6.1 Alkyl Halides

Chapter 6 Alkyl Halides

NE NE PHAR PHAR 109 Organic 109 Organic Chemistry Chemistry Assist.Prof

Assist.Prof . . Banu Banu Keşanlı Keşanlı

Chapter 6 2

6.1 Alkyl Halides

ÎThe polarity of a carbon-halogen bond leads to the carbon having a partial positive charge

ÎIn alkyl halides this polarity causes the

carbon to become activated to substitution

reactions with nucleophiles

Chapter 6 3

¾ Carbon-halogen bonds get less polar, longer and

weaker in going from fluorine to iodine

Chapter 6 4

4.3E Nomenclature of Alkyl Halides (RX)

Î In IUPAC nomenclature halides are named as substituents on the parent chain

Î Halo and alkyl substituents are considered

to be of equal ranking

Chapter 6 5

• Common nomenclature of simple alkyl halides

is accepted by IUPAC and still used

Chapter 6 6

• If the carbon is attached to one other carbon that carbon is primary (1

) and the alkyl halide is also 1

• If the carbon is attached to two other carbons, that carbon is secondary (2

) and the alkyl

halide is 2

•If the carbon is attached to three other

carbons, the carbon is tertiary (3

) and the alkyl

halide is 3

Chapter 6 7

6.3 Nucleophilic Substitution Reactions (S _N ) ÎIn this reaction a nucleophile is species with

an unshared electron pair which reacts with an electron deficient carbon

ÎA leaving group is substituted by a nucleophile

ÎExamples of nucleophilic substitution

Chapter 6 8

6.4 Nucleophile

ÎThe nucleophile reacts at the electron deficient carbon

ÎA nucleophile may be any molecule with an

unshared electron pair

Chapter 6 9

6.5 Leaving Group

ÎA leaving group is a substituent that can leave as a relatively stable entity

ÎIt can leave as an anion or a neutral species

Chapter 6 10

Transition state

¾ Rate determining step is bimolecular

¾ Methyl and 1° alkyl halides undergo S

2 type nucleophilic substitutions

S _N 2 Reactions

HO ^- + HO δ ⁻ CH ₃ Cl δ ⁻

CH ₃ Cl HO CH ₃ + Cl ^-

Chapter 6 11

6.6 Kinetics of a Nucleophilic Substitution Reaction: An S

2 Reaction

• The rate equation reflects this dependence

• S _N 2 reaction: substitution,

nucleophilic, 2nd order (bimolecular)

Chapter 6 12

A Mechanism for the S

2 Reaction

ÎA transition state is the high energy state of the reaction

• It is an unstable entity with a very brief existence (10

s)

ÎIn the transition state of this reaction bonds are partially formed and broken

• Both chloromethane and hydroxide are involved in the transition state and this explains why the reaction is second order

»

Chapter 6 13

A Mechanism for the S

2 Reaction

Mechanism of a Reaction: The events that are

postulated to take place at the molecular level as

reactants become products

Chapter 6 14

6.9 The Stereochemistry of S

2 Reactions

ÎStereochemistry can be controlled in S _N 2 reactions

• Backside attack of nucleophile results in an

inversion of configuration

Chapter 6 15

¾ In cyclic systems a cis compound can react

and become trans product

Chapter 6 16

Transformations Using S _N 2 Reactions

Chapter 6 17

¾ Rate determining step is unimolecular

¾ Tertiary halides show S

1 type nucleophilic substitution reactions

6.10 S _N 1 Reactions

(CH ₃ ) ₃ CCl ^slow (CH ₃ ) ₃ C ⁺ + Cl-

(CH ₃ ) ₃ C ^{+ H 2 O} (CH ₃ ) ₃ C OH + H ₃ O ⁺

Chapter 6 18

6.10 The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S

1 Reaction

Îtert-Butyl chloride undergoes substitution with hydroxide

ÎThe rate is independent of hydroxide

concentration and depends only on

concentration of tert-butyl chloride

Chapter 6 19

¾ S _N 1 reaction: Substitution, nucleophilic, 1st order (unimolecular)

¾ The rate depends only on the concentration of the alkyl halide

¾ Only the alkyl halide (and not the

nucleophile) is involved in the transition

state of the step that controls the rate

Chapter 6 20

6.11 A Mechanism for the S

1 Reaction

ÎStep 1 is rate determining (slow) because it requires the formation of unstable ionic

products

ÎIn step 1 water molecules help stabilize the

ionic products

Chapter 6 21

Chapter 6 22

6.12 Carbocations

Î A carbocation has only 6 electrons, is sp

hybridized and has an empty p orbital

Î The more highly substituted a carbocation

is, the more stable it is and the easier it is to

form

Chapter 6 23

ÎHyperconjugation stabilizes the carbocation by donation of electrons from an adjacent carbon- hydrogen or carbon-carbon σ bond into the

empty p orbital

• More substitution provides more opportunity

for hyperconjugation

Chapter 6 24

6.13 The Stereochemistry of S _N 1 Reactions ÎWhen the leaving group leaves from a

stereogenic center of an optically active

compound in an S

1 reaction, racemization will occur

• This is because an achiral carbocation intermediate is formed

Racemization: transformation of an optically

active compound to a racemic mixture

Chapter 6 25

Chapter 6 26

Solvolysis

ÎA molecule of the solvent is the nucleophile in a substitution reaction

• If the solvent is water the reaction is a

hydrolysis

Chapter 6 27

6.14 Factors Affecting the Rate of S

1 and S

2 Reactions

• The Effects of the Structure of the Substrate

z S

2 Reactions

ÎIn S

2 reactions alkyl halides show the

following general order of reactivity

Chapter 6 28

ÎSteric hinderance: the spatial arrangement of the atoms or groups at or near a reacting site hinders or retards a reaction

