Organic chemistry with biological applications

John E. McMurry

Chapter 13

Alcohols, Phenols, and Thiols; Ethers and Sulfides - all with Video Answers

Educators

Chapter Questions

Problem 1

Give IUPAC names for the following compounds:

Ricajoy Montero

Ricajoy Montero

Numerade Educator

Problem 2

Draw structures corresponding to the following IUPAC names:
(a) 2-Ethylbut-2-en-1-ol
(b) Cyclohex-3-en-1-ol
(c) trans-3-Chlorocycloheptanol
(d) Pentane-1,4-dithiol
(e) 2,4-Dimethylphenol
(f) o-(2-Hydroxyethyl)phenol

Katie Miller

Numerade Educator

Problem 3

Rank the following substances in order of increasing acidity:
(a) Phenol, $p$ -methylphenol, $p$ -(trifluoromethyl)phenol
(b) Benzyl alcohol, phenol, $p$ -hydroxybenzoic acid

Katie Miller

Numerade Educator

Problem 4

$p$ -Nitrobenzyl alcohol is more acidic than benzyl alcohol, but $p$ -methoxybenzyl alcohol is less acidic. Explain.

Katie Miller

Numerade Educator

Problem 5

Which would you expect to be more acidic, methanethiol or thiophenol, $\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{SH}$ ? Explain.

Raghvendra Singh

Raghvendra Singh

Numerade Educator

Problem 6

Predict the products of the following reactions:

Grigoriy Sereda

Grigoriy Sereda

Numerade Educator

Problem 7

What reagent would you use to accomplish each of the following reactions?

Arun Bana

Numerade Educator

Problem 8

What carbonyl compounds give the following alcohols on reduction with LiAlH $_{4}$ ? Show all possibilities.

Katie Miller

Numerade Educator

Problem 9

Show the products obtained from addition of methylmagnesium bromide to the following compounds:
(a) Cyclopentanone
(b) Hexan-3-one

Katie Miller

Numerade Educator

Problem 10

Use a Grignard reaction to prepare the following alcohols:
(a) 2-Methylpropan-2-ol
(b) 1 -Methylcyclohexanol
(c) 2 -Phenylbutan-2-ol
(d) Benzyl alcohol

Katie Miller

Numerade Educator

Problem 11

Use the reaction of a Grignard reagent with a carbonyl compound to synthesize the adjacent compound:

Katie Miller

Numerade Educator

Problem 12

What product(s) would you expect from dehydration of the following alcohols with $\mathrm{POCl}_{3}$ in pyridine? Indicate the major product in each case.

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Rabia Bibi

Numerade Educator

Problem 13

What alcohols would give the following products on oxidation?

rb

Rabia Bibi

Numerade Educator

Problem 14

What products would you expect from oxidation of the following compounds with $\mathrm{CrO}_{3}$ in aqueous acid? With the Dess-Martin periodinane?
(a) Hexan-1-ol
(b) Hexan-2-ol
(c) Hexanal

Katie Miller

Numerade Educator

Problem 15

TMS ethers can be removed by treatment with fluoride ion as well as by acidcatalyzed hydrolysis. Propose a mechanism for the reaction of cyclohexyl TMS ether with LiF. Fluorotrimethylsilane is a product.

Katie Miller

Numerade Educator

Problem 16

But-2-ene-1-thiol is one component of skunk spray. How would you synthesize this substance from methyl but-2-enoate?

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 17

Name the following ethers and sulfides according to IUPAC rules:

Vasu Makani

Numerade Educator

Problem 18

Why do you suppose only symmetrical ethers are prepared by the sulfuric acid-catalyzed dehydration procedure? What product(s) would you expect if ethanol and propan-1-ol were allowed to react together? In what ratio would the products be formed if the two alcohols were of equal reactivity?

