Download Ethers, Epoxides and Sulfides

KOT 222 Organic Chemistry II
CHAPTER 14
ETHERS, EPOXIDES,
and SULFIDES
1
Ethers
¾ Formula: R-O-R’, where R and R’ maybe alkyl or
aryl groups.
Symmetrical ethers:
CH3
Unsymmetrical ethers:
O CH3
O CH3
O
2
Structure and Polarity
sp3 hybridized
Bulky alkyl groups enlarge
the angle
3
Boiling Points
¾ Large dipole moments resulting in dipole-dipole
interactions.
¾ Similar to alkanes of comparable MW.
¾ Much lower than alcohols of comparable MW.
4
Hydrogen Bond Acceptor
¾ Ether cannot form hydrogen bond with another
ether molecule.
¾ Its lone pair electron can form a hydrogen bond
with hydrogen bond donor with O-H or N-H.
5
Ethers as Solvents
¾ Nonpolar substances are more soluble in ethers
than in alcohols.
¾ Ether has large dipole moment, so polar solutes
also dissolve.
¾ Ethers solvate cations but not small anions.
¾ Ethers are nonhydroxylic, so they do not react
with strong bases.
6
Ether Complexes
Grignard reagents:
Ethers share their lone pairs of
electrons with the magnesium,
stabilize the reagent and keep it
in the solution.
Electrophiles, BH3:
Ether’s nonbonding electrons
stabilize BH3.
Metal cations:
Crown ethers solvate metal
cations by complexing the metal
in the center of the ring. Allowing
polar inorganic salts to dissolve
in nonpolar organic solvents.
H
_
+
O B H
H
BH3 THF
7
Nomenclature of Ethers
a) Common names
a) Alkyl alkyl ether
b) Current rule: alphabetical order
c) Old rule: order of increasing complexity
d) Symmetrical: use dialkyl, or just alkyl.
CH3
CH3CH2
O CH2CH3
diethyl ether or
ethyl ether
CH3
O C
CH3
CH3
t-butyl methyl ether or
methyl t-butyl ether
8
b) IUPAC names
b) Alkoxy alkane
c) Complex alkyl group as the root name, the
rest is the alkoxy group.
CH3
CH3
O C
O CH3
CH3
CH3
2-methyl-2-methoxypropane
Methoxycyclohexane
9
c) Cyclic ethers
¾ Heterocyclic compounds, O is the heteroatom.
Epoxides (Oxiranes):
¾ three-membered cyclic ethers.
H
H
peroxybenzoic acid
O
H
cyclohexene
H
cyclohexene oxide
H
5
4
CH3
H
6
3
1
2
1
O
O
H
trans-1,2-epoxy-4methylcyclohexane
H
H3CO
CH3
2
3
H
trans-2-methoxy-3-methyloxirane
10
Oxetanes:
1
O
4
¾ four-membered cyclic ethers.
O
H3 C
3
CH2CH3
2
H 3C
H
2-ethyl-3,3-dimethyloxetane
Furans (Oxolanes):
¾ five-membered cyclic ethers.
O
O
tetrahydrofuran, THF
Pyrans (Oxanes):
O
¾ six-membered cyclic ethers.
O
tetrahydropyran, THP
11
Dioxanes:
¾ six-membered cyclic ethers with two oxygen atoms.
¾ the most common is 1,4-dioxane.
¾1,4-dioxane fused with two benzene rings to give a
dioxin.
O
O
O
O
1,4-dioxane
dibenzo-1,4-dioxane, dioxin
12
Spectroscopy of Ethers
¾ Infrared spectroscopy
™ moderate to strong C-O stretching around 1000 to
1200 cm-1.
™ lack of C=O and O-H absorption bands suggests an
ether.
¾ NMR spectroscopy
H
C
H
C δ65 - δ90
13
O
H δ3.5 - δ4
1
13
¾ Mass spectrometry
™ Common fragmentations are:
14
Mass spectrum of diethyl ether
15
Williamson Ether Synthesis
¾ Most reliable and versatile ether synthesis.
¾ SN2 attack of alkoxide ion on 1o alkyl halide or
tosylate.
CH3
CH3
O H
+
K
CH3
CH3
CH3
CH3
_
O
+ CH3CH2
CH3
CH3
_ +
O K
CH3
H
C
H
CH3
Br
CH3
_
O CH2CH2CH3 + Br
CH3
16
Alkoxymercuration-Demercuration
¾ Use mercuric acetate with an alcohol to add
RO-H to a double bond and form the
Markovnikov product.
17
Bimolecular Dehydration of Alcohols
¾ Industrial method, not good lab synthesis.
¾ The alcohol must have 1o alkyl group.
CH3CH2
O H + H O CH2CH3
H2SO4
CH3CH2 O CH2CH3
140°C
¾ Bulky alkyl group and high temperature lead to
the formation of alkene (unidehydration).
H2SO4
CH3 CH CH3
OH
H 2C
CH
CH3
+
H 2O
180oC
18
Cleavage of Ethers
¾ Ethers are unreactive toward base, but
protonated ethers can undergo substitution
reactions with strong acids.
¾ Alcohol leaving group is replaced by a halide.
¾ Reactivity: HI > HBr >> HCl
R-O-R’
excess HX
R-X + R’-X
SN2 substitution mechanism
19
Mechanism for cleavage
Step 1: Protonation of ether
Step 2: SN2 cleavage of the protonated ether
Step 3: Conversion of alcohol to alkyl halide
CH3OH + HBr
CH3Br + H2O
SN1: 2o & 3oalcohols
SN2: 1o alcohol
20
Phenyl Ether Cleavage
¾ Give alkyl halides and phenols as products.
