Orientation in Aromatic compounds.ppt

Orientation in substitution reactio

1. ORIENTATION in electrophilic
substitution reaction on benzene ring
•The process in which position of
incoming electrophile in already
substituted benzene is determined.
275

2. 276

3. The direction of the reaction
•The activating group directs the reaction to
the ortho or para position, which means the
electrophile substitute the hydrogen that is on
carbon 2 or carbon 4. The deactivating group
directs the reaction to the meta position,
which means the electrophile substitute the
hydrogen that is on carbon 3 with the
exception of the halogens that is a
deactivating group but directs the ortho or
para substitution.
277

4. 278

5. Substituents determine the reaction
direction by resonance or inductive effect
•Resonance effect is the conjugation between the ring
and the substituent, which means the delocalizing of
theπ�electrons between the ring and the
substituent.
•Inductive effect is the withdraw of the sigma ( the
single bond ) electrons away from the ring toward
the substituent, due to the
higherelectronegativityof the substituent compared
to the carbon of the ring.
279

6. Activating groups (ortho or para
directors)
•When the substituents like -OH have an
unshared pair of electrons, the resonance
effect is stronger than the inductive effect
which make these substituents stronger
activators, since this resonance effect direct
the electron toward the ring. In cases where
the subtituents is esters or amides, they are
less activating because they form resonance
structure that pull the electron density away
from the ring.
280

7. MECHANISM
281

8. CONTINOU…….
•By looking at the mechanism above, we can see how
groups donating electron direct the ortho, para
electrophilic substition. Since the electrons locatinn
transfer between the ortho and para carbons, then
the electrophile prefer attacking the carbon that has
the free electron.
•Inductive effect of alkyl groups activates the
direction of the ortho or para substitution, which is
when s electrons gets pushed toward the ring.
282

9. Deactivating group (meta
directors)
•The deactivating groups deactivate the ring by
the inductive effect in the presence of an
electronegative atom that withdraws the
electrons away from the ring.
•we can see from the mechanism above that
when there is an electron withdraw from the
ring, that leaves the carbons at the ortho, para
positions with a positive charge which is
unfavorable for the electrophile, so the
electrophile attacks the carbon at the meta
positions.
283

10. 284

11. CONTINUE…..
•we can see from the mechanism above that
when there is an electron withdraw from the
ring, that leaves the carbons at the ortho, para
positions with a positive charge which is
unfavorable for the electrophile, so the
electrophile attacks the carbon at the meta
positions.
285

12. Halogens are an exception
•Halogens are an exception of the deactivating
group that directs the ortho or para
substitution. The halogens deactivate the ring
by inductive effect not by the resonance even
though they have an unpaired pair of
electrons. The unpaired pair of electrons gets
donated to the ring, but the inductive effect
pulls away theselectrons from the ring by the
electronegativity of the halogens.
286

13. CONTINUE……
•EXAMPLES
287

14. The CH
3Group is and ortho, para Director
288

15. The O-CH
3Group is an ortho, para
Director
289

16. EXAMPLES OF META DIRECTING
GROUPS
290

17. Acyl groups are meta Directors
291

18. •orientation or directive effect can be
explained by studying the all the possible
resonance structure of the sigma complex
formed as a result of the electrophile at ortho,
meta and para positions for different types of
monosubstituted benzene
292

19. a)Ortho-para directing groups which having electron
releasing inductive effect (+I effect):
•Ex: Alkyl groups (-R) has +I effect i.e electron
releasing effect. Let’s study the sigma
complexes(carbocation intermediate) which
are formed by attacked of electrophile (+E) at
ortho, para and meta position of mono
substituted benzene ( toluene).
293

20. 294

21. •The sigma complex or carbocation
intermediate is a resonance hybrid of three
Structure. Alkyl group has electron releasing
effect so it is disperse the positive charges and
stabilize the carboncation. Structure 1&5
effect is maximum because +ve charge is
present at the position of carbon where the
methyl group is attached.
295

22. •b)Ortho-para directing groups which are
having electron withdrawing (-I effect) and
electron releasing (+R or +M effect)
resonance or mesomeric effect:
•Ex -NH2 group. Various sigma complexes or
intermediate resulting from attract of
electrophile Ortho-para and meta positions.
•
296

23. 297

24. •At Ortho and para positions the sigma
complex obtained resonance hybrid of four
Structure, at meta position only three.
Structure 4 and 7 are more stable as positive
charges delocalised on the nitrogen atom as
well as ring carbon atom.
298

25. Meta directing groups:
•all meta directing groups ( -NO2, CN, COOH,-
CHO, -SO3H) are electron withdrawing in
nature. They have both electron withdrawing
inductive and resonance effect i.e -I and -R
effect.
299

