Jones M., Fleming S.A. Organic Chemistry

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10.13 Summary 459

9. Dihalides

Vicinal dihalide, anti addition, X = Br or Cl

Vicinal dihalide, mostly anti addition,

X = Br or Cl, further reaction likely

Geminal dihalide, X = Br, Cl, or I,

double HX addition

RR CC

excess

10. Vicinal Diols

syn Addition

anti Addition

–

1. KMnO

2. H

O/HO

O /H

O/HO

HO OH

1. OsO

2. H

syn Addition

12. Ketones

This is only one example; there is a different

product for every 1,3-dipole; alkynes work too

11. Heterocyclic Five-Membered Rings

An ozonide is an intermediate; other reagents

will also decompose the ozonide

Forms methyl ketones, never the aldehyde

1. O

2. Zn/CH

COOH

O /H

Hg(OAc)

13. Epoxides (Oxiranes)

syn Addition

COOOH

14. Tetrahalides

The intermediate vicinal dihalide can be isolated

excess

15. Vinyl Halides

Markovnikov addition and it’s hard to stop here;

a second addition of H X occurs

X = Br or Cl

460 CHAPTER 10 Additions to Alkenes 2 and Additions to Alkynes

Common Errors

What psychopathology exists in this chapter comes not so

much from “something everyone always gets wrong” or from an

overwhelmingly difficult concept, but from the mass of detail.

There have been those who have succumbed to despair at sort-

ing out all the stereochemical nuances, at dealing with the many

new mechanisms and synthetic methods—at just making

rational sense of all the material in this chapter and Chapter 9.

There certainly is a lot of information, and you must be very

careful to keep your new synthetic methods properly cataloged.

There is a unifying principle that may help you to keep from

getting lost in the mechanism jungle: “Lewis acids (electrophiles)

react with Lewis bases (nucleophiles).”

The Lewis base or nucleophile in most of the reactions in

this chapter and Chapter 9 is the π bond of an alkene or an

alkyne. The Lewis acids or electrophiles are numerous, but most

add to give either an intermediate, or a stable three-membered

ring (not all, however; hydrogenation does not, and 1,3-dipolar

addition leads to a host of five-membered rings).

The three-membered rings are themselves often prone to

further reaction with nucleophiles, and the final products of

reaction may be quite far removed in structure from the start-

ing material! Moreover, not all the mechanistic details are

known about all these processes. There are reactions about

which we need much more information. The reactions of

alkynes with halogens and HX are examples, and even hydro-

genation has a complicated mechanism, still somewhat

obscure to organic chemists.

A good technique that helps one not to get too over-

whelmed or lost is to anchor oneself in one or two specific

reactions and then to generalize; to relate other reactions to

the anchor reaction. For example, the polar addition of

hydrogen chloride and hydrogen bromide to alkenes

(p. 365) is within anyone’s ability to master. Extensions to

hydration reactions of alkenes and alkynes and to hydrobora-

tion become easier if the analogy with the anchor is always

kept in mind. Similarly, use the reaction of alkenes with Br

as an anchor on which to hang the other ring-forming

addition reactions. It is useful to start a set of mechanism

cards to go along with your synthesis cards in order to keep

track of the detail.

10.14 Additional Problems

PROBLEM 10.29 Show the reaction you would use to synthe-

size bromoethene if your only source of carbon is acetylene.

PROBLEM 10.30 Show how you would make 2-azidobutane if

your only source of carbon is 1-butene.

PROBLEM 10.31 Show how you would make trans-2-methoxy-

cyclohexanol starting with cyclohexene.

PROBLEM 10.32 Show how you would make cis-1-bromo-2-

methoxycyclohexane from cyclohexene and any other reagents

you might need.

PROBLEM 10.33 Show the major organic product(s) expected

when 1-methylcyclohexene reacts with the following reagents.

Pay close attention to stereochemistry and regiochemistry

where appropriate.

