Lecture Notes - Rajendra€¦ · Reaction at the meta position gives a sigma complex whose positive...
Transcript of Lecture Notes - Rajendra€¦ · Reaction at the meta position gives a sigma complex whose positive...
Lecture Notes
Paper – II
Group-B (Organic Chemistry)
Unit – 5 (Aromatic compound)
Part-4
For
B.Sc. (Part-4)
Honours & Subsidiary
Jai Prakash University, Chapra
By
Dr. Tanu Gupta
Assistant Professor
DEPARTMENT OF CHEMISTRY
RAJENDRA COLLEGE, CHAPRA
(+) (+) H
(+) (+)
Electrophilic Substitution Reactions of
Substituted Benzenes Halogens are deactivating groups, yet they are ortho, para-directors because the halogens
are strongly electronegative, withdrawing electron density from a carbon atom through
the σ-bond, and the halogens have nonbonding electrons that can donate electron density
through π-bonding. If an electrophile reacts at the ortho or para position, the positive
charge of the sigma complex is shared by the carbon atom bearing the halogen. The
nonbonding electrons of the halogen can further delocalize the charge onto the halogen,
giving a halonium ion structure. This resonance stabilization allows a halogen to be pi-
donating, even though it is sigma-withdrawing.
ortho attack
Br
para attack
Br
meta attack
Br
E
(+)
E
(+)
H
(+)
(+)
(+)
H
E
bromonium ion
Reaction at the meta position gives a sigma complex whose positive charge is not
delocalized onto the halogen-bearing carbon atom. Therefore, the meta
intermediate is not stabilized by the halonium ion structure. Scheme 1 illustrates
the preference for ortho and para substitution in the nitration of chlorobenzene.
Cl Cl Cl Cl
chlorobenzene
HNO3
H2SO4
NO2
NO2
NO2
ortho-isomer meta-isomer para-isomer
(35% yield) (1% yield) (64% yield)
Scheme 1
Ortho-para ratio differs with the size of the substituents. Nitration of toluene
preferably gives ortho as the major product where the activating substituent is
methyl group. Electrophilic substitution reaction of ethyl substituted benzene,
however, gives ortho and para isomers equally. Bulky substituent such as tert-
butyl benzene preferably gives para-isomer as the major product (Scheme 2).
CH3 CH3 CH3
HNO3
H2SO4
NO2
NO2
toluene ortho-isomer para-isomer
major minor
CH2CH3 CH2CH3 CH2CH3
HNO3
H2SO4
NO2
NO2
ethylbenzene ortho-isomer para-isomer
50% 50%
C(CH3)3 C(CH3)3 C(CH3)3
HNO3
H2SO4
NO2
NO2
tert-butylbenzene ortho-isomer para-isomer minor
Scheme 2
major
3
3
2
Benzenes which are having a meta director (a deactivating group) on the ring, will
be too unreactive to undergo either Friedel-Crafts alkylation or Friedel-Crafts
Acylation (Scheme 3).
SO3H
H C Cl AlCl3
No reaction
benzenesulfonic acid
NO2
nitrobenzene
O
H C Cl AlCl3
No reaction
Scheme 3
Aniline and N-substituted anilines also do not undergo Friedel-Crafts reactions
because the lone pair on the amino group will form complex with the Lewis acid
and converting the substituent into a deactivating meta director. Tertiary aromatic
amines, however, can undergo electrophilic substitution because the tertiary
amino group is a strong activator (Scheme 4).
NH2
AlCl3
H N AlCl3
aniline
N(CH3)3 N(CH3)3 N(CH3)3
1) HNO3
CH3COOH
2) OH- N,N-dimethylaniline
NO2
NO2
ortho-isomer para-isomer
Scheme 4
Phenols are highly reactive substrates for electrophilic aromatic substitution
because of the presence of a strong activating group. So phenols can be alkylated
or acylated using relatively weak Friedel-Crafts catalysts such as HF (Scheme 5).
