Iodobenzene diacetate mediated oxidation of N-substituted hydrazones of chalcones: An efficient regioselective synthesis of 1,3,5-trisubstituted pyrazoles

Article abstract of DOI:10.1080/00397910802640038

Iodobenzene diacetate, a relatively benign nonmetallic oxidant, has been utilized efficiently for the oxidation of N-substituted hydrazones of chalcones to afford 1,3,5-trisubstituted pyrazoles under mild reaction conditions.

Full text of DOI:10.1080/00397910802640038

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Iodobenzene Diacetate
Mediated Oxidation of N-
Substituted Hydrazones
of Chalcones: An Efficient
Regioselective Synthesis of
1,3,5-Trisubstituted Pyrazoles
Ranjana Aggarwal a & Rajiv Kumar a
a Department of Chemistry , Kurukshetra University ,
Kurukshetra, Haryana, India
Published online: 12 May 2009.
To cite this article: Ranjana Aggarwal & Rajiv Kumar (2009) Iodobenzene Diacetate
Mediated Oxidation of N-Substituted Hydrazones of Chalcones: An Efficient
Regioselective Synthesis of 1,3,5-Trisubstituted Pyrazoles, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry,
39:12, 2169-2177, DOI: 10.1080/00397910802640038
To link to this article: http://dx.doi.org/10.1080/00397910802640038
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Synthetic Communications1, 39: 2169–2177, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802640038
Iodobenzene Diacetate Mediated Oxidation
of N-Substituted Hydrazones of Chalcones:
An Efficient Regioselective Synthesis
of 1,3,5-Trisubstituted Pyrazoles
Ranjana Aggarwal and Rajiv Kumar
Department of Chemistry, Kurukshetra University, Kurukshetra,
Haryana, India
Abstract: Iodobenzene diacetate, a relatively benign nonmetallic oxidant, has
been utilized efficiently for the oxidation of N-substituted hydrazones of
chalcones to afford 1,3,5-trisubstituted pyrazoles under mild reaction conditions.
Keywords: Iodobenzene diacetate, oxidative cyclization, regioselective, N-
substituted hydrazones of chalcones, 1,3,5-trisubstituted pyrazoles
INTRODUCTION
Generally, regioselective synthesis of 1,3,5-trisubstituted pyrazoles are
accomplished by the oxidation of 4,5-dihydropyrazoles, obtained by con-
densation of hydrazines with chalcone derivatives using a number of oxi-
dizing agents.[1–4] But the versatility of this reaction is somewhat limited
because the hydrazines with electron-withdrawing groups such as 4-
nitrophenyl and 2,4-dinitrophenyl do not cyclize to 4,5-dihydropyrazoles;
instead, formation of corresponding hydrazones has been witnessed even
in strongly acidic conditions.[5] Cyclization of these hydrazones to 4,5-
dihydropyrazoles has been achieved only in an extremely strong acidic
medium (HBr-AcOH).[6] Oxidative cyclization of aryl hydrazones of
Received July 28, 2008.
Address correspondence to Ranjana Aggarwal, Department of Chemistry,
Kurukshetra University, Kurukshetra 136 119, Haryana, India. E-mail:
ranjana67in@yahoo.com
2169

2170
R. Aggarwal and R. Kumar
chalcones to pyrazoles has been induced using lead tetraacetate,[1] mange-
nese dioxide,[2] thianthrene cation radical,[7] and anodic oxidation.[8] We
herein report oxidative transformation of N-substituted hydrazones of
chalcones 3 to 1,3,5-trisubstituted pyrazoles 4 with iodobenzene diacetate
(IBD) that leads to the expeditious formation of the title compounds in
excellent yields.
