北京化工大学：《有机化学》课程教学资源（习题与答案）Chapter 17 Aldehydes and Ketones：The Carbonyl Group.pdf_大学文库

Nomenclature of carbonyl compounds presents a bit of a problem in that several alternative names may be possible for almost any compound. For example, one can give any of several names to the structure above: 3-Methyl-2-butanone (IUPAC) and isopropyl methyl ketone (common) are just two that are still in current use. Be prepared for some variety, especially in common names! The old (and I mean old) naming system for phenyl ketones is especially entertaining. That for C6H5COR was derived by combining the (common) name of the carboxylic acid RCO2H (dropping the final -ic acid and adding an o if one wasn’t already there) with the suffix -phenone. So, C6H5COCH3 is acet(ic acid) o phenone acetophenone; C6H5CO(CH2)4CH3 is valer(ic acid) o phenone valerophenone; C6H5COC6H5 is benzo(ic acid) phenone benzophenone; and so on. No, it doesn’t make much sense to me, either, but that’s what people called them. 17-2. Structural and Physical Properties The polarized carbonyl group is the key to the physical and chemical properties of carbonyl compounds. Although they have polarizations comparable to those found in haloalkanes, carbonyl compounds have a negatively polarized oxygen capable of hydrogen bonding to protic solvents. They are therefore much more water soluble than haloalkanes, for instance. The carbon–oxygen double bond is also considerably stronger than the carbon–carbon double bond in alkenes. One consequence of the relatively strong CPO bond is its tendency to form whenever possible. Whereas additions to CPC bonds are usually quite exothermic, many additions to CPO bonds are not and, indeed, are often reversible, with equilibrium constants near 1. Later you will see a number of reactions that generate carbonyl groups in ways that, at first glance, seem rather surprising. 17-3. Spectroscopy A few noteworthy points are brought up here. Infrared spectroscopy is very useful for characterization of carbonyl compounds: The band for the CPO stretch is very intense and located in a region of the spectrum (usually 1690–1750 cm1 ) that is free from strong absorptions of other functional groups. The precise location of this peak is also useful in establishing the nature of the groups attached to the carbonyl carbon. 13C NMR spectroscopy exhibits signals near 200 ppm for the carbonyl carbon, and the aldehydic (also called ‘formyl’) hydrogen (OCHO) resonates in the range 9.5–10.0 ppm in the 1 H NMR. 17-4. Preparation of Aldehydes and Ketones: A Review The number of methods that exist to synthesize carbonyl compounds is impressive to the point of being intimidating. But don’t be put off by this situation. Each reaction is presented in an appropriate, logical context. This section mainly reiterates carbonyl syntheses that you’ve seen before, perhaps just with a few new examples to help reinforce those original presentations. 17-5. Reactivity of the Carbonyl Group: Mechanisms for Addition This chapter concentrates solely on one type of reaction: addition across the carbon–oxygen double bond of a carbonyl group. Carbonyl additions are polar reactions that exactly follow pathways that would be expected by electrostatics. The two main mechanisms described in this section are distinguished by the order of addition. Strong nucleophiles, Nuc (which may be added directly or formed by the reaction of a base with NucOH), add to the C Nucleophiles attach here O Electrophiles attach here (CH3)2CHC CH3 O Keys to the Chapter • 305 1559T_ch17_304-322 11/3/05 10:48 Page 305

