Chapter 18 519 Solutions to Problems 1, If the ketone functional group were anywhere else in these compounds, they would not be ketones and, therefore, would not have the "one" suffix. a, 3-methylpentanal, f-methylvaleraldehyde b. 4-heptanone, dipropyl ketone ¢. 2-methyl-4-heptanone, isobutyl propyl ketone 4d. 4-phenylbutanal, y-phenylbutyraldehyde e. 4-ethylhexanal, -ethylcaproaldehyde f. I-hepten-3-one, butyl vinyl ketone 3. a, G-hydroxy-3-heptanone —_b. 2-oxocyclohexylmethanenitrile _¢. 3-formylpentanamide 4. a, 2-Heptanone is more reactive because it has less steric hindrance. ‘There is little difference in the amount of steric hindrance provided at the carbonyl carbon (the site of nucleophilic attack) by a pentyl and a propyl group because they differ at a point somewhat removed from the site of nucleophilic attack. The difference in size between a methyl group and a propyl group is significant at the site of nucleophilic attack. 1 1 CH,CCH,CHCH,CH,CH, CH;CH,CH,CCH,CH,CH, 2-heptanone 4-heptanone b. para-Nitroacetophenone is more reactive because the electron-withdrawing nitro group makes the carbonyl carbon more susceptible to nucleophilic attack compared with an electron-donating methoxy group. 9° YQ g S4{p—los CHC -o* 5. a. Two isomers are obtained because the reaction creates an asymmetric carbon in the product. CH,CH,CH; — CH,CH,CHy 1. CH,CH,Mgbr SoC Meer 2. H30" cH CH tl r CH;CCH,CH,CH; 7H; BC" cHCH, OH HO (S)-3-methyl-3-hexanol _()-3-methyl-3-hexanol . Only one compound is obtained because the product does not have an asymmetric carbon, OH i 1. CHjMgBr I CH;CCH,CH,CH, oa CH,CCH,CHCH, . Hy CH,520 10. Chapter 18 i CH,CCH,CH, + CH,CH,CH;MgBr tl CHCH,CCH,CH,CH, + CH3MgBr ‘The Grignard reagent will react with the proton from the carboxylic acid, forming an alkane and a carboxylate ion. 9 ° it te 2+ mi RCOH + RMgBr ——™ RCO + RH + Mg” + Br a. Solved in the text. b. 9 7 1. CH;COR + 2CH,MgBr 4. CH,COR + 2CH,CH;MgBr ° i 2. — Solved in the text. 6 CH;COR + 2 gs If a secondary alcohol is formed from the reaction of a formate ester with excess Grignard reagent, the two alkyl substituents of the alcohol will be identical because they both come from the Grignard reagent. Therefore, only the following two alcohols can be prepared that way. CHsGHCHs CH,CH,CHCH,CH, OH on If the compound is alkylated after nucleophilic attack, the alkylation on oxygen will compete with alkylation on carbon, 1 o* OH - CH,CH,CH i Ht i SS HC=CCHCH,CH, +> HC=CCHCH,CH;oh 12, 13. 14. Chapter 18 521 SBS cecc, NE C=CCH, = “NH. - SRCES yceccr,cH, NE ‘C=CCH,CH, i CH,CCH; gs alt CH,CC=CCH,CH, (on + R,NH Ss ean b. The only difference is in the first step of the mechanism: in imine hydrolysis the acid protonates the nitrogen; in enamine hydrolysis, the acid protonates the #-carbon. 20. catalytic a a. Oro + CH,CH,NH, == C=ncn.ct, + 10 bee CECH b. Oe + CHCHNH = Oe + 1,0 CH,CH, Nen,ci, catalytic — © ¢S-<=0 + CH,(CH,),NH, == O¥—camccry.c15 +H,0 cH, CH; onal a. Ore: Ow E OO +0 Cc CH; HsChapter 18 525 a b. c. NO, 2 mom c=N 9 cay’ it0, 21. nO \wnwn, cH,cr/ : aoe Because the ketone is symmetrical, Eaand Z isomers are not possible for this compound. 