Organic chemistry with biological applications

John E. McMurry

Chapter 15 Carboxylic Acids and Nitriles - all with Video Answers

Educators

Chapter Questions

10:31

Problem 1

Give IUPAC names for the following compounds:

Ricajoy Montero

Numerade Educator

06:10

Draw structures corresponding to the following IUPAC names:
(a) 2,3-Dimethylhexanoic acid
(b) 4 -Methylpentanoic acid
(c) trans-Cyclobutane-1,2-dicarboxylic acid
(d) $o$ -Hydroxybenzoic acid
(e) $(9 Z, 12 Z)$ -Octadeca-9,12-dienoic acid
(f) Pent-2-enenitrile

Ian Kaigh

Numerade Educator

05:30

Problem 3

Assume you have a mixture of naphthalene and benzoic acid that you want to separate. How might you take advantage of the acidity of one component in the mixture to effect a separation?

Ian Kaigh

Numerade Educator

07:19

Problem 4

The $K_{\mathrm{a}}$ for dichloroacetic acid is $3.32 \times 10^{-2} .$ Approximately what percentage of the acid is dissociated in a $0.10 \mathrm{M}$ aqueous solution?

Ian Kaigh

Numerade Educator

11:51

Problem 5

Calculate the percentages of dissociated and undissociated forms present in the following solutions:
(a) $0.0010 \mathrm{M}$ glycolic acid $\left(\mathrm{HOCH}_{2} \mathrm{CO}_{2} \mathrm{H} ; \mathrm{p} K_{\mathrm{a}}=3.83\right)$ at $\mathrm{pH}=4.50$
(b) $0.0020 \mathrm{M}$ propanoic acid $\left(\mathrm{p} K_{\mathrm{a}}=4.87\right)$ at $\mathrm{pH}=5.30$

Ian Kaigh

Numerade Educator

02:39

Problem 6

Which would you expect to be a stronger acid, the lactic acid found in tired muscles or acetic acid? Explain.

Ian Kaigh

Numerade Educator

04:01

Problem 7

Dicarboxylic acids have two dissociation constants, one for the initial dissociation into a monoanion and one for the second dissociation into a dianion. For oxalic acid, $\mathrm{HO}_{2} \mathrm{C}-\mathrm{CO}_{2} \mathrm{H}$, the first ionization constant is $\mathrm{pK}_{\mathrm{a} 1}=1.2$ and the second ionization constant is $\mathrm{p} K_{\mathrm{a} 2}=4.2$. Why is the second carboxyl group so much less acidic than the first?

Ian Kaigh

Numerade Educator

04:00

Problem 8

The $\mathrm{p} K_{\mathrm{a}}$ of $p$ -cyclopropylbenzoic acid is $4.45 .$ Is cyclopropylbenzene likely to be more reactive or less reactive than benzene toward electrophilic bromination? Explain.

Ian Kaigh

Numerade Educator

02:54

Problem 9

Rank the following compounds in order of increasing acidity. Don't look at a table of $\mathrm{p} K_{\mathrm{a}}$ data to help with your answer.
(a) Benzoic acid, $p$ -methylbenzoic acid, $p$ -chlorobenzoic acid
(b) $p$ -Nitrobenzoic acid, acetic acid, benzoic acid

Ian Kaigh

Numerade Educator

03:26

Problem 10

How would you prepare the following carboxylic acids?
(a) $\left(\mathrm{CH}_{3}\right)_{3} \mathrm{CCO}_{2} \mathrm{H}$ from $\left(\mathrm{CH}_{3}\right)_{3} \mathrm{CCl}$
(b) $\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CO}_{2} \mathrm{H}$ from $\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{Br}$

Isaac Huidobro

Numerade Educator

01:41

Problem 11

How might you prepare 2 -phenylethanol from benzyl bromide? More than one step is needed.

Mikayla Stephens

Numerade Educator

02:55

Problem 12

How would you prepare the following carbonyl compounds from a nitrile?

