北京化工大学：《有机化学》课程教学资源（习题与答案）Chapter 21 Amines and Their Derivatives：Functional Groups Containing Nitrogen.pdf_大学文库

21 Amines and Their Derivatives: Functional Groups Containing Nitrogen Amines represent the last of the simple functional groups that you will encounter in organic chemistry. They are not entirely new to you, of course. They popped up as early as Chapter 6, as the results of nucleophilic substitution reactions between ammonia and haloalkanes. More recently, you have been introduced to amine syntheses starting from carboxamides and nitriles (Sections 20-6 through 20-8). As usual, the chapter begins by presenting the usual body of descriptive information concerning the properties of amines as a class of compounds. It then focuses in more detail on the limitations and variations associated with several amine syntheses, finishing with sections on their reactions. Amines are of substantial importance biologically. But unlike other biologically important compound classes, amines are not involved in a very wide range of distinctly different types of reactions. Thus, you should find this aspect of amine chemistry relatively manageable. Outline of the Chapter 21-1 Nomenclature 21-2, 21-3, 21-4 Physical, Spectroscopic, and Acid-Base Properties of Amines Qualitative and quantitative characteristics of the functional group. 21-5, 21-6, 21-7 Synthesis Guidelines for choosing synthetic strategies. 21-8 through 21-10 Reactions Mostly extensions of earlier material; a couple of special reactions, too. Keys to the Chapter 21-1. Nomenclature To an even greater extent than with most other compounds, common names for amines are still almost universally used. It is therefore necessary to be able to recognize structures from either their alkylamine- or aniline-based name. The systematic alkanamine method looks tricky at first but becomes simple once you recognize that it works in much the same way that the IUPAC alcohol (alkanol) naming system works. 21-2 through 21-4. Properties of Amines Amines are related to alcohols in the same way that ammonia is related to water. This parallel makes the properties of amines easy to predict, because the main qualitative difference is simply that N is less electronega- 373 1559T_ch21_373-388 10/18/05 18:42 Page 373

374 • Chapter 21 AMINES AND THEIR DERIVATIVES: FUNCTIONAL GROUPS CONTAINING NITROGEN tive than O. So, hydrogen bonding in amines is present, but it is weaker than in alcohols; deshielding of nearby 1 H and 13C NMR signals is observed but to a lesser extent than in alcohols; IR spectra are similar; mass spectra are rather predictable. Tertiary amines (R3N) may be viewed as nitrogen analogs of ethers (R2O). By the way, all these nice, tidy analogies do not extend to the smells possessed by most amines. Whereas alcohols tend to have, at worst, somewhat heavy, sweetish odors, amines, at best, smell like ammonia, and, at worst, richly deserve the common names that have been bestowed upon some of their representatives. These include names like cadaverine, putrescine, and skatole. Dead fish would be an improvement. The acid-base properties of amines are an extension of what you know about ammonia: They are weaker acids and stronger bases than are water or alcohols. It will repay you many times over, however, to go over the information involving pKa’s and pKb’s of these molecules. The qualitative ability to handle acid-base concepts is one of the more useful capabilities you can take out of a course in organic chemistry. 