22, The lone pair on the nitrogen that is attached to the carbonyl carbon is in resonance with the carbonyl group. This nitrogen, therefore, cannot act as a nucleophile since its lone pair is not available for nucleophilic attack. not nucleophil mle? o f as. 1s nucleophilic HNNH-C-NH, —<—= H,NNH-C=NH, R-C-H + 24, Electron-withdrawing groups decrease the stability of the aldehyde and increase the stability of the hydrate. Therefore, the three electron-withdrawing chlorines cause trichloroacetaldehyde to have a large equilibrium constant for hydrate formation. [hydrate] = [aldehyde] [0]526 Chapter 18 25. Because an electron-withdrawing substituent decreases the stability of a ketone and increases the stability of a hydrate, the compound with the electron-withdrawing para-nitro substituents has the largest equilibrium constant for addition of water. 26. 27. When a tetrahedral intermediate collapses, the intermediate that is formed is very unstable because of the positive charge on the sp” oxygen atom. In the case of an acetal or ketal, the only way to form a neutral species is to reform the acetal or ketal. In the case of a hydrate, a neutral species can be formed by loss of a proton.Chapter 18 527 28. a, Hemiacetals are unstable in basic solution because the base can remove a proton from an OH group, thereby providing an oxyanion that has sufficient driving force to expel the basic “OR group. O-H > R-C-H c OR [or b. In order for an acetal to form, the CH3O group in the hemiacetal must eliminate an “OH group. Hydroxide ion is too basic to be eliminated by a CH3O group, but water can be eliminated by a CH3O group. Since the OH group must be protonated before it can be eliminated, acetal formation must be carried out in an acidic solution. ~GcH, R-C-H + H,0 | ¢. Hydrate formation can be catalyzed by hydroxide ion because a group does not have to be eliminated after hydroxide ion attacks the aldehyde or ketone 29, OH a CH,OH b. NaBHy 30. An acetal has a very poor leaving group (CH;0°). 9cHy CHy—C—H OcH,528 Chapter 18 31. Nitric acid is an oxidizing agent and primary amines are easily oxidized. So one product would be nitrobenzene. If excess nitric acid is present, nitrobenzene can be converted to meta-dinitrobenzene. NH, NO, NO, HN 05 HNOS H)SO, H,S0, 00. 2 32, a A B= C —™ pp — FE — F = 80% 0,800.80 0.80x0.64 0.80x0.51 080x041 0.80 x 0.33 64% 51% 41% 33% 26% b. G —~ H — 1 26% 0.80x0.26 0.80 x 0.21 21% 17% 33, a. HOCH,CH,CH,Br + (CH3)3SiCI LCHCHL)SN, (CH,),Si0CH,CH,CHBr ve| m0 (CH),SiOCH,CH,CHCHCHs ACHEO O7 Mg*Br fo" HOCH,CH,CH,CHCH ou (CH),Si0CH,CH,CH,MgBrChapter 18 529 33. oO { \ tl OL 0 e HH HCl + HOCH,CH,OH <== Mey 30° Br Br MgBr ° i CA HCl 10) COOH coo” 34, a 1. Solved in the text. 3. (CoHs),C=O + CH;CH=P(CgHs)3 or (CoHs),C=P(CoHs)3 + CHyCH=O Oo (re + CHCHCH=PC dH), 4g (\-k + CH=PCdi) L=P(C Hs “ ( )=rcate. + CHsCH,CH=0 oe or (Sk + CH,;=0 b. 1. Solved in the text, 2 CH;CH,CH,Br 3, CH,Br 4. CH;CH,Br or (C6Hs),CHBr © C) or ©\—cunse eae 2.530 Chapter 18 35. To review how to determine whether an asymmetric carbon has the R or S configuration, see Section 5.6. b. a Cc. CH,MgBr c: ZN ae My cH, ScH,CH,CH, ht, CHAO CHs 3 No enantiomers are possible because the ‘compound does not have an asymmetric carbon. 