A novel and simple solvent free method for nucleophilic aromatic substitution of inactive aryl halides

Article abstract of DOI:10.1081/SCC-200026216

A simple, high yield, and short time method for nucleophilic displacement reaction of inactive aryl halides is reported. The reaction is performed in microwave oven under thermal condition with montmorillonite supported AgNO ₃.

Full text of DOI:10.1081/SCC-200026216

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A Novel and Simple Solvent
Free Method for Nucleophilic
Aromatic Substitution of
Inactive Aryl Halides
Mohammed M. Hashemi a & Maryam Akhbari a
a Department of Chemistry, Sharif University of
Technology, P.O. Box 11365‐9516, Tehran, Iran
Version of record first published: 10 Jan 2011.
To cite this article: Mohammed M. Hashemi & Maryam Akhbari (2004): A Novel
and Simple Solvent Free Method for Nucleophilic Aromatic Substitution of Inactive
Aryl Halides, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 34:15, 2783-2787
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 15, pp. 2783–2787, 2004
A Novel and Simple Solvent Free Method for
Nucleophilic Aromatic Substitution of
Inactive Aryl Halides
*
Mohammed M. Hashemi and Maryam Akhbari
Department of Chemistry, Sharif University of Technology, Tehran, Iran
ABSTRACT
A simple, high yield, and short time method for nucleophilic displacement
reaction of inactive aryl halides is reported. The reaction is performed in
microwave oven under thermal condition with montmorillonite supported
AgNO3.
Key Words: Aryl halides; Nucleophilic substitution; Solvent free;
Montmorillonite K10.
INTRODUCTION
Nucleophilic aromatic substitution (SNAr) reactions constitute an active field
of organic chemistry, which is very important from the viewpoints of both prac-
tical applications[1] and the theory of nucleophilic reaction mechanisms.[2,3]
*
Correspondence: Mohammed M. Hashemi, Department of Chemistry, Sharif
University of Technology, P.O. Box 11365-9516, Tehran, Iran; E-mail: mhashemi@
sharif.edu.
2783
DOI: 10.1081/SCC-200026216
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

2784
Hashemi and Akhbari
It has long been known that an ortho- or para-nitro group strongly acti-
vates the condensation of a halobenzene with a nucleophilic reagent such as
a hydroxide[4] or an alkoxide ion,[5] a halide ion,[6] a mercaptide ion[7] or an
amine.[4,8]
It has been found that the order of activation in this reaction is NO2 ꢀ
CH3SO2 . CN . CH3CO.[8]
In absence of the electron withdrawing groups the proposed mechanism is
elimination–addition (Aryn mechanism).[9]
The nucleophilic substitution of inactive aryl halides is a very difficult
reaction and the reported methods require vigorous conditions such as
high pressure[10] and temperature,[11] very active nucleophiles[9,12] or special
solvents,[5,7,13] give low yields,[5,13] or long reaction time.[13]
Solid-phase organic reactions have found widespread utility in organic
synthesis.[14–16] A simple filtration allows the products to be recovered in
these reactions.
Microwave-assisted rapid organic reactions constitute an emerging tech-
nology that makes experimentally and industrially important organic synthesis
more effective and more eco-friendly than conventional reactions.[17,18] In
continuation of our studies on microwave-assisted organic reactions,[17,19]
we developed a very simple and convenient procedure for nucleophilic
aromatic substitution reactions catalyzed by montmorillonite K10 supported
AgNO3 under microwave irradiation and solvent-free condition (Sch. 1).
The tendency of Agþ cation to react with halides makes this cation a suitable
candidate for these reactions, which is in accord with experimental results
(Table 1).
The polarity of the reagents and the intermediates makes them good can-
didates for reaction in a microwave oven, and the interaction of the surface
with halides and counter ion of Agþ facilitate the reaction.
It is interesting that in spite of the previously known methods,[1–4,6] para-
and ortho-nitro, aryl halides do not react in these conditions.
Although we have not experimentally established the mechanism of the
reactions, according to Table 1, it seems that the attack of nucleophile does
not play an important role before leaving the halide ion, and probably Agþ
cation with absorption of halide ion, makes an active intermediate from aryl
halides which can react with even weak nucleophiles such as hydroxide and
Scheme 1.

Nucleophilic Aromatic Substitution of Inactive Aryl Halides
2785
Table 1. Nucleophilic substitution of aryl halides and phenyl tosylate.
Time
b (sec)
Yield (%)
Entry
Ar
X
Nu
a (hr)
a
b
1
2
Ph
Ph
Br
Cl
Cl
Cl
F
2OH
2OH
2CN
2CN
2CN
2CN
2OH
2OH
2OH
2OH
2.0
2.2
2.3
2.3
1.5
2.5
2.5
3.0
2.5
1.5
1.0
5
5
68
63
70
54
54
10
10
0
78
69
63
72
77
5
3
4-Methyl, phenyl
Ph
Ph
8
4
4
5
6
6
4-Nitro, phenyl
4-Nitro, phenyl
2-Nitro, phenyl
1-Naphtyl
2-Naphtyl
Ph
Cl
Cl
Cl
Br
Br
Br
10
12
20
9
7
22
0
8
9
48
53
62
73
81
71
10
11a
9
(S22
)
5
Note: a, Thermal condition. b, Microwave irradiation.
aThe yield refers to diphenyl sulfide.
benzoate anions. Therefore, the presence of a strong electron withdrawing
group decreases the yield and increases the time of the reaction (entries 6–8).
In the case of S22, the product is diphenyl sulfide and thiophenol was not
observed.
Using solvents in these types of reactions reduces the activity of some
nucleophiles and causes the rate to drop.[7]
Elimination of solvent, simple experimental procedure and work-up, high
yields, and mild conditions are the most significant aspects of this method.
EXPERIMENTAL
Aryl halides were purchased from Fluka, Meck and Aldrich. Phenyl tosy-
late was prepared by treatment of phenol with tosyl chloride in acetonitrile.
1
All products are known compounds and identified by their IR, H-NMR,
13C-NMR data, and mps.
Preparation of Supported AgNO3
To a solution of AgNO3 (3.38 g in 100 mL of water), montmorillonite K10
(15 g) was added and the mixture stirred for 30 min, water was evaporated in

2786
Hashemi and Akhbari
vacuum and the residue dried in an oven at 1008C for 1 hr to give 13.2 g of
AgNO3/montmorillonite reagent.
Reaction of Nucleophiles with Aryl Halides.
General Procedure
Aryl halide (2 mmol), sodium salt of nucleophile (2–3 mmol), and 2 g of
supported AgNO3 were mixed thoroughly in a mortar. The reaction mixture
was then irradiated in a domestic microwave oven for the indicated time, at
850 W or heated in a bath water in 968C (Table 1). The progress of reaction
was monitored by TLC using ethyl acetate/petroleum ether as eluent. The
mixture was extracted first with chloroform and then with methanol, and the
solvent was removed by rotary evaporation. Further purification by column
chromatography and recrystallization (for solid products) gave the desired
products.
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Received in the USA September 29, 2003