JC

Jared Cellini

Numerade Educator

Problem 19

How would you prepare the following ethers using a Williamson synthesis?
(a) Methyl propyl ether
(b) Anisole (methyl phenyl ether)
(c) Benzyl isopropyl ether
(d) Ethyl 2,2-dimethylpropyl ether

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 20

Rank the following halides in order of their reactivity in the Williamson synthesis:
(a) Bromoethane, 2-bromopropane, bromobenzene
(b) Chloroethane, bromoethane, 1 -iodopropene

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 21

Predict the products of the following reactions:

Grigoriy Sereda

Grigoriy Sereda

Numerade Educator

Problem 22

Write a mechanism for the acid-catalyzed cleavage of tert-butyl cyclohexyl ether with trifluoroacetic acid to yield cyclohexanol and 2 -methylpropene.

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 23

Predict the major product of the following reactions:

Susan Hallstrom

Susan Hallstrom

Numerade Educator

Problem 24

What product would you expect from Claisen rearrangement of but-2-enyl phenyl ether?

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 25

15-Crown-5 and 12 -crown- 4 ethers selectively complex $\mathrm{Na}^{+}$ and $\mathrm{Li}^{+}$, respectively. Make models of these crown ethers, and compare the sizes of the cavities.

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 26

Give IUPAC names for the following compounds:

Ricajoy Montero

Ricajoy Montero

Numerade Educator

Problem 27

Draw the structure of the carbonyl compound(s) from which each of the following alcohols might have been prepared, and show the products you would obtain by treatment of each alcohol with
(i) $\mathrm{NaH}$
(ii) $\mathrm{SOCl}_{2}$
and (iii) the Dess-Martin periodinane reagent:

Lottie Adams

Numerade Educator

Problem 28

Show the product, including stereochemistry that would result from $\mathrm{S}_{\mathrm{N}} 2$ reaction of the following epoxide with methylamine $\left(\mathrm{CH}_{3} \mathrm{NH}_{2}\right)$

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 29

Predict the product from reaction of the following substance (redbrown $=\mathrm{Br}$ ) with:
(a) $\mathrm{PBr}_{3}$
(b) Aqueous $\mathrm{H}_{2} \mathrm{SO}_{4}$
(c) SOCl $_{2}$
(d) Dess-Martin periodinane
(e) $\mathrm{Br}_{2}, \mathrm{FeBr}_{3}$

Katie Miller

Numerade Educator

Problem 30

Predict the product from reaction of the following substance with:
(a) $\mathrm{NaBH}_{4}$; then $\mathrm{H}_{3} \mathrm{O}^{+}$
(b) $\mathrm{LiAlH}_{4}$; then $\mathrm{H}_{3} \mathrm{O}^{+}$
(c) $2 \mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{MgBr}$; then $\mathrm{H}_{3} \mathrm{O}^{+}$

Ian Kaigh

Numerade Educator

Problem 31

Give IUPAC names for the following compounds:

Ricajoy Montero

Ricajoy Montero

Numerade Educator

Problem 32

Draw and name the eight isomeric alcohols with formula $\mathrm{C}_{5} \mathrm{H}_{12} \mathrm{O}$. Which are chiral?

Lottie Adams

Numerade Educator

Problem 33

Which of the eight alcohols you identified in Problem 13.32 react with $\mathrm{CrO}_{3}$ in aqueous acid? Show the products you would expect from each reaction.

Lottie Adams

Numerade Educator

Problem 34

Named $bombykol$, the sex pheromone secreted by the female silkworm moth has the formula $\mathrm{C}_{16} \mathrm{H}_{30} \mathrm{O}$ and the systematic name $(10 E, 12 Z)$. hexadeca-10,12-dien-1-ol. Draw bombykol showing correct geometry for the two double bonds.

Katie Miller

Numerade Educator

Problem 35

$Carvacrol$ is a naturally occurring substance isolated from oregano, thyme, and marjoram. What is its IUPAC name?

Katie Miller

Numerade Educator

Problem 36

Give IUPAC names for the following compounds:

Ricajoy Montero

Ricajoy Montero

Numerade Educator

Problem 37

How would you prepare the following ethers?

