Nafion NR50 catalyzed A3-coupling for the synthesis of propargylamines via C-H activation

Article abstract of DOI:10.1007/BF03249079

A one-pot, three-component coupling reaction of aldehydes, amines and alkyne (A3-coupling) via C-H activation using perflorinated resinsulphonic acid (Nafion NR50) as a recyclable and environmentally benign catalyst for the synthesis of proparg

Full text of DOI:10.1007/BF03249079

J. Iran. Chem. Soc., Vol. 8, No. 2, June 2011, pp. 462-469.
JOURNAL OF THE
Iranian
Chemical Society
ꢀ
ꢀꢀꢀꢀꢀꢀꢀ
®
3
Nafion NR50 Catalyzed A -Coupling for the Synthesis of Propargylamines via C-H
Activation
M. Kidwai* and A. Jahan
Green Chemistry Research Laboratory, Department of Chemistry, The University of Delhi, Delhi-110007, India
(
Received 17 July 2010, Accepted 1 October 2010)
3
A one-pot, three-component coupling reaction of aldehydes, amines and alkyne (A -coupling) via C-H activation using
®
perflorinated resinsulphonic acid (Nafion NR50) as a recyclable and environmentally benign catalyst for the synthesis of
propargylamine derivatives is described. This protocol avoids the use of heavy metals, co-catalysts and produces the
propargylamines in excellent yields.
3
®
Keywords: A -Coupling, Nafion NR50, Solid acid catalyst, Recyclability, Propargylamines
INTRODUCTION
and nitration [8,9].
Multicomponent coupling reactions (MCRs) provide a
viable synthetic strategy to access complicated structures from
rather simple starting material via a one-pot methodology, and
in particular, exhibit high atom economy and selectivity [10].
A typical example of such a process that has been studied
widely in recent years is three-component coupling of
The increasing awareness of the environmental cost of
traditional acid-catalyzed chemical processes has created an
opportunity for the development of new solid acid-based
approaches to many important industrial reactions [1,2]. The
replacement of conventional, toxic and polluting Bronsted and
Lewis acid catalysts by eco-friendly reusable solid acid
heterogeneous catalysts like acidic zeolites, clays, sulfated
zirconia and ion exchange resins is an area of current interest
3
aldehydes, amines and alkynes (A -coupling) via C-H
activation [11,12]. The propargylamines that result from A -
3
coupling reactions are versatile building blocks for the organic
synthesis. They are generally used as precursors for the
synthesis of N-containing heterocyclic compounds such as
pyrrolidines, oxazoles and pyrroles [13] and also act as key
intermediates [14] for the construction of biologically active
compounds like isosteres, β-lactams, oxotremorine substrates,
conformationally restricted peptides, and therapeutic drug
molecules [15]. Traditionally, propargylamines have been
synthesized by nucleophilic attack of lithium acetylides or
Grignard reagents to imines [16]. In recent years, enormous
progress has been made in expanding the scope of the direct
addition of alkynes to carbon-nitrogen double bonds either
from prepared imines or from aldehydes and amines in one-
pot procedure by several transition-metal catalysts via C-H
[
3-6]. The use of solid acid catalysts instead of liquid ones has
many advantages such as reduced equipment corrosion, ease
of product separation, recycling of the catalyst and
environmental acceptability.
In recent years, resins containing perfluorosulphonic acid
groups such as Nafion®NR50 [7] (copolymer of
tetrafluroethylene and perfluoro-2-(fluorosulfonylethoxy)
propyl vinyl ether), which is strongly acidic in nature, and
chemically and thermally stable, has been found to be an
excellent catalyst for a variety of major organic reactions like
alkylation, acylation, esterification, etherification, dehydration
*Corresponding author. E-mail: kidwai.chemistry@gmail.com

Kidwai & Jahan
activation of terminal alkynes. These include Ag(I) salts [17],
Au(I)/Au(II) salts [18], Au(III)-salen complexes [19], Cu(I)
and phenylacetylene (1.5 mmol) in CH CN (5 ml) were put.