RESULTS AND DISCUSSION
Synthesis of 1,3,5-trisubstituted pyrazoles 4 is depicted in Scheme 1. The
key intermediates, hydrazones 3, were prepared in varying yields by con-
densation of N-substituted hydrazines 2 with appropriately substituted
chalcones 1 in refluxing ethanol containing two or three drops of acetic
acid. Efforts to cyclize the hydrazones 3 to the corresponding 4,5-
dihydropyrazoles failed in high-boiling solvents such as dimethylforma-
mide (DMF) and dimethyl sulfoxide (DMSO) and also by conventional
methods (i.e., refluxing in EtOH=AcOH–EtOH=glacial AcOH). Subse-
quently, oxidative intramolecular cyclization of hydrazones 3 with 1.2
equivalents of IBD in dichloromethane furnished the corresponding pyr-
azoles 4 but in small yields. The optimum yields of the products were
obtained when 1.5 equivalents of IBD were used. It is worth mentioning
here that the reaction between 2-hydrazino-3-methylquinoxaline with
unsymmetrical aryl- and heteroaryl diketones to achieve the title com-
pounds resulted in the formation of isomeric pyrazoles as the major
products, along with formation of triazolo[4,3-a]quinoxaline.[9]
Formation of hydrazones 3 and pyrazoles 4 was confirmed on the
basis of their IR, NMR (1H, 13C, 19F), elemental analysis, and mass
spectrometry (MS) data. In IR, 3 showed a characteristic absorption
Scheme 1. Synthesis of 1,3,5-trisubstituted pyrazoles.

Synthesis of 1,3,5-Trisubstituted Pyrazoles
2171
band for NH group at ꢀ3350 cmꢁ1 and two bands at ꢀ1600 and
1
ꢀ1550 cmꢁ1 due to the C¼C and C¼N stretch. The H NMR of 3d–h
exhibited two doublets of one proton intensity each at around d 6.8
and 8.1 (Jtrans ¼ 16.5 Hz) due to the trans olefinic protons, whereas in case
of chalcones 1, the corresponding protons resonated at about d 7.5 and
7.8 (J ¼ 15.6 Hz). In 13C NMR of 3, two olefinic carbons resonated at
1
113 and 139 Hz. H NMR of pyrazoles 4 showed the disappearance of
both olefinic protons rather a singlet of one proton intensity correspond-
ing to pyrazole 4-H was observed at about d 6.85. Also, in 13C NMR, C-4
carbon of pyrazole resonated at d 104 Hz, indicating the formation of
pyrazole. The known compounds were confirmed by comparison of their
melting points with those reported in the literature.[8]
It is quite likely that the reaction mechanism does not involve the
intermediacy of 4,5-dihydropyrazoles because no trace of them has been
detected in the reaction mixture. Moreover, the reaction requires only 1.5
equivalents of IBD to transform 3 into 4. Had the dihydropyrazoles
been the intermediate, the reaction would have consumed more than 2
equivalents of IBD.
CONCLUSION
In conclusion, we have developed a general, practical, and efficient pro-
cedure for the regioselective synthesis of 1,3,5-trisubstituted pyrazoles
using IBD as an oxidizing agent. The present protocol has several advan-
tages: mild reaction conditions, operational and experimental simplicity,
optimum yields, and use of an ecofriendly reagent.
EXPERIMENTAL
The IR spectra of the compounds were recorded on a Buck Scientific IR
1
M-500 spectrophotometer using KBr pellets (nmax in cmꢁ1); H and 13C
NMR spectra were measured on a Bruker instrument at 300 and 75 MHz,
respectively. Chemical shifts are expressed in d-scale downfield from
tetramethylsilane (TMS) as an internal standard.
Typical Procedure for the Preparation of Chalcone Hydrazone 3
Chalcone 1 (0.1 mmol) was added to a solution of hydrazine 2 (0.1 mmol)
in ethanol (20 ml). The solution was warmed, and then two or three drops
of acetic acid were added to it. It was refluxed for 6 h. The progress of the

2172
R. Aggarwal and R. Kumar
reaction was monitored by thin-layer chromatography (TLC). A yellow
solid separated out during refluxing. The reaction mixture was cooled;
the solid thus separated was filtered, washed with cold ethanol, and
recrystallized from ethanol to give 3. All the hydrazones (3d–h) were
prepared following this procedure.
