北京化工大学：《有机化学》课程教学资源（双语习题与答案）Chapter 08 Hydroxy Functional Group：Alcohols（Properties, Preparation, and Strategy of Synthesis）.pdf_大学文库

Keys to the Chapter • 133 Outline of the Chapter 8-1 Nomenclature A description of both systematic and common naming systems for these very common molecules. 8-2 Physical Properties A new factor is introduced: hydrogen bonding. 8-3 Acidity and Basicity of Alcohols Similarities and differences with water, the simplest inorganic relative. 8-4 Industrial Preparation of Alcohols A brief survey of methods for the preparation of commercially useful alcohols. 8-5 Synthesis of Alcohols by Nucleophilic Substitution 8-6 Oxidation and Reduction Alcohols and carbonyl compounds are interconverted in oxidation–reduction processes, opening up many synthetic possibilities. 8-7 Organometallic Reagents A detour, introducing compounds containing negatively polarized, nucleophilic carbon atoms. 8-8 Organometallic Reagents in the Synthesis of Alcohols The most important general alcohol syntheses: addition of nucleophilic carbon compounds to carbonyl groups. 8-9 An Introduction to Synthetic Strategy How to look at a “target” molecule and logically “plan” its synthesis using sequences of several reactions. Keys to the Chapter 8-1 and 8-2. Nomenclature and Physical Properties Two points need to be made concerning nomenclature. First, alcohols have been around for a long time, and the common names given in this section are still in widespread use and need to be learned and understood. Second, there is an order of precedence when there are two or more different functional groups in a molecule. This precedence order determines the numbering. The alcohol group is of fairly high ranking on this list, whereas halogens are near the bottom. So, The physical properties of alcohols are strongly influenced by the hydrogen bonding ability of the OH group. As in water, the hydroxy hydrogen in an alcohol and a lone pair on a highly electronegative atom (typically F, O, or N) can participate in an unusually strong form of dipole–dipole (electrostatic) interaction. Although much weaker than an ordinary covalent bond, this effect may be worth several kcal mol1 and is Cl Br OH This compound is 4-bromo-2-chlorocyclopentanol. Note that the OH is understood to be attached to carbon 1 in the ring. Cl OH CH3CHCH2CHCH3 This compound is 4-chloro-2-pentanol (not 2-chloro-4-pentanol). 1559T_ch08_132-147 10/30/05 11:59 Page 133

much stronger than any other dipole–dipole attraction, which is why it merits the special name hydrogen bonding. Remember, the requirements for hydrogen bonding are hydrogens, such as those attached to very electronegative atoms (e.g., N, O, F), and electronegative atoms with lone pairs (again, mainly N, O, and F) to attract them. 8-3. Acidity and Basicity of Alcohols If you understand the acidic and basic nature of water, then you will need to learn only a little bit that is new here with alcohols. The equilibrium processes are qualitatively similar: The differences arise from the presence of the R group (instead of an H), which can affect the relative stabilities of the three species involved. Simple alkyl groups generally destabilize both ROH2 and RO in solution, relative to ROH, more than H3O and OH are destabilized, relative to water. So most ordinary alcohols are both weaker acids and weaker bases than water. Electron-withdrawing substituents in R (such as halogens) will stabilize RO, however, thereby making ROH a stronger acid (see entries in Table 8-2). The acidity and basicity of alcohols will play major roles in many of their reactions. When an alcohol acts as a base and is protonated by a strong acid, becoming ROH2 , it then contains a good leaving group and is capable of both substitution and elimination reactions (Chapter 9). When an alcohol acts as an acid and loses a proton, it becomes RO, a good nucleophile and strong base capable of entering into E2 and SN2 reactions (Chapters 6 and 9). So this chemistry really serves as a general entry to the more extensive survey of reactions of alcohols coming up later. 8-5. Synthesis of Alcohols by Nucleophilic Substitution After a section on industrial methods, a review covering SN2 and SN1 routes to alcohols is presented. Primary alcohols may be prepared by SN2 displacement reactions of HO with appropriate substrates (e.g., primary haloalkanes). This approach sometimes works for secondary systems, but elimination often interferes. To a limited extent, both secondary and tertiary alcohols may be formed in SN1 reactions with water as the nucleophile. However, the chemistry described in the remainder of the chapter provides much more versatile and reliable means of synthesizing alcohols. 8-6. Oxidation and Reduction Carbonyl compounds such as ketones and aldehydes are useful precursors (starting materials) for the synthesis of alcohols. Reaction with the hydride reagents NaBH4 and LiAlH4 converts aldehydes to primary alcohols. The same process converts ketones to secondary alcohols. These hydride reductions are the first of many H3O H2O HO ROH2 ROH RO As a base (adds H) As an acid (loses H) O O CH3 CH3 CH3 CH3 O O O O H H H CH3 CH3 H CH3 CH3 Strong “hydrogen bonding” type dipole–dipole attractions in methanol Weak dipole–dipole attractions in dimethyl ether 134 • Chapter 8 HYDROXY FUNCTIONAL GROUP: ALCOHOLS: PROPERTIES, PREPARATION, AND STRATEGY OF SYNTHESIS 1559T_ch08_132-147 10/30/05 11:59 Page 134