3
®
To this, Nafion NR50 (0.25 gm) was added and the reaction
mixture was stirred at 70-80 °C for the appropriate time
mentioned in Table 4 under nitrogen atmosphere. The progress
of the reaction was monitored by TLC. After completion of
the reaction, the reaction mixture was cooled. The organic
layer was extracted with diethyl ether and the remaining
salts [20], Hg Cl [21] and Cu/Ru [22] bimetallic system under
2
2
homogeneous conditions. Recently, Au(III) [23], Ag(I) [24] in
ionic liquids, and Cu-supported hydroxyapatite [25] were used
3
to catalyze A -coupling reactions. Also, more sophisticated
alternative energy sources like microwave [20], and ultrasonic
[
26] radiation have been used in the presence of Cu(I) salt.
These reagents, however, are used in stoichiometric
®
Nafion NR50 was reused for further reactions. The organic
layer was dried over anhydrous Na
2
SO and the solvent was
4
amounts and are often lost at the end of the reaction (non-
recyclable) and require drastic reaction conditions. Most of
these reactions took place either in toxic solvents [17] or in the
presence of expensive ones [27]. Thus, there has been an
ongoing interest to develop solid acid catalysts for C-H bond
activation of terminal alkynes [28] under mild reaction
conditions.
removed in vacuo. The crude product was subjected to
purification by silica gel column chromatography using 20%
ethyl acetate and 80% hexane as an eluent to yield the
propargylamines (4a-n). The structures of all the products
were unambiguously established on the basis of their spectral
1
13
analysis (IR, H NMR, C NMR and GC/MS mass spectral
data).
As a part of our ongoing experiments for the development
of new synthetic methods using of recyclable heterogeneous
catalysts in organic synthesis [29,30], herein, we wish to
report, for the first time, a simple and highly efficient
methodology for the synthesis of propargylamines in excellent
1-(1,3-Diphenyl-prop-2-ynyl)-piperidine (4a). Yellowish
-1
oil; IR (film/cm ): νmax = 3051, 2936, 2253, 1617, 1520, 1451,
1
1320, 1160; H NMR (CDCl , 400 MHz): δ = 7.35-7.16 (m,
3
10H, 2Ph), 4.56 (s, 1H, CH), 2.62-2.56 (m, 4H, 2CH ), 1.91-
2
®
13
yields using Nafion NR50 as a recyclable and heterogeneous
1.85 (m, 4H, 2CH ), 1.50-1.35 (m, 2H, CH ); C NMR
2
2
solid acid catalyst.
(
CDCl , 100 MHz): δ = 138.7, 132.1, 128.5, 128.2, 128.1,
3
1
27.6, 123.4, 88.1, 86.3, 62.5, 50.9, 26.3, 24.5. m/z (GC/MS,
EXPERIMENTAL
HRMS) 275.68 (M+1, C H N requires 275.17).
20
21
1
-[1-(4-Methylphenyl)-3-phenyl-prop-2-ynyl)-
Chemicals and Apparatus
-
1
piperidine (4b). Slightly yellowish oil; IR (film/cm ): ν
939, 2815, 2278, 1580, 1510, 1319, 1154; H NMR (CDCl ,
400 MHz): δ = 7.61-7.56 (m, 9H, 2Ph), 4.78 (s, 1H, CH),
.61-2.52 (m, 4H, 2CH
=
max
IR spectra were recorded on Perkin Elmer FTIR-1710
spectrophotometer using Nujol or KBr pellets. IR frequency,
1
2
3
-1
1
13
ν
max was measured in cm . H NMR and C NMR (400 and
00 MHz, respectively) spectra were recorded on Bruker
2
2
2
), 2.40 (s, 3H, CH
3
), 1.73-1.64 (m, 4H,
1
13
CH ), 1.58-1.45 (m, 2H, CH
2
2
); C NMR (CDCl , 100 MHz):
3
Avance 400 Spectrometer. The chemical shifts, δ, are given in
ppm, relative to internal standard, tetramethylsilane (TMS).