Data for 3
4-Nitrophenyl Hydrazone of 1-(Phenyl)-3-(p-fluorophenyl)propenone 3a
Yield 56%; mp 128ꢂC. MS m=z 361 (Mþ). Anal. calcd. for
C21H16FN3O2: found C, 69.78; H, 4.25; N, 11.69, required C, 69.80; H,
1
4.46; N, 11.63. IR (KBr): 3355, 1597, 1552 cmꢁ1; H NMR (300 MHz,
CDCl3): d 6.29 (d, J ¼ 16.8 Hz, 1H, 2-H), 7.03–7.06 (m, 3H, 20, 60, 4000-
H), 7.17 (d, J ¼ 16.8 Hz, 1H, 3-H), 7.33–7.90 (m, 8H, 200, 300, 500, 600, 2000,
3000, 5000, 6000-H), 8.16 (d, 2H, 30, 50-H, J ¼ 8.7 Hz); 13C NMR (75 MHz,
CDCl3): d 112.30, 116.68 (d, 2JC-F ¼ 21.75 Hz), 124.53, 125.89 (d, 3JC-F
¼
8.25 Hz), 126.58, 128.81, 128.98, 130.02, 130.66, 130.77, 132.31, 144.65,
1
151.09, 153.36, 158.52 (d, JC-F ¼ 240.5 Hz).
4-Benzoyl Hydrazone of 1-(Phenyl)-3-(p-chlorophenyl)propenone 3c
Yield 65%; mp 120ꢂC. MS m=z 360 (Mþ), 362 (M þ 2). Anal. calcd. for
C22H17ClN2O: found C, 73.12; H, 4.55; N, 7.58, required C, 73.23; H,
4.75; N, 7.76. IR (KBr): 3354, 1643, 1600, 1575 cmꢁ1 1H NMR
;
(300 MHz, CDCl3): d 6.40 (d, J ¼ 16.5 Hz, 1H, 2-H), 7.293–7.41 (m,
9H, 200, 300, 500, 600, 2000, 3000, 4000, 5000, 6000-H), 7.48–7.66 (m, 6H, 3, 20, 30, 40,
50, 60-H); 13C NMR (75 MHz, CDCl3): d 122.51, 128.20, 128.33, 128.49,
128.67, 129.02, 129.25, 129.58, 129.96, 130.33, 133.39, 134.50, 138.04,
143.30, 158.6, 170.5.
3-Methylquinoxalin-2-yl Hydrazone of 1-Phenyl-3-
(p-chlorophenyl)propenone 3d
Yield 78%; mp 138ꢂC. MS m=z 398 (Mþ), 400 (M þ 2). Anal. calcd. for
C24H19ClN4: found C, 72.15; H, 4.75; N, 13.65; required C, 72.27; H,
1
4.80; N, 14.05, IR (KBr): 3351, 1592, 1550 cmꢁ1; H NMR (300 MHz,
CDCl3) d: 2.58 (s, 3H, CH3), 6.83 (d, J ¼ 16.5 Hz, 1H, 2-H), 6.91–7.09
(m, 2H, 60, 70-H), 7.21–7.25 (m, 3H, 80, 300, 500-H), 7.38–7.43 (m, 5H, 200,
600, 2000, 4000, 6000-H), 7.56–7.60 (m, 3H, 50, 3000, 5000-H), 8.04 (d, J ¼ 16.5 Hz,
1H, 3-H);13C NMR (75 MHz, CDCl3): d 21.04, 113.05, 119.98, 121.82,

Synthesis of 1,3,5-Trisubstituted Pyrazoles
2173
127.44, 127.85, 128.02, 128.06, 128.23, 128.48, 128.64, 129.13, 129.99,
133.90, 133.97, 136.40, 139.41, 142.30, 158.52, 162.04.
