Organic Chemistry

T.W. Graham Solomons, Craig B. Fryhle, Scott A. Snyder

Chapter 19

Condensation and Conjugate Addition Reactions of Carbonyl Compounds - all with Video Answers

Educators

Chapter Questions

Problem 1

(a) Write a mechanism for all steps of the Claisen condensation that take place when ethyl propanoate reacts with ethoxide ion. (b) What products form when the reaction mixture is acidified?

Zubair Abdulla

Zubair Abdulla

Numerade Educator

Problem 2

since the products obtained from Claisen condensations are $\beta$ -keto esters, subsequent hydrolysis and decarboxylation of these products gives a general method for the synthesis of ketones. Show how you would employ this technique in a synthesis of 4-heptanone.

Shazia Naz

Numerade Educator

Problem 3

(a) What product would you expect from a Dieckmann condensation of diethyl heptanedioate? (b) Can you account for the fact that diethyl pentanedioate (diethyl glutarate) does not undergo a Dieckmann condensation?

Shazia Naz

Numerade Educator

Problem 4

Write mechanisms that account for the products that are formed in the crossed Claisen condensation illustrated earlier between ethyl phenylacetate and dicthyl carbonate.

Zubair Abdulla

Numerade Educator

Problem 5

What products would you expect to obtain from each of the following crossed Claisen condensations?
$$\begin{array}{ll}
\text { (a) Ethyl propanoate }+\text { diethyl oxalate } \frac{(1) \mathrm{NaOEt}}{(2) \mathrm{H}_{0} \mathrm{O}^{+}} & \text {(b) Ethyl acetate }+\text { ethy } \mathrm{f} \text { formate } \frac{(1) \mathrm{NaOEt}}{(2) \mathrm{H}_{0} \mathrm{O}^{+}}
\end{array}$$

Shazia Naz

Numerade Educator

Problem 6

Show how you might synthesize each of the following compounds using, as your starting materials, esters, ketones, acyl halides, and so on:
(FIGURE CAN'T COPY)

Shazia Naz

Numerade Educator

Problem 7

The acid-catalyzed aldol condensation of acetone (just shown) also producs some 2.6-dimethylhepta-2,5-dien-4-one. Give a mechanism that explains the formation of this product.

Zubair Abdulla

Numerade Educator

Problem 8

Heating acetone with $\mathrm{H}_{2} \mathrm{SO}_{4}$ leads to the formation of mesitylene (1,3,5-trimethylbenzene). Propose a mechanism for this reaction.

Shazia Naz

Numerade Educator

Problem 9

(a) Provide a mechanism for the aldol addition of propanal shown here.
(FIGURE CAN'T COPY)
(b) How can you account for the fact that the product of the aldol addition is 3-hydroxy-2-methylpentanal and not 4-hydroxyhexanal?
(c) What products would be formed if the reaction mixture were heated?

Zubair Abdulla

Numerade Educator

Problem 10

Show how each of the following products could be synthesized from butanal:
(a) 2 -Ethyl-3-hydroxyhexanal
(b) 2 -Ethylhex-2-en-1-ol
(c) 2 -Ethylhexan- 1 -ol
(d) 2 -Ethylhexane-1,3-diol (the insect repellent " $6-12 "$ ")

Zubair Abdulla

Numerade Educator

Problem 11

Outlined below is a synthesis of a compound used in perfumes, called lily aldehyde. Provide all of the missing structures.
$$p \text { -tert-Butylbenzyl alcohol } \frac{\mathrm{PCC}}{\mathrm{CH}_{2} \mathrm{Cl}_{2}} \mathrm{C}_{11} \mathrm{H}_{14} \mathrm{O} \frac{\text { propanal }}{\mathrm{HO}^{-}} \mathrm{C}_{14} \mathrm{H}_{18} \mathrm{O} \frac{\mathrm{H}_{2}, \mathrm{Pd} / \mathrm{C}}{\mathrm{CH}_{2} \mathrm{Cl}_{2}} \text { lily aldehyde }\left(\mathrm{C}_{14} \mathrm{H}_{18} \mathrm{O}\right)$$

Shazia Naz

Numerade Educator

Problem 12

When excess formaldehyde in basic solution is treated with ethanal, the following reaction takes place:
(FIGURE CAN'T COPY)

Write a mechanism that accounts for the formation of the product.