Anupa Sharad Medhekar

Anupa Sharad Medhekar

Numerade Educator

Problem 38

What Grignard reagent and what carbonyl compound might you start with to prepare the following alcohols?

Stefan Kaliszuk

Stefan Kaliszuk

Numerade Educator

Problem 39

What carbonyl compounds would you reduce to prepare the following alcohols? List all possibilities.

Lottie Adams

Numerade Educator

Problem 40

What carbonyl compounds might you start with to prepare the following compounds by Grignard reaction? List all possibilities.
(a) 2-Methylpropan-2-ol
(b) 1-Ethylcyclohexanol
(c) 3-Phenylpentan-3-ol
(d) 2-Phenylpentan-2-ol

Lottie Adams

Numerade Educator

Problem 41

How would you synthesize the following alcohols, starting with benzene and other alcohols of six or fewer carbons as your only organic reagents?

Alexander Cheng

Alexander Cheng

Numerade Educator

Problem 42

Predict the products of the following ether cleavage reactions:

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 43

What products would you obtain from reaction of pentan-1-ol with the following reagents?
(a) $\mathrm{PBr}_{3}$
(b) $\mathrm{SOCl}_{2}$
(c) $\mathrm{CrO}_{3}, \mathrm{H}_{2} \mathrm{O}, \mathrm{H}_{2} \mathrm{SO}_{4}$
(d) Dess-Martin reagent

Katie Miller

Numerade Educator

Problem 44

How would you prepare the following compounds from 2 -phenylethanol? More than one step may be required.
(a) Styrene $\left(\mathrm{PhCH}=\mathrm{CH}_{2}\right)$
(b) Phenylacetaldehyde (PhCH $_{2}$ CHO)
(c) Phenylacetic acid $\left(\mathrm{PhCH}_{2} \mathrm{CO}_{2} \mathrm{H}\right)$
(d) Benzoic acid
(e) Ethylbenzene
(f) 1-Phenylethanol

Anish Wadhwa

Numerade Educator

Problem 45

How would you prepare the following compounds from 1 -phenylethanol? More than one step may be required.
(a) Acetophenone $\left(\mathrm{PhCOCH}_{3}\right)$
(b) $m$ -Bromobenzoic acid
(c) $p$ -Chloroethylbenzene
(d) 2-Phenylpropan-2-ol
(e) Methyl 1-phenylethyl ether
(f) 1-Phenylethanethiol

Anish Wadhwa

Numerade Educator

Problem 46

How would you carry out the following transformations?

KY

Kexin Yang

Numerade Educator

Problem 47

How would you carry out the following transformations? More than one step may be required.

Ian Kaigh

Numerade Educator

Problem 48

When 4 -chlorobutan-1-ol is treated with a strong base such as sodium hydride, NaH, tetrahydrofuran is produced. Suggest a mechanism.

Alkendra Singh

Numerade Educator

Problem 49

What product would you expect from cleavage of tetrahydrofuran with HI?

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 50

How would you prepare the following substances from cyclopentanol? More than one step may be required.
(a) Cyclopentanone
(b) Cyclopentene
(c) 1 -Methylcyclopentanol
(d) trans-2-Methylcyclopentanol

Anish Wadhwa

Numerade Educator

Problem 51

What products would you expect to obtain from reaction of 1 -methylcyclohexanol with the following reagents?
(a) HBr
(b) NaH
(c) $\mathrm{H}_{2} \mathrm{SO}_{4}$
(d) $\mathrm{Na}_{2} \mathrm{Cr}_{2} \mathrm{O}_{7}$

Katie Miller

Numerade Educator

Problem 52

How would you prepare $o$ -hydroxyphenylacetaldehyde from phenol? More than one step is required.

