Efficient iodine-catalyzed one pot synthesis of highly functionalised pyrazoles in water

Article abstract of DOI:10.1039/c3nj01149f

An efficient one pot multi-component sequential reaction of phenyl hydrazine, malanonitrile and a diverse range of aldehydes to afford highly functionalised pyrazoles is reported. The reaction proceeds in water using molecular iodine as a catalyst, with no by-product formation, and involves simple operation requiring no column chromatography. Thus, this protocol fulfils all of the criteria that define green chemistry. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014.

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Efficient iodine-catalyzed one pot synthesis of
highly functionalised pyrazoles in water
Cite this:DOI: 10.1039/c3nj01149f
Madhulika Srivastava,a Pratibha Rai,a Jaya Singhb and Jagdamba Singh*a
Received (in Montpellier, France)
23rd September 2013,
Accepted 8th October 2013
An efficient one pot multi-component sequential reaction of phenyl hydrazine, malanonitrile and a
diverse range of aldehydes to afford highly functionalised pyrazoles is reported. The reaction proceeds
in water using molecular iodine as a catalyst, with no by-product formation, and involves simple
operation requiring no column chromatography. Thus, this protocol fulfils all of the criteria that define
green chemistry.
DOI: 10.1039/c3nj01149f
www.rsc.org/njc
Increasingly, chemists are looking for one-pot multi-component iodine. For example, Kulathu I. Sathiyanarayanan et al. synthe-
reactions (MCRs) in order to make desired compounds.1a MCRs sised 1-((phenylthio)(phenyl)methyl)pyrrolidin-2-one4a with the
have many significant advantages such as their time efficiency1b use of iodine. B. V. Subba Reddy and co-workers have reported
and reaction step economy,1c due to the simultaneous formation the synthesis of naphthopyranopyrimidines4b catalysed by
of two or more bonds,1d resulting overall in a better chemical iodine under solvent free conditions. Javad Mokhtari et al.
yield than a corresponding multi-step synthesis. The conven- synthesised spiro[indoline-3,40-pyrrolo[1,2-a]quinoxalin]-2-one4c
tional multi-step synthesis of molecules involves more than one in the presence of iodine, which not only enhanced the yield of
step, including the purification of compounds after each indivi- the product but also considerably reduced the reaction time.
dual step,1e which leads to two main disadvantages: synthetic
inefficiency and the production of large quantities of waste.
With these three aspects of green synthesis in mind,5 we
have searched for a nucleus which shows outstanding perfor-
Significant attention has been paid to MCRs in the aqueous mance in the fields of pharmaceutical chemistry6 and agricul-
phase,2a primarily because of the high synthetic efficiency of ture.7 Of the nitrogen heterocycles, the pyrazole moiety is a
these protocols and also their inherent safety,2b due to the versatile lead molecule in pharmaceutical development. It also
special physical and chemical properties of water such as its has a wide range of biological activities such as antimicrobial,8a
high dielectric constant, its ability to dissolve a large number of antitumor,8b anti-inflammatory8c antiviral,9a analgesic,9b anti-
different chemical compounds by means of hydrogen bonding2c, diabetic,9c anti-obesity,10a and anticonvulsant activities.10b In
nonflammability,2d cost effectiveness,2e high availability,2f ease addition, pyrazole derivatives are used as inhibitors of HIV-1
of handling, and most important of all, the non toxic nature of reverse transcriptase.10a Moreover, pyrazole oxime11a ethers
water,2g making it synonymous with the term ‘‘green solvent’’.1e have proven to be very important, as they show antitumor
These properties of water are highly beneficial compared to and cytotoxic activity. Some pyrazole derivatives show bio-
those of organic solvents.
