CHE 240 Unit IV Stereochemistry, Substitution and Elimination Reactions CHAPTER SIX Terrence P. Sherlock Burlington County College 2004.

CHE 240Unit IV

Stereochemistry, Substitution and Elimination Reactions

CHAPTER SIX

Terrence P. Sherlock

Burlington County College

2004

Chapter 6 2

Polarity and Reactivity• Halogens are more electronegative than C.• Carbon-halogen bond is polar, so carbon has

partial positive charge.• Carbon can be attacked by a nucleophile.• Halogen can leave with the electron pair.

=>

CH

HH

Br

+ -

Chapter 6 3

Classes of Alkyl Halides

• Methyl halides: only one C, CH3X

• Primary: C to which X is bonded has only one C-C bond.

• Secondary: C to which X is bonded has two C-C bonds.

• Tertiary: C to which X is bonded has three C-C bonds. =>

Chapter 6 4

Classify These:

CH3 CH CH3

Cl

CH3CH2F

(CH3)3CBr CH3I =>

Chapter 6 5

Dihalides• Geminal dihalide: two halogen atoms

are bonded to the same carbon

• Vicinal dihalide: two halogen atoms are bonded to adjacent carbons.

C

H

H

H

C

H

Br

Br

geminal dihalide

C

H

H

Br

C

H

H

Br

vicinal dihalide

=>

Chapter 6 6

IUPAC Nomenclature

• Name as haloalkane. • Choose the longest carbon chain, even if the

halogen is not bonded to any of those C’s.• Use lowest possible numbers for position.

CH3 CH CH2CH3

Cl CH3(CH2)2CH(CH2)2CH3

CH2CH2Br

2-chlorobutane 4-(2-bromoethyl)heptane=>

Chapter 6 7

Systematic Common Names

• Name as alkyl halide.

• Useful only for small alkyl groups.

• Name these:

CH3 CH CH2CH3

Cl

(CH3)3CBr

CH3 CH

CH3

CH2F =>

Chapter 6 8

“Trivial” Names

• CH2X2 called methylene halide.• CHX3 is a haloform.• CX4 is carbon tetrahalide.• Examples:

CH2Cl2 is methylene chlorideCHCl3 is chloroform CCl4 is carbon tetrachloride.

=>

Chapter 6 9

Uses of Alkyl Halides• Solvents - degreasers and dry cleaning fluid• Reagents for synthesis of other compounds

• Anesthetic: Halothane is CF3CHClBrCHCl3 used originally (toxic and carcinogenic)

• Freons, chlorofluorocarbons or CFC’sFreon 12, CF2Cl2, now replaced with Freon 22,

CF2CHCl, not as harmful to ozone layer.

• Pesticides - DDT banned in U.S. =>

Chapter 6 10

Dipole Moments

• = 4.8 x x d, where is the charge (proportional to EN) and d is the distance (bond length) in Angstroms.

• Electronegativities: F > Cl > Br > I• Bond lengths: C-F < C-Cl < C-Br < C-I• Bond dipoles: C-Cl > C-F > C-Br > C-I

1.56 D 1.51 D 1.48 D 1.29 D

• Molecular dipoles depend on shape, too!

=>

Chapter 6 11

Boiling Points

• Greater intermolecular forces, higher b.p.dipole-dipole attractions not significantly different

for different halidesLondon forces greater for larger atoms

• Greater mass, higher b.p.• Spherical shape decreases b.p.

(CH3)3CBr CH3(CH2)3Br 73C 102C =>

Chapter 6 12

Densities

• Alkyl fluorides and chlorides less dense than water.

• Alkyl dichlorides, bromides, and iodides more dense than water. =>

Chapter 6 13

Halogenation of Alkanes

• All H’s equivalent. Restrict amount of halogen to prevent di- or trihalide formation

• Highly selective: bromination of 3C =>

+ HBr

H

BrhBr2+

H

H

90%

+ HBrCH3 C

CH3

CH3

Brh

Br2+CH3 C

CH3

CH3

H

Chapter 6 14

Allylic Halogenation

• Allylic radical is resonance stabilized.

• Bromination occurs with good yield at the allylic position (sp3 C next to C=C).

• Avoid a large excess of Br2 by using N-bromosuccinimide (NBS) to generate Br2 as product HBr is formed.

N

O

O

Br + HBr N

O

O

H + Br2 =>

Chapter 6 15

Reaction Mechanism

Free radical chain reactioninitiation, propagation, termination.

