Improved protocol for Thorpe reaction: Synthesis of 4-amino-1-arylpyrazole using solid-liquid phase-transfer conditions

Article abstract of DOI:10.1080/00397910701767023

Solid-liquid phase-transfer conditions were employed for the first time in the Thorpe reaction to synthesize 4-amino-1-aryl-3,5-substituted-1H-pyrazoles 3. Aryl amines were diazotized and coupled with various active methylene compounds such as cyano aceta

Full text of DOI:10.1080/00397910701767023

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Improved Protocol for Thorpe Reaction:
Synthesis of 4‐Amino‐1‐arylpyrazole using
Solid–Liquid Phase‐Transfer Conditions
Nirmal D. Desai a & Rina D. Shah b
a Loyola Center for Research and Development , Navrangpura, Ahmedabad,
India
b M. G. Science Institute, Organic Synthesis Laboratory , Navrangpura,
Ahmedabad, India
Published online: 28 Jan 2008.
To cite this article: Nirmal D. Desai & Rina D. Shah (2008) Improved Protocol for Thorpe Reaction: Synthesis
of 4‐Amino‐1‐arylpyrazole using Solid–Liquid Phase‐Transfer Conditions, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 38:3, 316-327, DOI:
10.1080/00397910701767023
To link to this article: http://dx.doi.org/10.1080/00397910701767023
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Synthetic Communicationsw, 38: 316–327, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701767023
Improved Protocol for Thorpe Reaction:
Synthesis of 4-Amino-1-arylpyrazole using
Solid–Liquid Phase-Transfer Conditions
Nirmal D. Desai1 and Rina D. Shah2
1Loyola Center for Research and Development, Navrangpura,
Ahmedabad, India
2Organic Synthesis Laboratory, M. G. Science Institute, Navrangpura,
Ahmedabad, India
Abstract: Solid–liquid phase-transfer conditions were employed for the first time in
the Thorpe reaction to synthesize 4-amino-1-aryl-3,5-substituted-1H-pyrazoles 3.
Aryl amines were diazotized and coupled with various active methylene compounds
such as cyano acetamide, cyanoacetophenone, malononitrile, and ethyl cyanoacetate,
resulting into a-arylhydrazononitriles 1. Cyclization of 1 using a-bromo ketones or
esters resulted in compounds 3.
Keywords: 4-amino-1-arylpyrazole, a-arylhydrazononitriles, 18-crown-6, phase-transfer
catalyst, Thorpe reaction
INTRODUCTION
The intermolecular Thorpe[1] reaction and its intramolecular version, Thorpe–
Zeigler[2] reaction, are two of the most promising lines in the chemistry of
five-member amino heterocycles. They are base catalyzed, and sodium or
potassium alkoxide,[3a–e] sodium hydride,[3f,g] potassium hydroxide,[3h]
lithium hydroxide,[3i] and potassium carbonate[1a,b] were employed fre-
quently. Radical alternatives,[4a] solvent-free[4b] strategies, and iridium
Received in India July 20, 2007
Address correspondence to Nirmal D. Desai, Loyola Center for Research and
Development, St. Xavier’s College, Navrangpura, Ahmedabad 380009, India.
E-mail: nirmal.desai@yahoo.com
316