An important aspect of the reaction is the choice of catalyst. etc., and pyranopyrazoles show antihypoglycemic activity.11e
A literature survey shows that many catalysts involve metals
Rimonabant,10b a pyrazole moiety also known as SR141716,
logical activities, for example, P38 MAP kinase,11b COX-2,11c,d
which are toxic,3a and detrimental to both health and the is used as an appetite suppressant in the treatment of obesity.
environment. Some catalysts are very difficult to remove from Similarly, viagra12 is used as an antihypertensive for the treat-
the reaction mixture while others are very expensive.3b We have ment of pulmonary arterial hypertension. Celebrex13 is a
searched for a catalyst which is metal free, non-toxic and mild.3c potential drug used in the treatment of arthritis. Pyrazole
Such catalysts have always attracted the attention of the synthetic derivatives are also used as anti-diabetic drugs, for example,
community, and one such catalyst is elemental iodine. Several 5-methyl pyrazole-3-carboxylic acid.14 Moreover, CDPPB acts as
research groups have implemented various strategies for the a positive allosteric modulator in scientific research while
synthesis of a desired product which are catalysed by molecular Deracoxib15 is a non-steroidal veterinary medicine used to treat
osteoarthritis in dogs.
In light of our recent work on organic reactions in water15
a Environmentally Benign Lab, Department of Chemistry, University of Allahabad,
and considering the well known broad spectrum qualities of
pyrazoles, we were motivated to devise a new protocol for the
211002 India. E-mail: dr.jdsau@gmail.com; Tel: +91 9415218507
b L R PG College, Sahibabad, UP, India
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Scheme 1 The present synthetic approach to pyrazoles.
synthesis of pyrazole derivatives from easily available and
simple starting materials: aldehyde (1), malanonitrile (2) and
phenylhydrazine (3), affording densely functionalized pyra-
zoles16 (Scheme 1).
Reagents (1), (2), and (3) were mixed in an equimolar ratio in
50 ml water. The reaction reached completion in 4 hours, giving
the product as a solid which contained some by-products as
well. To overcome this shortcoming, we performed the experi-
ment in a sequential manner,17 based on a conclusion drawn
from our previous work15 which proved that the addition of
reagents in a sequential manner provides the product in
excellent yield, with a corresponding reduction in the amount
of by-products. So we again attempted to achieve the desired
product in high yield with excellent purity. We took 50 ml of
water, to which was added reagent 1 followed by 2. After 2 min
when the reaction mixture had turned white, reagent 3 was
added. Only one spot appeared on a TLC plate after 2 h 30 min.
Thus, this minute procedural change led to an increase in the
product yield and a reduction in the overall reaction time. The
product formation takes place via a Knoevenagel reaction
followed by a Michael addition, intermolecular cyclisation
and oxidation, as depicted in Scheme 2.
Scheme 2
derivatives.
A
plausible pathway for the synthesis of the pyrazole
Table 1 The effect of temperature on the yield of the product
Entry
Temp
Timea (min)
Yieldb (%)
We performed a series of these reactions in this sequential
manner, over a varied range of temperatures (Table 1). When
the reaction was carried out at 40 1C, the product was formed in
50 min. At 60 1C the product formation took place in only
20 min, but when the temperature was increased to 80 1C and
above, the product was obtained as a gummy residue.
1
3
4
5
6
7
RT
40
50
60
70
80
150
50
35
20
—
60
75
78
82
—
—
—
Due to the insufficient yields obtained in these reactions, we
catalysed the reaction using a Lewis acid, which is electron
deficient and polarises the carbonyl group of the aldehyde. We
carried out the reaction using various types of Lewis acids and
discovered that molecular iodine was the best among all of the
a
b
Time taken by reaction using the sequential method. Yield of
isolated, purified product.
Table 2 Product yields obtained with different types of Lewis acid catalyst
traditional Lewis acids (Table 2, entry 1). A considerable Entry
Lewis acid (20 mol%)
Yield (%)
improvement was observed in the reaction with the use of
1
I2
92
88
85
84
83
molecular iodine and the yield of the product was raised to
92%. 20 mol% iodine (Table 3, entry 3) was an ideal concen-
tration for the catalysis of the reaction. When we used 15 mol%
and 10 mol% iodine (Table 3, entries 1 and 2), the yield of the
obtained product was low, while further increasing the amount
of iodine beyond 20 mol% did not affect the yield at all.