4. i CH,MgBi a " ZN ae a cH,CH, ‘CH,CH,CH; CH,Chh, W'CHACHLCHS CH, s 36. a oOo “407, oO . O ‘The above synthesis will also form an elimination product (cyclohexene). The following procedure will give a greater yield of the target molecule because the substitution product is favored by a weak base (see page 423 of the text), and the substitution product can be hydrolyzed to the target compound. 6 O° i) ir Ul OCCH; OH oO CH,CO™ il Ce OO oon excessChapter 18 531 Br Hi e Cr P(CoHs)3 or (CaHS)s CH (CH) Li Oo" 33 PCH) CHACH Li c. CH (CoHs);P=O + Br MgBr 2 CH,CH,0H f Mg, LZA = E,0 eae 2. HzO H,SO, |A ,CHCH CHCH, CH=CH, . = oH + HO fc Gi Chones532 Chapter 18 31. OH 1 © CH,C=CHCCH; CH, CH; oH 4. CH3¢—CH3CCHs CH, 38. If the initial reaction of the cf,-unsaturated ketone with sodium borohydrate is conjugate addition, a ketone will be formed, which is then reduced to a saturated alcohol. ° 0 OH L.NaBHy LNaBHy 2EOR 2. OH a saturated alcohol If the initial reaction of the @,B-unsaturated ketone with sodium borohydrate is direct addition, the final product will be an ,B-unsaturated alcohol, which won't be further reduced. 9 OH 1.NaBH, 2. EtOH unsaturated alcohol A sterically hindered ketone will be less likely to undergo direct addition and, therefore, more likely to undergo conjugate addition, the pathway that does not form an unsaturated alcohol. ‘Thus, the nonsterically hindered ketone will give a higher yield of unsaturated alcohol. 39. 9 9 i j ZN Ay a. cHycH=ch ‘ocr, BBE crycucHy’ “ocHy 9 Br fo) il iL c. ¢ Ss cH,OH eS b. cH,cH=cH ‘cl = ciycu=cht “oc,4a. Chapter 18 533 ° a 1 oN NH CH,CHCHY ou. c CH;CH=CH ‘OCH; 7 4 NH, ° c, ¢ C. 4 NH; NH, \ \. 7 4. CH,CH=CH ‘cl = cH,CH=cH” Sy, = cH,cuciy ‘NH, 1 a. CHsCHCH CH, oO I b. CHjCH=CHCH,CH,CH I © CHsSHCH;CH,CCH,CH,CHCH, CH, CH . tl CHCCH,CCH, i ©. CH\CH,CCHCH,CH,CHs Br QCH,CH, a. CH;CH;CH OCH,CH, NNH, ‘CCH,CH, © €¥-crrcrien, ou 4. CH;CH,CHCH, NH, ‘CH; il CHyCH,CHCH,CH,CH ° Br i CH CH)CH; t t CHjCCHCH,CH,CH CH, ou © CHyCH,CCH,CH, CaN f. CHjCH,CH,CH,OH + CH;CH,OH tT] Qe & CH CH,CH,CCH, ° bh CH; ‘C=N534 Chapter 18 2. 1 q CHjCH,CH > CH,CH,CCH,CH; > CH,CHCH,CCH,CH, > CH; i ? aoe CHyCHACHCCH,CH, > CHsCHCHCCHCH,CH, > | CH,CH,SHC—CCHsCH, CH; CH CHs CH; CH, Ba, i R-C-H R'CH=CH, 1.NaBH, rs 1. BH,/THF 2. q #30" /2 HO" H,02 R-C-OH LLiAIHy RCH,Br 2,30" {. CH;COO™ ° ' 2.H,0" 1, LiAlHy R-C-OR —=——+—» RCH,OH HI 2 HAO is <—\— cH,0cH, 1. LiAlH, R'MgBr g Aly LLiAIH iain 2.H,0° R—-C—cl ~2H,0° | 2.H,0' igBr~ 0 ° ° 2Ho’ /\ i R-C-O-C-R —H,C=O b. The reaction of a Grignard reagent with an epoxide. ¢. The reaction of a Grignard reagent with an epoxide and the reaction of a Grignard reagent with formaldehyde. In each of these reactions, a new carbon-carbon bond is