¾ Phenol cannot react further to become halide.
OH
O CH2CH3
HBr
+ CH3CH2
Br
21
Autoxidation of Ethers
¾ A spontaneous oxidation by atmospheric
oxygen.
¾ Ether is slowly oxidexed to hydroperoxide and
dialkyl peroxide.
¾ Highly explosive!!!
22
Sulfides (Thioethers)
¾ Analogues of ethers, R-S-R’.
¾ Named like ethers:
™Common names – “sulfide” replacing
“ether”
™IUPAC names – “alkylthio” replacing
“alkoxy”
S CH3
methyl phenyl sulfide
or
methylthiobenzene
23
Synthesis of Sulfides
¾ Easily synthesized by Williamson ether synthesis.
¾ Thiolate ion as the nucleophile.
¾ Sulfur is larger and more polarized than oxygen.
¾ Thiolates are better nucleophiles, weaker bases,
than alkoxides.
Br
C H3
C
_
C H3
H
2° halide
C H 3S
C H 3O H
SC H3
C H3
C
C H3
H
Substitution product
24
Sulfide Reactions
¾ Sulfides are easily oxidized to sulfoxides and
sulfones.
sulfoxide
sulfone
¾ Sulfides are often used as mild reducing agents.
25
¾ Sulfides are relatively strong nucleophiles.
- sulfur is large and more polarizable, its
valence electrons are less tightly held.
¾ Sulfides attack unhindered alkyl halides to give
sulfonium salts.
¾ Sulfonium salts are good alkylating agents.
CH3
N
+
CH3
S
CH3
N
CH3
+
CH3
S
CH3
26
Synthesis of Epoxides
¾ Epoxide is a three-membered cyclic ether.
¾ Also called as oxirane.
¾ Can be synthesized from:
1. Peroxyacid epoxidation
2. Base-promoted cyclization of
halohydrins
27
Peroxyacid Epoxidation
¾ Converts alkenes to epoxides (oxidation).
¾ Weakly acidic peroxyacid that is soluble in
aprotic solvents is used.
¾ A one-step, concerted reaction.
¾ Epoxide retains the stereochemistry of the
alkene used.
28
Cyclization of Halohydrins
¾ A variation of the Williamson ether synthesis.
¾ Treatment of a halohydrin with a base leads to
an epoxide through internal SN2 attack.
¾ Halohydrins are synthesized by treating alkenes
with aqueous solutions of halogens (X2/H2O).
29
Formation of halohydrin
¾ By treating alkenes with aqueous solution of halogens.
¾ Bromine water and chlorine water add across double
bonds with Markovnikov orientation.
Cyclization to give epoxide
30
Reactions of Epoxides
¾ Large ring strain energy causes epoxides more
reactive than ethers.
¾ Epoxides react both under acidic and basic
conditions which cause the opening of the ring.
¾ The products depend primarily on the solvent
used.
31
Acid-catalyzed Ring Opening
In Water
¾ Epoxides are hydrolyzed to give glycols (trans
diols) with anti stereochemistry.
SN2
32
Direct anti hydroxylation of alkene:
33
In Alcohols
¾ Produces an alkoxy alcohol with anti stereochemistry.
34
Using Hydrohalic Acids
¾ Produce a 1,2-dihalide.
¾ The reaction is analogous to the cleavage of
ethers by HBr or HI.
35
Biosynthesis of Steroids
¾ Involved an acid-catalyzed opening of squalene2,3-epoxide.
36
The process repeats and leads to…
37
Base-Catalyzed Ring Opening
¾ Strong bases and nucleophiles do not cleave
ethers as alkoxide ion is a poor leaving group.
¾ Epoxide’s high ring strain makes it susceptible to
nucleophilic attack.
38
Mechanism:
39
¾With aqueous hydroxide, a trans 1,2-diol is
formed.
¾With alkoxide in alcohol, a trans 1,2-alkoxy
alcohol is formed.
¾These are the same products that were
formed in acid.
¾Different products are formed in acid and
base if epoxide is unsymmetrical.
40
Amine can also open epoxides.
Use excess ammonia to get good yields of
ethanolamine.
41
Orientation of Epoxide Opening
¾ Unsymmetrically substituted epoxides give
different products under acid-catalyzed and
base-catalyzed conditions.
42
Under basic conditions:
Base attacks the least hindered carbon in an SN2
displacement
_
O
O
HC
CH2
CH3
HC
OCH2CH3
CH3CH2OH
CH2
CH3 OCH2CH3
OH
HC
CH2
CH3 OCH2CH3
Under acidic conditions:
The nucleophile attacks the protonated epoxide at the
most substituted carbon.
H
O+
HC
CH3CH2OH
CH2
CH3
OH
H3C
HC CH2
2CH3
H OCH
+
OH
H3C
HC CH2
OCH2CH3
43
In protonated epoxide, sharing of the positive
charge can be represented as below:
The nucleophile attack the more substituted
carbon, which can better support the positive
charge and more electrophilic.
44
Reactions with Grignard and
Organolithium Reagents
• Strong base opens the epoxide ring by
attacking the less hindered carbon.
OH
MgBr
O
H2C
CHCH3
1) ether
+
2) H3O
CH2
CHCH3
+
45
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