2
3
4
5
InCl3
Fecl3
SnCl2
ZnCl2
At 60 1C, alcoholic solvents and water gave approximately
Thus iodine catalyses the reaction at each step.18 Not only the same yield (Table 4, entries 1–3). For non polar solvents
was the yield of the product increased, but the rate of reaction such as toluene, the product was obtained in negligible yield
was increased as well, resulting in a shorter reaction time. (Table 3, entry 4). Water conducts heat more readily than any
Iodine is one of the most abundant elements, and its toxicity is other liquid except mercury. Due to the desired parameters of
relativity low in comparison to that of catalysts in which metal green chemistry, we chose water as the solvent for the synthesis
is present.
of the desired product.
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Table 3 Optimisation of catalyst concentration
including the use of water as a solvent and iodine as a catalyst,
a short reaction time and simple handling. The most important
aspect of the adopted method is that it requires no purification
of the desired product. This method achieves all of the criteria
that define green chemistry, reducing waste, material hazard,
risk and cost.
Entry
Iodine (mol%)
Yield (%)
1
2
3
4
5
10
15
20
30
40
85
88
92
92
92
Table 4 Optimization studies of the effects of solvent
General methods
A. General information
Reagents were obtained from commercial suppliers, and used
without further purification unless otherwise specified by a
reference. All reactions were performed using oven-dried glass-
ware. Organic solutions were concentrated using a Buchi rotary
evaporator. TLC was performed using silica gel GF254 (Merck)
plates. Melting points were determined by the open glass capillary
method and are uncorrected. IR spectra were recorded in KBr on a
Perkin-Elmer 993 IR spectrophotometer, and 1H NMR spectra
were recorded on a Bruker AVII 400 spectrometer in CDCl3 using
TMS as an internal reference with chemical shift values being
reported in ppm. All coupling constants ( J) are reported in Hertz
(Hz). 13C NMR spectra were recorded on the same instrument at
100 MHz in CDCl3 and TMS was used as an internal reference.
Mass (EI) spectra were recorded on a JEOL D-300 mass spectro-
meter. Elemental analyses were performed using a Coleman
automatic carbon, hydrogen and nitrogen analyzer.
Entry
Solvent
Yielda (%)
1
2
3
4
5
H2O
92
89
85
15
20
CH3OH
CH3CH2OH
C6H5CH3
THF
a
Yield of isolated, purified product.
Table 5 Synthesis of pyrazole derivatives
Entry
Ra
2
3
Time (min)
Yieldb (%)
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4-OCH3
H
2-Cl
2
2
2
2
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
3
3
6
7
5
5
7
8
4
4
5
6
7
8
5
6
92
91
92
93
90
88
93
94
92
87
86
87
88
91
4-Cl
2-OCH3
3-4-Di methoxy
3-NO2
B. General procedure for the synthesis of pyrazoles (4a to 4n)
50 ml water was transferred into a round bottom flask, to which
was added 20 mol% iodine, aldehyde (1 mmol) and malano-
nitrile (1 mmol). Phenyl hydrazine was then added (1 mmol).
After completion of the reaction in the appropriate time
(Table 5), the reaction mixture was diluted with water (with a
small amount of Na2S2O3). The solid crude products were
collected by filtration, washed with water and dried. Thus,
the isolated product was obtained, and was tested by TLC
producing a single spot on the TLC plate (silica gel coated
aluminium plates, Merk). Products 5c (semi solid) and 5i
(liquid) were extracted with ethyl acetate (3 times). After com-
pletion of the reaction (monitored by TLC), the combined
organic phases were dried over anhydrous Na2SO4, filtered
and evaporated to yield the final pure product. All resulting
solid products (except 5i and 5c) were recrystallised from hot
ethanol.
4-NO2
4-F
4-N-Dimethyl
4-CH3
1-OH
3-CN
4-OCH3
3
3(4Cl)
a
b
R is a substituent on the aldehyde. Yield of isolated, purified
product.
