Efficient Microwave-Assisted Cyanation of Aryl Bromides

Article abstract of DOI:10.1081/SCC-120030308

Aryl nitriles were easily prepared from the corresponding bromides and copper cyanide in good yields through microwave-accelerated Rosenmund-von Braun reaction in N-methylpyrrolidinone (NMP) under ambient pressure.

Full text of DOI:10.1081/SCC-120030308

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Efficient Microwave‐Assisted Cyanation of Aryl
Bromide
a
a
a
b
Liangzhen Cai , Xin Liu , Xiaochun Tao & Dong Shen
a
Department of Chemistry, East China University of Science and Technology, Shanghai,
China
b
Chemical Physics Lab, Science College, East China University of Science and
Technology, Shanghai, 200237, China
Version of record first published: 21 Aug 2006.
To cite this article: Liangzhen Cai, Xin Liu, Xiaochun Tao & Dong Shen (2004): Efficient Microwave‐Assisted Cyanation
of Aryl Bromide, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 34:7, 1215-1221
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w
SYNTHETIC COMMUNICATIONS
Vol. 34, No. 7, pp. 1215–1221, 2004
Efficient Microwave-Assisted Cyanation of
Aryl Bromide
1
Liangzhen Cai, Xin Liu, Xiaochun Tao, and Dong Shen
1
1
2,*
1
2
Department of Chemistry and Chemical Physics Lab, Science College,
East China University of Science and Technology, Shanghai, China
ABSTRACT
Aryl nitrileswere easilypreparedfrom thecorrespondingbromidesand copper
cyanide in good yields through microwave-accelerated Rosenmund–von
Braun reaction in N-methylpyrrolidinone (NMP) under ambient pressure.
Key Words: Microwave irradiation; Cyanation; Aryl bromide; Aryl
nitriles.
INTRODUCTION
Aryl nitriles are valuable intermediates that can be converted into
[1]
compounds with a broad spectrum of functionalities. Usually, aryl nitriles
*
Correspondence: Dong Shen, Chemical Physics Lab, Science College, East China
University of Science and Technology, Shanghai 200237, China; Fax: 0086-021-
4252018; E-mail: shen@ecust.edu.cn.
6
1
215
DOI: 10.1081/SCC-120030308
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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1
216
Cai et al.
[2]
[3]
were synthesized by dehydration of aryl carboxamides or aldoximes.
Another commonly used method for the preparation of aryl nitriles is coupling
[4]
of aryl halide with copper cyanide (the Rosenmund–von Braun reaction).
This reaction is usually carried out in polar solvents such as nitrobenzene,
0
N,N -dimethylformamide (DMF) or dimethylsulfoxide (DMSO) using excess
of CuCN at 150–2508C. The long reaction time (typically 15 hr) and high
temperature limit the application of this reaction.
Microwave-assisted chemical synthesis has attracted considerable atten-
[
5]
tion in recent years. Using microwave irradiation in chemical synthesis
can significantly reduce reaction time and also improve yield, selectivity,
[6]
and purity of the product in many cases. Alterman and Hallberg have
described the cyanation of aryl bromide with zinc cyanide catalyzed by
Pd(Ph P) under microwave irradiation. In this case, the reaction time could
3
4
be shortened to 2.5 min or less. More recently, Arvela et al. have reported
the microwave-promoted CuCN-mediated Rosenmund–von Braun reaction
[
7]
of aryl iodides. However, these two reactions were conducted in sealed
tubes. The potential hazard of explosion caused by rapid dielectric heating
in the sealed tubes would inhibit the wider use of these methods. Therefore,
it would be advantageous to use methods with inexpensive reagents under
ambient pressure for such transformations.
We report herein the use of microwave heating technique in CuCN-
mediated Rosenmund–von Braun reaction in the absence of catalyst such as
Pd or Ni complex (Sch. 1).
In order to optimize the reaction conditions, the effect of solvents was
first studied. N-methylpyrrolidinone (NMP), DMF, DMSO and 1,2-dimethyl-
imidazole (DMI) were tested for the cyanation of bromobenzene with CuCN
under microwave irradiation (Fig. 1). NMP was found to be the best solvent
for this reaction based on conversion rate and reaction time, possibly because
of its high boiling point, efficient coupling with microwave irradiation (micro-
wave-active solvent), and excellent solubility of CuCN. DMI and DMSO are
also good solvents for this transformation, but DMI is the most expensive
one among these solvents. In the case of DMSO, the obnoxious odor of
dimethyl sulfide emitted at elevated temperature limits its application.
Cyanation of various aryl bromides was next examined under microwave
irradiation. All reactions were conducted in NMP, with 1.1–1.3 equiv. of
Scheme 1. Cyanation of aryl bromide using MW irradiation.

