有机化学结构与功能5th答案sg_ch17

1、17 Aldehydes and Ketones: The Carbonyl Group Congratulations! You have finally gotten to the first of several chapters that examine the chemistry of carbonyl compounds: the most important ones in organic chemistry. Why are they so important? They are extremely ver- satile in carboncarbon bond format

2、ion, and, therefore, synthesis. Carbonyl compounds contain an electrophilic carbonyl carbon (which you already know about from Chapter 8) as well as a potentially nucleophilic carbon next to it (which you will learn about shortly). This “double-barreled” functional capability is unique among the sim

3、ple compound classes. The importance of carbonyl compounds extends to biological chemistry as well, where the carbonyl group plays a central role in biochemical synthesis of naturally occurring molecules. Outline of the Chapter 17-1Naming the Aldehydes and Ketones 17-2Structural and Physical Propert

4、ies 17-3Spectroscopy 17-4Preparation of Aldehydes and Ketones: A Review 17-5Reactivity of the Carbonyl Group: Mechanisms of Addition One of two major reaction patterns for carbonyl compounds. 17-6, 17-7, 17-8Addition of Water and Alcohols to Aldehydes and Ketones Hydrates, hemiacetals, acetals, and

5、protecting groups. 17-9Addition of Amines to Aldehydes and Ketones 17-10Deoxygenation of the Carbonyl Function Reduction of CPO to CH2. 17-11, 17-12Addition of Carbon Nucleophiles to Aldehydes and Ketones With mechanistic details and synthetic applications. 17-13, 17-14Oxidations of Aldehydes and Ke

6、tones Keys to the Chapter 17-1.Naming the Aldehydes and Ketones Most of the material in these sections is of a relatively routine nature, so only a few points of special interest, or with special implications, will be mentioned. 304 1559T_ch17_304-322 11/3/05 10:48 Page 304 Nomenclature of carbonyl

7、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 iso- propyl methyl ketone (common) are just two that are still in current use. Be pr

8、epared for some variety, espe- cially in common names! The old (and I mean old) naming system for phenyl ketones is especially entertain- ing. 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 wasnt already th

9、ere) with the suffix -phenone. So, C6H5COCH3is acet(ic acid) ?o ?phenone ?acetophenone; C6H5CO(CH2)4CH3is valer(ic acid) ?o ?phenone ?valerophe- none; C6H5COC6H5is benzo(ic acid) ? phenone ? benzophenone; and so on. No, it doesnt make much sense to me, either, but thats what people called them. 17-2

10、.Structural and Physical Properties The polarized carbonyl group is the key to the physical and chemical properties of carbonyl compounds. Al- though they have polarizations comparable to those found in haloalkanes, carbonyl compounds have a nega- tively polarized oxygen capable of hydrogen bonding

11、to protic solvents. They are therefore much more water soluble than haloalkanes, for instance. The carbonoxygen double bond is also considerably stronger than the carboncarbon double bond in alkenes. One consequence of the relatively strong CPO bond is its tendency to form whenever possible. Whereas

12、 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.Spectrosc

13、opy A few noteworthy points are brought up here. Infrared spectroscopy is very useful for characterization of car- bonyl compounds: The band for the CPO stretch is very intense and located in a region of the spectrum (usu- ally 16901750 cm?1) that is free from strong absorptions of other functional

14、groups. The precise location of this peak is also useful in establishing the nature of the groups attached to the carbonyl carbon. 13C NMR spec- troscopy exhibits signals near ? ? 200 ppm for the carbonyl carbon, and the aldehydic (also called formyl) hydrogen (OCHO) resonates in the range ? ? 9.510

15、.0 ppm in the 1H 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 in- timidating. But dont be put off by this situation. Each reaction is presented in an appropriate, logical context. This s

16、ection mainly reiterates carbonyl syntheses that youve seen before, perhaps just with a few new exam- ples 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 carb

17、onoxygen 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 nu- cleophiles, Nuc?(which may be added directl

18、y or formed by the reaction of a base with NucOH), add to the C ? OElectrophiles attach hereNucleophiles 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)

19、. Conversely, addition of weaker nucleophiles, especially neutral N O OucH, 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 kno

20、wn. 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 carb

21、onyl group, which can generally be catalyzed by either base or acid. 1. If NucOH isProduct is H2OAldehyde or ketone hydrate R?OHHemiacetal R?SHHemithioacetal R?NH2or R2?NHHemiaminal The second is really carbocation chemistry. When NucOH is R?OH, or R?SH, the product in the reaction shown above may h

22、ave 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, Grig

23、nards, 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, R?NH2, further reaction of the hemiaminal gives a

24、n imine, containing a carbonnitrogen double bond. Alternatively, when the nucleophile is R?2NH, 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 produ

25、ct 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 orig- inal aldehyde or ketone and the free nucleophile. Acid OH CCCC NR?2 NR?2 H (H or R) Enamine (H or R) ? H2O Acid OH RCC NHR? (H or R)R NR?

