
10-44
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 H
1,2-shift of a
hydride ion
+
+
O-H
H
A 2° carbocation
Step 4: proton transfer to solvent gives the alkene
H
H O +
H
+
E1
+
+
+H O H
H
trans-2-Butene cis-2-Butene
10-45
Dehydration of ROH
 Dehydration
with rearrangement occurs by a
carbocation rearrangement
+
H
OH
3,3-Dimethyl2-butanol
-H2 O
+
H2 O
A 2° carbocation
intermediate
+
+ H3 O+
2,3-Dimethyl2-butene
A 3° carbocation
intermediate
H2 O
+ H3 O+
2,3-Dimethyl1-butene
10-46
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
10-47
Pinacol Rearrangement
 The
products of acid-catalyzed dehydration of a
glycol are different from those of alcohols
HO
OH
2,3-Dimethyl-2,3-butanediol
(Pinacol)
O
H2 SO4
+ H2 O
3,3-Dimethyl-2-butanone
(Pinacolone)
10-48
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 oxonium ion
O H
H
Step 2: loss of water gives a carbocation intermediate
HO
H
O H
HO
+ H2 O
A 3o carbocation
intermediate
10-49
Pinacol Rearrangement
Step 3: a 1,2- shift of methyl gives a more stable
carbocation
H O
H O
H O
A resonance-stabilized cation intermediate
Step 4: proton transfer to solvent completes the reaction
H
H2 O
+
O
H3 O
+
+
O
10-50
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 primar y
alcohol
[O]
O
CH3 -C- H
An aldehyde
[O]
O
CH3 -C- OH
A car boxylic
acid
• to an aldehyde is a two-electron oxidation
• to a carboxylic acid is a four-electron oxidation
10-51
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
CrO3
+ H2 O
H2 SO4
Chromium(VI)
oxide
K2 Cr 2 O7
Potassium
dichromate
H2 SO4
H2 CrO 4
Chromic acid
H2 Cr 2 O7
H2 O
2 H2 CrO 4
Chromic acid
10-52
Oxidation: 1° ROH
 Oxidation
of 1-octanol gives octanoic acid
• the aldehyde intermediate is not isolated
O
1-Hexanol
H2 CrO4
OH
H2O, acetone
H
Hexanal
(not isolated)
O
OH
Hexanoic acid
10-53
Oxidation: 2° ROH
 2°
alcohols are oxidized to ketones by chromic
acid
OH
+ H2 CrO4
2-Isopropyl-5-methylcyclohexanol
(Menthol)
O
acetone
+ Cr
3+
2-Isopropyl-5-methylcyclohexanone
(Menthone)
10-54
Chromic Acid Oxidation of ROH
• Step 1: formation of a chromate ester
OH
O
+ HO-Cr-OH
H
Cyclohexanol
fast and
reversible
O
O-Cr-OH
O
+ H2 O
H
An alkyl chromate
O
• Step 2: reaction of the chromate ester with a base,
here shown as H2O
chromium(VI)
chromium(IV)
O
O
H
H
slow, rate
Cr-OH determining
O
H
O + O+ H +
H
Cyclohexanone
O
-
Cr-OH
O
O
H
10-55
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 aldehyde
fast and
reversible
OH
R-C-OH
H2 CrO4
H
An aldehyde
hydrate
O-CrO3 H
R-C-OH
H2 O
H
O
R-C-OH + HCrO3 - + H3 O+
A carboxylic
acid
10-56
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
pyridinium ion
chlorochromate ion
CrO3 + HCl
+
ClCrO3
N
Pyridine
-
N
H
Pyridinium chlorochromate
(PCC)
• PCC is selective for the oxidation of 1° alcohols to
aldehydes; it does not oxidize aldehydes further to
carboxylic acids
10-57
Oxidation: 1° ROH
• PCC oxidizes a 1° alcohol to an aldehyde
O
PCC
OH
H
Geraniol
Geranial
• PCC also oxidizes a 2° alcohol to a ketone
OH
Menthol
PCC
O
Menthone
10-58
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 a NAD+
A pyridine
ring
The business
+
end of NAD
O
OH
N
Nicotinic acid
(Niacin; Vitamin B6)
O