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Microwave-Assisted Cyanation of Aryl Bromide
1217
Figure 1. Conversions under different solvents.
CuCN and the results were summarized in Table 1. A dramatic decrease in
reaction times, as well as comparable yields to the traditional methods were
observed with all reactions as compared. The microwave irradiation reduced
the reaction times to 20–30 min from 10 to 18 hr with conventional thermal
[
4d]
heating. For example, the microwave-assisted cyanation of 5-bromoindole
Entry 8) was finished in 30 min, and this transformation needs at least 18 hr
(
to completion if using thermal method.
In summary, we have developed a general and efficient microwave-
assisted approach for the cyanation of aryl bromides with CuCN under ambi-
ent pressure. This method is experimentally simple, and gave good yields
within short time.
EXPERIMENTAL
All reactions were performed in a MW-800 multimode microwave
reactor. Reagents and solvents were obtained from commercial sources and
used as received. All products are known and gave physical (mps or bps) and
1
spectra ( H NMR, IR and MS) data consistent with the assigned structures.
Melting points were determined with a X-4 micro melting point apparatus
and are uncorrected. IR spectra were recorded on a Nicolet Nexus 470 FT-IR

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1
218
Cai et al.
Table 1. MW-assisted CuCN-mediated synthesis of aryl nitriles in NMP.
a
Time
(min)
Yield
(%)
M.p. (obs.)
(8C)
M.p. (lit.)
(8C)
Entry
1
Substrates
20
25
90
85
oil
—
[
8]
2
37–38
38
[
9]
3
4
5
6
7
25
20
20
30
25
87
56
78
75
68
83–84
148–149
223–224
55–56
86–87
[
8]
148–150
[
10]
222
[
12]
56–57
[
10]
224–225
227
[
11]
8
30
79
102–104
104–106
a
Isolated yields.
1
spectrophotometer in KBr. H NMR spectra were measured on a Brucker AM
500 (500 MHz) spectrometer using TMS as internal standard.
Microwave-Enhanced Cyanation of Aryl
Bromides—General Procedure
A mixture of aryl bromide (10 mmol), CuCN (1.2 g, 13 mmol), and 10 mL
of NMP was subjected to microwave irradiation (200 W) under ambient pres-
sure for an optimized time listed in Table 1. The reaction was monitored
by TLC. After irradiation, the mixture was cooled to room temperature
and then diluted with 20 mL of ice water. The precipitates were collected
by filtration and treated with aqueous ammonia. The crude product was
taken up into chloroform followed by filtration. After removal of the
solvent, the product was further purified by recrystallization from aqueous
ethanol.

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Microwave-Assisted Cyanation of Aryl Bromide
1219
Spectral data of the selected products:
2
1
4
-Phenylbenzonitrile (Entry 3): FT-IR n
(KBr, cm ): 2225, 1605,
max
1
485, 1113, 1078, 847; H NMR dH (CDCl ): 7.76–7.68 (m, 4H,
1
PhH), 7.63–7.60 (m, 2H, PhH), 7.50–7.43 (m, 3H, PhH).
3
2
1
1
5
,4-Dicyanobenzene (Entry 5): FT-IR n
1
(KBr, cm ): 2280, 2230,
max
1
610, 1305, 1015; H NMR d (CDCl ): 7.81 (s, 4H, PhH).
H 3
2
(KBr, cm ): 3390, 2200, 1250,
1
-Cyanoindole (Entry 8): FT-IR n
max
1
1
7
100; H NMR d (DMSO-d ): 6.64–7.48 (m, 2H, CH 55 CH), 7.59–
H 6
.67 (m, 2H, PhH), 8.15 (s, 1H, PhH), 11.72 (s, 1H, NH).
ACKNOWLEDGMENTS
This work was supported by Ministry of Education P.R.C. and East China
University of Science and Technology.
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Received in Poland September 29, 2003

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