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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".

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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

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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