Transcript Ethers H-Bonding in Ethers Solvation Crown Ethers Can Act as Phase Transfer Catalysts.

Ethers
H-Bonding in Ethers
Solvation
Crown Ethers Can Act as
Phase Transfer Catalysts
Nomenclature
Br
O
OCH3
but yl ethyl et her (common)
or
1-ethoxybut ane (IUP AC)trans 1-bromo-2-methoxycyclopent an
O
CH3CH2O
OH
CH3CH2O
ethyl (Z) 1-propenyl ether (common)
or
(Z) 1-et hoxy-1-propene (IUP AC)4,4-diethoxy-2-cyclohexenol
Alkene Oxides, Oxiranes or Epoxides
O
CH2=CH2
ethylene
[O]
CH2
CH2
ethylene oxid
oxirane
1,2-epoxyet hane
Several Naming Methods
O
OCH3
O
cis 3-met hoxycyclopentene oxi
(E) 2-met hyl-3-hexene oxide
trans 2-et hyl-3-isopropyloxirane
(E) 2-met hyl-3,4-epoxyhexane cis 3-met hoxy-1,2-epoxycyclopen
Epoxide groups are Common in
Biologically Active Molecules
Periplenone B
female cockroach sex pheromone
O
O
O
A New Class of Anti-tumor Agents
Epothilone B
ant icancer drug from soil bacteria
O
S
H
OH
N
O
O
OH
O
LS-16
2,4
exo, exo, exo6,7-dicarbomethoxy-3,8-diaxatricyclo[3.2.1.0
]octane
Epoxides are Extremely Reactive
Williamson Ether Synthesis
Preparation of Unsymmetrical Ethers
Williamson Ether Synthesis: SN2
Oxymercuration Hydration
Markovnikov addition
Regiospecific Reaction
1) Hg(OAc) 2 in
THF/H2O
2) NaBH4
OH
H
Alkoxymercuration
Use an Alcohol Instead of H2O
CH3
CH3
1) Hg(OAc)2, CH3CH2OH
2) NaBH4
OCH2CH3
H
OCH3
1) Hg(OAc)2
in CH3OH
2) NaBH4
Me ch an i sm i s Markovn i kov oxym e rcu rati on
HgOAc OAc
+
Hg(OAc)2
in CH3OH
 OAc
Hg

Hg
+
OCH3
H
OAc
OCH3
Hg
OCH3
OAc
OAc
H
NaBH4 (H )
OCH3
H
Intramolecular Alkoxymercuration
OH
1) Hg(OAc)2
2) NaBH4
O
Epoxide Preparation
From Alkenes
O
O
RCOOH
H
O
H
in CH2Cl2
R
C
O
O
Cl
H
O
CO3H
MCPBA
meta chloroperoxybenzoic acid
+ RCOH
Epoxide Preparation
From Halohydrins
Br
Br2 in H2O
OH
CH3
+ enant iomer
CH3
NaH
O
CH3
+ H2 + NaCl
Mechanism
O H
Br
bromohydrin
O
H:
Br
int ramolecular S
N2
O
Propose a Mechanism
O
OH
Br2
+ HBr
Br
Reaction of Ethers
Unsymmetrical Ethers
H
Br
HBr
O
OH
Br
+
HBr
H
O
Br
SN2
Br
Examples
O
OH
HI
SN 2
OCH(CH3)2
I
HBr
E2
OH
+ CH2=CHCH3
+ HBr
Base Catalyzed Ring-Opening
of Epoxides
Base Opens Ring from
Unhindered Side
OH
O
NaOCH3 in CH3OH
H
OCH3
O Na
OCH3
regenerates base cat alyst
OCH3
Grignard Reagents open
Epoxides
O
RCO3H
CH3MgBr
OH
MgBrO
CH3
+ enant.
H 3O
+
CH3
Ring-Opening is Sterically
Controlled
CH2CH3
OH
O
CH3
1) CH3CH2MgBr
+
2) H3O
CH3
base ope n s e poxi de at l e ss hi nde re d site
Acid Catalyzed Ring-Opening
Aqueous and in Alcohol
Regiochemistry
Ring Opens at More Hindered Site
+
H , CH3OH
OH
O
OCH3
OH
O
CH3OH
H
OCH3
CH3OH
H
Different Regiosomers
Why does Acid Catalyzed
Opening Give Inversion?
O
CH3CH2
CH3
NaOH, H2O
(S)
+
H 3O
HO
CH3CH2
CH3
CH2OH
(S)
HO
CH3
CH3CH2
CH2OH
(R)
Propose a Mechanism
Br
O
1) NaOCH3
2) heat
CH3OCH2
O
+ NaBr
2 Successive SN2 Reactions
OCH3
Br
1) NaOCH3
2) heat
O
Br
CH3O
O
CH3OCH2
O
+ NaBr
Provide a Mechanism
OH
+
H , H2O
O
OH
Benzene Toxicity
cyctochrome
P -450
non-polar
fat soluble
enzyme
H2O
O
OH
"benzene epoxide"
glutathione
O2
enzyme
Covalent Adduct
DNA
O
HO
RS
OH
OH
O
O