3-Methylquinoxalin-2-yl Hydrazone of 1-(p-Fluorophenyl)-
3-phenylpropenone 3e
Yield 78%; mp 132ꢂC. MS m=z 382 (Mþ). Anal. calcd. for C24H19FN4:
found C, 75.25; H, 4.95; N, 14.34; required C, 75.37; H, 5.01; N, 14.65;
1
IR (KBr): 3364, 1598, 1553 cmꢁ1; H NMR (300 MHz, CDCl3) d: 2.65
(s, 3H, CH3), 6.92 (d, J ¼ 16.5 Hz, 1H, 2-H), 6.99–7.20 (m, 4H, 60, 70,
3000, 5000-H), 7.28–7.41 (m, 4H, 80, 200, 400, 600-H), 7.52–7.55 (m, 2H, 300,
500-H), 7.64–7.69 (m, 3H, 50, 2000, 6000-H), 8.11 (d, J ¼ 16.5 Hz, 1H, 3-H);
19F NMR (CDCl3) d: ꢁ111.89; 13C NMR (75 MHz, CDCl3): d 21.04,
2
114.30, 115.58 (d, JC-F ¼ 21.7 Hz), 120.87, 123.08, 127.32, 127.85,
3
128.70, 129.12, 129.45, 129.54, 131.55 (d, JC-F ¼ 8.25 Hz), 133.59, 134.39,
1
136.81, 140.15, 145.72, 158.51, 163.77 (d, JC-F ¼ 247.5 Hz), 162.32.
3-Methylquinoxalin-2-yl Hydrazone of 1-(p-Fluorophenyl)-
3-(p-methoxyphenyl) Propenone 3f
Yield 82%; mp 144ꢂC. MS m=z 412 (Mþ). Anal. calcd. for C25H21FN4O:
found C, 72.78; H, 5.01; N, 14.20; required C, 72.80; H, 5.13; N, 13.58. IR
1
(KBr): 3365, 1602, 1561 cmꢁ1; H NMR (300 MHz, CDCl3) d: 2.65 (s,
3H, CH3), 3.84 (s, 3H, OCH3), 6.82 (d, J ¼ 16.5 Hz, 1H, 2-H), 6.91 (d,
J ¼ 8.7 Hz, 2H, 300, 500-H), 7.02–7.20 (m, 4H, 60, 70, 3000, 5000-H), 7.26–7.31
(m, 1H, 80-H), 7.48 (d, J ¼ 8.7 Hz, 2H, 200, 600-H), 7.63–7.68 (m, 3H,
50, 2000, 6000-H), 7.99 (d, J ¼ 16.5 Hz, 1H, 3-H); 19F NMR (CDCl3)
d: ꢁ112.10; 13C NMR (75 MHz, CDCl3): d 21.08, 55.35, 113.91,
114.31, 115.23 (d, 2JC-F ¼ 21.7 Hz), 118.42, 122.65, 128.40, 129.06, 129.29,
3
4
130.99, 131.29 (d, JC-F ¼ 8.25 Hz), 133.25, 134.30, 134.32 (d, JC-F
¼
3 Hz), 139.64, 145.30. 158.57, 160.65, 162.31, 163.40 (d, 1JC-F ¼ 246.7 Hz).
3-Methylquinoxalin-2-yl Hydrazone of 1-(p-Fluorophenyl)-
3-(p-methylphenyl) Propenone 3g
Yield 83%; mp 134ꢂC. MS m=z 396 (Mþ), Anal. calcd. for C25H21FN4:
found C, 75.78; H, 5.25; N, 14.62; required C, 75.74; H, 5.34; N, 14.13,
1
IR (KBr): 3354, 1596, 1549 cmꢁ1; H NMR (300 MHz, CDCl3) d: 2.38
(s, 3H, CH3) 2.65 (s, 3H, CH3), 6.98 (d, J ¼ 16.5 Hz, 1H, 2-H), 7.02–
7.20 (m, 6H, 60, 70, 300, 500, 3000, 5000-H), 7.26–7.31 (m, 1H, 80-H), 7.43 (d,
J ¼ 8.1 Hz, 2H, 200, 600-H), 7.64–7.69 (m, 3H, 50, 2000, 6000-H), 8.08 (d,

2174
R. Aggarwal and R. Kumar
J ¼ 16.5 Hz, 1H, 3-H); 19F NMR (CDCl3) d: ꢁ112.01; 13C NMR
2
(75 MHz, CDCl3): d 21.10, 21.40, 113.93, 115.26 (d, JC-F ¼ 21.7 Hz),
3
119.59, 122.70, 127.54, 128.42, 129.11, 129.56, 130.93, 131.29 (d, JC-F
8.25 Hz), 133.27, 133.77, 134.22, 139.95, 139.51, 145.37, 158.57, 162.17,
1
163.54 (d, JC-F ¼ 245.0 Hz).
