Organic chemistry with biological applications

John E. McMurry

Chapter 4

Organic Compounds: Cycloalkanes and Their Stereochemistry - all with Video Answers

Educators

Chapter Questions

Problem 1

Give IUPAC names for the following cycloalkanes:

Ricajoy Montero

Ricajoy Montero

Numerade Educator

Problem 2

Draw structures corresponding to the following IUPAC names:
(a) 1,1-Dimethylcyclooctane
(b) 3-Cyclobutylhexane
(c) 1,2-Dichlorocyclopentane
(d) 1,3-Dibromo-5-methylcyclohexane

Tyler Roberts

Numerade Educator

Problem 3

Name the following cycloalkane:

Tyler Roberts

Numerade Educator

Problem 4

Name the following substances, including the cis- or trans- prefix:

Grigoriy Sereda

Grigoriy Sereda

Numerade Educator

Problem 5

Draw the structures of the following molecules:
(a) trans-1-Bromo-3-methylcyclohexane
(b) cis-1,2-Dimethylcyclobutane
(c) trans-1-tert-Butyl-2-ethylcyclohexane

Bobby Barnes

University of North Texas

Problem 6

Prostaglandin $\mathrm{F}_{2 \alpha}$, a hormone that causes uterine contraction during childbirth, has the following structure. Are the two hydroxyl groups $(-\mathrm{OH})$ on the cyclopentane ring cis or trans to each other? What about the two carbon chains attached to the ring?

Tyler Roberts

Numerade Educator

Problem 7

Name the following substances, including the cis- or trans- prefix (redbrown $=\mathrm{Br}$ ):

Bobby Barnes

University of North Texas

Problem 8

Each $\mathrm{H} \leftrightarrow$ H eclipsing interaction in ethane costs about $4.0 \mathrm{~kJ} / \mathrm{mol}$. How many such interactions are present in cyclopropane? What fraction of the overall $115 \mathrm{~kJ} / \mathrm{mol}$ (27.5 kcal/mol) strain energy of cyclopropane is due to torsional strain?

Bobby Barnes

University of North Texas

Problem 9

cis-1,2-Dimethylcyclopropane has more strain than trans-1,2-dimethylcyclopropane. How can you account for this difference? Which of the two compounds is more stable?

Bobby Barnes

University of North Texas

Problem 10

How many $\mathrm{H} \leftrightarrow \mathrm{H}$ eclipsing interactions would be present if cyclopentane were planar? Assuming an energy cost of $4.0 \mathrm{~kJ} / \mathrm{mol}$ for each eclipsing interaction, how much torsional strain would planar cyclopentane have? Since the measured total strain of cyclopentane is $26 \mathrm{~kJ} / \mathrm{mol}$, how much of the torsional strain is relieved by puckering?

Bobby Barnes

University of North Texas

Problem 11

Two conformations of $c i s-1,3$ -dimethylcyclobutane are shown. What is the difference between them, and which do you think is likely to be more stable?

Tyler Roberts

Numerade Educator

Problem 12

Draw two different chair conformations of cyclohexanol (hydroxycyclohexane) showing all hydrogen atoms. Identify each position as axial or equatorial.

Bobby Barnes

University of North Texas

Problem 13

Draw two different chair conformations of trans-1,4-dimethylcyclohexane, and label all positions as axial or equatorial.

Bobby Barnes

University of North Texas

Problem 14

Identify each of the colored positions-red, blue, and green-as axial or equatorial. Then carry out a ring-flip, and show the new positions occupied by each color.

Bobby Barnes

University of North Texas

Problem 15

What is the energy difference between the axial and equatorial conformations of cyclohexanol (hydroxycyclohexane)?

Bobby Barnes

University of North Texas

Problem 16

Why do you suppose an axial cyano (-CN) substituent causes practically no 1,3-diaxial steric strain $(0.4 \mathrm{~kJ} / \mathrm{mol})$ ? Use molecular models to help with your answer.

Bobby Barnes

University of North Texas

Problem 17

Look at Figure 4.12 on page $103,$ and estimate the percentages of axial and equatorial conformations present at equilibrium in bromocyclohexane.

Bobby Barnes

University of North Texas

Problem 18

Draw the more stable chair conformation of the following molecules, and estimate the amount of strain in each:
(a) trans-1-Chloro-3-methylcyclohexane
(b) cis-1-Ethyl-2-methylcyclohexane
(c) cis-1-Bromo-4-ethylcyclohexane
(d) cis-1-tert-Butyl-4-ethylcyclohexane

Bobby Barnes

University of North Texas

Problem 19

Identify each substituent in the following compound as axial or equatorial, and tell whether the conformation shown is the more stable or less stable chair form (green $=\mathrm{Cl}$ ):

Bobby Barnes

University of North Texas

Problem 20

Which isomer is more stable, cis-decalin or trans-decalin? Explain.

Bobby Barnes

University of North Texas

Problem 21

Look at the following structure of the female hormone estrone, and tell whether each of the two indicated ring-fusions is cis or trans.

