CHEM 494 Lecture 8 - Chemistryramsey1.chem.uic.edu/chem494/page7/files/CHEM 494 Lecture 8.pdf ·...

University of Illinois at ChicagoUICCHEM 494

Special Topics in Chemistry

Prof. Duncan WardropOctober 22, 2012

CHEM 494 - Lecture 7



Chapter 19

Preparation of Alkenes Elimination

UICUniversity of Illinois at Chicago CHEM 494, Spring 2010 Slide

Lecture 8: November 5

Dehydration can be “Coupled” with Other Chemical Transformation

3

Two-step, one-pot transformation involves a Friedel-Crafts reaction (see, Chapter 12) and dehydration of the resulting 3° alcohol

N

Cl

O

NMe

HFN

NMe

ClHF

N

NMe

ClOH

Loratidine (Claritin)



Rate of Alcohol DehydrationMirrors Ease of Carbocation Formation

4

rate of dehydration = 3º > 2º > 1º alcohol

tertiaryalcohol (3º)

secondaryalcohol (2º)

primaryalcohol (1º) OH

OH

OH

H

H

H

tertiarycation (3º)

secondarycation (2°)

primarycation (1°)

Reac

tivity

Stab

ility

UICUniversity of Illinois at Chicago CHEM 494, Fall 2012 Slide


Predict the product for the following reaction scheme.

Self Test Question

5

A. B.

C. D.

E. no reaction

OHβHβ

HβHβ

HH

HβHβ

HβHβ

-H2O

-Hβ+

OH H2SO4

140 ºC?



Predict the product for the following reaction scheme.

Self Test Question

6

A. B.

C. D.

E. no reaction

H2SO4

140 ºC?

OH

-H2O

-Hβ+ or -Hβ+

OH

H HβHβ

Hβ

Hβ

HβHβ Hβ



Chapter 19

Regioselectivity & Stereoselectivity of Dehydration



A.

B.

C.

D.

E.

What is the product(s) of the following reaction?

Self Test Question

8

HO

H2SO4

80 ºC?

O2S



Types of Selectivity in Organic Chemistry

9

There are three forms of selectivity to consider . . . .

Chemoselectivity: which functional group will react

Regioselectivity: where it will react

Stereoselectivity: how it will react with regards to stereochemical outcome

. . . for each transformation, always question which of these are factors are at play.



Regioselectivity of Elimination

10

Regioselectivity: Where Will It React?

Preferential reaction at one site of a single functional group over other sites that could undergo the same reaction

CHEM 232 Definition, 2009

+ +HO

H2SO4

80 ºC

10% (identical) 90%

CH3H3C

CH3HO

H H




11




+

OH

H3PO4

heat

CH3 CH3 CH3

84% 16%

OHCH3

HβHβ

Hβ

2 different leaving group/Hβ relationships



Greek Lettering & Elimination Reactions

12

NomenclatureThe α-carbon is the one to which the leaving group is initially bonded, and the carbon chain from this may be labelled β (beta), γ (gamma), δ (delta) etc, following Greek alphabet. Use primed letters for chains branching at α-carbon

Cl

CH2

CH2

CH3H2C

H3C

Hα

β

γ

δ

β'

γ'



Regioselectivity of EliminationZaitsev Rule

13

1 Hs on this β carbon



Zaitsev RuleWhen elimination can occur in more than one direction, the major alkene is the one formed by loss of a H atom from the β carbon having the fewest hydrogens

CH3HOCH3 CH3

CH3

CH3 CH3

CH3KHSO4

heat87% 13% 0%

+ +

CH3HOH

CH3

HH β β

β

α

OSO

Na+ -O OH

hydrosulfate



Considering Stereo & Regioselectivity

14

Combine Zaitsev’s Rule and observations about stereoselectivity to predict the major products of dehydration (elimination)

trisubstituted trisubstituted disubstituted disubstituted

most stable alkenes have largest groups on each carbon trans to each other

major product

OHH2SO4

80 ºC



What is the major product expected for the reaction scheme below?

Self Test Question

15

A.

B.

C.

D.

E.

HO

H2SO4

80 ºC?



Chapter 19

E1 & E2 Mechanisms of Alcohol Dehydration



Organic Mechanisms (SN1)

17

OH

OH

HClH Cl

fast & reversible

alkyloxonium ion

MeMe

Me

H2Ocarbocation(t-butyl cation)

slow

t-butyl chloride

fastCl Cl



Remember Curved Arrow Notation?