carbonyl carbon first, followed (usually) by protonation of oxygen (which may be a separate step). Conversely, addition of weaker nucleophiles, especially neutral NOucH, is helped by prior protonation of the carbonyl oxygen to give the highly electrophilic group. Whichever way the reaction proceeds in any given case, its scope is very broad, and many useful types of addition products are known. These are the subjects of the remaining sections of the chapter. 17-6 through 17-9. Addition of Water, Alcohols, and Amines to Aldehydes and Ketones There are actually two fundamentally different types of reactions in these sections. The first is the reversible addition of a nucleophile to a carbonyl group, which can generally be catalyzed by either base or acid. 1. If NucOH is Product is H2O Aldehyde or ketone hydrate ROH Hemiacetal RSH Hemithioacetal RNH2 or R2NH Hemiaminal The second is really carbocation chemistry. When NucOH is ROH, or RSH, the product in the reaction shown above may have its OH group replaced by a second Nuc. This reaction occurs by the SN1 mechanism and leads to relatively stable acetal or thioacetal products. As the text section shows, these latter two kinds of compounds are resistant to attack by many kinds of basic or nucleophilic reagents, such as RLi, Grignards, and hydrides. Conversion of an aldehyde or ketone CPO to an acetal or thioacetal is a handy way of protecting it when you need to react some other functional group in a molecule with a strong base or nucleophile. When NucOH is a primary amine, RNH2, further reaction of the hemiaminal gives an imine, containing a carbon–nitrogen double bond. Alternatively, when the nucleophile is R2NH, an enamine results. 2a. 2b. 2c. For all practical purposes, acid-catalyzed reaction of an aldehyde or a ketone with any of the nucleophiles listed in reaction 1 will continue straight through to the product of reactions 2a, 2b, and 2c, as the case may be. Conversely, acid-catalyzed hydrolysis of any of the latter products will proceed back all the way to the original aldehyde or ketone and the free nucleophile. Acid OH C C C C NR2 NR2 H (H or R) Enamine (H or R) H2O Acid OH R C C NHR (H or R) R NR Imine (H or R) H2O Acid OH R C C (OR or SR) ( ( ROH or RSH (H or R) R (OR or SR) (OR or SR) If ROH: Acetal If RSH: Thioacetal (H or R) H2O O Base or acid R C Aldehyde or ketone (H or R) Nuc H OH R C Nuc (H or R) C OH 306 • Chapter 17 ALDEHYDES AND KETONES: THE CARBONYL GROUP 1559T_ch17_304-322 11/3/05 10:48 Page 306

17-10. Deoxygenation of the Carbonyl Function The reduction of CPO to CH2 may be achieved in three ways: Raney nickel desulfurization of thioacetals (Section 17-8), Clemmensen reduction (Section 16-5), and, as described here, Wolff-Kishner reduction. Because there are many ways to make carbonyl compounds, and carbonyl compounds are great places to start for making new carbon–carbon bonds, you will find that carbonyl groups are often present when complex molecules are made from simpler ones. This will be especially evident in Chapters 18–20 and 23. Deoxygenation will be useful if you need to get rid of a carbonyl group that has been used to construct bonds in a large molecule but is not wanted in the final product. The example of Friedel-Crafts alkanoylation followed by deoxygenation is just the first that you will see. 17-11 and 17-12. Addition of Carbon Nucleophiles to Aldehydes and Ketones Grignard reagents and alkyllithiums are examples of highly reactive “carbanionic” reagents (i.e., they behave like carbanions). In this section less highly energetic carbanionic reagents are introduced. Cyanide ion is the simplest, and the products of its addition to aldehydes and ketones, cyanohydrins, have some limited synthetic utility. Ylide reagents containing phosphorus are much more useful, particularly in the regiospecific synthesis of alkenes, because the double bond is fixed in a single position determined entirely by the starting compounds in the reaction. 17-13. Baeyer-Villiger Oxidation of Ketones Baeyer-Villiger oxidation of ketones to carboxylic esters is significant for two reasons. Mechanistically, it involves a nucleophilic addition to a carbonyl group, which is no big deal. The nucleophile, however, is a peroxidic species, which can lead to rearrangement, forming a new oxygen–carbon bond. You might recall a somewhat related mechanistic rearrangement, the migration of a group from boron to oxygen during the oxidation of alkylboranes with basic hydrogen peroxide. The second reason the Baeyer-Villiger reaction is significant is that it cleaves a carbon–carbon bond. You have seen only a very small number of reactions capable of this (e.g., ozonolysis; Chapter 12). The power of this method to be a synthetic tool lies both in its high selectivity when the carbonyl compound is not symmetrical (see discussion of migratory aptitudes) and in the subsequent chemistry available from the ester or acid, which will be covered shortly. R R B R R R B O R HO H2O OOH, Rearrangement: R migrates to O R R R B O OH New C O bond O O R C R H2O OOCCH3, O Rearrangement: R migrates to O O R R C O OC CH3 O O R C O New C O bond R OCCH3 Exclusive regioisomer (Mixture of E and Z stereoisomers) O C R R RCH Typical phosphorus ylide P(C6H5)3 RCH CRR (C6H5)3P O Keys to the Chapter • 307 1559T_ch17_304-322 11/3/05 10:48 Page 307