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.
H O H R O R

Uses Since 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 *&+.%&'
H H B H H B H H 2 O 2 H + _ O B H H

,rown ethers are macrocyclic ethers# which help to solvate metal cations# and thus allow inorganic salts to dissolve in organic solvents.

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O O O O 18-Crown-6

O O

./-,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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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 naming the groups on either side of the o!ygen# e.g. methyl ethyl ether &+,O,&5,&+. ;U-<, names ethers by taking the more comple! alkyl group the root name# and naming the remaining part as an alko!y group. E.g.
H3C O-CH2CH3 methoxyethane H OCH3 methoxycyclohexane

Cl H H OCH3 trans-1-chloro-2-methoxycyclobutane

H2C O-H H2C O-CH2CH3 2-ethoxyethanol

,yclic Ethers 9aming these heterocyclic compounds depends on the ring si1e and number of o!ygens. ;t can be confusing at first:"

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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
H H3C O H

CH-CH2CH3 OCH3 c s-2,3-e!oxy-"-methoxyhexane

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.
O H3C CH3 H oxetane 2-ethyl-3,3-d methyloxetane O CH2CH3

%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.".

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OCH3 #uran tetrahydro#uran $%H&' 3-methoxy#uran

-yrans %hese are si! membered rings with one o!ygen and two double bonds.
H H H H H H H H H CH3 H O H O tetrahydro!yran $%H('

O !yran

"-methyl!yran

$io!anes %hese are si! membered rings with two o!ygens.

O O 1,"-d oxane O O CH3

"-methyl-1,3-d oxane

Ether Synthesis (Recap) Billiamson synthesis

OH 1')*a 2')CH3-CH2-O%s ethoxycyclohexane O-CH2CH3

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<lko!ymercuration-$emercuration
1')H+$O,c'2,)CH3OH 2')*aBH"

CH3$CH2'3 CH CH2

CH3$CH2'3 CH CH3 OCH3 2-methoxyhexane $-ar.o/n .o/)!roduct'

*imolecular dehydration of <lcohols

H20O",)1"1oC

2 CH3 OH

CH3-O-CH3

Reactions of Ethers %ypically ethers are stable and chemically inert# although they can undergo two types of reaction cleavage# o!idation". ,leavage Ethers are cleaved by &-*r and &-;# generating the corresponding alkyl halides. R-O-R 6 e!cess &-C R-C 6 R-C Ethers are stable to bases# but acidic conditions leads to the protonation of the ether o!ygen# which then can undergo substitution reactions.
H Br 2BrH O CH2CH3 + CH3CH2-Br CH3CH2-OH H-Br Br2 CH3CH2-Br
-

CH3CH2-O-CH2CH3

CH3CH2

CH3CH2

H O H +

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Et-O-Et 6 &-*r Et*r 6 EtO& Et-O-Et 6 5&-*r 5Et*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.
H O CH2CH3 + 23!henol CH3CH2-3

O CH2CH3

H 3

OH

%he reaction stops at the phenol stage since the sp5 carbon 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 Dangerous in the laboratory".
CH3 CH3 H O H CH3 CH3 CH3 CH3 CH3 CH3 H O O-O-H + H O O CH3 CH3 CH3 CH3 CH3 hydro!erox de d al.yl!erox de

excess)O2 months

%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!yacid epo!ide and carbo!ylic acid

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E.g.

H H

-C(B,

H O H e!oxycyclohexane

O Cl O-O-H

-C(B,

3,-*< is one of the most common epo!idising reagents. Epo!idations work better for electron rich double bonds.
CH3 CH3 -C(B, CH3 O CH3

Synthesis from &alohydrins Bhen halohydrins are treated with base# an intramolecular cyclisation occurs# and epo!ides are formed.
O-H 4
-

2OH 4

O-

4-

Recall that halohydrins are produced from alkenes by reaction with halogens in the presence of water. ,hlorine water or related reagents".
Cl2,)H2O *aOH H O H

H Cl HO H

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<cid ,ataly1ed ring Opening Epo!ides react to release their considerable 5>kcal?mol" strain energy. Recall that the acidic hydrolysis of epo!ides gives anti diols.
H O H H2O2 trans-cyclo!entane-1,2-d ol H H O H + H O+ H H H OH H OH

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%his overall transformation alkene anti .#5-diol" can be achieved in one step by reaction with aDueous pero!yacids.
CH3CO3H H+,)H2O H OH H OH

Epo!ides can be ring opened by alcohols with acidic catalysis to generate alko!y alcohols with anti stereochemistry.
H O H RO-H H H O H + H O+ H H H OH H OR

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&ydrohalic <cids Epo!ides react with &-C to produce halohydrins# which react further with &-C to generate .#5-dihalides.

H O H

H Br

H O+ H Br2
-

H OH H Br H-Br Br H H Br

m xture)o# c s)and)trans

&owever it is synthetically easier =ust to add C5 to an alkene".

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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 Ea than the corresponding straight chain ether.

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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.
H O H HO2
-

H OH OH

H2O

H OH H OH

H O H

H3CO-+*a CH3OH

H OH H OCH3

Orientation of Ring Opening Unsymmetrical epo!ides give products with different regiochemistry with basic opening compared to acidic opening.
CH3 OH H3C H CH3CH2O H

H+,)CH3CH2-OH H3C CH2 H3C O CH3CH2O-)+*a CH3OH

CH3 OCH2CH3 H3C H HO H

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Under basic conditions# the alko!ide simply attacks the least sterically hindered epo!ide carbon in an S95 displacement.

H3C

CH3 OCH2CH3 CH3CH2OCH3OH CH2 H3C H H3C O O- H

CH3 OCH2CH3 H3C H HO H

Under acidic conditions# the alcohol seems to attack the more hindered carbon# but it is more complicated. %he protonated epo!ide has several resonance structures.

H3C CH2 H3C O + H $3'

H3C

+ CH 2

H3C

+ CH2

H3C O H $33'

H3C O H $333'

Structure ;; is a major contributor 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. Hlike mechanism. Remember the differences in the S9. to S95 spectrum. SubstrateI +o to .oJ 9ucleophileI weak or strong" to strongJ Keaving (roupI )good to good or bad". Lets figure this out in class.

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Organometallic Reagents
H3C CH2 H3C O (h--+Br 5ther H3C O- H
+

CH3 (h H -+Br

H3O+

CH3 (h H3C OH H H

(rignard and organolithium reagents also attack epo!ides at the least hindered carbon to generate alcohols after acidic workup".

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