An amide group
NH2
N
Ad
Nicotinamide adenine
+
dinucleotide (NAD )
The plus sign in NAD+
represents this charge
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)
10-59
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+ + 2 e-
N+
Ad
NAD+
(oxidized form)
oxidation
H H
O
CNH2
N
Ad
NADH
(reduced form)
10-60
Oxidation of Alcohols by NAD+
• NAD+ is the oxidizing in a wide variety of enzymecatalyzed reactions, two of which are
+
CH3 CH2 OH + NAD
Ethanol
OH
+
CH3 CHCOO + NAD
Lactate
alcohol
dehydrogenase
O
CH3 CH + NADH + H+
Ethanal
(Acetaldehyde)
lactate
dehydrogenase
O
CH3 CCOO + NADH + H+
Pyruvate
10-61
Oxidation of Alcohols by NAD+
• mechanism of NAD+ oxidation of an alcohol
-
B
•
•
1
E
B
H
H
•
•
•
•
•
•
•
•
C
C
O 2
3
HH
O
O
C-NH2
4-5
N+
Ad
NAD+
E
reduction
of NAD+
oxidation
of NADH
H H O
C-NH2
••
N
Ad
NADH
• 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 face10-62
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
10-63
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 periodate
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
10-64
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 trans isomer is
unreactive toward
periodic acid
O
HIO4
O
The cis isomer forms
a cyclic periodate and
is cleaved
10-65
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 oxygen
10-66
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
OH
HS
2-Sulfanylethanol
1-Butanethiol
2-Methyl-1-propanethiol
(2-Mercaptoethanol)
(Butyl mercaptan)
(Isobutyl mercaptan)
SH
SH
10-67
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
bp (°C)
Alcohol
Methanol 65
Ethanol
78
1-Butanol 117
• the boiling points of ethanethiol and its constitutional
isomer dimethyl sulfide are almost identical
CH3 CH2 SH
Ethanethiol
(bp 35°C)
CH3 SCH3
Dimethyl sulfide
(bp 37°C)
10-68
Thiols: Physical Properties
 Low-molecular-weight
thiols = STENCH
• the scent of skunks is due primarily to these two thiols
SH
SH
2-Butene-1-thiol 3-Methyl-1-butanethiol
(Isopentyl 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-propanethiol
2-Propanethiol
(tert-Butyl mercaptan) (Isopropyl mercaptan)
10-69
Thiols: preparation
 The
most common preparation of thiols depends
on the very high nucleophilicity of hydrosulfide
ion, HS+
-
SN 2
ethanol
CH3 (CH2 ) 8 CH2 I + Na SH
Sodium
1-Iododecane
hydrosulfide
O
+
+
Na SH + ICH2 CO Na
Sodium
Sodium
hydrosulfide iodoacetate
SN 2
+ -
CH3 (CH2 ) 8 CH2 SH + Na I
1-Decanethiol
O
+ +
HSCH2 CO Na + Na I
Sodium mercaptoacetate
(Sodium thioglycolate)
10-70
Thiols: acidity
 Thiols
are stronger acids than alcohols
CH3 CH2 OH + H2 O
+
CH3 CH2 O + H3 O
CH3 CH2 SH + H2 O
CH3 CH2 S
-
+ H3 O+
pK a = 15.9
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
(Stronger acid)
CH3 CH2 S- Na+ +
H2 O
pKa 15.7
(Weaker acid)
10-71
Thiols: oxidation
 The
sulfur atom of a thiol can be oxidized to
several higher oxidation states
[O]
R-S-H
A thiol
[O]
R-S-S-R
A disulfide
O
R-S-OH
A sulfinic
acid
[O]
O
R-S-OH
O
A sulfonic
acid
• the most common reaction of thiols in biological
systems in interconversion between thiols and
disulfides, -S-S2 RSH +
A thiol
1 O
2
2
RSSR + H2 O
A disulfide
10-72
Alcohols
and
Thiols
End of Chapter 10
10-73