Zubair Abdulla

Numerade Educator

Problem 13

When pseudoionone is treated with $\mathrm{BF}_{3}$ in acetic acid, ring closure takes place and $\alpha$ - and $\beta$ -ionone are produced. This is the next step in the vitamin A synthesis.
(FIGURE CAN'T COPY)

Grigoriy Sereda

Grigoriy Sereda

Numerade Educator

Problem 14

(a) Write resonance structures for the anion of acetonitrile that account for its being much more acidic than ethane. (b) Give a step-by-step mechanism for the condensation of benzaldehyde with acetonitrile.

Zubair Abdulla

Numerade Educator

Problem 15

Starting with ketones and aldehydes of your choice, outline a directed aldol synthesis of each of the following using lithium enolates:
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 16

Assuming that dehydration occurs, write the structures of the two other products that might have resulted from the aldol cyclization just given. (One of these products will have a five-membered ring and the other will have a seven-membered ring.)

Zubair Abdulla

Numerade Educator

Problem 17

What starting compound would you use in an aldol cyclization to prepare each of the following?
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 18

What experimental conditions would favor the cyclization process in an intramolecular aldol reaction over intermolecular condensation?

Shazia Naz

Numerade Educator

Problem 19

What product would you expect to obtain from the base-catalyzed Michael reaction of (a) 1,3 -diphenylprop-2-en-1-one (Section $19.5 \mathrm{A}$ ) and acetophenone and
(b) 1,3 -diphenylprop-2-en-1-one and cyclopentadiene? Show all steps in each mechanism.

Zubair Abdulla

Numerade Educator

Problem 20

When acrolein (propenal) reacts with hydrazine, the product is a dihydropyrazole:
Suggest a mechanism that explains this reaction.
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 21

(a) Propose step-by-step mechanisms for both transformations of the Robinson annulation sequence just shown. (b) Would you expect 2 -methylcyclohexane- 1,3 -dione to be more or less acidic than cyclohexanone? Explain your answer.

Zubair Abdulla

Numerade Educator

Problem 22

Outline reasonable mechanisms that account for the products of the following Mannich reactions:
(FIGURE CAN'T COPY)

Ronald Prasad

Numerade Educator

Problem 23

Write a structural formula for the product from each of the following reactions.
(FIGURES CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 24

Show all steps in the following syntheses. You may use any other needed reagents but you should begin with the compound given.
(FIGURE CAN'T COPY)

Shazia Naz

Numerade Educator

Problem 25

Write structural formulas for both of the possible products from the following Dieckmann condensation, and predict which one would likely predominate.
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 26

Write structural formulas for both of the possible products from the following Dicckmann condensation, and predict which one would likely predominate.
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 27

When a Dieckmann condensation is attempted with diethyl succinate, the product obtained has the molecular formula $\mathrm{C}_{12} \mathrm{H}_{16} \mathrm{O}_{6} .$ What is the structure of this compound?

Shazia Naz

Numerade Educator

Problem 28

Show how the diketone at the right could be prepared by a condensation reaction:

Shazia Naz

Numerade Educator

Problem 29

In contrast to the reaction with dilute alkali (Section 18.6), when concentrated solutions of NaOH are used, acetoacetic esters undergo cleavage as shown below. Provide a mechanistic explanation for this outcome.
(FIGURE CAN'T COPY)

Tom Rutherford

Numerade Educator

Problem 30

Write a detailed mechanism for the following reaction.
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 31

In the presence of sodium ethoxide the following transformation occurs. Explain.
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 32

Thymine is one of the heterocyclic bases found in DNA. Starting with ethyl propanoate and using any other needed reagents, show how you might synthesize thymine.
(FIGURE CAN'T COPY)

Shazia Naz

Numerade Educator

Problem 33

Predict the products from each of the following aldol reactions.
(FIGURES CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 34

What four $\beta$ -hydroxy aldehydes would be formed by a crossed aldol reaction between the following compounds?
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 35

Show how each of the following transformations could be accomplished. You may use any other required reagents.
(FIGURE CAN'T COPY)

Anish Wadhwa

Numerade Educator

Problem 36

What starting materials are needed to synthesize each of the following compounds using an aldol reaction?
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 37

What reagents would you use to bring about each step of the following syntheses?