In order to gain insight into the role of the electronic effect
on the reaction, the reaction was performed with a range of
aldehydes possessing different electron withdrawing and elec-
tron donating substituents. It was found that an aldehyde with
an electron withdrawing substituent (Table 5, entries 4g and
4h) provided a better result in comparison to those having an
electron donating substituent. In contrast, a lower yield was
obtained with phenyl hydrazine having an electron withdraw-
ing group and vice versa. Thus we concluded that the synthesis
could best be carried out at 60 1C with malanonitrile 2,
phenylhydrazine 3, a variety of aldehydes, and 20 mol% iodine,
giving the respective highly functionalised pyrazoles in excel-
lent yields of 85–94% (Table 5).
5-Amino-3-(4-methoxyphenyl)-1-phenyl-1H-pyrazole-4-carbonitrile
(4a). Light brown white solid, melting point: 106–108 1C. IR
(KBr) nmax 3350, 3270, 3030, 2820, 2630, 2215, 1540, 860 cmÀ1
;
1H NMR (400 MHz, CDCl3) d (ppm) 7.83–7.85 (m, 1H), 7.67
(s, 1H), 7.58–7.61 (m, 2H), 7.24–7.28 (m, 1H), 7.09 (d, J = 7.6,
2H), 7.00 (m, 1H), 6.89–6.93 (m, 2H), 6.83 (t, 1H) 3.83 (s, 3H);
13C NMR (100 MHz, CDCl3) d (ppm) 160.03, 144.93, 143.44,
137.43, 128.10, 127.58, 127.10, 119, 114.11, 112.66, 99.98, 59.33,
55.35; EIMS (m/z) 290 (M)+. Anal. calcd for C17H14N4O; C, 70.33;
H, 4.86; N, 19.30; found: C, 70, H, 4.89; N, 19.28.
To summarise, we have efficiently synthesised a series of
pyrazole derivatives in good yields using an eco-friendly
approach. The adopted route has many significant features
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5-Amino-1,3-diphenyl-1H-pyrazole-4-carbonitrile (4b). White (s, 1H), 7.75 (s, 1H) 7.57 (t, J = 7.6 Hz, 1H), 7.34 (t, J = 7.2 Hz,
solid, melting point: 159–160 1C. IR (KBr) nmax 3483, 3344, 3081, 2H), 7.17 (d, J = 8.4 Hz, 2H), 6.95 (t, J = 7.2 Hz, 1H); 13C NMR
2357, 1589, 1422, 1251, 1124, 1110, 1065 cmÀ1 1H NMR (100 MHz, CDCl3) d (ppm) 156.43, 149.26, 144.26, 137.73,
;
(400 MHz, CDCl3) d (ppm) 7.74 (d, J = 7.2 Hz, 2H), 7.71 134.32, 131.82, 129.93, 129.87, 122.68, 122.10, 121.37, 113.43,
(s, 1H). 7.63 (s, 1H), 7.40 (t, J = 7.6 Hz, 2H), 7.36 (m, 3H), 112.46; EIMS (m/z) 305 (M)+. Anal. calcd for C16H11N5O2; C,
7.16–7.29 (d, J = 7.6 Hz, 2H), 6.92 (t, J = 7.2 Hz, 1H); 13C NMR 62.95; H, 3.63; N, 22.94; found: C, 62.92; H, 3.65; N, 22.92.
(100 MHz, CDCl3) d (ppm) 156.52, 150.42, 146.09, 137.85,
5-Amino-3-(4-nitrophenyl)-1-phenyl-1H-pyrazole-4-carbonitrile
135.77, 129.74, 128.05, 127.9, 126.64, 120.56, 113.25, 112.82; (4h). Red solid, melting point: 164–166 1C. IR (KBr) nmax.3465,
EIMS (m/z): 260 (M)+. Anal. calcd for C16H12N4; C, 73.83; H, 4.65; 3355, 3105, 2354, 1610, 1417, 1456, 1345, 1256, 1133, 1108,
N, 21.52; found: C, 73.80; H, 4.67; N, 21.54.
