CHEM261F24notesch11
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University of Alberta**We aren't endorsed by this school
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CHEM 261
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Chemistry
Date
Dec 17, 2024
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14
Uploaded by BaronKingfisher4060
Chp 11 1 Chapter 11 – Alcohols and Ethers (A lot of this sec6on is review) Note/review: Ethershave an oxygen atom that is flanked by two iden4cal or different alkyl, alkenyl, or aroma4c groups, R-O-R, R-O-R’, R-O-Ar, R-O-CH=CR2, etc. Nomenclature– we covered already (know general naming; i.e., ethyl methyl ether, ethanol, phenol, etc.) Common cyclic ethersglucose(notice all substituents are equatorial)PhOOHOHOOHOOHOHCH3bidensyneoside B(an antiallergic agent from Bidens parvifloraWILLD)a synthetic analogue tobidensyneoside BOHOHOOHOHOHOHOHOOHOHOOOOOoxirane orethylene oxide(an epoxide)tetrahydrofuranOfuranpyran1,4-dioxane
Chp 11 2 Physical proper9es– b.p. of alcohols are generally higher than ethers of similar MW. The higher the MW, the more b.p. increases. Branching lowers b.p. (as seen before). Why alcohols higher b.p.? H-bonding Small alcohols tend to be soluble in water but become less soluble with longer alkyl chains (greasy groups). More OH’s (diol, triol, etc. increases H2O solubility). Synthesis of Alcohols (review) Industrial processes: Synthesis gas MeOH is made on a mul4billion-pound scale from a mixture of CO and H2called synthesis gas Conversion of alkyl halides to alcohols, as in Sec9on 8 Not really useful, however, because these reac4ons are not usually selec4ve. Covered already: Hydrobora4on-oxida4on and oxymercura4on/demercura4on CO + 2H2CH3OHCu–ZnO–Cr2O3, 250 °C, 50–100 atmBrH2O or HO–OHbut also
Chp 11 3 Alkyl Halides from Alcohols The reac4on of primary and secondary alcohols in the presence of acid (HX) can be complicated by elimina9on and rearrangement. The use of PBr3or SOCl2helps avoid these problems. (no mechanism, just know these reac4ons) Reflux= hea4ng the reac4on to the boiling point of the solvent to control temperature Deriva9ves of AlcoholsConversion of alcohols to good leaving groups Alcohols can be converted to mesylates, tosylates, and triflates, which are all excellent leaving groups. ROHROHPBr3SOCl2, Et2Oreflux(1° or 2° alcohol)RClRBrto form chloridesto form bromides+ HCl(1° or 2° alcohol)aryl alcohols do not work!ArOHPBr3orArXSOCl2X
Chp 11 4 General reac4on: (you do not need to learn/memorize this for the final) OSOCH3OSOOSOCF3CH3mesyl grouptosyl grouptriflyl groupOSOOCH3OSOOOSOOCF3CH3mesylatetosylatetriflateOHPhMsCl or TsClOSO2RPhR = Me or p-tolylbase*OSOClR+OSOClROPhHOSOROPhH*e.g., pyridine,or R3N:N:
Chp 11 5 No4ce the trend here – it will be very important in CHEM 263. Reac4on of alkyl sulfonates with nucleophile give inversionof the stereochemistry, since the reac4on proceeds via an SN2 mechanism: Protec9on of Alcohols as Silyl Ethers with TBDMS-Cl (tert-butyldimethylsilyl chloride) Very, very useful for “synthesis” Alcohols are acidic (pKa ~16), and they are also reac4ve toward many different reagents. Some4mes it is necessary to "protect” them in order to carry out a reac4on at some other place on a molecule; called a “protec4ng group” or some4mes a “blocking group” HOTsOTsClNEt3NuNu–cholesterol(a steroid)SN2