Synthesis of 4-Amino-1-arylpyrazole
317
hydride complexes[4c] also have been applied to intramolecular as well as
intermolecular Thorpe reactions. Yet, a little to our surprise, no attempt has
been made to employ comprehensive strategies for the Thorpe reaction
involving phase-transfer conditions.
Pyrazoles are an important class of heteroaromatic ring systems that find
extensive use in the agrochemical industry and pharmaceutical industries.[5]
More recently, extensive studies have focused on pyrazoles for exhibiting
cyclooxygenase-2 (COX-2), nonnucleoside HIV-1 reverse transcriptase
inhibitory properties[6,7] and in a novel class of synthetic Hsp90 inhibitor.[8]
By far the most prevalent method of obtaining pyrazoles is by the reaction
of 1,3-diketones with hydrazine, hydrazine derivatives,[9] and the nitrene
insertion reaction.[10] However, if
a diversity-oriented synthesis of
pyrazoles[11] is desired, this method becomes cumbersome as each 1,3-
diketone must be purified and is often obtained as a mixture of condensation
products. Furthermore, most electrophilic functional groups such as
aldehydes, nitriles, esters, and alkyl halides do not survive the transformation.
Other methods for the synthesis of pyrazoles that do not require 1,3-
diketones have been reported[12] but tend to have serious drawbacks such as
being step intensive. In light of this, and in continuation of our interest in
the use of phase-tansfer catalysis (PTC) in heterocycles,[13] described herein
are the results of a study that has culminated in the development of a
process for the efficient synthesis of 4-amino-1-aryl-3,5-substituted-1H-
pyrazoles 3. Comparative study of the Thorpe reaction with and without
phase-transfer catalyst was also carried out.
RESULTS AND DISCUSSION
Nonsubstituted and substituted aryl amines were diazotized and coupled with
cyanoacetamide, cyanoacetophenone, malononitrile, and ethyl cyanoacetate
according to the method prescribed in literature,[14] affording 2-arylhydrazo-
nocyanoacetamide 1a, ethyl 2-arylhydrazonocyanoacetophenone 1b, 2-aryl-
hydrazonomalononitriles 1c–e, and ethyl 2-arylhydrazonocyanoacetates
1f–l, respectively, in very good yields.
Thorpe reaction[1ab] of a-arylhydrazononitriles 1 with a-bromo ketone or
ester in DMF/K2CO3/Et3N resulted in 4-amino-1-aryl-3,5-substituted-1H-
pyrazoles 3 (Table 1). A similar reaction by Kaja et al.[15] resulted in very
poor yields, and moreover, reagents need to be used in excess to improve
the yields. In view of these findings, we decided to set an improved
protocol by introducing phase-transfer conditions for the Thorpe reaction.
All reactions were carried out at 60–708C or slightly warmer. Potassium
hydroxide along with 18-crown-6 was our choice of catalyst, and acetonitrile
was used as solvent. There was significant improvement in the reaction time
and yields, and workup was clean compared to the methods reported so
far.[1ab,15] However, any alteration in molar quantities of the catalyst

Table 1. Synthesis of 4-amino-1-aryl-3,5-substituted-1H-pyrazoles 3a–o
With PTC
Without PTC DMF/
K2CO3/Et3N
Liquid–liquid PTC
conditiona TBHSO4b
Solid–liquid PTC
conditionc18-Crown-6
Yield (%)
Time
(h) Toluene MeCN
Yield
(%)
Entry
R
R1
R2
Time (h)
Time (h)
Yield (%)
Mp (8C) found/lit.
3a
3b
3c
3d
3e
3f
H
H
CONH2
COC6H5
6–8
6–8
6–8
6–8
6–8
6–8
—
80
60
68
88
86
27
—
80
70
—
—
—
—
—
—
3.5
3
58
49
55
66
52
35
40
65
50
47
40
42
43
50
55
2.5
2
74
67
66
86
64
60
58
79
72
70
73
53
70
69
78
84
80
79
94
91
67
65
87
81
78
87
62
90
86
89
192–93 (lit. 189–90)[1a]
199–200 (lit. 194–96)[1a]
138–39 (lit. 134–36)[1a]
143–44 (lit. 140–42)[1a]
123 (lit. 120–22)[1a]
125–26 (lit. 121–23)[15]
132–33
173–74 (lit. 170–72)[1a]
110–11 (lit. 91–92)[1a]
100
CONH2 COOC2H5
COC6H5 COC6H5
COC6H5 COOC2H5
H
3.5
3.5
3.5
3.5
3.5
3
2.5
2.5
2.5
2.5
2.5
2
H
H
CN
CN
CN
COOC2H5
COOC2H5
COOC2H5
3-Br
3-Cl-4-F
H
3g
3h
3i
COOC2H5 COC6H5
COOC2H5 COOC2H5
COOC2H5 COOC2H5
COOC2H5 COOC2H5
COOC2H5 COOC2H5
6–8
6–8
—
H
3.5
3
2
3j
3-Cl
4-Cl
4-F
2.5
2
3k
3l
—
—
3.5
3.5
3
127–28
109–10
2.5
2
3m
3n
3o
4-OCH3 COOC2H5 COOC2H5
4-CH3 COOC2H5 COOC2H5
3-Cl-4-F COOC2H5 COOC2H5
—
—
149–50
118
155–56
3.5
3
2
2.5
—
Note: PTC ¼ phase-transfer catalyst.
aCH2Cl2/KOH (aq. 40% w/v).
bTetrabutylammoniumhydrogensulfate.
c18-Crown-6, KOH (solid), CH3CN.