1094 cmÀ1; 1H NMR (400 MHz, CDCl3), d 8.25 (d, J = 7.6 Hz, 2H)
5-Amino-3-(2-chlorophenyl)-1-phenyl-1H-pyrazole-4-carbonitrile 8.03 (s, 1H), 7.74–7.77 (m, 3H), 7.20–7.34 (m, 2H), 7.18 (d, J =
(4c). Semi solid, IR (KBr) nmax, 3475, 3425, 3150, 2520, 2335, 7.6 Hz, 2H), 6.96 (s, 1H); 13C NMR (100 MHz, CDCl3) d (ppm)
1660, 1575, 765, 720, cmÀ1; 1H NMR (400 MHz, CDCl3) d (ppm) 156.53, 149.56, 145.26, 137.73, 135.32, 131.72, 130.93, 129.90,
7.61 (s, 2H) 7.58 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.28– 122.78, 122.15, 123.47, 113.43, 112.36; EIMS (m/z) 305 (M)+.
7.32 (m, 2H), 7.15 (d, J = 7.6 Hz, 2H), d 6.94 (t, J = 7.6 Hz, 1H); Anal. calcd for C16H11N5O2; C, 62.95; H, 3.63; N, 22.94; found:
13C NMR (100 MHz, CDCl3) d (ppm) 154.82 144.87, 144.43, C, 62.93; H, 3.66; N, 22.95.
139.44, 138.52, 137.90, 129.41, 128.54, 127.04, 119.34, 117.25,
5-Amino-3-(4-fluorophenyl)-1-phenyl-1H-pyrazole-4-carbo-
112.84, 114.04, 99.48; EIMS (m/z) 294 (M)+, 296 (M + 2)+. Anal. nitrile (4i). Yellow oil, IR (KBr) nmax 3465, 3410, 3143, 2545,
calcd for C16H11ClN4 C, 65.20; H, 3.76; N, 19.01; found: C, 2220, 1650, 1650, 1320, 840 cmÀ1; H NMR (400 MHz, CDCl3)
1
65.24; H, 3.79; N, 19.05.
d 7.89–7.96 (m, 2H), 7.63 (s, 1H), 7.57–7.62 (m, 2H), 7.25–7.27
5-Amino-3-(4-chlorophenyl)-1-phenyl-1H-pyrazole-4-carbonitrile (m, 2H), 7.11 (d, J = 7.6, 1H), 6.90–6.93 (m, 3H); 13C NMR
(4d). Cream colour solid, melting point: 128–130 1C. IR (KBr) (100 MHz, CDCl3) d (ppm) 157.56, 144.93, 144.51, 136.32,
nmax 3460, 3380, 3130, 2520, 2253, 1660, 1570 cmÀ1; H NMR; 138.47, 130.56, 129.01, 128.31, 127.41, 119.32, 116.56, 115.67,
1
(400 MHz, CDCl3) d (ppm) 7.66 (s, 2H) 7.64 (d, J = 8.4 Hz, 2H), 113.34; EIMS (m/z) 278 (M)+. Anal. calcd for C16H11FN4; C,
7.36 (d, J = 8.4 Hz, 2H), 7.29–7.33 (m, 2H), 7.16 (d, J = 7.6 Hz, 69.06; H, 3.98; N, 19.99; found: C, 69.04; H, 4.01; N, 19.98.
2H), d 6.95 (t, J = 7.4 Hz, 1H); 13C NMR (100 MHz, CDCl3)
4-Amino-1-(4-(dimethylamino)phenyl)-3-phenyl-1H-pyrazole-
d (ppm) 154.23, 143.41, 142, 133, 130, 129, 127, 126, 119.41, 5-carbonitrile (4j). Yellow solid, melting point: 105–107 1C. IR
115.65; EIMS (m/z) 294 (M)+, 296 (M + 2)+. Anal. calcd for (KBr) nmax 3430, 3320, 3180, 2810, 2545, 2230, 1640, 1580 cmÀ1
;
C
16H11ClN4; C, 65.20; H, 3.76; N, 19.01; found: C, 65.18; H, 1H NMR (400 MHz; CDCl3) d (ppm) = 7.81–7.84 (m, arom., 4H),
3.78; N, 19.03.
