1559T_ch09_148-17411/03/0518:56Pa9e15 ⊕ EQA Keys to the Chopler·153 ubs of alcohols gs8 Rearrangements? uncommon common common common 9-8.Reactions of Ethers As mentioned in the introduction to this study guide chapter,the chemistry of ethers is very limited,showing ard nuc displacemen reactivity only under fairly 21 As is the cas a strong acid.Then reaction can occur with a good nucleophile Nue-+R-R R-Nuc +H-6-R Good leaving group 一 CH-6-cH,soCH一-CH, CH3-O-CH,+CH;CH2OH (Not CH:CH2-0-CH3) For the s.nucleophilic ether cleay es are limited to good nucleophiles that are weakly basic like Brand which can exist in the presence of strong acid.(If you look back now at the reactions of alcohols you'll see the same onsid g there.too.)Methyl and alkyl ethers reactv worse thanfor S the latter mechanism is more typical,however)
Keys to the Chapter • 153 This section concludes the coverage of alcohol chemistry for now. A summary chart concerning the various conditions for substitution and elimination reactions follows. SUMMARY CHART Substitution and elimination reactions of alcohols Substitution Strong acid Strong acid with poor nucleophile, via inorganic with good e.g., H2SO4, in alcohol as solvent ester, e.g., nucleophile, Type of RSO2Cl, e.g., conc. Lower Higher alcohol then IE HI temperatures temperatures Methyl SN2 SN2 SN2 SN2 1° SN2 SN2 SN2 E2 2° SN2 SN1 SN1 E1 3° SN1 SN1 SN1 E1 Rearrangements? uncommon common common common 9-8. Reactions of Ethers As mentioned in the introduction to this study guide chapter, the chemistry of ethers is very limited, showing a tendency toward nucleophilic displacement reactivity only under fairly special conditions. As is the case with alcohols, for any kind of nucleophilic displacement to occur to an ether (SN1 or SN2), the leaving group (alkoxide in this case) has to be improved. This improvement is again done most simply by protonation with a strong acid. Then reaction can occur with a good nucleophile. Good leaving group Notice that the nucleophile in such a reaction cannot ever be a strong base! A strong base cannot be present together with the strong acid needed to protonate the ether: They would just neutralize each other. Addition of a strongly basic nucleophile to an already protonated ether is also no good. All that would happen would be loss of the proton from the protonated ether to the base; no nucleophilic displacement would occur. For these reasons, nucleophilic ether cleavages are limited to good nucleophiles that are weakly basic like Br and I, which can exist in the presence of strong acid. (If you look back now at the reactions of alcohols, you’ll see the same considerations applying there, too.) Methyl and 1° alkyl ethers react via the SN2 mechanism, whereas 3° ethers follow an SN1 pathway. Least reactive are 2° ethers (worse than 1° for SN2, and worse than 3° for SN1; the latter mechanism is more typical, however). 9-9. Reactions of Oxacyclopropanes Strained cyclic ethers (e.g., oxacyclopropanes) react with acid like ordinary ethers do, only faster. Order of CH3 CH3 CH3 O CH3 O CH3) H Then add CH3CH2ONa H2SO4 (Basic!) O CH3 O CH3 (Acidic) CH3CH2OH (Not CH3CH2 O Nuc R O R R Nuc H R O H 1559T_ch09_148-174 11/03/05 18:56 Page 153
