4_10388_378.doc
TRANSCRIPT
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Ethers And Epoxides
Ethers are a class of compound of the general formula R-O-R.
R and R can be alkyl or aryl.
Structure
Ethers can be thought of as alkyl analogues of water.
UsesSince ethers are relatively unreactive and are somewhat polar due to the
lone pairs on the o!ygen"# they are commonly used as solvents for organic
reactions. $iethyl ether and %&'# the (rignard reaction".
Ethers will often form comple!es with molecules that have vacant orbitals#
enabling )unstable molecules to be used as reagents.
E.g. &ydroboration uses *&+.%&'
,rown ethers are macrocyclic ethers# which help to solvate metal cations#
and thus allow inorganic salts to dissolve in organic solvents.
age
H O H R O R
BH
BHH
H
H
H
O
2 O B
H
H
H+ _
2
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/-,rown-0 is the ideal si1e to incorporate a potassium ion# and allows
organic solutions of ionic potassium salts to be prepared purple ben1ene#
23nO4".
age5
O
O
O
OO
O
26
18-Crown-6
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Ethers 7differentially8 solvate cations and anions. %he cations are strongly
bonded to the lone pairs of the ether# leaving the anions more available
for attack S95# 23nO4# :"
9omenclature of ethers
,ommon names 7trivial names8 of ethers add the suffi! ether after namingthe groups on either side of the o!ygen# e.g. methyl ethyl ether
&+,O,&5,&+.
;U
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Epo!ides
%hese + membered rings are named using the term 7epo!y8 as one
substituent bridging two ad=acent , atoms. 9O% like cyclopropane"
5 + 4 > 0
? ? @ A A A
cis refers to the substituents# not the epo!ide which must be cis?syn".
Epo!ides have considerable ring strain.
O!etanes
%hese are four membered rings with one o!ygen.
%hey are not considered a substituent but a ring such as cyclobutane. %he O
atom is understood as being in the first position.
O!etanes have ring strain# but not as much as epo!ides.
'urans
%hese are five membered rings with one o!ygen and two double bonds.
'uran is an 7aromatic8 molecule as is ben1ene.".
age4
O O
H3C
CH3
CH2CH3
H
oxetane 2-ethyl-3,3-dmethyloxetane
H
H3C
H
CH-CH2CH3O
cs-2,3-e!oxy-"-methoxyhexane
OCH3
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yrans
%hese are si! membered rings with one o!ygen and two double bonds.
$io!anes
%hese are si! membered rings with two o!ygens.
Ether Synthesis (Recap)
Billiamson synthesis
age>
O O O
#uran tetrahydro#uran
$%H&'
OCH3
3-methoxy#uran
OH
HH H
H
H
!yran
OH
HH CH3
H
H
"-methyl!yran
O
tetrahydro!yran$%H('
O
O
1,"-doxane
O
O
"-methyl-1,3-doxane
CH3
OH1' *a
2' CH3-CH2-O%s
O-CH2CH3
ethoxycyclohexane
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Et-O-Et 6 &-*r Et*r 6 EtO&
Et-O-Et 6 5&-*r5Et*r
%he alcohol produced reacts to generate a second molecule of alkyl halide.
henyl ethers are slightly different# and cleave to give alkyl halides and
phenols.
%he reaction stops at the phenol stage since the sp5carbon of the ,-O bond
does not allow the reDuired S9 or S95 reactions to generate the second
molecule of aryl halide.
O!idation of Ethers
Ethers may auto-o!idi1e if left in the presence of o!ygen for e!tended
periods of time Dangerousin the laboratory".
%he pero!ides and hydropero!ides are unstable and e!plosive.
Epo!ides
Unlike straight chain ethers# epo!ides are very reactive release of ring
strain"# and are useful intermediates because of their chemical versatility.