(a) D

/Pd/C

(b) Br

/CCl

/CH

(d) Hg(OAc)

O, then NaBD

in base (no stereochemical

preference in this reaction)

(e) 1. B

(BH

)/THF; 2. H

/HO



(f) CF

COOOH

(g) CH

, hν

(h) 1. O

;2.(CH

)

(i) 1. OsO

; 2. NaHSO

(j)

PROBLEM 10.34 Show in detail how both enantiomers of

product are formed in Problem 10.33a.

PROBLEM 10.35 Predict the major product(s), including

stereochemistry where relevant, for the bromination reaction

(Br

/CCl

) with each of the following alkenes:

(a) 1-pentene

(b) cis-2-pentene

(d) cis-3-hexene

(e) trans-3-hexene

PROBLEM 10.36 Which of the products in the previous prob-

lem are chiral and which are achiral?

PROBLEM 10.37 Predict the possible products in the reaction

between bromine in water with the following alkenes:

(a) cyclobutene

(b) trans-2-butene

(d) cis-2-hexene

10.14 Additional Problems 461

(a)

CCH

HBr

excess

(b)

CCH

excess

(c)

CCH

O/H

(d)

2. H

/NaOH

(e)

Lindlar

catalyst

(f)

(a) (b) (c)

(h) (i)

(j)

(d)

(e) (f) (g)1

PROBLEM 10.38 Show the major organic products expected

when the following acetylenes react with the reagents shown.

Pay attention to stereochemistry and regiochemistry where

appropriate.

PROBLEM 10.40 What reagents would you use to convert the

following starting materials into the products shown? There are

no restrictions on reagents, but you must start from the mol-

ecule shown.

(e)

(f)

(b)

(a)

(c)

(d)

HO OH

(g)

C CH

(h)

HO OH

PROBLEM 10.39 Devise syntheses for the following molecules

starting from 3,3-dimethyl-1-butene (1). You may use any inor-

ganic reagent (no carbons), and the following “special” organic

reagents: diazomethane, carbon tetrachloride, tert-butyl alcohol,

tert-butyl iodide, Hg(OAc)

, carbon, (CH

)

S, trifluoroperacetic

acid, strychnine, and Igor Likhotvorik’s famous boiled goose-in-

a-kettle. Your answers may be very short, and no mechanisms

are required.

462 CHAPTER 10 Additions to Alkenes 2 and Additions to Alkynes

(a)

(f) (g) (h)

(

) (j)

(b) (c) (d)

(e)

OCH

COOH

From

(a)

(b)

(d)

(e)

(f)

(c)

(h)

(g)

(i)

(j)

PROBLEM 10.41 Devise syntheses for the following molecules

starting from methylenecyclopentane (1). You may use any

inorganic reagent (no carbons), and the following “special”

organic reagents: diazomethane, carbon tetrachloride, tert-butyl

alcohol, methyl alcohol, ethyl alcohol, tert-butyl iodide,

Hg(OAc)

, carbon, (CH

)

S, trifluoroperacetic acid, and the

secret contents of Zhou Enlai’s favorite veggie dumplings. Your

answers may be very short, and no mechanisms are required.

PROBLEM 10.42 Provide syntheses for the following molecules

starting from the indicated compound. You may use any appro-

priate reagents you need, including Mrs. Tao’s incredible baby

eels in white pepper sauce.

PROBLEM 10.43 Draw four possible products for the reaction of

(R)-3-methylcyclopentene with bromine in methanol. Show the

reaction pathway for the compound you think would be the major

product and explain why you think it would be the major product.

PROBLEM 10.44 Which of the products in the previous prob-

lem are chiral and which are achiral?

PROBLEM 10.45 In Section 10.2b (p. 414), we considered two

possible mechanisms for the addition of Br

to alkenes. Ultimately,

a stereochemical experiment that used a ring compound was

used to decide the issue in favor of a mechanism in which addi-

tion proceeded through a bromonium ion rather than an open

carbocation. Use a detailed stereochemical analysis to show how

the experimental results shown below are accommodated by an

intermediate bromonium ion but not by an open carbocation.

PROBLEM 10.46 Explain the following regiochemical results

mechanistically.