¼
3-Methylquinoxalin-2-yl Hydrazone of 1-(p-Fluorophenyl)-
3-(p-chlorophenyl) Propenone 3h
Yield 75%; mp 156ꢂC. MS m=z 416 (Mþ), 418 (M þ 2). Anal. calcd. for
C24H18ClFN4: found C, 69.36; H, 4.25; N, 13.69; required C, 69.15; H,
1
4.35; N, 13.44. IR (KBr): 3362, 1598, 1559 cmꢁ1; H NMR (300 MHz,
CDCl3) d: 2.67 (s, 3H, CH3), 6.88 (d, J ¼ 16.5 Hz, 1H, 2-H), 7.03–7.23
(m, 4H, 60, 70, 3000, 5000-H), 7.32–7.34 (m, 1H, 80-H), 7.37 (d, J ¼ 8.4 Hz,
2H, 300, 500-H), 7.48 (d, J ¼ 8.4 Hz, 2H, 200, 600-H), 7.66–7.69 (m, 3H, 50,
2000, 6000-H), 8.11 (d, J ¼ 16.5 Hz, 1H, 3-H); 19F NMR (CDCl3) d:
ꢁ111.74; 13C NMR (75 MHz, CDCl3): d 21.10, 113.98, 115.35 (d, 2JC-F
¼
21.0 Hz), 121.04, 122.84, 128.47, 128.67, 129.05, 129.19, 130.81, 131.23
3
(d, JC-F ¼ 8.25 Hz), 133.31, 134.01, 134.96, 135.06, 138.23, 145.54,
1
158.39, 161.50, 163.43 (d, JC-F ¼ 240.0 Hz).
General Procedure for the Preparation of Pyrazole
4 from Chalcone Hydrazone 3
Iodobenzene diacetate (0.48 g, 0.0015 mol) in portions was added to a
solution of 3 (0.001 mol) in dichloromethane (20 ml) over a period of
10 min. The resulting mixture was allowed to stir for 6 h at room tempera-
ture. The progress of reaction was monitored with the help of TLC.
When the reaction was complete, excess solvent was distilled off in a
vacuum to give a gummy residue containing the product and iodoben-
zene. The residue was triturated with petroleum ether to remove iodoben-
zene; a yellow compound was obtained, which was recrystallized from
methanol to give 4.
Data for 4
3-Phenyl-1-(4-nitrophenyl)-5-(p-fluorophenyl)pyrazole 4a
Yield 69%; mp 110ꢂC. MS m=z 359 (Mþ). Anal. calcd. for
C21H14FN3O2: found C, 67.18; H, 3.55; N, 12.01; required C, 67.12; H,
3.75; N, 11.69. IR (KBr): 1497, 1445 cmꢁ1; 1H NMR (300 MHz, CDCl3):

Synthesis of 1,3,5-Trisubstituted Pyrazoles
2175
d 6.86 (s, 1H, 4-H), 7.10–8.44 (m, 13H, 20, 30, 50, 60, 200, 300, 500, 600, 2000, 3000,
4000, 5000, 6000-H); 13C NMR (75 MHz, CDCl3): d 102.41, 116.45 (d,
3
2JC-F ¼ 21.75 Hz), 124.17, 124.52, 125.91, 128.60, 128.68 (d, JC-F
¼
7.5 Hz), 130.67, 131.96, 132.07, 138.62, 144.61, 146.71, 150.72, 158.92
1
(d, JC-F ¼ 240.7 Hz).
