Show how you would synthesize each compound, starting with

Problem 2P What characteristics of the methyl benzoate spectrum rule out an aldehyde or carboxylic acid functional group giving the absorption at 1723 cm-1?

Problem 3P Aldehydes, ketones, carboxylic acids, and esters all give strong carbonyl stretching absorptions in the IR spectrum. How can you use other peaks in their IR spectra to distinguish among these four common functional groups?

Name the following carboxylic acid derivatives, giving both a common name and an IUPAC name where possible. (a) (b) (c) (d) (e) (f) (g) (h) (i)

Which of the following proposed reactions would take place quickly under mild conditions?

The IR spectra shown next may include a carboxylic acid, an ester, an amide, a nitrile, an acid chloride, or an acid anhydride. Determine the functional group suggested by each spectrum, and list the specific frequencies you used to make your decision.

Problem 6P (a) Propose a mechanism for the reaction of benzyl alcohol with acetyl chloride to give benzyl acetate. (b) Propose a mechanism for the reaction of benzoic acid with acetyl chloride to give acetic benzoic anhydride. (c) Propose a second mechanism for the reaction of benzoic acid with acetyl chloride to give acetic benzoic anhydride. This time, let the other oxygen of benzoic acid serve as the nucleophile to attack the carbonyl group of acetyl chloride. Because proton transfers are fast between these oxygen atoms, it is difficult to differentiate between these two mechanisms experimentally. (d) Propose a mechanism for the reaction of aniline with acetic anhydride to give acetanilide. (e) Propose a mechanism for the reaction of aniline with ethyl acetate to give acetanilide. What is the leaving group in your proposed mechanism? Would this be a suitable leaving group for an SN2 reaction?

An unknown compound of molecular formula \(C_{5} H_{9} N O\) gives the IR and NMR spectra shown here. The broad NMR peak at disappears when the sample is shaken with \(D_{2} O\). Propose a structure, and show how it is consistent with the absorptions in the spectra. Equation transcription: Text transcription: C{5} H{9} N O D{2} O

For each set of IR and NMR spectra, determine the structure of the unknown compound. Explain how your proposed structure fits the spectra. (a) \(C_{2} H_{5} N O\) (b) \(\mathrm{C}_{5} \mathrm{H}_{8} \mathrm{O}_{2}\) Equation transcription: Text transcription: C{2} H{5} N O {C}{5}{H}{8}{O}{2}

Problem 8P Show how you would synthesize the following esters from appropriate acyl chlorides and alcohols. (a) ethyl propionate (b) phenyl 3-methylhexanoate (c) benzyl benzoate (d) cyclopropyl cyclohexanecarboxylate (e) tert-butyl acetate (f) diallyl succinate

Show how you would use appropriate acyl chlorides and amines to synthesize the following amides. (a) N,N-dimethylacetamide (b) acetanilide \(\left(\mathrm{PhNHCOCH}_{3}\right)\) (c) cyclohexanecarboxamide (d) Equation transcription: Text transcription: {PhNHCOCH}{3})

Problem 10P (a) Show how you would use acetic anhydride and an appropriate alcohol or amine to synthesize (i) benzyl acetate, (ii) N,N-diethylacetamide. (b) Propose a mechanism for each synthesis in part (a).

Problem 11P Propose a mechanism for the reaction of benzyl acetate with methylamine. Label the attacking nucleophile and the leaving group, and draw the transition state in which the leaving group leaves.

Problem 17P (a) Explain why we speak of acidic hydrolysis of an ester as acid-catalyzed, but of basic hydrolysis as base-promoted. (b) Soap manufacturers always use base to hydrolyze fats, and never acid. Suggest two reasons that basic hydrolysis is preferred.

Problem 12P When ethyl 4-hydroxybutyrate is heated in the presence of a trace of a basic catalyst (sodium acetate), one of the products is a lactone. Propose a mechanism for formation of this lactone.