OH OH OH OH
HF H H
CH3
CH3
3C C 3
phenol 2-propanol H3C
CH3
4-isopropylphenol 2-isopropylphenol
Scheme 5
Phenoxide ions, generated by treating a phenol with sodium hydroxide, are even
more reactive than phenols toward electrophilic aromatic substitution. It gives
tribromosubstituted phenol when reacts with excess bromine and salicylic acid
when reacts with carbon dioxide (Scheme 6).
Br2
x
OH Br Br
(e cess)
OH O
NaOH
H2O
phenol phenoxide
ion
1. CO2
2. H+
Br
2,4,6-tribromophenol
OH
COOH
salicylic acid
Scheme 6
Nucleophilic Substitution Aryl halides do not react with nucleophiles under the standard reaction conditions
because the electron clouds of aryl ring repel the approach of a nucleophile. Nucleophiles
can displace halide ions from aryl halides, if there are strong electron-withdrawing
groups ortho or para to the halide. This class of reactions is called nucleophilic aromatic
substitution reaction (Scheme 7).
Cl
NO2
NO2
2 NH3
heat
pressure
NH2
NO2
NO2
1- chloro-2,4-dinitrobenzene 2,4-dinitroaniline
O2N
Cl
NO2
H2O, 40C
O2N
OH
NO2
NO2 NO2
2- chloro-1,3,5-trinitrobenzene picric acid
Scheme 7
Electron-withdrawing substituents such as nitro group make the ring reactive
towards nucleophilic aromatic substitution but without at least one powerful
electron-withdrawing group, the nucleophilic aromatic substitutions would be
difficult. The mechanism of nucleophilic aromatic substitution cannot be the SN2
mechanism because aryl halides cannot achieve the correct geometry for back-
side approach of a nucleophile. The SN1 mechanism also cannot be involved.
Consider the reaction of 2,4-dinitrochlorobenzene with a nucleophile (Scheme 8).
When a nucleophile attacks the carbon bearing the chlorine, a negatively charged
sigma complex results. The negative charge is delocalized over the ortho and
para carbons of the ring and further delocalized into the electron-withdrawing
nitro groups. Loss of chloride from the sigma complex gives the nucleophilic
substituted product.
Step 1: Attack by the nucleophile gives a sigma complex
Cl
NO2
NO2
Nu-
slow
Cl Nu
NO2
NO2
Cl Nu O N
O
Cl Nu O N
O
Cl Nu O N
O
Cl Nu O N
O
N N
O O O O N N
O O O O sigma complex
Step 2: Loss of leaving group gives the product
Cl Nu
NO2
NO2
fast
-Cl-
Scheme 8
Nu
NO2
NO2
The leaving group ability of halogen in nucleophilic aromatic substitution reaction
is following the order: F > Cl > Br > I. The incoming group should be a stronger
base than the group that is being replaced (Scheme 9).
F
MeO-
OMe
F-
NO2 NO2
1-fluoro-4-nitrobenzene 1-methoxy-4-nitrobenzene
Br
CH3
HN
NO2
NO2 H3C NH2
OH-
NO2
NO2 H2O
1-bromo-2,4-dinitrobenzene N-ethyl-2,4-dinitroaniline
Scheme 9
Benzyne Mechanism
Although chlorobenzene does not contain an electron-withdrawing group, it can undergo
a nucleophilic substitution reaction in the presence of a very strong base but the incoming
substituent does not always end up on the carbon vacated by the leaving group. For
example, when chlorobenzene is treated with amide ion in liquid ammonia, aniline is
obtained as the product. Half of the product has the amino group attached to the carbon
vacated by the leaving group, but the other half has the amino group attached to the
carbon adjacent to the carbon vacated by the leaving group. This is confirmed by isotopic
labeling method (Scheme 11).
