Organic Chemistry

Janice Gorzynski Smith

Chapter 24 Carbonyl Condensation Reactions - all with Video Answers

Educators

Chapter Questions

03:23

Problem 1

Draw the aldol product formed from each compound.

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02:10

Problem 2

Which carbonyl compounds do $not$ undergo an aldol reaction when treated with $^-$OH in H$_2$O?

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02:08

Problem 3

What unsaturated carbonyl compound is formed by dehydration of each $\beta$-hydroxy carbonyl
compound?

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01:25

Problem 4

Acid-catalyzed dehydration of $\beta$-hydroxy carbonyl compounds occurs by the mechanism
discussed in Section 9.8. With this in mind, draw a stepwise mechanism for the following reaction.

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03:55

Problem 5

What aldehyde or ketone is needed to prepare each compound by an aldol reaction?

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01:59

2-Pentylcinnamaldehyde, commonly called flosal, is a perfume ingredient with a jasmine-like odor.
Flosal is an $\alpha$,$\beta$-unsaturated aldehyde made by a crossed aldol reaction between benzaldehyde ($\mathrm{C}_6\mathrm{H}_5\mathrm{CHO}$) and heptanal ($\mathrm{CH}_3\mathrm{CH}_2\mathrm{CH}_2\mathrm{CH}_2\mathrm{CH}_2\mathrm{CH}_2\mathrm{CHO}$), followed by dehydration. Draw a stepwise mechanism for the following reaction that prepares flosal.

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02:47

Problem 7

Draw the products formed in each crossed aldol reaction.

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04:16

Problem 8

Draw the products formed in the crossed aldol reaction of phenylacetaldehyde (C6H5CH2CHO) with
each compound: (a) $\mathrm{CH}_2(\mathrm{COOEt})_2$; (b) $\mathrm{CH}_2(\mathrm{COCH}_3)_2$; (c) $\mathrm{CH}_3\mathrm{COCH}_2\mathrm{CN}$.

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06:12

Problem 9

What aldol product is formed when two molecules of butanal react together in the presence of base? What reagents are needed to convert this product to each of the following compounds?

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02:52

Problem 10

What carbonyl starting materials are needed to prepare each compound using a directed aldol reaction?

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03:59

Problem 11

A key step in the synthesis of donepezil (trade name Aricept) is a directed aldol reaction that forms $\alpha$,$\beta$-unsaturated carbonyl compound $\textbf{X}$. What carbonyl starting materials are needed to prepare $\textbf{X}$ using a directed aldol reaction? What reagents are needed to convert $\textbf{X}$ to donepezil?

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02:02

Problem 12

Draw a stepwise mechanism for the conversion of 2,6-heptanedione to 3-methyl-2-cyclohexenone
with NaOEt, EtOH.

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02:26

Problem 13

What cyclic product is formed when each 1,5-dicarbonyl compound is treated with aqueous $-$OH?

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01:44

Problem 14

Following the two-step reaction sequence depicted in Figure 24.5, write out the steps needed to
convert $\textbf{A}$ to $\textbf{B}$.

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03:06

Problem 15

What $\beta$-keto ester is formed when each ester is used in a Claisen reaction?

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04:26

Problem 16

What crossed Claisen product is formed from each pair of compounds?

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02:49

Problem 17

Avobenzone is a conjugated compound that absorbs ultraviolet light with wavelengths in the 320$-$400 nm region, so it is a common ingredient in commercial sunscreens. Write out two different crossed Claisen reactions that form avobenzone.

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02:12

Problem 18

Draw the products of each reaction.

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02:28

Problem 19

Two steps in a synthesis of the analgesic ibuprofen, the chapter-opening molecule, include a carbonyl condensation reaction, followed by an alkylation reaction. Identify intermediates $\textbf{A}$ and $\textbf{B}$ in the synthesis of ibuprofen.

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02:17

Problem 20

What two $\beta$-keto esters are formed in the Dieckmann reaction of the following diester?

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01:40

Problem 21

Which of the following compounds can serve as Michael acceptors?

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04:21

Problem 22

What product is formed when each pair of compounds is treated with NaOEt in ethanol?

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02:07

Problem 23

What starting materials are needed to prepare each compound by the Michael reaction?

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05:26

Problem 24

Draw the products when each pair of compounds is treated with $\mathrm{CH}_3\mathrm{CH}_2\mathrm{O}^-$, $\mathrm{CH}_3\mathrm{CH}_2\mathrm{OH}$ in a
Robinson annulation reaction.

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03:22

Problem 25

What starting materials are needed lo synthesize each compound by a Robinson annulation?