Suppose we have some optically pure -butyl acetate that has been "labeled" with the heavy \({ }^{18} O\) isotope at one oxygen atom as shown. (a) Draw a mechanism for the hydrolysis of this compound under basic conditions. Predict which of the products will contain the \({ }^{18} O\) label. Also predict whether the butan- 2 -ol product will be pure , pure , or racemized. (b) Repeat part (a) for the acid-catalyzed hydrolysis of this compound. (c) Explain how you would prove experimentally where the \({ }^{18} O\) label appears in the products. (\({ }^{18} O\) is not radioactive. Equation transcription: Text transcription: ^{18} O

Problem 13P Complete the mechanism for this acid-catalyzed transesterification by drawing out all the individual steps. Draw the important resonance contributors for each resonance-stabilized intermediate.

Propose a mechanism for the base-promoted hydrolysis of -butyrolactone:

Problem 15P (a) Propose a mechanism for the acid-catalyzed reaction of salicylic acid with acetic anhydride. (b) Explain why a single drop of sulfuric acid dramatically increases the reaction rate.

Propose a mechanism for the following ring-opening transesterification. Use the mechanism in Problem 21-13 as a model. \(\mathrm{CH}_{3} \mathrm{OH}\) \(\mathrm{OCH}_{3}\) Equation transcription: Text transcription: {CH}{3}{OH} {OCH}{3}

Problem 20P Propose a mechanism for the hydrolysis of N,N-dimethylacetamide (a) under basic conditions. (b) under acidic conditions.

Problem 22P Propose a mechanism for the basic hydrolysis of benzonitrile to the benzoate ion and ammonia.

Problem 23P The mechanism for acidic hydrolysis of a nitrile resembles the basic hydrolysis, except that the nitrile is first protonated, activating it toward attack by a weak nucleophile (water). Under acidic conditions, the proton transfer (tautomerism) involves protonation on nitrogen followed by deprotonation on oxygen. Propose a mechanism for the acid-catalyzed hydrolysis of benzonitrile to benzamide.

Problem 19P Draw the important resonance contributors for both resonance-stabilized cations (in brackets) in the mechanism for acid-catalyzed hydrolysis of an amide.

Problem 21P The equilibrium for hydrolysis of amides, under both acidic and basic conditions, favors the products. Use your mechanisms for the hydrolysis of N,N-dimethylacetamide to show which steps are sufficiently exothermic to drive the reactions to completion.

Problem 24P (a) In which step(s) of the hydride reduction of an ester does the compound undergo reduction? (Hint: Count the bonds to oxygen.) (b) Propose a mechanism for the reduction of octanoyl chloride by lithium aluminum hydride.

Problem 26P Draw a mechanism for the acidic hydrolysis of the magnesium salt shown above to acetophenone.

Problem 27P Draw a mechanism for the reaction of propanoyl chloride with 2 moles of phenylmagnesium bromide.

Give the expected products of lithium aluminum hydride reduction of the following com- pounds (followed by hydrolysis). (a) butyronitrile (b) N-cyclohexylacetamide (c) -caprolactam \(\mathrm{CH}_{3}\) \(\mathrm{CH}_{2} \mathrm{CH}_{3}\) Equation transcription: Text transcription: {CH}{3} {CH}{2}{CH}{3}

Problem 29P Draw a mechanism for the acylation of anisole by propionyl chloride. Recall that Friedel–Crafts acylation involves an acylium ion as the electrophile in electrophilic aromatic substitution.

Problem 28P Show how you would add a Grignard reagent to an ester or a nitrile to synthesize (a) 4-phenylheptan-4-ol (b) heptan-4-ol (c) pentan-2-one

Problem 30P Show how Friedel–Crafts acylation might be used to synthesize the following compounds. (a) acetophenone (b) benzophenone (c) n-butylbenzene

Problem 31P (a) Give the products expected when acetic formic anhydride reacts with (i) aniline and (ii) benzyl alcohol. (b) Propose mechanisms for these reactions.

Problem 32P Show how you would use anhydrides to synthesize the following compounds. In each case, explain why an anhydride might be preferable to an acid chloride. (a) n-octyl formate (b) n-octyl acetate (c) phthalic acid monoamide (d) succinic acid monomethyl ester

Problem 33P Propose a mechanism for the formation of 9-hydroxynonanoic acid lactone, as shown in the preceding figure.

