1、Organic ChemistryStructureuThe functional group of an ether is an oxygen atom bonded to two carbon atoms in dialkyl ethers,oxygen is sp3 hybridized with bond angles of approximately 109.5.in dimethyl ether,the C-O-C bond angle is 110.3H HH HO OH HC CH HH HH HC CStructure in other ethers,the ether ox
2、ygen is bonded to an sp2 hybridized carbon in ethyl vinyl ether,for example,the ether oxygen is bonded to one sp3 hybridized carbon and one sp2 hybridized carbonC CH H3 3C CH H2 2-O O-C CH H=C CH H2 2E Et th ho ox xy ye et th he en ne e(E Et t h hy yl l v vi in ny yl l e et th he er r)Nomenclature:e
3、thersuIUPAC:the longest carbon chain is the parent name the OR group as an alkoxy substituentuCommon names:name the groups bonded to oxygen in alphabetical order followed by the word 2-Methoxy-2-2-Methoxy-2-methylpropanemethylpropane(tert-tert-Butyl methyl ether)Butyl methyl ether)EthoxyethaneEthoxy
4、ethane(Diethyl ether)(Diethyl ether)CH3CH3CH3CH2OCH2CH3CH3OCCH3trans-trans-2-Ethoxy-2-Ethoxy-cyclohexanolcyclohexanolOCH2CH3OHNomenclature:ethersuAlthough cyclic ethers have IUPAC names,their common names are more widely used IUPAC:prefix shows oxygen in the ring the suffixes-,-,-,and-show three,fou
5、r,five,and six atoms in a saturated ringO O x xi ir ra an ne e(E Et th hy yl le en ne e o ox xi i d de e)O O x xo ol la an ne e(T Te et tr ra ah hy yd dr ro of fu ur ra an n)O O x xa an ne e(T Te et tr ra ah hy yd dr ro op py yr ra an n)1 1,4 4-D D i io ox xa an ne eO OO O1 12 23 3O OO OO OO OO O x
6、xe et ta an ne ePhysical PropertiesuAlthough ethers are polar compounds,only weak dipole-dipole attractive forces exist between their molecules in the pure liquid statePhysical PropertiesuBoiling points of ethers are lower than alcohols of comparable MW close to those of hydrocarbons of comparable M
7、W uEthers are hydrogen bond acceptors they are more soluble in H2O than are hydrocarbonsPreparation of Ethers SN2 displacement of halide,tosylate,or mesylate by alkoxide ion2 2-M M e et th ho ox xy yp pr ro op pa an ne e(I Is so op pr ro op py yl l m m e et th hy yl l e et th he er r)I Io od do om m
8、 e et th ha an ne e(M M e et th hy yl l i io od di id de e)S So od di iu um mi is so op pr ro op po ox xi id de e+C C H H3 3C C H H3 3C C H H3 3I IC C H H3 3C C H H O O-N N a a+C C H H3 3C C H H O O C C H H3 3N N a a+I I-S SN N2 2Preparation of Ethers yields are highest with methyl and 1 halides,low
9、er with 2 halides(competing -elimination)reaction fails with 3 halides(-elimination only)C CH H3 3C CH H3 3C CH H3 3C CO O-K K+C CH H3 3B Br rS SN N2 2C CH H3 3C CH H3 3C CH H3 3C CO O C CH H3 3K K+B Br r-+P Po ot ta as ss si iu um mt te er rt t-b bu ut to ox xi id de eB Br ro om m o om m e et t h h
10、a an ne e(M M e et th hy yl l b br ro om m i id de e)2 2-M M e et th ho ox xy y-2 2-m m e et th hy yl lp pr ro op pa an ne e(t te er rt t-B Bu ut ty yl l m m e et th hy yl l e et th he er r)C CH H3 3C CH H3 3C CH H3 3C CB Br rC CH H3 3O O-N Na a+E E2 2C CH H3 3C CH H3 3C C=C CH H2 2C CH H3 3O O H HN
