Facile and Efficient Synthesis of Bicyclic ortho-Aminocarbonitrile Derivatives Using Nanostructured Diphosphate Na2CaP2O7

Full text of DOI:10.1080/00304948.2020.1752606

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
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Facile and Efficient Synthesis of Bicyclic
ortho-Aminocarbonitrile Derivatives Using
Nanostructured Diphosphate Na2CaP2O7
Behrooz Maleki & Hojat Veisi
To cite this article: Behrooz Maleki & Hojat Veisi (2020) Facile and Efficient Synthesis of Bicyclic
ortho-Aminocarbonitrile Derivatives Using Nanostructured Diphosphate Na2CaP2O7, Organic
Preparations and Procedures International, 52:3, 232-237, DOI: 10.1080/00304948.2020.1752606
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ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
2020, VOL. 52, NO. 3, 232–237
https://doi.org/10.1080/00304948.2020.1752606
OPPI BRIEF
Facile and Efficient Synthesis of Bicyclic
ortho-Aminocarbonitrile Derivatives Using Nanostructured
Diphosphate Na2CaP2O7
Behrooz Malekia and Hojat Veisib
b
aDepartment of Chemistry, Hakim Sabzevari University, Sabzevar, Iran; Department of Chemistry,
Payame Noor University, Tehran, Iran
ARTICLE HISTORY Received 21 December 2018; Accepted 20 November 2019
One of the most helpful strategies for the synthesis of the title compounds1 is that of
multicomponent reactions (MCRs). In MCRs three or more reactants form products
such that all or most of the initial atoms are present in the final product. This has clear
benefits in terms of cost, efficiency and environmental stewardship.2–4 There are some
literature methods for the synthesis of ortho-aminocarbonitrile derivatives, and these
include using such reagents as N-butylpyridinium tetrafluoroborate [BPy]BF4,5 ammo-
nium acetate,6 imidazole,7 ethanediamine,8 b-1-imidazol-2,3,4,6-tetraacetyl-D-glucopyra-
nosyl
bromide
([Bmim-G]þ[Br]-),9
ortho-benzenedisulfonimide
(OBS)
or
triethylammonium acetate (TEAA),10 and 1-butyl-3-methylimidazolium tetrafluorobo-
rate ([BMIm][BF4])11 as catalysts. Although all of the above synthetic methods have
advantages, they also suffer from some limitations such as long reaction times, low
yields, and extensive work-up. We would now like to report our method for the synthe-
sis of ortho-aminocarbonitrile derivatives by condensation of aldehydes (1 equiv.) and
malononitrile (2 equiv.) with cyclohexanone (1 equiv) utilizing the nanostructured
12–18
diphosphate Na2CaP2O7
as catalyst (Scheme 1).
This was done in continuation of our previous studies.19–31 In order to obtain the
best conditions for our reaction, we optimized the parameters as listed in Table 1. We
found that the best conditions for this reaction constituted reflux in ethanol in the pres-
ence of 30 mol% of nanostructured diphosphate Na2CaP2O7. To illustrate the effect of
nanostructured diphosphate Na2CaP2O7 in promoting the formation of the bicyclic
ortho-aminocarbonitriles, the model reaction was performed under the optimized reac-
tion conditions but in the absence of catalyst. No significant product formation was
observed even after 240 min (Entry 7).
In order to explore the extent of this reaction, we investigated the use of several alde-
hydes as substrates. Moreover, the scope and efficiency of the reaction were explored
for cyclopentanone (entries 4l-4m). The results are listed in Table 2.
The recyclability of the nanocatalyst in the reaction among benzaldehyde, malonon-
trile and cyclohexanone was evaluated in the presence of 30 mol % nanocatalyst. After
CONTACT Behrooz Maleki
b.maleki@hsu.ac.ir
Department of Chemistry, Hakim Sabzevari University, Sabzevar,
96179-76487, Iran.
Supplemental data for this article can be accessed here.
ß 2020 Taylor & Francis Group, LLC

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
233
Scheme 1. Synthesis of bicyclic ortho-aminocarbonitrile derivatives.