H H

BrH

+ HBrBr

Br

H Br

+ Br

=>

2 BrBr2h

Chapter 6 16

Substitution Reactions

• The halogen atom on the alkyl halide is replaced with another group.

• Since the halogen is more electronegative than carbon, the C-X bond breaks

heterolytically and X- leaves.

• The group replacing X- is a nucleophile. =>

C C

H X

+ Nuc:-C C

H Nuc

+ X:-

Chapter 6 17

Elimination Reactions

• The alkyl halide loses halogen as a halide ion, and also loses H+ on the adjacent carbon to a base.

• A pi bond is formed. Product is alkene.• Also called dehydrohalogenation (-HX).

=>

C C

H X

+ B:- + X:- + HB C C

Chapter 6 18

SN2 Mechanism

• Bimolecular nucleophilic substitution.

• Concerted reaction: new bond forming and old bond breaking at same time.

• Rate is first order in each reactant.

• Walden inversion. =>

CH

Br

HH

H O CHO Br

H

HH

CHO

H

HH

+ Br-

Chapter 6 19

SN2 Energy Diagram

• One-step reaction.

• Transition state is highest in energy. =>

Chapter 6 20

Uses for SN2 Reactions• Synthesis of other classes of compounds.• Halogen exchange reaction.

=>

Chapter 6 21

SN2: Nucleophilic Strength• Stronger nucleophiles react faster.• Strong bases are strong nucleophiles, but

not all strong nucleophiles are basic.

=>

Chapter 6 22

Trends in Nuc. Strength

• Of a conjugate acid-base pair, the base is stronger: OH- > H2O, NH2

- > NH3

• Decreases left to right on Periodic Table. More electronegative atoms less likely to form new bond: OH- > F-, NH3 > H2O

• Increases down Periodic Table, as size and polarizability increase: I- > Br- > Cl-

=>

Chapter 6 23

Polarizability Effect

=>

Chapter 6 24

Bulky Nucleophiles

Sterically hindered for attack on carbon, so weaker nucleophiles.

CH3 CH2 O ethoxide (unhindered)weaker base, but stronger nucleophile

C

CH3

H3C

CH3

O

t-butoxide (hindered)stronger base, but weaker nucleophile

=>

Chapter 6 25

Solvent Effects (1)Polar protic solvents (O-H or N-H) reduce

the strength of the nucleophile. Hydrogen bonds must be broken before nucleophile can attack the carbon.

=>

Chapter 6 26

Solvent Effects (2)

• Polar aprotic solvents (no O-H or N-H) do not form hydrogen bonds with nucleophile

• Examples:

CH3 C Nacetonitrile C

O

H3C CH3

acetone =>

dimethylformamide (DMF)

CH

O

NCH3

CH3

Chapter 6 27

Crown Ethers• Solvate the cation,

so nucleophilic strength of the anion increases.

• Fluoride becomes a good nucleophile.

O

O

O

O

OO

K+

18-crown-6

CH2Cl

KF, (18-crown-6)

CH3CN

CH2F

=>

Chapter 6 28

SN2: Reactivity of Substrate

• Carbon must be partially positive.• Must have a good leaving group• Carbon must not be sterically hindered.

=>

Chapter 6 29

Leaving Group Ability

• Electron-withdrawing

• Stable once it has left (not a strong base)

• Polarizable to stabilize the transition state.

=>

Chapter 6 30

Structure of Substrate

• Relative rates for SN2: CH3X > 1° > 2° >> 3°

• Tertiary halides do not react via the SN2 mechanism, due to steric hindrance. =>

Chapter 6 31

Stereochemistry of SN2

Walden inversion

=>

Chapter 6 32

SN1 Reaction

• Unimolecular nucleophilic substitution.• Two step reaction with carbocation

intermediate.• Rate is first order in the alkyl halide, zero

order in the nucleophile.• Racemization occurs.

=>

Chapter 6 33

SN1 Mechanism (1)

Formation of carbocation (slow)

(CH3)3C Br (CH3)3C+

+ Br-

=>

Chapter 6 34

SN1 Mechanism (2)• Nucleophilic attack

(CH3)3C+

+ H O H (CH3)3C O H

H

(CH3)3C O H

H

H O H+ (CH3)3C O H + H3O+

=>

• Loss of H+ (if needed)

Chapter 6 35

SN1 Energy Diagram

• Forming the carbocation is endothermic

• Carbocation intermediate is in an energy well.

