23-1

2323

Organic Organic ChemistryChemistry

William H. Brown & William H. Brown & Christopher S. FooteChristopher S. FooteWilliam H. Brown & William H. Brown & Christopher S. FooteChristopher S. Foote

23-2

2323Conjugated Conjugated

DienesDienesChapter 23Chapter 23

23-3

2323 Conjugated DienesConjugated Dienes Dienes are divided into three groups

• from heats of hydrogenation, we can compare relative stabilities of conjugated and unconjugated dienes

CH2=CHCH=CHCH3CH2=CHCH2CH=CH2 CH2=C=CHCH2CH3

1,4-Pentadiene(an unconjugated diene)

1,3-Pentadiene(a conjugated diene)

1,2-Pentadiene(a cumulated diene)

23-4

2323 Conjugated DienesConjugated Dienes. ΔHo

-237 (-56.5)1,3-Butadiene

-126 (-30.1)

-127 (-30.3)

kJ (kcal)/molStructural FormulaName

1-Pentene

1-Butene

trans-1,3-Pentadiene

1,4-Pentadiene

trans-2-Butene -115 (-27.6)

cis-2-Butene -120 (-28.6)

-226 (-54.1)

-254 (-60.8)

23-5

2323 Conjugated DienesConjugated Dienes• conjugation of the double bonds in 1,3-butadiene

gives an extra stability of approximately 17 kJ (4.1 kcal)/mol

2H2+ catalyst ΔHo = 2(-127 kJ /mol) = -254 kJ/mol)

2 2

2H2catalyst

+ ΔH0 = -237 kJ /mol

23-6

2323 Conjugated DienesConjugated Dienes

• the pi system of butadiene is derived from the combination of four 2p atomic orbitals; there are two bonding MOs and two antibonding MOs

23-7

2323 Conjugated SystemsConjugated Systems• systems containing conjugated double bonds, not just

those of dienes, are more stable than those containing unconjugated double bonds

3-Cyclohexenone(less stable)

2-Cyclohexenone(more stable)

O O

23-8

2323 1,2- and 1,4-Addition1,2- and 1,4-Addition Addition of 1 mole of HBr to butadiene at -78°C

gives a mixture of two constitutional isomers

• we account for these products by the following two-step mechanism

1-Bromo-2-butene10%

(1,4-addition)

-78°C

+

+

3-Bromo-1-butene90%

(1,2-addition)

CH2=CH-CH=CH2 HBr

CH2=CH-CH-CH2 CH2-CH=CH-CH2

1,3-ButadieneH HBr Br

23-9

2323 1,2- and 1,4-Addition1,2- and 1,4-Addition• the key intermediate is a resonance-stabilized allylic

carbocation

(1,4-Addition)(1,2-Addition)

+

+ +

Br HBrH

CH2=CH-CH=CH2 H-Br

CH2=CH-CH-CH2 CH2-CH=CH-CH2

CH2=CH-CH-CH2 CH2-CH=CH-CH2

Br-

Br-

H H

23-10

2323 1,2- and 1,4-Addition1,2- and 1,4-Addition Addition of 1 mole of Br2 to butadiene at -15°C

also gives a mixture of two constitutional isomers

• we account for the formation of these 1,2- and 1,4-addition products by a similar mechanism

-15°C

3,4-Dibromo-1-butene(54%)

(1,2-addition)

1,4-Dibromo-2-butene(46%)

(1,4-addition)

+

+

1,3-Butadiene

CH2=CH-CH=CH2 Br2

CH2-CH=CH-CH2CH2-CH-CH=CH2

Br Br Br Br

23-11

2323 Additional Exptl InfoAdditional Exptl Info• for addition of HBr at -78°C and Br2 at -15°C, the 1,2-

addition products predominate; at higher temperatures (40° to 60°C), the 1,4-addition products predominate

• if the products of low temperature addition are warmed to the higher temperature, the product composition becomes identical to the higher temperature distribution; the same result can be accomplished using a Lewis acid catalyst, such as FeCl3 or ZnCl2

• if either pure 1,2- or pure 1,4- addition product is dissolved in an inert solvent at the higher temperature and a Lewis acid catalyst added, an equilibrium mixture of 1,2- and 1,4-product forms; the same equilibrium mixture is obtained regardless of which isomer is used as the starting material