Table 1. Optimizing reaction conditions.a
Entry
Amount of Na2CaP2O7 (mol %)
Conditions
Time (h)
Temperature (ꢀC)
Yield (%)
1
2
3
4
5
6
7
30
30
30
30
20
20
Reflux/EtOH
Reflux/H2O
Reflux/MeOH
Solvent-free
Solvent-free
Reflux/EtOH
Reflux/EtOH
4
4
4
5
6.5
6
4
80
100
65
80
80
80
80
92
70
68
55
45
82
b
c
-
-
aReaction conditions: benzaldehyde (1 mmol), malononitrile (0.14 g, 2 mmol) and cyclohexanone (1 mmol) in
5 ml ethanol.
bIn the absence of catalyst.
cNo product 4a observed.
Table 2. Synthesis of bicyclic ortho-aminocarbonitrile derivatives.
mp (0C)
Entry
Products (4a-m)
n
Yielda (%)
Time (min)
Found
Lit.
4a
4b
4c
4d
4e
4f
4g
4h
4i
R ¼ 4H
1
1
1
1
1
1
1
1
1
1
1
0
0
92
89
84
78
88
90
95
80
90
83
89
90
90
240
300
420
300
360
390
360
420
390
320
300
420
360
255-257
264-266
266-268
251-253
261-263
254-256
262-264
251-253
265-267
239-241
262-264
214-216
220-222
255-2575
265-2685
271-2725
248-2505
257-2605
261-2625
264-2655
254-2555
264-26610
245-2485
265-2675
215-21711
219-22111
R ¼ 4-Br
R ¼ 2-Cl
R ¼ 4-Cl
R ¼ 2,4-Cl
R ¼ 4-OMe
R ¼ 2-OMe
R ¼ 3,4-OMe
R ¼ 4-NO2
R ¼ 2-Br
4j
4k
4l
R ¼ 4-F
R ¼ 4-OMe
R ¼ 4-F
4m
completing the reaction, the catalyst was separated from the reaction mixture easily by
filtration and washed with acetone, calcinated at 500 ꢀC for 1h and re-used in the same
reaction. The nanocatalyst could be re-used at least 6 times without significant loss
in activity.
In order to demonstrate the effectiveness of the present method in comparison with
previously reported results in the literature, we have compared some of the results for
the preparation of bicyclic ortho-aminocarbonitrile derivatives in Table 3. They show
that nanostructured diphosphate Na2CaP2O7 is the most efficient catalyst with respect
to the reaction time and yields of the products.

234
B. MALEKI AND H. VEISI
Table 3. Comparison of methods.
Compounds
Conditions
Time (min)
Yield (%)
Present work
240
300
120
1440
240
360
92
83
90
86
83
93
0
[BPy]BF4/solvent-free/60 C5
Ammonium acetate/EtOH-H2O/50-60 0C6
Ethanediamine/MeOH/rt8
[Bmim-G]þ[Br]-/solvent-free/rt9
OBS/EtOH/reflux10
4a
Present work
360
300
120
300
360
95
87
92
89
86
0
[BPy]BF4/solvent-free/60 C5
Ammonium acetate/EtOH-H2O/50-60 0C6
[Bmim-G]þ[Br]-/solvent-free/rt9
OBS/EtOH/reflux10
H3CO
CN
CN
NH2
CN
4g
In conclusion, a facile, efficient, multicomponent reaction is presented for the synthe-
sis of the title compounds in the presence of nanostructured diphosphate Na2CaP2O7.
The main benefits include use of a catalyst that is known to be safe and non-volatile,
affordable, easy to separate and convenient to recycle.
Experimental section
1
All reagents were obtained from commercial sources. H and 13C NMR spectra were
determined on a Bruker DRX-400 Avance spectrometer in CDCl3 or DMSO-d6, and
shifts are given in ppm downfield from tetramethylsilane (TMS) as an internal standard.
IR spectra were recorded as KBr pellets on a Shimadzu 435-U-04 spectrophotometer.
Melting points were determined by an Electrothermal 9200 apparatus and are uncor-
rected. The catalyst was prepared according to the method previously described.14 Data
on the recycling experiments are available from the corresponding author upon request.