18

curved arrows show the movement of

electrons; never atoms electronsatoms

resonance: electrons in a covalent bond moving

out to an atom

resonance: lone pair of electrons moving in between two atoms to

form a new covalent bond

bond making: lone pair of electrons

forming a new bond to another atom

bond breaking: electrons in a bond

leaving to most electronegative atom

H3C N

OCH3

CH3

H3C N

OCH3

CH3H

OH H H3O+

H3C O

OH

H3C O

O+ H



Mechanism of Dehydration (E1)

19

Step OneProton Transfer (Protonation)

pKa = -3.0

OH

OH

H

fast & reversible

alkyloxonium ion

OSO

O OHHOSO

O OH




20

Step TwoDissociation

OH

H MeMe

MeH2O

carbocation(t-butyl cation)

slow




21

Step ThreeCarbocation Capture β-Deprotonation!

CH2Me

Me


alkene(2-methylpropene)

OSO

O OHH

OSO

O OH

H

Me Me

sulfuric acid(regenerated)

fast

OSO

O OHalkyl hydrogen

sulfate(product of SN1)



Hughes-Ingold Nomenclature

22

E1

overall reaction = β-Eliminationrate determining step (RDS) involves on species = unimolecular

rate = k[alkyl oxonium ion] = %rst order

eliminationunimolecular

OH

H MeMe

MeH2O


slow



Each Step of E1 Mechanism is Reversible

23

OH

OH

H

fast &reversible

CH2Me

Me

H2O

slow &reversible

OSO

O OHHOSO

O OH

OSO

O OH

H

Me Me

fast &reversible

If all steps in E1 are reversible, what drives the reaction forward?



Alkenes Isolated from Dehydration Reactions by Distillation

24

• alkenes have much lower boiling points than alcohols

• alcohols have higher boiling points (b.p.) because of larger van der Waals forces, including strong hydrogen-bonding

• by removing alkenes through distillation (boiling), equilibrium is shifted toward products (LeChatlier Principle) until no more reactants remain

OH

4-methyl-2-pentanolbp = 132 ºC

trans-4-methyl-2-pentenebp = 59 ºC

H2SO4

2-methyl-1-pentenebp = 62 ºC

cis-4-methyl-2-pentenebp = 58 ºC

+ + + +





Why Can’t Hydrogen Halides Be Used for Elimination Reactions?

OH

OH

H

fast &reversible

CH2Me

Me

slow &reversible

ClH

HO

HMe

Me

fast &reversible

Clalkyl chloride

(product of SN1)

Cl fast &irreversible

H

Cl

ClH

nucleophilicaddition

N u c l e o p h i l i c a d d i t i o n o f chloride (Cl–) to a carbocation is not reversible



Reactivity Explained

26

R1 OH

R3R2

H3O+

R1 OH2

R3R2

H2O

R1 R3

R2 R1 = CR2 = CR3 = C

R2 R3

R2 R1 = CR2 = CR3 = H

3º Carbocation

2º Carbocation

• 3º carbocations are more stable than 2º = 3º lower in energy

• smaller activation energy leading to 3º carbocation results in faster reaction



Bimolecular Substitution - SN2 Mechanism(from Lecture 8)

27

• C-O bond breaks at the same time the nucleophile (Br) forms the C-X bond

• RDS is nucleophilic attack; bimolecular, therefore Ingold notation = SN2

• fewer steps does not mean faster reaction

H3C OH

H Br

Step 1Protonation

H3C OH

BrH

HO

H+

H3C Br

H3C H

H

‡CH3

C

H H

OBrH

Hδ+

δ-

Step 2Nucleophilic Attack

fast

slow (rate-determining)



Dehydration of Primary AlcoholsProceeds via E2 Mechanism

28




OH3C

H

H

fast &reversibleO

SO

O OHHOSO

O OH

H H

slow

H3C O

H

H3C CH

H

1° Cation

HHH2C

O

OSO

OHO

Hβ

HH

Step 1Protonation

Step 2β-Deprotonation(elimination)



Regioselectivity & Stereoselectivity of Dehydration



A.

B.

C.

D.

E.

What is the product(s) of the following reaction?

Self Test Question

30

HO

H2SO4

80 ºC?

