anti-addition acidic conditions S N basic conditions CH 18: Ethers and Epoxides

Transcription

1 rgnic Chemistry Notes y Jim Mxk C 18: Ethers nd Epoxides jim.mxk@nu.edu Topics: Nming ethers nd understnding ethers inertness Prepring ethers vi Willimson ether synthesis: S N 2 vs E 2 ection of ethers in strong cidic solution Epoxides Synthesis nd rectivity Acid ring opening to give oth steric nd electronic products: Both S N 1 nd S N 2 Bse ring opening to give steric products: S N 2 Connections: Sustitution- > 1 1 C 2 C X Sustitution- > 1 C 2 cidic conditions nti-ddition Nu =,, X Nu Nu Product depends on Sustitution sic conditions S N 2 S N 2 Nu Nu =,, X, (from Grignrd) nd (from LA) C18-1

2 rgnic Chemistry Notes y Jim Mxk Ethers nd Epoxides Nming ethers: Common: Tke the sustituent nmes of ech side of the nd dd ether Nme: C 3 C 2 C 2 C 3 (C 3 ) 2 CC 2 Ph (C 3 ) 3 CC 3 jim.mxk@nu.edu IUPAC: Tke the shortest chin nd mke it sustituent with (lkoxy)lkne. Nme the ove. Epoxides re cyclic ethers se on 3-memered ring. Since epoxides re mde from lkenes, we usully cll them y the lkene nme followed y oxide. The IUPAC nme is epoxy denoting the positions. (e.g. 1,2-epoxy-) Physicl properties: Why does ethnol oil t 78 0 while diethyl ether oils ner room temperture? Why is ethnol completely solule in wter nd oils s 95:5 mixture with wter, while diethyl ether is used s n extrction solvent with wter? When mixed with wter, ether seprtes y more thn 97% (there is tiny soluility Do you know why? Wht technique must we use to del with the soluility of ether in wter fter the extrction?) When ether is mixed with wter does it go to the top or ottom? ow cn you tell? Assume similr volume for the unit of n orgnic (C 2 ) vs 2. Which one would e most dense? C 2 2 Synthesis of ethers: Ethers re mde from lkenes like lcohols or from S N 2 rection etween n lkoxide (lcohol nion) nd n lkyl hlide or tosylte. From lkenes nd lcohols Predict the product of the rection of ethnol + propene (1) cid g(ac) 2 // (2) NB 4 Willimson Ether Synthesis S N 2 rection of lkoxide with lkyl hlide Let s consider the synthesis of MTBE, gs dditive to oxygente the fuel. C 3 C 3 C 3 3 C (1) Creting the Nucleophile = lkoxide nion ydroxide is never used ecuse the rection + N does not led clenly to lkoxide. Why? C18-2

3 rgnic Chemistry Notes y Jim Mxk jim.mxk@nu.edu There re two methods for creting the lkoxide ion clenly: ne is N. Given pk( 2 )=38, predict the direction nd mgnitude of the rection of methnol + N But the est wy is to rect the lcohol with metllic N. The generl rection works like this: (note this is n cid/se nd redox rection): Given pk( 2 ) = N(s) 2 N (g) Any unsymmeticl ether cn e mde from the lkoxide from one side nd the lkyl hlide from the other side or the reverse. Usully, there is correct wy nd wrong wy. First let s try this pproch: methnol methoxide + tert-utyl romide? Drw out the rection scheme: C 3 N C 3 3 C - 3 C C 3 This strtegy does not work to mke MTBE. Why? The rection mechnism here is. The min orgnic product is? C 2 3 C - 3 C C 3 If we reverse the nucleophile nd the lkyl romide, would this e etter wy to mke TBME? ( 3 C) 3 C N ( 3 C) 3 C - 3 C Summry Sustitution Pttern ective Type Lest Sustituted Electrophile = - Most Sustituted Nucleophile = - + N -- ections of ethers: Ethers cn e cleved y strong cids. Why must the cid e so strong? Write the rrows for the clevge of TF (tetrhydrofurn) with I? I + - I I S N N I 1 3 Wht is the driving force of the lower rection? Becuse of the inertness of ethers, ethers re used s rection nd extrction solvents. C18-3

4 rgnic Chemistry Notes y Jim Mxk jim.mxk@nu.edu Synthesis of epoxides Epoxides re generlly mde from the rection of lkenes with peroxy cid. A norml croxylic cid hs the form -C. A peroxy cid hs n extr oxygen: C 3 The most common cid used is clled MCPBA for met-chloroperenzoic cid. Drw it. Why do you think MCPBA is met? Why Cl? ow would you mke MCPBA from enzene? The generl rection goes like this. propene + MCPBA propylene oxide or 1,2-epoxypropne. Is this rection oxidtion? Does it mke chirl product? MCPBA C 3 C 3 C2 Wht is the stereochemistry of the epoxide? C 3 3 C 3 C C 3 3 C C 3 Wht is the stereochemistry from trns-2-utene + MCPBA Drw the rection of cis-2-utene + MCPBA 3 C C 3 Wht is the stereochemistry? ections of epoxides ecuse epoxides hve strin, they re much more rective thn regulr ethers. Epoxides cn e ring opened y either cid or sic conditions. C18-4

5 rgnic Chemistry Notes y Jim Mxk jim.mxk@nu.edu Acidic conditions: Wek nucleophiles. Acids cn protonte the oxygen in the epoxide ring mking it etter leving group nd the crons in the epoxide more. Below is the ring opening of cyclohexene oxide with queous cid. Note only the ttchment of wter on C is shown. Wter cn lso ttch to C. MCPBA Wht is the product of the wter, coming onto C? 3 + Wht is the reltionship etween the wter rection t C vs C? Wht mechnism is this most like from efore? Wht is the role of the + here? ow could you mke the cis diol? When nother nucleophile like Cl - is used, the rection of 1 0 /2 0 epoxide: 1,2-epoxyutne with Cl gives mixture of products. 3 C Cl 3 C + Cl Cn you see the pluses nd minuses of the either product? 1-chloro () is promoted y. 2-chloro () is promoted y. When the epoxide is on tertiry C, then the most sustituted cron is sustituted with the wek nucleophile. Consider the rection of 1-methyl-1,2-epoxycyclohexne with. Why does it go one wy nd not oth? C 3 C comine ions most stle Cro ction C18-5

6 rgnic Chemistry Notes y Jim Mxk jim.mxk@nu.edu Bsic conditions. Strong Nucleophiles. Bsic conditions re just S N 2 rections. The regiochemistry is lwys on the lest sustituted. Question out the rections ove: Cn there e strong nucleophile under cidic conditions? Wht kind of solvent is usully used in S N 2? Another method for forming 1,2-diols is with N nd n epoxide. MCPBA Consider the rection of 1,2-epoxyutne with ethoxide: 2 moles - 3 C Etonly why? Another common rection is the rection of Grignrds: EtMg = Et:- Mg + 3 C only why? Another rection with strong nucleophile is the rection with LA (: - ) LA = :- 3 C only why? All of the sic rections must e cidified on workup to give n lcohol. Prctice: Wht strong nucleophile nd epoxide were used to mke these lcohols? C 3 C 3 C18-6

7 rgnic Chemistry Notes y Jim Mxk ections with epoxides DNA dmge y romtics (BP) jim.mxk@nu.edu Key Synthetic Step in synthesis of phenylephrine - N C3 + 2 N C 3 2 N C 3 C 2 3 S 3 S This procedure is rther pined, ut ll the steps re sed on rections you hve studied. Why would this procedure never relly e used? C18-7