20.14: Additional Problems
- Page ID
- 459765
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)Visualizing Chemistry
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Problem 20-19
The following carboxylic acid can’t be prepared from an alkyl halide by either the nitrile hydrolysis route or the Grignard carboxylation route. Explain.
Electrostatic potential maps of anisole and thioanisole are shown. Which do you think is the stronger acid, p-methoxybenzoic acid or p-(methylthio)benzoic acid? Explain.
The following carboxylic acid can’t be prepared from an alkyl halide by either the nitrile hydrolysis route or the Grignard carboxylation route. Explain.
Electrostatic potential maps of anisole and thioanisole are shown. Which do you think is the stronger acid, p-methoxybenzoic acid or p-(methylthio)benzoic acid? Explain.
Mechanism Problems
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Problem 20-22
Predict the product(s) and write the mechanism of each of the following reactions:
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Problem 20-23
Predict the product(s) and write the mechanism of each of the following reactions:
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Problem 20-24
Predict the product(s) and write the complete mechanism of each of the following reactions:
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Problem 20-25
Acid-catalyzed hydrolysis of a nitrile to give a carboxylic acid occurs by initial protonation of the nitrogen atom, followed by nucleophilic addition of water. Review the mechanism of base-catalyzed nitrile hydrolysis in Section 20.7 and then predict the products for the following reactions. Write the steps involved in the acid-catalyzed reaction, using curved arrows.
(a)
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Problem 20-26
Nitriles can be converted directly to esters by the Pinner reaction, which first produces an iminoester salt that is isolated and then treated with water to give the final product. Propose a mechanism for the Pinner reaction using curved arrows to show the flow of electrons at each step.
cyanogenic glycosides, such as lotaustralin, release hydrogen cyanide, HCN, when treated with aqueous acid. The reaction occurs by hydrolysis of the acetal linkage to form a cyanohydrin, which then expels HCN and gives a carbonyl compound. (a)
Show the mechanism of the acetal hydrolysis and the structure of the cyanohydrin that results.
Propose a mechanism for the loss of HCN, and show the structure of the carbonyl compound that forms.
2-Bromo-6,6-dimethylcyclohexanone gives 2,2-dimethylcyclopentanecarboxylic acid on treatment with aqueous NaOH followed by acidification, a process called the Favorskii reaction. Propose a mechanism.
Naturally occurring compounds called terpenoids, which we’ll discuss in Section 27.5, are biosynthesized by a pathway that involves loss of CO2 from 3-phosphomevalonate 5-diphosphate to yield isopentenyl diphosphate. Use curved arrows to show the mechanism of this reaction.
In the Ritter reaction, an alkene reacts with a nitrile in the presence of strong aqueous sulfuric acid to yield an amide. Propose a mechanism.
Naming Carboxylic Acids and Nitriles
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cis-1,2-Cyclohexanedicarboxylic acid
Heptanedioic acidcis-1,2-Cyclohexanedicarboxylic acid
The eight carboxylic acids with the formula C6H12O2
Pregabalin, marketed as Lyrica, is an anticonvulsant drug that is also effective in treating chronic pain. The IUPAC name of pregabalin is (S)-3-(aminomethyl)-5-methylhexanoic acid. (An aminomethyl group is –CH2NH2.) Draw the structure of pregabalin.
Isocitric acid, an intermediate in the citric acid cycle of food metabolism, has the systematic name (2R,3S)-3-carboxy-2-hydroxypentanedioic acid. Draw the structure.