Nicholas Sacco

Numerade Educator

00:54

Problem 13

How would you prepare 4-methylpentan-1-ol starting with a nitrile? More than one step is needed

Grigoriy Sereda

Numerade Educator

02:44

Problem 14

Cyclopentanecarboxylic acid and 4 -hydroxycyclohexanone have the same formula $\left(\mathrm{C}_{6} \mathrm{H}_{10} \mathrm{O}_{2}\right)$, and both contain an $-\mathrm{OH}$ and a $\mathrm{C}=\mathrm{O}$ group. How could you distinguish between them by IR spectroscopy?

Ian Kaigh

Numerade Educator

04:47

Problem 15

How could you distinguish between the isomers cyclopentanecarboxylic acid and 4 -hydroxycyclohexanone by ${ }^{1} \mathrm{H}$ and ${ }^{13} \mathrm{C}$ NMR spectroscopy? (See Problem 15.14.

Ian Kaigh

Numerade Educator

05:42

Problem 16

Give IUPAC names for the following carboxylic acids (red-brown $=\mathrm{Br}$ ):

Ian Kaigh

Numerade Educator

03:05

Problem 17

Would you expect the following carboxylic acids to be more acidic or less acidic than benzoic acid? Explain. (Red-brown $=\mathrm{Br}$.)

Ian Kaigh

Numerade Educator

03:11

Problem 18

The following carboxylic acid can't be prepared from an alkyl halide by either the nitrile hydrolysis route or the Grignard carboxylation route. Explain.

Ian Kaigh

Numerade Educator

03:52

Problem 19

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.

Ian Kaigh

Numerade Educator

03:52

Problem 20

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.

Ian Kaigh

Numerade Educator

07:56

Problem 21

Draw structures corresponding to the following IUPAC names:
(a) cis-Cyclohexane-1,2-dicarboxylic acid
(b) Heptanedioic acid
(c) Hex-2-en-4-ynoic acid
(d) 4-Ethyl-2-propyloctanoic acid
(e) 3-Chlorophthalic acid
(f) Triphenylacetic acid
(g) Cyclobut-2-enecarbonitrile
(h) $m$ -Benzovlbenzonitrile

Ian Kaigh

Numerade Educator

08:53

Problem 22

Draw and name the following:
(a) The eight carboxylic acids with the formula $\mathrm{C}_{6} \mathrm{H}_{12} \mathrm{O}_{2}$
(b) Three nitriles with the formula $\mathrm{C}_{5} \mathrm{H}_{7} \mathrm{~N}$

Ian Kaigh

Numerade Educator

03:29

Problem 23

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 $-\mathrm{CH}_{2} \mathrm{NH}_{2} .$ ) Draw the structure of pregabalin.

Ian Kaigh

Numerade Educator

02:51

Problem 24

Isocitric acid, an intermediate in the citric acid cycle of food metabolism, has the systematic name $(2 R, 3 S)$ -3-carboxy-2-hydroxypentanedioic acid. Draw the structure.

Ian Kaigh

Numerade Educator

04:02

Problem 25

Order the compounds in each set in order of increasing acidity:
(a) Acetic acid, oxalic acid, formic acid
(b) $p$ -Bromobenzoic acid, $p$ -nitrobenzoic acid, 2,4 -dinitrobenzoic acid
(c) Fluoroacetic acid, 3 -fluoropropanoic acid, 4 -fluorobutanoic acid

Ian Kaigh

Numerade Educator

05:01

Problem 26

Arrange the compounds in each set in order of increasing basicity
(a) Magnesium acetate, magnesium hydroxide, methylmagnesium bromide
(b) Sodium benzoate, sodium $p$ -nitrobenzoate, sodium acetylide
(c) Lithium hydroxide, lithium ethoxide, lithium formate

Ian Kaigh

Numerade Educator

02:45

Problem 27

Calculate $K_{\mathrm{a}}$ 's for the following acids:
(a) Citric acid, $\mathrm{pK}_{\mathrm{a}}=3.14$
(b) Tartaric acid, $\mathrm{pK}_{\mathrm{a}}=2.98$

Ian Kaigh

Numerade Educator

04:11

Problem 28

Thioglycolic acid, $\mathrm{HSCH}_{2} \mathrm{CO}_{2} \mathrm{H}$, a substance used in depilatory agents (hair removers) has $\mathrm{pK}_{\mathrm{a}}=3.42 .$ What is the percent dissociation of thioglycolic acid in a buffer solution at $\mathrm{pH}=3.00 ?$

Ian Kaigh

Numerade Educator

08:26

Problem 29

In humans, the final product of purine degradation from DNA is uric acid, $\mathrm{p} K_{\mathrm{a}}=5.61$, which is excreted in the urine. What is the percent dissociation of uric acid in urine at a typical $\mathrm{pH}=6.0 ?$ Why do you think uric acid is acidic even though it does not have a $\mathrm{CO}_{2} \mathrm{H}$ group?

