COOH HO CH 3. (g) o-orsellinic acid

Transcription

1 Problems Chapter Important Concepts 1. Carboxylic acids are named as alkanoic acids. The carbonyl carbon is numbered 1 in the longest chain incorporating the carboxy group. icarboxylic acids are called alkanedioic acids. Cyclic and aromatic systems are called cycloalkanecarboxylic and benzoic acids, respectively. In these systems the ring carbon bearing the carboxy group is assigned the number The carboxy group is approximately trigonal planar. Except in very dilute solution, carboxylic acids form dimers by hydrogen bonding. 3. The carboxylic acid proton chemical shift is variable but relatively high (d ), because of hydrogen bonding. The carbonyl carbon is also relatively deshielded but not as much as in aldehydes and ketones, because of the resonance contribution of the hydroxy group. The carboxy function shows two important infrared bands, one at about 171 cm 21 for the C P bond and a very broad band between 25 and 33 cm 21 for the H group. The mass spectrum of carboxylic acids shows facile fragmentation in three ways. 4. The carbonyl group in carboxylic acids undergoes nucleophilic displacement via the addition elimination pathway. ddition of a nucleophile gives an unstable tetrahedral intermediate that decomposes by elimination of the hydroxy group to give a carboxylic acid derivative. 5. Lithium aluminum hydride is a strong enough nucleophile to add to the carbonyl group of carboxylate ions. This process allows the reduction of carboxylic acids to primary alcohols. Problems 27. Name (IUPC or Chemical bstracts system) or draw the structure of each of the following compounds. (a) Cl H 3 C r G H (b) H (c) CPC G ( ) 2CH C 2 H (d) CH (e) $ H C 2 H (f) Cl CPC H 2 C G H C 2 H (g) H H o-rsellinic acid (i) 4-minobutanoic acid (also known as G, a critical participant in brain biochemistry); (j) meso-2,3-dimethylbutanedioic acid; (k) 2-oxopropanoic acid (pyruvic acid); (l) trans-2-formylcyclohexanecarboxylic acid; (m) (Z)-3-phenyl-2-butenoic acid; (n) 1,8-naphthalenedicarboxylic acid. 28. Name each of the following compounds according to IUPC or Chemical bstracts. Pay attention to the order of precedence of the functional groups. (a) H Cl (b) H CH (c) H CH 29. Rank the group of molecules shown here in decreasing order of boiling point and solubility in water. Explain your answers. (d) (h) CH 2 C 2 H CH CH Phthalic acid CH N 2 CH CH CH 2 H 3. Rank each of the following groups of organic compounds in order of decreasing acidity. (a) CH 2 C 2 H, CCH 2 H, CH 2 CH 2 H (b) rch 2 C 2 H, ClCH 2 C 2 H, FCH 2 C 2 H

2 G 914 Chapter 19 Carboxylic cids Cl Cl (c) CHCH 2 C 2 H, ClCH 2 CH 2 CH 2 C 2 H, CH 2 CHC 2 H (d) CF 3 C 2 H, Cr 3 C 2 H, ( ) 3 CC 2 H N 2 (e) CH, 2 N CH, 2 N CH, CH 31. Propose a structure for a compound that displays the spectroscopic data that follow. The molecular ion in the mass spectrum appears at m/z IR ñ (s) and 3 (s, broad) cm H NMR: d 5.94 (t, J 5 7. Hz, 6 H), 1.59 (m, 4 H), 2.36 (quin, J 5 7. Hz, 1 H), and 12.4 (broad s, 1 H) ppm; 13 C NMR: 11.7, 24.7, 48.7, and 183. ppm. Preparation of Carboxylic cids section number RCR H or H, H 2 RCH 2 H K 2 Cr 2 7, H, H 2 RCH xidant (i.e., Cr 3, KMn 4, g, Cu 2, H 2 2, HN 3, 2 Rh 3, r 2 ) RMgr C 2 RCq N H or H, H 2 ther product: RH 8-5, 19-9, 2-1, , , 19-5, 19-6, 24-4, , 2-8, 26-2 ECH R H 2-1, , , 2-6, Product: CH Products: ther product: HCH RCH H or H, H 2 H or H, H 2 H or H, H 2, KMn 4, H, HI 4, H 2 H 2, Pd C RCCl RCCR RCN R R R H HCCR H RCCH 2

3 G G G RCR 9-4, 19-9 RH, H RC 19-4 H R H C 19-4 H H RCX (X P Cl, r) 19-8 SCl2 or Pr3 Reactions of Carboxylic cids section number RCCR RCN R R RCH2H , 26-4, 26-6, RCCl R HN R, or CC LilH4 E C H R H RCHCH r Substrate: RCH2CH r2, P RCCH2R 23-2 Substrate: RCCHCH R RCH2CH RCH Substrate: HCCHCH R Substrate: RCHCH H Fe 3, H22 915

