Polyvinylpolypyrrolidone-supported boron trifluoride: A high-loaded, polymer-supported Lewis acid for the Ritter reaction

Article abstract of DOI:10.1007/s00706-008-0007-4

A Mild and efficient method for preparing amides by reaction of nitriles with benzhydrol and tertiary alcohols is described using polyvinylpolypyrrolidone-supported boron trifluoride. Selective amidation of benzhydrol in the presence of primary benzyl alcohols was also achieved.

Full text of DOI:10.1007/s00706-008-0007-4

Monatsh Chem (2009) 140:53–56
DOI 10.1007/s00706-008-0007-4
ORIGINAL PAPER
Polyvinylpolypyrrolidone-supported boron trifluoride:
a high-loaded, polymer-supported Lewis acid
for the Ritter reaction
Moslem Mansour Lakouraj Æ Masoud Mokhtary
Received: 5 May 2008 / Accepted: 26 May 2008 / Published online: 27 September 2008
Ó Springer-Verlag 2008
Abstract A Mild and efficient method for preparing
amides by reaction of nitriles with benzhydrol and tertiary
alcohols is described using polyvinylpolypyrrolidone-sup-
ported boron trifluoride. Selective amidation of benzhydrol
in the presence of primary benzyl alcohols was also
achieved.
which utilizes an excess amount of concentrated sulfuric
acid, is generally suitable for tertiary alcohols, but this
strongly acidic medium limits its use, especially for acid-
sensitive substrates. Therefore, several modifications have
been attempted to improve Ritter reaction conditions.
Some alternative reagents used for this purpose are
-
Ph2C?ClSb-Cl6 [14], NO2?BF4 [15], NOPF6 [16],
Keywords Ritter reaction ꢀ Polyvinylpolypyrrolidone ꢀ
Boron trifluoride ꢀ Nitriles ꢀ Amides
(CF3SO2)2O [17], FeCl3ꢀ6H2O [18], BF3–Et2O [19], Fe3?
-
Montmorillonite [20], Mg(HSO4)2 [21], NHPI-CAN [22],
t-butylacetate [23], HCO2H [24], Bi(OTf)3 [25], 7-Tetra-
chlorobenzo[d][1,2,3,]dioxoborol-2-ol
[26],
hetero-
Introduction
polyacid [27], CeCl3ꢀ7H2O/AcCl [28], and P2O5/SiO2 [29].
However, many of these methods suffer from at least
one of the following disadvantage: unavailability of the
reagent, vigorous reaction conditions, strong protic and
aqueous media, reagent high cost and toxicity, tedious
workup procedures, unsatisfactory yields, long reaction
time, instability, and hygroscopic nature of the reagent. On
the other hand, catalyst recovery presents some unique
advantages, such as waste reduction, lower cost, simple
product isolation, energy savings, and environmental
compatibility in chemical production both in laboratory
and industrial processes.
Boron trifluoride is widely used in organic syntheses as a
Lewis acid, including Friedel-Crafts alkylation [1, 2] and
acylation [3, 4] reactions, conversion of aldehydes and
ketones in to gem-difluoro compounds [5], cation-assisted
rearrangement reactions [6, 7], Diels-Alder reactions [8],
polymerization, etc. [9, 10]. However, boron trifluoride is
highly water sensitive, irritant, and has to be used in a
carefully dried apparatus. Furthermore, all work must be
carried out in an efficient fume hood, and its recovery
from the reaction mixture results in a significant source of
waste, which on an industrial scale is environmentally
unacceptable.
Therefore, substantial investigations have been per-
formed to introduce novel supported catalysts and chemical
reagents. These include dispersing catalysts on inorganic
beds such as metal oxide, alumina, silica, and zeolite.
However, the supported catalyst becomes part of the waste
stream after a few reaction cycles due to hydrolysis and
leaching of the active species. In addition, several exam-
ples of polymer-supported catalysts are also reported in the
literature [30].
The Ritter reaction makes possible the conversion of a
group, capable of giving a relatively stable carbonium ion,
to a substituted amide by reaction with a nitrile in the
presence of a strong acid [11–13]. The classical method,
M. M. Lakouraj (&) ꢀ M. Mokhtary
Department of Organic-Polymer Chemistry,
Faculty of Chemistry, Mazandaran University,
Babolsar 47416, Iran
There is a number of advantages in using polymer-
supported catalysts over conventional catalysis. The reac-
tions can be performed under mild conditions, and product
e-mail: lakouraj@umz.ac.ir
123