Ian Kaigh

Numerade Educator

03:14

Problem 30

Following are some $\mathrm{pK}_{\mathrm{a}}$ data for simple dibasic acids. 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?
$
\begin{array}{llcc}
\text { Name } & \text { Structure } & \mathbf{p} \boldsymbol{K}_{\mathbf{a} 1} & \mathbf{p} \boldsymbol{K}_{\mathbf{a} 2} \\
\hline \text { Oxalic } & \mathrm{HO}_{2} \mathrm{CCO}_{2} \mathrm{H} & 1.2 & 4.2 \\
\text { Succinic } & \mathrm{HO}_{2} \mathrm{C}\left(\mathrm{CH}_{2}\right)_{2} \mathrm{CO}_{2} \mathrm{H} & 4.2 & 5.6 \\
\text { Adipic } & \mathrm{HO}_{2} \mathrm{C}\left(\mathrm{CH}_{2}\right)_{4} \mathrm{CO}_{2} \mathrm{H} & 4.4 & 5.4
\end{array}
$

Ian Kaigh

Numerade Educator

04:02

Problem 31

Order the compounds in each of the following sets according to increasing acidity:
(a) Acetic acid, phenol, benzoic acid
(b) Benzoic acid, phenol, $p$ -bromobenzoic acid
(c) Chloroacetic acid, propanoic acid, difluoroacetic acid

Ian Kaigh

Numerade Educator

06:51

Problem 32

How could you convert butanoic acid into the following compounds? More than one step may be required.
(a) Butan-1-ol
(b) 1 -Bromobutane
(c) Pentanoic acid
(d) But-1-ene

Ian Kaigh

Numerade Educator

05:34

Problem 33

How could you convert each of the following compounds into butanoic acid? More than one step may be required.
(a) Butan-1-ol
(b) 1-Bromobutane
(c) But-1-ene
(d) 1-Bromopropane

Ian Kaigh

Numerade Educator

03:43

Problem 34

How could you convert butanenitrile into the following compounds? More than one step may be required.
(a) Butan-1-ol
(b) Butanal
(c) Pentanoic acid

Ian Kaigh

Numerade Educator

07:20

Problem 35

How would you prepare the following compounds from benzene? More than one step is required in each case.
(a) $m$ -Chlorobenzoic acid
(b) $p$ -Bromobenzoic acid
(c) Phenylacetic acid, $\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CH}_{2} \mathrm{CO}_{2} \mathrm{H}$

Ian Kaigh

Numerade Educator

03:00

Problem 36

Predict the product of the reaction of $p$ -methylbenzoic acid with each of the following:
(a) $\mathrm{CH}_{3} \mathrm{MgBr}$ in ether, then $\mathrm{H}_{3} \mathrm{O}^{+}$
(b) $\mathrm{KMnO}_{4}, \mathrm{H}_{3} \mathrm{O}^{+}$
(c) $\mathrm{LiAlH}_{4},$ then $\mathrm{H}_{3} \mathrm{O}^{+}$

Ian Kaigh

Numerade Educator

05:29

Problem 37

Using ${ }^{13} \mathrm{CO}_{2}$ as your only source of labeled carbon, along with any other compounds needed, how would you synthesize the following compounds?
(a) $\mathrm{CH}_{3} \mathrm{CH}_{2}{ }^{13} \mathrm{CO}_{2} \mathrm{H}$
(b) $\mathrm{CH}_{3}{ }^{13} \mathrm{CH}_{2} \mathrm{CO}_{2} \mathrm{H}$

Ian Kaigh

Numerade Educator

03:22

Problem 38

Which method-Grignard carboxylation or nitrile hydrolysis-would you use for each of the following reactions? Explain.

Ian Kaigh

Numerade Educator

05:09

Problem 39

Hexane-1,6-diamine, a starting material needed for making nylon, can be made from buta-1,3-diene. How would you accomplish this synthesis?