23-12

2323 1,2- and 1,4-Addition1,2- and 1,4-Addition We interpret these results using the concepts of

kinetic and thermodynamic control of reactions Kinetic control:Kinetic control: the distribution of products is

determined by their relative rates of formation• in addition of HBr and Br2 to a conjugated diene, 1,2-

addition occurs faster than 1,4-addition

CH2=CH-CH-CH3 CH2-CH=CH-CH3

a 2° allylic carbocation(greater contribution)

a 1° allylic carbocation(lesser contribution)

++

23-13

2323 1,2- and 1,4-Addition1,2- and 1,4-Addition Thermodynamic control:Thermodynamic control: the distribution of

products is determined by their relative stabilities• in addition of HBr and Br2 to a butadiene, the 1,4-

addition product is more stable than the 1,2-addition product

BrCH2

C C

H

H CH2Br

BrCH2CHCH=CH2

Br

3,4-Dibromo-1-butene (less stable alkene)

+

(E)-1,4-Dibromo-2-butene (more stable alkene)

23-14

2323 1,2- and 1,4-Addition1,2- and 1,4-Addition Is it a general rule that where two or more

products are formed from a common intermediate, that the thermodynamically less stable product is formed at a greater rate?

No• whether the thermodynamically more or less stable

product is formed at a greater rate from a common intermediate depends very much on the particular reaction and reaction conditions

23-15

2323 Diels-Alder ReactionDiels-Alder Reaction Diels-Alder reaction:Diels-Alder reaction: a cycloaddition reaction of a

conjugated diene and certain types of double and triple bonds• dienophile: diene-loving• Diels-Alder adduct: the product of a Diels-Alder

reaction

Diels-Alder adduct3-Buten-2-one(a dienophile)

1,3-Butadiene(a diene)

+

O O

3-Buten-2-one(a dienophile)

1,3-Butadiene(a diene)

+

O O

23-16

2323 Diels-Alder ReactionDiels-Alder Reaction• alkynes also function as dienophiles

• cycloaddition reactioncycloaddition reaction:: a reaction in which two reactants add together in a single step to form a cyclic product

Diels-Alder adductDiethyl 2-butynedioate(a dienophile)

+

1,3-butadiene (a diene)

COOEt

COOEt

COOEt

COOEt

23-17

2323 Diels-Alder ReactionDiels-Alder Reaction• we write a Diels-Alder reaction in the following way

• the special value of a D-A reaction is that it

(1) forms six-membered rings

(2) forms two new C-C bonds at the same time

(3) is stereospecific and regioselective

DieneDieno-phile

Adduct

23-18

2323 Diels-Alder ReactionDiels-Alder Reaction• the conformation of the diene must be s-cis

s-Trans conformation

(lower in energy)

s-Cis conformation

(higher in energy)

23-19

2323 Diels-Alder ReactionDiels-Alder Reaction• (2Z,4Z)-2,4-hexadiene is unreactive in Diels-Alder

reactions because nonbonded interactions prevent it from assuming the planar s-cis conformation

(2Z,4Z)-2,4-Hexadiene

s-trans conformation(lower energy)

s-cis conformation(higher energy)

methyl groupsforced closer thanallowed by vander Waals radii

23-20

2323 Diels-Alder ReactionDiels-Alder Reaction• reaction is facilitated by a combination of electron-

withdrawing substituents on one reactant and electron-releasing substituents on the other

CyclohexeneEthylene1,3-Butadiene

200°Cpressure

3-Buten-2-one

140°C+

1,3-Butadiene

O O

+

2,3-Dimethyl-1,3-butadiene

+ 30°C

3-Buten-2-one

O O

23-21

2323 Diels-Alder ReactionDiels-Alder ReactionElectron-WithdrawingGroups

Electron-ReleasingGroups

-C N (cyano)

-OR (ether)

-OOCR (ester)

-CHO (aldehyde, ketone)

-COOH (carboxyl)

-COOR (ester)

-NO2 (nitro)

-CH3, alkyl groups

23-22

2323 Diels-Alder ReactionDiels-Alder Reaction• the Diels-Alder reaction can be used to form bicyclic

systems

+

roomtemperature

170°CDiene Dienophile

Dicyclopentadiene(endo form)

H

H

23-23

2323 Diels-Alder ReactionDiels-Alder Reaction• exo and endo are relative to the double bond derived

from the diene

the double bondderived fromthe diene

endo (inside)

exo (outside) relative tothe doublebond

23-24

2323 Diels-Alder ReactionDiels-Alder Reaction• for a Diels-Alder reaction under kinetic control, endo

orientation of the dienophile is favored

Methyl bicyclo[2.2.1]hept-5-en-endo-2-carboxylate

Methylpropenoate

Cyclopentadiene

+ OCH3

O

H

COOCH3

COOCH3redraw

23-25

2323 Diels-Alder ReactionDiels-Alder Reaction• the configuration of the dienophile is retained

COOCH3

COOCH3 COOCH3

COOCH3

A cis dienophile)