54
M. M. Lakouraj, M. Mokhtary
Fig. 1 The chemical structure
of polyvinylpolypyrrolidone-
supported boron trifluoride
purification is simplified because of the use of an insoluble
solid support. Many reactions can be carried out cleanly,
rapidly, and in high yields. Polymer-supported catalysts
can also be recycled after use. However, mainly, the
polystyrene-based polymer-bound Lewis acid catalysts
show relatively low activity, and the activity of the catalyst
decreases due to insufficient stability of the aromatic ring
of the polymer and slow diffusion of substrate into the
network. Furthermore, the actual loading is limited by
Lewis-acid-catalyzed cross linking of chloromethyl groups
within the polystyrene-based resin. One of the most
effective procedures to enhance the maximal loading of the
carrier material is obtained by using low molecular weight
functional monomers [31]. Poly(vinylpyrrolidone) is a
blood plasma extender that can act as carrier for a variety
of compounds in the bloodstream and has been used as a
retardant for drugs and to eliminate toxins [32]. It displays
a strong binding affinity toward small molecules, and its
iodine complex, povidone-iodine, is widely used as an anti-
infective agent in clinical treatment [33].
n
-
+
N
O-BF3
Characterization of the Lewis-acid sites present on the
polymer was performed by recording the Fourier transform
infrared spectroscopy (FT-IR) spectrum of PVPP-BF3,
which shows a strong broad absorption at 1,000–1,200 cm-1
for the BF bonds and a weak absorption at 1,654 cm-1
corresponds to the unreacted amide group on the backbone
(Fig. 2). 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/g [34, 35].
The catalytic activity of PVPP-BF3 was tested using the
reaction of benzhydrol with acetonitrile (Table 1). Low
boiling nitriles could be used both as solvent and substrate.
Reactions with high-boiling or solid nitriles could be per-
formed in 1, 2-dichloroethane as the solvent under reflux
condition. According to the FT-IR of the recycled catalyst
and titration analysis, the acidic sites remain unchanged.
But in reuse, a lower conversion is observed after three
cycles relative to the freshly prepared catalyst. A variety of
To develop a high-loading polymer-supported catalyst
that can offer catalyst recoverability and also maintain
long-term stability and activity, and in connection with our
interest in design and application of functionalized poly-
mers, we introduce here the polymeric Lewis-acid catalyst
polyvinylpolypyrrolidone-supported boron trifluoride
(PVPP-BF3). It can be used as a stable bench-top catalyst
for selective amidation of benzhydrol and tertiary alcohols
with nitriles. In contrast to boron trifluoride, which is
extremely moisture sensitive, this reagent is not hygro-
scopic and retains its activity after several months of
storage. Interestingly, this reagent not only gives good
product yields, but PVPP-BF3 is also easily regenerated
and can be reused several times (Scheme 1).
PVPP-BF3
R-OH
+
R'-CN
R-NHCO-R'
reflux / 1,2-dichloroethane
R = (Ph)2CH, (CH3)3C, PhCH2(CH3)2C, adamantane
R' = Ar, vinyl, ClCH2, CH3
Scheme 1
Results and discussion
In this study, PVPP-BF3 is obtained by simple complexa-
tion of boron trifluoride with the cross-linked PVPP
(Fig. 1). The use of linear polyvinylpyrrolidone was not
satisfactory for complexation with boron trifluoride due to
formation of a sticky gum.
Fig. 2 The Fourier transform infrared spectroscopy (FT-IR) spectrum
of polyvinylpolypyrrolidone (PVPP) and polyvinylpolypyrrolidone-
supported boron trifluoride (PVPP-BF3) complex
123

