Microwave assisted aromatic nucleophilic substitution reaction under solventless condition

Article abstract of DOI:10.1081/SCC-120018702

We report here microwave assisted aromatic nucleophilic substitution reaction of 1-chloro-4-nitrobenzene with different phenoxides.

Full text of DOI:10.1081/SCC-120018702

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Microwave Assisted Aromatic Nucleophilic Substitution
Reaction Under Solventless Condition
a
a
Geeta L. Rebeiro & Bhushan M. Khadilkar
a
Organic Chemistry Research Laboratory , Applied Chemistry Division , University Institute
of Chemical Technology , Matunga, Mumbai, India
Published online: 15 Aug 2006.
To cite this article: Geeta L. Rebeiro & Bhushan M. Khadilkar (2003) Microwave Assisted Aromatic Nucleophilic Substitution
Reaction Under Solventless Condition, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 33:8, 1405-1410, DOI: 10.1081/SCC-120018702
To link to this article: http://dx.doi.org/10.1081/SCC-120018702
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Õ
SYNTHETIC COMMUNICATIONS
Vol. 33, No. 8, pp. 1405–1410, 2003
Microwave Assisted Aromatic Nucleophilic
Substitution Reaction Under
Solventless Condition
y
Geeta L. Rebeiro* and Bhushan M. Khadilkar
Organic Chemistry Research Laboratory, Applied
Chemistry Division, University Institute of Chemical
Technology, Matunga, Mumbai, India
ABSTRACT
We report here microwave assisted aromatic nucleophilic substitu-
tion reaction of 1-chloro-4-nitrobenzene with different phenoxides.
*
Correspondence: Geeta L. Rebeiro, Organic Chemistry Research Laboratory,
Applied Chemistry Division, University Institute of Chemical Technology,
Matunga, Mumbai 400 019, India; E-mail: geeta_rebeiro@hotmail.com.
y
Dedicated to my late guide, Dr. B. M. Khadilkar (Principal author).
1
405
DOI: 10.1081/SCC-120018702
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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1
406
Rebeiro and Khadilkar
Aromatic nucleophilic substitution reaction of 1-chloro-4-nitroben-
zene with various phenoxides represents a synthetically important reaction
0
to produce substituted-4 -nitrodiphenyl ethers (Sch. 1). In fact, p-nitrodi-
1]
phenyl ether is a key intermediate for the synthesis of local anesthetic,
[
[
2]
[3]
fungicides, bactericides as well as polyimide end-capping agents.
[4]
0
2,4-Dichloro-4 -nitrodiphenyl ether commonly called as Nitrofen is a well
known herbicide. However, synthetic procedures for the preparation of
[5]
[
6]
[7,8]
ethers require high reaction temperatures, catalysts,
[
dipolar aprotic
polar solvents—both conventionally as well as under microwave
9]
[
10]
heating.
ether synthesis.
The diaryl ethers have also been prepared by Ullmann’s
[11]
With the growing concern to develop safer technologies, microwave
assisted ‘‘solvent-free’’ reactions are especially appealing for providing an
environmentally benign system. The use of solvents in microwaves gives
rise to elevated temperatures and consequently high pressures posing
hazards. These problems have been overcome to a large extent by carry-
ing out reactions in the modified oven or under ‘‘dry’’ conditions either
by using solid supports or ‘‘neat’’ state reactions.
As a part of our ongoing program to develop microwave assisted
solvent-free reactions and to study the ‘‘specific’’ microwaves effects, we
carried out aromatic nucleophilic substitution reaction of 1-chloro-4-
nitrobenzene (PNCB) with substituted phenols using KOH as a base in
a solvent-free environment in a microwave cavity.
For comparison the reactions were carried out under conventional
heating in an oil bath, preheated to the microwave end temperature
(temperature noted immediately after microwave exposure). The results
of microwave and oil bath heating are illustrated in Table 1.
The experimental results showed that in the case of oil bath heating
the yields are lower, the exception being that in case of o-chlorophenol,
the yields were comparative. This indicates the possibility of specific
microwave effects in some of the reactions excluding o-chlorophenol.
But the exact mode of microwave action in the reaction is difficult to
understand. Hence, we irradiated the reagents and products separately
Scheme 1.