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01:45

Problem 26

Draw the aldol product formed from each pair of starting materials using $^-$OH, H$_2$O

Colton K

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02:22

Problem 27

What steps are needed to convert $\textbf{A}$ to $\textbf{B}$?

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03:51

Problem 28

Draw the product formed from an aldol reaction with the given starting material(s) using $^-$OH, H$_2$O.

a. $(\mathrm{CH}_3)_2\mathrm{CHCHO}$ only

b. $(\mathrm{CH}_3)_2\mathrm{CHCHO} + \mathrm{CH}_2 = 0$

c. $\mathrm{C}_6\mathrm{H}_5\mathrm{CHO} + \mathrm{CH}_3\mathrm{CH}_2\mathrm{CH}_2\mathrm{CHO}$

d. $(\mathrm{CH}_3\mathrm{CH}_2)_2\mathrm{C}=\mathrm{O}$ only

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02:52

Problem 29

What four $\beta$-hydroxy aldehydes are formed by a crossed aldol reaction of $\mathrm{CH}_3\mathrm{CH}_2\mathrm{CH}_2\mathrm{CHO}$ and $\mathrm{C}_6\mathrm{H}_5\mathrm{CH}_2\mathrm{CHO}$?

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02:57

Problem 30

Draw the product formed in each directed aldol reaction.

Colton K

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02:36

Problem 31

Draw the product formed when each dicarbonyl compound undergoes an intramolecular aldol reaction followed by dehydration.

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05:02

Problem 32

What starting materials are needed to synthesize each compound using an aldol or similar reaction?

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02:37

Problem 33

A published synthesis of the analgesic nabumetone uses a crossed aldol reaction to form $\textbf{X}$. What is the structure of $\textbf{X}$? $\textbf{X}$ is converted to nabumetone in one step by hydrogenation with H$_2$ and Pd-C. (See Problem 23.29 for another way to make nabumetone.)

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01:39

Problem 34

What product is formed when a solution of $\textbf{A}$ and $\textbf{B}$ is treated with mild base? This reaction is the first step in the synthesis of rosuvastatin (sold as a calcium salt under the trade name Crestor), a drug used to treat patients with high cholesterol.

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03:16

Problem 35

What dicarbonyl compound is needed to prepare each compound by an intramolecular aldol reaction?

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02:23

Problem 36

Identify the structures of $\textbf{C}$ and $\textbf{D}$ in the following reaction sequence.

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03:16

Problem 37

Explain why ketone $\textbf{K}$ undergoes aldol reactions but ketone $\textbf{J}$ does not.

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03:42

Problem 38

Draw the Claisen product formed from each ester.

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02:47

Problem 39

What four compounds are formed from the crossed Claisen reaction of $\mathrm{CH}_3\mathrm{CH}_2\mathrm{CH}_2\mathrm{CH}_2\mathrm{CO}_2\mathrm{Et}$ and $\mathrm{CH}_3\mathrm{CH}_2\mathrm{CO}_2\mathrm{Et}$?

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04:51

Problem 40

Draw the product formed from a Claisen reaction with the given starting materials using $^-$OEt, EtOH.

a. $\mathrm{CH}_3\mathrm{CH}_2\mathrm{CH}_2\mathrm{CO}_2\mathrm{Et} + \mathrm{C}_6\mathrm{H}_5\mathrm{CO}_2\mathrm{Et}$
b. $\mathrm{CH}_3\mathrm{CH}_2\mathrm{CH}_2\mathrm{CO}_2\mathrm{Et} + (\mathrm{CH}_3)_2\mathrm{C} = \mathrm{O}$
c. $\mathrm{EtO}_2\mathrm{CC}(\mathrm{CH}_3)_2\mathrm{CH}_2\mathrm{CH}_2\mathrm{CH}_2\mathrm{CO}_2\mathrm{Et}$
d. $\mathrm{CH}_3\mathrm{CH}_2\mathrm{CO}_2\mathrm{Et} + (\mathrm{EtO})_2\mathrm{C} = \mathrm{O}$

Colton K

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03:53

Problem 41

What starting materials are needed to synthesize each compound by a crossed Claisen reaction?

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03:45

Problem 42

Even though $\textbf{B}$ contains three ester groups, a single Dieckmann product results when $\textbf{B}$ is treated with NaOCH$_3$ in CH$_3$OH, followed by H$_3$O$^+$. Draw the structure and explain why it is the only product formed.

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02:13

Problem 43

Draw the product formed from a Michael reaction with the given starting materials using $^-$OEt, EtOH.

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03:39

Problem 44

What starting materials are needed to prepare each compound using a Michael reaction?