Dimethyl cis-4-cyclohexene- 1,2-dicarboxylate

+

COOCH3

H3COOC COOCH3

COOCH3

A transdienophile)

Dimethyl trans-4-cyclohexene- 1,2-dicarboxylate

+

23-26

2323 Diels-Alder ReactionDiels-Alder Reaction Mechanism• no evidence for the participation of either radical of

ionic intermediates• chemists propose that the Diels-Alder reaction is a

pericyclic reaction

Pericyclic reactionPericyclic reaction: a reaction that takes place in a single step, without intermediates, and involves a cyclic redistribution of bonding electrons

23-27

2323 Aromatic Transition StatesAromatic Transition States Hückel criteria for aromaticity:Hückel criteria for aromaticity: the presence of

(4n + 2) pi electrons in a ring that is planar and fully conjugated

Just as aromaticity imparts a special stability to certain types of molecules and ions, the presence of (4n + 2) electrons in a cyclic transition state imparts a special stability to certain types of transition states• reactions involving 2, 6, 10, 14.... electrons in a cyclic

transition state have especially low activation energies and take place particularly readily

23-28

2323 Aromatic Transition StatesAromatic Transition States• decarboxylation of -keto acids and -dicarboxylic

acids (Section 17.9)

• Cope elimination of amine N-oxides (Section 22.11)

O OH

O

OH

C

O

O

OCO2+

enol ofa ketone

(A cyclic six-membered transition state)

O

heat

••+

-

A cyclic six-memberedtransition state

N,N-dimethyl-hydroxylamine

C C

H NCH3

CH3

N

CH3

CH3

OHC C

:

An alkene

+

23-29

2323 Aromatic Transition StatesAromatic Transition States• the Diels-Alder reaction

We now look at examples of two more reactions that proceed by aromatic transition states• Claisen rearrangement• Cope rearrangement

DieneDieno-phile

Adduct

23-30

2323 Claisen RearrangementClaisen Rearrangement Claisen rearrangement:Claisen rearrangement: a thermal rearrangement

of allyl phenyl ethers to o-allyl phenols

Allyl phenyl ether

200-250°C

2-Allylphenol

O OH

23-31

2323 Claisen RearrangementClaisen RearrangementO

Allyl phenyl ether

heat

OH

o-Allylphenol

O

H

A cyclohexadienone intermediate

keto-enoltautomerism

O

Transition state

23-32

2323 Claisen RearrangementClaisen RearrangementExample 23.7Example 23.7 Predict the product of this Claisen rearrangement

O

trans-2-Butenyl phenyl ether

heat

23-33

2323 Cope RearrangementCope Rearrangement Cope rearrangement:Cope rearrangement: a thermal isomerization of

1,5-dienes

3,3-Dimethyl-1,5-hexadiene

2-Methyl-2,6- hexadiene

heat

23-34

2323 Cope RearrangementCope RearrangementExample 23.8Example 23.8 Predict the product of these Cope rearrangements

(a)

(b)

350°C

OH

H

320°C

23-35

2323 Prob 23.21Prob 23.21Draw the structural formula for the Diels-Alder adduct of cyclopentadiene with each of the following.

(a) (b)

(d)(c) CH3 OCC CCOCH3HC CH

CH2=CHCl CH2=CHCOCH3

O

OO

23-36

2323 Prob 23.22Prob 23.22Propose structural formulas for A and B, and specify the configuration of B.

(B)(A)

200°C+ CH2=CH2 C7H10

1. O3

2. (CH3)2SC7H10O2

23-37

2323 Prob 23.24Prob 23.24Draw a Lewis structure for butadiene sulfone, and show by curved arrows the path of this reverse Diels-Alder reaction.

Sulfur dioxide1,3-ButadieneButadiene sulfone

+140°C SO2SO

O

23-38

2323 Prob 23.25Prob 23.25This triene undergoes an intramolecular Diels-Alder reaction to give the bicycloalkene on the right. Show how the triene is coiled to give this product, and show by curved arrows how the product is formed.