4 916 Chapter 19 Carboxylic cids 32. (a) n unknown compound has the formula C 7 H 12 2 and infrared spectrum (p. 917). To which class does this compound belong? (b) Use the other spectra (NMR-, p. 917, and F, p. 919; IR-, E, and F, pp ) and spectroscopic and chemical information in the reaction sequence to determine the structures of compound and the other unknown substances through F. References are made to relevant sections of earlier chapters, but do not look them up before you have tried to solve the problem without the extra help. (c) nother unknown compound, G, has the formula C 8 H 14 4 and the NMR and IR spectra labeled G (p. 92). Propose a structure for this molecule. (d) Compound G may be readily synthesized from. Propose a sequence that accomplishes this efficiently. (e) Propose a completely different sequence from that shown in (b) for the conversion of C into. (f) Finally, construct a synthetic scheme that is the reverse of that shown in (b); namely, the conversion of into. C 6 H 1 13 C NMR: ppm 1 H NMR- 1. Hg(C ) 2, H 2 2. NaH 4 Section 12-7 C 6 H 12 C 13 C NMR: ppm Cr 3, H 2 S 4, acetone, C Section 8-6 C 6 H 1 13 C NMR: ppm IR- CH 2 PP(C 6 H 5 ) 3 Section C 7 H 12 E IR-E 1. H 3, THF 2. H, H 2 2 Section 12-8 C 7 H 14 F IR-F 1 H NMR-F Na 2 Cr 2 7, H 2, H 2 S 4 Section Give the products of each of the following reactions. (a) ( ) 2 CHCH 2 C 2 H 1 SCl 2 uy (b) ( ) 2 CHCH 2 C 2 H 1 Cr uy (c) CH H CH 2 H (d) CH NH 3 (e) Product of (d), heated strongly (f) Phthalic acid [Problem 27(h)], heated strongly 34. When 1,4- and 1,5-dicarboxylic acids, such as butanedioic (succinic) acid (Section 19-8), are treated with SCl 2 or Pr 3 in attempted preparations of the diacyl halides, the corresponding cyclic anhydrides are obtained. Explain mechanistically. 35. Reaction review. Without consulting the Reaction Road Map on p. 914, suggest reagents to convert each of the following starting materials into hexanoic acid: (a) hexanal; (b) methyl hexanoate; (c) 1-bromopentane; (d) 1-hexanol: (e) hexanenitrile. 36. Reaction review II. Without consulting the Reaction Road Map on p. 915, suggest reagents to convert hexanoic acid into each of the following compounds: (a) 1-hexanol; (b) hexanoic anhydride; (c) hexanoyl chloride; (d) 2-bromohexanoic acid; (e) ethyl hexanoate; (f) hexanamide. 37. Fill in suitable reagents to carry out the following transformations. H (a) ( ) 2 CHCH 2 CH uy ( ) 2 CHCH 2 C 2 H (b) CH CHC 2 H (c) r C 2 H (d) H Cl H H (e) H (f) ( ) 3 CC 2 H uy ( ) 3 CC 2 CH( ) 2

5 Problems Chapter Transmittance (%) IR IR cm 1 Wavenumber 1 H NMR 4 H 2 H 4 H MHz 1 H NMR spectrum ppm (δ) δ (g) NH N CH3 H E C

6 918 Chapter 19 Carboxylic cids 1 Transmittance (%) IR IR cm 1 Wavenumber 1 Transmittance (%) IR-E IR cm 1 Wavenumber 38. Propose syntheses of each of the following carboxylic acids that employ at least one reaction that forms a carbon carbon bond. (a) CH 2 CH 2 CH 2 CH 2 CH 2 C 2 H H (b) CHCH 2 C 2 H (c) H 3 C C C 2 H

7 Problems Chapter H NMR 2 H 5 H 4 H 2 H 1 H ( ) 4 Si F 3-MHz 1 H NMR spectrum ppm (δ) δ 1 Transmittance (%) IR-F IR cm 1 Wavenumber 39. (a) Write a mechanism for the esterification of propanoic acid with 18 -labeled ethanol. Show clearly the fate of the 18 label. (b) cid-catalyzed hydrolysis of an unlabeled ester with 18 -labeled water (H 2 18 ) leads to incorporation of some 18 into both oxygens of the carboxylic acid product. Explain by a mechanism. (Hint: You must use the fact that all steps in the mechanism are reversible.)