General procedure for the synthesis of compounds 4a-k using nanostructured
diphosphate NaCaP2O7
Na2CaP2O7 was added to a mixture of the aldehyde (1 mmol), malononitrile (0.14 g,
2 mmol) and cyclohexanone (1 mmol) in a 10 mL flask; ethanol (2 mL) was added and
the mixture was brought to reflux using an oil bath for heating. The progress of reac-
tion was controlled by TLC (silica gel; hexane-ethyl acetate, 4:1). After completing the
reaction, 2 ml acetone was added to the reaction mixture. After stirring (1 min), the
nanocatalyst was easily filtered off. The filtered reaction mixture was poured onto
crushed ice to precipitate the product, which was filtered off and dried to give
pure material.

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
235
Spectroscopic data of representative compounds
2-Amino-4a,5,6,7-tetrahydro-4-phenyl-4H-naphthalene-1,3,3-tricarbonitrile (4a)
IR (KBr): 3417, 3342, 3240, 2927, 2869, 2202, 1605, 1600, 1442, 1407, 1272, 1097,
1
879 cmꢁ1; H NMR (400 MHz, DMSO-d6): d 0.84-0.90 (m, 1H, CH), 1.45-1.48 (m, 2H,
CH2), 1.67-1.73 (m, 1H, CH), 2.02-2.08 (m, 1H), 2.17-2.21 (m, 1H), 2.73-2.89 (m, 1H),
3.53 (d, 1H), 5.73 (s, 1H), 7.35 (s, 2H), 7.43-7.59 (m, 5H); 13C NMR (100 MHz, DMSO-
d6): d 20.96, 24.83, 26.97, 33.84, 42.82, 50.55, 81.57, 112.32, 112.52, 116.11, 120.34,
128.56, 128.81, 128.90, 134.59, 143.52.
Anal. Calcd. for C19H16N4: C, 75.98; H, 5.37; N, 18.61. Found: C, 75.89; H, 5.48; N, 18.99.
2-Amino-4a,5,6,7-tetrahydro-4-(4-bromophenyl)naphthalene-1,3,3(4H)-tricarbonitrile (4b)
IR (KBr): 3419, 3343, 3234, 2920, 2856, 2200, 1641, 1589, 1492, 1483, 1407, 1263, 1074,
1
1010, 819 cmꢁ1; H NMR (400 MHz, DMSO-d6): d 0.80-0.90 (m, 1H), 1.44-1.47 (m,
2H), 1.67-1.69 (m, 1H), 2.06-2.21 (m, 2H), 2.73-2.80 (m, 1H), 3.62 (d, 1H), 5.73 (s, 1H),
7.27-7.33 (m, 2H), 7.38 (s, 2H), 7.49 (s, 1H), 7.65 (s, 1H); 13C NMR (100 MHz, DMSO-
d6): d 20.88, 24.78, 26.76, 33.83, 42.23, 55.79, 81.47, 111.78, 112.56, 116.03, 120.55,
120.59, 122.15, 128.03, 130.05, 243.76, 157.75.
Anal. Calcd. for C19H15BrN4: C, 60.17; H, 3.99; N, 14.77. Found: C, 60.44; H, 4.15; N, 15.03.
2-Amino-4a,5,6,7-tetrahydro-4-(2-chlorophenyl)naphthalene-1,3,3(4H)-tricarbonitrile (4c)
IR (KBr): 3440, 3353, 3186, 2943, 2844, 2210, 1625, 1465, 1438, 1388, 1478, 1271, 1035,
1
776, 740 cmꢁ1; H NMR (400 MHz, DMSO-d6): d 0.78-0.87 (m, 1H), 1.36-1.46 (m, 2H),
1.66-1.69 (m, 1H), 2.04-2.21 (m, 2H), 2.86-2.89 (m, 1H), 3.89 (d, 1H), 5.77 (s, 1H), 7.42
(s, 2H), 7.48-7.54 (m, 2H), 7.63 (d, 1H), 7.77 (d, 1H); 13C NMR (100 MHz, DMSO-d6):
d 20.79, 24.72, 26.09, 34.51, 41.61, 46.45, 81.52, 111.53, 112.22, 115.93, 120.88, 127.84,
128.36, 129.15, 130.13, 130.59, 131.78, 135.10, 143.41.