Suggest the most appropriate reagent for each synthesis, and explain your choice.

Show how you would synthesize each compound, starting with an ester containing no more than eight carbon atoms. Any other necessary reagents may be used. 1. \(P h_{3} C-O H\) 2. \(\left(\mathrm{PhCH}_{2}\right)_{2} \mathrm{CHOH}\) 3. \(\mathrm{PhCONHCH}_{2} \mathrm{CH}_{3}\) 4. \(P h_{2} \subset H O H\) 5. \(\mathrm{PhCH}_{2} \mathrm{Oh}\) 6. \(P h C O O H\) 7. \(\mathrm{PhCH}_{2} \mathrm{COOCH}\left(\mathrm{CH}_{3}\right)_{2}\) 8. \(\mathrm{PhCH}_{2}-\mathrm{C}\left(\mathrm{CH}_{2} \mathrm{CH}_{3}\right)_{2}\) 9. \(H P-\left(C H_{2}\right)_{8}-O H\) Equation transcription: Text transcription: P h_{3} C-O H ({PhCH}{2}){2}{CHOH} {PhCONHCH}{2}{CH}{3} P h{2} subset H O H {PhCH}{2}{Oh} P h C O O H {PhCH}{2}{COOCH}({CH}{3}){2} {PhCH}{2}-{C}(CH}{2}{CH}{3}){2} H P-(C H{2}){8}-O H

Show how you would accomplish the following synthetic transformations. You may use any necessary reagents. (a) -ethylbenzamide benzylethylamine (b) ethyl benzoate -ethylbenzamide (c) pyrrolidine -acetylpyrrolidine (d) -aminobutyric acid pyrrolidine

Show how you would accomplish the following syntheses using amides as intermediates. You may use any necessary reagents. (a) benzoic acid benzyldimethylamine (b) pyrrolidine -ethylpyrrolidine (c) cyclopentanecarboxylic acid cyclopentanecarbonitrile

Show how you would convert the following starting materials to the indicated nitriles: (a) phenylacetic acid phenylacetonitrile (b) phenylacetic acid -phenylpropionitrile (c) -chloronitrobenzene -chlorobenzonitrile

Problem 40P Propose a mechanism for the reaction of methyl isocyanate with 1-naphthol to give Sevin® insecticide.

Show how each transformation may be accomplished by using a nitrile as an intermediate. You may use any necessary reagents. (a) hexan-1-ol heptan-1-amine (b) cyclohexanecarboxamide cyclohexyl ethyl ketone (c) octan-1-ol decan-2-one

For each heterocyclic compound, (i) Explain what type of acid derivative is present. (ii) Show what compounds would result from complete hydrolysis. (iii) Are any of the rings aromatic? Explain.

Give appropriate names for the following compounds:

Problem 42SP Draw structures to correspond with the following common and systematic names: (a) phenyl formate (b) cyclohexyl benzoate (c) cyclopentyl phenylacetate (d) N-butylacetamide (e) N,N-dimethylformamide (f) benzoic propionic anhydride (g) benzamide (h) ?-hydroxyvaleronitrile (i) ?-bromobutyryl chloride (j) ?-butyrolactone (k) phenyl isocyanate (l) cyclobutyl ethyl carbonate (m) ?-caprolactam (n) trichloroacetic anhydride (o) ethyl N-methyl carbamate

Problem 44SP Predict the major products formed when benzoyl chloride (PhCOCl) reacts with the following reagents. (a) ethanol (b) sodium acetate (c) aniline (d) anisole and aluminum chloride (e) excess phenylmagnesium bromide, then dilute acid (f) LiAlH(O-t-Bu)3

Predict the products of the following reactions. (a) phenol acetic anhydride (b) phenol acetic formic anhydride (c) aniline phthalic anhydride (d) anisole succinic anhydride and aluminum chloride

Predict the products of saponification of the following esters. \(\mathrm{CH}_{3} \mathrm{CH}_{2}-\mathrm{C}-\mathrm{OCH}_{2} \mathrm{CH}_{3}\) Equation transcription: Text transcription: {CH}{3}{CH}{2}-{C}-{OCH}{2}{CH}{3}

Show how you would accomplish the following syntheses in good yields.