• In tertiary and neopentyl halides, the reacting

carbon is too sterically hindered to react

Chapter 6 29

• ^S

1 reactions

ÎGenerally only tertiary halides undergo S

1 reactions because only they can form

relatively stabilized carbocations

Chapter 6 30

Solvent Effects on S

2 Reactions: Polar Protic and Aprotic Solvents

Polar Protic Solvents

• Polar solvents have a hydrogen atom attached to strongly electronegative atoms

• They solvate nucleophiles and make them less

reactive

Chapter 6 31

¾Larger nucleophilic atoms are less solvated and therefore more reactive in polar protic solvents

¾Larger nucleophiles are also more polarizable and can donate more electron density

*Relative nucleophilicity in polar solvents:

Chapter 6 32

ÎPolar Aprotic Solvents

• Polar aprotic solvents do not have a

hydrogen attached to an electronegative

atom

Chapter 6 33

• Polar aprotic solvents solvate cations well but

leave anions unsolvated because positive centers

in the solvent are sterically hindered

Chapter 6 34

• Polar aprotic solvents lead to generation of

“naked” and very reactive nucleophiles

• Trends for nucleophilicity are the same as for basicity

• They are excellent solvents for S

2 reactions

Chapter 6 35

z The Nature of the Leaving Group

ÎThe best leaving groups are weak bases which are relatively stable

• The leaving group can be an anion or a neutral molecule

ÎLeaving group ability of halides:

ÎOther very weak bases which are good

leaving groups:

Chapter 6 36

ÎThe poor leaving group hydroxide can be

changed into the good leaving group water

by protonation

Chapter 6 37

Summary S

1 vs. S

2

ÎIn both types of reaction alkyl iodides react

the fastest because of superior leaving group

ability

Chapter 6 38

6.16 Elimination Reactions of Alkyl Halides Dehydrohalogenation

ÎUsed for the synthesis of alkenes

• Elimination competes with substitution reaction

• Strong bases such as alkoxides favor

elimination

Chapter 6 39

Chapter 6 40

6.17 The E2 Reaction

Î E2 reaction involves concerted removal of the proton, formation of the double bond, and departure of the leaving group

Î Both alkyl halide and base concentrations

affect rate and therefore the reaction is 2nd

order

Chapter 6 41

E2 Reaction Mechanism

Chapter 6 42

6.18 The E1 Reaction

ÎThe E1 reaction competes with the S

1

reaction and likewise goes through a

carbocation intermediate

Chapter 6 43

E1 Reaction Mechanism

Chapter 6 44

Chapter 6 45

A Summary of Substitution and Elimination Reactions

Halide Type

S_N 1 S_N 2 E1 E2

RCH₂ X (primary)

Does not occur

Highly favored

Does not occur

Occurs when strong bases are used

R₂ CHX (secondary)

Can occur with benzylic

allylic halides

Occurs in competitio

n with E2 reaction

Can occur with benzylic and allylic

halides

Favored when strong bases are used

R₃ CX (tertiary)

Favored in hydroxylic

solvents

Does not occur

Occurs in competitio n with S_N 1

reaction

Favored when bases are

used

6.20 Reaction Types of Alkyl Halides

Chapter 6 46

Preparation of Alkyl Halides

¾ From radical halogenation of alkenes

e.g. allylic bromination with N-bromosuccinimide (NBS) and light

¾From alkenes by addition of HBr and HCl

C C C

H

C C C

Br

NBS CCl

C C C C

H Br + HBr

hν ,

Chapter 6 47

11.12 Conversion of Alcohols into Alkyl Halides

Î Hydroxyl groups are poor leaving groups, and as such, are often converted to alkyl

halides when a good leaving group is needed

Î Three general methods exist for conversion of alcohols to alkyl halides, depending on the classification of the alcohol and the halogen desired

Î Reaction can occur with phosphorus

tribromide, thionyl chloride or hydrogen

halides

Chapter 6 48

¾From alcohols

• Reaction with HX, where X=Cl, Br, I

Reactivity order 3°>2°>1°

C OH

H C

X HX H

Ether

• Reaction of 1° and 2° alcohols with SOCl

C

OH

H C

Cl SOCl

H

Pyridine

• Reaction of 1° and 2° alcohols with PBr

C OH

H C

Br PBr ₃ H

Ether

Chapter 6 49

• By using hydrogen halides, HX

Examples

Chapter 6 50

• By using PBr

Chapter 6 51

• By using SOCl

Chapter 6 52

12.7 Reactions of Organolithium and Organo-magnesium Compounds

z Reactions with Compounds Containing Acidic Hydrogen Atoms

ÎOrganolithium and Grignard reagents

behave as if they were carbanions and they

are therefore very strong bases