O2S



Types of Selectivity in Organic Chemistry

31

There are three forms of selectivity to consider . . . .

Chemoselectivity: which functional group will react

Regioselectivity: where it will react

Stereoselectivity: how it will react with regards to stereochemical outcome

. . . for each transformation, always question which of these are factors are at play.




32




+ +HO

H2SO4

80 ºC

10% (identical) 90%

CH3H3C

CH3HO

H H




33




+

OH

H3PO4

heat

CH3 CH3 CH3

84% 16%

OHCH3

HβHβ

Hβ

2 different leaving group/Hβ relationships



Greek Lettering & Elimination Reactions

34

NomenclatureThe α-carbon is the one to which the leaving group is initially bonded, and the carbon chain from this may be labelled β (beta), γ (gamma), δ (delta) etc, following Greek alphabet. Use primed letters for chains branching at α-carbon

Cl

CH2

CH2

CH3H2C

H3C

Hα

β

γ

δ

β'

γ'



Regioselectivity of EliminationZaitsev Rule

35




Zaitsev RuleWhen elimination can occur in more than one direction, the major alkene is the one formed by loss of a H atom from the β carbon having the fewest hydrogens

CH3HOCH3 CH3

CH3

CH3 CH3

CH3KHSO4

heat87% 13% 0%

+ +

CH3HOH

CH3

HH β β

β

α

OSO

Na+ -O OH

hydrosulfate



Considering Stereo & Regioselectivity

36

Combine Zaitsev’s Rule and observations about stereoselectivity to predict the major products of dehydration (elimination)

trisubstituted trisubstituted disubstituted disubstituted

most stable alkenes have largest groups on each carbon trans to each other

major product

OHH2SO4

80 ºC



What is the major product expected for the reaction scheme below?

Self Test Question

37

A.

B.

C.

D.

E.

HO

H2SO4

80 ºC?



Section: 5.12

E1 & E2 Mechanisms of Alcohol Dehydration



Organic Mechanisms (SN1)

39

OH

OH

HClH Cl

fast & reversible

alkyloxonium ion

MeMe

Me

H2Ocarbocation(t-butyl cation)

slow

t-butyl chloride

fastCl Cl



Remember Curved Arrow Notation?

40

curved arrows show the movement of

electrons; never atoms electronsatoms

resonance: electrons in a covalent bond moving

out to an atom

resonance: lone pair of electrons moving in between two atoms to

form a new covalent bond

bond making: lone pair of electrons

forming a new bond to another atom

bond breaking: electrons in a bond

leaving to most electronegative atom

H3C N

OCH3

CH3

H3C N

OCH3

CH3H

OH H H3O+

H3C O

OH

H3C O

O+ H




41

Step OneProton Transfer (Protonation)

pKa = -3.0

OH

OH

H

fast & reversible

alkyloxonium ion

OSO

O OHHOSO

O OH




42

Step TwoDissociation

OH

H MeMe

MeH2O


slow




43

Step ThreeCarbocation Capture β-Deprotonation!

CH2Me

Me


alkene(2-methylpropene)

OSO

O OHH

OSO

O OH

H

Me Me

sulfuric acid(regenerated)

fast

OSO

O OHalkyl hydrogen

sulfate(product of SN1)



Hughes-Ingold Nomenclature

44

E1

overall reaction = β-Eliminationrate determining step (RDS) involves on species = unimolecular

rate = k[alkyl oxonium ion] = %rst order

eliminationunimolecular

OH

H MeMe

MeH2O


slow



Each Step of E1 Mechanism is Reversible

45

OH

OH

H

fast &reversible

CH2Me

Me

H2O

slow &reversible

OSO

O OHHOSO

O OH

OSO

O OH

H

Me Me

fast &reversible

If all steps in E1 are reversible, what drives the reaction forward?



Alkenes Isolated from Dehydration Reactions by Distillation

46

• alkenes have much lower boiling points than alcohols

• alcohols have higher boiling points (b.p.) because of larger van der Waals forces, including strong hydrogen-bonding

• by removing alkenes through distillation (boiling), equilibrium is shifted toward products (LeChatlier Principle) until no more reactants remain

OH

4-methyl-2-pentanolbp = 132 ºC

trans-4-methyl-2-pentenebp = 59 ºC

H2SO4


cis-4-methyl-2-pentenebp = 58 ºC

+ + + +





Why Can’t Hydrogen Halides Be Used for Elimination Reactions?