formed.Chapter 18 535 9 on a 1 NaBH, 2.130 ° OH b. L.NaBH SO. 2.H,0 a 9 OH Br © 1, NaBH, PBry 2.H,0° ° NH, a, + NH; red Br CEN CH;NH e 7 product of ¢ o CH. CH CHsy,-CHs f H; + CHNH ——> a CH, i Br CH=CH, & + (CH)=CH),CuLi —She O product of ¢ Br product of ¢536 Chapter 18 9 h, NHNH, HOF A —_o Zn(Hg), HCI, A “9 OH 1. NaBH, H,SO, i 2.H30 a Ba i HO. CH,CH; CH,CH; CH,CH, 1. CH,CH,MgBr SO, so 2 2H CHCHs CH)CH, ° aad + CHj;CH=P(CH3);. —= 45, 46. The greater the electron-withdrawing ability of the para substituent, the greater the Keq for hydrate formation. ‘O oO i i ° é u i i ‘Ons a CHO’Chapter 18 537 47. 1. H,C=O a. cHOH PBS cHp, re CHsMgBr —7——=CH,CH,OH 2 Bry M 1. ethylene oxide be cH, a CisBr = CH,MgBr tio CH;CH,CH,OH 48. a ¥-¢-0 + crncHty C tiny _-CH,CH; CH,CH, on b. CH3CH,CCH, ‘OHS CH,CH; CH; O CHCH. I « 3 i. CHYGCH,CCH, Br OH NCH,CH, 1 4. CHsCHCCH,CH, & ‘ CH,CH, j. CH;NHCH,CH,COCH, a *8—CH,CH. I cucu, be Si _ H.N-C-NH, —2° HN=C-NH, H.N—C—NHp + CH;CH,SH ——— H.N—C-NH, + CH;CH,S” 0 +QH b. CH CH,CH,CH,CH,SH538 Chapter 18 50. The offset shows there is a signal at ~11.8 ppm, indicating an aldehyde. The HNMR spectrum is that of benzaldehyde. Phenylmagnesium bromide, therefore, must react with a compound with ‘one carbon atom to form an alcohol that can be oxidized by the mild oxidizing agent (MnO3) to benzaldehyde. Therefore, Compound Z must be formaldehyde, Oo 1. phenylmagnesium bromide c= ore €S-cr0n ee C\-tn formaldehyde 2+ 430 Compound Z 51. CH,CH,CH;NH LF => oOChapter 18 539 Cy /ess® OL. 9 ‘0 OCH:CH, 1 U8 Ou ‘07 SocH, cH, 52. a, three signals in the !H NMR spectrum b. three signals in the I3C NMR spectrum il 1 CH Mgp: gh oH CH,CCH,CH,CocH, 1:®*2es CHsMsBr CH;CCH,CH,CCH, 2.1, H,0 I i CH; CH; 53, © HC Oo H.C eG oe Ky a. CH,CH,CECH, CH,CH,CH,CH, Cha c. oq 7 OH H,C\—CH, CH,CHy a ae Scu,cx, 34, 9 i & —CH,CH,CCH,CH,CH,CH; + CS: ° tl CCH;CH; + CH,CH,CH,CH,MgBr oO (\ CCH,CH,CH,CH; + CHjCH)MgBr540 55. 56. 87. Chapter 18 I b. CH\CH;CCH,CH;,CH; + CH;CH)MgBr i CH;CH,CCH,CH, + CH,CH,CH,MgBr i CHjCH,CH,COCH;CH, + 2CH;CH)MgBr HO. (C=N OH HO. (CH, 9 © Che cn ‘CaN CaN ‘CH, 9° Because there is excess cyanide ion. 9 . OL ° ‘CH, 9 a. e f CH CH CH, ‘Br ‘CH,CH; 'SCH,CH; Enovid would have its carbonyl stretch at a higher frequency. The carbonyl group in Norlutin hhas some single-bond character because of the conjugated double bonds. This causes the carbon- oxygen bond to be easier to stretch than the carbon-oxygen bond in Enovid that is not involved. in Tesonance. ‘07 SC : R | Norlutin ‘The absorption bands at 1600 cm, 1500 cml, and > 3000 cm in the IR spectrum indicate the compound has a benzene ring. The absorption band 1720 cm’! suggests it is a ketone with the carbonyl group not conjugated with the benzene ring. ‘The broad signal at 1.8 ppm in the !H NMR spectrum indicates an OH group. We also see there are three different kinds of hydrogens (other than the OH group and the benzene ring hydrogens). ‘The doublet at 1.2 ppm indicates a methyl group adjacent to a carbon bonded to one hydrogen, and the doublet at 