11、 N a a+B Br r-+2 2-B Br ro om m o o-2 2-m m e et th hy yl lp pr ro op pa an ne eS So od di iu um mm m e et th ho ox xi id de e2 2-M M e et th hy yl lp pr ro op pe en ne ePreparation of EthersuAcid-catalyzed dehydration of alcohols diethyl ether and several other ethers are made on an industrial scal
12、e this way a specific example of an SN2 reaction in which a poor leaving group(OH-)is converted to a better one(H2O)2 2C CH H3 3C CH H2 2O OH HH H2 2S SO O4 41 14 40 0 C CC CH H3 3C CH H2 2O O C CH H2 2C CH H3 3H H2 2O O+E Et th ha an no ol lD D i ie et th hy yl l e et t h he er rPreparation of Ethe
13、rs Step 1:proton transfer gives an oxonium ion Step 2:nucleophilic displacement of H2O by the OH group of the alcohol gives a new oxonium ionC CH H3 3C CH H2 2-O O-H HO OO OH H-O O-S S-O O-H HC CH H3 3C CH H2 2-O O-H HH HO OO O-O O-S S-O O-H H+A A n n o ox xo on ni iu um m i io on n+f fa as st t a a
14、n nd dr re ev ve er rs si ib bl le eC CH H3 3C CH H2 2-O O-H HC CH H3 3C CH H2 2-O O-H HH HS SN N2 2H HC CH H3 3C CH H2 2-O O-C CH H2 2C CH H3 3H HO O-H HA A n ne ew w o ox xo on ni iu um m i io on n+Preparation of EthersStep 3:proton transfer to solvent completes the reactionC CH H3 3C CH H2 2-O O-
15、C CH H2 2C CH H3 3H HH HO O-H HC CH H3 3C CH H2 2-O O-C CH H2 2C CH H3 3H H O O-H HH H+p pr ro ot to on n t tr ra an ns sf fe er r+Preparation of EthersuAcid-catalyzed addition of alcohols to alkenes yields are highest using an alkene that can form a stable carbocation and using methanol or a 1 alco
16、hol that is not prone to undergo acid-catalyzed dehydration+acid acidcatalystcatalyst2-M ethoxy-2-m ethyl2-M ethoxy-2-m ethylpropanepropaneC C H H3 3C C H H3 3C C H H3 3C C H H3 3C C=C C H H2 2C C H H3 3O O H HC C H H3 3C C O O C C H H3 3Preparation of Ethers Step 1:protonation of the alkene gives a
17、 carbocation Step 2:reaction of the carbocation(an electrophile)with the alcohol(a nucleophile)gives an oxonium ionC CH H3 3C CH H3 3C C=C CH H2 2H HO OH HC CH H3 3C CH H3 3C CH H3 3C CC CH H3 3O OH HC CH H3 3+C CH H3 3C CC CH H3 3C CH H3 3H H O OC CH H3 3O OC CH H3 3C CC CH H3 3H HC CH H3 3C CH H3
18、3+Preparation of EthersStep 3:proton transfer to solvent completes the reactionC CH H3 3O OH HO OC CH H3 3C CH H3 3C CC CH H3 3H HC CH H3 3C CH H3 3O OH HH HO OC CH H3 3C CC CH H3 3C CH H3 3C CH H3 3+Cleavage of EthersuEthers are cleaved by HX to an alcohol and a haloalkane cleavage requires both a
19、strong acid and a good nucleophile;therefore,the use of concentrated HI(57%)and HBr(48%)cleavage by concentrated HCl(38%)is less effective,primarily because Cl-is a weaker nucleophile in water than either I-or Br-R R-O O-R R +H H-X XR R-O O-H H +R R-X XCleavage of EthersuA dialkyl ether is cleaved t
20、o two moles of haloalkaneO O2 2H HB Br rB Br rH H2 2O Oh he ea at t+2 2D D i ib bu ut ty yl l e et th he er r1 1-B Br ro om m o ob bu ut ta an ne eCleavage of Ethers Step 1:proton transfer to the oxygen atom of the ether gives an oxonium ion Step 2:nucleophilic displacement on the 1 carbon gives a h