2-Amino-4a,5,6,7-tetrahydro-4-(2,4-dichlorophenyl)naphthalene-1,3,3(4H)-tricarbonitrile (4e)
IR (KBr): 3440, 3357, 2941, 2916, 2206, 1623, 1589, 1471, 1384, 1265, 1103, 813,
1
815 cmꢁ1; H NMR (400 MHz, DMSO-d6): d 0.78-0.87 (m, 1H), 1.39-1.47 (m, 2H),
1.67-1.70 (m, 1H), 2.09-2.22 (m, 2H), 2.87-2.94 (m, 1H), 3.88 (d, 1H), 5.77 (s, 1H), 7.45
(s, 2H), 7.59-7.86 (m, 3H); 13C NMR (100 MHz, DMSO-d6): d 20.67, 24.69, 26.66,
34.07, 41.46, 46.51, 81.62, 111.40, 111.98, 115.88, 121.06, 128.13, 129.08, 129.63, 131.70,
132.55, 133.85, 134.59, 143.03.
2-Amino-4a,5,6,7-tetrahydro-4-(3,4-dimethoxyphenyl)naphthalene-1,3,3(4H)-tricarbo-
nitrile (4h)
IR (KBr): 3434, 3330, 3226, 2943, 2831, 2208, 1650, 1595, 1508, 1463, 1259, 1143, 1018,
1
815, 763 cmꢁ1; H NMR (400 MHz, DMSO-d6): d 0.85-0.88 (m, 1H), 1.50-1.53 (m, 2H),
1.67-1.69 (m, 1H), 2.01-2.20 (m, 2H), 2.73-2.88 (m, 1H), 3.43 (t, 1H), 3.73-3.78 (d, 6H),
5.72 (s, 1H), 6.96 (s, 1H), 7.09-7.14 (m, 2H), 7.35 (s, 2H); 13C NMR (100 MHz, DMSO-
d6): d 20.99, 24.85, 26.91, 30.71, 35.71, 43.05, 50.38, 50.84, 55.58, 81.59, 110.30, 11.26,
111.90, 112.47, 116.15, 119.22, 120.26, 124.66, 126.85, 128.93, 143.53, 162.25.

236
B. MALEKI AND H. VEISI
2-Amino-4a,5,6,7-tetrahydro-4-(4-nitrophenyl)naphthalene-1,3,3(4H)-tricarbonitrile (4i)
IR (KBr): 3429, 3350, 3222, 2931, 2842, 2202, 1637, 1600, 1514, 1342, 1274, 862,
1
721 cmꢁ1; H NMR (400 MHz, DMSO-d6): d 0.81-0.90 (m, 1H), 1.39-1.48 (m, 2H),
1.66-1.70 (m, 1H), 2.08-2.22 (m, 2H), 2.87-2.89 (m, 1H), 3.80 (d, 1H), 5.75 (s, 1H), 7.40
(s, 2H), 7.66 (s, 1H), 7.83 (s, 1H), 7.97-7.99 (m, 2H).
5-Amino-1,2,7,7a-tetrahydro-7-(4-methoxyphenyl)indene-4,6,6-tricarbonitrile (4l)
IR (KBr): 3423, 3332, 3242, 2968, 2936, 2846, 2208, 1650, 1612, 1585, 1452, 1393, 1275,
1
1020, 841, 803, 780 cmꢁ1; H NMR (400 MHz, CDCl3): d 1.26-1.34 (m, 1H), 2.02-2.09
(m, 1H), 2.43-2.48 (m, 2H), 3.14 (d, 1H), 3.35-3.43 (m, 1H), 3.84 (s, 3H), 5.07 (s, 2H),
5.83 (d, 1H), 6.89 (d, 2H), 7.40 (d, 2H).
5-Amino-1,2,7,7a-tetrahydro-7-(4-fluorophenyl)indene-4,6,6-tricarbonitrile (4m)
IR (KBr): 3420, 3336, 3244, 2948, 2850, 2210, 1650, 1610, 1590, 1458, 1310, 1281, 1010,
1
844, 806 cmꢁ1; H NMR (400 MHz, CDCl3): d 1.23-1.36 (m, 1H), 2.01-2.08 (m, 1H),
2.40-2.49 (m, 2H), 3.18 (d, 1H), 3.36-3.43 (m, 1H), 5.09 (s, 2H), 5.85 (d, 1H), 7.15(d,
2H), 7.45 (d, 2H).
Acknowledgment
The authors thank the Research Council of Hakim Sabzevari University for partial support of
this work.
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