3.6 ppm are due to protons on a carbon that has the carbon bonded to one hydrogen on one side of it and the electron-withdrawing OH group on the other side. ‘The IR spectrum is the spectrum of 2-phenylpropanal and the 'H NMR spectrum is the spectrum of 2-phenyl-I-propanol.Chapter 18 S41 1 1NaBH, Oat — C-prcn.0n I 2. H,0 I CH, CH, 58. The difference in the two reactions is a result of the difference in the leaving ability of a sulfonium group and a phosphonium group. Because the sulfonium group is a weaker bas, itis a better leaving group. Therefore, itis eliminated by the oxyanion. RH Secatt, 9—PCoH)s CHCH,CH xen, — > CH, CH,CH-CH), CHSCHLCH cH, —— > _CH;CH,CH—CH, + (CH;))S 59, ° a I 1. excess CH;MgBr cocH, SS CMe fo 2. H30) cH, 9 9 is a= Locus, 1 l(CHs:CHCHs}oAlll -78 °C i 2.H,0 « Mg. CH;CH,CH,CH,Br sc CH,CH,CH;,CH,MgBr mon CH,CH,CH,CH,COH or H30 cHcH,CH,0H,Br SS% cH,CH,CH,CH.C=N ae CH,CH,CH,CH,COH d. 1 LiAIBy HC yo =H” OH Br +NH,CH; NHCH; e PBr, CH3NH3 ad HO,542 Chapter 18 60. oO I I 1 oN 8. CH,CCH,CH,COCH,CH, + CHs7MgBr. ——e CH,CCH;CHsGOCH;CHs cH, o> ‘ CH3, 0. CH. 0. HO) - 0 3 CH,CH,OH —@— CH,CH,0 + cur J =< oa Tora, ° rm * *OH ‘o 4° Hb ca; ‘60 Bt CHO CH,Chapter 18 543 61. a. The OH group on C-5 of glucose reacts with the aldehyde group in an intramolecular reaction, forming a cyclic hemiacetal. Because the reaction creates a new asymmetric carbon, two cyclic hemiacetals can form, one with the R configuration at the new asymmetric carbon and one with the $ configuration hemiacetal hemiacetal H—}—0H HO—}—-H H—}—OH H—-—OH > HO H ° - HO——H ° H——0OH H——OH HS Hy CH,OH CH,OH b. The two products can be drawn in their chair conformations by putting the largest group (CH,OH) in the equatorial position and then putting the other groups in axial or equatorial positions depending on whether they are cis or trans to one another. The hemiacetal on the left has all but one of its OH groups in the more stable equatorial position, while the hemiacetal on the right has all its OH groups in the equatorial position. Therefore, the hemiacetal on the right is more stable. less stable bemaezal 62. H CH,OH 208 HO quer H HH Ht HH H OHN—-H H om oss aS more stable P(CéHs)3 + CH,CH,Br — S$! CH,CHP (Cells) cHycay a € D-cutnbcaio, hemiacetal __ fi ~{\ ‘CH Orson CH,544 Chapter 18 63. * oY CH; H. tL Hl 6) CH,CH == CH,CH ——= CH;CH HCCH; ——> : 4 TAS A bo Q Q H,C~ ~O~ ~CH, i oA CH,CH HC“ + { CH; oko 64. Converting the Fischer projection of (R)-mandelonitrile into a weds You to see that attack of cyanide ion occurred on the Si face (decreasing priorities on the face Closest to the observer are in a counterclockwise direction). 