The mass spectra were recorded on Jeol, NMS DX 303 at 70
eV or on a KC455 Waters TOF MS spectrometer. The
temperature of the reaction mixture was measured through
AZ, Mini Gun Type, Non-Contact IR thermometer, Model No.
δ = 137.3, 135.8, 132.1, 129.0, 128.7, 128.5, 127.1, 123.6,
7.9, 86.6, 62.8, 62.4, 50.9, 26.4, 24.7, 21.4. m/z (GC/MS,
HRMS): 290.19 (M+1, C21 23N requires 289.18).
-[1-(4-Methoxyphenyl)-3-phenyl-prop-2-ynyl)-
8
H
1
-1
piperidine (4c). Slightly yellowish oil; IR (film/cm ): νmax
015, 2943, 2812, 2203, 1523, 1318, 1168, 1041; H NMR
CDCl , 400 MHz): δ = 7.81-7.69 (m, 9H, 2Ph), 4.80 (s, 1H,
CH), 3.74 (s, 3H, OCH ), 2.65-2.55 (m, 4H, 2CH ), 1.80-1.74
m, 4H, CH ), 1.59-1.45 (m, 2H, CH ); C NMR (CDCl , 100
MHz): δ = 158.3, 132.2, 130.4, 129.3, 128.6, 128.2, 123.0,
=
1
3
(
8
868. The melting points were determined on Thomas Hoover
3
melting point apparatus and are uncorrected. The purity of the
compounds was checked on TLC (silica gel coated aluminium
sheets, Silica gel 60 F254, E. Merck, Germany).
3
2
1
3
(
2
2
3
1
3
14.0, 85.6, 82.6, 58.8, 55.3, 26.1, 24.2. m/z (GC/MS, HRMS)
General
Procedure
for
the
Synthesis
of
05.90 (M+1, C H NO requires 305.18).
Propargylamines
21 23
1
-[1-(4-Bromophenyl)-3-phenyl-prop-2-ynyl)-
In a 50 ml round bottom flask, aromatic aldehydes/
heterocylic aldehydes (1 mmol), secondary amines (1.2 mmol)
-1
piperidine (4d). Yellowish oil; IR (film/cm ): ν = 3040,
max
ꢀ
463

®
3
Nafion NR50 Catalyzed A -Coupling for the Synthesis of Propargylamines
1
2
955, 2815, 2780, 2270, 1544, 1495, 1314, 1169, 1052. H
1-(1,3-Diphenyl-prop-2-ynyl)-morpholine (4i). Slightly
-1
NMR (CDCl
3
, 400 MHz): δ = 7.92-7.89 (m, 9H, 2Ph), 4.81 (s,
), 1.79-1.66 (m, 4H, 2CH ), -
); C NMR (CDCl , 100 MHz): δ =
yellowish oil; IR (film/cm ): νmax = 3050, 2965, 2301, 1584,
1
1
1
1
6
3
H, CH), 2.66-2.52 (m, 4H, 2CH
2
2
1480, 1320, 1151, 756; H NMR (CDCl
3
, 400 MHz): δ = 7.70-
1
3
.50-1.46 (m, 2H, CH
2
3
7.42 (m, 10H, 2Ph), 4.83 (s, 1H, CH), 3.09-2.94 (m, 4H,
1
3
38.1, 132.1, 130.1, 128.4, 128.3, 123.1, 121.5, 88.6, 88.5,
1.8, 52.5, 61.8, 52.9, 26.3, 24.5. m/z (GC/MS, HRMS)
54.17 (M+1, C H NBr requires 353.08).
2CH ), 2.67-2.57 (m, 4H, 2CH ); C NMR (CDCl , 100
2
2
3
MHz): δ = 139.6, 131.2, 128.7, 128.3, 128.1, 127.2, 122.6,
86.7, 80.1, 66.1, 59.3, 52.3. m/z (GC/MS, HRMS) 278.22
(M+1, C H NO requires 277.15).
