(a) The Key Mechanism for Fischer esterification omitted

A student synthesized Compound (below). To purify the compound, he extracted it into aqueous base and then acidified the solution to protonate the acid so that he could extract it back into ether. When he evaporated the ether, he found that his product had been converted entirely into Compound \(\mathrm{CH}_{3}\) \(\mathrm{CH}_{2} \mathrm{CO}_{2} \mathrm{H}\) \(O H\) (a) What is the functional group that forms the ring in Compound 1? In Compound 2? (b) How many carbon atoms are there in Compound 1? In Compound 2? Where did the other carbon atoms go? (c) When did the reaction occur: When the student added the base, or when he added the acid? (d) Propose a mechanism for the conversion of Compound 1 to Compound 2. Equation transcription: Text transcription: {CH}{3} {CH}{2}{CO}{2}{H} O H

Suppose you have just synthesized heptanoic acid from heptan-1-ol. The product is contam- inated by sodium dichromate, sulfuric acid, heptan-1-ol, and possibly heptanal. Explain how you would use acid–base extractions to purify the heptanoic acid. Use a chart, like that in Figure 20-3, to show where the impurities are at each stage.

Problem 1P Draw the structures of the following carboxylic acids. (a) ?-methylbutyric acid (b) 2-bromobutanoic acid (c) 4-aminopentanoic acid (d) cis-4-phenylbut-2-enoic acid (e) trans-2-methylcyclohexanecarboxylic acid (f) 2,3-dimethylfumaric acid (g) m-chlorobenzoic acid (h) 3-methylphthalic acid (i) ?-aminoadipic acid (j) 3-chloroheptanedioic acid (k) 4-oxoheptanoic acid (l) phenylacetic acid

Problem 5P Phenols are less acidic than carboxylic acids, with values of pKa around 10. Phenols are deprotonated by (and therefore soluble in) solutions of sodium hydroxide but not by solutions of sodium bicarbonate. Explain how you would use extractions to isolate the three pure compounds from a mixture of p-cresol (p-methylphenol), cyclohexanone, and benzoic acid.

Rank the compounds in each set in order of increasing acid strength. 1. \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{COOH}\) \(\mathrm{CH}_{3} \mathrm{CHBrCOOH}\) \(\mathrm{CH}_{3} \mathrm{CBr}_{2} \mathrm{COOH}\) 2. \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CHBrCOOH}\) \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CHBrCH}_{2} \mathrm{COOH}\) \(\mathrm{CH}_{3} \mathrm{CHBrCH}_{2} \mathrm{CH}_{2} \mathrm{COOH}\) 3. \(\mathrm{CH}_{3} \mathrm{CHCOOH}\) Equation transcription: Text transcription: {CH}{3}{CH}{2}{COOH} {CH}{3}{CHBrCOOH} {CH}{3}{CBr}{2}{COOH} {CH}{3}{CH}{2}{CH}{2}{CHBrCOOH} {CH}{3}{CH}{2}{CHBrCH}{2}{COOH} {CH}{3}{CHBrCH}{2}{CH}{2}{COOH} {CH}{3}{CHCOOH}

Name the following carboxylic acids (when possible, give both a common name and a systematic name). \(\mathrm{COOH}\) \(\mathrm{CH}_{2} \mathrm{CH}_{3}\) \(\mathrm{CH}_{3}\) \(\text { HOOC }\) \(\mathrm{COOH}\) \(H_{3} C\) Equation transcription: Text transcription: {COOH} {CH}{2}{CH}{3} {CH}{3} { HOOC } {COOH} H{3} C

The proton and \(13 c\) NMR spectra of a compound of formula are shown here. Determine the structure of this amine, and give peak assignments for all of the protons in the structure. Equation transcription: Text transcription: 13 c

Problem 9P Draw all four resonance forms of the fragment at m/z 73 in the mass spectrum of pentanoic acid.