Keys to the Chapter • 135 examples that you will see of nucleophilic additions to the electrophilic carbons of carbonyl groups. This is one of the most important classes of reactions in organic chemistry. The second part of this text section introduces the oxidation of alcohols to aldehydes and ketones, the reverse of reduction. Alcohol oxidation is very useful in that it produces a carbonyl group, the most important functional group of all. Note the two types of reagents based on Cr(VI): PCC (pyridinium chlorochromate, pyH CrO3Cl), which is specifically intended for oxidation of primary alcohols to aldehydes, and aqueous dichromate, which oxidizes secondary alcohols to ketones, but overoxidizes 1° alcohols to carboxylic acids. With these aspects of alcohol preparation and chemistry as background, we now turn to a discussion of molecules that will greatly expand our ability to make bonds: compounds with nucleophilic carbon atoms. 8-7. Organometallic Reagents So far the only kind of polarized carbons we’ve looked at in any detail is the (electrophilic) carbon that results from its attachment to a very electronegative atom: If we were to seek a logical way to link two carbon atoms in a synthetic process, we would try to take advantage of electrostatics and find molecules with carbons, which could combine with the carbons above. That’s very nice, but where can we find carbon atoms? Logically, if carbons result from attachment to electronegative atoms, then carbons should result from attachment to electropositive atoms. Metals are the most electropositive elements, so the way to get a (nucleophilic) carbon would be to attach it to a metal. Compounds with carbon–metal bonds are called organometallic compounds and are sources of nucleophilic carbons. This section describes the preparations of some organometallic compounds. These reactions are easy to do, and the reagents you get are very useful in synthesis. The R groups in RLi and RMgX also act as very strong bases. They are protonated by even weak acids like water or ammonia, giving the hydrocarbon RH as the product: 8-8. Organometallic Reagents in the Synthesis of Alcohols We now come to the primary value of these reagents: their ability to react as nucleophiles toward the electrophilic carbon in carbonyl compounds In a reaction mechanistically analogous to the hydride additions of Section 8-6, organometallic reagents add nucleophilic carbon to aldehydes and ketones, resulting in alcohols, and making a new carbon–carbon bond in the process. At the end of the next section, you will find a summary chart of the major types of reactions that convert carbonyl compounds to alcohols. 8-9. An Introduction to Synthetic Strategy In order to learn how to devise sensible ways to make large organic molecules from small ones (a typical task of synthesis), you need to approach the problem systematically. First, note that the reactions you are learning can be classified into two categories: 1. Reactions that exchange one functional group for another but do not make or break any carbon–carbon bonds. These are called functional group interconversions, and a simple example is CH3I NaOH n CH3OH NaI C O). ( “H “R ” ” RH From even weakly Weak acid acidic molecules (e.g., H2O, ROH, NH3) Strong base (as in ROM) C X C O Haloalkane C OH Alcohol C OR Ether Carbonyl C N Nitrile 1559T_ch08_132-147 10/30/05 11:59 Page 135