(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 38

The hydrogen atoms of the $\gamma$ carbon of crotonaldehyde are appreciably acidic (p $K_{z} \cong 20$ ).
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 39

Provide a mechanism for the following reaction.
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 40

When the aldol reaction of accealdehyde is carried out in $D_{2} O$, no deuterium is found in the methyl group of unreacted aldchyde. However, in the aldol reaction of acetone, deuterium is incorporated in the methyl group of the unreacted acetone. Explain this difference in behavior.

Zubair Abdulla

Numerade Educator

Problem 41

Write mechanisms that account for the products of the following reactions:
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 42

Condensations in which the active hydrogen compound is a $\beta$ -keto ester or a $\beta$ -diketone often yield products that result from one molecule of aldehyde or ketone and two molecules of the active methylene component, as shown below. Suggest a reasonable mechanism that accounts for the formation of these products.
(FIGURE CAN'T COPY)

Shazia Naz

Numerade Educator

Problem 43

The following reaction illustrates the Robinson annulation reaction (Section $19.7 \mathrm{A}$ ). Provide a mechanism.
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 44

What is the structure of the cyclic compound that forms after the Michael addition of 1 to 2 in the presence of sodium ethoxide?
(FIGURE CAN'T COPY)

Shazia Naz

Numerade Educator

Problem 45

Synthesize (a) and (b) from cyclopentanone and (c) from diethyl malonate. You may use any other reagents necessary.
(FIGURE CAN'T COPY)

Ronald Prasad

Numerade Educator

Problem 46

Provide a mechanism for the following reaction.
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 47

Predict the products of the following reactions.
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 48

Predict the products from the following reactions.
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 49

The mandibular glands of queen bees secrete a fluid that contains a remarkable compound known as "queen substance." When even an exceedingly small amount of the queen substance is transferred to worker bees, it inhibits the development of their ovaries and prevents the workers from bearing new queens. Queen substance, a monocarboxylic acid with the molecular formula $\mathrm{C}_{10} \mathrm{H}_{16} \mathrm{O}_{3},$ has been synthesized by the following route:
(EQUATION CAN'T COPY)
On catalytic hydrogenation, queen substance yields compound D, which, on treatment with iodine in sodium hydroxide and subsequers acidification, yields a dicarboxylic acid $\mathbf{E} ;$ that is,
$$
\text { Queen substance } \frac{\mathrm{H}_{2}}{\mathrm{Pd}} \mathbf{D}\left(\mathrm{C}_{10} \mathrm{H}_{18} \mathrm{O}_{3}\right) \frac{(1) \mathrm{l}_{2} \mathrm{in} \mathrm{aq} . \mathrm{NaOH}}{(2) \mathrm{H}_{3} \mathrm{O}^{+}} \mathbf{E}\left(\mathrm{C}_{9} \mathrm{H}_{16} \mathrm{O}_{4}\right)
$$
Provide structures for the queen substance and compounds $A-E .$

Joanna Quigley

Numerade Educator

Problem 50

Outline a racemic synthesis of Darvon (below), an analgesic compound whose use has been discontinued, starting with ethyl phenyl ketone.
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 51

Show how dimedone can be synthesized from malonic ester and 4-methyl-3-penten-2-one (mesityl oxide) under basic conditions.
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 52

Write the mechanistic steps in the cyclization of cthyl phenylacetoacetate (ethyl 3-oxo-4-phenylbutanoate) in concentrated sulfuric acid to form naphthoresorcinol ( 1.3-naphthalenediol).

Zubair Abdulla

Numerade Educator

Problem 53

When an aldehyde or a ketone is condensed with cthyl $\alpha$ -chloroacetate in the presence of sodium ethoxide, the product is an $\alpha, \beta$ -epoxy ester called a glycidic ester. The synthesis is called the Darzens condensation.
(FIGURE CAN'T COPY)
(a) Outline a reasonable mechanism for the Darzens condensation. (b) Hydrolysis of the epoxy ester leads to an cpoxy acid that, on heating with pyridine, furnishes an aldehyde. What is happening here?
(c) Starting with $\beta$ -ionone (Practice Problem 19.13 ), show how you might synthesize the following aldehyde. This aldehyde is an intermediate in an industrial synthesis of vitamin A.
(FIGURE CAN'T COPY)