Synthesis of 4-Amino-1-arylpyrazole
319
resulted in undesired by-products; a similar observation was made for the
solvent.
Given the frequent appearance of pyrazole fragments in pharmaceutical
compounds, we sought to expand the scope of this potentially useful
phase-transfer method and optimize its efficiency. To optimize the synthesis
of 3, different phase-transfer catalysts and solid–liquid and liquid–liquid
phase-transfer conditions were examined (Table 1). For liquid–liquid
phase-transfer conditions, CH2Cl2/KOH (aq. 40% w/v), lack of reactivity
was observed in the presence of catalysts such as tetrabutylammonium
bromide (TBAB) and triethylbenzylammonium chloride (TEBA). Results
also showed concomitant decomposition of both reactants after prolonged
heating (24 h, 60–708C). Employing tricaprylmethylammonium chloride
(Aliquatw) was also unsuccessful. However, under similar conditions, tetrabu-
tylammonium hydrogen sulfate (TBHSO4) proved to be a better catalyst, and
compounds 3 were obtained in yields of 35–66%. Reducing the catalyst
loading or changing the solvent resulted in a significant decrease in the
yields. Increasing the temperature past 708C had little effect on the yields.
Finally, in solid–liquid phase-transfer conditions, the use of 18-crown-6
KOH along with acetonitrile or toluene as a solvent resulted in the
formation of the product 3a–o; however, in acetonitrile, the yields were
excellent (Scheme 1).
A plausible mechanism for the Thorpe reaction is proposed in Scheme 2.
The initial HBr removal from a-bromo ketone or ester and a-arylhydrazono-
nitriles 1 resulting into the intermediate 2, followed by intramolecular nucleo-
philic addition of -CH- onto the nitrile group, gave imines that could yield an
enamine and also aromatic system for the formation of 4-amino-1-aryl-3,5-
substituted-1H-pyrazoles 3.
In conclusion, we have described a simple, clean, and convenient
synthesis of 4-amino-1-aryl-3,5-substituted-1H-pyrazole 3, which is an
important building block for the construction of various fused heterocycles.
A comparison of conventional method, liquid–liquid PTC, and solid–liquid
PTC suggests that the solid–liquid PTC conditions using 18-crown-6 is the
method of choice with excellent yields. The ease with which the phase-
transfer catalyst reacts presents new opportunities for expanding the Thorpe
reaction for the synthesis of numerous heterocycles, a use that remains
almost unexplored.
EXPERIMENTAL
Melting points were determined by an electrothermal method in an open
capillary tube and are uncorrected. The IR spectra were recorded in
1
centimeters21 for KBr pellets on a Buck-500 spectrophotometer. The H
NMR spectra were recorded on a Bruker 300-MHz spectrophotometer in
CDCl3 using TMS as internal standard, and the chemical shifts are

320
N. D. Desai and R. D. Shah
Scheme 1.
expressed in d ppm. MS spectra were recorded on a Jeol SX-102 mass spec-
trophotometer under electron-impact (EI) ionization. Elemental analyses were
performed on a Carlo Erba 1108 microanalyzer or Elementar’s Vario EL III
microanalyzer. The purity of the compounds was routinely checked by thin-
layer chromatography (TLC) using silica gel G, and spots were exposed in
iodine vapor.
Synthesis of 4-Amino-1-aryl-3,5-substituted-1H-pyrazole 3a–o,
General Procedures
Method 1: Solid–Liquid Phase-Transfer Catalysis Conditions
a-Arylhydrazononitrile 1 (5 mmol) was added to the well-stirred solution of
toluene or MeCN (20 mL), powdered KOH (0.700 g, 12.5 mmol), and 18-
crown-6 (0.132 g, 0.5 mmol) and stirred for 30 m. To this a-bromo ketone
or ester (8 mmol) were added portionwise. The reaction mixture was further
stirred at 70–808C for 1.5–2 h (TLC). The solvent was distilled under
reduced pressure, and the reaction mixture was poured onto crushed ice