8 92 Chapter 19 Carboxylic cids 1 H NMR 6 H H 4 H ( ) 4 Si G 3-MHz 1 H NMR spectrum ppm (δ) δ 1 Transmittance (%) IR-G 1742 IR cm 1 Wavenumber 4. Give the products of reaction of propanoic acid with each of the following reagents. (a) SCl 2 (b) Pr 3 (c) CH 2 Cr 1 pyridine (d) ( ) 2 CHH 1 HCl (e) CH 2 NH 2 (f) Product of (e), heated strongly (g) LilH 4, then H 1, H 2 (h) r 2, P 41. Give the product of reaction of cyclopentanecarboxylic acid with each of the reagents in Problem 4.

9 Problems Chapter When methyl ketones are treated with a halogen in the presence of base, the three hydrogen atoms on the methyl carbon are replaced to give a CX 3 -substituted ketone. This product is not stable under the basic conditions and proceeds to react with hydroxide, ultimately furnishing the carboxylic acid (as its conjugate base) and a molecule of HCX 3, which has the common name haloform (i.e., chloroform, bromoform, and iodoform, for X 5 Cl, r, and I, respectively). For example: ð ð ðð RCCr 3 ð šh RC š ð HCr 3 Propose a series of mechanistic steps to convert the tribromoketone into the carboxylate. What is the leaving group? Why do you think this species is capable of acting as a leaving group in this process? 43. Interpret the labeled peaks in the mass spectrum of 2-methylhexanoic acid (MS-H). 1 MS 74 Relative abundance 5 87 CH 2 CH 2 CH 2 CHCH MS-H m/z Suggest a preparation of hexanoic acid from pentanoic acid. 45. Give reagents and reaction conditions that would allow efficient conversion of 2-methylbutanoic acid into (a) the corresponding acyl chloride; (b) the corresponding methyl ester; (c) the corresponding ester with 2-butanol; (d) the anhydride; (e) the N-methylamide; (f) CH 2 CHCH 2 H r (g) CH 2 CC 2 H 46. Treatment of 4-pentenoic acid (margin) with r 2 in the presence of dilute aqueous base yields a nonacidic compound with the formula C 5 H 7 r 2. (a) Suggest a structure for this compound and a mechanism for its formation. (b) Can you find a second, isomeric product whose formation is also mechanistically reasonable? (c) iscuss the issues that contribute to determining which of the two is the major product in this reaction. (Hint: Review Section 12-6.) H 4-Pentenoic acid 47. Show how the Hell-Volhard-Zelinsky reaction might be used in the synthesis of each of the following compounds, beginning in each case with a simple monocarboxylic acid. Write detailed mechanisms for all the reactions in one of your syntheses.

10 922 Chapter 19 Carboxylic cids (a) CH 2 CHC 2 H NH 2 (b) CHC 2 H C 2 H (c) H H (d) H 2 CCH 2 SSCH 2 C 2 H (e) ( CH 2 ) 2 NCH 2 C 2 H (f) (C 6 H 5 ) 3 PCHC 2 H r 48. The Hell-Volhard-Zelinsky reaction produces only bromocarboxylic acids. However, modified procedures have been developed to convert acyl chlorides into a-chloro- and a-bromoacyl chlorides by reaction with N-chloro- and N-bromobutanimide (N-chloro- and N-bromosuccinimide, NCS and NS: Section 14-2), respectively. Reaction with I 2 gives a-iodoacyl chlorides. (SCl 2 is used as the solvent to maintain the acyl chloride functional group.) Suggest a mechanism for any one of these processes. CNH 2 cetamide -utyrolactone C 6 H 5 CH 2 CH 2 CCl NCS, HCl, SCl 2, 7 C NS, Hr, SCl 2, 7 C I 2, HI, SCl 2, 85 C C 6 H 5 CH 2 CHClCCl 84% C 6 H 5 CH 2 CHrCCl 71% C 6 H 5 CH 2 CHICCl 75% 49. How would you expect the acidity of acetamide to compare with that of acetic acid? With that of acetone? Which protons in acetamide are the most acidic? Where would you expect acetamide to be protonated by very strong acid? 5. ttempted Cr 3 oxidation of 1,4-butanediol to butanedioic acid results in significant yields of g-butyrolactone. Explain mechanistically. 51. Following the general mechanistic scheme given in Section 19-7, write detailed mechanisms for each of the following substitution reactions. (Note: These transformations are part of Chapter 2, but try to solve the problem without looking ahead.) (a) CCl CH 2 H CCH 2 HCl (b) H CNH 2 H 2 CH NH Suggest structures for the products of each reaction in the following synthetic sequence. H H N 1. H, H 2. ( ) 2 CPCHCH 2 r 3. H, H 2 C 14 H 22 H HCH 2 CH 2 H, H C 16 H 26 2 I 1. 3, CH 2 Cl 2 2. Zn, CH 3. KMn 4, NaHC 3 IR: 1745 cm 1 IR: 1675 and 1745 cm 1 IR: 167 cm 1 C 13 H 2 4 J IR: 1715 and 3 (broad) cm 1 1. H, H 2 2. NaH 4 C 11 H 18 3 Catalytic H, C 11 H 16 2 K IR: 1715, 3 (broad), and 335 cm 1 L IR: 177 cm 1

