11.1 ethers, sulfides and epoxides - 11 structure, nomenclature, properties ether synthesis -...
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11.1Ethers, Sulfides and Epoxides - 11
Structure, nomenclature, propertiesEther synthesis - Williamson synthesis (SN2)
H+/ROH addition to olefins (chapt 6)Reactions - acid catalyzed cleavage of ethers (SN2/SN1/E1)
[oxidation out]Ethers as Protecting Groups (Gps).Epoxides - oxirane nomenclature
Preparation: epoxidation, halohydrinReactions - nucleophilic cleavage (SN2/SN1/E1)[sulfides out]
Synthesis (continued)
[blue - repeat of earlier chemistry]
O
HCH3
CH3
H
11.2
Structure - tetrahedral (sp3) oxygen & carbon
Ethers, Sulfides and Epoxides - 11
diethyl ether O ~109
tetrahydrofuran or THF
O
dihydropyran O
11.3
Nomenclature - ether group is a substituent
Ethers, Sulfides and Epoxides - 11
2-cyclopentenol
HOO
4-ethoxy-2-cyclopentenol
(1S,4R)-4-ethoxy-2-cyclopenten-1-ol
11.4
Nomenclature of Ethers
trans-2-propoxycyclohexanol
2-methyl-2-methoxypropane(t-butyl methyl ether)
OH
O
H3CC
H3C
O
CH3
CH3
11.5
Properties - polar C-O covalent bonds
But low dielectric constant
Ethers, Sulfides and Epoxides - 11
O
+
-
+
Hydrogen bond acceptor (Lewis base)
O
+
-
+
HO
CH3
11.6
X HO
?
OH X
?O
Two ways to prep benzyl ethyl ether
Ethers, Sulfides and Epoxides - 11
Williamson ether synthesisSN2 substitution
recall similar problems in chapter 9 (9.46, 9.48 and 9.49)
11.7
O
OH X XHO
??
Two ways benzyl ethyl ether can be prepared
Specifically how would each be done?Nucleophic form of the alcohol?Solvent?
- alkoxide- polar - aprotic- benzylic substrate Which way should be best?
Ethers, Sulfides and Epoxides - 11
11.8
Preparation of Ethers
O
Br+
O
OCCH3
CH3
CH3
CH3Br + CH3OCCH3
CH3
CH3
look at Problem 9.49b
11.9
H+/ROH addition to olefins, “hydration-like”
Ethers, Sulfides and Epoxides - 11
OO
H
H++
Recall/review addition problems 6.29, 6.34a
11.10
Ethers, Sulfides and Epoxides - 11
Reactions - acid catalyzed cleavage of ethers
O
HBr
BrBr+
SN2SN1/E1
11.11
Ethers Protecting Groups
Ethers, Sulfides and Epoxides - 11
O
H
O
HBr
Br OR
O
H
want
H2N-
(xs)
Problem 6.33: alcohol “interferes” with Br2 addition.
OBr
H
OBr
11.12
Ether Protecting Groups
Ethers, Sulfides and Epoxides - 11
O
H
O
HBr
Br OR
O
H
want
H2N-
(xs)
Problem 6.33: alcohol “interferes” with Br2 addition. Protecting group (Pg) = blocking group
O
Pg
+Pg
Br2
O
PgBr
Br
-Pg1
2
3
11.13
Protecting group characteristics
Ethers, Sulfides and Epoxides - 11
O
H
O
HBr
Br OR
O
H
want
H2N-
(xs)
O
Pg
+Pg
Br2
O
PgBr
Br
-Pg1
2
3Pg “Requirements”• On efficient • Inert to rx• Off efficient
Problem 6.33: alcohol “interferes” with Br2 addition. Protecting group (Pg) = blocking group
11.14
Ethers, Sulfides and Epoxides - 11
TMS ethers
O
H
O
HBr
Br ORwant
trimethylsilyl etheror TMS ether
O
Si
pyridine Si Cl
CH3
H3C
CH3
O
SiBr
BrBr2
H+/H2O or F-
11.15
Crown Ethers - Crown Ethers - not coveredCyclic polyethers
The parent name is crown, preceded by a number describing the size of the ring followed by the number of oxygen atoms in the ring, e.g
18-crown-6
O
OO
