Title: Chapter 16 Ethers, Epoxides, and Sulfides
1Chapter 16Ethers, Epoxides, and Sulfides
Dr. Wolf's CHM 201 202
16-1
2Nomenclature of Ethers, Epoxides, and Sulfides
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16-2
3Substitutive IUPAC Names of Ethers
- name as alkoxy derivatives of alkanes
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4Functional Class IUPAC Names of Ethers
- name the groups attached to oxygen in
alphabetical order as separate words "ether"
is last word
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5Substitutive IUPAC Names of Sulfides
- name as alkylthio derivatives of alkanes
(methylthio)cyclopentane
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6Functional Class IUPAC Names of Sulfides
- analogous to ethers, but replace ether as
lastword in the name by sulfide.
cyclopentyl methyl sulfide
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7Names of Cyclic Ethers
O
O
O
Oxirane(Ethylene oxide)
Oxolane(tetrahydrofuran)
Oxetane
O
O
O
Oxane(tetrahydropyran)
1,4-Dioxane
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8Names of Cyclic Sulfides
S
S
S
Thiirane
Thiolane
Thietane
S
Thiane
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9Structure and BondinginEthers and Epoxides
- bent geometry at oxygen analogousto water and
alcohols, i.e. sp3 hybidization
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10Bond angles at oxygen are sensitiveto steric
effects
O
O
H
H
CH3
H
105
108.5
O
CH3
CH3
112
132
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11An oxygen atom affects geometry in much thesame
way as a CH2 group
most stable conformation of diethyl
etherresembles pentane
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12An oxygen atom affects geometry in much thesame
way as a CH2 group
most stable conformation of tetrahydropyranresemb
les cyclohexane
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13Physical Properties of Ethers
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14Ethers resemble alkanes more than alcoholswith
respect to boiling point
boiling point
- Intermolecular hydrogenbonding possible in
alcohols not possible in alkanes or ethers.
36C
35C
O
117C
OH
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15Ethers resemble alcohols more than alkaneswith
respect to solubility in water
solubility in water (g/100 mL)
very small
7.5
- Hydrogen bonding towater possible for
ethersand alcohols not possible for alkanes.
O
9
OH
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16Crown Ethers
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17Crown Ethers
- structure cyclic polyethers derived from
repeating OCH2CH2 units - properties form stable complexes with metal ions
- applications synthetic reactions involving
anions
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1818-Crown-6
- negative charge concentrated in cavity inside
the molecule
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1918-Crown-6
- negative charge concentrated in cavity inside
the molecule
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2018-Crown-6
K
- forms stable Lewis acid/Lewis base complex with
K
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2118-Crown-6
K
- forms stable Lewis acid/Lewis base complex with
K
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22Ion-Complexing and Solubility
KF
not soluble in benzene
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23Ion-Complexing and Solubility
KF
benzene
add 18-crown-6
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24Ion-Complexing and Solubility
F
K
benzene
18-crown-6 complex of K dissolves in benzene
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25Ion-Complexing and Solubility
K
benzene
F carried into benzene to preserve
electroneutrality
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26Application to organic synthesis
- Complexaton of K by 18-crown-6 "solubilizes"
salt in benzene - Anion of salt is in a relatively unsolvated
state in benzene (sometimes referred to as a
"naked anion") - Unsolvated anion is very reactive
- Only catalytic quantities of 18-crown-6 are
needed
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27Example
KF
CH3(CH2)6CH2Br
CH3(CH2)6CH2F
18-crown-6
(92)
benzene
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28Preparation of Ethers
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29Acid-Catalyzed Condensation of Alcohols
2CH3CH2CH2CH2OH
CH3CH2CH2CH2OCH2CH2CH2CH3
(60)
Discussed earlier in Section 15.7
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30Addition of Alcohols to Alkenes
H
(CH3)2CCH2 CH3OH
(CH3)3COCH3
tert-Butyl methyl ether
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31The Williamson Ether Synthesis
- Think SN2!
- primary alkyl halide alkoxide nucleophile
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32Example
CH3CH2CH2CH2ONa CH3CH2I
CH3CH2CH2CH2OCH2CH3 NaI
(71)
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33Another Example
CH3CHCH3
ONa
(84)
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34Another Example
Alkoxide ion can be derived from primary,
secondary, or tertiary alcohol
Alkyl halide must be primary
CH3CHCH3
ONa
(84)
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35Origin of Reactants
CH3CHCH3
CH2OH
OH
HCl
Na
CH3CHCH3
CH2Cl
ONa
CH2OCHCH3
(84)
CH3
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36What happens if the alkyl halide is not primary?
CH3CHCH3
CH2ONa
Br
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37What happens if the alkyl halide is not primary?
