北京化工大学：《有机化学》课程教学资源（双语习题与答案）Chapter 09 Further Reactions of Alcohols and the Chemistry of Ethers.pdf_大学文库

Keys to the Chapter • 149 Outline of the Chapter 9-1 Preparation of Alkoxides A selection of methods for deprotonation of alcohols. 9-2 Alkyloxonium Ions: Substitution and Elimination Reactions of Alcohols A section describing the conversion of the alcohol OH into a leaving group. 9-3 Carbocation Rearrangements A new reaction pathway for carbocations. 9-4 Esters from Alcohols A brief overview of esters and their synthetic uses. 9-5, 9-6, and 9-7 Properties and Preparations of Ethers The alcohol oxygen as a nucleophile. 9-8 Reactions of Ethers What little there is, anyway. 9-9 Reactions of Oxacyclopropanes Putting a normally unreactive functional group into a strained ring. 9-10 Sulfur Analogs of Alcohols and Ethers The parallels between oxygen and sulfur compounds. 9-11 Physiological Properties and Uses of Alcohols and Ethers Keys to the Chapter 9-1. Preparation of Alkoxides We have already seen how the acidity of alcohols resembles the acidity of water. Here two general approaches are presented for the removal of a proton from an alcohol to form an alkoxide ion: reaction with strong bases (such as [(CH3)2CH]2N or hydride) and reaction with active metals (especially alkali metals). Alkoxides are readily available species whose reactions will be explored at several places in this chapter. 9-2. Alkyloxonium Ions: Substitution and Elimination Reactions of Alcohols The other side of the acid-base story for alcohols is their basicity: Just like water, they can be protonated by strong acid, making alkyloxonium ions. These turn out to be very important in the chemistry of alcohols, because they allow reactions that involve cleavage of the carbon–oxygen bond. This bond is hard to break under neutral or basic conditions, and a comparison with haloalkanes shows why: Haloalkanes already possess a good leaving group (halide ion), whereas alcohols do not. For instance, compare the following reactions. Alcohols require improvement of their leaving group before they can become substrates in substitution reactions. The most common way to do this is protonation of the oxygen atom with strong acid. This reaction converts a bad leaving group (HO) into a good one (H2O, about as good as Br). Then, 1° alcohols can undergo SN2 reactions, and 2° and 3° alcohols can undergo SN1 reactions. Common nucleophiles in these processes are halide ions, which form haloalkanes, and other molecules of alcohol, which form ethers. As Nuc Good leaving group R X R Nuc X Nuc Bad leaving group R OH R Nuc HO 1559T_ch09_148-174 10/30/05 18:03 Page 149

150 • Chapter 9 FURTHER REACTIONS OF ALCOHOLS AND THE CHEMISTRY OF ETHERS always, eliminations can compete with these substitutions, especially at high temperatures, and alkenes are the products of the very important acid-catalyzed dehydration of alcohols. 9-3. Carbocation Rearrangements So far you have seen two reactions of carbocations: combination with a nucleophile (the second step of the SN1 process) and loss of a proton (the second step of the E1 process). There are more, as you might expect. After all, carbocations are very reactive species, and they will do just about anything to find sources of electrons. They can even attack unsuspecting atoms or groups in their own molecule, moving the atom or group together with its bonding electrons, from its original location to the positively charged carbon. Such shifts of atoms or groups from one place in a molecule to another are called rearrangements. The most common kind of rearrangement is that shown in this text section: shift of a hydride (H: ) or an alkyl group from one atom to another, with the electrons of the breaking bond, to generate a more stable carbocation from a less stable one. The most typical example is a rearrangement that changes a 2° carbocation into a 3° one, a thermodynamically favorable process. Other common types of shifts turn 2° ions into new 2° ions and 3° ions into new 3° ions. All these are liable to occur whenever “rearrangeable” carbocations are formed, namely, in the first steps of SN1 or E1 reactions of appropriately constructed molecules. In addition, protonated 1° alcohols like 2,2-dimethyl-1-propanol can sometimes change directly to 2° or 3° carbocations via simultaneous ionization and rearrangement, even though they don’t undergo simple ionization to 1° ions. A short list of examples of the main types follows. 1. 2° n 2° via hydride shift 2a. 2° n 3° via hydride shift 2b. 2° n 3° via alkyl shift 3a. 3° n 3° via hydride shift 3b. 3° n 3° via alkyl shift (CH3)2CC(CH3)2 CH3 (CH3)2CC(CH3)2 CH3 Reversible (CH3)2CC(CH3)2 H (CH3)2CC(CH3)2 H Reversible (CH3)2CCHCH3 CH3 (CH3)2CCHCH3 CH3 Normally not reversible; but product ion can undergo 3 3 interconversion; see next example (CH3)2CCHCH3 H (CH3)2CCHCH3 H Reversible but normally favored in direction shown CH3CHCHCH3 H CH3CHCHCH3 H Readily reversible 1559T_ch09_148-174 11/03/05 19:36 Page 150

