Switch of reaction pathway induced by solid support and ultrasound

Article abstract of DOI:10.1080/00397911.2010.524338

The influence of activation methods and solid support on the reaction course of benzyl bromide, KCN, and toluene has been investigated. When KCN is not supported on alumina, the reaction under the mechanical agitation follows the aromatic electrophilic substitution pathway, while the reaction under sonication follows nucleophilic substitution. However, when KCN supported on alumina is employed, only the nucleophilic substitution product is obtained under both ultrasound and mechanical agitation. Copyright Taylor & Francis Group, LLC.

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Switch of Reaction Pathway Induced by
Solid Support and Ultrasound
Tan L. H. Doan a & Thach N. Le a
a Department of Organic Chemistry, Faculty of Chemistry, University
of Science, Vietnam National University–Hochiminh City, Hochiminh
City, Vietnam
Accepted author version posted online: 20 Jul 2011. Version of
record first published: 06 Oct 2011
To cite this article: Tan L. H. Doan & Thach N. Le (2012): Switch of Reaction Pathway Induced
by Solid Support and Ultrasound, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 42:3, 337-340
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Synthetic Communications1, 42: 337–340, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.524338
SWITCH OF REACTION PATHWAY INDUCED BY SOLID
SUPPORT AND ULTRASOUND
Tan L. H. Doan and Thach N. Le
Department of Organic Chemistry, Faculty of Chemistry, University of
Science, Vietnam National University–Hochiminh City,
Hochiminh City, Vietnam
GRAPHICAL ABSTRACT
Abstract The influence of activation methods and solid support on the reaction course of
benzyl bromide, KCN, and toluene has been investigated. When KCN is not supported on
alumina, the reaction under the mechanical agitation follows the aromatic electrophilic
substitution pathway, while the reaction under sonication follows nucleophilic substitution.
However, when KCN supported on alumina is employed, only the nucleophilic substitution
product is obtained under both ultrasound and mechanical agitation.
Keywords Benzyl bromide; electrophilic aromatic substitution; mechanical agitation;
nucleophilic substitution; potassium cyanide; ultrasonic irradiation
INTRODUCTION
In recent years, ultrasonic power has been widely applied in chemical processes
because of its impressive effects on reactions.[1,2] It is mainly employed as an activation
method for various reactions such as Michael addition,[3] Cannizzaro reaction,[4] and
Diels–Alder cycloaddition.[5] The influence of ultrasound on nucleophilic substitution
has also been investigated, for example, in the synthesis of diaryl ethers,[6] the reaction
of t-alkyl halides with zinc and titanium thiocyanate,[7] and nucleophilic aromatic
substitution on haloarenes.[8] Solid supports have proved to be a prospective media
for numerous reactions.[9] Therefore, the combination of inorganic supports such as
alumina and ultrasonic irradiation should provide interesting results.[10]
Received December 18, 2009.
Address correspondence to Le Ngoc Thach, Department of Organic Chemistry, Faculty of
Chemistry, University of Science, Vietnam National University–Hochiminh City, 227, Nguyen Van Cu
St., Hochiminh City, Vietnam. E-mail: lenthach@hcm.vnn.vn
337

338
T. L. H. DOAN AND T. N. LE
Scheme 1. Influence of conditions on the reaction pathway.[11]
In 1984, Takashi Ando and coworkers found that the reaction between benzyl
bromide and potassium cyanide in toluene–alumina mixture afforded different
products under ultrasonic irradiation and mechanical agitation. They obtained a
mixture of o- and p-benzyltoluene in 75% yield if mechanical agitation was applied.
In contrast, the same reaction mixture produced benzyl cyanide as the sole product
in 71% yield under ultrasonic irradiation. The reaction pathway switched from
Friedel–Crafts reaction to nucleophilic substitution (Scheme 1).
However, there are some issues that may need to be clarified by further studies
such as the role of alumina in both reactions and what else, beside activation
methods, can affect the reaction course. We report here our new findings to provide
better understanding of the reaction behavior.
RESULTS AND DISCUSSION
All reactions were carried out under nonsolvent conditions. The same molar
quantity (5.0 mmol) of benzyl bromide, potassium cyanide, and toluene were mixed
with alumina (1.0 g, Merck, type for column chromatography, neutral, activity 1)
at 50 ꢀC for 24 h. As summarized in Table 1, mechanical agitation gave a mixture
of o- and p-benzyltoluene in 65% yield if unsupported KCN was used while ultrasonic
Table 1. Effect of solid support and activation methods
GC yield (%)
Entry
Condition
C6H5CH2CN C6H5CH2C6H4CH3
KCN not supported on Al2O3
1
2
Mechanical agitation
Ultrasonic irradiation
0
19
65
10
KCN supported on Al2O3
3
4
Mechanical agitation
Ultrasonic irradiation
59
79
0
0

SWITCH OF REACTION PATHWAY
339
irradiation (Power Sonic 450 laboratory cleaner, 100 W, 40 kHz) produced benzyl
bromide in 19% yield along with a mixture of o- and p-benzyltoluene (10%). To
our surprise, both ultrasonic irradiation and mechanical agitation yielded more than
50% of the cyanide substitution product if KCN supported on alumina (KCN=Al2O3,
with potassium cyanide approximately 37% in weight)[12] was employed.
CONCLUSIONS
As we can see from Table 1, the form of KCN (supported or not supported on
alumina) is more important than activation methods in term of determining the
reaction pathway. The electrophilic aromatic substitution is completely shut down
if supported KCN is employed. This result can be explained because KCN supported
on alumina shields the active sites on the surface of alumina, which catalyzes the
Friedel–Crafts reaction. In addition, when KCN is supported on alumina, this inor-
ganic support loosens the ionic bond between Kþ and ꢁCN. As consequence, ꢁCN
becomes the stronger nucleophile to attack benzyl bromide. On the other hand, the
erosive effect of ultrasound on the alumina surface also contributes to break this
ionic bond, leading to greater yield of substitution product when ultrasonic
irradiation is applied (Table 1, entry 4).
In contrast, if KCN is not supported on alumina, the active sites on alumina
can initiate the formation of benzyl cation from benzyl bromide. The benzyl cation
then reacts with toluene in the reaction mixture to afford the electrophilic substi-
tution products. However, the effect of ultrasound is not clear in this case.
EXPERIMENTAL
Preparation of KCN Supported on Alumina
Potassium cyanide (10.00 g) is completely dissolved in pure water (50.00 mL),
and then alumina (16.00 g) is added. After stirring at room temperature for 1 h, water
is removed by a rotary evaporator to afford potassium cyanide supported on alumina
containing 38.46% (w=w) KCN.[12]
Scheme 2. Mechanism of SN2.
Scheme 3. Mechanism of SE.

340
T. L. H. DOAN AND T. N. LE
General Procedure
Benzyl bromide (5.0 mmol), toluene (5.0 mmol), potassium cyanide (5.0 mmol),
and alumina (1.0 g), or KCN supported on alumina (0.85 g) are combined in a 50-mL
round-bottom flask. The reaction mixture is put under mechanical agitation or
ultrasonic irradiation (Power Sonic 450, 100 W, 40 kHz) at 50 ꢀC for 24 h. The solid
is filtered off and washed exhaustively by dichloromethane. Solvents are then evapo-
rated, and the residue is weighed and analyzed by GC (Shimadzu GC–17A) to
calculate the gas chromatography yield.
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