136 • Chapter 8 HYDROXY FUNCTIONAL GROUP: ALCOHOLS: PROPERTIES, PREPARATION, AND STRATEGY OF SYNTHESIS 2. Reactions that make or break carbon–carbon bonds. In the text Section 8-8 you saw several very typical examples of this kind of reaction. There are transformations that overlap the two categories (for instance, SN2 reactions with cyanide), but let’s just keep things simple for now. Next, you should draw a chart of the general functional group interconversions that we’ve seen so far. This is how it would look at the moment: It is absolutely necessary to know these interconversion patterns, because they provide the framework for designing synthetic strategy. Suppose we wish to synthesize an alcohol starting with an alkane. From this chart, we see immediately that we have no direct method for converting alkanes to alcohols. We must first make a haloalkane and then use it in another reaction to make an alcohol. We set up the proposed synthesis in just that way and insert the specific reagents necessary to carry out the two synthetic steps: Note that it is not enough to use the general labels “radical halogenation” or “SN2 reaction” in the synthesis equations; the actual reagents have to be given. All right. What about carbon–carbon bond-forming reactions? Syntheses requiring the formation of new bonds are best approached via the retrosynthetic analysis described in the text. One works backward on paper, imagining disconnecting bonds in the desired product molecule, looking for methods that can put together the necessary bonds in an efficient way from reasonable starting molecules. Functional group interconversions are applied as necessary. Notice that by combining the oxidation of alcohols with the one main carbon–carbon bond-forming reaction you’ve had so far—addition of Grignard reagents to carbonyl compounds to make alcohols—you can now assemble pretty big molecules via synthetic schemes of several steps. The key is the following sequence, made possible by the capability to oxidize alcohols to carbonyl compounds: Take some time to look over the examples in the text. Note the preferability of some routes over others, based on efficient incorporation of small molecules into large ones. Finally, apply the techniques to the probOxidation Addition of Grignard with m Alcohols with carbons n carbons Aldehyde or ketone with n carbons New alcohol with n m carbons CH4 Cl2, hv HO CH4 CH3OH CH3Cl CH3OH No direct method A sensible synthesis Alkanes Haloalkanes Alcohols Carbonyl compounds Lots of other things Halogenation Reduction SN reactions SN reactions Alkenes E reactions Reduction reactions Oxidation reactions Functional Group Interconversions 1559T_ch08_132-147 10/30/05 11:59 Page 136

138 • Chapter 8 HYDROXY FUNCTIONAL GROUP: ALCOHOLS: PROPERTIES, PREPARATION, AND STRATEGY OF SYNTHESIS 24. (a) Ethanol hydrogen bonds to water. Chloroethane is attracted to water by dipole forces. Ethane is nonpolar and attracted least to water. (b) Solubility decreases as the relative size of the nonpolar portion of a molecule increases. 25. Intramolecular hydrogen bonding stabilizes the gauche conformation of 1,2-ethanediol, shown at right, but not the anti form. In 2-chloroethanol, similar hydrogen bonding can occur (although it is weaker because of poorer overlap between the large Cl 3p lone pair orbital with the small hydrogen): So the conformational ratio of 2-chloroethanol should be more like that of 1,2-ethanediol than 1,2-dichloroethane, in which hydrogen bonding is absent. 26. (a) The diequatorial conformation of the diol is shown below, left. It is stabilized in two ways, relative to the diaxial form. First, the OOH groups are larger than OH, and therefore sterics favors the diequatorial. Second, the two hydroxy groups are close enough in the trans-1,2-diequatorial conformation to form an internal hydrogen bond (below, right). The energy of this conformation is further lowered by the strength of this hydrogen bond, about 2 kcal mol1 . (b) As the models of the diol in part (a) show, adjacent diequatorial substituents are in rather close proximity. A Newman projection view further illustrates this point, revealing that the groups are in a gauche relationship. Replacement of the two hydroxy hydrogens with very bulky silyl groups makes the diequatorial form less stable than the diaxial, because the 1,2-silyl-silyl steric interference is greater than the alternative, two pairs of 1,3-silyl-hydrogen diaxial interactions. In addition, with the hydrogens gone from the oxygen atoms no hydrogen bonding is possible to help lower the energy of the diequatorial form. Compare the structures: Diequatorial Diaxial OSi[CH(CH3)2]3 H OSi[CH(CH3)2]3 H H H H H H H OSi[CH(CH3)2]3 OSi[CH(CH3)2]3 OSi[CH(CH3)2]3 OSi[CH(CH3)2]3 H H H OSi[CH(CH3)2]3 OSi[CH(CH3)2]3 H H H O O H H H OH OH H trans-1,2-Cyclohexanediol (both _ OH groups equatorial) O H H H H H Cl O H H H H H HO 1559T_ch08_132-147 10/30/05 11:59 Page 138