21-5, 21-6, and 21-7. Synthesis By the time you finish reading these sections of the text, you will be aware of the fact that the first amine synthesis you learned, alkylation of NH3 via SN2 reaction, is also generally the worst amine synthesis as well. It is much better to use any one of the special N-containing nucleophiles that give clean monoalkylation products, which can then be turned into amines. For simple systems lacking sensitive functional groups, all the methods will work comparably well. The choice becomes more critical if the molecule is more sensitive. For example, 1. N3 , 2. LiAlH4 would be a poor choice for the conversion of Br(CH2)3COCH3 into the corresponding amine, because the ketone will be reduced by the hydride reagent along with the azide group. The ketone could be protected before starting, but a better solution would be the Gabriel sequence, which involves hydrolysis instead of reduction in the second step. An important additional amine synthesis in this section is reductive amination of aldehydes and ketones. In particular, reductive amination of a ketone is a better way to make an amine attached to a 2° alkyl group than is SN2 reaction with a 2° haloalkane. You’ve already seen how to make an amine with one more carbon by using SN2 reaction with CN, followed by reduction. What would you do, however, if you faced the particularly nasty problem of needing to make an amine attached to a 3° alkyl group (R3CNH2)? That’s tricky, because SN2 reactions won’t work. If you could add a carbon somehow to get to R3CCONH2, then you would be all set to use one of the above rearrangements, right? O.K., think about that one for awhile. You will find help in Section 19-6. The solution will be given in the answer to Problem 35(b). 21-8 through 21-10. Reactions Beyond simple displacement reactions in which an amine behaves as a nucleophile, there is a small group of specialized reactions of amines, each of which has a very specific use. The Hofmann elimination has been more important in structure determination than anything else. It is frequently combined with the Mannich reaction, however, to make an important synthetic entry to cyclic carbonyl compounds with methylene groups next to the carbonyl (see Problem 46). Such structures are present in many naturally occurring (plant-derived) antitumor agents. The nitrosation reactions and the chemistry of diazoalkanes are also used in synthesizing just certain specific types of compounds, like cyclopropanes. The mechanisms here are more involved, however, and an understanding of their steps at this point is helpful because similar types of chemistry will be seen again later, in Chapter 22. As you plow through this, try to focus on the relationship of each mechanistic step to processes you’ve seen before. Almost all of this chemistry is based on relatively fundamental sorts of events, like protonation and deprotonation, combined with elimination or addition. Solutions to Problems 24. (a) 3-Hexanamine, 3-aminohexane; (b) N-methyl-2-propanamine, 2-(methylamino)propane, isopropylmethylamine; (c) 2-chlorobenzenamine, o-chloroaniline; 1559T_ch21_373-388 10/18/05 18:42 Page 374

Solutions to Problems • 375 (d) N-methyl-N-propylbenzenamine; N-methyl-N-propylaniline; (e) N,N-dimethylmethanamine (common: trimethylamine); N,N-dimethylaminomethane; (f) 4-(N,N-dimethylamino)-2-butanone (only satisfactory name); (g) 6-chloro-N-cyclopentyl-N,5-dimethyl-1-hexanamine (numbers refer to substituents on parent hexane chain); 1-chloro-6-(N-cyclopentyl-N-methylamino)-2-methylhexane; (h) N,N-diethyl-2-propen-1-amine, 3-(N,N-diethylamino)-1-propene 25. (a) (b) (c) HOCH2CH2NH2 (d) 26. (a) 5–7 kcal mol1 , approximately equal to Ea for inversion. (b) Methyl anion is isoelectronic with ammonia and, likewise, is tetrahedral (sp3 hybridized). Methyl radical and cation, with one and two fewer electrons, respectively, are more stable when trigonal planar. They gain bond strength by rehybridizing to use sp2 orbitals in the bonds, with either a singly occupied or vacant p orbital “left over.’’ The sp2 scheme is not as good for the anion or for the ammonia because two electrons in an unhybridized p orbital is quite unfavorable in the absence of other stabilizing influences: Such electrons are far from and attracted only poorly by the atom’s nucleus. 27. The odd atomic weights suggest that each contains a single nitrogen. The total number of hydrogens is available from the NMR, so the number of carbons can be determined by difference: m/z 129 14 (one N) 19 (19 H’s) weight of carbons. Weight of carbons 96 n 8 carbons; C8H19N is the formula for each of these unknowns. Degrees of unsaturation (see Section 11-8): Hsat 16 2 1 (for the N) 19; compounds are saturated. Notice that the signal at 2.7 is not split by the ONH2 hydrogens (as is the case for alcohols as well). The splittings nicely reveal the number of neighboring H’s. MS: m/z 30 for [CGH2ON .. H2 mn CH2PN G H2] fragment. All that remains is to insert C4H8, and the simplest way to do that is as CH3(CH2)7NH2 (1-octanamine). Other isomers would show additional methyl signals in the NMR near 0.9–1.0. Perhaps a CH2 and an NH2? (Signals at 1.3 and 1.4). MS: m/z 114 is [M CH3] , 72 is [M (CH3)3C], and 58 is most likely an iminium ion. Before guessing, notice that there are no NMR B NMR: (CH3)3C 1.0(s) Likely, 1.2 Also two equivalent methyl groups 2 CH3 , CH3 A NMR: 0.9(t) 2.7(t) 2.3 CH2 and CH2 CH2 NH2 NH2 Cl CH2CH2NHCH2CH3 N(CH3)2 1559T_ch21_373-388 10/18/05 21:02 Page 375

Resonance stabilization of conjugate acids enhances base strengths. 34. (a) Not at all. This process adds a carbon (the CN group), making 1-pentanamine. (b) Not at all. SN2 reactions with tertiary haloalkanes are not possible. (c) Well. (d) Poorly. Further alkylation can occur, making (e) Poorly. The haloalkane, although primary, is highly branched and will not react well in SN2 reactions. (f), (g) Well. (h) Poorly. Four-membered rings are strained and difficult to form. The method would work well for a five- or six-membered ring. (i) Not at all. Reaction shown is for a benzene, not a cyclohexane compound. (j) Well. 35. (CH3CH2)2O solvent and H, H2O work-up are understood for Grignard and LiAlH4 reactions. (a) 1. NaN3, DMSO, 2. LiAlH4. (b) You need to be devious. Add a carbon and then take it out again! (d) 1. NaN3, 2. LiAlH4 (makes primary amine), 3. H2CPO [makes imine; use one equivalent only, to avoid dimethylation (Problem 50)], 4. NaBH3CN, CH3CH2OH (completes reductive amination). Note how CH3 group is introduced as formaldehyde, with a subsequent reduction step. (e) Same as (b). (h) No simple way to improve the situation. (i) Start with and do reactions shown, making The H2, Pt (Section 15-2) will slowly hydrogenate the ring. 36. CH3CH2NH2, (CH3CH2)2NH, (CH3CH2)3N, and (CH3CH2)4N. 37. Make pseudoephedrine from phenylpropanolamine using reductive amination. As suggested in Problem 35(d), use one equivalent of H2CPO to avoid dimethylation. 38. Secondary (general structure RRNH). (a) 1. CH3CH2NH2, H, 2. NaBH3CN, CH3CH2OH; (b) 1. NaN3, DMF, 2. LiAlH4, THF, 3. CH3CHO, H, 4. NaBH3CN, CH3CH2OH; (c) 1. SOCl2, 2. NH3, 3. Br2, NaOH, H2O, 4. CH3CHO, H, 5. NaBH3CN, CH3CH2OH 39. (a) Lots of ways! Bromobutane azide, then LiAlH4 reduction, or bromopropane cyanide, then LiAlH4, or bromobutane phthalimide salt, then hydrolysis. H2C O, NaBH3CN RNH2 RNHCH3 Br NH2. Br 1. Mg 2. CO2 1. SOCl2 2. NH3 (CH3)3CCl (CH3)3CCOH O Br2, NaOH, H2O (Hofmann rearrangement) (CH3)3CCNH2 (CH3)3CNH2 O ( ( NCH3. 2 NH2 C NH2 NH2 NH2 C NH2 NH2 NH2 C NH2 NH2 NH2 C NH2 NH2 Guanidine 378 • Chapter 21 AMINES AND THEIR DERIVATIVES: FUNCTIONAL GROUPS CONTAINING NITROGEN 1559T_ch21_373-388 10/18/05 18:42 Page 378