Bobby Barnes

University of North Texas

Problem 22

Name the following cycloalkanes:

Shahina -

Numerade Educator

Problem 23

Name the following compound, identify each substituent as axial or equatorial, and tell whether the conformation shown is the more stable or less stable chair form (green $=\mathrm{Cl}$ ):

Bobby Barnes

University of North Texas

Problem 24

A trisubstituted cyclohexane with three substituents-red, green, and blue-undergoes a ring-flip to its alternative chair conformation. Identify each substituent as axial or equatorial, and show the positions occupied by the three substituents in the ring-flipped form.

Bobby Barnes

University of North Texas

Problem 25

The following cyclohexane derivative has three substituents-red, green, and blue. Identify each substituent as axial or equatorial, and identify each pair of relationships (red-blue, red-green, and bluegreen as cis or trans.

Tyler Roberts

Numerade Educator

Problem 26

Glucose exists in two forms having a 36: 64 ratio at equilibrium. Draw a skeletal structure of each, describe the difference between them, and tell which of the two you think is more stable (red $=\mathrm{O}$ ).

Bobby Barnes

University of North Texas

Problem 27

Draw the five cycloalkanes with the formula $\mathrm{C}_{5} \mathrm{H}_{10}$.

Bobby Barnes

University of North Texas

Problem 28

Draw two constitutional isomers of $c i s-1,2$ -dibromocyclopentane.

Tyler Roberts

Numerade Educator

Problem 29

Draw a stereoisomer of trans-1,3-dimethylcyclobutane.

Bobby Barnes

University of North Texas

Problem 30

Tell whether the following pairs of compounds are identical, constitutional isomers, stereoisomers, or unrelated.
(a) cis-1,3-Dibromocyclohexane and trans-1,4-dibromocyclohexane
(b) 2,3 -Dimethylhexane and 2,3,3 -trimethylpentane
(c)

Bobby Barnes

University of North Texas

Problem 31

Draw three isomers of trans-1,2-dichlorocyclobutane, and label them as either constitutional isomers or stereoisomers.

Bobby Barnes

University of North Texas

Problem 32

Identify each pair of relationships among the -OH groups in glucose (red-blue, red-green, red-black, blue-green, blue-black, green-black) as cis or trans.

Bobby Barnes

University of North Texas

Problem 33

Draw 1,3,5 -trimethylcyclohexane using a hexagon to represent the ring. How many cis-trans stereoisomers are possible?

Bobby Barnes

University of North Texas

Problem 34

Hydrocortisone, a naturally occurring hormone produced in the adrenal glands, is often used to treat inflammation, severe allergies, and numerous other conditions. Is the indicated -OH group in the molecule axial or equatorial?

Bobby Barnes

University of North Texas

Problem 35

A 1,2 -cis disubstituted cyclohexane, such as $c i s-1,2$ -dichlorocyclohexane, must have one group axial and one group equatorial. Explain.

Bobby Barnes

University of North Texas

Problem 36

A 1,2 -trans disubstituted cyclohexane must have either both groups axial or both groups equatorial. Explain.

Bobby Barnes

University of North Texas

Problem 37

Why is a 1,3 -cis disubstituted cyclohexane more stable than its trans isomer?

Bobby Barnes

University of North Texas

Problem 38

Which is more stable, a 1,4 -trans disubstituted cyclohexane or its cis isomer?

Bobby Barnes

University of North Texas

Problem 39

cis-1,2-Dimethylcyclobutane is less stable than its trans isomer, but cis1,3-dimethylcyclobutane is more stable than its trans isomer. Draw the most stable conformations of both, and explain.

Tyler Roberts

Numerade Educator

Problem 40

From the data in Figure 4.12 and Table 4.1 , estimate the percentages of molecules that have their substituents in an axial orientation for the following compounds:
(a) Isopropylcyclohexane
(b) Fluorocyclohexane
(c) Cyclohexanecarbonitrile, $\mathrm{C}_{6} \mathrm{H}_{11} \mathrm{CN}$

Bobby Barnes

University of North Texas

Problem 41

Assume that you have a variety of cyclohexanes substituted in the positions indicated. Identify the substituents as either axial or equatorial. For example, a 1,2 -cis relationship means that one substituent must be axial and one equatorial, whereas a 1,2 -trans relationship means that both substituents are axial or both are equatorial.
(a) 1,3 -Trans disubstituted
(b) 1,4 -Cis disubstituted
(c) 1,3 -Cis disubstituted
(d) 1,5 -Trans disubstituted
(e) 1,5 -Cis disubstituted
(f) 1,6 -Trans disubstituted

Bobby Barnes

University of North Texas

Problem 42

Draw the two chair conformations of cis-1-chloro-2-methylcyclohexane. Which is more stable, and by how much?

Bobby Barnes

University of North Texas

Problem 43

Draw the two chair conformations of trans-1-chloro-2-methylcyclohexane. Which is more stable?

Bobby Barnes

University of North Texas

Problem 44

Galactose, a sugar related to glucose, contains a six-membered ring in which all the substituents except the -OH group indicated below in red are equatorial. Draw galactose in its more stable chair conformation.

Bobby Barnes

University of North Texas

Problem 45

Draw the two chair conformations of menthol, and tell which is more stable.

