Download Ethers and Epoxides

1





An ether has two organic groups (alkyl, aryl, or
vinyl) bonded to the same oxygen atom, R–O–R
Diethyl ether is used industrially as a solvent
Tetrahydrofuran (THF) is a solvent that is a cyclic
ether
Epoxides contain a C-O-C unit which make-up a
three membered ring
Thiols (R–S–H) and sulfides (R–S–R) are sulfur (for
oxygen) analogs of alcohols and ethers
2
3

Ethers are named two ways:

As alkoxy derivatives of alkanes

Derived by listing the two alkyl groups in the
general structure of ROR’ in alphabetical order as
separate words and adding the word ether
 When both alkyl groups are the same, the prefix di-
precedes the name of the alkyl group
 (Ethers can be described as symmetrical or
unsymmetrical)
4
CH3CH2 O CH2CH3
Diethyl ether
Ethoxyethane
CH3CH2 O CH3
Ethyl methyl ether
Methoxyethane
CH3CH2 O CH2CH2CH2Cl
3-Chloropropyl ethyl ether
1-Chloro-3-ethoxypropane
5

Epoxides (oxiranes)

“epoxy” always preceeds the name of the alkane
O
O
1,2-Epoxycyclohexane
2-Methyl-2,3-epoxybutane
6
OCH3
1
O
6
O
2
O
7
3
O
Br
4
O
Cl
8
O
Br
5
Br
OCH3
7
1.
Isopropyl methyl ether
2.
4-t-butoxy-1-cyclohexene
3.
Phenyl propyl ether
4.
O- nitro anisole
8



R–O–R ~ tetrahedral bond angle (112° in
dimethyl ether)
Oxygen is sp3-hybridized
Oxygen atom gives ethers a slight dipole
moment (diethyl ether 1.2 D)
9
CH3CH2OCH2CH3
Diethyl ether
bp =35oC
solubility in water: 7.5 g/100mL
CH3CH2CH2CH2CH3
Pentane
bp =36oC
solubility in water: insoluble
CH3CH2CH2CH2OH
1-Butanol
bp =117oC
solubility in water: 9 g/100mL
10

Acid catalyzed synthesis of ethers:
2
OH
butanol
H2SO4
O
130oC
Dibutyl ether
+ H2O
Limited to symmetrical ethers. WHY?
11
HCl
2
OH
O
+
130 C
H
OH
H O
H3 O+
+
Cl-
H
O
H
O+
H---Cl
H
+
H3O+
+
H
O+
-
Cl
O
12

Williamson ether synthesis
•Metal alkoxides react with primary alkyl halides by an
SN2 pathway to yield ethers.
•Secondary and tertiary substrates react following an
E2 mechanism
13
OH
O – Na+
NaH
O
THF
+
CH3CH2----I
+
H2
+
NaI
THF
O
H
O– Na+
THF
+
Na+ H-
CH3CH2----I
+
H2
O
NaI
+
14
O
CH3CH2O
+ CH3CH2Br
+
Br
SN2
E2
?
?
15
How would you prepare the following
compounds using a Williamson synthesis?

Methyl propyl ether

Anisole (methyl phenyl ether)
16
Br
O
+ CH3CH2CHCH3
17



React alkene with an alcohol and mercuric
acetate or trifluoroacetate
Demercuration with NaBH4 yields an ether
Overall Markovnikov addition of alcohol to
alkene
18
19
20



Ethers are generally unreactive
Strong acid will cleave an ether at elevated
temperature
HI, HBr produce an alkyl halide from less
hindered component by SN2 (tertiary ethers
undergo SN1)
21
22
Note that the halide attacks the protonated ether at
the less highly substituted site.
23
24



Specific to allyl aryl ethers, ArOCH2CH=CH2
Heating to 200–250°C leads to an o-allylphenol
Result is alkylation of the phenol in an ortho position
25


Concerted pericyclic 6-electron, 6-membered
ring transition state
Mechanism consistent with 14C labeling
26
27


Cyclic ethers behave like acyclic ethers, except
if ring is 3-membered
Dioxane and tetrahydrofuran are used as
solvents
28




Three membered ring ether is called an
oxirane (root “ir” from “tri” for 3-membered;
prefix “ox” for oxygen; “ane” for saturated)
Also called epoxides
Ethylene oxide (oxirane; 1,2-epoxyethane) is
industrially important as an intermediate
Prepared by reaction of ethylene with oxygen
at 300 °C and silver oxide catalyst
29
30

Treat an alkene with a peroxyacid
31
peroxyacetic acid
H
C6H5
H
O
O
+
H5C6
H
(E)-1,2-diphenylethene
O
H
CH3
C6H5
O
H5C6
OH
+
O
H
trans-1,2-diphenyloxirane
CH3
acetic acid
32



Addition of HO-X to an alkene gives a halohydrin
Treatment of a halohydrin with base gives an epoxide
Intramolecular Williamson ether synthesis
33
34



Water adds to epoxides with dilute acid at
room temperature
Product is a 1,2-diol (on adjacent C’s: vicinal)
Mechanism: acid protonates oxygen and water
adds to opposite side (anti-addition)
35
36

1,2-ethanediol from acid catalyzed hydration of
ethylene

Widely used as automobile antifreeze (lowers freezing
point of water solutions)
37


Anhydrous HF, HBr, HCl, or HI combines with
an epoxide
Gives trans product
38
39
40


Strain of the three-membered ring is relieved on
ring-opening
Hydroxide cleaves epoxides at elevated
temperatures to give trans 1,2-diols

Complete the reaction
O
CH2
OH-
H2O, 100oC
Methylenecyclohexane
oxide
41
O
-
CH2
OH
O–
CH 2OH
H
O
H
OH
CH 2OH
+
-
OH
100 C
42
43


Adds –CH2CH2OH to the Grignard reagent’s hydrocarbon
chain
Acyclic and other larger ring ethers do not react
44

Thiols (RSH), are sulfur analogs of alcohols


Named with the suffix -thiol
SH group is called “mercapto group”
45
1
SH
2
SH
Br
3
SH
46
1.
Cyclopentanethiol
2.
3-methyl-4-heptanethiol
3.
4-ethyl-4-isopropyl-2-methyl-3-hexanethiol
47

Sulfides (RSR), are sulfur analogs of ethers

Named by rules used for ethers, with sulfide in
place of ether for simple compounds and alkylthio
in place of alkoxy
48
1
2
3
4
S
S
ethyl phenyl sulfide
sec-butyl isopropyl sulfide
49

From alkyl halides by displacement with a
sulfur nucleophile such as SH

The alkylthiol product can undergo further
reaction with the alkyl halide to give a
symmetrical sulfide, giving a poorer yield of the
thiol
50



Thiolates (RS) are formed by the reaction of a thiol
with a base
Thiolates react with primary or secondary alkyl halide
to give sulfides (RSR’)
Thiolates are excellent nucleophiles and react with
many electrophiles
51