Polyvinylpolypyrrolidone-supported boron trifluoride; Highly efficient catalyst for the synthesis of N-tert-butyl amides

Article abstract of DOI:10.1155/2012/632574

Highly efficient method for the preparation of N-tert-butyl amides by reaction of nitriles with tert-butyl acetate is described using polyvinylpolypyrrolidone-supported boron trifluoride (PVPP-BF₃) at 70 °C in good to excellent yields. Selective amidation of benzonitrile in the presence of acetonitrile was also achieved. polyvinylpolypyrrolidone-boron trifluoride complex shows non-corrosive and stable solid catalyst elevated Lewis acid property.

Full text of DOI:10.1155/2012/632574

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
http://www.ejchem.net
2012, 9(2), 576-582
Polyvinylpolypyrrolidone-Supported
Boron Trifluoride; Highly Efficient Catalyst for the
Synthesis of N-tert-Butyl Amides
MASOUD MOKHTARY1* and FARANAK NAJAFIZADEH2
1Department of Chemistry, Rasht Branch,
Islamic Azad University, Rasht, Iran
2Department of Chemistry, Science and Research,
Amol Branch, Islamic Azad University, Amol, Iran
mmokhtary@iaurasht.ac.ir
Received 7 July 2011; Revised 1 October 2011; Accepted 19 October 2011
Abstract: Highly efficient method for the preparation of N-tert-butyl amides
by reaction of nitriles with tert-butyl acetate is described using
polyvinylpolypyrrolidone-supported boron trifluoride (PVPP-BF3) at 70 °C in
good to excellent yields. Selective amidation of benzonitrile in the presence of
acetonitrile was also achieved. polyvinylpolypyrrolidone-boron trifluoride
complex shows non-corrosive and stable solid catalyst elevated Lewis acid
property.
Keywords: Polyvinylpolypyrrolidone, Boron trifluoride, Nitriles, Tert-butyl acetate, Tert-butyl amide.
Introduction
Among the reported routes, use of the Ritter reaction is an attractive method for the
synthesis of amide. The Ritter reaction makes possible the conversion of a group, easily
converted to relatively stable carbonium ion to a substituted amide by reaction with a nitrile
in the presence of strong acid1. The conversion of a nitrile to the corresponding N-tert butyl
amide is a very important transformation in organic synthesis. The product N-tert-butyl
amides are pharmaceutically applicable2 and also serve as precursors to the corresponding
amines. The classical Ritter reaction involves the reaction of alkenes and of tertiary and
benzylic alcohols with nitriles in the presence of conc. sulfuric acid3-5. As an alternative to
sulfuric acid, other acid catalysts such as (CF3SO2)2O6, BF3.Et2O7, Fe (III) -
9
12
montmorillonite8, Mg(HSO4)2 , Bi(OTf)310, CeCl3.7H2O/AcCl11, P2O5/SiO2 and nafion13
have been employed to improve the classical Ritter reaction. The Ritter reaction using tert-
butyl acetate instead of tert-butyl alcohol was also reported by sulfuric acid14,15
,
18
FeCl3.6H2O16, I2 17 and ZnCl2/SiO2
.
However, most of these methods suffer from at least one of the following disadvantage:
vigorous reaction conditions, strong protic and aqueous media, high cost and toxicity of the
reagent, tedious work-up procedures, unsatisfactory yields, and instability and hygroscopic