3-Phenyl-1-benzoyl-5-(p-chlorophenyl)pyrazole 4c
Yield 58%; mp 137ꢂC. MS m=z 358 (Mþ), 360 (M þ 2). Anal. calcd. for
C22H15ClN2O: found C, 73.56; H, 4.13; N, 7.67; required C, 73.64; H,
1
4.21; N, 7.81. IR (KBr): 1496, 1453 cmꢁ1; H NMR (300 MHz, CDCl3)
d 6.93 (s, 1H, 4-H), 7.23–7.41 (m, 9H, 200, 300, 500, 600, 2000, 3000, 4000, 5000,
6000-H), 7.87–7.97 (m, 5H, 20, 30,40, 50, 60-H); 13C NMR (75 MHz, CDCl3):
d 103.41, 127.40, 128.45, 128.65, 129.01, 129.07, 129.44, 129.73, 133.82,
134.35, 134.68, 136.51, 136.78, 142.32, 152.2, 180.2.
3-Phenyl-1-(3-methylquinoxalin-2-yl)-5-(p-chlorophenyl)pyrazole 4d
Yield 56%; mp 145ꢂC. MS m=z 396 (Mþ), 398 (M þ 2). Anal. calcd. for
C24H17ClN4: found C, 72.66; H, 4.26; N, 14.24; required C, 72.63; H,
1
4.32; N, 14.12. IR (KBr): 1497, 1452 cmꢁ1; H NMR (300 MHz, CDCl3)
d: 2.6 (s, 3H, CH3), 6.9 (s, 1H, 4-H), 7.16–7.28 (m, 4H, 200, 300, 400, 500-H),
7.33–7.42 (m, 5H, 2000, 3000, 4000, 5000, 6000-H), 7.67–7.74 (m, 2H, 60, 70-H),
7.85–8.01(m, 2H, 50, 80-H); 13C NMR (75 MHz, CDCl3): d 29.68,
104.9, 126.01, 127.79, 128.51, 128.72, 128.94, 129.05, 129.45, 130.00,
130.13, 130.83, 130.98, 131.09, 135.32, 139.54, 139.70, 142.05, 151.43,
153.10.
3-(p-Fluorophenyl)-1-(3-methylquinoxalin-2-yl)-5-phenylpyrazole 4e
Yield 65%; mp 158ꢂC. MS m=z 380 (Mþ). Anal. calcd. for C24H17FN4:
found C, 75.74; H, 4.65; N, 14.60; required C, 75.77; H, 4.50; N, 14.73.
IR (KBr): 1487, 1442 cmꢁ1 1H NMR (300 MHz, CDCl3) d: 2.47 (s,
;
3H, CH3), 6.84 (s, 1H, 4-H), 7.04–7.09 (m, 2H, 3000, 5000-H), 7.19 (m,
5H, 200, 300, 400, 500, 600-H), 7.60–7.77 (m, 2H, 60, 70-H), 7.82–7.87 (m,
2H, 2000, 6000-H), 7.94–8.02 (m, 2H, 50, 80-H); 19F NMR (CDCl3)
d: ꢁ113.51; 13C NMR (75 MHz, CDCl3): d 21.60, 104.36, 115.62 (d,
3
4
2JC-F ¼ 21.75 Hz), 127.75 (d, JC-F ¼ 7.5 Hz), 128.69 (d, JC-F ¼ 3.75 Hz),
128.13, 128.29, 128.30, 128.93, 129.22, 129.62, 129.89, 130.25, 139.86,
142.12, 146.78, 146.84, 151.98, 152.47, 162.96 (d, JC-F ¼ 249 Hz).
1

2176
R. Aggarwal and R. Kumar
3-(p-Fluorophenyl)-1-(3-methylquinoxalin-2-yl)-5-(p-methoxyphenyl)-
pyrazole 4f
Yield 62%; mp 148ꢂC. MS m=z 410 (Mþ). Anal. calcd. for C25H19FN4O:
found C, 73.02; H, 4.72; N, 14.05; required C, 73.16; H, 4.67; N, 13.65. IR
1
(KBr): 1489, 1450 cmꢁ1; H NMR (300 MHz, CDCl3) d: 2.50 (s, 3H,
CH3), 3.75 (s, 3H, OCH3), 6.77 (d, J ¼ 7.8 Hz, 2H, 300, 500-H), 6.84 (s,
1H, 4-H), 7.13–7.27 (m, 4H, 200, 600, 3000, 5000-H), 7.76–7.82 (m, 2H, 60,
70-H), 7.92–7.94 (m, 2H, 2000, 6000-H), 8.08–8.11 (m, 2H, 50, 80-H); 19F
NMR (CDCl3) d: ꢁ113.70; 13C NMR (75 MHz, CDCl3): d 21.50, 55.20,
2
3
103.69, 114.20, 115.56 (d, JC-F ¼ 21.75 Hz), 121.99, 127.72 (d, JC-F
¼
4
7.5 Hz), 128.36, 129.02 (d, JC-F ¼ 3.75 Hz), 129.28, 129.45, 129.86,
130.85, 139.95, 142.13, 146.64, 146.72, 152.10, 152.42, 159.87, 163.05
1
(d, JC-F ¼ 247.5 Hz).