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 53

Imagine that you have treated $(2 R, 3 R)-2,3$ -epoxy-3-methylpentane with aqueous acid to carry out a ring-opening reaction.
(a) Draw the epoxide showing stereochemistry.
(b) Draw and name the product showing stereochemistry.
(c) Is the product chiral? Explain.
(d) Is the product optically active? Explain.

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 54

Epoxides are reduced by treatment with lithium aluminum hydride to yield alcohols. Propose a mechanism for this reaction.

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 55

The red fox (Vulpes vulpes) uses a chemical communication system based on scent marks in urine. One component of fox urine is a sulfide. Mass spectral analysis of the pure scent-mark component shows $\mathrm{M}^{+}=116,$ IR spectroscopy shows an intense band at $890 \mathrm{~cm}^{-1},$ and 1H NMR spectroscopy reveals the following peaks. Propose a structure for the molecule. [Note: $\left(\mathrm{CH}_{3}\right)_{2} \mathrm{~S}$ absorbs at $\left.2.1 \mathrm{\delta} .\right]$
$1.74 \delta(3 \mathrm{H},$ singlet $) ; 2.11 \delta(3 \mathrm{H},$ singlet $) ; 2.27 \delta(2 \mathrm{H},$ triplet $, J=4.2 \mathrm{~Hz})$
$2.57 \delta(2 \mathrm{H},$ triplet $, J=4.2 \mathrm{~Hz}) ; 4.73 \delta(2 \mathrm{H},$ broad $)$

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 56

Anethole, $\mathrm{C}_{10} \mathrm{H}_{12} \mathrm{O}$, a major constituent of the oil of anise, has the ${ }^{1} \mathrm{H}$ NMR spectrum shown. On oxidation with $\mathrm{Na}_{2} \mathrm{Cr}_{2} \mathrm{O}_{7},$ anethole yields $p$ -methoxybenzoic acid. What is the structure of anethole? Assign all peaks in the NMR spectrum, and account for the observed splitting patterns.

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 57

Propose a structure consistent with the following spectral data for a compound $\mathrm{C}_{8} \mathrm{H}_{18} \mathrm{O}_{2}$ :
$\mathrm{IR}$ : $3350 \mathrm{~cm}^{-1}$
${ }^{1} \mathrm{H}$ NMR: $\quad 1.24 \delta(12 \mathrm{H},$ singlet $) ; 1.56 \delta(4 \mathrm{H},$ singlet $) ; 1.95 \delta(2 \mathrm{H},$ singlet

Zubair Abdulla

Numerade Educator

Problem 58

The ${ }^{1} \mathrm{H}$ NMR spectrum shown is that of 3 -methylbut-3-en-1-ol. Assign all the observed resonance peaks to specific protons, and account for the splitting patterns.

Lottie Adams

Numerade Educator

Problem 59

When 2 -methylpentane- 2,5 -diol is treated with sulfuric acid, dehydration occurs and 2,2-dimethyltetrahydrofuran is formed. Suggest a mechanism for this reaction. Which of the two oxygen atoms is most likely to be eliminated, and why?

Nicholas Sacco

Numerade Educator

Problem 60

Methyl aryl ethers, such as anisole, are cleaved to iodomethane and a phenoxide ion on heating with LiI in DMF. Propose a mechanism for this reaction.

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 61

tert-Butyl ethers can be prepared by the reaction of an alcohol with 2-methylpropene in the presence of an acid catalyst. Propose a mechanism.

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 62

Why do you suppose HI and HBr are more effective than HCl in cleaving ethers?

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 63

Evidence for carbocation intermediates in the acid-catalyzed dehydration of alcohols comes from the observation that rearrangements sometimes occur. Propose a mechanism to account for the formation of 2,3-dimethylbut-2-ene from 3,3-dimethylbutan-2-ol.

Ronald Prasad

Numerade Educator

Problem 64

Acid-catalyzed dehydration of 2,2 -dimethylcyclohexanol yields a mixture of 1,2 -dimethylcyclohexene and isopropylidenecyclopentane. Propose a mechanism to account for the formation of both products.