Problem 6P Oxidation of a primary alcohol to an aldehyde usually gives some over-oxidation to the carboxylic acid. Assume you have used PCC to oxidize pentan-1-ol to pentanal. (a) Show how you would use acid–base extraction to purify the pentanal. (b) Which of the expected impurities cannot be removed from pentanal by acid–base extractions? How would you remove this impurity?

The IR spectrum of trans-oct-2-enoic acid is shown. Point out the spectral characteristics that allow you to tell that this is a carboxylic acid, and show which features lead you to conclude that the acid is unsaturated and conjugated.

(a) Why do most long-chain fatty acids show a large peak in the mass spectrum at m/z 60? (b) Use equations to explain the prominent peaks at \(m / z 74\) and \(m / z 87\) in the mass spectrum of 2-methylpentanoic acid. (c) Why doesn’t the mass spectrum of 2-methylpentanoic acid show a large peak at \(m / z 60\)? Equation transcription: Text transcription: m / z 74 m / z 87 m / z 60

Problem 12P (a) The Key Mechanism for Fischer esterification omitted some important resonance forms of the intermediates shown in brackets. Complete the mechanism by drawing all the resonance forms of these two intermediates. (b) Propose a mechanism for the acid-catalyzed reaction of acetic acid with ethanol to give ethyl acetate. (c) The principle of microscopic reversibility states that a forward reaction and a reverse reaction taking place under the same conditions (as in an equilibrium) must follow the same reaction pathway in microscopic detail. The reverse of the Fischer esterification is the acid-catalyzed hydrolysis of an ester. Propose a mechanism for the acid-catalyzed hydrolysis of ethyl benzoate, PhCOOCH2CH3.

Most of the Fischer esterification mechanism is identical with the mechanism of acetal formation. The difference is in the final step, where a carbocation loses a proton to give the ester. Write mechanisms for the following reactions, with the comparable steps directly above and below each other. Explain why the final step of the esterification (proton loss) cannot occur in acetal formation, and show what happens instead.

Show how you would synthesize the following carboxylic acids, using the indicated starting materials. (a) oct-4-ynebutanoic acid (b) trans-cyclodecene decanedioic acid (c) bromobenzene phenylacetic acid (d) butan-2-ol 2-methylbutanoic acid (e) p-xylene terephthalic acid l ( f ) allyl iodide but-3-enoic acid

Problem 14P A carboxylic acid has two oxygen atoms, each with two nonbonding pairs of electrons. (a) Draw the resonance forms of a carboxylic acid that is protonated on the hydroxyl oxygen atom. (b) Compare the resonance forms with those given previously for an acid protonated on the carbonyl oxygen atom. (c) Explain why the carbonyl oxygen atom of a carboxylic acid is more basic than the hydroxyl oxygen.

Problem 15P Show how Fischer esterification might be used to form the following esters. In each case, suggest a method for driving the reaction to completion. (a) methyl salicylate (b) methyl formate (bp 32 °C) (c) ethyl phenylacetate

The mechanism of the Fischer esterification was controversial until 1938, when Irving Roberts and Harold Urey of Columbia University used isotopic labeling to follow the alcohol oxygen atom through the reaction. A catalytic amount of sulfuric acid was added to a mixture of 1 mole of acetic acid and 1 mole of special methanol containing the heavy isotope of oxygen. After a short period, the acid was neutralized to stop the reaction, and the components of the mixture were separated. (a) Propose a mechanism for this reaction. (b) Follow the labeled \({ }^{18} \mathrm{O}\) atom through your mechanism, and show where it will be found in the products. (c) The \({ }^{18} \mathrm{O}\) isotope is not radioactive. Suggest how you could experimentally determine the amounts \({ }^{18} \mathrm{O}\) of in the separated components of the mixture. Equation transcription: Text transcription: ^{18}{O}