Polyvinylpolypyrrolidone-supported boron trifluoride
55
Table 1 Amidation of benzhydrol and tertiary alcohols with nitriles using polyvinylpolypyrrolidone-supported boron trifluoride (PVPP-BF3)
Nitriles
Alcohols
Producta
Time/h
Yield/%b
M.p./°C (Ref.)
CH3CN
Ph2CHOH
1 MeCONHCHPh2
2
88
75
90
70
68
65
65
55
45
40
40
68
60
145–147 (144–6) [20]
168–169 (170–1) [20]
174–176 (176–7) [24]
151–154
PhCN
Ph2CHOH
2 PhCONHCHPh2
2.5
3
p-MeC6H4CN
m-MeC6H4CN
o-MeC6H4CN
p-ClC6H4CH2CN
ClCH2CN
CH2=CHCN
PhCN
Ph2CHOH
3 p-MeC6H4CONHCHPh2
4 m-MeC6H4CONHCHPh2
5 o-MeC6H4CONHCHPh2
6 p-ClC6H4CH2CONHCHPh2
7 ClCH2CONHPh2
Ph2CHOH
3
Ph2CHOH
3
177–179
Ph2CHOH
3
158–160
Ph2CHOH
4
126–127 (125–6) [20]
179–180 (178–9) [24]
133–135 (133–4) [20]
117–118 [23]
Ph2CHOH
8 CH2=CHCONHCHPh2
9 PhCONHC(Me)3
3
(Me)3COH
(Me)3COH
PhCH2C(Me)2OH
1-Admantanol
1-Admantanol
4
p-MeC6H4CN
PhCN
10 p-MeC6H4CONHC(Me)3
11 PhCONHC(Me)2CH2Ph
12 PhCONH-ad
4
4
102–103
PhCN
4
154–156
CH3CN
13 MeCONH-ad
4
150–151 (148–9) [14]
a
1
All the products were characterized by infrared (IR), H NMR spectra and comparison with authentic samples
b
All yields refer to isolated products
N-benzhydrylamides was prepared from benzhydrol to the
Experimental
corresponding nitriles in the presence of a catalytic amount
of PVPP-BF3 in good yields (Table 1, entries 1–8). Alifatic
tertiary alcohols were converted to the corresponding
amides in moderate yields (Table 1, entries 9–13). Primary
benzylic alcohols do not undergo amidation with nitriles
under the same condition, and in some cases only afforded
a low yield of products. Attempts for amidation of primary
and secondary saturated alcohols were unsuccessful. It is
worth mentioning that the corresponding amide in each
case was isolated by simple filtration of the catalyst fol-
lowed by crystallization from the crude filtrate.
PVPP was purchased from Fluka. Other chemicals were
purchased from Merck Chemicals. Melting points were
recorded on an electrothermal melting-point apparatus.
Nuclear magnetic resonance (NMR) spectra were recorded
in CDCl3, with TMS as an internal standard on a Bruker
advance DRX 500 MHz spectrometer. IR spectra were
determined on an SP-1100, P-UV-Com instrument. Product
purity determination was accomplished by thin-layer
chromatography (TLC) on silica gel polygram SIL G/UV
254 plates. Products were separated by simple filtration and
identified by comparison IR and 1H NMR spectra with
those reported for authentic samples.
Additionally, the reaction’s chemoselectivity was eval-
uated via competitive PVPP-BF3-catalyzed Ritter reaction
of equimolar amounts of benzhydrol and p-chlorobenzyl
alcohol in acetonitrile under reflux conditions. It was found
that benzhydrol reacted with acetonitrile to give the cor-
responding amide in high yield, whereas p-chlorobenzyl
alcohol remained unchanged (Fig. 3).
Polyvinylpolypyrrolidone–boron trifluoride complex
(PVPP-BF3)
To a suspension of 3 g PVPP in 25 cm3 CH2Cl2, a solution
of 5 cm3 BF3ꢀOEt2 in 15 cm3 CH2Cl2 was added dropwise
and the mixture stirred for 1 h at room temperature. The
resulting resin was filtered and washed with 2 9 10 cm3
CH2Cl2 and dried in a vacuum desiccator to give a stable
and nonhygroscopic powder.
In conclusion, we synthesized a novel form of supported
boron trifluoride that is stable, nonhygroscopic, easy to
prepare and handle, shows a high loading of Lewis acid,
and represents effective catalytic activity for the selective
amidation of benzhydroles and tert-butyl alcohols with
nitriles.
Ritter reaction of benzhydrol: general procedure
A solution of 1 mmol benzhydrol and 2 mmol nitrile in
5 cm3 1,2-dichloroethane was prepared; 3 mmol PVPP-
BF3 was added to the solution, and the reaction mixture
was stirred for 2–4 h under reflux condition until TLC
analysis showed that no benzhydrol remained. The reaction
mixture was filtered and washed with 2 9 5 cm3 CH2Cl2,
Ph2CHOH
Ph2CHNHCOMe(88%)
PVPP-BF3
+
+
reflux/ CH3CN
-ClC H CH OH
-ClC H CH2NHCOMe(0%)
p
p
6
4
2
6
4
Fig. 3 Competitive amidation of benzhydrol versus p-chlorobenzyl
alcohol
123

56
M. M. Lakouraj, M. Mokhtary
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proper amides in 40–90% yields.
N-Benzhydryl-3-methylbenzamide (4, C21H19NO)
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1,525; 1,503; 1,494; 752; 702 cm-1. H NMR (500 MHz,
CDCl3) d = 2.48 (s, 3H); 6.38 (d, J = 7.8 Hz, 1H); 6.49 (d,
J = 8 Hz, 1H); 7.25–7.47(m, 14H) ppm.
N-Benzhydryl-2-(4-chlorophenyl)acetamide
(6, C21H18NOCl)
Yield 65%; m. p.: 158–160°C. IR (KBr): vꢀ ¼ 3; 307; 1,649;
1
1,541; 1,503; 1,489; 772; 693 cm-1. H NMR (500 MHz,
CDCl3) d = 3.62 (s, 2H); 6.11 (d, J = 10 Hz, 1H); 6.27 (d,
J = 8 Hz, 1H); 7.15–7.36(m, 14H) ppm.
N-(1,1-Dimethyl-2-phenylethyl)benzamide
(11, C17H19NO)
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1,638; 1,542; 1,222; 735 cm-1 1H NMR (500 MHz,
.
CDCl3) d = 1.50 (s, 6H); 5.22 (s, 2H); 5.74 (br, 1H);
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N-(1-Adamantyl)benzamide (12, C17H21NO)
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2,852; 1,633; 1,537; 1,451; 1,282; 716; 692 cm-1 1H
.
NMR (500 MHz, CDCl3) d = 1.73–1.79(br, 6H); 2.1(br,
9H); 5.85 (br, 1H); 7.3–7.76 (m, 5H) ppm.
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Acknowledgments We are grateful to Mazandaran University for
financial assistance of this work.
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