20
20
1
-[1-(4-Chlorophenyl)-3-phenyl-prop-2-ynyl)-
1
9
19
-1
piperidine (4e): Yellowish oil; IR (film/cm ): ν
2
NMR (CDCl
1
1
1
5
= 3042,
1-[1-(4-Methylphenyl)-3-phenyl-prop-2-ynyl)-
max
1
947, 2811, 2783, 2240, 1549, 1492, 1316, 1167, 1055; H
morpholine (4j). Colorless solid, m.p.: 80.5-81.5 °C; IR
-1
1
3
, 400 MHz): δ = 7.91-7.84 (m, 9H, 2Ph), 4.85 (s,
), 1.71-1.62 (m, 4H, 2CH ),
); C NMR (CDCl , 100 MHz): δ =
(film/cm ): νmax = 3360, 3048, 2972, 2308, 1592; H NMR
(CDCl , 400 MHz): δ = 7.45-7.32 (m, 9H, 2Ph), 4.77 (s, 1H,
CH), 3.22-3.17 (m, 4H, 2CH ), 2.66-2.54 (m, 4H, 2CH ), 2.33
(s, 3H, CH ); C NMR (CDCl , 100 MHz): δ = 136.2, 134.7,
H, CH), 2.65-2.50 (m, 4H, 2CH
2
2
3
1
3
.51-1.43 (m, 2H, CH
2
3
2
2
1
3
37.4, 134.2, 131.3, 130.4, 128.4, 128.3, 115.2, 86.9, 80.9,
9.2, 53.3, 25.0, 24.1. m/z (GC/MS, HRMS) 310.17 (M+1,
3
3
128.6, 128.3, 128.2, 122.6, 86.8, 80.9, 66.0, 59.2, 52.2, 21.7.
C H ClN requires 309.13).
m/z (GC/MS, HRMS) 292.01 (M+1, C H NO requires
2
0
20
20 21
1
-[1-(4-Nitrophenyl)-3-phenyl-prop-2-ynyl)-piperidine
291.16).
-1
(
1
4f). Yellowish oil; IR (film/cm ): ν = 2945, 2849, 2190,
685, 1597, 1334, 1155, 1089; H NMR (CDCl , 400 MHz):
δ = 7.89-7.75 (m, 9H, 2Ph), 4.83 (s, 1H, CH), 2.59-2.48 (m,
1-[1-(4-Methoxyphenyl)-3-phenyl-prop-2-ynyl)-
morpholine (4k). Yellowish oil; IR (film/cm ): ν = 3045,
2962, 2312, 1594, 1349, 1190, 1017, 713; H NMR (CDCl
max
1
-1
3
max
1
3
,
4
H, 2CH
2
), 1.65-1.55 (m, 4H, 2CH
C NMR (CDCl , 100 MHz): δ = 138.5, 138.0, 129.7, 128.4,
28.1, 123.6, 122.6, 86.8, 80.0, 59.1, 53.2, 25.3, 24.1. m/z
2
), 1.53-1.41 (m, 2H, CH
2
);
400 MHz): δ = 7.56-7.33 (m, 9H, 2Ph), 4.73 (s, 1H), 3.89-3.73
(m, 3H), 2.26-2.16 (m, 4H), 1.56-1.25 (m, 4H); C NMR
1
3
13
3
1
(CDCl , 100 MHz): δ = 159.1, 132.2, 128.8, 128.4, 128.2,
3
(
GC/MS, HRMS) 320.87 (M+1, C H N O requires 320.15).
122.6, 112.8, 86.3, 80.6, 66.1, 55.8, 52.3. m/z (GC/MS,
2
o
20
2
2
1
-[1-(2-Furfuryl)-3-phenyl-prop-2-ynyl)-piperidine
HRMS) 307.98 (M+1, C H NO requires 307.16).