21、aloalkane and an alcohol the alcohol is then converted to an haloalkane by another SN2 reactionC CH H3 3C CH H2 2-O O-C CH H2 2C CH H3 3H HO OH HH HC CH H3 3C CH H2 2-O O-C CH H2 2C CH H3 3H HH HO OH H+A A n n o ox xo on ni iu um m i io on nf fa as st t a an nd dr re ev ve er rs si ib bl le eB Br r:
22、-C CH H3 3C CH H2 2-O O-C CH H2 2C CH H3 3H HS SN N2 2C CH H3 3C CH H2 2-B Br rH HO O-C CH H2 2C CH H3 3+Cleavage of Ethersu3,allylic,and benzylic ethers are particularly sensitive to cleavage by HX tert-butyl ethers are cleaved by HCl at room temp in this case,protonation of the ether oxygen is fol
23、lowed by C-O cleavage to give the tert-butyl cationO OH HC Cl l+O O H H+S SN N1 1+C C l l-C Cl lA A 3 3 c ca ar rb bo oc ca at ti io on ni in nt te er rm m e ed di ia at te eA A t te er rt t-b bu ut ty yl le et th he er rOxidation of EthersuEthers react with O2 at a C-H bond adjacent to the ether ox
24、ygen to give hydroperoxides reaction occurs by a radical chain mechanism a compound containing the OOH groupO OO O2 2O OO O-O O-H HA A h hy yd dr ro op pe er ro ox xi id de eD D i ie et th hy yl l e et th he er r+O OO O2 2O OO O-O O-H HD D i ii is so op pr ro op py yl l e et th he er r+A A h hy yd d
25、r ro op pe er ro ox xi id de eSilyl Ethers as Protecting GroupsuWhen dealing with compounds containing two or more functional groups,it is often necessary to protect one of them(to prevent its reaction)while reacting at the other suppose you wish to carry out this transformation4 4-P Pe en nt ty yn
26、n-1 1-o ol l4 4-H H e ep pt ty yn n-1 1-o ol lO O H HH HO O H H?Silyl Ethers as Protecting Groups the new C-C bond can be formed by alkylation of an alkyne anion the OH group,however,is more acidic(pKa 16-18)than the terminal alkyne(pKa 25)treating the compound with one mole of NaNH2 will give the a
27、lkoxide anion rather than the alkyne anionO O H HH HN Na a+N NH H2 2-O O-N N a a+H HN NH H3 3p pK Ka a 2 25 5p pK Ka a 1 16 6-1 18 8+Silyl Ethers as Protecting GroupsuA protecting group must add easily to the sensitive group be resistant to the reagents used to transform the unprotected functional g
28、roup(s)be removed easily to regenerate the original functional groupuIn this chapter,we discuss trimethylsilyl(TMS)and other trialkylsilyl ethers as OH protecting groupsSilyl Ethers as Protecting GroupsuSilicon is in Group 4A of the Periodic Table,immediately below carbon like carbon,it also forms t
29、etravalent compounds such as the followingO O=S Si i=O OC CH H3 3-S Si i-C CH H3 3C CH H3 3C CH H3 3C CH H3 3-S Si i-C Cl lC CH H3 3C CH H3 3H H-S Si i-H HH HH HS Si il li ic co on n d di io ox xi id de eT Te et tr ra am m e et th hy yl ls si il la an ne eC Ch hl lo or ro ot tr ri im m e et th hy yl
30、 ls si il la an ne eS Si il la an ne eSilyl Ethers as Protecting GroupsuAn-OH group can be converted to a silyl ether by treating it with a trialkylsilyl chloride in the presence of a 3 amineR RC CH H2 2O O H HC Cl l-S Si i-C CH H3 3C CH H3 3C CH H3 3E Et t3 3N NR RC CH H2 2O O-S Si i-C CH H3 3C CH
