Draw the important resonance contributors for both resonance-stabilized cations (in

Name the following carboxylic acid derivatives, giving both a common name and an IUPAC name where possible. (a) PhCOOCH2CH(CH3)2 (b) PhOCHO (c) PhCH(CH3)COOCH3 (d) PhNHCOCH2CH(CH3)2 (e) CH3CONHCH2Ph (f) CH3CH(OH)CH2CN (g) (CH3)2CHCH2COBr (h) Cl2CHCOCl (i) (CH3)2CHCOOCHO O O C (j) O O (k) PhCONH (l) O O O (m) OH CN (n) H H COOH CN (o) Br (p) COCl CH2CH3 N O CH3 (q) N CH3 O C (Hint: Named as a piperidine derivative.)

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

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?

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.

For each set of IR and NMR spectra, determine the structure of the unknown compound. Explain how your proposed structure fits the spectra. (a) C3H5NO (b) C5H8O2

(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.

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

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 (\(PhNHCOCH_3\)) (c) cyclohexanecarboxamide

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

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.

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.

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 following ring-opening transesterification. Use the mechanism in Problem 21-13 as a model.

(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.

Suppose we have some optically pure (R)-2-butyl acetate that has been labeled with the heavy 18O isotope at one oxygen atom as shown. CH3 C O C O CH2CH3 CH3 H 18 (a) Draw a mechanism for the hydrolysis of this compound under basic conditions. Predict which of the products will contain the 18O label. Also predict whether the butan-2-ol product will be pure (R), pure (S), or racemized. (b) Repeat part (a) for the acid-catalyzed hydrolysis of this compound. (c) Explain how you would prove experimentally where the 18O label appears in the products. (18O is not radioactive.)

(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.

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

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

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

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.

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

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.

(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.

Give the expected products of lithium aluminum hydride reduction of the following compounds (followed by hydrolysis). (a) butyronitrile (b) N-cyclohexylacetamide (c) e@caprolactam (d) O O N (d) H (e) N CH3 C CH2CH3 O (e) (f) CN

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

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

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.

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.

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

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

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

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. (a) Ph3COH (b) (PhCH2)2CHOH (c) PhCONHCH2CH3 (d) Ph2CHOH (e) PhCH2OH (f) PhCOOH (g) PhCH2COOCH(CH3)2 PhCH2 C(CH2CH3)2 OH (h) (i) HO(CH2) 8OH

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

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

Show how you would convert the following starting materials to the indicated nitriles: (a) phenylacetic acid \(\rightarrow\) phenylacetonitrile (b) phenylacetic acid \(\rightarrow\) 3-phenylpropionitrile (c) p-chloronitrobenzene \(\rightarrow\) p-chlorobenzonitrile

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

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

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.

Name carboxylic acid derivatives, draw the structures from their names.

Compare the physical properties of acid derivatives, and explain the unusually high boiling points and melting points of amides. Compare the relative reactivity of esters, thioesters, amides, nitriles, anhydrides, and acid chlorides. (Problems 21-51, 52, 59, 60, and 62)

Interpret the spectra of acid derivatives, and use spectral information to determine the structures. Show how the carbonyl stretching frequency in the IR depends on the structure of the acid derivative. (Problems 21-52, 61, 64, 65, 66, 67, 68, 69, and 70)

Propose single-step and multistep syntheses of acid derivatives from compounds containing other functional groups. Propose multistep synthesis using acid derivatives as starting materials and intermediates. (Problems 21-48, 50, 53, 54, 55, and 57)

Show how acid derivatives hydrolyze to carboxylic acids under either acidic or basic conditions. Explain why some acid derivatives (amides, for example) require much stronger conditions for hydrolysis than other derivatives.

Show how acid derivatives are easily interconverted by nucleophilic acyl substitution from more reactive derivatives to less reactive derivatives under acidic or basic conditions. Show how acid chlorides serve as activated intermediates to convert acids to other acid derivatives. (Problems 21-46, 49, 51, 58, and 63)

Predict the products, propose mechanisms for the reactions of carboxylic acid derivatives with reducing agents, alcohols, amines, and organometallic reagents such as Grignard, organolithium, and organocuprate reagents.