26. 300

27. •Structure 3 and 5 are highly unstable as
electron withdrawing nitro groups attached to
the carbon atom which are having +ve charge.
So sigma complex intermediate from Ortho
&para attack are resonance hybrid of 2
Structure. Ortho-para attacking sigma
complex are less stable than meta attack.
Electrophilic substitution reaction is occurs
slowly in nitrobenzene than Benzene.
•
301

28. 302302
12.9: Rate and Regioselectivity in Electrophilic Aromatic
Substitution -The nature of a substituent already present on
the benzene ring affects the rateand regioselectivity(relative
position) of electrophilic aromatic substitution.
A substituent (-X) is said to be activatingif the rate of electrophilic
aromatic substitution of the substituted benzene (C
6H
5X) is
fasterthan benzene.
A substituent (-X) is said to be deactivatingif the rate of
electrophilic aromatic substitution of the substituted benzene
(C
6H
5X) is slowerthan benzene.
Relative rate of nitration:CF
3 CH
3
benzene toluene(trifluoromethyl)benzene
2.5 x 10
-5
1 20-25
deactivating activating

29. 303303(trifluoromethyl)benzene
CH
3
toluene
H
2SO
4, HNO
3
CH
3
NO
2
CH
3
CH
3
NO
2
NO
2
+
o-nitrotoluene
(63%)
m-nitrotoluene
(3%)
CF
3
H
2SO
4, HNO
3
CF
3
NO
2
CF
3
CF
3
NO
2
NO
2
+
o-nitro-(trifluoromethyl)
benzene
(6%)
m-nitro-(trifluoromethyl)
benzene
(91%)
p-nitro-(trifluoromethyl)
benzene
(3%)
p-nitrotoluene
(34%)
+
+
A substituent (-X) is said to be an ortho-para directorif it directs
an incoming electrophile to positions ortho and/or para to itself.
A substituent (-X) is said to be an meta directorif it directs
an incoming electrophile to position meta to itself.

30. 304304
Substituents are characterized as either electron-donating or
electron-withdrawing and alter the electron density of the
aromatic ring through:
1. Inductive effects: ability of a substituent to donate or withdraw
electron density through -bonds due to electronegativity
differences and bond polarities of a functional group
2. Resonance effects: ability of a substituent to donate or
withdraw electrons through non-bonding pairs of electrons or
overlap-bonds (conjugation).X
X= F, Cl,
Br, I
C
N
C
O
R

+

+

-

+

-
N
O
O

-

-
Electron-withdrawing groups
CH
3
Electron-donating group C
N
C
O
R
N
O
O
X OCH
3
Electron-donating groupsElectron-withdrawing groups

31. 305305
The rate (activating or deactivating) and regiochemistry
(ortho-para vs meta directing) can be understood by examining
the influence of the substituent on the stability of the cyclohexa-
dienyl cation intermediate.
12.10: Rate and Regioselectivity in the Nitration of Toluene:
Regioselectivity: The carbocation intermediate from o-or
p-addition can be stabilized by the substituent through inductive
effects and hyperconjugation.CH
3
ortho
meta
para
63%
3%
34%

32. 306306
Activating groups increase the rate of electrophilic aromatic
substitution at all positions of the ring.
Partial rate factors -relative rate of electrophilic aromatic
substitution compared to benzene
Electron rich aromatic rings are more nucleophlic.
All activating group donate electrons through inductive effects
and/or resonance. Electron-donating groups stabilize the
carbocation intermediate of electrophilic aromatic substitution. CH
3
4242
2.52.5
58
C
4.54.5
33
75
CH
3H
3C
H
3C

33. 307307
12.11: Rate and Regioselectivity in the Nitration of
(Trifluoromethyl)benzene-Regioselectivity: The carbocation
intermediate from o-or p-addition is destabilized by the
electron-withdrawing substituent. This directs addition to the
m-position. CF
3
ortho
meta
para
6%
91%
3%

34. 308308
Dactivating groups decrease the rate of electrophilic aromatic
substitution at all positions of the ring.
Partial rate factors -relative rate of electrophilic aromatic
substitution compared to benzeneCF
3
4.5 x 10
-64.5 x 10
-6
6.7 x 10
-5
6.7 x 10
-5
4.5 x 10
-6
Electron deficient aromatic rings are less nucleophlic.
All deactivating group withdraw electrons through inductive
effects and/or resonance. Electron-withdrawing groups
destabilize the carbocation intermediate of electrophilic aromatic
substitution.