31、H3 3C CH H3 3E Et t3 3N N H H+C Cl l-+C C h hl lo or ro ot tr ri i-m m e et th hy yl ls si il la an ne eA A t tr ri im m e et th hy yl ls si il ly yl le et th he er r+T Tr ri ie et th hy yl l-a am m i in ne eT Tr ri ie et th hy yl l-a am m m m o on ni iu um mc ch hl lo or ri id de eSilyl Ethers as P
32、rotecting Groups replacement of one of the methyl groups of the TMS group by tert-butyl gives a tert-butyldimethylsilyl(TBDMS)group,which is considerably more stable than the TMS group other common silyl protecting groups include the TES and TIPS groupsS Si i C Cl lM M e eM M e eM M e eS Si i C Cl l
33、M M e eM M e eS Si i C Cl lS Si i C Cl lE Et tE Et tE Et tT Tr ri im m e et th hy yl ls si il ly yl lc ch hl lo or ri id de e(T TM M S SC C l l)t t-B Bu ut ty yl ld di im m e et th hy yl ls si il ly yl lc ch hl lo or ri id de e(T TB BD D M M S SC Cl l)T Tr ri ii is so op pr ro op py yl ls si il ly y
34、l lc ch hl lo or ri id de e(T TI IP PS SC Cl l)T Tr ri ie et th hy yl ls si il ly yl lc ch hl lo or ri id de e(T TE ES SC C l l)Silyl Ethers as Protecting Groups silyl ethers are unaffected by most oxidizing and reducing agents,and are stable to most nonaqueous acids and bases the TBDMS group is sta
35、ble in aqueous solution within the pH range 2 to 12,which makes it one of the most widely used-OH protecting groups silyl blocking groups are most commonly removed by treatment with fluoride ion,generally in the form of tetrabutylammonium fluorideR RC CH H2 2O OS Si iF F-B Bu u4 4N N+F F-T TH H F FR
36、 RC CH H2 2O O H HS Si iF FA A T TB BD D M M S S-p pr ro ot te ec ct te ed da al lc co oh ho ol l+Silyl Ethers as Protecting Groups we can use the TMS group as a protecting group in the conversion of 4-pentyn-1-ol to 4-heptyn-1-olO O H HH HO OH H2 2.N N a a+N NH H2 2-3 3.B Br r4 4-H H e ep pt ty yn
37、n-1 1-o ol l4 4-P Pe en nt ty yn n-1 1-o ol lS Si iO O S Si i C CH H3 3O OH H+1 1.(C CH H3 3)3 3S Si i C Cl lC CH H3 3C CH H3 3C CH H3 3C CH H3 3C CH H3 34 4.B Bu u4 4N N+F F-F F S Si i C CH H3 3C CH H3 3C CH H3 3Epoxides a cyclic ether in which oxygen is one atom of a three-membered ring simple epo
38、xides are named as derivatives of oxirane where the epoxide is part of another ring system,it is shown by the prefix common names are derived from the name of the alkene from which the epoxide is formally derivedOxiraneOxirane(Ethylene oxide)(Ethylene oxide)CH2H2CO1 12 23 3cis-cis-2,3-Dimethyloxiran
39、e2,3-Dimethyloxirane(cis-cis-2-Butene oxide)2-Butene oxide)1,2-Epoxycyclohexane1,2-Epoxycyclohexane(Cyclohexene oxide)(Cyclohexene oxide)COCHCH3HH3CHHO1 12 2Synthesis of EpoxidesuEthylene oxide,one of the few epoxides manufactured on an industrial scale,is prepared by air oxidation of ethyleneOxiran
40、eOxirane(Ethylene oxide)(Ethylene oxide)CH2H2CO2CH2=CH2Ag2+O2Synthesis of EpoxidesuThe most common laboratory method is oxidation of an alkene using a peroxycarboxylic acid(a peracid)CO-COOHMg2+CH3COOHCOOHClMagnesium Magnesium monoperoxyphthalatemonoperoxyphthalate(MMPP)(MMPP)2Peroxyacetic acidPerox
