1. Electrophilic substitution reactions, such as halogenation, sulfonation, alkylation, and nitration, commonly occur on aromatic compounds like benzene. These reactions involve attack by an electrophile. 2. The orientation of a second substituent on a monosubstituted benzene ring is determined by factors such as the kinetics, electron density, and stability of the reaction intermediate. The first substituent activates or deactivates certain positions of the ring. 3. When two or more substituents are present on a benzene ring, their directing effects can reinforce each other, oppose each other, or have no effect, determining the position of additional substituents. The more

1. Mekanisme Reaksi
Substitusi Elektrofilik (SE)
reaksi substitusi elektrofilik, pada umumnya terjadi
pada senyawa aromatik, dan penyerangnya adalah
sebuah elektrofil (E+
)
Khususnya pada senyawa benzena

2. Mekanisme reaksinya:
E + Katalis E+
+ katalis
Dua tahapan yaitu;
1. pembentukan elektrofil dengan bantuan katalis
Elektrofil (E+)
2. Penyerangan elektrofil pada cincin benzena

3. Beberapa contoh pembentukan elektrofil:
dengan bantuan katalis
RCl + AlCl3 R+
+ AlCl4
-
Br2 + FeBr3 Br+
+ FeBr4
-
HNO3 + H2SO4 NO2
+
+ H2O
H2SO4 (berasap) SO3H+
+ HSO4
-
Elektrofil (E+)

4. HNO3 + H2SO4 NO2
+
+ H2O

6. 1. Beberapa reaksi SE pada cincin benzena
halogenasi
Sulfonasi
alkilasi asilasi
nitrasi

7. Contoh:
asilasi Friedel-Crafts
Mekanisme reaksinya.................
Mekanisme reaksinya.................

8. Bagaimana membuat senyawa tersebut dari
benzena....?

9. asilasi Friedel-Crafts dalam industri pembuatan bensaldehid

10. Contoh:
alkilasi Friedel-Crafts
Notice the stabilization of
formed carbocation as
electrophile

11. Benzene alkylation with akene
Benzene alkylation with an alcohol

12. Obtain the mayor product and its reaction mechanism
when an alkylhalide is reacted with benzene by Friedel-
Crafts alkylation
1. chloroetane
2.chloropropane
3. 2-chlorobutane
4. 1-chloro-2,2-dimetihylpropane
5. 1-chloro-2-methylpropane

13. 2. Fungsionalization og subtituted benzene
tersubstitusi (Second substituen)
Orto /Para Atau Meta
If G is electron or
releasing activated
benzene ring
If G is electron
withdrawing or
deactivated benzene
ring
G is first subtituen and
direct the second subtituen
(E+
) and effect reaction
rate

14. Three factors effect aromatic SE reactivity:
(1) Kinetics
(2) Electron density
(3) Stability of formed complex (related to the present
of resonance)
Kinetis,
Second substituen orientation can be determined by
subtituent constanta formula
k = equilibrium constante with substituent
ko = equilibrium constante without substituent
β = RX factor
σ = substituent constante

15. Electron density,
Substract electron density is effected by first subtituen. It
can be noticed from their effect: mesomery (M) and
inductive effect (I).
Examples:
Subtituen –NH2 (M) = + dan (I) = - o,p directing
Subtituen –CH3 (M) = + dan (I) = + o,p directing (Ekstrim)
Subtituen –Cl dan –OH (M) = + dan (I) = - o,p directing
Subtituen –NO2 (M) = - dan (I) = - m directing (Ekstrim)

16. Complex stability
Resonance structure showed stability grade. Second subtituen orientation on
aromatics (benzene): 0,p or m, is depend on stabilisation resonance
Examples:
Draw the resonance structure of monosubtituted benzene
when react with electrophile as second subtituent on
otho, para, dan meta position. Find the most stable
carbocationl

18. Several Substituents
G Orientation Rate
R- / Ar- orto , para faster
-OH / -OR orto , para Faster
- NH2, NHR, NR2 orto , para Faster
- X (halogen) orto , para Slower
-C=O meta Slower
- CN meta Slower
- NO2 meta Slower
- SO3H meta Slower

20. Both subtituen can undergo sinergism or antagonis effetc for
third substituen involve sterical effect
3. Third Substituted Benzene

21. • A methoxy group is ortho, para-directing, and a carbonyl
group is meta-directing. The open positions of the ring that
are activated by the methoxy group in p-
methoxyacetophenone are also those that are meta to the
carbonyl, so the directing effects of the two substituents
reinforce each other. Nitration of p-methoxyacetophenone
yields 4-methoxy-3-nitroacetophenone.

22. • All the substituents in 2,6-dibromoanisole are ortho,
para-directing, and their effects are felt at
• different positions. The methoxy group, however, is a far
more powerful activating substituent
• than bromine, so it controls the regioselectivity of
nitration.

24. There are several factors effect the third substitue to
1.
Observe and give your conclution:
...............................................
..............................................

25. 2.
What is your conclution:
...............................................
..............................................

26. 3.
What is your conclution
...............................................
..............................................

27. Dalam sintesis turunan senyawa
benzena, pengarah ini sangat penting
diperhatikan. Misalnya pada sinteis
bromonitrobenzena, kedudukan
kedua substituen saling menentukan.
Faktor substituen mana yang
didahulukan

29. For Piridin compound occurs at C3
4. Electrophilic substitution on heterocyclic aromatic compound

30. Furan,pirol, tiofen occurs at C 2 dan C3
(mainly)

32. How to synthesize compound below from
benzene

33. How to synthesize compound
below from benzene

34. How to synthesize compound below from benzene

36. 36
Disubstituted Benzenes
1. When the directing effects of two groups reinforce, the new substituent is located on the position
directed by both groups.

37. 37
2. If the directing effects of two groups oppose each other, the more powerful activator “wins out.”

38. 38
3. No substitution occurs between two meta substituents because of crowding.

39. 39
Synthesis of Benzene Derivatives
In a disubstituted benzene, the directing effects indicate which substituent must be added to the ring
first.
Let us consider the consequences of bromination first followed by nitration, and nitration first,
followed by bromination.

40. 40
Pathway I, in which bromination precedes nitration, yields the desired product.
Pathway II yields the undesired meta isomer.

41. 41
Halogenation of Alkyl Benzenes
Benzylic C—H bonds are weaker than most other sp3
hybridized C—H bonds, because
homolysis forms a resonance-stabilized benzylic radical.
As a result, alkyl benzenes undergo selective bromination at the weak benzylic C—H
bond under radical conditions to form the benzylic halide.

42. 42

43. 43
Note that alkyl benzenes undergo two different reactions depending on the reaction
conditions:
• With Br2 and FeBr3 (ionic conditions), electrophilic aromatic substitution occurs,
resulting in replacement of H by Br on the aromatic ring to form ortho and para
isomers.
• With Br2 and light or heat (radical conditions), substitution of H by Br occurs at the
benzylic carbon of the alkyl group.