Problem 17P (a) The solution given for Solved Problem 20-1 was missing some important resonance forms of the intermediates shown in brackets. Complete this mechanism by drawing all the resonance forms of these intermediates. Do your resonance forms help to explain why this reaction occurs under very mild conditions (water with a tiny trace of acid)? (b) Finish the solution for Solved Problem 20-1 by providing a mechanism for the acidcatalyzed hydrolysis of ethyl formate. Reference: Problem 20-1: Draw the structures of the following carboxylic acids. (a) ?-methylbutyric acid (b) 2-bromobutanoic acid (c) 4-aminopentanoic acid (d) cis-4-phenylbut-2-enoic acid (e) trans-2-methylcyclohexanecarboxylic acid (f) 2,3-dimethylfumaric acid (g) m-chlorobenzoic acid (h) 3-methylphthalic acid (i) ?-aminoadipic acid (j) 3-chloroheptanedioic acid (k) 4-oxoheptanoic acid (l) phenylacetic acid

Show how to synthesize the following compounds, using appropriate carboxylic acids and amines. \(\mathrm{N}\left(\mathrm{CH}_{2} \mathrm{CH}_{3}\right)_{2}\) \(N H-C-C H_{3}\) \(N\left(C H_{3}\right)_{2}\) Equation transcription: Text transcription: {N}({CH}{2}{CH}{3}){2} N H-C-C H{3} N(C H{3}){2}

Problem 20P Propose a mechanism for conversion of the dianion to the ketone under mildly acidic conditions.

Problem 21P Show how the following ketones might be synthesized from the indicated acids, using any necessary reagents. (a) propiophenone from propionic acid (two ways, using alkylation of the acid and using Friedel–Crafts acylation) (b) methyl cyclohexyl ketone from cyclohexanecarboxylic acid

Show how you would synthesize the following compounds from the appropriate carboxylic acids or acid derivatives. \(\mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{OH}\) \(\mathrm{CH}_{2} \mathrm{CHO}\) \(\mathrm{CH}_{2} \mathrm{OH}\) Equation transcription: Text transcription: {CH}{2}{CH}{2}{OH} {CH}{2}{CHO} {CH}{2}{OH}

Problem 22P Propose a mechanism for the reaction of benzoic acid with oxalyl chloride. This mechanism begins like the thionyl chloride reaction, to give a reactive mixed anhydride. Nucleophilic acyl substitution by chloride ion gives a tetrahedral intermediate that eliminates a leaving group, which then fragments into carbon dioxide, carbon monoxide, and chloride ion.

Problem 23P Propose mechanisms for the nucleophilic acyl substitutions to form ethyl benzoate and N-methylacetamide as shown on the previous page.

Give the IUPAC names of the following compounds. \(\mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{C}=\mathrm{CCOOH}\) \(\mathrm{COOH}\) \(\mathrm{CH}_{3} \mathrm{CH}\left(\mathrm{NH}_{2}\right) \mathrm{CH}(\mathrm{OH}) \mathrm{COOH}\) \(\left(\mathrm{CH}_{3}\right) \mathrm{C}=\mathrm{CHCOOH}\) \(O_{2} N\) \(\mathrm{NO}_{2}\) Equation transcription: Text transcription: {CH}{2}{CH}{2}{C}={CCOOH} {COOH} {CH}{3}{CH}({NH}{2}){CH}({OH}){COOH} {CH}{3}{C}={CHCOOH} O{2} N {NO}{2}

Problem 24P Show how you would use an acid chloride as an intermediate to synthesize (a) N-phenylbenzamide (PhCONHPh) from benzoic acid and aniline. (b) phenyl propionate (CH3CH2COOPh) from propionic acid and phenol.

Give both IUPAC names and common names for the following compounds.

Problem 27SP Draw the structures of the following compounds. (a) ethanoic acid (b) terephthalic acid (c) magnesium formate (d) malonic acid (e) dichloroacetic acid (f) salicylic acid (g) zinc undecanoate (athlete’s-foot powder) (h) sodium benzoate (a food preservative) (i) sodium fluoroacetate (Compound 1080, a controversial coyote poison)

Problem 28SP Show how you would use extractions with a separatory funnel to separate a mixture of the following compounds: benzoic acid, phenol, benzyl alcohol, aniline.

