7 7-1 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Introduction to Organic...

77

7-1Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.

Introduction to Introduction to Organic Organic

ChemistryChemistry2 ed2 ed

William H. BrownWilliam H. Brown

77


Alkyl Alkyl HalidesHalides

Chapter 7Chapter 7

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StructureStructure• Alkyl halideAlkyl halide: : a compound containing a halogen

atom covalently bonded to an sp3 hybridized carbon atom• given the symbol RX

A haloalkane

(an alkyl halide)

R X

77


Vinylic and Aryl HalidesVinylic and Aryl Halides• if the halogen is bonded to an sp2 hybridized carbon,

the compound is called a vinylic halide• if the halogen is bonded to a benzene ring, it is called

an aryl halide, given the symbol Ar-X

• we do not study vinylic and aryl halides in this chapter

A haloalkene

(a vinylic halide)

C C

R

R

X

R

X

A haloarene

(an aryl halide)

77


NomenclatureNomenclature• locate the parent alkane• number the parent chain to give the substituent

encountered first, be it halogen or an alkyl group, the lower number

• halogen substituents are indicated by the prefixes fluoro-, chloro-, bromo-, and iodo- and listed in alphabetical order with other substituents

3-Bromo-2-methylpentane 2,3-Dichlorobutane

B r C H3

C l C l

C H3

C H C H C H3C H

3C H

2C H C H C H

3

1 12 2 3345 4

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NomenclatureNomenclature• for haloalkenes, numbering is determined by the

location of the C-C double bond

4-Bromo-

cyclohexene

B r

1

2

3

4

C H3

C C H = C H2

C H3

C l

3-Chloro-3-

methyl-1-butene

1234

5

6

77


NomenclatureNomenclature• common names - name the alkyl group followed by the

name of the halide

3-Chloropropene

(Allyl chloride)

Chloroethene

(Vinyl chloride)

Chloroethane

(Ethyl chloride)

CH3

CH2

Cl CH2

=CHCl CH2

=CHCH2

Cl

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NomenclatureNomenclature• several polyhaloalkanes are common solvents and are

generally referred to by their common or trivial names

Dichloromethane

(Methylene chloride)

Trichloromethane

(Chloroform)

Trichloroethylene

(Trichlor)

1,1,1-Trichloroethane

(Methyl chloroform)

CHCl 3CH 2 Cl 2

CCl2

=CHClCH3

CCl3

77


Freons & Their AlternativesFreons & Their Alternatives• The Freons are chlorofluorocarbons (CFCs).

Among the most widely used are/were

• Nonozone-depleting alternatives are hydrofluorocarbons (HFCs) and hydrochlorofluorocarbons (HCFCs) including

C C l 3 F

Trichlorofluoromethane

(Freon-11)

C C l 2 F 2

Dichlorodifluoromethane

(Freon-12)

C H2

F C F3

HFC-134a

C H C l2

C F3

HCFC-123

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Nucleophilic SubstitutionNucleophilic Substitution

• Nucleophilic substitutionNucleophilic substitution: any reaction in which one nucleophile is substituted for another

• NucleophileNucleophile: a molecule or ion that donates a pair of electrons to another molecule or ion to form a new covalent bond: a Lewis base

nucleophilic

substitution++ C NuC XNu

-X

-

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Nucleophilic SubstitutionNucleophilic Substitution• One of the most important reactions of alkyl

halides

a thiol (a mercaptan)HS -

CH3

SH

an ether

an alcohol

Reaction:

+-

+CH3

NuCH3

Br Br

RO -

HO -

Nu

CH3

OH

CH3

OR

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Nucleophilic SubstitutionNucleophilic Substitution

+

an alcohol (after

proton transfer)

an alkylammonium ion

an alkyl iodide

H

I -

NH3

HOH

CH3

I

CH3

NH3

+

CH3

O-H

a sulfide (a thioether)RS -

CH3

SR

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MechanismsMechanisms• Chemists propose two limiting mechanisms for

nucleophilic aliphatic substitution• a fundamental difference between them is the timing of

bond-breaking and bond-forming steps

• they are designated SN1 and SN2

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Mechanism - SMechanism - SNN22• Bond breaking and bond forming occur

simultaneously• S = substitution

N = nucleophilic

2 = bimolecular• Bimolecular reactionBimolecular reaction: a reaction in which two

reactants are involved in the transition state of the rate-limiting step

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Mechanism - SMechanism - SNN22• Simultaneous backside attack of the nucleophile

and departure of the leaving group

C Br

H

H

H

HO-

+

C

H

H H

HO Br

δ - δ -

T ransition state with simultaneous

bond breaking and bond forming

C

H

H

H

HO + Br-

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Mechanism - SMechanism - SNN11• Bond breaking is complete before bond forming

begins• S = substitution

N = nucleophilic

1 = unimolecular• Unimolecular reactionUnimolecular reaction: a reaction in which only