Chp 11 6 Synthesis of Ethers Dehydra9on of alcohols HOBr+Et2O0 °Cthen H3O+HOSiClweak base(pyridine)OSi=TBDMSOtert-butyldimethylsilyl = TBDMSTBDMSOF–NBu4+(tetrabutyl-ammoniumfluoride(TBAF)a protected alcoholNuNue.g., Nu =NaRNuNuBrBrEtOHH2SO4140 °CEtOEtCH3CH2OHHCH3CH2OHEt
Chp 11 7 But compe44ve elimina4on limits (severely) the u4lity of this method! i.e., This method cannot be used for unsymmetrical ethers. i.e., Williamson ether synthesis. Nucleophilic subs9tu9on to give an ether X = Br, I, OMs, OTs, OTf Electrophile =almost always 1°, otherwise E2 elimina4on competes ROH =1° or 2° alcohol, and some4mes 3° alcohol EtOHH2SO4180 ˚CandOHH2SO4heatEtOH + BuOHH2SO4heatEtOEt + EtOBu + BuOBuROH + NaOH + R'CH2–X ROR'alcoholelectrophilebaseSN2
Chp 11 8 Ex. An introduc4on to intramolecularreac4ons: Cyclic ether forma4on The rate of the cycliza4on reac4on depends on the size of the cycle. It is intramolecular, so entropically it is very favorable for smaller rings. O–+NaBr+ODMSOO–+NaTsO+ODMSOHOBrOHOHOBrOHOOOOOOO356478≥>>≥>relative rate ofreaction basedon ring size
Chp 11 9 A brief summary: Forma9on of t-butyl ethers: A special case (Important from a mechanis9c viewpoint) R CH2CH2OHR CH2CH2OTsR CH2CH2OCH2R’R CH2CH2BrR CH2CH2ClR CH2CH2ONaSOCl2Et2O, refluxPBr3TsClbase1. base2. R’CH2BrNaH(BuLi)TBDMS-ClpyridineR CH2CH2OSitBuMe2POCl3RCH=CH2RCH2OH+CH3CH3H2SO4RCH2O
Chp 11 10 Reac9ons of Ethers (very few) This is one reason that they make very good solvents for organic reac4ons! They will form peroxides from reac4on with O2(be careful with old bofles of ethers!) Forma9on of EpoxidesReac9on of an alkene with a peroxyacid such as mCPBA (meta-chloroperbenzoic acid). This reac4on is stereospecific, i.e., stereochemistry of the alkene is not lost in the reac4on EtOEt 2 EtX + HOEtHX, Δfor exampleOHBr, ΔHOBrOO2OOOHmCPBACH3OH3CmCPBAandOZ-alkeneE-alkeneClOOOHClCOOHOorOCH3H3CHOCH3HHH3CH(meta-chloroperbenzoic acid)
Chp 11 11 FYI: Sharpless Epoxida9on (Nobel Prize in 2001). Enan9oselec9ve. Reac9ons of Epoxides Because of ring strain, the epoxide is easy to "open" in the reac4on with a nucleophile. mCPBAOHHOHH+OHHtBuOOH, Ti(Oi-Pr)4CH2Cl2, –20 °C,(+)–DETtBuOOH, Ti(Oi-Pr)4CH2Cl2, –20 °C,(–)–DETOHHOHHCO2EtHOHCO2EtHHOCO2EtHOHCO2Et(–)–DET(+)–DETa racemic mixture(diethyl tartrate)
Chp 11 12 With acid catalysis and a weak nucleophile. Gives stereospecific product forma4on (and ogen regiospecific) normally via an SN2 reac4on With a good nucleophile – No4ce that this is one case where –OR is leaving group, because of the strained three membered ring. Add a weak acid (even water) as the second step to provide a proton. weak acid,weak nulceophile*OCH3OHCH3NuOCH3HOCH3H*e.g., H2O, ROHOMeOHMeHOH+/H2O
Chp 11 13 Gives stereospecific product forma4on via an SN2 reac4on The reac4on can be selec4ve for the least subs4tuted carbon (less steric shielding) An(1,2-Dihydroxyla9on(complimentary to syndihydroxyla4on seen earlier; OsO4) i.e., OCH3CH3NuO–1. Nu–weak acid2. Weak acidNu–CH3NuOHNu– : for exampleRO–RS–H–OOHNuMeMeNu–
Chp 11 14 Crown EthersCharles Pedersen received the 1987 Nobel Prize in chemistry for the discovery of the synthesis and binding proper4es of crown ethers. Donald Cram and Jean-Marie Lehn shared this prize as well, and they collec4vely brought supramolecular chemistryto the front page of newspapers.