1 OH OH & (+s = Or = CH3 oH H 7 2k (R)-mandelonitrile ° 1 a Os: + (CgHs);P=CHCH,CH,CH, or HtCoHs)s, (-a1 + O=CHCH,CH;CH, 9 P(CeHs)3 b. S + (CeHs)s3P=CHCH;CH; or GS + O=CHCH,CH;Chapter 18 545 9 tl i © (Shs + catoye=en—(_Y) oO P(C6Hs)3, 4. + (CsHs);P=CH, or + O=CH, 66. ° CH, O I 1, (CH)=CH),CuLi rit CHsG=CHCH SOF CH= CHECHCH 5B , CHy p CH 1. CHSLi 2.H,0* CH; OH I CHy=CHECH,CHCH, 61.546 Chapter 18 NH + HCH on ——S> 68. The compound that gives the 'H NMR spectrum is 2-phenyl-2-butanol. ou €S—poncr, CH ‘Therefore, the compound that reacts with methylmagnesium bromide is 1-phenyl-I-propanone. t a Xe CcH,cH, -CHMagr €\—Fexscn, 2. H,0) CH, 69. il (CH,)sSiC] 1. CE Men oe a. CHsGHCH,COCH, (CBS CH,CHCH,COCH; — Sm cHcHCH,tcH, H. OH (CHICH)N OsiccHy, 83° OH CH, b. Cl MgCl Z CL (CH);SiCL Cr Mee Cx Eyc7 ‘OH (CCH ‘OSi(CH3); ‘OSi(CH3)3 foo COOH . coo" On" 8 ox — ‘OH ‘OSi(CH);Chapter 18 547 ° t\ [\ a do © & CAs HOCH,CH,OH CHs _Mg Hy =i na EL,0 Br Br MgBr Q LZ\ 2. HCl, HO ° 11 Cy CH; CH,CH,OH 70. S CHy‘NEN o . + CH)-N=N ——» OO —> O + Ny 71. a. The COOH group that is closest to the electron-withdrawing keto group is the more acidic COOH group. iol tt HOC-CCH,COH 22 pKa =3.98 PKa= b. The data show that the amount of hydrate decreases with increasing pH until about pH = 6 and that increasing the pH beyond 6 has no effect on the amount of hydrate. oii é tint Hoc—ccH,con + HO —Hy yot—dcx,Con oxaloacetic acid On hydrate A hydrate is stabilized by electron-withdrawing groups. A COOH group is electron withdrawing, but a COO- group is much less so. In acidic solutions, where both carboxylic acid groups are in their acidic (COOH) forms and, therefore, stabilize the hydrate, the compound exists as essentially all hydrate. As the pH of the solution increases and the COOH groups become COO- groups, the amount of hydrate decreases. Above pH = 6, where both carboxyl groups are in their basic (COO-) forms, there is only a small amount of hydrate,548 Chapter 18 2 CH, OBt LALA, 8 (BOF + CHYCHCH, —> cH,CH-P0L¢uHACH, Br OE OEt 7 b. —OEt Mi a ¢—CHs — CH; R. CH, Ncac’ + (E10),PO) <—— 7 R ‘CH; ° i it 1. (HOyP + BrCH,CCH; ——» (E(O)P—CH,CCH, + CH,CH;Br pr 1 (E10);P—CHCCH, 9 1 i) CH;CH,CH CH,CH,CH=CHCCH, <=Chapter 18 549 q q Tee 1 2. (HOP! + CH,CHCOCH, ——~ GO,P—CH—CocH, + CH,CH,Br Br ° Br oO O CH,O NYT “och 1 oot <——M—€ o,P—c—Ccocr, 2. XF cas — ‘C—CH,CH, Cj HnCHs © -oH or ie x HO: a x x 8 The negative p value obtained when hydrolysis is carried out in a basic solution indicates that electron-donating substituents increase the rate of the reaction. ‘This means thatthe rate- determining step must be protonation of the carbon the first step), because the more electron- donating the substituent, the greater the negative charge on the carbon and the easier it will be to protonate. b. The positive p value obtained when hydrolysis is carried out in an acidic solution indicates that clectron-withdrawing substituents increase the rate of the reaction. This means that the rate-determining step must be attack of water on the imine carbon to form the tetrahedral intermediate, because electron withdrawal increases the electrophilicity of the imine carbon, making it more susceptible to nucleophilic attack580 Chapter 18 14. OH fy fo ¢ OCHS CH ~ 4 HB old B DH ‘C-CH,; +> (pte > Cries + CH,OH CHChapter 18 551 a Poona, cH, OH i I 92 CHCH=CCH: c™ I 3 a + CH\CH=CH—CCH, §=——= enol ) oO © cH, 9 imine cH, 9 ducuecr, + hydrolysis CHCH,CCH, — oO ketone 7