160°C

23-39

2323 Prob 23.26Prob 23.26Draw a structural formula for the Diels-Alder adduct.

Diels-Alder adduct 0°C

O

23-40

2323 Prob 23.27Prob 23.27Propose a structural formula for the product of this intramolecular Diels-Alder reaction.

heat An intramolecularDiels-Alder adduct

23-41

2323 Prob 23.28Prob 23.28Draw a structural formula for the product of this Diels-Alder reaction, and show the stereochemistry of the adduct.

CHO+

COOEt

COOEt

23-42

2323 Prob 23.29Prob 23.29Propose a synthesis for the starting diene from cyclopentanone and acetylene. Rationalize the stereochemistry of the target dicarboxylic acid.

+COOH

COOH

H H

O

O

O

O

O

O

23-43

2323 Prob 23.30Prob 23.30Propose a structural formula for compound A.

CH3OC-C C-COCH3+

Warburganal

H

CHOOH

CHOA

Diels-Alder reaction

6 steps

O O

23-44

2323 Prob 23.31Prob 23.31Predict the product of each Diels-Alder reaction.

+(a) (b) ON

OCCH3

OCCH3

CH

O

OCH3

O

C(CH3 )3

O

O

(d)(c) + +N

N

O

O

NCH3N

N

N

N

COOCH3

COOCH3

CH2=CHCH3

+(e)C H

NC

N

H

+

23-45

2323 Prob 23.32Prob 23.32Show how (1) and (2) react to give (3).

+

(1) (2) (3)

Dimethyl acetylene-dicarboxylate

Cyclopentadienyl- cyclopentadiene

CH3 OOCC CCOOCH3

COOCH3COOCH3

23-46

2323 Prob 23.33Prob 23.33Provide a mechanism for each step in this sequence.

+heat

Bicyclo[2.2.1]-2,5-heptadieneCl

CH2=CHCl

C2H5 ONa

C2H5 OHH

23-47

2323 Prob 23.34Prob 23.34Propose a structural formula for A, and a mechanism for formation of the bicyclic product of this sequence.

NH2

COOH

Anthranilicacid

NaNO2, HCl[A]

O

+ CO2 + N2O

23-48

2323 Prob 23.35Prob 23.35Propose a mechanism for the following reaction, which is known alternatively as an allylic rearrangement or a conjugate addition.

OR

OH1. R2CuLi

2. H2O

CH3

R = CH3CH2CH2CH2

C6H5

23-49

2323 Prob 23.36Prob 23.36All attempts to prepare cyclopentadienone give only a Diels-Alder adduct. Cycloheptatrienone, however, has been prepared by several methods and is a stable compound. Draw a structural formula for the Diels-Alder adduct, and account for the differences in stability of the two ketones.

Cycloheptatrienone

a Diels-Alderadduct2

Cyclopentadienone

O O

23-50

2323 Prob 23.37Prob 23.37Show how to synthesize the tricyclic diene on the left from 2-bromopropane, cyclopentadiene, and 2-cyclohexenone.

O

+

O

PPh3

+

BrHH H

H

23-51

2323 Prob 23.38Prob 23.38Propose a mechanism for this Claisen rearrangement.

heatO OH

23-52

2323 Prob 23.39Prob 23.39Provide a mechanism for each reaction

OHCH3O

O

CH3O

H

H

O

COOCH3

COOCH3

O

HOH OCH3

OCH3

O

H

heat

THF(a)

(b)

(c)

heat

heat

23-53

2323 Prob 23.40Prob 23.40Propose a mechanism for this example of a Carroll reaction.

heat+

6-Methyl-5-hepten-2-one

CO2

O

O

OO

23-54

2323 Prob 23.41Prob 23.41Use curved arrows to show the flow of electrons in each photoisomerization.

7-Dehydrocholesterol

light

Precalciferol

HO

H3C

H3C R

RH3C

H3C

HO

(s-cis conformation)Cholecalciferol (vitamin D3)

HO

H2C

H3C R

light

23-55

2323 Prob 23.42Prob 23.42Draw a structural formula for the product of this reaction, and show the stereochemistry of the product.

+ O

O

O

23-56

2323 Prob 23.43Prob 23.43Propose a mechanism for the formation of A, and show how A can be converted to tolciclate. Use 3-methyl-N-methylaniline as the source of the amine nitrogen, and thiophosgene, Cl2C=S, as the source of C=S group.

I

Br

OCH3Mg, OCH3

S

O N

CH3

CH3

(A)

Tolciclate

?

4-Bromo-3-iodoanisole

23-57

2323

Conjugated Conjugated DienesDienes

End Chapter 23End Chapter 23