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) \(\gamma\)-hydroxyvaleronitrile (i) \(\alpha\)-bromobutyryl chloride (j) \(\beta\)-butyrolactone (k) phenyl isocyanate (l) cyclobutyl ethyl carbonate (m) \(\delta\)-caprolactam (n) trichloroacetic anhydride (o) ethyl N-methyl carbamate

Give appropriate names for the following compounds:

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 Ph CH CH2 NH2 + 1 equivalent of acetic anhydride OH (e) Ph CH CH2 NH2 + excess acetic anhydride OH

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.

Predict the products of saponification of the following esters.

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

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

Predict the products of the following reactions.

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.

An ether extraction of nutmeg gives large quantities of trimyristin, a waxy crystalline solid of melting point \(57^{\circ} \mathrm{C}\). The IR spectrum of trimyristin shows a very strong absorption at \(1733 \mathrm{~cm}^{-1}\). 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.

Two widely used pain relievers are aspirin and acetaminophen. Show how you would synthesize these drugs from phenol. O O NH aspirin COOH O C CH3 H O C CH3 acetaminophen

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

Grignard reagents add to carbonate esters as they add to other esters. (a) Predict the major product of the following reaction. diethyl carbonate CH3CH2 O C O CH2CH3 O (1) excess PhMgBr (2) H3O+ (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.

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) \(\text { hept-6-en-1-ol } \longrightarrow \varepsilon \text {-caprolactone }\) (b) methoxybenzene \(\longrightarrow\) p-methoxybenzamide (c) (d)

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?

In each part, rank the compounds in order of increasing rate of nucleophilic attack at C=O by a strong nucleophile like methoxide.

Explain this curious result. What does this reaction tell you about the relative reactivity of esters and ketones? 1 eq. CH3COOCH3 + 1 eq. PhMgBr 0.5 eq. CH3COOCH3 + 0.5 eq. Ph C OH Ph CH3

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.

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.

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.

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 d 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.

The mass spectrum of ethyl butyrate shows two even-numbered fragments: at m>z 60 and m>z 88. These ions can be explained by a double McLafferty rearrangement: an initial McLafferty followed by a second rearrangement on the ion from the first. Show the cyclic transition states implicated in the two rearrangements, as well as the structures of the expected ions of masses 88 and 60. (Hint: begin with the ester side.) O O ethyl butyrate, mw 116

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.

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.

The IR spectrum, 13C NMR spectrum, and 1 H NMR spectrum of an unknown compound (C6H8O3) appear next. Determine the structure, and show how it is consistent with the spectra.

An unknown compound of molecular formula \(C_5H_9NO\) gives the IR and NMR spectra shown here. The broad NMR peak at \(\delta 7.55\) disappears when the sample is shaken with \(D_2O\). Propose a structure, and show how it is consistent with the absorptions in the spectra.

(A true story.) A chemist wanted to make the ethyl ester of 2-formylbenzoic acid, but the spectra of the product did not meet her expectations. The IR of product Z had an ester carbonyl, but no aldehyde absorption nor any absorption in the OH region. The HNMR data are given. What is the structure of Z? Propose a mechanism for its formation.

Macrolide antibiotics, including erythromycin and azithromycin (Zithromax®), contain a large ring lactone. One of the largest ever reported is Gargantulide A, the structure of which was determined by the research group of Prof. William Gerwick of the Scripps Institution of Oceanography (Organic Letters, 2015, 17, 1377–1380). Isolated from a Streptomyces bacterium, it kills pathogenic bacteria like MRSA and Clostridium difficile, but it proved too toxic to the test animals to continue further testing. (a) Identify the lactone that makes this a macrolide structure. (b) How many rings does this structure contain? How many atoms are in the largest ring? (c) Many complex NMR experiments were used to determine the stereochemistry of most, but not all, of the chiral centers. How many chiral centers does the structure contain?