Organic Chemistry IVBenzene and Its Derivates

Indra Yudhipratama

Outline Aromaticity

Huckel’s rule The Reactions (Electrophilic

Substitution) Halogenation Friedel-Craft’s Reaction

Alkylation and acylation Nitration and sulphonation Oxidation and reduction of

benzene derivates

Disubstitution (Ortho, meta, para directing groups)

Phenol and aniline The relative acidity of phenol The relative basicity of aniline Diazoniums compounds

The Main Features The bond length is between C – C and C=C (1.38 A)

Due to delocalised electron (resonance structure)

The Main Features The structure is planar Each carbon has p orbital that forms π bonding Maximum bonding benzene should planar

p Cloud Formation in Benzene

Aromaticity (Hückel’s Rules) Huckel’s rules define the classification of aromatic and non-aromatic

molecule. The criteria of aromatic molecule:

All the atoms are sp2 hybridised and in planar cyclic arrangement.All atoms are sp2 but not a cyclic. Hence, non-aromatic

There is non-sp2 atom. Hence, non-aromatic

All atoms are sp2 and a cyclic. Hence, could be aromatic

Huckel’s rules

Huckel’s rule Number of π-electrons is (4n+2), How to calculate π-electrons?

based on the structure, p-orbitals in sp2 arrangement has 1 electron

Has 6 π-electrons (4n+2, n=1)Hence, aromatic

Has 4 π-electrons (4n, n=1)Hence, anti-aromatic

Huckel’s Rule (summary)

Is the molecule has no non-sp2

atoms?

YES NO

How many π-electrons in the

molecule?

4n+2 Not 4n+2

aromatic Anti-aromatic

non-aromatic

Huckel’s rules

Porphyrin ring in the haem groupN

NH N

HN

OHO

HOO

Huckel’s rule

Which molecules are aromatic?

Is this molecule aromatic?

N

HN

6 π-electrons 2 π-electrons

The reactions

Benzene undergoes electrophilic substitution

Doesn’t undergo electrophilic addition

The consequence of aromatic properties

E+E

+ H+

Cl2

Cl

Cl

The reactions - Halogenation Halogenation. E.g. chlorination

Via:

The presence of Lewis acid (e.g. AlCl3) helps benzene to react with Cl2

Cl2

AlCl3

Cl

Cl

Al

Cl

Cl

Cl Cl

Cl

Al

Cl

Cl

Cl Cl

H

Cl

H

Cl

H

Cl

H

Cl Cl

The Reactions – Friedel-Crafts Reaction

Friedel-Crafts Reaction (Alkylation) To substitute with hydrocarbon chain

Via:

Cl

AlCl3

Cl

Al

Cl

Cl

Cl

Cl

Al

Cl

Cl Cl

Electrophilic generation

H

The reactions Friedel-Crafts Reaction

There is a problem for this reaction when longer alkyl halide is used

Rearrangement of the electrophile (carbocation)

Trying to find the most stable carbocation

Cl

AlCl3

+

+ +

ClAlCl3

H

H

The Reactions Friedel-Crafts Reaction (Acylation) To substitute with R-CO –

Via:

Electrophilic generation acylium ion stabilised by resonance. Both structures are valid.

Cl

O

AlCl3

O

Cl

O

Cl

Al

Cl

Cl

Cl

O

Cl

Cl ClO

O

The reactions

Acylation can be used to get around the ‘messy’ long chain alkylation.

O

O

H

O

Cl

O

AlCl3

O

H2NNH2

KOH

The Reactions The nitration (concentrated sulphuric acid as catalyst)

Via:

HNO3

conc. H2SO4

NO2

O

N

O

OHO

S

OH

O O

H

O

N

O

OH2O

N

O

O

N

O NO2

H

NO2

The Reactions

Sulphonation

Via:

conc. H2SO4 or

SO3, conc. H2SO4

SO3H

HO

S

O

O O

H

HO

S

OH

O O

H2O

S

OH

O O

S

OO

OH

S

OO

OHO

S

O

O O

H

The reactions Sulphonation

Producing strong sulphonic acid

S O

O

HO

SO3H

H

SO3H

The Reactions The Oxidation of toluene

Where R is alkyl group The Reduction of Aniline

ROH

O

1 ) K M n O 4 , O H -, H e a t

2 ) H 3 O +

NO2 NH2F e

H C l

aniline

The Reactions Formation of Diazonium salts

Diazonium salts is a good precursor compound for: Halogenation formation of phenol deamination coupling reaction of arenediazonium salts

NH2 N+ N

Cl-

N a N O 2 , H C l

H 2 O

0 - 1 5 oC

The Reactions

The Reactions Coupling reaction of arenediazonium salts

Where Q is activating group ( –OH, –NR3).