Problem 29SP Arrange each group of compounds in order of increasing basicity. (a)CH 3 COO - , ClCH 2 COO - ,and PhO- (b) sodium acetylide, sodium amide, and sodium acetate (c) sodium benzoate, sodium ethoxide, and sodium phenoxide (d) pyridine, sodium ethoxide, sodium acetate

Problem 30SP Predict the products (if any) of the following acid–base reactions. (a) acetic acid + ammonia (b) phthalic acid + excess NaOH (c) p-toluic acid + potassium trifluoroacetate (d) ?-bromopropionic acid + sodium propionate (e) benzoic acid + sodium phenoxide

Rank the following isomers in order of increasing boiling point, and explain the reasons for your order of ranking. \(\mathrm{OCH}_{2} \mathrm{CH}_{2} \mathrm{OH}\) \(\mathrm{CH}_{3}-\mathrm{C}-\mathrm{OCH}_{2} \mathrm{CH}_{3}\) \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2}-\mathrm{C}-\mathrm{OH}\) Equation transcription: Text transcription: {OCH}{2}{CH}{2}{OH} {CH}{3}-{C}-{OCH}{2}{CH}{3} {CH}{3}{CH}{2}{CH}{2}-{C}-{OH}

Arrange each group of compounds in order of increasing acidity. (a) phenol, ethanol, acetic acid (b) p-toluenesulfonic acid, acetic acid, chloroacetic acid (c) benzoic acid, o-nitrobenzoic acid, m-nitrobenzoic acid (d) butyric acid, - bromobutyric acid, -bromobutyric acid \(\mathrm{COOH}\) \(\mathrm{CI}\) \(B r\) Equation transcription: Text transcription: {COOH} {CI} B r

Given the structure of ascorbic acid (vitamin C): (a) Is ascorbic acid a carboxylic acid? (b) Compare the acid strength of ascorbic acid \(\left(p K_{a}=4.71\right)\) with acetic acid. (c) Predict which proton in ascorbic acid is the most acidic. (d) Draw the form of ascorbic acid that is present in the body (aqueous solution,pH = 7.4 ). Equation transcription: Text transcription: (p K{a}=4.71)

Predict the products, if any, of the following reactions.

What do the following \(p K_{a}\)values tell you about the electron-withdrawing abilities of nitro, cyano, chloro, and hydroxyl groups? Equation transcription: Text transcription: p K{a}

Show how you would accomplish the following syntheses efficiently (you may use any necessary reagents). (a) trans-1-bromobut-2-ene trans-pent-3-enoic acid (two ways) (b) hex-3-ene propanoic acid (c) but-2-enal but-2-enoic acid (d) hexanoic acid hexanal

Predict the products and propose mechanisms for the following reactions.

When pure (S)-lactic acid is esterified by racemic butan-2-ol, the product is 2-butyl lactate, with the following structure: (a) Draw three-dimensional structures of the two stereoisomers formed, specifying the configuration at each asymmetric carbon atom. (Using your models may be helpful.) (b) Determine the relationship between the two stereoisomers you have drawn.

Show how you would accomplish the following multistep syntheses. You may use any additional reagents and solvents you need.

The following NMR spectra correspond to compounds of formulas (A) \(\mathrm{C}_{9} \mathrm{H}_{10} \mathrm{O}_{2}\), (B) \(\mathrm{C}_{4} \mathrm{H}_{6} \mathrm{O}_{2}), and (C) \(\mathrm{C}_{6} \mathrm{H}_{10} \mathrm{O}_{2}\), respectively. Propose structures, and show how they are consistent with the observed absorptions. Equation transcription: Text transcription: {C}{9}{H}{10}{O}{2} {C}{4}{H}{6} {O}{2} {C}{6}{H}{10}{O}{2}

In the presence of a trace of acid, -hydroxyvaleric acid forms a cyclic ester (lactone). \(\mathrm{HO}-\mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CH}_{2}-\mathrm{COOHS}\) -hydroxyvaleric acid (a) Give the structure of the lactone, called -valerolactone. (b) Propose a mechanism for the formation of -valerolactone. Equation transcription: Text transcription: {HO}-{CH}{2}{CH}{2}{CH}{2} {CH}{2}-{COOHS}