Ian Kaigh

Numerade Educator

04:26

Problem 40

How would you carry out the following transformations?

Kexin Yang

Numerade Educator

04:04

Problem 41

Propose a structure for a compound $\mathrm{C}_{6} \mathrm{H}_{12} \mathrm{O}_{2}$ that dissolves in dilute $\mathrm{NaOH}$ and shows the following ${ }^{1} \mathrm{H}$ NMR spectrum: $1.08 \delta(9 \mathrm{H},$ singlet $)$ $2.2 \delta(2 \mathrm{H},$ singlet $)$, and $11.2 \delta$ ( $1 \mathrm{H}$, singlet).

Ian Kaigh

Numerade Educator

02:46

Problem 42

What spectroscopic method could you use to distinguish among the following three isomeric acids? Tell what characteristic features you would expect for each acid.

Ian Kaigh

Numerade Educator

04:35

Problem 43

How could you use NMR (either ${ }^{13} \mathrm{C}$ or ${ }^{1} \mathrm{H}$ ) to distinguish between the following isomeric pairs?

Ian Kaigh

Numerade Educator

05:49

Problem 44

Compound A, $\mathrm{C}_{4} \mathrm{H}_{8} \mathrm{O}_{3}$, has infrared absorptions at 1710 and 2500 to $3100 \mathrm{~cm}^{-1}$ and has the ${ }^{1} \mathrm{H}$ NMR spectrum shown. Propose a structure for $\mathbf{A}$.

Ian Kaigh

Numerade Educator

02:33

Problem 45

Calculate $\mathrm{pK}_{\mathrm{a}}$ 's for the following acids:
(a) Lactic acid, $K_{\mathrm{a}}=8.4 \times 10^{-4}$
(b) Acrylic acid, $K_{\mathrm{a}}=5.6 \times 10^{-6}$

Ian Kaigh

Numerade Educator

02:24

Problem 46

Nitriles can be prepared from aldehydes by a two-step procedure that involves formation of an imine with $\mathrm{NH}_{2} \mathrm{OH}$, followed by dehydration with SOCl $_{2}$. Show the mechanism of the reaction.

Lottie Adams

Numerade Educator

01:30

Problem 47

In plants, terpenes (see Something Extra in Chapter 7 ) are biosynthesized by a pathway that involves loss of $\mathrm{CO}_{2}$ from 3 -phosphomevalonate 5 -diphosphate to yield isopentenyl diphosphate. Use curved arrows to show the mechanism of this reaction.

Ian Kaigh

Numerade Educator

02:54

Problem 48

A chemist in need of 2,2 -dimethylpentanoic acid decided to synthesize some by reaction of 2 -chloro-2-methylpentane with $\mathrm{NaCN}$, 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?

Ian Kaigh

Numerade Educator

05:46

Problem 49

Show how you might prepare the anti-inflammatory agent ibuprofen starting from isobutylbenzene. More than one step is needed.

Anupa Sharad Medhekar

Numerade Educator

08:56

Problem 50

Cyanogenic glycosides, such as lotaustralin (Section 15-7), release hydrogen cyanide, HCN, when treated with aqueous acid. The reaction occurs by hydrolysis of the acetal linkage to form a cyanohydrin-a compound with a hydroxyl group and a cyano group bonded to the same carbon. The cyanohydrin then expels HCN and gives a carbonyl compound.
(a) Show the mechanism of the acetal hydrolysis (see Section $14-8$ ) and the structure of the cyanohydrin that results.
(b) Propose a mechanism for the loss of HCN, and show the structure of the carbonyl compound that forms.

Ian Kaigh

Numerade Educator

10:39

Problem 51

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 $15-7$, and then write all the steps involved in the acid-catalyzed reaction, using curved arrows to represent electron flow in each step.