20
21
2
-1
(
2
4g). Sticky compound; IR (film/cm ): ν
367, 2250, 1560, 1314, 1156; H NMR (CDCl , 400 MHz):
δ = 7.52-7.47 (m, 5H, Ph), 6.34-6.12 (m, 3H, furfuryl) 4.86 (s,
= 2920, 2850,
1-[1-(4-Chlorophenyl)-3-phenyl-prop-2-ynyl)-
max
1
-1
morpholine (4l). Yellowish oil; IR (film/cm ): ν = 3040,
3
max
1
2965, 1619, 1520, 1411, 1338, 1175, 1069; H NMR (CDCl ,
3
1
1
H, CH), 3.10-2.86 (m, 4H, 2CH
2
), 1.66-1.59 (m, 4H, 2CH
2
),
400 MHz): δ = 7.50-7.32 (m, 9H, 2Ph), 4.62 (s, 1H, CH),
1
3
13
.50-1.38 (m, 2H, CH
2
); C NMR (CDCl , 100 MHz):
3
3.54-3.47 (m, 4H, 2CH
(CDCl
2
2
), 2.62-2.59 (m, 4H, 2CH ). C NMR
δ = 152.5, 142.1, 128.2, 128.3, 122.7, 110.6, 86.8, 80.9, 60.5,
3
, 100 MHz): δ = 136.2, 134.7, 131.1, 129.1, 128.6,
2
4.7, 24.5. m/z (GC/MS, HRMS) 265.93 (M+1, C H NO
122.7, 88.8, 84.3, 67.1, 59.5, 49.6. m/z (GC/MS, HRMS)
18
19
requires 265.15).
312.38 (M+1, C H ClNO requires 311.11).
19
18
1
-[1-(1-Cyclohexyl)-3-phenyl-prop-2-ynyl)-piperidine
1-(1,3-Diphenyl-prop-2-ynyl)-pyrolidine
(4m).
-1
-1
(
3
4h). Yellowish Oil; IR (film/cm ): ν = 3054, 2842, 2334,
334, 1585, 1318, 1156, 890; H NMR (CDCl , 400 MHz):
Yellowish oil; IR (film/cm ): ν = 3040, 2965, 2807, 2694,
max
max
1
1
2278, 1619, 1520, 1411, 1338, 1175, 756; H NMR (CDCl ,
3
3
δ = 7.54-7.52 (m, 2H, CH ), 7.26-7.23 (m, 3H, CH ), 3.12 (d,
400 MHz): δ = 7.63-7.58 (m, 10H, 2Ph), 4.20 (s, 1H, CH),
2
3
13
J = 8.2Hz, 1H), 2.65-2.44 (m, 4H, CH
2
), 2.34-2.14 (m, 4H),
2.44-1.83 (m, 8H, 4CH
2
). C NMR (CDCl
3
, 100 MHz): δ =
2
1
1
2
.15-2.19 (m, 2H), 1.83-1.70 (m, 4H), 1.48-1.37 (m, 4H),
139.1, 131.0, 128.6, 128.2, 126.8, 123.5, 86.1, 86.0, 59.4,
1
3
.35-1.12 (m, 3H); C NMR (CDCl
3
, 100 MHz): δ = 131.9,
58.6, 50.5, 23.6. m/z (GC/MS, HRMS) 262.03 (M+1, C19
requires 261.15).
19
H N
28.3, 128.0, 122.7, 89.4, 86.6, 64.2, 38.8, 33.1, 30.5, 27.9,
6.0, 25.3, 24.9, 24.5. m/z (GC/MS, HRMS) 282.41 (M+1,
1-[1-(4-Methoxyphenyl)-3-phenyl-prop-2-ynyl)-
-1
C H NO requires 281.21).
pyrolidine (4n). Yellowish oil; IR (film/cm ): ν = 3076,
1
8
19
max
ꢀ
464

Kidwai & Jahan
1
2
4
(
961, 2811, 2646, 1522, 1490, 1348, 1145; H NMR (CDCl ,
Increasing the loading of the catalyst up to 0.35 gm produced
the desired propargylamines in 96% yield. Moreover, the
increase in the concentration of the catalyst not only promoted
the reaction but also resulted in an increase of the yield and a
decrease in time (Table 1).