Two of the methods for converting alkyl halides to carboxylic acids are covered in Sections 20-8B and 20-8C. One is formation of a Grignard reagent followed by addition of carbon dioxide and then dilute acid. The other is substitution by cyanide ion, followed by hydrolysis of the resulting nitrile. For each of the following conversions, decide whether either or both of these methods would work, and explain why. Show the reactions you would use. \(C H_{2} B r\) \(B r\) \(\text { HO }\) Equation transcription: Text transcription: C H{2} B r B r { HO }

Problem 42SP (a) Hydrogen peroxide (HOOH) has a pKa of 11.6, making it roughly 10,000 times as strong an acid as water (pKa = 15.7 ). Explain why H2O2 is a stronger acid than H2O. (b) In contrast to part (a), peroxyacetic acid (pKa = 8.2 ) is a much weaker acid than acetic acid (pKa= 4.74). Explain why peroxyacetic acid is a weaker acid than acetic acid. (c) Peroxyacetic acid ( bp = 105oC) has a lower boiling point than acetic acid ( bp = 118oC), even though peroxyacetic acid has a higher molecular weight. Explain why peroxyacetic acid is more volatile than acetic acid.

The IR, NMR, and mass spectra are provided for an organic compound. (a) Consider each spectrum individually, and tell what characteristics of the molecule are apparent from that spectrum. (b) Propose a structure for the compound, and show how your structure fits the spectral data. *(c) Explain why an important signal is missing from the proton NMR spectrum.

(A true story) The manager of an organic chemistry stockroom prepared unknowns for a "Ketones and Aldehydes" experiment by placing two drops of the liquid unknowns in test tubes and storing the test tubes for several days until they were needed. One of the unknowns was misidentified by every student. This unknown was taken from a bottle marked "Heptaldehyde." The stockroom manager took an IR spectrum of the liquid in the bottle and found a sharp carbonyl stretch around \(1720 \mathrm{~cm}^{-1}\) and small, sharp peaks around 2710 and \(2810 \mathrm{~cm}^{-1}\). The students complained that their spectra showed no peaks at 2710 or \(2810 \mathrm{~cm}^{-1}\), but a broad absorption centered over the \(300 c m^{-1}\) region and a carbonyl peak around \(1715 \mathrm{~cm}^{-1}\). They also maintained that their samples are soluble in dilute aqueous sodium hydroxide. (a) Identify the compound in the stockroom manager's bottle and the compound in the students' test tubes. (b) Explain the discrepancy between the stockroom manager's spectrum and the students' results. (c) Suggest how this misunderstanding might be prevented in the future. Equation transcription: Text transcription: 1720 \mathrm{~cm}^{-1} 2810 \mathrm{~cm}^{-1} 300 c m^{-1} 1715 \mathrm{~cm}^{-1}

Problem 46SP The relative acidities of carboxylic acids (and, by inference, the stabilities of their carboxylate ions) have been used to compare the electron-donating and electron-withdrawing properties of substituents. These studies are particularly valuable to distinguish between inductive and resonance effects on the stabilities of compounds and ions. Some examples: (a) The pKa of phenylacetic acid is 4.31, showing that phenylacetic acid is a stronger acid than acetic acid. Is the phenyl group electron-donating or electron-withdrawing in the ionization of phenylacetic acid? (b) The phenyl group is a mild ortho, para-director in electrophilic aromatic substitution. Is the phenyl group electrondonating or electron-withdrawing in electrophilic aromatic substitution? How can you resolve the apparent contradiction? (c) 4-Methoxybenzoic acid is a weaker acid than benzoic acid, but methoxyacetic acid is a stronger acid than acetic acid. Explain this apparent contradiction. (d) Methyl groups are usually electron-donating, and propanoic acid is a weaker acid than acetic acid. Yet 2,6-dimethylbenzoic acid is a stronger acid than benzoic acid, but 2,6-dimethylphenol is a weaker acid than phenol. Explain these confusing experimental results.