Synthesis
Recall alkene and pero!yacidepo!ide and carbo!ylic acid
age
O CH2CH3 H O CH2CH3
H
+
-
OH
CH3CH2-
!henol
CH3
H
CH3
O
CH3
H
CH3
excess O2
months
CH3
H
CH3
O
CH3
O-O-H
CH3
CH3
H
CH3
O O
CH3
CH3
CH3
hydro!eroxde dal.yl!eroxde
+
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E.g.
3,*< is one of the most common epo!idising reagents.
Epo!idations work better for electron rich double bonds.
Synthesis from &alohydrinsBhen halohydrins are treated with base# an intramolecular cyclisation
occurs# and epo!ides are formed.
Recall that halohydrins are produced from alkenes by reaction with halogens
in the presence of water. ,hlorine water or related reagents".
age/
Cl O-O-H
O
C(B
H
H
C(BH
H
O
e!oxycyclohexane
CH3
CH3
C(BCH3
CH3
O
4
O-H
4
O--OH
O4
-
Cl2, H2O
H ClHO H
*aOH
OH H
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kcal?mol" strain energy.
Recall that the acidic hydrolysis of epo!ides gives antidiols.
ageF
O
H
H H O
H
H+
O
H
H
H+
H2O
OH
HOH
H
trans-cyclo!entane-1,2-dol
-H+
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%his overall transformation alkeneanti #5-diol" can be achieved in one
step by reaction with aDueous pero!yacids.
Epo!ides can be ring opened by alcohols with acidic catalysis to generate
alko!y alcohols with antistereochemistry.
&ydrohalic
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*ase ,ataly1ed Ring Opening
9ormal ethers do not undergo nucleophilic substitution or eliminations
because the alko!ide anion is not a good leaving group. %hat is why acid
catalysis is reDuired".
Epo!ides are different though. %he release of strain when an epo!ide is
opened more than compensates for the poor leaving group ability# and so
epo!ides will open under nucleophilic conditions.
'igure 4-/
%he strained epo!ide has a lower Eathan the corresponding straight chain
ether.
age
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%he reaction of hydro!ide or alko!ide" with a symmetric epo!ide generates
anti diols or alko!y alcohols" identical to those produced under acidic
conditions.
Orientation of Ring Opening
Unsymmetrical epo!ides give products with different regiochemistry with
basicopening compared to acidicopening.
age5
O
H
H
OH
HOH
H
HO-
OH
HO-
H
H2O
CH2
H3C
H3C O
H+, CH3CH2-OH
CH3CH2O- +
*a
CH3OH
H3CCH3
CH3CH2O
OH
H
H
H3C
CH3
HO
OCH2CH3
H
H
O
H
H
OCH3
HOH
H
H3CO-+
*a
CH3OH
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Under basic conditions# the alko!ide simply attacks the least sterically
hindered epo!ide carbon in an S95 displacement.
Under acidic conditions# the alcoholseemsto attack the more hindered
carbon# but it is more complicated.
%he protonated epo!ide has several resonance structures.
Structure ;; is a majorcontributor since the cation is more highly substituted
and therefore more stable.
%he nucleophile attacks the carbon with greatest positive partial charge. %his
gives an S9 Hlikemechanism. Remember the differences in the S9 to S95
spectrum. SubstrateI +oto oJ 9ucleophileI weak or strong" to strongJ
Keaving (roupI )good to good or bad".Lets figure this out in class.
age+
CH2
H3C
H3C O
CH3CH2O-
H3C
CH3
O-
OCH2CH3
H
H H3C
CH3
HO
OCH2CH3
H
HCH3OH
CH2
H3C
H3C O
H
+
CH2
H3C
H3C O
H
+ CH2
H3C
H3C O
H
+
$' $' $'
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Organometallic Reagents
(rignard and organolithium reagents also attack epo!ides at the least
hindered carbon to generate alcohols after acidic workup".
age4
CH2
H3C
H3C O
(h-Br
5ther
H3C
CH3
O-
(h
H
H
+Br
H3O+
H3C
CH3
OH
(h
H
H