OH

OH

H

fast &reversible

CH2Me

Me

slow &reversible

ClH

HO

HMe

Me

fast &reversible

Clalkyl chloride

(product of SN1)

Cl fast &irreversible

H

Cl

ClH

nucleophilicaddition

N u c l e o p h i l i c a d d i t i o n o f chloride (Cl–) to a carbocation is not reversible



Reactivity Explained

48

R1 OH

R3R2

H3O+

R1 OH2

R3R2

H2O

R1 R3

R2 R1 = CR2 = CR3 = C

R2 R3

R2 R1 = CR2 = CR3 = H

3º Carbocation

2º Carbocation

• 3º carbocations are more stable than 2º = 3º lower in energy

• smaller activation energy leading to 3º carbocation results in faster reaction



Bimolecular Substitution - SN2 Mechanism(from Lecture 8)

49




H3C OH

H Br

Step 1Protonation

H3C OH

BrH

HO

H+

H3C Br

H3C H

H

‡CH3

C

H H

OBrH

Hδ+

δ-

Step 2Nucleophilic Attack

fast

slow (rate-determining)



Dehydration of Primary AlcoholsProceeds via E2 Mechanism

50




OH3C

H

H

fast &reversibleO

SO

O OHHOSO

O OH

H H

slow

H3C O

H

H3C CH

H

1° Cation

HHH2C

O

OSO

OHO

Hβ

HH

Step 1Protonation

Step 2β-Deprotonation(elimination)



Addition Reactions of Alkenes



Addition Reactions of Alkenes

52

C C X Y+ additionC CX Y

C C H H+ hydrogenationC CH H

C C H X+hydrogen

halide additionC CH X

C C H Br+free radical

bromine addition C CH Br

C C +sulfuric acid

addition C CH OSO3H

C C H OH+ hydrationC CH OH

O SO

OOHH



Hydrogenation

53

Pd/C, CH3CH2OH

• exothermic reaction (-∆Hº), but high Eact - catalyst required

• catalysts are heterogeneous transition metals (Pd, R

• solvent is typically an alcohol (e.g. ethanol, CH3CH2OH)

• metals are insoluble (heterogeneous mixture)

• heat of hydrogenation = -∆Hº



Heat of Hydrogenation (-∆Hº)

54



Heat of Hydrogenation (-∆Hº)

55

H

H H

H

Alkene -∆Hº (kJ/mol) example

ethylene 136

monosubstituted 126

cis-disubstituted 119

terminally disubstituted 117

trisubstituted 112

tetrasubstituted 110

Since only the double bond is undergoing the reaction, heat of hydrogenation is independent of the number of carbon atoms in the molecule



General Mechanism forHeterogenious Hydrogenation

56

catalyst surface

H H

catalyst surfaceMII

HH

catalyst surfaceMII

HH

oxidativeaddition

d

σ∗

catalyst surfaceMII

H H

coordinationinsertion

reductiveelimination

H H

M0

reaction takes places at the surface of the catalyst (many metal atoms combined)



Step 1: Oxidative Addition

57

catalyst surface

H H

M0

catalyst surfaceMII

H H

oxidativeaddition

d

σ∗

• hydrogen (H2) is added to metal• metal is oxidized from M0 to MII

Pd0

H H

H HPdII



Step 2: Coordination

58

catalyst surfaceMII

H H

catalyst surfaceMII

H H coordination

• metal is a Lewis acid (electron acceptor)• π-bond is a lewis base (electron donor)• coordination = Lewis acid/base complex

H HPdIIH HPdII



Step 3: Insertion

59

catalyst surfaceMII

H H

catalyst surfaceMII

H H

insertion

• two carbon atoms inserted between Pd-H• formation of a weak metal-carbon σ-bond• formation of a strong C-H σ-bond• break a weak metal-H σ-bond

H HPdIIH

PdIIH



Step 4: Reductive Elimination

60

catalyst surface

H H

M0

d

σ∗

catalyst surfaceMII

H H


H H

• metal is reduced from MII to M0

• last σ C-H -bond is formed from the same face of alkene as previous

• metal is a catalyst; it is regenerated

H

PdIIH H H



Complete Mechanism

61

oxidativeaddition

coordinationinsertion


H H

Pd0

H H

H HPdII

H HPdII

H

PdIIH



Syn Addition of Hydrogen

62

• as a consequence of mechanism, both hydrogens are added to the same face of the π-bond: syn addition