152 • Chapter 9 FURTHER REACTIONS OF ALCOHOLS AND THE CHEMISTRY OF ETHERS 9-4. Esters from Alcohols The reversible reaction of alcohols and carboxylic acids to make organic esters is presented here only to alert you to the major connection alcohols have with esters. Esters are the most common and most important carboxylic acid derivatives, and their chemistry will be explored in detail in several places during the last third of the course. Inorganic esters serve useful purposes as synthetic intermediates for certain functional group interconversions. Here, alternative ways to transform alcohols into haloalkanes using these compounds are shown to be often superior to the more “classical” method involving acid-catalyzed substitution. Whereas the latter is frequently susceptible to rearrangement, the phosphorus and sulfur reagents presented here can often allow substitutions to occur without having rearrangements interfere with the course of the reaction. This is most noticeable with 2° alcohols. Upon protonation of a 2° alcohol, SN1 reactivity (i.e., carbocation chemistry) predominates. In contrast, the leaving groups of inorganic esters derived from 2° alcohols exhibit a more moderate and well-behaved SN2 reactivity. This can be very useful. With these reactions and the other reactions so far described in this chapter, the chart of functional group interconversions first presented in Chapter 8 has grown to look like this: 9-6 and 9-7. Synthesis of Ethers In Chapters 6 and 7 we saw examples of both substitution and elimination reactions involving alcohols and alkoxides in reactions with haloalkanes and related compounds. For general calibration purposes, please refer now to the Summary Chart in the last “Keys to the Chapter” section of Chapter 7 of this study guide (“Major reactions of haloalkanes with nucleophiles”). Alkoxides derived from smaller alcohols are comparable to hydroxide—strongly basic and unhindered—and give excellent results in SN2 reactions with both methyl and 1° halides (fourth column, rows 1 and 2). These are the prototypical Williamson ether syntheses, and several are illustrated in the text. Increased bulk in either the alkoxide [e.g., (CH3)2CHO or (CH3)3CO] or the haloalkane (branched 1°, 2°, etc.) tends to increase the amount of E2 reaction at the expense of SN2 chemistry (refer to the “three questions” for favoring elimination or substitution, also in Chapter 7 of the text and also this study guide). Obviously, 3° halides are worthless in the Williamson ether synthesis because they give only elimination products upon reaction with the strongly basic alkoxide reagent. Normal considerations of kinetics and stereochemistry apply, of course, to these substitution and elimination processes. In contrast with alkoxides, alcohols are poor nucleophiles, like water (see second column in “Major reactions of haloalkanes with nucleophiles” chart). However, alcohols can act as nucleophiles to make ethers in either of two ways: strongly acidic conditions when no other nucleophiles are present, and solvolytic (SN1) conditions with 2° and 3° halides. Typical examples of each are presented. Alkanes Haloalkanes Alkenes Alcohols Carbonyl compounds Lots of other things Functional Group Interconversions Halogenation Reduction E reactions E reactions SN reactions SN reactions SN reactions Reduction reactions Oxidation reactions 1559T_ch09_148-174 10/30/05 18:03 Page 152

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