PROBLEM 10.47 Predict the major product for the following

reactions:

CCl

cis-2-Butene Racemic dibromide

CCl

trans-2-Butene meso Dibromide

HOR

Major product

roduct

HOR

–

ORNa

2) NaBH

1) Hg(OAc)

C(CH

)

Pd/C

2) NaOH/H

1) BH

/THF

2) Na

1) OsO

10.14 Additional Problems 463

–

A bromoh

drin

100 ⬚C, 3 h

(73%)

(Not observed)

COOOH

(a) (b) (c)

(d)

(cis or

trans)

PROBLEM 10.49 Treatment of cis-2-butene with Br

gives a product (C

OBr), that reacts with sodium hydride

to give a meso compound of the formula C

O. With the

same sequence of reagents, trans-2-butene gives a different

compound (a racemic mixture) of the same formula, C

Explain mechanistically, paying close attention to stereochemi-

cal relationships.

PROBLEM 10.50 The difference in nucleophilicity between

differently substituted alkenes can lead to selectivity in the

epoxidation reaction. Rationalize the position of faster

epoxidation in the 1,4-cyclohexadiene below and explain your

reasoning.

PROBLEM 10.48 In Section 10.4a (p. 423), you saw that

epoxidation of an alkene with a peracid such as trifluoroper-

acetic acid results in addition of an oxygen atom to the alkene

in such a way as to preserve in the product epoxide the

stereochemical relationships originally present in the alkene.

That is, cis alkene leads to cis epoxide, and trans alkene leads

to trans epoxide. There is another route to epoxides that

involves cyclization of halohydrins. Use cis-2-butene as a sub-

strate to analyze carefully the stereochemical outcome of this

process. What happens to the original alkene stereochemistry

in the product?

PROBLEM 10.51 There is one alcohol that can be synthesized

in one or two easy steps from each of the following precursors.

What is the alcohol, and how would you make it from each

starting material?

NaOH

COOOH

(a)

NaOH/H

KMnO

(b)

Periodate intermediate

PROBLEM 10.52 Show the final products of the reactions

below. Pay attention to stereochemistry.

PROBLEM 10.53 Glycols react with periodic acid to form a

cyclic periodate intermediate.The periodate then decomposes

to a pair of carbonyl compounds.

If the product from (b) in Problem 10.52 is cleaved with

periodic acid, what would be the final product of the reaction

sequence?

From a synthetic point of view, this two-step sequence—the

treatment of an alkene with basic permanganate followed by

periodate cleavage—is equivalent to what other direct method

of cleaving carbon–carbon double bonds? What other way do

you know to convert an alkene into a pair of carbonyl

compounds?

PROBLEM 10.54 Why doesn’t the product of Problem 10.52a

react with periodate?

464 CHAPTER 10 Additions to Alkenes 2 and Additions to Alkynes

No reaction

Formaldehyde

2-Butanone

Isobutyraldehyde

Pd/C

1. O

2. (CH

)

1. O

2. (CH

)

Formaldehyde

1. O

2. H

HOOC COOH

COOH

1. O

2. H

R = CH

hexane

PROBLEM 10.56 α-Terpinene (1) and γ-terpinene (2) are

isomeric compounds (C

) that are constituents of many

plants. Upon catalytic hydrogenation, they both afford

1-isopropyl-4-methylcyclohexane. However, on ozonolysis

followed by oxidative workup, each compound yields different

products. Provide structures for 1 and 2 and explain your

reasoning.

PROBLEM 10.57 In practice, it is often very difficult to isolate

ozonides from ozonolysis of tetrasubstituted double bonds.The

product mixture depends strongly on reaction conditions, but

the products shown in the next column can all be isolated.

Construct reasonable arrow formalisms for all of them.

PROBLEM 10.58 Ozonolysis of 1 in solvent acetone

(dimethyl ketone) leads to 2 as the major product. Explain.

PROBLEM 10.59 trans-β-Methylstyrene reacts with phenyl azide

to give a single product, triazoline (1). What other stereoisomeric

products might have been produced? Draw an arrow formalism

for this reaction and explain what mechanistic conclusions can be

drawn from the formation of a single isomer of 1.

PROBLEM 10.60 Triazoline (1) (formed in Problem 10.59)

decomposes upon photolysis or heating to give aziridine (2).