Predict the products of the following reactions.

Propose mechanisms for the following reactions. Does this reaction proceed with retention, inversion, or racemization of the asymmetric carbon atom?

Phosgene is the acid chloride of carbonic acid. Although phosgene was used as a war gas in World War I, it is now used as a reagent for the synthesis of many useful products. Phosgene reacts like other acid chlorides, but it can react twice. (a) Predict the products formed when phosgene reacts with excess propan-2-ol. (b) Predict the products formed when phosgene reacts with 1 equivalent of methanol, followed by 1 equivalent of aniline. (c) tert-Butyloxycarbonyl chloride is an important reagent for the synthesis of peptides and proteins (Chapter 24). Show how you would use phosgene to synthesize tert-butyloxycarbonyl chloride.

Problem 52SP An ether extraction of nutmeg gives large quantities of trimyristin, a waxy crystalline solid of melting point 57 °C. The IR spectrum of trimyristin shows a very strong absorption at 1733 cm-1. Basic hydrolysis of trimyristin gives 1 equivalent of glycerol and 3 equivalents of myristic acid (tetradecanoic acid). (a) Draw the structure of trimyristin. (b) Predict the products formed when trimyristin is treated with lithium aluminum hydride, followed by aqueous hydrolysis of the aluminum salts.

Problem 46SP Acid-catalyzed transesterification and Fischer esterification take place by nearly identical mechanisms. Transesterification can also take place by a base-catalyzed mechanism, but all attempts at base-catalyzed Fischer esterification (using –OR “, for example) seem doomed to failure. Explain why Fischer esterification cannot be catalyzed by base.

Two widely used pain relievers are aspirin and acetaminophen. Show how you would synthesize these drugs from phenol. \(O-C-C H_{3}\) \(N H-C-C H_{3}\) Equation transcription: Text transcription: O-C-C H_{3} N H-C-C H{3}

Show how you would accomplish the following syntheses. Some of these conversions may require more than one step. (a) isopentyl alcohol isopentyl acetate (banana oil) (b) 3 -ethylpentanoic acid -ethylpentanenitrile (c) isobutylamine -isobutylformamide (d) ethyl acetate 3-methylpentan-3-ol (e) cyclohexylamine -cyclohexylacetamide (f) bromocyclohexane dicyclohexylmethanol

Grignard reagents add to carbonate esters as they add to other esters. (a) Predict the major product of the following reaction. \(\mathrm{CH}_{3} \mathrm{CH}_{2}-\mathrm{O}-\mathrm{C}-\mathrm{O}-\mathrm{CH}_{2} \mathrm{CH}_{3}\) \(\frac{(1) \text { excess } \mathrm{Ph} M g B r}{(2) \mathrm{H}_{3} \mathrm{O}^{+}}\) (b) Show how you would synthesize 3 -ethylpentan-3-ol using diethyl carbonate and ethyl bromide as your only organic reagents. *(c) Diethyl carbonate is a liquid reagent that is easy to handle. In contrast, phosgene is a highly toxic and corrosive gas. Show how you might use diethyl carbonate instead of phosgene to make Lexan®.. Also show how you might use diethyl carbonate instead of methyl isocyanate to make Sevin® insecticide. Equation transcription: Text transcription: {CH}{3}{CH}{2}-{O}-{C}-{O}-{CH}{2}{CH}{3} frac{(1){ excess }{Ph} M g B r}{(2){H}{3}{O}^{+}}

Problem 56SP One mole of acetyl chloride is added to a liter of triethylamine, resulting in a vigorous exothermic reaction. Once the reaction mixture has cooled, 1 mole of ethanol is added. Another vigorous exothermic reaction results. The mixture is analyzed and found to contain triethylamine, ethyl acetate, and triethylammonium chloride. Propose mechanisms for the two exothermic reactions.