Synthesis of 4-Amino-1-arylpyrazole
321
Scheme 2.
(20 g) and neutralized with acetic acid (50% v/v). The products thus obtained
were filtered, washed with water, dried, and crystallized from absolute ethyl
alcohol.
Method 2: Liquid–Liquid Phase-Transfer Catalysis Conditions
a-arylhydrazononitrile 1 (5 mmol) was added to the stirred mixture of CH2Cl2
(15 mL), KOH solution (5 mL, 40% w/v), and TBHSO4 (1.69 g, 5 mmol) at
room temperature. To this, a-bromo ketone or ester (8 mmol) was added por-
tionwise in 30 m. The reaction mixture was stirred further at room temperature
for 2.5–3 h (TLC). The organic phase was separated and washed with water,
acetic acid (10% v/v), and water. The solvent was distilled under reduced
pressure and cooled to 5–108C; the solid thus obtained was filtered, washed
with chilled methanol, and crystallized from absolute ethyl alcohol.
Data
4-Amino-5-benzoyl-1-phenyl-1H-pyrazole-3-carboxamide (3a)[1a]
IR (KBr): n ¼ 3590, 3450, 3370, 3200 (NH), 1696, 1640 (C55O), 1616, 1504
1
(C55C, C55N ring) cm21. H NMR (300 MHz, CDCl3): 1.35 (t, J ¼ 7.2 Hz

322
N. D. Desai and R. D. Shah
3H, OCH2CH3), 4.29 (q, 2H, OCH2CH3), 5.60 (br S, 2H, NH2 at C4), 7.30–
7.90 (m, 5H, Ar-H þ NH2 exchangeable with D2O). MS (EI): m/z ¼ 306 (Mþ).
Anal. calcd. for C17H14N4O2 (306.32): C, 66.66; H, 4.61; N, 18.29. Found: C,
66.84; H, 4.44; N, 18.10.
Ethyl 4-Amino-3-carbamoyl-1-phenyl-1H-pyrazole-5-carboxylate (3b)[1a]
IR (KBr): n ¼ 3490, 3450, 3360, 3190 (NH), 1712, 1686 (C55O), 1604, 1500
1
(C55C, C55N ring) cm21. H NMR (300 MHz, CDCl3): 1.30 (t, J ¼ 7.2 Hz
3H, OCH2CH3), 4.25 (q, 2H, OCH2CH3), 5.65 (br S, 2H, NH2 at C4),
7.32–7.88 (m, 5H, Ar-H þ NH2 exchangeable with D2O). MS (EI): m/z ¼ 274
(Mþ). Anal. calcd. for C13H14N4O3 (274.28): C, 56.93; H, 5.14; N, 20.43.
Found: C, 56.95; H, 5.34; N, 20.32.
4-Amino-3,5-dibenzoyl-1-phenyl-1H-pyrazole (3c)[1a]
IR (KBr): n ¼ 3500, 3400 (NH), 1652, 1624 (C55O), 1616, 1500 (C55C,
C55N ring) cm21 1H NMR (300 MHz, CDCl3): 5.55 (br S, 2H, NH2),
.
7.30–7.90 (m, 15H, Ar-H). MS (EI): m/z ¼ 367 (Mþ). Anal. calcd. for
C23H17N3O2 (367.4): C, 75.19; H, 4.66; N, 11.44. Found: C, 75.35; H, 4.86;
N, 11.30.
Ethyl 4-Amino-3-benzoyl-1-phenyl-1H-pyrazole-5-carboxylate (3d)[1a]
IR (KBr): n ¼ 3490, 3370 (NH), 1732, 1684 (C55O), 1604, 1516 (C55C,
1
C55N ring) cm21. H NMR (300 MHz, CDCl3): 1.30 (t, J ¼ 7.2 Hz 3H,
OCH2CH3), 4.27 (q, 2H, OCH2CH3), 5.52 (br S, 2H, NH2), 7.33–7.89
(m, 10H, Ar-H). MS (EI): m/z ¼ 335 (Mþ). Anal. calcd. for C19H17N3O3
(335.36): C, 68.05; H, 5.11; N, 12.53. Found: C, 68.15; H, 5.01; N, 12.65.
Ethyl 4-Amino-3-cyano-1-phenyl-1H-pyrazole-5-carboxylate (3e)[1a]
IR (KBr): n ¼ 3460, 3350 (NH), 2220 (CN), 1708 (C55O), 1616, 1500 (C55C,
1
C55N ring) cm21. H NMR (300 MHz, CDCl3): 1.35 (t, J ¼ 7.2 Hz 3H,
OCH2CH3), 4.29 (q, 2H, OCH2CH3), 5.48 (br S, 2H, NH2), 7.30–7.85
(m, 5H, Ar-H). MS (EI): m/z ¼ 256 (Mþ). Anal. calcd. for C13H12N4O2
(256.26): C, 60.93; H, 4.72; N, 21.86. Found: C, 61.05; H, 4.88; N, 21.92.
Ethyl 4-Amino-3-cyano-1-(3-bromophenyl)-1H-pyrazole-5-
carboxylate (3f)[15]
IR (KBr): n ¼ 3440, 3320 (NH), 2210 (CN), 1712 (C55O), 1616, 1500 (C55C,
1
C55N ring) cm21. H NMR (300 MHz, CDCl3): 1.33 (t, J ¼ 7.2 Hz 3H,
OCH2CH3), 4.31 (q, 2H, OCH2CH3), 5.50 (br S, 2H, NH2), 7.22–7.78