Acidity of Carboxylic Acids
In humans, the final product of purine degradation from DNA is uric acid, pKa = 5.61, which is excreted in the urine. What is the percent dissociation of uric acid in urine at a typical pH = 6.0? Why do you think uric acid is acidic even though it does not have a CO2H group? Some pKa data for simple dibasic acids is shown. How can you account for the fact that the difference between the first and second ionization constants decreases with increasing distance between the carboxyl groups? Reactions of Carboxylic Acids and Nitriles How would you carry out the following transformations? 1,6-Hexanediamine, a starting material needed for making nylon, can be made from 1,3-butadiene. How would you accomplish the synthesis?Acetic acid, oxalic acid, formic acid
Magnesium acetate, magnesium hydroxide, methylmagnesium bromide
Ka’s of the following acids:
(a)
Lactic acid, Ka = 8.4 × 10–4Ka’s of the following acids:
(a)
Citric acid, pKa = 3.14Thioglycolic acid, HSCH2CO2H, a substance used in depilatory agents (hair removers) has pKa = 3.42. What is the percent dissociation of thioglycolic acid in a buffer solution at pH = 3.0?
Name
Structure
pK1
pK2
Oxalic
HO2CCO2H
1.2
4.2
Succinic
HO2CCH2CH2CO2H
4.2
5.6
Adipic
HO2C(CH2)4CO2H
4.4
5.4
1-Butanol
1-Butanol
1-Butanol
m-Chlorobenzoic acid
p-methylbenzoic acid with each of the following:
(a)
LiAlH4, then H3O+13CO2 as your only source of labeled carbon, along with any other compounds needed, how would you synthesize the following compounds?
(a)
CH3CH213CO2H
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(c)
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3-Methyl-2-hexenoic acid (mixture of E and Z isomers) has been identified as the substance responsible for the odor of human sweat. Synthesize the compound from starting materials having five or fewer carbons.
Spectroscopy
What spectroscopic method could you use to distinguish among the following three isomeric acids? Tell what characteristic features you would expect for each acid. Compound A, C4H8O3, has infrared absorptions at 1710 and 2500 to 3100 cm–1 and has the 1H NMR spectrum shown. Propose a structure for A. General Problems Show how you might prepare the anti-inflammatory agent ibuprofen starting from isobutylbenzene. More than one step is needed. Propose a synthesis of the anti-inflammatory drug fenclorac from phenylcyclohexane. The pKa’s of five p-substituted benzoic acids (YC6H4CO2H) are listed below. Rank the corresponding substituted benzenes (YC6H5) in order of their increasing reactivity toward electrophilic aromatic substitution. If benzoic acid has pKa = 4.19, which of the substituents are activators and which are deactivators? The following pKa values have been measured. Explain why a hydroxyl group in the para position decreases the acidity while a hydroxyl group in the meta position increases the acidity. Identify the missing reagents a–f in the following scheme: Propose a structure for a compound, C4H7N, that has the following IR and 1H NMR spectra: Carboxylic acids having a second carbonyl group two atoms away lose CO2 (decarboxylate) through an intermediate enolate ion when treated with base. Write the mechanism of this decarboxylation reaction using curved arrows to show the electron flow in each step.Propose a structure for a compound C6H12O2 that dissolves in dilute NaOH and shows the following 1H NMR spectrum: 1.08 δ (9 H, singlet), 2.2 δ (2 H, singlet), and 11.2 δ (1 H, singlet).
13C or 1H) to distinguish between the following pairs of isomers?
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A chemist in need of 2,2-dimethylpentanoic acid decided to synthesize some by reaction of 2-chloro-2-methylpentane with NaCN, followed by hydrolysis of the product. After the reaction sequence was carried out, however, none of the desired product could be found. What do you suppose went wrong?
p-Aminobenzoic acid (PABA) was once widely used as a sunscreen agent. Propose a synthesis of PABA starting from toluene.
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Substituent Y
–Si(CH3)3
4.27
–CH═CHC≡N
4.03
–HgCH3
4.10
–OSO2CH3
3.84
–PCl2
3.59
(b)
1H NMR spectra shown here belong to crotonic acid (trans-CH3CH
C7H12O2: 25.5 δ (2°), 25.9 δ (2°), 29.0 δ (2°), 43.1 δ (3°), 183.0 δ (4°)