Zubair Abdulla

Numerade Educator

Problem 65

Epoxides react with Grignard reagents to yield alcohols. Propose a mechanism.

Colton K

Numerade Educator

Problem 66

Rank the following substituted phenols in order of increasing acidity:

Zubair Abdulla

Numerade Educator

Problem 67

Reduction of butan- 2 -one with $\mathrm{NaBH}_{4}$ yields butan- 2 -ol. Is the product chiral? Is it optically active? Explain.

Lottie Adams

Numerade Educator

Problem 68

Reaction of ( $S$ )-3-methylpentan-2-one with methylmagnesium bromide followed by acidification yields 2,3-dimethylpentan-2-ol. What is the stereochemistry of the product? Is the product optically active?

Anish Wadhwa

Numerade Educator

Problem 69

Testosterone is one of the most important male steroid hormones. When testosterone is dehydrated by treatment with acid, rearrangement occurs to yield the product shown. Propose a mechanism to account for this reaction.

Courtney Burson

Courtney Burson

Numerade Educator

Problem 70

Dehydration of trans-2-methylcyclopentanol with $\mathrm{POCl}_{3}$ in pyridine yields predominantly 3 -methylcyclopentene. Is the stereochemistry of this dehydration syn or anti? Can you suggest a reason for formation of the observed product?

Zubair Abdulla

Numerade Educator

Problem 71

2,3-Dimethylbutane-2,3-diol has the common name pinacol. On heating with aqueous acid, pinacol rearranges to pinacolone, 3,3 -dimethylbutan-2-one. Suggest a mechanism.

Zubair Abdulla

Numerade Educator

Problem 72

As a rule, axial alcohols oxidize somewhat faster than equatorial alcohols. Which would you expect to oxidize faster, cis-4-tert-butylcyclohexanol or trans-4-tert-butylcyclohexanol? Draw the more stable chair conformation of each molecule.

Zubair Abdulla

Numerade Educator

Problem 73

Propose a synthesis of bicyclohexylidene, starting from cyclohexanone as the only source of carbon.

Grigoriy Sereda

Grigoriy Sereda

Numerade Educator

Problem 74

Identify the reagents a-f in the following scheme:

Madi Sousa

Numerade Educator

Problem 75

Identify the reagents a-e in the following scheme:

Madi Sousa

Numerade Educator

Problem 76

Disparlure, $\mathrm{C}_{19} \mathrm{H}_{38} \mathrm{O}$, is a sex attractant released by the female gypsy moth, Lymantria dispar. The ${ }^{1} \mathrm{H}$ NMR spectrum of disparlure shows a large absorption in the alkane region, 1 to $2 \delta$, and a triplet at $2.8 \delta$. Reaction of disparlure, first with aqueous acid and then with $\mathrm{KMnO}_{4}$, yields two carboxylic acids identified as undecanoic acid and 6 -methylheptanoic acid. $\left(\mathrm{KMnO}_{4}\right.$ cleaves 1,2 -diols to yield carboxylic acids. $)$ Neglecting stereochemistry, propose a structure for disparlure. The actual compound is a chiral molecule with $7 R, 8 S$ stereochemistry. Draw disparlure, showing the correct stereochemistry.

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 77

Galactose, a constituent of the disaccharide lactose found in dairy products, is metabolized by a pathway that includes the isomerization of UDP-galactose to UDP-glucose, where UDP = uridylyl diphosphate. The enzyme responsible for the transformation uses $\mathrm{NAD}^{+}$ as cofactor. Propose a mechanism.