1559Tch09148-17410/30/0518:03Page154 154.chapter9 FURTHER REACTIONS OF ALCOHOLS AND THE CHEMISTRY OF ETHERS reactivity is again31.At a 1 carbon,the reaction clearly takes place via an Sx2 mechanism to displace the protonated oxygen. -CH2-CH2 At 2 and 3 carbons,the reaction may be described as an "SN2-like SyI reaction."To clarify this,let's look at three ways to draw the Lewis structure of protonated trimethyloxacyclopropane. carbo H CH: a- H LC-0 H CH, H CH; H C ated molecule.It may look odd to e resonanc carbocations). H H- Nuc -CH; Likely resonance hybrid Reaction of this protonated molecule with a nucleophile will therefore occur at the 3 carbon,which is the beca oxygccubocation-like hch cast partially expect for an S2 reaction (see illustration above).For these reasons.the Sv1 and S2 labels really don't
154 • Chapter 9 FURTHER REACTIONS OF ALCOHOLS AND THE CHEMISTRY OF ETHERS reactivity is again 3° 2° 1°. At a 1° carbon, the reaction clearly takes place via an SN2 mechanism to displace the protonated oxygen. At 2° and 3° carbons, the reaction may be described as an “SN2-like SN1 reaction.” To clarify this, let’s look at three ways to draw the Lewis structure of protonated trimethyloxacyclopropane. These are actually three resonance forms of the protonated molecule. It may look odd to draw resonance forms where a whole single bond is missing, but such pictures (“no-bond structures”) are useful in some cases, provided you recognize that the individual forms are not real and that only the intermediate resonance hybrid really counts. In the case above, the resonance hybrid will probably look more like the alkyloxonium and 3° carbocation structures than the 2° carbocation structure (because 2° carbocations are worse than 3° carbocations). Reaction of this protonated molecule with a nucleophile will therefore occur at the 3° carbon, which is the most carbocation-like, as you would expect for an SN1 reaction. However, because of the position of the oxygen leaving group, which is at least partially bonded to the 3° carbon, the nucleophile can attach to the 3° carbon only from the side opposite the oxygen, resulting in inversion at that carbon atom, as you would expect for an SN2 reaction (see illustration above). For these reasons, the SN1 and SN2 labels really don’t H O H C C CH3 CH3 CH3 Likely resonance hybrid Nuc Nuc H H C C O CH3 CH3 CH3 O H Trimethyloxacyclopropane H C C CH3 CH3 CH3 Alkyloxonium ion H O H C C CH3 CH3 CH3 3 Carbocation H O H C C CH3 CH3 CH3 2 Carbocation 2 carbon 3 carbon CH2 CH2 HO H O CH2 CH2 O H CH2 CH2 Cl Cl 1559T_ch09_148-174 10/30/05 18:03 Page 154
1559T_ch09_148-17410/30/0518:03Pa9e155 ⊕ EQA Solutions to Problems.155 which C-bond breaks,but the direction of also react with basic nuc .This is an S2 process that displaces an alkoxide. nng str the energy content sucn t tively charge tdeucpisctioe to small-ring ctbers brea ote Small E. *0 c+CH,一CH :-CHz-CHz-O Nue-CH3 +O-CHs Reaction coordinate- 9-10.Sulfur Analogs of Alcohols and Ethers This short section expands on the obvious parallels between oxygen and sulfur that arise as a result of their relationship in the periodic table.As you saw earlier.the larger sized atoms are more nucleophilic.bu ess ba cludes a variety of oxidized species.Common examples are SO2 and HSO.New systems introduced here in- clude sulfonic acids(RSO3H).sulfoxides(RSOR).and sulfones(RSO2R). Solutions to Problems 25.Equilibrium always lies on the side with the weaker acid-base pai (a)Left;(b)left;(c)right:(d)right. 26.(a)CH,CH,CH,I (b)(CH)CHCH,CH,Br (Both by S2 mechanisms) (d)(CH CH)CCl (Both by Sxl mechanisms)