Prashant Bana

Numerade Educator

Problem 46

There are four cis-trans isomers of menthol (Problem 4.45 ), including the one shown. Draw the other three.

Bobby Barnes

University of North Texas

Problem 47

The diaxial conformation of $c i s-1,3$ -dimethylcyclohexane is approximately $23 \mathrm{~kJ} / \mathrm{mol}(5.4 \mathrm{kcal} / \mathrm{mol})$ less stable than the diequatorial conformation. Draw the two possible chair conformations, and suggest a reason for the large energy difference.

Tyler Roberts

Numerade Educator

Problem 48

Approximately how much steric strain does the 1,3 -diaxial interaction between the two methyl groups introduce into the diaxial conformation of cis-1,3-dimethylcyclohexane? (See Problem $4.47 .$ )

Bobby Barnes

University of North Texas

Problem 49

In light of your answer to Problem $4.48,$ draw the two chair conformations of 1,1,3 -trimethylcyclohexane and estimate the amount of strain energy in each. Which conformation is favored?

Bobby Barnes

University of North Texas

Problem 50

One of the two chair structures of $c i s-1$ -chloro-3-methylcyclohexane is more stable than the other by $15.5 \mathrm{~kJ} / \mathrm{mol}$ (3.7 kcal/mol). Which is it? What is the energy cost of a 1,3 -diaxial interaction between a chlorine and a methyl group?

Bobby Barnes

University of North Texas

Problem 51

We saw in Problem 4.20 that cis-decalin is less stable than transdecalin. Assume that the 1,3 -diaxial interactions in $c i s$ -decalin are similar to those in axial methylcyclohexane [that is, one $\mathrm{CH}_{2} \leftrightarrow \mathrm{H}$ interaction costs $3.8 \mathrm{~kJ} / \mathrm{mol}(0.9 \mathrm{kcal} / \mathrm{mol})]$, and calculate the magnitude of the energy difference between cis- and trans-decalin.

Bobby Barnes

University of North Texas

Problem 52

Using molecular models as well as structural drawings, explain why trans-decalin is rigid and cannot ring-flip whereas cis-decalin can easily ring-flip.

Tyler Roberts

Numerade Educator

Problem 53

trans-Decalin is more stable than its cis isomer, but cis-bicyclo[4.1.0] heptane is more stable than its trans isomer. Explain.

Bobby Barnes

University of North Texas

Problem 54

As mentioned in Problem 3.53 , the statin drugs, such as simvastatin (Zocor), pravastatin (Pravachol), and atorvastatin (Lipitor) are the most widely prescribed drugs in the world.
(a) Are the two indicated bonds on simvastatin cis or trans?
(b) What are the cis/trans relationships among the three indicated bonds on pravastatin?
(c) Why can't the three indicated bonds on atorvastatin be identified as cis or trans?

Niamat Khuda

Numerade Educator

Problem 55

myo-Inositol, one of the isomers of 1,2,3,4,5,6 -hexahydroxycyclohexane, acts as a growth factor in both animals and microorganisms. Draw the most stable chair conformation of myo-inositol.

Nicole Krahulik

Nicole Krahulik

Numerade Educator

Problem 56

How many cis-trans stereoisomers of myo-inositol (Problem 4.55 ) are there? Draw the structure of the most stable isomer.

Bobby Barnes

University of North Texas

Problem 57

The German chemist J. Bredt proposed in 1935 that bicycloalkenes such as 1 -norbornene, which have a double bond to the bridgehead carbon, are too strained to exist. Explain. (Making a molecular model will be helpful.)

Bobby Barnes

University of North Texas

Problem 58

Tell whether each of the following substituents on a steroid is axial or equatorial. (A substituent that is "up" is on the top face of the molecule as drawn, and a substituent that is "down" is on the bottom face.)
(a) Substituent up at C3
(b) Substituent down at C7
(c) Substituent down at C11

Bobby Barnes

University of North Texas

Problem 59

Amantadine is an antiviral agent that is active against influenza type A infection. Draw a three-dimensional representation of amantadine, showing the chair cyclohexane rings.

Tyler Roberts

Numerade Educator

Problem 60

Here's a difficult one. There are two different substances named trans1,2-dimethylcyclopentane. What is the relationship between them? (We'll explore this kind of isomerism in the next chapter.)

Tyler Roberts

Numerade Educator

Problem 61

Ketones react with alcohols to yield products called acetals. Why does the all-cis isomer of 4 -tert-butylcyclohexane-1,3-diol react readily with acetone and an acid catalyst to form an acetal, but other stereoisomers do not react? In formulating your answer, draw the more stable chair conformations of all four stereoisomers and the product acetal from each.

Bobby Barnes

University of North Texas

Problem 62

Alcohols undergo an oxidation reaction to yield carbonyl compounds on treatment with $\mathrm{CrO}_{3}$. For example, 2-tert-butylcyclohexanol gives 2-tert-butylcyclohexanone. If axial -OH groups are generally more reactive than their equatorial isomers, which do you think reacts faster the cis isomer of 2 -tert-butylcyclohexanol or the trans isomer? Explain.

Bobby Barnes

University of North Texas