CH3CHCH3
CH2ONa
Br
CHCH3
H2C
CH2OH
Elimination by the E2 mechanism becomesthe major
reaction pathway.
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38Reactions of EthersA Review and a Preview
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39Summary of reactions of ethers
- No reactions of ethers encountered to this
point. - Ethers are relatively unreactive.
- Their low level of reactivity is one reason why
ethers are often used as solvents in chemical
reactions. - Ethers oxidize in air to form explosive
hydroperoxides and peroxides.
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40Acid-Catalyzed Cleavage of Ethers
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41Example
HBr
CH3CHCH2CH3
CH3CHCH2CH3
CH3Br
heat
OCH3
Br
(81)
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42Mechanism
CH3
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43Mechanism
CH3
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44Mechanism
CH3CHCH2CH3
Br
CH3
HBr
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45Cleavage of Cyclic Ethers
HI
ICH2CH2CH2CH2I
150C
(65)
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46Mechanism
ICH2CH2CH2CH2I
HI
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47Mechanism
ICH2CH2CH2CH2I
HI
O
H
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48Mechanism
ICH2CH2CH2CH2I
HI
HI
O
H
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49Preparation of EpoxidesA Review and a Preview
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50Preparation of Epoxides
Epoxides are prepared by two major methods.Both
begin with alkenes.
- reaction of alkenes with peroxy acids(Section
6.19) - conversion of alkenes to vicinalhalohydrins,
followed by treatmentwith base (Section 16.10)
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51Conversion of Vicinal Halohydrinsto Epoxides
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52Example
H
NaOH
O
H2O
H
(81)
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53Example
H
NaOH
O
H2O
H
(81)
O
via
H
H
Br
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54Epoxidation via Vicinal Halohydrins
Br
Br2
H2O
OH
antiaddition
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55Epoxidation via Vicinal Halohydrins
Br
Br2
NaOH
H2O
O
OH
antiaddition
inversion
- corresponds to overall syn addition ofoxygen to
the double bond
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56Epoxidation via Vicinal Halohydrins
Br
H3C
Br2
H
NaOH
H3C
H
CH3
H
H2O
H
O
CH3
OH
antiaddition
inversion
- corresponds to overall syn addition ofoxygen to
the double bond
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57Epoxidation via Vicinal Halohydrins
Br
H3C
Br2
H3C
H
H
NaOH
H3C
H
H
CH3
CH3
H
H2O
H
O
CH3
OH
antiaddition
inversion
- corresponds to overall syn addition ofoxygen to
the double bond
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58Reactions of EpoxidesA Review and a Preview
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59Reactions of Epoxides
- All reactions involve nucleophilic attack at
carbon and lead to opening of the ring. - An example is the reaction of ethylene oxide
with a Grignard reagent (discussed in Section
15.4 as a method for the synthesis of alcohols).
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60Reaction of Grignard Reagentswith Epoxides
R
CH2
CH2
OMgX
H3O
RCH2CH2OH
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61Example
CH2
H2C
O
1. diethyl ether 2. H3O
(71)
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62In general...
Reactions of epoxides involve attack by
anucleophile and proceed with ring-opening.For
ethylene oxide
NuH
NuCH2CH2OH
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63In general...
For epoxides where the two carbons of thering
are differently substituted
Nucleophiles attack herewhen the reaction
iscatalyzed by acids
Anionic nucleophilesattack here
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64Nucleophilic Ring-OpeningReactions of Epoxides
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65Example
NaOCH2CH3
CH3CH2OH
(50)
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66Mechanism
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67Mechanism
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68Mechanism
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69Mechanism
CH3CH2
O
O
CH2CH2
H
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70Example
KSCH2CH2CH2CH3
ethanol-water, 0C
(99)
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71Stereochemistry
OCH2CH3
H
H
OH
(67)
- Inversion of configuration at carbon being
attacked by nucleophile - Suggests SN2-like transition state
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72Stereochemistry
CH3
H3C
R
R
H
NH3
H
OH
O
H2N
H
R
H2O
S
H
H3C
CH3
(70)
- Inversion of configuration at carbon being
attacked by nucleophile - Suggests SN2-like transition state
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73Stereochemistry
CH3
H3C
R
R
H
NH3
H
OH
O
H2N
H
R
H2O
S
H
H3C
CH3
(70)
H3C
H
d
d-
O
H3N
H
H3C
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74Anionic nucleophile attacks less-crowded carbon
NaOCH3
CH3OH
(53)
- consistent with SN2-like transition state
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75Anionic nucleophile attacks less-crowded carbon
1. diethyl ether 2. H3O
(60)
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76Lithium aluminum hydride reduces epoxides