O
OO
11.16Ethers, Sulfides and Epoxides – Chapter 11
Structure, nomenclature, properties of Ethers Preparation:
• Ether synthesis – Williamson Synthesis
• H+/ROH addition to olefinsReactions - acid catalyzed cleavage of ethers Ethers as Protecting Groups (Gps).Epoxides - nomenclature Preparation: epoxidation, halohydrinReactions - nucleophilic cleavage
O
HCH3
CH3
H
11.17
Ethers, Sulfides and Epoxides - 11Nomenclature - epoxy (substituent) or oxirane
4,5-epoxycycloheptene
(ignore - not questioned)
(4S,5R)-4,5-epoxycycloheptene
oxirane
ether
O
H
H
special 3-membered ringCl
O HH
[ (3S,4S)-2-chloro-3,4-epoxyheptane ]
11.18
Ethers, Sulfides and Epoxides - 11
Prep of epoxides/oxiranes
OO R
O
H
+O
HO R
O
+
O R
OO
H
+
O R
O
11.19
Ethers, Sulfides and Epoxides - 11
Prep of epoxides - better mechanistic view
OO R
OH
+
OO R
O
H
+O
HO R
O
+
OO R
OH
stereospecific like bromine addition
11.20
other epoxide sources - halohydrins/base
mechanism
intramolecular “SN2”
Et CC
H
HH
Br2
H2O (xs)
Et C
C
H
H
H
OH
Br
Et C
C
H
H
H
O:B
See problem 9.50, same reaction
11.21
chapter 6
Other sources of epoxides - halohydrins/base
Et C
C
H
H
H
OH
Br
Et C
C
H
H
H
O:B
Et C
C
H
H
H
OH
:B
Et C
C
H
HH
Br2
H2O
Et C
C
H
H
HBr
H
O
H
11.22Reactions H+ or Lewis Acid Opening
B: or Lewis Base Opening
O OH
OH
H+
H2O
O OH
OH
HO-
H2O
of epoxides :
11.23Reactions H+ or Lewis Acid Opening
of epoxides:
mechanism?
O OH
OH
H+
H2O
OH2
OH
OH
H
O
H
11.24Reactions B: or Lewis Base Opening
of epoxides:
Mechanism?
O OH
OH
HO-
H2O
O
OH
-OH
HO
H
11.25
1,2-transdiol
Stereochemistry
1,2-cisdiol
Recall: OH
OH
OsO4
ROOH
O OH
OH
H+ /H2O
HO- /H2O
11.26Regioselectivity
O
1o-less hindered3o more hindered
SN2 like
O O
OCH3:Nu:OCH3
O
OCH3
H
protonsource
11.27
OH+
O
O-H
CH3HO-CH3
O
H
Regioselectivity
SN1 likeOH
OH
O CH3
H
O CH3
H
11.28
O
N
R
R
H
O
SR
1.
2. H2O
O
S
R = H, alkylH
R
H NR
R
O
N
R
R
H
O
N
R
R
Hexample epoxyresin
11.29
Application of Epoxy Chemistry
O
O
O
O
+ H2N NH2
Cl
Cl
2 1
11.30
O
O
+ H2N NH22 1R
R'
N
H
H N
H
HO
O_
R
R'N
H N
H
HO
OHR
R'
Reaction
Continues
amineepoxide
Application of Epoxy Chemistry
11.31
N
R'
N
H2C C
H
OH
RH2CC
H
OH
R
CH2
HCC
H2
HC
OH OH
N
H2C C
H
OHH2CC
H
OH
R N
H2C C
H
OH
RH2CC
H
OH
NCH2
HCC
H2CHR
OH OH
R'
NCH2
HC RC
H2
HC
OH OH
R'
N
R'
N
H2C C
H
OHH2CC
H
OH
CH2
HCC
H2
HC
OH OH
R R
R R
N
H2C C
H
OHH2CC
H
OH
R
NCH2
HCC
H2CHR
OH OH
R'
R
R
N
H2C C
H
OH
RH2CC
H
OH
NCH2
HC RC
H2
HC
OH OH
R'
R
R
Application of Epoxy Chemistry
11.32
Application of Epoxy Chemistry
11.33
Application of Epoxy Chemistry
11.34
O
1. LAH[ H:- ]
O
H
H2. H2O
lithium aluminum hydride H B- H
H
H
Na+
like sodium borohydride
H Al- HH
H
C
O
+
Li+
H
H
[ :H ]
C
O
HH
HH+
H2O C
O
HH
H
H
11.35
O
C N:
HOR O
C N:
H
O
C C R1.
O
C CR
O
C C
HR
2. H OR
C
H
H
C CH3
H
H
O
1.
O
1.
O
C
H
HC CH3
H
HOH
C
H
HC CH3
H
H2. H2O
11.36Ethylene Oxide – ethylene oxide is a valuable building block for
organic synthesis because each of its carbons has a functional group
Na+CN-
CH3NH2
C C-Na+CH3
OH
O N
OH
CH3H
N COH
N OCH3
O
H2SO4
H2/M
N
OH
CH3
OH
N N-HCH3
OH
H2N
SOCl2
NH3
N
Cl
CH3
Cl
(1)(2)
(3) (4) (6)
(8)(5) (7)