Tom Rutherford

Numerade Educator

Problem 54

The Perkin condensation is an aldol-type condensation in which an aromatic aldchyde (ArCHO) reacts with a carboxylic acid anhydride, $\left(\mathrm{RCH}_{2} \mathrm{CO}\right)_{2} \mathrm{O},$ to give an $\alpha, \beta$ -unsaturated acid $\left(\mathrm{Ar} \mathrm{CH}=\mathrm{CRCO}_{2} \mathrm{H}\right)$. The catalyst that is usually employed is the potassium salt of the carboxylic acid $\left(\mathrm{RCH}_{2} \mathrm{CO}_{2} \mathrm{K}\right) .$ (a) Outline the Perkin condensation that takes place when benzaldehyde reacts with propanoic anhydride in the presence of potassium propanoate. (b) How would you use a Perkin condensation to prepare $p$ -chlorocinnamic acid, $p-\mathrm{ClC}_{6} \mathrm{H}_{4} \mathrm{CH}=\mathrm{CHCO}_{2} \mathrm{H} ?$

Ronald Prasad

Numerade Educator

Problem 55

(a) Infrared spectroscopy provides an easy method for deciding whether the product obtained from the addition of a Grignard reagent to an $\alpha, \beta$ -unsaturated ketone is the simple addition product or the conjugate addition product. Explain. (What peak or peaks would you look for:) (b) How might you follow the rate of the following reaction using UV spectroscopy?
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 56

Allowing acetone to react with 2 molar equivalents of benzaldehyde in the presence of $\mathrm{KOH}$ in ethanol leads to the formation of compound $\mathbf{X}$. The $^{13} \mathrm{C}$ NMR spectrum of $\mathbf{X}$ is given in Fig. $19.1 .$ Propose a structure for compound $\mathbf{X}$.
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 57

(+) Fenchone is a terpenoid that can be isolated from fennel oil. ( $\pm$ )-Fenchone has bece synthesized through the following route. Supply the missing intermediates and reagents (a)-(k).
(FIGURE CAN'T COPY)

Shazia Naz

Numerade Educator

Problem 58

For each of the following questions, please provide a route that could reasonably be expected to convert the starting material into the product. In each case, more than one reaction is required, and reactions you have learned in previous chapters may be needed to solve
the problem.
(FIGURE CAN'T COPY)

Lottie Adams

Numerade Educator

Problem 59

For each of the following, identify the product (represented by A and B) that would be formed through the indicated sequence of the steps from the given starting material.
(FIGURE CAN'T COPY)

Lottie Adams

Numerade Educator

Problem 60

Develop a synthesis for the following molecule using only the indicated materials as sources for the carbon atoms that appear in the final product. As a hint, you will need to draw upon several reactions from earlier chapters to come up with a successful solution, and you may have to use some of the carbon sources more than one time.
(FIGURE CAN'T COPY)

Ian Kaigh

Numerade Educator

Problem 61

Provide a mechanism for each of the following reactions.
(FIGURE CAN'T COPY)

Zubair Abdulla

Numerade Educator

Problem 62

(a) Deduce the structure of product A, which is highly symmetrical:
(FIGURE CAN'T COPY)
The following are selected spectral data for $\mathbf{A}$ :
MS $(m / z): 220\left(\mathrm{M}^{\dagger}\right)$
IR $\left(\mathrm{cm}^{-1}\right): 2930,2860,1715$
$$\begin{aligned}
&\left.^{1} \mathrm{H} \mathrm{NMR}(\mathscr{S}): 1.25(\mathrm{m}), 1.29(\mathrm{m}), 1.76(\mathrm{m}), 1.77(\mathrm{m}), 2.14(\mathrm{s}), \text { and } 2.22(\mathrm{t}) ; \text { (area ratios } 2: 1: 2: 1: 2: 2, \text { respectively }\right)\\
&^{13} \mathrm{C} \mathrm{NMR}(\delta): 23\left(\mathrm{CH}_{2}\right), 26\left(\mathrm{CH}_{2}\right), 27\left(\mathrm{CH}_{2}\right), 29(\mathrm{C}), 39(\mathrm{CH}), 41\left(\mathrm{CH}_{2}\right), 46\left(\mathrm{CH}_{2}\right), 208(\mathrm{C})
\end{aligned}$$
(b) Write a mechanism that explains the formation of A.

Arpit Gupta

Numerade Educator

Problem 63

(a) Draw mechanisms to account for the following two transformations, each of which leads to the same product. (b) Why are these new products favored over the starting materials under these conditions?
(FIGURE CAN'T COPY)

Lottie Adams

Numerade Educator