Cl NH2
* NaNH2 *
liq. NH3
NH2
chlorobenzene aniline
Scheme 11
*
Br
When p-bromotoluene is treated with amide ion in liquid ammonia, 50:50 mixtures of p-
toludine and m-toludine is obtained (Scheme 12).
Br NH2
NaNH2
liq. NH3
CH3 CH3 CH3
NH2
p-bromotoluene p-toludine m-toludine
Scheme 12
From the above examples one can conclude that the reaction takes place by a
mechanism that forms an intermediate in which the two adjacent carbons are
equivalent. The experimental observations evidence the formation of a benzyne
intermediate where there is triple bond between the two adjacent carbons atoms of
benzene. In the first step of the mechanism, the strong base removes a proton
from the position ortho to the halogen. The resulting anion expels the halide ion,
thereby forming benzyne (Scheme 13).
Br
H
CH3
NH2
-Br-
CH3 CH3
carbanion benzyne
Scheme 13
NH2
NH2 NH2
The incoming nucleophile can attack either carbons of the “triple bond” of
benzyne (Scheme 14). Protonation of the resulting anion forms the substitution
product. The overall reaction is an elimination-addition reaction. Substitution at
the carbon that was attached to the leaving group is called direct substitution.
Substitution at the adjacent carbon is called cine (Greek: movement)
substitution.
NH2 NH2
H
CH3 CH3 CH3
p-toludine
H NH2
H
NH2
CH3 CH3 CH3
m-toludine
Scheme 14
H NH2
X
As halide leaves with its bonding electrons from the carbanion, an empty sp2
orbital remains that overlaps with the filled orbital adjacent to it, giving additional
bonding between these two carbon atoms. The two sp2 orbitals are directed 60°
away from each other, so their overlap is not very effective. Triple bonds are
usually linear but the triple bond in benzyne is a highly strained, so it is a very
reactive intermediate. Amide ion is a strong nucleophile, attacking at either end of
the benzyne triple bond. Subsequent protonation gives the product (Scheme 15).
Step 1: Deprotonation adjacent to the leaving group gives a carbanion
X
Nu-
H
Step 2: The carbanion expels the leaving group to give a "benzyne" intermediate.
Step 3: The nucleophile attacks at either end of the reactive benzyne triple bond.
Nu
Nu-
Step 4: Reprotonation gives the product
Nu Nu
H Nu H
Scheme 15
X
Benzyne is too unstable to be isolated but can be trapped by Diels-Alder reaction with
anthracene or furan. For example, Anthracene reacts with benzyne to give a symmetrical
cage structure (Scheme 16).
benzyne anthracene
Scheme 16
Reduction Catalytic hydrogenation of benzene to cyclohexane takes place at high temperatures and
pressures. Platinum, palladium, nickel, ruthenium or rhodium is used as catalyst. The
reduction cannot be stopped at an intermediate stage as these alkenes are reduced faster
than benzene (Scheme 17).
3 H2, pressure
Pt, Pd, or Ni
benzene cyclohexane
CH3 3 H2, pressure
CH3
CH3
Ru or Rh
CH3
m-xylene 1,3-dimethylcyclohexane
Scheme 17
Benzene and its derivatives can be reduced to nonconjugated cyclic dienes by treating
sodium or lithium liquid ammonia (Scheme 18). This reduction is called Birch
reduction.
Li, NH3 (l)
EtOH, Et2O
Scheme 18
A solution of sodium or lithium in liquid ammonia contains solvated electrons that can
add to benzene, forming a radical anion. The strongly basic radical anion abstracts a
proton from the alcohol, giving a cyclohexadienyl radical. The radical quickly adds
another solvated electron to form a cyclohexadienyl anion which is then protonated to
give the reduced product (Scheme 19).
Step 1: Formation of solvated electrons
NH3 Na or Li NH3 e- Na+
solvated electron
Step 2: Formation of a radical
H H
e-
H OR
H H
H
H H
radical
RO-
Step 3: Formation of the product
H H H H
e- H OR
RO-
H H H H H H
carbaion
Scheme 19