Colton K

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06:46

Problem 45

$\beta$-Vetivone is isolated from vetiver, a perennial grass that yields a variety of compounds used in traditional eastern medicine, pest control, and fragrance. In one synthesis, ketone $\textbf{A}$ is converted to $\beta$-vetivone by a two-step process: Michael reaction, followed by intramolecular aldol reaction. (a) What Michael acceptor is needed for the conjugate addition? (See Problem 23.63
for another method to form the bicyclic ring system of $\beta$-vetivone.) (b) Draw a stepwise mechanism for the aldol reaction, which forms the six-membered ring.

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06:42

Problem 46

Draw the product of each Robinson annulation from the given starting materials using $^-$OH in H$_2$O solution.

Colton K

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05:22

Problem 47

What starting materials are needed to synthesize each compound using a Robinson annulation?

Ian Kaigh

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07:50

Problem 48

Draw the organic products formed when butanal ($\mathrm{CH}_3\mathrm{CH}_2\mathrm{CH}_2\mathrm{CHO}$) is treated with each reagent.

a. $^-$OH, H$_2$O
b. $^-$OH, CH$_2 = \mathrm{O}$, H$_2$O
c. [1] LDA; [2] CH$_3$CHO; [3] H$_2$O
d. CH$_2$(CO$_2$Et)$_2$, NaOEt, EtOH
e. [1] CH$_3$Li; [2] H$_2$O
f. $\mathrm{NaBH}_4$, CH$_3$OH
g. H$_2$ , Pd-C
h. HOCH$_2$CH$_2$OH, TsOH
i. CH$_3$NH$_2$, mild acid
j. (CH$_3$)$_2$NH, mild acid
k. CrO$_3$, H$_2$SO$_4$
I. Br$_2$, CH$_3$COOH
m. $\mathrm{Ph}_3\mathrm{P}=\mathrm{CH}_2$
n. NaCN, HCI
o. [1] LDA; [2] CH$_3$I

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05:06

Problem 49

Draw the organic products formed in each reaction.

Ian Kaigh

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06:20

Problem 50

Fill in the lettered reagents needed for each reaction.

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03:27

Problem 51

Identify compounds $\textbf{A}$ and $\textbf{B}$, two synthetic intermediates in the 1979 synthesis of the plant growth hormone gibberellic acid by Corey and Smith. Gibberellic acid induces cell division and elongation, thus making plants tall and leaves large.

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02:37

Problem 52

When acetaldehyde (CH$_3$CHO) is treated with three equivalents of formaldehyde ($\mathrm{CH}_2= \mathrm{O}$) in the presence of aqueous $\mathrm{Na}_2\mathrm{CO}_3$,
(HOCH$_2$)$_3$CCHO is formed as product. Draw a stepwise mechanism for this process.

Colton K

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11:49

Problem 53

In theory, the intramolecular aldol reaction of 6-oxoheptanal could yield the three compounds shown. It turns out, though, that 1-acetylcyclopentene is by far the major product. Why are the other two compounds formed in only minor amounts? Draw a stepwise mechanism to show how all three products are formed.

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03:28

Problem 54

Draw a stepwise mechanism for the following cyclization reaction.

Colton K

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04:18

Problem 55

Draw a stepwise mechanism for the following variation of the aldol reaction, often called a nitro aldol reaction.

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05:04

Problem 56

Draw a stepwise mechanism for the following Robinson annulation. This reaction was a key step in a synthesis of the steroid cortisone by R. B. Woodward and co-workers at Harvard University in 1951.

Colton K

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06:42

Problem 57

Reaction of $\textbf{X}$ and phenylacetic acid forms an intermediate $\textbf{Y}$, which undergoes an intramolecular reaction to yield rofecoxib. Rofecoxib is a nonsteroidal anti-inflammatory agent once marketed under the trade name Vioxx, now withdrawn from the market because of increased risk of heart attacks from long-term use in some patients. Identify $\textbf{Y}$ and draw a stepwise mechanism for its conversion to rofecoxib.

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02:20

Problem 58

Green polymer synthesis$-$the preparation of polymers by environmentally friendly methods using starting materials that are not derived from petroleum$-$is an active area of research. One example is the polymerization of tulipalin A, a natural product derived from tulips, to afford polytulipalin. Polytulipalin has properties similar to some petroleum-derived polymers, but its availability from a natural source has made it a possible attractive alternative to these polymers. Polymerization occurs in the presence of a strong base (B:), and each new C$-$ C bond in polytulipalin is formed by a Michael reaction. Draw a stepwise mechanism for the formation of one C $-$ C bond in polytulipalin. (See Section 31.8 for other aspects of green polymer chemistry.)