Polyvinylpolypyrrolidone-Supported Boron Trifluoride 577
nature of the reagent. Substantial investigations have been done to introduce novel supported
catalysts and chemical reagents. These include dispersing catalysts on inorganic supports
such as metal oxide, alumina, silica, and zeolite. There are a number of advantages in using
of polymer supported catalysts over the conventional catalysis. The reactions can be
performed under mild condition and purification of the product is simplified because of the
use of an insoluble solid support. Polymer supported catalysts can also be recycled after use.
Poly (vinyl pyrrolidone) displays a strong binding affinity toward small molecules, its iodine
complex, povidon-iodine, is widely used as an anti-infective agent in clinical treatments19. In
spite of boron trifluoride etharate, PVPP-BF3 is non-corrosive and stable solid catalyst
elevated Lewis acid property. Following our interest on the use of the Ritter reaction for the
21
synthesis of polyamides20, polyether amides and amidation of benzhydrol with nitriles via
polyvinylpolypyrrolidone-boron trifluoride (PVPP-BF3) 22, we found that PVPP-BF3 can be
used for the preparation of N-tert-butyl amides by tert-butyl acetate in good to excellent
yields (Scheme 1). This method leads to the development of eco-friendly protocols.
Interestingly, this reagent not only gives good yields of the products but also PVPP-BF3 is
easily regenerated and can be reused several times and retains its activity after several
months of storage.
PVPP-BF3
+ CH3CO2C(CH3)3
R-CN
R-CONHC(CH3)3
ClCH2CH2Cl
70 oC/2-5 h
R= alkyl or aryl
Scheme 1
Experimental
Polyvinylpolypyrrolidone (PVPP) was purchased from Fluka chemical company. Other
chemicals were purchased from Merck chemical company. Melting points were recorded on
an electro thermal melting point apparatus. The NMR spectra were recorded in CDCl3 with
TMS as an internal standard on a Bruker advance DRX 400 MHz spectrometer. IR spectra
were determined on a SP-1100, P-UV-Com instrument. Products were separated by simple
filtration, and identified by comparison IR, and 1H NMR spectra, with those reported for
authentic samples.
Catalyst preparation
In this method boron trifluoride etherate was immobilized on polyvinylpolypyrrolidone to
give a stable polymeric Lewis acid reagent according to our previous article22. To a
suspension of 3 g PVPP in 25 ml CH2Cl2, a solution of 5 ml BF3.Et2O in 15 ml CH2Cl2 was
added dropwise and the mixture stirred for 1 h at room temperature. The resulting resin was
filtered and washed with 2 × 10 ml CH2Cl2 and dried in a vacuum desiccator to give a stable
and non hygroscopic powder.
Synthesis of tert-butyl amides: General procedure
To a solution of 3 mmol nitrile and 3 mmol tert-butyl acetate in 5 mL 1,2-dichloroethane was
added 3 mmol (0.3 g) PVPP-BF3 and the reaction mixture was stirred for 2-5 h at 70 oC until TLC
analysis showed that no nitrile remained. The reaction mixture was filtered, and the solvent was
evaporated on a rotatory evaporator under diminished pressure. The solid residue was
recrystalized from water to afford pure crystals of the corresponding amides in 72-96% yields.
N-tert-butyl-benzamide (1)

578 MASOUD MOKHTARY et al.
1
FT- IR (KBr): υ = 3322, 3064, 2962, 1638, 1537, 1482, 858 cm-1. H NMR (400 MHz,
CDCl3) δ = 1.47 (s, 9H), 6.04 (br s, 1H), 7.52 (d, 2H), 7.58 (d, 2H) ppm.
N-tert-butyl-4-chlorobenzamide (2)
1
FT- IR (KBr): υ = 3322, 3067, 2927, 1639, 1529, 1540, 1483, 1315, 1220 cm-1. H NMR
(400 MHz, CDCl3) δ = 1.49 (s, 9H), 5.94 (br s, 1H), 7.29 (d, 2H) 7.66 (d, 2H) ppm.
N-tert-butyl-4-methylbenzamide (3)
1
FT- IR (KBr): υ = 3351, 3029, 2971, 1639, 1542, 1447, 1311 cm-1. H NMR (400 MHz,
CDCl3) δ = 1.49 (s, 9H), 2.37 (s, 3H), 5.96 (br s, 1H), 7.18 (d, 2H), 7.61 (d, 2H) ppm.
N-tert-butyl-3-methylbenzamide (4)
1
FT- IR (KBr): υ = 3382, 2962, 1643, 1529, 1447, 748 cm-1. H NMR (400 MHz, CDCl3)
δ = 1.49 (s, 9H), 2.4 (s, 3H), 5.95 (br s, 1H), 7.28-7.56 (m, 4H) ppm.
N-tert-butyl-4-hydroxybenzamide (5)
1
FT- IR (KBr): υ = 3274, 3068, 2969, 1639, 1548, 1307, 935 cm-1. H NMR (400 MHz,
CDCl3) δ = 1.49 (s, 9H), 5.97 (br s, 1H), 6.84 (d, 2H), 7.59 (d, 2H) ppm.
N,N’-di-tert-butylterphtalamide (6)
1
FT-IR (KBr): υ = 3301, 2969, 1639, 1546, 1324, 864 cm-1. H NMR (400 MHz, CDCl3)
δ = 1.50 (s, 18H), 5.97 (br s, 2H), 7.77 (s, 4H) ppm.
N,N’-di-tert-butylisophtalamide (7)
1
FT-IR (KBr): υ = 3272, 3068, 2969, 1639, 1548, 1307, 680 cm-1. H NMR (400 MHz,
CDCl3) δ = 1.49 (s, 18H), 6 (br s, 2H), 7.28-8.11 (m, 4H) ppm.
N-tert-butylacrylamide (8)
1
FT-IR (KBr): υ = 3263, 3072, 2964, 1656, 1567, 1403, 1226 cm-1. H NMR (400 MHz,
CDCl3) δ = 1.39 (s, 9H), 5.55 (dd, 1H), 5.82 (br s, 1H), 6.02-6.16 (m, 1H), 6.16-6.29 (m,
1H) ppm.
N-tert-butylchloromethylacetamide (9)
1
FT-IR (KBr): υ = 3311, 2977, 1683, 1554, 1222, 673 cm-1. H NMR (400 MHz, CDCl3)
δ = 1.40 (s, 9H), 3-96 (s, 2H), 6.38 (br s, 1H) ppm.
Ethyl 3-(tert-butylamino)3-oxopropanoate (10)
1
FT-IR (KBr): υ = 2991, 2979, 1720, 1629, 1498, 1043, 736 cm-1. H NMR (400 MHz,
CDCl3) δ = 1.45 (s, 9H), 1.47 (t, 3H), 2.43(s, 2H), 4.54 (q, J=6.8, 2 H) 11.25 (br, s, 1H) ppm.
Results and Discussion
Characterization of the Lewis-acid sites present on the polymer was performed by recording
the FT-IR spectrum of PVPP-BF3, which shows a strong broad absorption at 1000-1060 cm-1
for the BF bonds and a moderate absorption at 1646 cm-1 corresponds to the imine group on
the backbone (Figure 1). The capacity of the reagent was determined by titration and found
to be 10 mmol/g, whereas its silica supported analogue has a loading capacity of less than 4
mmol/g23,24
.