35. 309309
12.12: Substituent Effects in Electrophilic Aromatic
Substitution: Activating Substituents
All activating substituents increase the rate of electrophilic
aromatic substitution and are ortho-para directors.
Nitration of phenol: the -OH is a very strong activating groupOH
ortho
meta
para
50%
0%
50%

36. 310310
Substituents that have an O or N atom directly attached to the
aromatic ring are strong activators. Phenol, anisole, and anilines
are very strong activators and do not require strong Lewis Acid
catalysts to undergo electrophilic aromatic substutution.
-alkyl, -vinyl, -aryl -OH, -OCH
3, -NH
2
activators strong activators very strong activatorsOC
O
R
H
NC
O
R
12.13: Substituent Effects in Electrophilic Aromatic
Substitution: Strongly Deactivating Substituents
Strong deactivators are meta directors
strong deactivators very strong deactivatorsCH
O
CR
O
COH
O
COR
O
CN SO
O
O
N
O
O
CF
3

37. 311311
12.14: Substituent Effects in Electrophilic Aromatic
Substitution: Halogens-Halogens are deactivating because
they are strong electron withdrawing groups (inductive effect);
however, they have non-bonding pairs of electrons and can also
donate electrons (resonance effect), and are ortho-para directors.Cl
ortho
meta
para
30%
1%
69%

38. 312312
12.15: Multiple Substituent Effects-The individual directing
effect of each substituent must be considered in order to
determine the overall directing effect of a disubstituted
benzene toward further electrophilic substitution.
Table 12.2, p. 491-NR
3
CN
-NO
2
-SO
3
H-CO
2
H
CR
O-CO
2
R
CH
O
-I
-Br-F
-Cl-H
alkyl
H
NCR
O
OCR
O
-OR-NH
2
-OH
strong deactivators
(meta directors)
strong activators
(ortho/para directors)
deactivators
(ortho/para directors)

39. 313313
1. When the individual directing effects of the two groups
reinforce, further electrophilic substitution is directed to the
common position.
2. When the individual directing effects of two groups oppose, the
stronger activating group has the dominant influence; however,
mixtures of productsare often produced.CH
3
NO
2
-CH
3
directs here
-NO
2
directs here
-CH
3
directs here
-NO
2
directs here
Br
2
, FeBr
3
CH
3
NO
2
Br OH
CH
3
-OH directs here
-CH
3
directs here
-OH directs here
-CH
3
directs here
Br
2
, FeBr
3
OH
CH
3
Br

40. 314314
3.Further substitution between two existing substituents
rarely occurs. Start with an ortho-disubstituted benzene to
synthesize 1,2,3-trisubstituted benzenesCH
3
-CH
3
directs here
-Cl directs here
-CH
3
directs here
-Cl directs here
Br
2
, FeBr
3
CH
3
Cl Cl
-CH
3
directs here-Cl directs here
CH
3
Br
Cl
Br
CH
3
Cl
Br
+
not observed
+ CHO
Br
-Br directs here
-CHO directs here
-CHO directs here
-Br directs here
CHO
Br
Cl
+
CHO
Br
Cl
Cl
2
, FeCl
3 CH
3
Br Br
Cl
-CH
3
directs here
-Br directs here
-Br directs here
-CH
3
directs here
-Br directs here
-Br directs here
-Cl directs here
-Cl directs here

41. 315315
12.16: Regioselective Synthesis of Disubstituted Aromatic
Compounds
Consider the directing effects of the substituents to determine
the order of their introduction to ensure the correct orientation
Friedel-Crafts reactions (alkylation, acylation) cannot be carried
out on strongly deactivated aromatics
Sometimes electrophilic aromatic substitution must be combined
with a functional group transformationCO
2H
NO
2 Br

42. 316316NO
2
Cl
m-director
deactivating
o,p-director
deactivating
o,p-director
activating

43. Why are halogensortho-,para-
directors?
•All activating groups are alsoortho-,para-
directors.
•Halogens (F, Cl, Br, I) are notable in that they
aredeactivatingortho-,para-directors. Why?
•In electrophilic aromatic substitution (EAS),
addition at theortho-orpara–position results
in a carbocation intermediate with a
resonance form containing a carbocation
directly adjacent to the directing group.
317

44. •Halogens have alone pairthat can form a pi-
bond with the adjacent carbocation.
•Even though halogens
aredeactivatingoverall, this “pi donation”
helps to stabilize the transition state leading
toortho–orpara-products, which is why they
areortho-,para-directors.
318

45. 319

46. Chlorination of nitrobenzene
320

47. 321
12.17: Substitution in Naphthalene (please read)
12.18: Substitution in Heterocyclic Aromatic Compounds
(please read)
Summary of electrophilic aromatic substitution of benzene
Zanger, M.; Gennaro, A. R.; McKee, J. R. J. Chem. Ed.1993, 70 (12) , 985-987SO
3H
X
(m-) (o-, p-)
NO
2 CH
2R
O R
(o-, p-)(m-) (m-)
Br R
(o-, p-)
CO
2H
(m-)
HNO
3,
H
2SO
4
X
2,
catalyst
RCH
2X,
AlCl
3
RCOCl,
AlCl
3
SO
3,
H
2SO
4
[O]
NBS,
h
[O]
[H]