7.65–7.83 (m, 2H), 7.65 (s, 1H), 7.25–7.29 (m, 2H), 7.14 (s, 2H),
5-Amino-3-(2-methoxyphenyl)-1-phenyl-1H-pyrazole-4-carbonitrile 3.15 (s, 6H); 13C NMR (100 MHz; CDCl3) d (ppm) 150.97, 145.03,
(4e). Red solid, melting point: 130–132 1C. IR (KBr) nmax 3480, 129.28, 128.18, 123.01, 127.82, 115.11, 113.4, 59.01, 40.10; EIMS
3410, 3120, 2830, 2545, 2238, 1650, 1580, 780, 720, cmÀ1
;
(m/z) 303 (M)+. Anal. calcd for, C18H17N5 C, 71.27; H, 5.65; N,
1H NMR (400 MHz, CDCl3) d (ppm) 7.82–7.84 (m, 1H), 7.66 23.09; found: C, 71.23; H, 5.68; N, 23.10.
(s, 1H), 7.57–7.60 (m, 2H), 7.23–7.26 (m, 1H), 7.10 (d, J = 7.6,
5-Amino-1-phenyl-3-p-tolyl-1H-pyrazole-4-carbonitrile (4k).
2H), 7.01 (m, 1H), 6.89–6.93 (m, 2H), 6.85 (t, 1H) 3.84 (s, 3H); Pink powder, melting point: 118–120 1C. IR (KBr) nmax 3484,
13C NMR (100 MHz, CDCl3) d (ppm) 161.01, 143.92, 143.37, 3318, 3098, 2927, 2358, 1598, 1418, 1255, 1125, 1123, 1094;
137.54, 137.40, 129.01 127.30, 128.44, 125.84, 118.92, 112.89, 1H NMR (400 MHz; CDCl3) d (ppm) 7.71 (s, 2H). 7.58 (d, J = 7.6
114.02, 56.01; EIMS (m/z) 290 (M). Anal. calcd for C17H14N4O; C, Hz, 2H), 7.30–7.34 (m, 2H), 7.22 (d, J = 7.6 Hz, 2H), 7.15 (d, J =
70.33; H, 4.86; N, 19.30; found: C, 70.31; H, 4. 87; N, 19.32.
7.76 Hz, 2H), 6.91 (dd, J = 3.4 Hz and J = 7.6 Hz, 1H), d (ppm)
5-Amino-3-(3,4-dimethoxyphenyl)-1-phenyl-1H-pyrazole-4- 2.42 (s, 3H); 13C NMR (100 MHz; CDCl3) d (ppm) 154.22. 150.95,
carbonitrile (4f). White solid, melting point: 120–123 1C. IR 145.13, 129.26, 128.15, 123.11, 127.84, 115.11, 113.40, 104.65,
(KBr) nmax 3310, 3190, 3050, 2840, 2650, 2200, 1535, 1630, 874, 21.92; EIMS (m/z) 274 (M)+. Anal. calcd for C17H14N4: C, 74.43;
725 cmÀ1; 1H NMR (400 MHz; CDCl3) d (ppm) 9.75 (s, 1H), 7.68– H, 5.14; N, 20.42; found: C, 74.41; H, 5.1; 7; N, 20.43.
7.69 (d, 1H, J = 2 Hz), 7.64 (s, 1H), 7.37–7.39 (m, 1H), 7.25–7.29
5-Amino-3-(2-hydroxyphenyl)-1-phenyl-1H-pyrazole-4-carbonitrile
(m, 4H arom.), 7.16 (s, 2H), 6.95–697 (d, 1H, J = 8.4), 3.77 (4l). Yellow solid, melting point: 160–162 1C. IR (KBr) nmax 3580,
(s, 3H), 3.79 (s, 3H); 13C NMR (100 MHz; CDCl3) d (ppm) 155. 45, 3487, 3343, 3122, 2354, 2195, 1602, 1413, 1182, 1055 cmÀ1
;
149.80, 148.02, 145.23, 144.46, 137.36, 129.43, 128.64, 127.36, 1H NMR (DMSO 400 MHz): d (ppm) 10.51 (s, 1H), 10.37 (s, 1H),
120.04, 115.48, 114.54, 112, 99.46, 56.10, 56.16; EIMS (m/z) 320 8.15 (s, 1H), 7.54 (dd, J = 1.6 Hz and J = 7.6 Hz, 1H), 7.24
(M)+. Anal. calcd for C18H16N4O2; C, 69.06; H, 5.03; N, 17.48; (dd, J = 7.6 Hz and J = 8.4 Hz, 2H), 6.94 (d, J = 7.6 Hz, 2H), 7.14–
found: C, 69.04; H, 5.06; N, 17.46.