Polyvinylpolypyrrolidone-Supported Boron Trifluoride 579
Wavelength/cm-1
Figure 1. The Fourier transform infrared spectroscopy (FT-IR) spectrum of polyvinylpoly-
pyrrolidone (PVPP) and (PVPP-BF3) complex.
A variety of N-tert-butylamides were prepared from tert-butyl acetate and the
corresponding nitriles in the presence of PVPP-BF3 in good to excellent yields (Table 1,
entries 1-10). It is worth mentioning that the corresponding amide in each case was isolated
by simple filtration of the catalyst followed by crystallization from the crude filtrate.
Additionally, a competitive reaction of tert-butyl acetate with equimolar amounts of
benzonitrile and acetonitrile lead to the selective formation of N-tert-butylbenzamide in
good yield, whereas acetonitrile remained unchanged (Scheme 2).
It is reasonable to assume that the present reaction is initiated by Lewis acidity and
oxophilicity of PVPP-BF3 which promote the Ritter reaction via coordination to oxygen atoms
of ester and facilitation of C-O cleavage by attack of nitrile group (Scheme 3). An interesting
feature of this method is that the spent resin can be regenerated at the end of the reaction after
washing with organic solvent and back to the starting polyvinylpolypyrrolidone-boron
triflouride complex and can be used several times without losing its activity.
PhCONHC(CH3)3
+
CH3CONHC(CH3)3
(90%)
(0%)
Ph-CN
+
CH3CN
PVPP-BF3
tert-butyl acetate
70oC, 2h
ClCH2CH2Cl/
Scheme 2

580 MASOUD MOKHTARY et al.
a
Table 1. Amidation of tert-butyl acetate with nitriles using of the PVPP-BF3 .
Yield
%
m.p.,
°C
Entry
1
Nitriles
Product
CONHtBu
Time/h
b
CN
2
90
135-136
129-132
99-102
CONHtBu
CONHtBu
CN
2
3
2
2
92
87
Cl
Cl
CN
H3C
H3C
H3C
CONHtBu
CONHtBu
CN
H3C
4
5
6
2
4
5
96
72
96-97
CN
189-192
HO
HO
CONHtBu
CONHtBu
CN
CN
92c 272-276
82c 204-207
tBuNHOC
tBuNHOC
NC
NC
7
8
5
3
74
128-131
CONH tBu
CN
ClCH2CONHtBu
ClCH2CN
9
3
3
95
84
79-81
89-93
t BuNHCOCH2COOEt
NCCH2COOEt
10
aAll entries were carried on nitrile (3 mmol), t-BuOAc (3 mmol) and PVPP-BF3 (3 mmol) in
1,2-dichloromethane (5 ml) at 70 °C. bAll yields refer to isolated products. CNitrile (1.5 mmol) is used.
Conclusion
We have developed a simple and efficient method for the modified Ritter reaction using
polyvinylpolypyrrolidone-boron trifluoride as a high loading of Lewis acid, which is stable,
easy to prepared and handle, and represent effective activity for the amidation of tert-butyl
acetate with nitriles. This method provides an easy access to a variety of tert-butyl amides.

Polyvinylpolypyrrolidone-Supported Boron Trifluoride 581
P
BF3
O
O
O
C(CH3)3
H3C
O
C(CH3)3
H3C
R-CN
+
R
C
N
C(CH3)3
BF3
P
-
CH3COO
OH
C
R
N
C(CH3)3
O
H2O
R
C N
C(CH3)3
H
n
+
-
N
O-BF3
BF3
P
PVPP-BF3
Scheme 3
Acknowledgment
We are grateful to Islamic Azad University, Rasht Branch and Islamic Azad University,
Science and Research, Amol Branch, for financial assistance in this work.
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