Synthesis of 4-Amino-1-arylpyrazole
323
(m, 4H, Ar-H). MS (EI): m/z ¼ 335 (Mþ). Anal. calcd. for C13H11BrN4O2
(335.16): C, 46.59; H, 3.31; N, 16.72. Found: C, 46.45; H, 3.41; N, 16.82.
Ethyl 4-Amino-3-cyano-1-(3-chloro-4-fluorophenyl)-1H-pyrazole-5-
carboxylate (3g)
IR (KBr): n ¼ 3460, 3310 (NH), 2210 (CN), 1716 (C55O), 1612, 1508 (C55C,
1
C55N ring) cm21. H NMR (300 MHz, CDCl3): 1.32 (t, J ¼ 7.2 Hz 3H,
OCH2CH3), 4.34 (q, 2H, OCH2CH3), 5.45 (br S, 2H, NH2), 7.32–7.88
(m, 3H, Ar-H). MS (EI): m/z ¼ 308 (Mþ). Anal. calcd. for C13H10ClFN4O2
(308.7): C, 50.58; H, 3.27; N, 18.15. Found: C, 50.45; H, 3.41; N, 18.12.
Ethyl 4-Amino-5-benzoyl-1-phenyl-1H-pyrazole-3-carboxylate (3h)[1a]
IR (KBr): n ¼ 3520, 3380 (NH), 1732, 1684 (C55O), 1604, 1516 (C55C,
1
C55N ring) cm21. H NMR (300 MHz, CDCl3): 1.35 (t, J ¼ 7.2 Hz 3H,
OCH2CH3), 4.29 (q, 2H, OCH2CH3), 5.75 (br S, 2H, NH2), 7.30–7.90
(m, 10H, Ar-H). MS (EI): m/z ¼ 335 (Mþ). Anal. calcd. for C19H17N3O3
(335.36): C, 68.05; H, 5.11; N, 12.53. Found: C, 68.12; H, 5.27; N, 12.45.
Diethyl 4-Amino-1-phenyl-1H-pyrazole-3,5-dicarboxylate (3i)[1a]
IR (KBr): n ¼ 3520, 3410 (NH), 1730, 1712 (C55O), 1612, 1504 (C55C,
C55N ring) cm21
.
1H NMR (300 MHz, CDCl3): 1.14–1.42 (t ꢀ 2, 6H,
OCH2CH3), 4.17–4.48 (q ꢀ 2, 4H, OCH2CH3), 5.47 (br S, 2H, NH2),
7.12–7.21 (m, 5H, Ar-H). MS (EI): m/z ¼ 303 (Mþ). Anal. calcd. for
C15H17N3O4 (303.31): C, 59.40; H, 5.65; N, 13.85. Found: C, 59.55; H,
5.58; N, 13.93.
Diethyl 4-Amino-1-(3-chlorophenyl)-1H-pyrazole-3,5-dicarboxylate (3j)
IR (KBr): n ¼ 3510, 3380 (NH), 1732, 1696 (C55O), 1604, 1516 (C55C,
C55N ring) cm21
.
1H NMR (300 MHz, CDCl3): 1.14–1.41 (t ꢀ 2, 6H,
OCH2CH3), 4.17–4.47 (q ꢀ 2, 4H, OCH2CH3), 5.50 (br S, 2H, NH2),
7.21–7.28 (m, 4H, Ar-H). MS (EI): m/z ¼ 337 (Mþ). Anal. calcd. for
C15H16ClN3O4 (337.76): C, 53.34; H, 4.77; N, 12.44. Found: C, 53.29; H,
4.70; N, 12.35.
Diethyl 4-Amino-1-(4-chlorophenyl)-1H-pyrazole-3,5-dicarboxylate (3k)
IR (KBr): n ¼ 3520, 3400 (NH), 1712, 1696 (C55O), 1604, 1516 (C55C,
C55N ring) cm21
.
1H NMR (300 MHz, CDCl3): 1.12–1.40 (t ꢀ 2, 6H,
OCH2CH3), 4.14–4.45 (q ꢀ 2, 4H, OCH2CH3), 5.47 (br S, 2H, NH2),
7.16–7.27 (m, 4H, Ar-H). MS (EI): m/z ¼ 337 (Mþ). Anal. calcd. for