Write two mechanisms for the conversion of 1 into 2; one a

concerted, one-step reaction, and the other a nonconcerted,

two-step process. How would you use the stereochemically

labeled triazoline (1) to tell which mechanism is correct?

acetone

BrH

CCH

BrH

trans -β-Methylstyrene

Ph =

h ν

or 

(no stereochemistry

implied in the drawing)

PROBLEM 10.55 Incomplete catalytic hydrogenation of a

hydrocarbon, 1 (C

), gives a mixture of three hydrocarbons,

2, 3, and 4. Ozonolysis of 3, followed by reductive workup,

gives formaldehyde and 2-butanone. When treated in the

same way, 4 gives formaldehyde and isobutyraldehyde.

Provide structures for compounds 1–4 and explain your

reasoning.

10.14 Additional Problems 465

hν

COOCH

Old carbene

C =

PROBLEM 10.61 Explain the formation of aziridine (2) in the

following reaction of azide (1). Hints: Draw a full Lewis struc-

ture for the azide, and see Section 10.4d (p. 431).

NaNH

CHC

CCH

CNaIC

NaC

–

PROBLEM 10.62 What does the formation of only cis aziri-

dine (2) from irradiation of azide (1) in cis-2-butene tell you

about the nature of the reacting species in Problem 10.61?

PROBLEM 10.63 A reaction of carbenes not mentioned in

the text is called “carbon–hydrogen insertion.” In this startling

reaction, a reactive carbene ultimately places itself between the

carbon and hydrogen of a carbon–hydrogen bond.

(a) Write two mechanisms for this reaction, one with a single-

step and the other having two steps.

PROBLEM 10.64 Contrast the results of hydroboration/oxida-

tion and mercury (Hg

2

)-catalyzed hydration for 2-pentyne

and 3-hexyne. Would any of these procedures be a practical

preparative method? Explain.

PROBLEM 10.65 Recall that terminal alkynes are among the

most acidic of the hydrocarbons (p. 129), and that the acetylide

ions can be used in S

2 alkylation reactions with an appropriate

alkyl halide. For example,

h ν

COOCH

(b) In 1959, in a classic experiment in carbene chemistry,

Doering and Prinzbach used

C-labeled isobutene to dis-

tinguish the two mechanisms. Explain what their results

mean. The figure shows only one product of the many

formed in the reaction. Focus on this compound only.

(a)

(b)

(c)

(d)

acetic acid

Br Br

(31%) (69%)

Provide syntheses for the following molecules, free of other

isomers. You must use alkynes containing no more than four car-

bon atoms as starting materials. You may use inorganic reagents

of your choice, and other organic reagents containing no more

than two carbon atoms. Mechanisms are not required.

PROBLEM 10.66 Many additions of bromine to acetylenes give

only trans dibromide intermediates. However, there are excep-

tions. Here is one. Explain why phenylacetylene gives both cis

and trans dibromides on reaction with bromine.

466 CHAPTER 10 Additions to Alkenes 2 and Additions to Alkynes

Use Organic Reaction Animations (ORA) to answer the

following questions:

PROBLEM 10.67 The second page of reactions on the ORA

CD has several reactions that are discussed in Chapter 10.

Select the “Stabilized alkene halogenation” animation. This

animation shows the calculated pathway for the bromination

of acenaphthylene (see Problem 10.7). Notice the energy dia-

gram for the reaction. What does the energy diagram tell you

about the intermediate? Stop the animation at the intermedi-

ate and click on the LUMO track. Notice the interesting pat-

tern of LUMO (or cation) density. Draw all the resonance

structures that are consistent with this calculated representa-

tion of the intermediate. Based on the LUMO picture, which

of the resonance structures that you have drawn contribute

most to the overall species? Which contribute least? Can you

guess why?

PROBLEM 10.68 The “Halohydrin formation” animation was

calculated using a symmetrical alkene.The symmetry of the

alkene means that nucleophilic addition to the bromonium

intermediate will not be regioselective. Select play for this reac-

tion. Stop at the first intermediate and observe the calculated

LUMO. Based on this data, where is the positive charge locat-

ed? Show four products that would be formed through nucleo-

philic attack at each of the places of LUMO density.