41、yacetic acid (Peracetic acid)(Peracetic acid)meta-meta-chloroperoxy-chloroperoxy-benzoic acidbenzoic acid(MCPBA)(MCPBA)OOOOSynthesis of EpoxidesuEpoxidation of cyclohexeneR RC CO O O O H HO OC CH H2 2C Cl l2 2O OH HH HR RC CO O H HO OA A c ca ar rb bo ox xy yl li ic c a ac ci id d1 1,2 2-E Ep po ox
42、xy yc cy yc cl lo oh he ex xa an ne e (C C y yc cl lo oh he ex xe en ne e o ox xi id de e)A A p pe er ro ox xy y-c ca ar rb bo ox xy yl li ic c a ac ci id dC C y yc cl lo oh he ex xe en ne e+R RC CO O O O H HO OC CH H2 2C Cl l2 2O OH HH HR RC CO O H HO OA A c ca ar rb bo ox xy yl li ic c a ac ci id
43、d1 1,2 2-E Ep po ox xy yc cy yc cl lo oh he ex xa an ne e (C C y yc cl lo oh he ex xe en ne e o ox xi id de e)A A p pe er ro ox xy y-c ca ar rb bo ox xy yl li ic c a ac ci id dC C y yc cl lo oh he ex xe en ne e+Synthesis of EpoxidesuEpoxidation is stereospecific:epoxidation of cis-2-butene gives onl
44、y cis-2,3-dimethyloxirane epoxidation of trans-2-butene gives only trans-2,3-dimethyloxiraneC CC CH H3 3C CH HC CH H3 3H HR RC CO O3 3H HH H3 3C CH HH HC CH H3 3C CC CO Ot tr ra an ns s-2 2-B Bu ut te en ne et tr ra an ns s-2 2,3 3-D D i im m e et th hy yl lo ox xi ir ra an ne e(a a r ra ac ce em m
45、i ic c m m i ix xt tu ur re e)H HC CH H3 3H H3 3C CH HC CC CO O+Synthesis of EpoxidesuA mechanism for alkene epoxidation must take into account that the reaction takes place in nonpolar solvents,which means that no ions are involved is stereospecific with retention of the alkene configuration,which
46、means that even though the pi bond is broken,at no time is there free rotation about the remaining sigma bond Synthesis of Epoxides uA mechanism for alkene epoxidation1 12 23 34 4C CC CO OH HO OO OC CR RO OC CC CO OC CR RO OH HSynthesis of EpoxidesuEpoxides are can also be synthesized via halohydrin
47、s the second step is an internal SN2 reactionC CH H3 3C CH H=C CH H2 2C Cl l2 2,H H2 2O OC CH H3 3C CH H-C CH H2 2O O H HC Cl lN N a aO O H H,H H2 2O OO OC CH H3 3C CH HC CH H2 2A A c ch hl lo or ro oh hy yd dr ri in n(r ra ac ce em m i ic c)P Pr ro op pe en ne eM M e et th hy yl lo ox xi ir ra an n
48、e e(r ra ac ce em m i ic c)S SN N2 2A A n n e ep po ox xi id de ei in nt te er rn na al l S SN N2 2+C Cl lC CC CO OC Cl lC CC CO OSynthesis of Epoxides halohydrin formation is both regioselective and stereoselective;for alkenes that show cis,trans isomerism,it is also stereospecific(Section 6.3F)con
49、version of a halohydrin to an epoxide is stereoselective account for the fact that conversion of cis-2-butene to an epoxide by the halohydrin method gives only cis-2,3-dimethyloxirane cis-cis-2,3-Dimethyloxirane2,3-Dimethyloxiranecis-cis-2-Butene2-ButeneCCHCH3HH3CCCH3CHOCH3H1.Cl2,H2O2.NaOH,H2OSynthe
50、sis of EpoxidesuSharpless epoxidation stereospecific and enantioselectiveO OH HR R1 1R R2 2R R3 3T T i i(O O-i i P Pr r)4 4T T i i(O O-i i P Pr r)4 4O OO O H HR R3 3R R2 2O O H HR R1 1O OR R3 3R R2 2O O H HR R1 1O OA AB BO O H HO O H H(-)-D D i ie et th hy yl l t ta ar rt tr ra at te e+(+)-D D i ie