3
00 MHz) δ = 7.62-7.59 (m, 9H, 2Ph), 4.89 (s, 1H, CH), 3.83
13
s, 3H), 2.62-1.80 (m, 8H, 4CH
MHz): δ =159.2, 132.2, 129.7, 128.4, 128.3, 122.6, 114.2,
6.0, 80.9, 56.9, 55.2, 23.0. m/z (GC/MS, HRMS) 292.35
M+1, C H NO requires 291.16).
2
); C NMR (CDCl
3
, 100
8
(
In addition, it was found that at higher temperatures
2
0
21
®
Nafion NR50 showed good catalytic activity at 70-80 °C and
RESULTS AND DISCUSSION
96% yield was obtained. However, at room temperature, lower
yields were obtained despite longer reaction times.
Comparable results were obtained when the reaction occurred
As a model reaction, we initially examined an efficient and
environmentally benign protocol for A -coupling of
3
®
at 70-80 °C with 0.25 g of Nafion NR50. Thus, to reduce the
benzaldehyde (1.0 mmol), piperidine (1.2 mmol), and
phenylacetylene (1.5 mmol) in the presence of Nafion NR50
amount of the catalyst, all optimizations were carried out at
70-80 °C with 0.25 g of Nafion NR50.
®
®
in acetonitrile at 70-80 °C under nitrogen atmosphere (Scheme
The nature of the reaction media has an important role in
3
®
1
). As a result, the expected reaction proceeded clearly to
A -coupling reaction in the presence of Nafion NR50 (0.25
gm). Among the various solvents studied such as acetonitrile,
methanol, THF, DCM and dioxane, acetonitrile was found to
be the most efficient solvent of choice (Table 2, entry 1) and
produce the desired propargylamine in 96% yield (4a).
The effect of catalyst loading was studied by carrying out
®
the experiments using different amounts of Nafion NR50.
R1
R2
N
Nafion®NR50, CH CN
R
3
R-CHO + R
R NH +
o
1 2
7
0-80 C, N atm
2
1
2
3
4a-n
Scheme 1. Coupling of benzaldehyde, piperidine and phenylacetylene catalyzed by
®
Nafion NR50
®
3
a
Table 1. Optimization of Concentration of Nafion NR50 for A -Coupling
CHO
N
Nafion®NR50, CH CN
3
+
+
o
7
0-80 C, N atm.
2
N
H
Entry
Catalyst
0
Time (h)
Yield (%)b
1
2
3
4
5
6
18
12
10
5
5
4
0
0.05
0.10
0.20
0.25
0.35
83
90
92
96
96
a
Reaction conditions: benzaldehyde (1.0 mmol), piperidine (1.2 mmol), phenylacetylene (1.5 mmol),
®
b
Nafion NR50 (0.5-0.35 g); solvent CH
3
CN (5 ml); temperature 70-80 °C, N
2
atm. Isolated yields.
ꢀ
465

®
3
Nafion NR50 Catalyzed A -Coupling for the Synthesis of Propargylamines
Table 2. Effect of Solvent on A -Couplinga
3
Entry
Solvent
Time (h)
Yield (%)b
1
2
3
4
Acetonitrile
Methanol
Tetrahydrofuran
Dichloromethane
Dioxane
5
5
5
5
5
96
92
87
0
5
0
a
Reaction conditions: benzaldehyde (1.0 mmol), piperidine (1.2 mmol), phenylacetylene (1.5 mmol),
®
b
Nafion NR50 (0.25 g); solvent CH CN (5 ml); temperature 70-80 °C, N atm. Isolated yields.
3
2
Ph
H
Rf = CF -CF2 CF
2
2
n
-
O
CF2 CF
CF3
O
RfSO
3
SO R + H
3
f
m
R1
R2
R
1
R2
N
N
+
H O
2
R-CHO + R R NH
1
2
CH
OH-
R
R
Ph
3
Scheme 2. Tentative mechanism for A -coupling
no products were obtained when the reaction took place in
dichloromethane or dioxane.
catalyst was recovered by forceps, washed with
dichloromethane, dried and a new reaction was then started
under similar reaction conditions (Table 3).