PROBLEM 10.69 Epoxidation of alkenes is thought to be a

concerted process. Select the “Alkene epoxidation” animation.

Does the energy diagram indicate this reaction is concerted?

Why do the methyl groups on the cis-2-butene rotate during

the reaction? This reaction occurs because of the weak

oxygen–oxygen bond of a peracid. Hydrogen peroxide (H

)

also has an oxygen–oxygen bond. Would this reaction mecha-

nism work with hydrogen peroxide?

Radical Reactions

467

11.1 Preview

11.2 Formation and Simple

Reactions of Radicals

11.3 Structure and Stability

of Radicals

11.4 Radical Addition to Alkenes

11.5 Other Radical Addition

Reactions

11.6 Radical-Initiated Addition

of HBr to Alkynes

11.7 Photohalogenation

11.8 Allylic Halogenation:

Synthetically Useful Reactions

11.9 Special Topic: Rearrangements

(and Nonrearrangements)

of Radicals

11.10 Special Topic: Radicals in Our

Bodies; Do Free Radicals Age

Us?

11.11 Summary

11.12 Additional Problems

RADICALS IN THE AIR It is radical initiation and propagation steps like those

shown in Figure 11.40 that are thought to be the cause of ozone depletion.

This chart shows ozone concentrations over the Antarctic in 2006.

468 CHAPTER 11 Radical Reactions

Wystan Hugh Auden (1907–1973) was one of the best known and most influential British poets of his generation.

Knowledge may have its purposes,

But guessing is always

More fun than knowing.

—W. H. AUDEN

WORKED PROBLEM 11.1 Find an exception to the generalization stated in this chap-

ter’s first paragraph. What reaction have we studied that involves no polar inter-

mediates and doesn’t have a highly polar transition state? Hint: Think “recent.”

ANSWER One example is the reaction studied in Section 10.4e (p. 433), the addi-

tion of a triplet carbene to an alkene. Only neutral intermediates are involved in

this reaction. Another example is hydrogenation, the conversion of an alkene and

hydrogen into an alkane (p. 411).

PROBLEM 11.2 Name a reaction that involves no intermediates but certainly has a

highly polar transition state.

ESSENTIAL SKILLS AND DETAILS

1. You have to be able to sketch the steps of chain reactions.This chapter introduces

initiation, propagation, and termination steps, which are quite common in radical

reactions. In a chain reaction, a repeating process keeps the reaction going until starting

materials are used up or termination occurs. It is important to be able to write

initiation, propagation, and termination steps.

2. Another important skill is understanding the factors that influence selectivity. In

synthesis, selectivity is everything, because the synthetic chemist seeks a single product

over all others. In order to maximize the formation of that single product, we need to

understand the factors that control selectivity. In this chapter, selectivity is discussed

in the context of the photochemical halogenation of alkanes. This reaction is more

important for understanding selectivity than for its use in synthesis.

3. N-Bromosuccinimide (NBS) is a standard reagent for inducing bromine into the allylic

and benzylic positions.

11.1 Preview

Although there have been many variations in the details, with few exceptions all of the

reactions we have studied so far have been polar ones.The S

1 and S

2 substitutions,the

addition reactions of HX and X

reagents,and the E1 and E2 reactions all involve cation-

ic electrophiles and anionic nucleophiles,or at least have obviously polar transition states.

Now we come to a series of quite different processes involving the decidedly non-

polar, neutral intermediates called radicals or, sometimes, free radicals. We will also

encounter chain reactions, in which a small number of radicals can set a repeating reac-

tion in motion. In such a case, a few starter molecules can determine the course of an

entire chemical process.

The question of selectivity is prominent in this chapter.What factors influence the abil-

ity of a reactive species to pick and choose among various reaction pathways? In partic-

ular, what is the connection between the energy of a reactive molecule and its reactivity?

Don’t forget—throughout our discussion of these radical reactions, the motion

of single electrons is shown with single-barbed, “fishhook” arrows (see p. 38).

We begin with a section on the formation and simple reactions of radicals and

then move on to structure before considering the more complicated chain reactions.

CONVENTION ALERT