Ian Kaigh

Numerade Educator

03:00

Problem 52

Predict the product of reaction of lithocholic acid, a steroid found in human bile, with each of the following reagents. Don't worry about the size of the molecule; concentrate on the functional groups.
(a) $\mathrm{CrO}_{3}, \mathrm{H}_{3} \mathrm{O}^{+}$
(b) $\mathrm{CH}_{3} \mathrm{MgBr}$, then $\mathrm{H}_{3} \mathrm{O}^{+}$
(c) $\operatorname{LiAlH}_{4}$, then $\mathrm{H}_{3} \mathrm{O}^{+}$

Ian Kaigh

Numerade Educator

05:58

Problem 53

The $\mathrm{pK}_{\mathrm{a}}$ 's of five $p$ -substituted benzoic acids $\left(\mathrm{YC}_{6} \mathrm{H}_{4} \mathrm{CO}_{2} \mathrm{H}\right)$ follow. Rank the corresponding substituted benzenes $\left(\mathrm{YC}_{6} \mathrm{H}_{5}\right)$ in order of their increasing reactivity toward electrophilic aromatic substitution. If benzoic acid has $\mathrm{pK}_{\mathrm{a}}=4.19$, which of the substituents are activators and which are deactivators?

Ian Kaigh

Numerade Educator

05:18

Problem 54

The following $\mathrm{pK}_{\mathrm{a}}$ 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.

Ian Kaigh

Numerade Educator

02:19

Problem 55

Identify the missing reagents $\mathbf{a}-\mathbf{e}$ in the following scheme:

Madi Sousa

Numerade Educator

03:08

Problem 56

2-Bromo-6,6-dimethylcyclohexanone gives 2,2-dimethylcyclopentanecarboxylic acid on treatment with aqueous $\mathrm{NaOH}$ followed by acidification, a process called the Favorskii reaction. The reaction takes place by initial nucleophilic addition to the carbonyl group, followed by a rearrangement with loss of bromide ion. Propose a mechanism.

Ian Kaigh

Numerade Educator

06:51

Problem 57

Propose a structure for a compound, $\mathrm{C}_{4} \mathrm{H}_{7} \mathrm{~N}$, that has the following IR and ${ }^{1} \mathrm{H}$ NMR spectra:

Tom Rutherford

Numerade Educator

04:22

Problem 58

The two ${ }^{1} \mathrm{H}$ NMR spectra shown here belong to crotonic acid (trans$\mathrm{CH}_{3} \mathrm{CH}=\mathrm{CHCO}_{2} \mathrm{H}$ ) and methacrylic acid $\left[\mathrm{H}_{2} \mathrm{C}=\mathrm{C}\left(\mathrm{CH}_{3}\right) \mathrm{CO}_{2} \mathrm{H}\right] .$ Which spectrum corresponds to which acid? Explain.

Ian Kaigh

Numerade Educator

06:20

Problem 59

Propose structures for carboxylic acids that show the following peaks in their ${ }^{13}$ C NMR spectra. Assume that the kinds of carbons $\left(1^{\circ}, 2^{\circ}, 3^{\circ},\right.$ or $4^{\circ}$ ) have been assigned by DEPT-NMR.
(a) $\mathrm{C}_{7} \mathrm{H}_{12} \mathrm{O}_{2}: 25.5 \delta\left(2^{\circ}\right), 25.9 \delta\left(2^{\circ}\right), 29.0 \delta\left(2^{\circ}\right), 43.1 \delta\left(3^{\circ}\right), 183.0 \delta\left(4^{\circ}\right)$
(b) $\mathrm{C}_{8} \mathrm{H}_{8} \mathrm{O}_{2}: 21.4 \delta\left(1^{\circ}\right), 128.3 \delta\left(4^{\circ}\right), 129.0 \delta\left(3^{\circ}\right), 129.7 \delta\left(3^{\circ}\right), 143.1 \delta$
$\left(4^{\circ}\right), 168.2 \delta\left(4^{\circ}\right)$

Ian Kaigh

Numerade Educator

04:39

Problem 60

We'll see in the next chapter that carboxylic acids react with alcohols to yield esters: $\mathrm{RCO}_{2} \mathrm{H}+\mathrm{R}^{\prime} \mathrm{OH} \rightarrow \mathrm{RCO}_{2} \mathrm{R}^{\prime}$. Propose a mechanism for the following reaction.

Ricajoy Montero

Numerade Educator

03:14

Problem 61

Carboxylic acids having a second carbonyl group two atoms away lose $\mathrm{CO}_{2}$ ( 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.

Ian Kaigh

Numerade Educator