Factors affecting Nuecleophilic substitution

reaction

Steric nature of the reactant

SN2----- CH3-X, R-CH2X, allylic,

benzylic

SN1----- R3-CX, allylic, benzylic

Nature of nucleophile

small, strong Nu- favors SN2----

OH-, CH3O-, CH3CH2O-, CN-, RS-, RCN-, Br-, I-

weak, small Nu- favors SN1----- H2O, CH3OH, CH3CH2OH, RSH, NH3, F

Solvent used

SN2---- low moderate polarity solvent as:

acetone, NMF

SN1----- moderate to high polarity solvents as:

water, methanol, ethanol

Leaving group

all halogens, except F , are good leaving group

water is good leaving group ( not OH)

Question: Explain WHY? then show the mechanism

R OH + HBr R-Br + H2O

R OH + HBr

H+

no reaction

Electrophilic Substitution Reactions

Benzene is treated with a mixture of concentrated nitric acid

and concentrated sulphuric acid at a temperature not

exceeding 50°C. As temperature increases there is a greater

chance of getting more than one nitro group, -NO2,

substituted onto the ring.

Nitrobenzene is formed.

or:

HH22SOSO44

heatheat

THE NITRATION OF BENZENETHE NITRATION OF BENZENE

If you are going to substitute an -NO2 group into the ring,

then the electrophile must be NO2+. This is called the

"nitronium ion" or the "nitryl cation", and is formed by

reaction between the nitric acid and sulphuric acid

The formation of the electrophile

The equation

THE HALOGENATION OF BENZENETHE HALOGENATION OF BENZENE

Benzene reacts with chlorine or bromine in an electrophilic

substitution reaction, but only in the presence of a catalyst.

The catalyst is either aluminium or ferric chloride (or

aluminium (ferric) bromide if you are reacting benzene with

bromine) or iron.

FeCl3

FeBr3

The formation of the electrophile

As a chlorine molecule approaches the benzene ring, the delocalised electrons in the ring repel electrons in the chlorine-chlorine bond

it is the slightly positive end of the chlorine molecule which acts as the electrophile. The presence of the aluminium chloride helps this polarisation.

Friedel-Crafts Acylation of Benzene Friedel-Crafts Acylation of Benzene

Named after Friedel and Crafts who discovered the reaction.

Reagent : normally the acyl halide (e.g. usually RCOCl) with

aluminum trichloride, AlCl3, a Lewis acid catalyst.

The AlCl3 enhances the electrophilicity of the acyl halide by

complexing with the halide.

FRIEDEL-CRAFTS ACYLATION OF FRIEDEL-CRAFTS ACYLATION OF BENZENE BENZENE

Electrophilic species : the acyl cation or acylium ion (i.e. RCO

+ ) formed by the "removal" of the halide by the Lewis acid

catalyst, which is stabilised by resonance as shown below.

Other sources of acylium can also be used such as acid anhydrides with AlCl3

Addition Reactions

16

• In an addition reaction, new groups X and Y are added to the starting material. A bond is broken and two bonds are formed.

17

• Addition and elimination reactions are exactly opposite. A bond is formed in elimination reactions, whereas a bond is broken in addition reactions.

The double bond dissolves back to single bond and new bonds reach out to A and B whose bond is also dissolving

C C C C

BA

C C

A B

A-B can be :

H-H H-OH H-X OH-OH OH-X

Draw the product of each of these examples of A-B when they add to 1-propene.

C C

H

H H

CH3

H-H H-OH H-X OH-OH OH-X

Addition reactions Addition reactions

A reaction in which an atom or group of atoms is added

to a molecule. divided into:

1.1- Electrophlic Addition

mechanism

H2C CH2 + HX CH3CH2X

X = Cl, Br, I

a. H2C CH2 H X+ H3C CH2 + X-

b. H3C CH2 + X- H3C CH2Xfast

slow

Electrophilic addition reactions - the general picture

Why?Why?

addition to unsymmetrical alkenes

According to Markovnikov's RuleAccording to Markovnikov's Rule

•Which is an empirical rule based on Markovnikov's experimental

observations on the addition of hydrogen halides to alkenes.

•The rule states that :

"when an unsymmetrical alkene reacts with a hydrogen halide to give

an alkyl halide, the hydrogen adds to the carbon of the alkene that

has the greater number of hydrogen substituentshas the greater number of hydrogen substituents, and the

halogen to the carbon of the alkene with the fewer number of

hydrogen substituents"

Addition of H-X Reactivity rank: HI > HBr > HCl > HF.