26、 Imine (H or R) ? H2O Acid OH RCC (OR? or SR?) ( R?OH or R?SH (H or R)R (OR? or SR?) (OR? or SR?) If R?OH: Acetal If R?SH: Thioacetal (H or R) ? H2O? O Base or acid RC Aldehyde or ketone ? NucH(H or R) OH RC Nuc (H or R) COH ? 306 Chapter 17 ALDEHYDES AND KETONES: THE CARBONYL GROUP 1559T_ch17_304-3

27、22 11/3/05 10:48 Page 306 17-10.Deoxygenation of the Carbonyl Function The reduction of CPO to CH2may 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 way

28、s to make carbonyl compounds, and carbonyl compounds are great places to start for mak- ing new carboncarbon 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 1820 and 23. Deoxygenation will be u

29、seful 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 Nucleophile

30、s 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 aldeh

31、ydes 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.

32、 17-13.Baeyer-Villiger Oxidation of Ketones Baeyer-Villiger oxidation of ketones to carboxylic esters is significant for two reasons. Mechanistically, it in- volves a nucleophilic addition to a carbonyl group, which is no big deal. The nucleophile, however, is a peroxidic species, which can lead to

33、rearrangement, forming a new oxygencarbon 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 cle

34、aves a carboncarbon 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 sym- metrical (see discussion of migratory aptitudes) and i

35、n the subsequent chemistry available from the ester or acid, which will be covered shortly. R BRR R BROR ? HO? H2O ? OOH, Rearrangement: R migrates to O R R ?B ROOH New CO bond OO CRR H2O ? OOCCH3, O Rearrangement: R migrates to O O ? R CROOCCH3 OO RCO New CO bond R ? ?OCCH3 ? ? Exclusive regioisome

36、r (Mixture of E and Z stereoisomers) CO R? R? RCH Typical phosphorus ylide ?P(C6H5)3O? (C6H5)3PRCHCR?R? Keys to the Chapter 307 1559T_ch17_304-322 11/3/05 10:48 Page 307 Solutions to Problems 20. (a)(b)(c) (d)(e)(f) 21. (a) 2,4-Dimethyl-3-pentanone(b) 4-Methyl-3-phenylpentanal (c) 3-Buten-2-one(d) t

37、rans-4-Chloro-3-butenal (e) 4-Bromo-2-cyclopentenone(f) cis-2-Ethanoyl-3-phenylcyclohexanone (cis-2-acetyl-3-phenylcyclohexanone) (g)(h) 22. Degrees of unsaturation for C8H12O, Hsat? 16 ? 2 ? 18; degrees of unsaturation ? (18 ? 2 12) ? 3 ? bonds or rings present. (a) 13C: Molecule contains (? ? 198.

38、6) and (? ? 139.8 and 140.7). O B 1H: Obvious features include ? ? 2.15 (s, 3 H), for CH3CO, and ? ? 6.78 (t, 1 H), for . Note the absence of any other alkene hydrogens. So we can start with these pieces: O B CH3OCO and , adding up to C5H6O Still needed are three more Cs, six more Hs, and another de

39、gree of unsaturation, which will have to be a ring. A simple way to put together a trial structure would be to finish a six-membered ring with three CH2groups, and then attach the acetyl group: This is not the only possible answer, but it is the actual molecule that gives the indicated spectra. O CH

40、3 H CH2 CC H CH2 CC CCCO CH O Cl CH3 H CH3C C CC H O O O NO2 1-(3-Nitrophenyl)ethanone O 1-Phenylethanone O 2,4-Dimethyl-3-pentanone O 3,3-Dimethyl-2-butanone O 5-Methyl-3-hexanone O 2-Butanone 308 Chapter 17 ALDEHYDES AND KETONES: THE CARBONYL GROUP 1559T_ch17_304-322 11/3/05 10:48 Page 308 (b) 13C