Hydride attacksless-crowdedcarbon
1. LiAlH4, diethyl ether 2. H2O
(90)
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77Acid-Catalyzed Ring-OpeningReactions of Epoxides
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78Example
CH3CH2OH
CH3CH2OCH2CH2OH
H2SO4, 25C
(87-92)
- CH3CH2OCH2CH2OCH2CH3 formed only on heating
and/or longer reaction times
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79Example
HBr
BrCH2CH2OH
10C
(87-92)
- BrCH2CH2Br formed only on heating and/or longer
reaction times
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80Mechanism
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81Mechanism
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82Figure 16.6 Acid-Catalyzed Hydrolysis of
Ethylene Oxide
Step 1
H2C
CH2
H2C
CH2
O
O
H
H
O
H
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83Figure 16.6 Acid-Catalyzed Hydrolysis of
Ethylene Oxide
Step 2
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84Figure 16.6 Acid-Catalyzed Hydrolysis of
Ethylene Oxide
Step 3
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85Acid-Catalyzed Ring Opening of Epoxides
Characteristics
- nucleophile attacks more substituted carbon of
protonated epoxide - inversion of configuration at site of
nucleophilic attack
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86Nucleophile attacks more-substituted carbon
OCH3
CH3OH
CH3CH
CCH3
C
H2SO4
CH3
OH
(76)
- consistent with carbocation character at
transition state
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87Nucleophile attacks more-substituted carbon
OCH3
CH3OH
d
d
CH3CH
CCH3
C
H2SO4
CH3
OH
(76)
d
- consistent with carbocation character at
transition state
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88Stereochemistry
H
OH
HBr
H
Br
(73)
- Inversion of configuration at carbon being
attacked by nucleophile
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89Stereochemistry
CH3
H3C
R
R
H
H
OH
O
CH3O
H
R
S
H
H3C
CH3
(57)
- Inversion of configuration at carbon being
attacked by nucleophile
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90Stereochemistry
CH3
H3C
R
R
H
H
OH
O
CH3O
H
R
S
H
H3C
CH3
H3C
H
d
d
d
H
O
CH3O
H
H
H3C
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91anti-Hydroxylation of Alkenes
H2O
HClO4
H
OH
H
OH
(80)
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92Epoxides in Biological Processes
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93Naturally Occurring Epoxides
- are common
- are involved in numerous biological processes
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94Biosynthesis of Epoxides
NADH
enzyme
NAD
C
C
H2O
O
- enzyme-catalyzed oxygen transfer from O2 to
alkene - enzymes are referred to as monooxygenases
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95Example biological epoxidation of squalene
O2, NADHmonoxygenase
- this reaction is an important step in the
biosynthesisof cholesterol
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96Preparation of Sulfides
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16-95
97Preparation of RSR'
- prepared by nucleophilic substitution (SN2)
S
R
NaSCH3
methanol
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98Oxidation of SulfidesSulfoxides and Sulfones
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99Oxidation of RSR'
R
R'
S
sulfide
sulfoxide
sulfone
- either the sulfoxide or the sulfone can be
isolated depending on the oxidizing agent and
reactionconditions
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100Example
water
(91)
- Sodium metaperiodate oxidizes sulfides to
sulfoxides and no further.
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101Example
- 1 equiv of H2O2 or a peroxy acid gives a
sulfoxide, 2 equiv give a sulfone
H2O2
(2 equiv)
(74-78)
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102Alkylation of SulfidesSulfonium Salts
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103Sulfides can act as nucleophiles
R"
R
X
R"
S
R
S
X
R'
R'
- product is a sulfonium salt
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104Example
CH3I
CH3(CH2)10CH2SCH3
CH3(CH2)10CH2SCH3
I
CH3
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105Spectroscopic Analysis of Ethers
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106Infrared Spectroscopy
- CO stretching 1070 and 1150 cm-1 (strong)
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107Figure 16.8 Infrared Spectrum of Dipropyl Ether
CH3CH2CH2OCH2CH2CH3
COC
Wave number, cm-1
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1081H NMR
- HCO proton is deshielded by O range isca. d
3.3-4.0 ppm.
d 1.4 ppm
d 0.8 ppm
d 0.8 ppm
CH3 CH2 CH2 OCH2 CH2 CH3
d 3.2 ppm
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109CH3 CH2 CH2 OCH2 CH2 CH3
Chemical shift (d, ppm)
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11013C NMR
Carbons of COC appearin the range d 57-87 ppm.
26.0 ppm
68.0 ppm
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111UV-VIS
Simple ethers have their absorption maximum at
about 185 nm and are transparent to ultraviolet
radiation above about 220 nm.
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112Mass Spectrometry
Molecular ion fragments to give
oxygen-stabilizedcarbocation.
CH3CH2O
CHCH2CH3
m/z 102
CH3
CH3CH2O
CH
CH3CH2O
CHCH2CH3
CH3
m/z 87
m/z 73
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113End of Chapter 16