It is an electrophilic addition reaction.

It Follows Markovnikov`s rule.

Markovnikov`s rule:

“In addition of HX to asymmetrical alkenes, the H+ of HX goes to the double-bonded carbon that already has the greatest number of hydrogens”

EXAMPLE:

Addition of HCl to 1-Propene.

It is a regioselective reaction, follow Markovnikov`s rule.

Cont.Addition of H-X

Anti-Markovnikov addition

EXAMPLE

Addition of HBr to 1-Propene in presence of peroxideperoxide.

In the presence of peroxides (chemicals containing the general structure ROOR'), HBr adds to a given alkene in an anti-Markovnikovfashion

WWU -- ChemistryWWU -- Chemistry

MarkovnikovMarkovnikov

Markovnikov

Not Markovnikov

WWU -- ChemistryWWU -- Chemistry

WWU -- ChemistryWWU -- Chemistry

MARKOVNIKOV RULEMARKOVNIKOV RULE

CH2

+ HCl

CH3

Cl

When adding HX to a double bond thehydrogen of HX goes to the carbonwhich already has the most hydrogens

..... conversely, the anion X adds to the mosthighly substituted carbon ( the carbon withmost alkyl groups attached).

WWU -- ChemistryWWU -- Chemistry

REGIOSELECTIVEREGIOSELECTIVE REACTION REACTION

CCH3

CH3

CH2 CCH3

CH3

CH3

Cl

+ CHCH3 CH2

Cl

CH3HCl

major minor

one of the possible products is formedin larger amounts than the other one

Compare

REGIOSPECIFICREGIOSPECIFIConly one of the possible products isformed (100%).

WWU -- ChemistryWWU -- Chemistry

Mechanism (Markovnikov)Mechanism (Markovnikov)

R CH CH2 R CH-CH2

R CH CH2 H

Br

1)+

+

slow

2)_ fast

+

+

H

Br

H

R CH-CH2

+H

Electrophile

Nucleophile

Secondary C+

Major product

WWU -- ChemistryWWU -- Chemistry

Mechanism (anti-Mechanism (anti-Markovnikov)Markovnikov)

R CH CH2R CH CH2

H

R CH CH2

H

R CH CH2 Br

H

1)+ slow

+2)

_ fast

+

+

H

Br

+

Minor!

Primary carbocation

WWU -- ChemistryWWU -- Chemistry

Markovnikov Addition to Markovnikov Addition to an Alkenean Alkene

C CH2

CH3

CH3

H X CH3 C CH2

CH3

X

H CH3 C CH2

CH3

H

X+ +

major product minor productX = Cl, Br, I

ADDITION OF H2O

• ADDITION OF H2O to alkene

• ADDITION OF H2O to aldehyde

HBr and HCl easily add to alkenes. Since water also is a molecule of the type HX which can donate a proton, H2O should be able to add to alkenes in the same way as HBr, for example, resulting in the hydration of an alkene. However, for the addition of H2O to alkenes to occur acid catalysts acid catalysts are required.

ADDITION OF H2O to alkene

ADDITION OF H2O to aldehyde

Form 1,1-diol (hydrate) what is the type of the reaction?????what is the type of the reaction?????

EXAMPLE: Formation of chloral hydrate.

2.2. Nucleophilic Addtion Nucleophilic Addtion

It is the most common reaction of aldehydes (RCHO) and ketones (RCOR)It is the most common reaction of aldehydes (RCHO) and ketones (RCOR)

e.g. e.g. The reaction of aldehydes and ketones with hydrogen cyanideThe reaction of aldehydes and ketones with hydrogen cyanide

hydroxynitriles.hydroxynitriles.

WWU -- ChemistryWWU -- Chemistry

MechanismMechanism

C CH21)+

+

slow

2)_ fast

+

+

H

Electrophile

Nucleophile

CH3

CH3

CH CH2

CH3

CH3 H

+C CH2

CH3

CH3 H

C CH2CH3

CH3 H

X

X

3 o C+

37

Classify each of the following as either substitution, elimination or addition reactions.

a)OH

Br

substitution

b)

addition

c)

OH

elimination

WWU -- ChemistryWWU -- Chemistry

SOME ADDITIONAL EXAMPLESSOME ADDITIONAL EXAMPLES

CH3

+ HCl

CH3

Cl

CH2

+ HCl

CH3

Cl

CH CH2 CH CH3

Cl+ HCl

only major product is shown