964 Chapter 20 Carboxylic Acid Derivatives 7. The functional group of nitriles is somewhat similar to that of the alkynes. The two component 2 atoms are sp hybridized. The IR stretching vibration appears at about 2250 cm 1. The hydrogens next to the cyano group are deshielded in 1H NMR. The 13C NMR absorptions for nitrile carbons are at relatively low fi eld (d , 112 – 126 ppm), a consequence of the electronegativity of nitrogen. Problems 30. Name (IUPAC system) or draw the structure of each of the following compounds. COCl O OO BB CH3 (a) I (b) (c) CF3COCCF3 OO O O BB B B (d) COCCH2CH3 (e) (CH3)3CCOCH2CH3 (f) CH3CNH (g) Propyl butanoate (h) Butyl propanoate (i) 2-Chloroethyl benzoate (j) N,N-Dimethylbenzamide (k) 2-Methylhexanenitrile (l) Cyclopentanecarbonitrile 31. Name each of the following compounds according to IUPAC or Chemical Abstracts rules. Pay attention to the order of precedence of the functional groups. CONH O O 2 OH (a) OCH3 (b) CO2CH2CH3 (c) NHCH3 (d) H Cl O CONH2 O 32. (a) Use resonance forms to explain in detail the relative order of acidity of carboxylic acid derivatives, as presented in Section 20-1. (b) Do the same, but use an argument based on inductive effects. O B 33. In each of the following pairs of compounds, decide which possesses the indicated property to CH3CN(CH3)2 the greater degree. (a) Length of C – X bond: acetyl fl uoride or acetyl chloride. (b) Acidity of the i boldface H: CH2(COCH3)2 or CH2(COOCH3)2. (c) Reactivity toward addition of a nucleophile: (i) an amide or (ii) an imide (as shown in the margin). (d) High-energy infrared carbonyl stretching O O B B frequency: ethyl acetate or ethenyl acetate. CH CNCCH 34. 3 A 3 Give the product(s) of each of the following reactions. CH3 O NH2 ii B (a) CH3CCl ϩ 2 O THF ϩ (b) ΂ ΂ CuLi Cl 2 O H3C O B A B Ϫ ° 2 CH2OH, N LiAl[OC(CH3)3]3H, THF, 78 C CH OCCl (c) H CCOOCCl (d) 2 3 A A CH2 OCCl H3C B O OCH3 H3C LiAl[OC(CH3)3]3H, THF, Ϫ78°C (e) H C CCl 3 B O Problems Chapter 20 965 35. Formulate a mechanism for the reaction of acetyl chloride with 1-propanol shown on p. 932. 36. Give the product(s) of the reactions of acetic anhydride with each of the following reagents. Assume in all cases that the reagent is present in excess. (a) (CH3)2CHOH (b) NH3 ϩ 1 (c) MgBr, THF; then H , H2O (d) LiAlH4, (CH3CH2)2O; then H , H2O 37. Give the product(s) of the reaction of butanedioic (succinic) anhydride with each of the reagents in Problem 36. 38. Formulate a mechanism for the reaction of butanedioic (succinic) anhydride with methanol shown on p. 935. 39. Give the products of reaction of methyl pentanoate with each of the following reagents under the conditions shown. 1 1 (a) NaOH, H2O, heat; then H , H2O (b) (CH3)2CHCH2CH2OH (excess), H 1 (c) (CH3CH2)2NH, heat (d) CH3MgI (excess), (CH3CH2)2O; then H , H2O 1 1 (e) LiAlH4, (CH3CH2)2O; then H , H2O (f) [(CH3)2CHCH2]2AlH, toluene, low temperature; then H , H2O 40. Give the products of reaction of g-valerolactone (5-methyloxa-2-cyclopentanone, Section 20-4) with each of the reagents in Problem 39. 41. Draw the structure of each of the following compounds: (a) b-butyrolactone; (b) b-valerolactone; (c) d-valerolactone; (d) b-propiolactam; (e) a-methyl-d-valerolactam; (f) N-methyl-g-butyrolactam. 42. Formulate a mechanism for the acid-catalyzed transesterifi cation of ethyl 2-methylpropanoate (ethyl isobutyrate) into the corresponding methyl ester. Your mechanism should clearly illustrate the catalytic role of the proton. 43. Formulate a mechanism for the reaction of methyl 9-octadecenoate with 1-dodecanamine shown on p. 939. 44. Reaction review. Suggest reagents to convert each of the following starting materials into the indicated product: (a) hexanoyl chloride into acetic hexanoic anhydride; (b) methyl hexanoate into N-methylhexanamide; (c) hexanoyl chloride into hexanal; (d) hexanenitrile into hexanoic acid; (e) hexanamide into hexanamine; (f) hexanamide into pentanamine; (g) ethyl hexanoate into 3-ethyl-3-octanol; (h) hexanenitrile into 1-phenyl-1-hexanone [C6H5CO(CH2)4CH3]. 45. Give the product of each of the following reactions. COOCH3 % 1. KOH, H2O ϩ H C 2. H , H2O 3 % O (CH ) CHNH , CH OH, ⌬ (a) (b) 3 2 2 3 0 O ´ COOCH3 CH3CH2 O 1. (CH3CH2)2O, 20°C B ϩ MgBr 2. H , H2O ϩ (c) CH3COCH3 excess 1. LDA, THF, Ϫ78°C CH A 3 CH 2. CH3I, HMPA Ϫ ° 3 ϩ COOCH 1. (CH3CHCH2)2AlH, toluene, 60 C D 3. H , H O 3 ϩ 2 2. H , H O (d) CHG (e) 2 COOCH2CH3 46. For each of the naturally occurring lactones below, draw the structure of the compound that would result from hydrolysis using aqueous base. Sedanenolide, major contributor to the fl avor of celery (a) O O 966 Chapter 20 Carboxylic Acid Derivatives H ´ Nepetalactone, major active component in catnip (b) (Caution: Do you notice anything unusual about one of the O ≥ functional