11 Problems Chapter S N 2 reactions of simple carboxylate ions with haloalkanes (Section 8-5) in aqueous solution generally do not give good yields of esters. (a) Explain why this is so. (b) Reaction of 1-iodobutane with sodium acetate gives an excellent yield of ester if carried out in acetic acid (as shown here). Why is acetic acid a better solvent for this process than water? C Na C 2 H, 1 C CH 2 CH 2 CH 2 I CH 2 CH 2 CH 2 C 95% 1-Iodobutane Sodium acetate utyl acetate Na I (c) The reaction of 1-iodobutane with sodium dodecanoate proceeds surprisingly well in aqueous solution, much better than the reaction with sodium acetate (see the following equation). Explain this observation. (Hint: Sodium dodecanoate is a soap and forms micelles in water. See Chemical Highlight 19-1.) CH 2 CH 2 CH 2 I (CH 2 ) 1 C 2 Na H 2 (CH 2 ) 1 CCH 2 CH 2 CH The iridoids are a class of monoterpenes with powerful and varied biological activities. They include insecticides, agents of defense against predatory insects, and animal attractants. The following reaction sequence is a synthesis of neonepetalactone, one of the nepetalactones, which are primary constituents of catnip. Use the information given to deduce the structures that have been left out, including that of neonepetalactone itself. C 1 H 16 2 M IR: 89, 1645, 1725 (very strong), and 175 cm 1 ase CH Cr 3, H 2 S 4, C C 1 H 14 2 N IR: 89, 163, 164, 172, and 3 (very broad) cm 1 H, H C 11 H 16 2 IR: 89, 163, 164 and 172 cm 1 1. icyclohexylborane, THF 2. H, H 2 2 C 11 H 18 3 P IR: 163, 172, and 3335 cm 1 H, H 2, Neonepetalactone IR: 1645 and 171 cm 1 UV max 241 nm 55. Propose two possible mechanisms for the following reaction. (Hint: Consider the possible sites of protonation in the molecule and the mechanistic consequences of each.) evise an isotope-labeling experiment that might distinguish your two mechanisms. CH H CH HCl, CH C 56. Propose a short synthesis of 2-butynoic acid, CqCC 2 H, starting from propyne. (Hint: Review Sections 13-2 and 13-5.) 57. The benzene rings of many compounds in nature are prepared by a biosynthetic pathway similar to that operating in fatty acid synthesis. cetyl units are coupled, but the ketone functions are not reduced. The result is a polyketide thiolester, which forms rings by intramolecular aldol condensation.

12 924 Chapter 19 Carboxylic cids CCH 2 CCH 2 CCH 2 CSprotein Polyketide thiolester o-rsellinic acid [for structure, see Problem 27(g)] is a derivative of salicylic acid and is prepared biosynthetically from the polyketide thiolester shown. Explain how this transformation might take place. Hydrolysis of the thiolester to give the free carboxylic acid is the last step. Team Problem 58. Section 19-9 showed you that 4- and 5-hydroxy acids can undergo acid-catalyzed intramolecular esterification to produce the corresponding lactone in good yield. Consider the following two examples of lactonization. ivide the analysis of the reaction sequences among your group. Propose reasonable mechanisms to explain the respective product formation. Na r 2, CH 2 Cl 2 H 3 C ^? r (Note stereochemistry!) 2 H H H, H 2 H H (Two diastereomers) H, H 2 H 3 C (Cis and trans isomers) Reconvene to present your mechanisms to each other. Preprofessional Problems 59. What is the IUPC name of the compound shown? (a) (E)-3-Methyl-2-hexenoic acid H 3 C C 2 H (b) (Z)-3-Methyl-2-hexenoic acid i f CPC (c) (E)-3-Methyl-3-hexenoic acid f i (d) (Z)-3-Methyl-3-hexenoic acid CH 2CH 2 H 6. Select the acid with the highest K a (i.e., lowest pk a ). C 2 H C 2 H (a) H 3 CC 2 H (b) I (c) Cl (d) Cl 2 CHC 2 H H 2 C 61. The acid whose structure is shown in the margin can best be prepared via one of these sequences. Which one? C( ) 3 (a) H 3 Cr r 3 CC 2 H K enzene (b) ( ) 3 CI Mg, ether C 2 H, H 2 (work-up) (c) KMn 4 (d) KMn 4 H 3 C C( ) 3 C( ) 3