7.18 (m, 1H), 6.84–6.89 (m, 2H), 6.74 (t, J = 7.2 Hz, 1H); 13C NMR
5-Amino-3-(3-nitrophenyl)-1-phenyl-1H-pyrazole-4-carbonitrile (DMSO, 100 MHz): d (ppm) 156.48, 152.20, 150.52, 145.52,
(4g). Saffron colour solid, melting point: 128–130 1C. IR (KBr) 138.03, 130.13, 130.01, 128.16, 125.40, 121.33, 120.23,
n
max 3455, 3321, 3111, 2355, 1592, 1477, 1445, 1343, 1328, 1266, 119.73, 116.82, 112.61; EIMS (m/z) 276 M+. Anal. calcd for
1149, 1120, 1092 cmÀ1; 1H NMR (400 MHz, CDCl3) d (ppm) 8.47
(s, 1H) 8.13 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 7.6 Hz, 1H), 7.88 4.43; N, 20.30.
C16H12N4O: C, 69.55; H, 4.38; N, 20.28; found: C, 69.50; H,
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5-Amino-3-(4-cynophenyl)-1-phenyl-1H-pyrazole-4-carbonitrile
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(4m). Yellow solid, melting point: 158–160 1C. IR (KBr)
nmax 3434, 3316, 3275, 2353, 2229, 1583, 1472, 1265, 1155,
1127, 1096 cmÀ1 1H NMR (CDCl3, 400 MHz): d (ppm) 10.72
;
(s, 1H), 7.85 (s, 1H), 7.77–7.81 (m, 4H), 7.24 (t, J = 7.2 Hz, 2H)
7.13 (d, J = 7.6 Hz, 2H), 6.82 (t, J = 7.2 Hz, 1H); 13C NMR
(100 MHz; CDCl3) d (ppm) 152.34, 146.19 137.83, 135.75,
129.70, 128.15, 127.09, 126.74, 120.56, 117.92, 115.61, 113.25,
112.82; EIMS (m/z) 285 (M)+. Anal. calcd for C17H11N5: C, 71.57;
H, 3.89; N, 24.55; found: C, 71.51; H, 3.75; N, 24.49.
5-Amino-1-(4-chlorophenyl)-3-phenyl-1H-pyrazole-4-carbonitrile
(4n). Pink solid, melting point: 133–135 1C. IR (KBr) nmax 3420,
3322, 3095, 2365, 1598, 1487, 1267, 1134, 1096, cmÀ1; 1H NMR
(CDCl3, 400 MHz): d (ppm) 7.70 (s, 1H), 7.66 (d, J = 7.6 Hz, 2H),
7.56 (s, 1H), 7.42 (t, J = 7.6 Hz, 2H), 7.06 (d, J = 8.8 Hz, 2H), 7.25
(d, J = 8.4 Hz, 2H), 7.33–7.36 (m, 1H); 13C NMR (CDCl3,
100 MHz): d (ppm) 155.92, 143.67, 138.37, 135.41, 132.28,
129.52, 129.09, 129.02, 126.60, 125.08, 114.22, 112.05; EIMS
(m/z) 294 (m+), 296 (M + 2). Anal. calcd for C16H11ClN4: C, 65.20;
H, 3.76; N, 19.01%; found: C64.11; H, 3.86; N, 19.10.
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We sincerely thank SAIF, Punjab University, Chandigarh, for
providing micro-analyses and spectra. The authors are also
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