groups after hydrolysis? H O O O g-Valerolactone, impotant in the fragrance industry (c) and a potential biofuel (d) A novel “green” process converts levulinic acid (4-oxopentanoic acid, CH3COCH2CH2COOH), which is readily obtained from waste biomass, into g-valerolactone by treatment with gaseous H2 in the presence of a special hydrogenation catalyst. Speculate on how this reaction may CH3 take place. O 47. N,N-Diethyl-3-methylbenzamide (N,N-diethyl-m-toluamide), marketed as DEET, is perhaps the most widely used insect repellent in the world and is especially effective in interrupting the transmission (CH3CH2)2N of diseases by mosquitoes and ticks. Propose one or more preparations of DEET (see structure, DEET margin) from the corresponding carboxylic acid and any other appropriate reagents. 48. Like many chiral pharmaceuticals, Ritalin, widely used to treat attention defi cit disorder, is synthe- sized and marketed as a racemic mixture. In 2003, a new and potentially practical synthetic route to 0 CO2CH3 the active enantiomer (see structure, margin) was described. The fi rst step is shown below, the reac- N ´ tion of dimethyl sulfate with a six-membered ring lactam. Propose a mechanism for this reaction. H C6H5 O Ritalin B CH OOOS OCH (Active stereoisomer) 3 B 3 O N O N OCH3 H O B 49. Formulate a mechanism for the formation of acetamide, CH3CNH2, from methyl acetate and ammonia. 50. Give the products of the reactions of pentanamide with the reagents given in Problem 39(a, e, f). Repeat for N,N-dimethylpentanamide. 51. Formulate a mechanism for the acid-catalyzed hydrolysis of 3-methylpentanamide shown on p. 948. (Hint: Use as a model the mechanism for general acid-catalyzed addition – elimination presented in Section 19-7.) 52. What reagents would be necessary to carry out the following transformations? (a) Cyclohexanecar- bonyl chloride y pentanoylcyclohexane; (b) 2-butenedioic (maleic) anhydride y (Z)-2-butene- 1,4-diol; (c) 3-methylbutanoyl bromide y 3-methylbutanal; (d) benzamide y 1-phenylmethanamine; (e) propanenitrile y 3-hexanone; (f) methyl propanoate y 4-ethyl-4-heptanol. 53. Nylon-6,6 was the fi rst completely synthetic fi ber, initially prepared in the mid-1930s at DuPont. It is a copolymer whose subunits are alternating molecules of 1,6-hexanediamine and hexanedioic (adipic) acid, linked by amide functions. (a) Write a structural representation of Nylon-6,6. (b) Hexanedinitrile (adiponitrile) may be used as a common precursor to both 1,6-hexanediamine and hexanedioic acid. Show the reactions necessary to convert the dinitrile into both the diamine and the diacid. (c) Formulate a mechanism for the conversion into the diacid under the reaction conditions that you chose in (b). 54. Upon treatment with strong base followed by protonation, compounds A and B undergo cis-trans isomerization, but compound C does not. Explain. [ COOCH3 [ CON(CH3)2 [ CONH2 ) ) ) COOCH3 CON(CH3)2 CONH2 A B C Problems Chapter 20 967 55. 2-Aminobenzoic (anthranilic) acid is prepared from 1,2-benzenedicarboxylic anhydride (phthalic anhydride) by using the two reactions shown here. Explain these processes mechanistically. O O O B ° 1. NaOH, Br2, 80 C COH ϩ NH3, 300°C 2. H , H2O O NH NH2 O O 1,2-Benzenedicarboxylic 1,2-Benzenedicarboximide 2-Aminobenzoic acid anhydride (Phthalimide) (Anthranilic acid) (Phthalic anhydride) 56. On the basis of the reactions presented in this chapter, write reaction summary charts for esters and amides similar to the chart for acyl halides (Figure 20-1). Compare the number of reactions for each of the compound classes. Is this information consistent with your understanding of the relative reactivity of each of the functional groups? 57. Show how you might synthesize chlorpheniramine, a powerful antihistamine used in several decongestants, from each of carboxylic acids A and B. Use a different carboxylic amide in each synthesis. N N N CHCH2COOH CHCH2CH2COOH CHCH2CH2N(CH3)2 Cl Cl Cl A B Chlorpheniramine 2 58. Although esters typically have carbonyl stretching frequencies at about 1740 cm 1 in the infra- O O red spectrum, the corresponding band for lactones can vary greatly with ring size. Three exam- ples are shown in the margin. Propose an explanation for the IR bands of these smaller ring O O lactones. 59. Upon completing a synthetic procedure, every chemist is faced with the job of cleaning glassware. 1735 cm؊1 1770 cm؊1 Because the compounds present may be dangerous in some way or have unpleasant properties, a little serious chemical thinking is often benefi cial before “doing the dishes.” Suppose that you O have just completed a synthesis of hexanoyl chloride, perhaps to carry out the reaction in Problem O 34(b); fi rst, however, you must clean the glassware contaminated with this acyl halide.