VS

Vivek Singh

Numerade Educator

Problem 78

Compound A, $\mathrm{C}_{5} \mathrm{H}_{10} \mathrm{O}$, is one of the basic building blocks of nature. All steroids and many other naturally occurring compounds are built from compound A. Spectroscopic analysis of A yields the following information:
IR: $\quad 3400 \mathrm{~cm}^{-1} ; 1640 \mathrm{~cm}^{-1}$
${ }^{1} \mathrm{H}$ NMR: $\quad 1.63 \delta(3 \mathrm{H},$ singlet $) ; 1.70 \delta(3 \mathrm{H},$ singlet $)$
$3.83 \delta(1 \mathrm{H},$ broad singlet $) ; 4.15 \delta(2 \mathrm{H},$ doublet, $J=7 \mathrm{~Hz})$
$5.70 \delta(1 \mathrm{H},$ triplet, $J=7 \mathrm{~Hz})$
(a) From the IR spectrum, what is the nature of the oxygen-containing functional group?
(b) What kinds of protons are responsible for the NMR absorptions listed?
(c) Propose a structure for A.

Zubair Abdulla

Numerade Educator

Problem 79

A compound of unknown structure gave the following spectroscopic data:
Mass spectrum: $\quad \mathrm{M}^{+}=88.1$
$\mathrm{IR}:$ $3600 \mathrm{~cm}^{-1}$
$\begin{array}{ll}1 \mathrm{H} \mathrm{NMR}: & 1.4 \delta(2 \mathrm{H}, \text { quartet, } J=7 \mathrm{~Hz}) ; 1.2 \delta(6 \mathrm{H}, \text { singlet }) ; \\ & 1.0 \delta(1 \mathrm{H}, \text { singlet }) ; 0.9 \delta(3 \mathrm{H}, \text { triplet }, J=7 \mathrm{~Hz}) \\ { }^{13} \mathrm{C} \text { NMR: } & 74,35,27,9 \delta\end{array}$
(a) Assuming that the compound contains $\mathrm{C}$ and $\mathrm{H}$ but may or may not contain O, give three possible molecular formulas.
(b) How many protons (H) does the compound contain?
(c) What functional group(s) does the compound contain?
(d) How many carbons does the compound contain?
(e) What is the molecular formula of the compound?
(f) What is the structure of the compound?
(g) Assign the peaks in the ${ }^{1} \mathrm{H}$ NMR spectrum of the molecule to specific protons.

Zubair Abdulla

Numerade Educator

Problem 80

The following ${ }^{1} \mathrm{H}$ NMR spectrum is that of an alcohol, $\mathrm{C}_{8} \mathrm{H}_{10} \mathrm{O}$. Propose a structure.

Zubair Abdulla

Numerade Educator

Problem 81

Compound A, $\mathrm{C}_{8} \mathrm{H}_{10} \mathrm{O}$, has the IR and ${ }^{1} \mathrm{H}$ NMR spectra shown. Propose a structure consistent with the observed spectra, and assign each peak in the NMR spectrum. Note that the absorption at $5.5 \delta$ disappears when $\mathrm{D}_{2} \mathrm{O}$ is added.

Anish Wadhwa

Numerade Educator

Problem 82

The reduction of carbonyl compounds by reaction with hydride reagents (H:-) and the Grignard addition by reaction with organomagnesium halides (R: $^{-+}$ MgBr) are examples of nucleophilic carbonyl addition reactions. What analogous product do you think might result from reaction of cyanide ion with a ketone?

Zubair Abdulla

Numerade Educator

Problem 83

Aldehydes and ketones undergo acid-catalyzed reaction with alcohols to yield hemiacetals, compounds that have one alcohol-like oxygen and one ether-like oxygen bonded to the same carbon. Further reaction of a hemiacetal with alcohol then yields an acetal, a compound that has two ether-like oxygens bonded to the same carbon.
(a) Show the structures of the hemiacetal and acetal you would obtain by reaction of cyclohexanone with ethanol.
(b) Propose a mechanism for the conversion of a hemiacetal into an acetal.

Mikayla Stephens

Mikayla Stephens

Numerade Educator

Problem 84

Propose a mechanism to account for the following transformation. What two kinds of reactions are occurring?

Mikayla Stephens

Mikayla Stephens

Numerade Educator