3-(p-Fluorophenyl)-1-(3-methylquinoxalin-2-yl)-5-(p-methylphenyl)-
pyrazole 4g
Yield 67%; mp 138ꢂC. MS m=z 394 (Mþ). Anal. calcd. for C25H19FN4:
found C, 76.15; H, 4.68; N, 14.38; required C, 76.12; H, 4.86; N, 14.20.
1
IR (KBr): 1494, 1455 cmꢁ1; H NMR (300 MHz, CDCl3) d: 2.29(s, 3H,
CH3), 2.51 (s, 3H, CH3), 6.89 (s, 1H, 4-H), 7.05–7.10 (m, 2H, 3000,
5000-H), 7.11–7.18 (m, 4H, 200, 300, 500, 600-H), 7.75–7.86 (m, 2H, 60, 70-H),
7.90–7.95 (m, 2H, 2000, 6000-H), 8.10–8.11 (m, 2H, 50, 80-H); 19F NMR
(CDCl3) d: ꢁ113.64; 13C NMR (75 MHz, CDCl3): d 18.97, 18.62,
2
3
101.43, 113.04 (d, JC-F ¼ 21 Hz), 125.19 (d, JC-F ¼ 8.25 Hz), 125.42,
125.82, 126.1, 126.4, 126.75, 126.90, 127.32, 128.31, 136.2, 137.3, 137.4,
1
138.9, 144.4, 149.9, 150.1, 162.05 (d, JC-F ¼ 232.5 Hz).
3-(p-Fluorophenyl)-1-(3-methylquinoxalin-2-yl)-5-(p-chlorophenyl)-
pyrazole 4h
Yield 72%; mp 165ꢂC. MS m=z 414 (Mþ), 416 (M þ 2). Anal. calcd. for
C24H16ClFN4: found C, 69.78; H, 3.99; N, 14.04; required C, 69.48; H,
1
3.89; N, 13.50. IR (KBr): 1498, 1456 cmꢁ1; H NMR (300 MHz, CDCl3)
d: 2.53 (s, 3H, CH3), 6.82 (s, 1H, 4-H), 7.04–7.09 (m, 2H, 3000, 5000-H), 7.15–
7.20 (m, 4H, 200, 300, 500, 600-H), 7.65–7.78 (m, 2H, 60, 70-H), 7.81–7.86 (m,
2H, 2000, 6000-H), 7.90–8.04 (m, 2H, 50, 80-H); 19F NMR (CDCl3) d:
ꢁ113.27;13C NMR (75 MHz, CDCl3): d 20.73, 103.67, 114.68 (d,
3
2JC-F ¼ 21.75 Hz), 126.75 (d, JC-F ¼ 7.5 Hz), 127.17, 127.42, 127.70,
127.98, 128.14, 128.45, 129.05, 129.99, 133.7, 138.6, 141.13, 144.6,
1
145.4, 150.7, 151.9, 162.95 (d, JC-F ¼ 232.5 Hz).

Synthesis of 1,3,5-Trisubstituted Pyrazoles
ACKNOWLEDGMENTS
2177
We thank the Council of Scientific and Industrial Research, New Delhi,
for financial assistance and a junior research fellowship to Rajiv Kumar.
Thanks are also due to Regional Sophisticated Analytical Instrumenta-
tion Facility, Central Drug Research Institute, Lucknow, India, for
providing 19F NMR spectra, mass spectrometry, and elemental analysis.
We also thank Professor S. P. Singh for helpful suggestions.
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