ꢀ
A possible mechanism has been proposed [17c,18b,20a,27]
involving the activation of C-H bond of the terminal alkyne
with Nafion NR50 as the catalyst (Scheme 2). The sulfur
After completing the search for the optimized conditions,
we chose a variety of structurally different aldehydes and
amines possessing a wide range of functional groups to find
®
acetylide intermediate thus generated will react with the
iminium ion prepared in-situ from aldehyde and secondary
amine to produce the corresponding propargylamines, water
®
3
out the scope and generality of Nafion NR50-promoted A -
coupling reaction. A variety of aromatic aldehydes were
coupled with secondary amines and phenylacetylene, It was
found out that aryl aldehydes possessing an electron-
withdrawing group (Table 4, entries 4-6) afforded better
yields, good reactivity, and lesser reaction times than the
electron-donating groups (Table 4, entries 2, 3) bound to the
benzene ring that required longer reaction times. Also,
heterocyclic aldehyde (Table 4, entry 7) displayed high
®
®
and Nafion NR50. The regenerated Nafion NR50 participates
further in the reaction and completes the catalytic cycle.
For the practical application of the catalyst Nafion®NR50,
the life-time of the catalyst and its level of reusability were
important factors. The catalyst showed excellent recyclability
and was reused for three to four runs with only some slight
drop in activity. After completion of a fresh reaction, the
ꢀ
466

Kidwai & Jahan
®
a
Table 3. Recycling of Nafion NR50
ꢀ
No. of cyclesa
Yield (%)b
Fresh
Run 1
Run 2
Run 3
Run 4
96
5
96
5
95
5
93
5
92
5
Time (h)
a
Reaction conditions: benzaldehyde (1.0 mmol), piperidine (1.2 mmol), phenylacetylene (1.5 mmol),
®
b
Nafion NR50 (0.25 g); solvent CH CN (5 ml); temperature 70-80 °C, N atm. Isolated yields.
3
2
®
3
a
Table 4. Nafion NR50 Catalyzed A -Coupling
Entry
Amine
R
Product
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Morpholine
Morpholine
C H
4-MeC H4
4-MeOC H4
4-BrC H4
4a
4b
4c
4d
4e
4f
4g
4h
4i
5.0
5.5
6.0
4.5
4.0
4.5
4.0
3.5
5.0
6.5
96
92
88
94
93
95
90
88
85
91
6
5
6
6
6
4-ClC
4-O NC
2-Furfuryl
6
H
4
2
6
H
4
Cyclohexyl
C H
6
5
1
0
4-MeC H4
4j
6
1
1
1
1
2
3
4
Morpholine
Morpholine
Pyrrolidine
Pyrrolidine
4-MeOC H4
4k
4l
4m
4n
7.0
4.5
6.5
7.5
87
90
87
84
6
4-ClC H4
6
C H
6
5
1
4-MeOC H4
6
a
Reaction conditions: benzaldehyde (1.0 mmol), piperidine (1.2 mmol), phenylacetylene (1.5 mmol),
®
b
Nafion NR50 (0.25 g); solvent CH
3
CN (5 ml); temperature 70-80 °C, N
2
atm. Isolated yields.
reactivity with good yield.
ACKNOWLEDGEMENTS
CONCLUSIONS
The author Anwar Jahan would like to thank University
Grants Commission, New Delhi, India for granting Junior
Research Fellowship. The authors also would like to
acknowledge the University Science Instrumentation Centre
(USIC), University of Delhi, Delhi, India for providing the
instrumental facilities to characterize the synthesized
compounds.
In conclusion, we have developed a simple, economical
and efficient methodology for A -coupling reaction of
aldehydes, amines, and alkyne in acetonitrile to produce the
propargylamines in excellent yield using Nafion NR50. It has
wide substrate applicability, gives high yields in short reaction
times and is easy to carry out. We believe that this
methodology will find widespread use in organic synthesis for
the preparation of propargylamines, due to the simplicity of
the system and ease of separation/reuse of the catalyst.
3
®
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