=>

Chapter 6 36

Rates of SN1 Reactions

• 3° > 2° > 1° >> CH3XOrder follows stability of carbocations (opposite to

SN2)

More stable ion requires less energy to form

• Better leaving group, faster reaction (like SN2)

• Polar protic solvent best: It solvates ions strongly with hydrogen bonding. =>

Chapter 6 37

Stereochemistry of SN1Racemization:

inversion and retention

=>

Chapter 6 38

Rearrangements

• Carbocations can rearrange to form a more stable carbocation.

• Hydride shift: H- on adjacent carbon bonds with C+.

• Methyl shift: CH3- moves from adjacent

carbon if no H’s are available.

=>

Chapter 6 39

Hydride Shift

CH3 C

Br

H

C

H

CH3

CH3CH3 C

H

C

H

CH3

CH3

CH3 C

H

C

H

CH3

CH3CH3 C

H

C

CH3

CH3

H

CH3 C

H

C

CH3

CH3

HNuc

CH3 C

H

C

CH3

CH3

H Nuc

=>

Chapter 6 40

Methyl Shift

CH3 C

Br

H

C

CH3

CH3

CH3CH3 C

H

C

CH3

CH3

CH3

CH3 C

H

C

CH3

CH3

CH3CH3 C

H

C

CH3

CH3

CH3

CH3 C

H

C

CH3

CH3

CH3

NucCH3 C

H

C

CH3

CH3

CH3 Nuc

=>

Chapter 6 41

SN2 or SN1?

• Primary or methyl• Strong nucleophile

• Polar aprotic solvent

• Rate = k[halide][Nuc]

• Inversion at chiral carbon

• No rearrangements

• Tertiary• Weak nucleophile (may

also be solvent)

• Polar protic solvent, silver salts

• Rate = k[halide]• Racemization of optically

active compound

• Rearranged products

=>

Chapter 6 42

E1 Reaction

• Unimolecular elimination

• Two groups lost (usually X- and H+)

• Nucleophile acts as base

• Also have SN1 products (mixture)

=>

Chapter 6 43

E1 Mechanism

• Halide ion leaves, forming carbocation.• Base removes H+ from adjacent carbon.• Pi bond forms. =>

H C

H

H

C

CH3

CH3

Br

C

H

H

H

C CH3

CH3

O

H

H

C

H

H

H

C CH3

CH3

C C

H

CH3

CH3

H+ H3O+

Chapter 6 44

A Closer LookO

H

H

C

H

H

H

C CH3

CH3

C C

H

CH3

CH3

H+ H3O+

=>

Chapter 6 45

E1 Energy Diagram

• Note: first step is same as SN1=>

Chapter 6 46

E2 Reaction

• Bimolecular elimination

• Requires a strong base

• Halide leaving and proton abstraction happens simultaneously - no intermediate. =>

Chapter 6 47

E2 Mechanism

H C

H

H

C

CH3

CH3

Br

C C

H

CH3

CH3

H

O

H+ H2O Br

-+

=>

Chapter 6 48

Saytzeff’s Rule

• If more than one elimination product is possible, the most-substituted alkene is the major product (most stable).

• R2C=CR2>R2C=CHR>RHC=CHR>H2C=CHR tetra > tri > di > mono

C C

Br

H

C

H

CH3

H

H

H

CH3

OH-

C CH

HC

H H

CH3

CH3

C

H

H

H

C

H

CCH3

CH3

+

=>minor major

Chapter 6 49

E2 Stereochemistry

=>

Chapter 6 50

E1 or E2?• Tertiary > Secondary• Weak base• Good ionizing solvent

• Rate = k[halide]• Saytzeff product• No required geometry

• Rearranged products

• Tertiary > Secondary• Strong base required• Solvent polarity not

important• Rate = k[halide][base]• Saytzeff product• Coplanar leaving

groups (usually anti)• No rearrangements

=>

Chapter 6 51

Substitution or Elimination?

• Strength of the nucleophile determines order: Strong nuc. will go SN2 or E2.

• Primary halide usually SN2.

• Tertiary halide mixture of SN1, E1 or E2

• High temperature favors elimination.

• Bulky bases favor elimination.

• Good nucleophiles, but weak bases, favor substitution. =>

Chapter 6 52

Secondary Halides?

Mixtures of products are common.

=>

Chapter 6 53

Chapter 6 54

POWER POINT IMAGES FROM “ORGANIC CHEMISTRY, 5TH EDITION”

L.G. WADEALL MATERIALS USED WITH PERMISSION OF AUTHOR

PRESENTATION ADAPTED FOR BURLINGTON COUNTY COLLEGEORGANIC CHEMISTRY COURSE

BY:ANNALICIA POEHLER STEFANIE LAYMAN CALY MARTIN