E.g.:

N+ N

Cl- +

Q

N

N Q

N+ N

Cl- +

OH

O+

NN

HH

Cl- OH

NN

N+ N

Cl- +

OH

OH

NN

Disubstitution of Benzene The benzene ring can be substituted with another FG more than once. The second position is determined by the first FG

Three possible positions:

ortho (1,2) meta (1,3) para (1,4)

CH3 NH2 OH ClCH3O OHONH2O

NH CH3

O

R

R1

R

R1

R

R1

Disubstitution of Benzene The determining factor

The nature of FG electron withdrawing (EW) or electron donating (ED) group

EW: the FG generally has partial positive charge It deactivate the benzene ring, so it is less reactive

ED: the FG generally has partial negative charge It activate the benzene ring, so it is more reactive

Disubstitution of Benzene

Disubstitution of Benzene E.g. Application for synthesis route

Phenol The structure

The relative acidity Acidity The easiness to release H+ (proton) The stability of the acid conjugate determine the relative acidity. The comparison with water and alcohol (e.g. ethanol)

OH

Phenol Let’s put water as the standard and the conjugate.

More stable the conjugate, more acid the substance. In ethoxide ions the alkyl group push the electrons increasing the charge In phenoxide ions, it forms a bigger resonance structure due to unbonding

p-orbital

OH

O H

H CH3

OH

O-

O-

HCH3

O-

Phenol The effect of substituent

The principle: The reduction of the charge The deactivating benzene substituent will make phenol more acidic The activating benzene substituent will make phenol less acidic.

Phenol 3-methylphenol 3-nitrophenol 3-chlorophenol

pKa = 9.89 pKa = 10.01 pKa = 8.28 pKa = 8.80

OH OH

CH3

OH

Cl

OH

NO2

Phenol

Predict the pKa of 2,4 dinitrophenol.

(a) 10.17

(c) 8.11

(d) 3.96

(b) 9.31

OH

NO2

NO2

Phenol Esterification of Phenol No reaction with carboxylic acid

Only react with acyl chloride or acetic anhydride

OH+ CH3

OH

O H 3 O +

No reaction

+Cl

OOH

+O

OOH

O

O

O

base

Phenol Suggest the products from the reactions below

OH

O

OH

EtOH

H3O+

O

OO

conc. H2SO4

O

O

OH

OH

O

O

O

Phenol How to distinguish with alcohol?

Since the phenol is more acidic than alcohol, so it can reacts with weaker base (e.g. NaHCO3)

Both of them can react with Na

OHNaHCO3

O

Na

+ CO2 + H2O

OHNaHCO3

OH O

NaNa

+ 1/2 H2

OH O

NaNa

+ 1/2 H2

Aniline The Basicity of amines

Basicity >< Acidity Basicity How easy a compound can accept H+

The case: The relative Basicity of ethylamine, amine, and aniline

The easiness of compound to accept H+

The availability of lone pair electrons on N atom

CH3 NH2 NH3

NH2

aniline

ammoniamethanamine

Aniline The reactions

Phenylamine cannot react in the similar way like amine. Phenylamine is not a better nucleophile than amine

the availability of the electrons on N atom to do the reaction

H N O 3

c o n c d H 2 S O 4

N+

O-

O

F e /S n

H C l

NH2 N a N O 2 , H C l

0 - 1 5 oC

N+ N

Cl-

NH2n-BuCl

NH2

n-BuCl

HN

This reaction can produce the other amines. Could you draw the other products?

Aniline Phenylamine could form an amide with acyl chloride.

Important synthetic pathway for aniline-based compound

NH2

Cl

O

HN

O

NH2

H2N

+Cl

O

O

Cl

HN

NH

O

O

n