320
Dinesh N Sawant and Bhalchandra M Bhanage
L2 (20 mol%), iodobenzene (0.5 mmol) and POCl3
2 mmol) under nitrogen atmosphere. The vessel was
(
then sealed with a septum under nitrogen atmosphere
and placed into the microwave cavity of standard
◦
microwave system at 160 C which was reached within
3
0 s and reaction mixture was pre-stirred for 2 min; then
reaction was performed for 50 min under microwave
irradiation. After completion, the reaction mixture was
cooled to room temperature and sealed tube was opened
(caution). The reaction mixture was poured into a satu-
rated solution of NaHCO (50 mL). The product was
3
extracted with ethyl acetate (4 × 20 mL). The combined
organic layers were dried over Na SO and evapo-
2
4
rated to afford the crude product which was purified
by column chromatography on silica gel (petroleum
ether/ethyl acetate combination) to afford the pure pro-
duct. The product was confirmed by GC, IR and GCMS
analysis.
Figure 1. Biologically active benzonitrile derivatives.
requires harsh reaction conditions and reagents restrict-
ing its application.22 Zhang et al. reported copper-
mediated cyanation of aryl halides with the combina-
tion of DMF and NH HCO as safe cyanide source;
4
3
but requirement of stoichiometric amount of copper
salt, high temperature and longer reaction time limits
3
. Results and discussion
23
its application. Recently, we have reported cyanide-
free protocol for cyanation using formamide as nitrile
source for the first time. However, our reported pro-
tocol requires longer reaction time 48 h.24 After first
report in 2000 by Alterman and Hallberg25 on cya-
nation using microwave heating, many protocols for
Reaction of iodobenzene and formamide with POCl as
3
an additive with palladium/Xantphos (L1) catalyst sys-
tem was chosen as a model reaction (table 1, entry 1).
Reactions were performed in specially designed sealed
microwave tubes of 10 mL capacity using standard
◦
microwave system at 150 C which was reached within
aryl nitriles synthesis were reported using microwave
3
0 s and reaction was performed for 20 min under
techniques an various metal cyanide source.2
6,27
How-
microwave irradiation. After work-up with NaHCO3
and subsequent extraction with ethyl acetate; the prod-
uct benzonitrile (41%) was obtained along with traces
of benzamide as side product (table 1, entry 1).
ever, till date, applicability of cyanide-free protocols
for aryl nitriles synthesis have not been explored under
microwave conditions (scheme 1). Herein, we report
for the first time a rapid microwave-promoted, sim-
ple, solvent-free, cyanide-free protocol for the syn-
28
CAUTION!
Encouraged by this result, various phosphine li-
gands were screened (table 1, entries 1–5) (figure 2). It
was observed that dppf also provided comparable yield
up to 39% as dppf is more economical than Xantphos,
a selected ligand of choice for further optimization
(table 1, entry 2). In order to increase yield of pro-
duct, role of various palladium-precursors were
thesis of aryl nitriles using Pd(OAc) /dppf as a new
2
catalytic system, which requires very short reaction
time (50 min).
2
. Materials and methods
A microwave tube (10 mL) was dried and charged with
degassed formamide (2 ml), Pd(OAc) (5 mol%), and
checked. Only Pd(OAc) was found to provide higher
2
2
yield with only traces of benzamide as side product
(
table 1, entry 2). However, use of PdCl provided
2
benzamide as well as benzonitrile as product and pres-
sure developed was more than 7 bar (table 1, entry 6).
Pd(tmhd) which was also screened resulted in rapid
2
increase in pressure in microwave tube up to more than
10 bar (table 1 entry 7). Next, we checked effect of cata-
lyst loading which showed that decreasing catalyst
loading and metal to ligand ratio leads to decrease
Scheme 1. Microwave-assisted cyanide-free synthesis of in yield of product (table 1, entries 8–12). Hence, it
aryl nitriles.
can be seen that 5 mol% of Pd(OAc) and 20 mol%
2