41、 NMR: One CPO (? ? 193.2) and two CPC groups (? ? 129.0, 135.2, 146.7, and 152.5) this time. O B 1H NMR: The carbonyl group is an aldehyde? ? 9.56 for OCOH?. At the other end, we have CH3OCH2OCH2O hhh 0.941.482.21 This adds up to C4H8O, leaving C4H4to account for. All four of these Hs are alkene hyd

42、rogens (? ? 5.87.1), so these could most simply be two OCHPCHO groups. The result: O B CH3CH2CH2CHPCHCHPCHCH 23. Each is a conjugated carbonyl compound, giving an intense UV absorption with ?max? 200 nm. The first spectrum matches with ?n?* absorption at 232 nm, and carbonyl nn?* absorption at 308 n

43、m. The second spectrum matches the diene-aldehyde, with the longer wavelength 272 nm band corresponding to the ?n?* absorption of the more extended conjugated system. 24. (a) MS: M?of 128 confirms that C8H16O is the molecular formula as well Hsat? 16 ? 2 ? 18; degrees of unsaturation ? (18 ? 2 16) ?

44、 1 ? bond or ring present IR, UV: A ketone CPO appears to be present NMR: are likely pieces, adding up to C6H12O; only C2H4are left to add in. Is 2-octanone a reasonable answer? MS: Base peak (m/z 43) is ; next largest is m/z 58, consistent with McLafferty rearrangement as follows: This answer seems

45、 quite reasonable. CH3CH2CH2 CH3CH2CH2CHCH2? CH2 m/z 58 CCH3 OH CH2C CH2 2-Octanone CH3 CH O H ? ? CH3C O ? CH3 0.9(t)2.0(s)2.2(t) CH2CH3C O CH2CH2, O CH3 Solutions to Problems 309 1559T_ch17_304-322 11/3/05 10:48 Page 309 25. (a) CrO3, H2SO4, acetone, or MnO2, CH2Cl2(better); (b) PCC, CH2Cl2;(c) 1.

46、 O3, CH2Cl2, 2. Zn, CH3COOH, H2O; (d) HgSO4, H2O, H2SO4;(e) same as (d); (f) 1. 2. H?H2O OO BB 26. (a) CH3CH2CH2CH ? HCH(b) OO BB (c) HCCH2CH2CH2CH2CH(d) 27. (a) Ask “How electrophilic is the carbon in question?”: (CH3)2CPO ?H ? (CH 3)2CPO ? (CH3)2CPNH Order of ketone and imine determined by electro

47、negativity. OOOOOO BBBBBB (b) CH3CCCCH3? CH3CCCH3? CH3CCH3 Adjacent carbonyl groups enhance each others reactivity by reinforcing the ?character of their respective carbons. (c) BrCH2CHO ? CH3CHO ? BrCH2COCH3? CH3COCH3Aldehydes are more reactive than ketones; halogen substituents increase reactivity

48、. 28. (a)(b)(c) 29. (a)(b)(c) 30. (a)(b)(c) 31. (a)The starting material equilibrates with this product. HO OCH3 OO OH OH OO OH OH H OO OH OH H O O 2O Cl, AlCl3,C O 310 Chapter 17 ALDEHYDES AND KETONES: THE CARBONYL GROUP 1559T_ch17_304-322 11/3/05 10:48 Page 310 (b)Only acid catalyzes acetal format

49、ion. (c)(d) (e)(f) 32. (a) In acid: In base: (b) In acid: In base: CH2CH2CH2CH2OH O C ? H O HO H O O? H OH? ? C CH2CH2CH2CH2OHCH2CH2CH2CH2OHH O H C H H ?O HO H O HO H3C O C H CH3OH ? O O? H3CCH H3C CH3O O OH H3CCH H3C H3C OH? C HH3C ?O OH H3CCH H3CH O OH H3CCH H3C CH3OH O H ? C H N(CH2CH3)2 CH3CH2S

50、CH3CH2S CH3 H3C CHCH2CH2CH3 OO CH2 CH3 NNHSO2 CH3 CH3 OCH3CH3O Solutions to Problems 311 1559T_ch17_304-322 11/3/05 10:48 Page 311 33. A 34. (a) Ketone hydrates do not contain the HOCOOH unit that is required for further oxidation to A occur. Oxidation beyond the ketone stage would require cleavage