Show how you would accomplish the following multistep syntheses, using the indicated starting material and any necessary reagents. (a) hept-6-en-1-ol -caprolactone (b) methoxybenzene -methoxybenzamide

The structures of four useful polymers are shown, together with some of their best-known products. In each case, (i) Determine the kind of polymer (polyamide, polyester, etc.). (ii) Draw the structures of the monomers that would be released by complete hydrolysis. (iii) Suggest what monomers or stable derivatives of the monomers might be used to make these polymers.

Problem 58SP Methyl p-nitrobenzoate has been found to undergo saponification faster than methyl benzoate. (a) Consider the mechanism of saponification, and explain the reasons for this rate enhancement. (b) Would you expect methyl p-methoxybenzoate to undergo saponification faster or slower than methyl benzoate?

Problem 59SP A student has just added ammonia to hexanoic acid and has begun to heat the mixture when he is called away to the telephone. After a long telephone conversation, he returns to find that the mixture has overheated and turned black. He distills the volatile components and recrystallizes the solid residue. Among the components he isolates are compounds A (a liquid; molecular formula C6H11N ) and B (a solid; molecular formula C6H13NO ). The infrared spectrum of A shows a strong, sharp absorption at 2247 cm-1. The infrared spectrum of B shows absorptions at 3390, 3200, and 1665 cm-1. Determine the structures of compounds A and B.

Problem 60SP In Section 21-16, we saw that Sevin® insecticide is made by the reaction of 1-naphthol with methyl isocyanate. A Union Carbide plant in Bhopal, India, once used this process to make Sevin® for use as an agricultural insecticide. On December 3, 1984, either by accident or by sabotage, a valve was opened that admitted water to a large tank of methyl isocyanate. The pressure and temperature within the tank rose dramatically, and pressure-relief valves opened to keep the tank from bursting. A large quantity of methyl isocyanate rushed out through the pressure-relief valves, and the vapors flowed with the breeze into populated areas, killing about 2500 people and injuring many more. (a) Write an equation for the reaction that took place in the tank. Explain why the pressure and temperature rose dramatically. (b) Propose a mechanism for the reaction you wrote in part (a). (c) Propose an alternative synthesis of Sevin®. Unfortunately, the most common alternative synthesis uses phosgene, a gas that is even more toxic than methyl isocyanate.

Problem 63SP The mass spectra of acid derivatives follow the principles shown in Chapter 18 for other carbonyl compounds and for alkoxy groups. Both McLafferty rearrangements and alpha-cleavages are common. The mass spectrum for butyl butanoate shows two prominent even-mass fragments at m/z 88 and m/z 60. Propose structures for these two fragments, and show what fragmentations produce them.

A chemist was called to an abandoned aspirin factory to determine the contents of a badly corroded vat. Knowing that two salvage workers had become ill from breathing the fumes, she put on her breathing apparatus as soon as she noticed an overpowering odor like that of vinegar but much more pungent. She entered the building and took a sample of the contents of the vat. The mass spectrum showed a molecular weight of 102, and the NMR spectrum showed only a singlet at \(\delta 2.15\). The IR spectrum, which appears here, left no doubt about the identity of the compound. Identify the compound, and suggest a method for its safe disposal. Equation transcription: Text transcription: delta 2.15

An unknown compound gives the NMR, IR, and mass spectra shown next. Propose a structure, and show how it is consistent with the observed absorptions. Show fragmentations that account for the prominent ion at \(m / z 69\) and the smaller peak at \(m / z 99\). Equation transcription: Text transcription: m / z 69 m / z 99

An unknown compound gives a mass spectrum with a weak molecular ion at \(m / z 113\) and a prominent ion at \(m / z 68\). Its NMR and IR spectra are shown here. Determine the structure, and show how it is consistent with the observed absorptions. Propose a favorable fragmentation to explain the prominent MS peak at \(m / z 68\). Equation transcription: Text transcription: m / z 113 m / z 68