324
N. D. Desai and R. D. Shah
C15H16ClN3O4 (337.76): C, 53.34; H, 4.77; N, 12.44. Found: C, 53.44; H,
4.98; N, 12.51.
Diethyl 4-Amino-1-(4-fluorophenyl)-1H-pyrazole-3,5-dicarboxylate (3l)
IR (KBr): n ¼ 3510, 3380 (NH), 1732, 1696 (C55O), 1604, 1516 (C55C,
C55N ring) cm21
.
1H NMR (300 MHz, CDCl3): 1.15–1.43 (t ꢀ 2, 6H,
OCH2CH3), 4.18–4.49 (q ꢀ 2, 4H, OCH2CH3), 5.53 (br S, 2H, NH2),
7.18–7.25 (m, 4H, Ar-H). MS (EI): m/z ¼ 321 (Mþ). Anal. calcd. for
C15H16FN3O4 (321.3): C, 56.07; H, 5.02; N, 13.08. Found: C, 56.19; H,
4.92; N, 12.95.
Diethyl4-Amino-1-(4-methoxyphenyl)-1H-pyrazole-3,5-dicarboxylate(3m)
IR (KBr): n ¼ 3490, 3390 (NH), 1724, 1704 (C55O), 1604, 1516 (C55C,
C55N ring) cm21
.
1H NMR (300 MHz, CDCl3): 1.16–1.49 (t ꢀ 2, 6H,
OCH2CH3), 3.78 (s, 3H, OCH3), 4.20–4.52 (q ꢀ 2, 4H, OCH2CH3), 5.51
(br S, 2H, NH2), 7.20–7.31 (m, 4H, Ar-H). MS (EI): m/z ¼ 333 (Mþ).
Anal. calcd. for C16H19N3O5 (333.34): C, 57.65; H, 5.75; N, 12.61. Found:
C, 57.50; H, 5.74; N, 12.69.
Diethyl 4-Amino-1-(4-methylphenyl)-1H-pyrazole-3,5-dicarboxylate (3n)
IR (KBr): n ¼ 3510, 3410 (NH), 1732, 1712 (C55O), 1604, 1516 (C55C,
C55N ring) cm21
.
1H NMR (300 MHz, CDCl3): 1.14–1.43 (t ꢀ 2, 6H,
OCH2CH3), 2.40 (s, 3H, CH3), 4.17–4.47 (q ꢀ 2, 4H, OCH2CH3), 5.47 (br
S, 2H, NH2), 7.19–7.27 (m, 4H, Ar-H). MS (EI): m/z ¼ 317 (Mþ). Anal.
calcd. for C16H19N3O4 (317.34): C, 60.56; H, 6.03; N, 13.24. Found: C,
60.72; H, 5.93; N, 13.44.
Diethyl 4-Amino-1-(3-chloro-4-fluorophenyl)-1H-pyrazole-3,5-
dicarboxylate (3o)
IR (KBr): n ¼ 3500, 3400 (NH), 1716, 1696 (C55O), 1604, 1516 (C55C,
C55N ring) cm21
.
1H NMR (300 MHz, CDCl3): 1.12–1.41 (t ꢀ 2, 6H,
OCH2CH3), 4.16–4.48 (q ꢀ 2, 4H, OCH2CH3), 5.41 (br S, 2H, NH2),
7.16–7.27 (m, 3H, Ar-H). MS (EI): m/z ¼ 355 (Mþ). Anal. calcd. for
C15H15ClFN3O4 (355.75): C, 50.64; H, 4.25; N, 11.81. Found: C, 50.44; H,
4.08; N, 12.01.
ACKNOWLEDGMENT
We thank the Regional Sophisticated Instrumentation Center, Central Drug
1
Research Institute, Lucknow and Chandigarh, India, for H NMR and mass

Synthesis of 4-Amino-1-arylpyrazole
325
spectral analysis and the principal and director of the Loyola Center for R & D,
St. Xavier’s College, Ahmedabad, India, for the facility to carry out this work.
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