51、of a carboncarbon bond, a difficult process (compare the Baeyer-Villiger oxidation; Section 17-13). (b) Think about it: If CrO3is added to an alcohol, what will be present in the mixture? There will be some aldehyde formed from oxidation, in the presence of an excess of unreacted alcohol. What react

52、ion occurs between aldehydes and alcohols? OOH BA RCH2OH ? RCH 3 4 RCH2OOCORHemiacetal formation (Section 17-7) A H (c) (1)Proper procedure for oxidation of primary alcohols to aldehydes (2)Hemiacetal forms and is oxidized; actual yield ? 54% 35. (a) H? OH OOH? H product (a bicyclic hemiacetal) OH O

53、? H O CH2CH2COCH2CH2CH2 O CH2CH2CH O SCH3 CH3CH2CH2CH ? HSCH3 CH3CH2CH2CH SCH3 product ? CH3SH ?H? H? ? SCH3 CH3CH2CH2CH OBF3 ? ?HOBF3 ? CH3CH2CH2CH SCH3 ? BF3HO BF3 HSCH3 ? ? CH3CH2CH2CHCH3CH2CH2CH OBF3O ?H? ? CH3CH2CH2CH CH3 ? BF3O SH 312 Chapter 17 ALDEHYDES AND KETONES: THE CARBONYL GROUP 1559T_

54、ch17_304-322 11/3/05 10:48 Page 312 (b) (c) See text sections 17-6 and 17-7 and Study Guide pp. 306307. 36. A double imine formation. Such a process may be carried out without catalysis, but mild acid is usually helpful. The mechanism for the first condensation is shown in detail, the second in abbr

55、eviated form. 37. H? ? ORHN OH RNH2? RH2NOH H2O H? N R ? H N R ? H RHNOH H CH3 ?H2O N N CH3 ?OH2 H CH3 ?H? N N CH3 product ? ? NH2 H C C O CH3 CH3 N C(As above) H C C O ? NH2 CH3 CH3 N C NH2 NH2 N HH OH C C O ? NH2 CH3 CH3 H O? C C O CH3 CH3 H ?OH2 C C O NH2 CH3 CH3 ?H2O N C HO OO ? ? HO O HO OH HOO

56、 H? OH ?O H OH O ?H? OO Solutions to Problems 313 1559T_ch17_304-322 11/3/05 10:48 Page 313 38. (a) (b) (c) (d) 39. Extended conjugation would be expected to shift the absorptions of these hydrazones to longer wavelength, just as it does with the parent ketones. So, 40. (a) H2NNH2, H2O, HO?, ? (Wolf

57、f-Kishner reduction of both carbonyl groups) (b) H2, Pd-C, CH3CH2OH (Selective reduction of alkene) CH3CH2CH2CH O Hydrazone ?max ? 358 nm (yellow) Bottle 2 CH3 C H C H CH O Hydrazone ?max ? 377 nm (orange) Bottle 1 C H C H CH O Hydrazone ?max ? 394 nm (red) Bottle 3 O Br O 1. Mg, THF O 2. CH3CH O OH

58、 O H?, H2O product 1. BH3, THF 2. H2O2, ?OH 3. PBr3H?, HOCH2CH2OH O O H2O H OO H etc. H H OHO HO H2O2PCC, CH2Cl2 1,5-pentanedialproduct, via H?, C6H5NH2 CH3CH2OH CrO3, H2O, H2SO4 3-pentanoneproduct CH3 product CH3 OH 1. H?, H2O 2. LiAlH4 OO CH2CH2 CH3CCH2CH2CH2C 2. Mg, THF 1. PBr3 3. CH3CCH3 O OO CH

59、2CH2 CH3CCH2CH2CH2OH H?, HOCH2CH2OH 314 Chapter 17 ALDEHYDES AND KETONES: THE CARBONYL GROUP 1559T_ch17_304-322 11/3/05 10:48 Page 314 (c) LiAlH4, (CH3CH2)2O (Selective reduction of aldehyde) (d) H?, cycloheptanone (Formation of an unusual acetal, nothing more) 41. In principle the double bond may be constructed in two ways using the Wittig reaction. The solution shown is the more likely. The alternative would require an alkynyl aldehyde, a compound that is difficult to prepare and is not very stable. 42. (a) (b)