• no anti-addition products are formed (addition of hydrogen to opposite faces)



Hydrogenation is Stereoselective

63

This methyl group sterically hinders hydrogen from approaching the π-bond from the top face

• both products are arise from syn additions of hydrogen to alkene

• stereoselective: preference for one stereoisomer when two or more are possible



Example of Syn Addition

64

C8H12

CH3 CH3

HO

HH

H

C8H12CH3CH3

HOH H

C8H12CH3CH3

HOH H

C8H12

CH3 CH3

HO

C8H12

CH3 CH3

HO

H HH

C8H12

CH3 CH3

HO

H H

2. Hydrogen absorbed on to catalyst surface. H-H bond cleaved.

3. π−System of alkene coordinates catalyst surface.

4. One hydrogen atom is transferred to alkene, forming C-catalyst bond.

5. Second hydrogen atom is transferred, breaking substrate-catalyst bond. Alkane diffuses away from catalyst.

1. Diatomic hydrogen and alkene are present in solution phase. No reaction occurs.

6. Steps 1-5 are repeated.



A.

B.

C.

D.

What is the major product of the following hydrogenation reaction?

Self Test Question

65

H2, Pd/C

CH3CH2OH

D

H

DH

D

HH

H

D

H

H

H

D

H

H

H

H

H

H

H

H

D

catalyst surfaceMIID

catalyst surfaceMII



Addition of Electrophiles to Alkene

66

C C H H+ hydrogenationC CH H

C C H X+hydrogen


C C H Br+free radical

bromine addition C CH Br

C C +sulfuric acid

addition C CH OSO3H

C C H OH+ hydrationC CH OH

O SO

OOHH



Electrophilic Addition of HX

67

δ+ δ–

electrophilenucleophile

C C H X+hydrogen




Reaction Conditions

68

• hydrogen halide: HX• common solvents: chloroform

(CHCl3) ,dichloromethane (CH2Cl2), pentane, acetic acid

• generally performed at low temperature (below 0 °C)

• generally a fast reaction

HHBr

CHCl3, -30 ºCH

Br

H H

H



Electrophilic Addition (AdE) Mechanism

69

• electrophilic addition: AdE• RDS = protonation of carbon• rate = k[alkene][hydrogen halide]• unlike oxygen and nitrogen, protonation of

carbon is slow• proceeds through carbocation intermediate

H Br

H

H H H

HBr

Br

H H

HProtonation(slow)

CationCapture(fast)



HX Addition is Regioselective

70

Regioselectivity



R

H

H

H

H X R

HH

H

HX

R

R

H

H

H X R

HR

H

HX

R

R

H

R

H X R

HR

H

RX

R

XH

H

HH

R

XR

H

HH

R

XR

H

RH

rather than

rather than

rather than



Markovnikov’s Rule

71

3º 2º

addition of HX to an unsymmetrically substituted alkene proceeds so that hydrogen (H) adds to the least substituted carbon and the halide (X) adds to the most substituted carbon atom

CH3HBr

CH2Cl2-40 ºC

H3C BrH H

H



A. 3-chloro-2,4-dimethylpentane

B. 2-chloroohexane

C. 2,3-dichloro-2,4-dimethylpentane

D. 2-chloro-2,4-dimethylpentane

E. 1-chloro-2,4-dimethylpentane

Predict the product when 2,4-dimethyl-2-pentene is treated with HCl?

Self Test Question

72

HCl Cl



Mechanistic Basis for Markovnikov’s Rule

73

H X

H X

H

H

X

+

X

X

3º carbocation

2º carbocation

3º alkyl halide

2º alkyl halide

X

H

H

• curved arrows do not indicate which carbon is protonated

• fastest protonation leads to more stable (more substituted) carbocation

• more substituted carbocation = more substituted alkyl halide



Mechanistic Basis for Markovnikov’s Rule

74

Hammond Postulate:transition state structure resembles closest energy

intermediate

• transition state resembles carbocation for endothermic RDS (late transition state)

• what stabilizes carbocation also stabilizes transition state

• lowest energy transition state leads to more substituted carbocation

CHEM 494 Lecture 8 - Chemistryramsey1.chem.uic.edu/chem494/page7/files/CHEM 494 Lecture 8.pdf ·...

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