one species is involved in the transition state of the rate-limiting step

77


Mechanism - SMechanism - SNN11• An SN1 mechanism is illustrated by the reaction

of 2-bromo-2-methylpropane (tert-butyl bromide) and methanol

C H3

C - B r

C H 3

+ C H3

O H C H3

C - O C H3

C H 3

+ H B r

2-Bromo-2-

methylpropane

Methanol tert -Butyl

methyl ether

m ethanol

C H3

C H3

77


Mechanism - SMechanism - SNN11• Step 1: ionization of the C-X bond to form a

carbocation intermediate

C

C H3

C H3

H3

C

+C

H3

C

H3

C

B r

H3

C

slow, rate-

limiting step

A carbocation intermediate;

carbon is trigonal planar

+ B r-

77


Mechanism - SMechanism - SNN11• Step 2: reaction of the carbocation (a Lewis acid) with

methanol (a Lewis base) to form an oxonium ion

C

C H 3

C H 3H 3 C

C

C H3

C H3

C H3

O

H3

C

H

C

H3

C

H 3 C

O

H3

C

H

C H3

+ C H3

O H

++ +

+

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Mechanism - SMechanism - SNN11• Step 3: proton transfer to solvent completes the

reaction

••

+

+

+

+ fastC

H3

C

H3

C

O

H3

C

O

CH3

H

OHO

CH3

CH3

H

H

CH3

H3

C

C

H3

C

H3

C

77


Stereochemistry of SStereochemistry of SNN11• For an SN1 reaction at a stereocenter, the product

is a racemic mixture

(R)-Enantiomer Planar carbocation

(achiral)

C

H

Cl

C6

H5

Cl

C+

C6

H5

H

Cl

CH3

OH-Cl-

-H+

77


Stereochemistry SStereochemistry SNN11

+

A racemic mixture

Cl

C6

H5

C6

H5

C OCH3

H

CH3

O C

H

Cl

(R)-Enantiomer(S)-EnantiomerPlanar carbocation

(achiral)

C+

C6

H5

H

Cl

CH3

OH

-H+

77


Evidence of SEvidence of SNN reactions reactions• What effect of does

• the structure of the nucleophile have on rate?• the structure of alkyl halide have on rate?• the structure of the leaving group have on rate?• the solvent have on the reaction mechanism?

77


NucleophilicityNucleophilicity• NucleophilicityNucleophilicity: a kinetic property measured by

the rate at which a Nu attacks a reference compound under a standard set of experimental conditions• for example, the rate at which a set of nucleophiles

displaces bromide ion from bromoethane in ethanol at 25°C

• Table 7.2 shows common nucleophiles and their relative nucleophilicities

77


NucleophilicityNucleophilicity

good

poor

B r-

, I-

H O-

, C H3

O-

, R O-

C H3

S-

, R S-

C H3

C O2

-, R C O

2

-

H2

O

C H3

O H , R O H

C H3

C O2

H , R C O2

H

N H3

, R N H2

, R2

N H , R3

N

C H3

S H , R S H , R2

S

Effectiveness Nucleophile

moderate

77


Structure of RXStructure of RX• SN1 reactions are governed by electronic factorselectronic factors,

namely the relative stabilities of carbocation intermediates• 3° > 2° > 1° > methyl

• SN2 reactions are governed by steric factorssteric factors, namely the relative ease of approach of the nucleophile to the site of reaction• methyl > 1° > 2° > 3°

77


Structure of RXStructure of RX• Reactivities for SN1 and SN2 are in opposite

directions

R3

CX R2

CHX RCH2

X CH3

X

(3°) (2°) (methyl)(1°)

Increasing stability of cation intermediate

Increasing ease of access to the reaction site

SN

1

SN

2

77


The Leaving GroupThe Leaving Group• The more stable the anion, the better the leaving

ability• the most stable anions are the conjugate bases of

strong acids

Increasing leaving ability

I-

> Br-

> Cl-

>> F-

> CH3

CO2

- > HO

- > NH

2

-

Stability of anion; strength of conjugate acid

77


Common Protic SolventsCommon Protic Solvents• Protic solventProtic solvent: a solvent that contains an -OH

group • These solvents favor SN1 reactions; the greater the

polarity of the solvent, the easier it is to form carbocations in it

Solvent Structure

water

formic acid

methanol

ethanol

H2

O

HCO2

H

CH3

OH

CH3

CH2

OH

acetic acid CH3

CO2

H

Solvent

Polarity

77


Common Aprotic SolventsCommon Aprotic Solvents• Aprotic solventAprotic solvent:does not contain an -OH group