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Aromatic Nucleophilic Substitution Reaction
1407
Table 1. Results of the reaction of 1-chloro-4-nitrobenzene with various
phenoxides in microwave and oil bath heating.
Microwave
Conventional heating
ꢀ
Time (s)/ Temp Yield Time Temp Yield M.p. ( C)
ꢀ
a
ꢀ
b
Entry
1
R
power (%) ( C)
(%)
72
(s)
( C)
(%) (reported)
–H
180/20, 92
220
98
Nil
60–62
(61–62)
2
2
0/30,
0/100
2
3
4
2,4-dichloro
2-Cl
300/100
480/100
36/100
160
186
176
63
66
61
300
480
40
160
186
176
8
58
70
(
(
70–71)
75–76
74–76)
2-OMe
Nil
104–106
106)
(
5
6
4-t-butyl
3-CH
360/100
105/10
106
118
78
50
360
120
110
125
20
13
54–56
64–66
65–66)
69–70
3
(
7
8
4-CH
2-CH
3
30/20
50/20,
126
124
73
64
30
60
126
124
Nil
Nil
3
Oil (37)
Oil
1
0/100
150/10,
0/20
47/100
9
2-CH
2
CH¼CH
2
120
124
87
67
240
47
120
124
Nil
Nil
9
1
0
2-OCH
3
,
Oil
4
-CH¼CHCH
3
a
Temperature noted down immediately after microwave exposure.
Temperature of preheated oil bath.
b
and noted down the rate of microwave absorption in terms of increase in
the temperature. In the case of the reaction of guaicol and l-chloro-4-
nitrobenzene, it was observed that the end temperature, after irradiating
guaicol, 1-chloro-4-nitrobenzene, and the product separately, was much
lesser than that of the reaction mixture (Table 2).
The reaction being typically an S 2 Ar reaction and it possess dispersal
N
of charge in the transition state, a possibility of microwave absorption by
such a transition state is likely. We propose that the rise in temperature
may be due to the pre-transition state assemblies of molecule that
absorbed microwave more efficiently to reach the transition state quickly.
This effect perhaps is because of induced dipole leading to higher
polarization. Similar results were obtained in case of phenol as well as
other substituted phenols, except in case of o-chlorophenol, the product
absorbed efficiently and the temperature increase was nearly as much as
the temperature of the reaction mixture (Table 3). Thus, increase in the

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Rebeiro and Khadilkar
Table 2. Individual MW absorption of the reaction of guaicol, 1-chloro-4-
nitrobenzene (PNCB) and KOH.
ꢀ
Time
(s)
Initial temp
ꢀ
Final temp
ꢀ
ÁT C
Compounds
Guaicol
(T
1
C)
(T
2
C)
(T
2
1
–T )
126
126
126
126
34
32
32
32
84
42
52
10
1
-Chloro-4-nitrobenzene
K-Salt guaicolþPNCB
176
44
154
12
Product
Table 3. Individual MW absorption of the reaction of o-chlorophenol, 1-chloro-
-nitrobenzene (PNCB) and KOH.
4
ꢀ
ÁT C
Time
(s)
Initial temp
ꢀ
Final temp
ꢀ
Compounds
(T
1
C)
(T
2
C)
2 1
(T –T )
o-Chlorophenol
1
480
480
480
480
32
32
32
32
80
48
88
-Chloro-4-nitrobenzene
K-Salt o-chlorophenolþPNCB
120
186
160
154
128
Product
temperature may be due to the microwave absorption by the product as
it formed in the reaction and no athermal effect was observed here. Hence
the yields in conventional heating were comparative with that in micro-
wave reaction (Entry 3, Table 1). This indicates that some microwave
effect (athermal effect) might be operating in some of the reactions where
lower or no yields were obtained in oil bath heating.
The reaction of 1-chloro-4-nitrobenzene with phenol was also carried
out in presence of a aprotic polar solvent like DMSO under microwave
irradiation. A comparison of the same reaction under identical conditions
was done in oil bath heating. Under both conventional and microwave
heating, phenol reacted with 1-chloro-4-nitrobenzene in DMSO to give
77% of the product in same reaction time (Table 4). As polar molecules
are known to absorb microwave energy, thereby allowing high reaction
temperatures to be reached very quickly. This has exactly happened when
DMSO was used as a solvent for the reaction, DMSO being a strong
microwave absorber. This can be accounted to as the ‘‘thermal’’ effect
that brings about the reaction due to direct heating of the reagent
molecules due to absorption of microwaves by the solvent.
In conclusion, we have developed a solventless method for the
synthesis of p-nitrodiphenyl ethers under microwave irrakation. As the

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Aromatic Nucleophilic Substitution Reaction
1409
Table 4. Results of microwave and oil bath heating using DMSO as a solvent.
Heating
ꢀ
ꢀ
R
Time (s) Temp ( C) Yield (%) Time (s) Temp ( C) Yield (%)
a
–
H
90
142
77
120
142
77
a
At 30% mw power for 90 s.
reaction does not make any use of solvent, the method is ecofriendly.
The experimental results do throw some light on specific microwave
(
athermal) effect in this type of reaction. But this is just the tip of an
ice-berg, more evidence is required to confirm our proposition on
pre-transition state molecular assemblies responsible for the ‘‘athermal’’
effect in aromatic nucleophlic substitution reaction of phenol and
1-chloro-4-nitrobenzene.
TYPICAL PROCEDURE
Phenol (13 mmol) and KOH (13 mmol) were irradiated in micro-
wave for a specified time between 30 and 90 s depending on the substrate
to dissolve KOH. 1-Chloro-4-nitrobenzene (10 mmol) was then added
and the mixture was irradiated in modified microwave oven with stirring
for a specified time and power. The end temperature was recorded
after the exposure. The reaction mixture was cooled to room tempera-
ture, ice and 10% NaOH was added to dissolve unreacted phenol.
The reaction mixture was extracted with the solvent and washed several
times with NaOH and then with water. The solvent was distilled off and
the solid obtained was recrystallized fiom alcohol. The reaction was
also carried out with 53 mmol, (7.9 g) substrate which gave comparative
yields.
The compounds were characterized from their melting points, IR,
1
and H NMR analysis. Microwave oven model used was IFB-neutron.
ACKNOWLEDGMENT
The authors are thankful to the G. D. Gokhale Trust for awarding
fellowship to one of the authors.

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Received in the Netherlands June 6, 2002