Solutions to Problems • 155 apply in a clear-cut way: SN1 considerations determine which COO bond breaks, but the direction of approach of the nucleophile (back-side attack) is characteristic of an SN2 process. Strained cyclic ethers also react with basic nucleophiles. This is an SN2 process that displaces an alkoxide, which is a very bad leaving group. The nucleophile has to be a good one because the leaving group (a negatively charged alkoxide ion) is a terrible one. The reaction follows the SN2 reactivity order of 1° 2° 3°. Normally alkoxides cannot be displaced in SN2 reactions. In oxacyclopropanes, however, ring strain raises the energy content such that suitably reactive nucleophiles can displace negatively charged oxygen leaving groups (see graph, below). The only reason this reaction occurs at all is that the displacement reaction breaks open a small, strained ring. Please note that this is a reaction unique to small-ring ethers. Unstrained ethers are unreactive toward basic nucleophiles. 9-10. Sulfur Analogs of Alcohols and Ethers This short section expands on the obvious parallels between oxygen and sulfur that arise as a result of their relationship in the periodic table. As you saw earlier, the larger sized atoms are more nucleophilic, but less basic. Thus comparisons of the chemical properties of pairs of species like HS vs. HO, H2S vs. H2O, and CH3SH vs. CH3OH are straightforward. Larger atoms are also more readily oxidized, and sulfur chemistry includes a variety of oxidized species. Common examples are SO2 and H2SO4. New systems introduced here include sulfonic acids (RSO3H), sulfoxides (RSOR), and sulfones (RSO2R). Solutions to Problems 25. Equilibrium always lies on the side with the weaker acid-base pair. (a) Left; (b) left; (c) right; (d) right. 26. (a) CH3CH2CH2I (b) (CH3)2CHCH2CH2Br (Both by SN2 mechanisms) (c) (d) I (CH3CH2)3CCl (Both by SN1 mechanisms) 1559T_ch09_148-174 10/30/05 18:03 Page 155
15597.ah09_148-17410/30/0518:03Pag0156 EQA 156.chapter9 FURTHER REACTIONS OF ALCOHOLS AND THE CHEMISTRY OF ETHERS 27.In each case the species are written in an order reflecting a sequence of rearrangement steps. eoudrarmaructures tothe righ re (a)CH,CHCHOH3.CH,CHCHs (Similar to rearrangement of 2.2-dimethyl-1-propanol in Section 9-3. (b)CH CHOH-CH,CH CHCHs (e)CH;CH2CH2CH2OH2.CH,CH2CHCH3 (d)(CH)2CHCH,OH2.(CH)C* (e)(CH)CCHCH,OH,.(CHCCHCH.(CHCCH(CH) Some mechanism arrows are included below to help you find your way CH; H C(CH3)3 CH C(CHa)2 ⊕ (h)CHs -CH CH CH CHs CH:CH CH:- CH; CH ons to exist for a long time,because the (a),(b)CH;CH-CH2 (c)CH,CH.CH-CH2.CH,CH-CHCH3(major product) (d)(CH:C=CH2 (e)(CH3)aCCH-CH2.(CH3)2C-C(CH3)2(major product). CH(CH H2C=C CH3
156 • Chapter 9 FURTHER REACTIONS OF ALCOHOLS AND THE CHEMISTRY OF ETHERS 27. In each case the species are written in an order reflecting a sequence of rearrangement steps. Rearrangements do not occur to an equal extent under all circumstances. Structures to the right are generally most stable. (a) CH3CH2CH2 OH2, CH3 CHCH3 (Similar to rearrangement of 2,2-dimethyl-1-propanol in Section 9-3.) (b) CH3CH OH2CH3, CH3 CHCH3 (c) CH3CH2CH2CH2 OH2, CH3CH2 CHCH3 (d) (CH3)2CHCH2 OH2, (CH3)3C (e) (CH3)3CCH2CH2 OH2, (CH3)3C CHCH3, (CH3)2 CCH(CH3)2 Some mechanism arrows are included below to help you find your way. (f ) (g) (h) 28. These conditions favor rearrangements. They allow carbocations to exist for a long time, because the reaction mixtures are strongly acidic and lack decent nucleophiles. (a), (b) CH3CHPCH2 (c) CH3CH2CHPCH2, CH3CHPCHCH3 (major product) (d) (CH3)2CPCH2 (e) (CH3)3CCHPCH2, (CH3)2CPC(CH3)2 (major product), CH3 H2C C CH(CH3)2 CH3 CH3 CH3 CH3 also CH3 CH3 CH3 CH3 CH3 H CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 C(CH3)3 CH3 C(CH3)2 CH3 H CH3 H CH3 1559T_ch09_148-174 10/30/05 18:03 Page 156