Colton K

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07:24

Problem 59

Coumarin, a naturally occurring compound isolated from lavender, sweet clover, and tonka bean, is made in the laboratory from o-hydroxybenzaldehyde by the reaction depicted below. Draw a stepwise mechanism for this reaction. Coumarin derivatives are useful synthetic anticoagulants.

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02:15

Problem 60

(a) Draw a stepwise mechanism for the reaction of ethyl 2,4-hexadienoate with diethyl oxalate in the presence of base. (b) How does your mechanism explain why a new carbon-carbon bond forms on C6? (c) Why is this reaction an example of a crossed Claisen reaction?

Colton K

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06:46

Problem 61

Convert acetophenone (C$_6$H$_5$COCH$_3$) into each compound by one or more steps. You may use any other organic compounds or required inorganic reagents.

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04:19

Problem 62

How would you convert cyclohexanone into each compound using any required inorganic reagents and needed organic compounds?

Colton K

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11:18

Problem 63

Devise a synthesis of each compound from cyclopentanone, benzene, and organic alcohols having $\leq$ 3 C's. You may also use any required organic or inorganic reagents.

Ian Kaigh

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05:06

Problem 64

Devise a synthesis of each compound from $\mathrm{CH}_3\mathrm{CH}_2\mathrm{CH}_2\mathrm{CO}_2\mathrm{Et}$, benzene, and alcohols having $\leq$ 2 C's. You may also use any required organic or inorganic reagents.

Colton K

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03:52

Problem 65

Devise a synthesis of 2-methylcyclopentanone from cyclohexene. You may also use any required reagents.

Ian Kaigh

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03:20

Problem 66

Octinoxate is an unsaturated ester used as an active ingredient in sunscreens. (a) What carbonyl compounds are needed to synthesize this compound using a condensation reaction? (b) Devise a synthesis of octinoxate from the given organic starting materials and any other needed reagents.

Colton K

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05:57

Problem 67

Answer the following questions about 2-acetylcyclopentanone.

a. What starting materials are needed to form 2-acetylcyclopentanone by a Claisen reaction that forms bond (a)?
b. What starting materials are needed to form 2-acetylcyclopentanone by a Claisen reaction that forms bond (b)?
c. What product is formed when 2-acetylcyclopentanone is treated with NaOCH$_2$CH$_3$,
followed by CH$_3$I?
d. Draw the Robinson annulation product(s) formed by reaction of 2-acetylcyclopentanone with methyl vinyl ketone ($\mathrm{CH}_2 = \mathrm{CHCOCH}_3$).
e. Draw the structure of the most stable enol tautomer(s).

Ian Kaigh

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05:57

Problem 68

Four steps in the synthesis of helminthosporal, a toxin produced by a wheat plant fungus, are shown below.

a. What compounds are needed to carry out Step [1)?
b. What compounds are needed to carry out Step [2]?
c. Write a detailed mechanism for Step [3].
d. Write a detailed mechanism for Step [4]. What is unusual about the product of this reaction?
e. Step [1] adds a formyl group (HCO$-$) and Step [3] removes it. Why was this apparently unnecessary process done?

Colton K

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05:10

Problem 69

Draw a stepwise mechanism for the following reaction, which was used in the synthesis of the ezetimibe (Section 20.6), a drug used to treat patients with high cholesterol.

Ian Kaigh

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02:25

Problem 70

Propose a stepwise mechanism for the following reaction of a $\beta$-keto ester. Suggest a reason why this rearrangement reaction occurs.

Colton K

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06:41

Problem 71

lsophorone is formed from three molecules of acetone $[(\mathrm{CH}_3)_2\mathrm{C}= \mathrm{O}]$ in the presence of base. Draw a mechanism for this process.

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04:39

Problem 72

Draw a stepwise mechanism for the following reaction. [$Hint$: Two Michael reactions are needed.]

Colton K

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11:34

Problem 73

4-Methylpyridine reacts with benzaldehyde (C$_6$H$_5$CHO) in the presence of base to form $\textbf{A}$. (a) Draw a stepwise mechanism for this reaction. (b) Would you expect 2-methylpyridine or 3-methylpyridine to undergo a similar type of condensation reaction? Explain why or why not.

Ian Kaigh

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05:49

Problem 74

Draw a stepwise mechanism for the following reaction, one step in the synthesis of the cholesterol-lowering drug pitavastatin, marketed in Japan as a calcium salt under the name Livalo.

Colton K

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04:27

Problem 75

Devise a stepwise mechanism for the following reaction, a key step in the synthesis of the antibiotic abyssomicin C. Abyssomicin C was isolated from sediment collected from almost 1000 ft below the surface in the Sea of Japan. [$Hint$: The mechanism begins with a Dieckmann reaction.]

Ian Kaigh

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