• it is more difficult to form carbocations in aprotic solvents

• these solvents favor SN2 reactions

diethyl ether

dichloromethane

Aprotic

Solvent Structure

dimethyl sulfoxide

acetone

CH2

Cl2

(CH3

CH2

)2

O

(CH3

)2

S=O

Solvent

Polarity

(CH3

)2

C=O

77


Summary of SSummary of SNN Rexns RexnsAlkyl Halide

CH3

X

methyl

RCH2

X

p rimary

R2

CHX

secondary

SN

2 SN

1

SN

2 favored SN

1 does not occur; the

methyl cation too unstable

SN

1 rarely occurs; 1° cations

rarely observed in solution

SN

1 favored in protic solvents

with poor nucleophiles

SN

2 favored in

aprotic solvents

with good

nucleophiles

SN

2 favored

77


Summary of SSummary of SNN Rexns Rexns

R3

CX

tertiary

Substitution

at stereocenter

SN

2 does not

occur; steric

hindrance

SN

1 favored; ease of

formation of 3°

carbocations

Inversion of

configuration

Racemization

Alkyl Halide SN

2 SN

1

77


SSNN1/S1/SNN2 Problems - 12 Problems - 1• Predict the type of mechanism for this reaction,

and the stereochemistry of the product

+

+

C l

O C H3

C H3

C H C H2

C H3

C H3

C H C H2

C H3

C H3

O H

H C l(R)-enantiomer

77


SSNN1/S1/SNN2 Problems - 22 Problems - 2• Predict the mechanism of this reaction

+

+

DMSO

C H3

C H3

C H3

C H C H2

I

C H3

C H C H2

B r N a+

I-

N a+

B r-

77


SSNN1/S1/SNN2 Problems - 32 Problems - 3• Predict the mechanism and the configuration of

product

+

+

acetone

B r

S C H 3

C H3

C H C H2

C H3 C H

3S

-N a

+

C H3

C H C H2

C H3

N a+

B r -

(S configuration)

77


-Elimination-Elimination• -Elimination-Elimination: removal of atoms or groups of

atoms from adjacent carbons to form a carbon-carbon double bond

α

C C +

An alkyl

halide

Base

An alkene

C H3

C H2

O-N a

+

C H3

C H2

O H

C H3

C H2

O H N a+

X -+

+C C

H X

77


-Elimination-Elimination• Example

C H3

( C H2

)7

C H2

C H2

B r

C H3

( C H2

)7

C H = C H2

α

( C H3

)3C O

-K

+

1-Bromodecane Potassium

tert-butoxide

( C H3

)3

C O H + K+

B r-

1-Decene

+

+

77


-Elimination-Elimination• Zaitsev ruleZaitsev rule: the major product of a -elimination

is the more highly substituted alkene

+

B r

C H3

C H = C C H3

C H3

C H2

C = C H2

C H3

C H2

C C H3

2-Methyl-2-butene

(major product)

C H3

C H2

O-N a

+

C H 3 C H 2 O HC H

3

2-Bromo-2-

methylbutane

C H3 C H

3

2-Methyl-1-butene

77


-Elimination-Elimination• Example (follows Zaitsev rule)

+

CH3

CH3

CH2

1-Methyl-

cyclopentene

(major product)

CH3

O-

Na+

CH3

OH

1-Bromo-1-methyl-

cyclopentane

Br

Methylene-

cyclopentane

77


-Elimination-Elimination• There are two limiting mechanisms for -

elimination reactions• E1 mechanismE1 mechanism: breaking of the R-X bond is complete

before reaction with base to break the C-H bond begins. Only R-X is involved in the rate-limiting step.

• E2 mechanismE2 mechanism: breaking of the R-X and C-H bonds is concerted. Both R-X and base are involved in the rate-limiting step.

77


E1 MechanismE1 Mechanism• Step 1: rate-limiting ionization of the C-X bond to form

a carbocation intermediate

slow, rate

limiting

+

(a 3° carbocation

intermediate)

C H3

- C - C H3

C H3

B r

C H3

- C - C H3

C H3

+ B r -

77


E1 MechanismE1 Mechanism• Step 2: proton transfer from the carbocation

intermediate to the base (in this case, the solvent)

fast

+

O

H

H3

C

C H2

= C - C H3

C H3

O

H

H3

C

H+

+

H - C H2

- C - C H3

C H3

77


E2 MechanismE2 Mechanism• A one-step mechanism; all bond-breaking and

bond-forming steps are concerted

+ H - C H - C H 2 - B r

C H3

C H 3 C H 2 O H C H 3 C H = C H 2+ + B r -

C H 3 C H 2 O-

77


Summary of E1 versus E2Summary of E1 versus E2

E2

Primary cations are rarely formed

in solution and, therefore, E1

reactions of primary halides are

rarely observed.

Halide Reaction Comments

primary

( R C H2

X )

E1

M a i n r e a c t i o n w i t h s t r o n g b a s e s

s u c h a s H O- a n d R O

-

77


Summary of E1 versus E2Summary of E1 versus E2

E2

E2

E1

secondary

tertiary



-

( R3

C - X )

( R2

C H - X )



-

M a i n r e a c t i o n w i t h w e a k b a s e s s u c h

a s C H3

C O2

- a n d R O H

E1 Common in reactions with weak

bases such as CH 3 CO 2

-

77


Alkyl Alkyl HalidesHalides

End Chapter 7End Chapter 7

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