Convenient Synthesis of Polyaza-3,4-bis(heteroaryl)pyrazoles

Article abstract of DOI:10.1080/00397911.2011.589039

GRAPHICAL ABSTRACT Reactions of a new series of bis-enaminones with some N- and C-nucleophiles proved to be convenient routes for syntheses of a variety of novel 3,4-bis(heteroaryl)pyrazoles. The structures of the compounds were elucidated on the basis of

Full text of DOI:10.1080/00397911.2011.589039

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Convenient Synthesis of Polyaza-3,4-
bis(heteroaryl)pyrazoles
Ahmad S. Shawalia & Adel J. M. Habouba
a Department of Chemistry, Faculty of Science, University of Cairo,
Giza, Egypt
Accepted author version posted online: 20 Jan 2012.Published
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Synthetic Communications1, 0: 1–14, 2015
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.589039
CONVENIENT SYNTHESIS OF
POLYAZA-3,4-BIS(HETEROARYL)PYRAZOLES
Ahmad S. Shawali and Adel J. M. Haboub
Department of Chemistry, Faculty of Science, University of Cairo,
Giza, Egypt
GRAPHICAL ABSTRACT
Abstract Reactions of a new series of bis-enaminones with some N- and C-nucleophiles
proved to be convenient routes for syntheses of a variety of novel 3,4-bis(heteroaryl)
pyrazoles. The structures of the compounds were elucidated on the basis of their spectral
and elemental analyses and by alternative synthesis wherever possible.
Keywords Enaminones; heterocycles; hydrazonoyl halides; pyrazoles
INTRODUCTION
Enaminones I have been extensively studied by numerous research groups all
over the world because they have proved to be versatile precursors for syntheses
of many heterocycles. At present, there are several review articles covering the vari-
ous aspects of their chemistry.[1] In contrast, bis-enaminones of the general formula
II, especially where R is a heteroaryl moiety, have received much less attention.[2] In
conjunction with our recent work[3] on heteroaryl-enaminones derived from hydra-
zonoyl halides, we extended our studies to explore the utility of such halides as pre-
cursors for synthesis of ter-heterocycles of type III, which have not been reported
hitherto. The interest in synthesis of such ter-heterocycles is because many synthetic
pyrazole derivatives have found uses in pharmaceutical, agrochemical, and photo-
graphic fields.[4–6] In this article, we report the results of our study of the reactions
=
of the bis-enaminones IV (R CH3; Ar ¼ XC5H4) with some N- and C-nucleophiles
(Chart 1).
Received April 25, 2011.
Address correspondence to Ahmad S. Shawali, Department of Chemistry, Faculty of Science,
University of Cario, Giza, Egypt. E-mail: as_shawali@mail.com
1

2
A. S. SHAWALI AND A. J. M. HABOUB
Chart 1.
RESULTS AND DISCUSSION
The precursor bis-enaminones 4 were prepared by condensation of the respect-
ive 3,4-bis(acetyl)pyrazole derivatives 3, each with dimethylformamide dimethylace-
tal (DMF-DMA), as previously described from our laboratory (Scheme 1).[7]
When each of the bis-enaminones 4a–c was refluxed with hydroxylamine
hydrochloride in ethanol in the presence of ammonium acetate, it yielded a single
product identified as the respective 3,4-bis(isoxazol-3-yl)pyrazole 6 rather than its
bis(isoxazol-5-yl)pyrazole 8 (Scheme 2). The assigned structure 6 was confirmed by
an alternative synthesis of 6b as a representative example of the series prepared.
Thus, reaction of the bis-oxime 9b, prepared from 3b and 2 equivalents of hydroxy-
lamine hydrochloride in refluxing ethanol in the presence of potassium hydroxide,
with DMF-DMA in refluxing xylene, gave a product that proved identical in all
respects to 6b isolated from reaction of 4b with hydroxylamine hydrochloride. On
the basis of this finding, the other isomeric structure 8 was discarded. The structures
1
of the products 6 were further established by their spectra. For example, their H
NMR spectra showed in each case two doublet signals near d 6.83 and 8.42 with
J ¼ 2.1 Hz assignable to the isoxazole ring protons, namely H-4 and H-5, respect-
Scheme 1.

POLYAZA-3,4-BIS(HETARYL) PYRAZOLES
3
Scheme 2.
ively. Their mass spectra showed, in addition to the molecular ion peak, a fragment
ion peak at m=z 68 corresponding to the isoxazolyl radical cation. To account for the
reformation of the products 6, it is assumed, as depicted in Scheme 2, that reaction of
4 with hydroxylamine starts with condensation to give 5 as intermediate, which
undergoes in situ cyclization via elimination of dimethylamine to give 6 as end pro-
ducts. This sequence is compatible with literature reports on reactions of hydroxyla-
mine hydrochloride with mono-enaminones, which afford the respective
isoxazol-3-yl derivatives.[8]
The bis-enaminones 4 reacted similarly with hydrazine hydrate and phenylhy-
drazine in refluxing ethanol to afford the respective 3,30:4,300-terpyrazoles 10 and 11
(Scheme 3). The structures of the latter products were elucidated on the basis of their
spectral and elemental analysis data. For example, their IR spectra revealed the
absence of the CO bands present in the spectra of the starting bis-enaminones 4.
In addition, the spectra of 10 revealed a broad NH band in the region n
1
3400–3200 cmꢀ1. Also, the H NMR spectra showed, in each case, two doublet sig-
nals in the regions d 6.39–6.42 and 7.66–7.82 with the same coupling constant
J ¼ 7 Hz assignable to H-4 and H-5 of the pyrazole ring residues, respectively. Simi-
larly, the 1H NMR spectra of the products 11a–c showed the signals of such protons
as two doublet signals near d 6.73 and 8.35 with the same coupling constant J ¼ 7 Hz.
Furthermore, the 1H NMR spectra of 10 exhibit a broad singlet (D2O-exchangeable)
at d 13.0 due to the NH proton resonance.

4
A. S. SHAWALI AND A. J. M. HABOUB
Scheme 3.
The reactivity of the bis-enaminones 4 toward 3-amino-1,2,4-triazole was next
examined to shed some light on its site selectivity, as such a reaction can theoretically
lead to either the 1,2,4-triazolo[1,5-a]pyrimidine 12 and=or its [4,3-a] isomer 13
(Scheme 4). In our hands, reaction of 4a–c with 3-amino-1,2,4-triazole in acetic acid
under reflux yielded, in each case, only one isolable product. The isolated products
were identified as 1,2,4-triazolo[1,5-a]pyrimidine derivatives 12a–c and not their
1
1,2,4-triazolo[4,3-a]pyrimidine isomers 13a–c on the basis of their H NMR spectra
1
(Scheme 4). For example, their H NMR spectra revealed in each case two doublet
signals near d 7.79 and 9.27 with J ¼ 9 Hz assignable to the two vicinal protons H-6
and H-7 of the pyrimidine ring residue in addition to a singlet signal at d 8.79 due to
the H-2 proton. Such assignments are consistent with literature reports on 1H NMR
spectra of 1,2,4-triazolo[1,5-a]pyrimidine and its [4,3-a] isomers.[9] To account for the
formation of the products 12, it is suggested that the studied reactions start with
Michael-type addition of the exocyclic NH2 group of the amine to the activated dou-
ble bond of 4 followed by in situ tandem elimination of dimethylamine and dehydra-
tive cyclization by condensation of the cyclic NH group with the enone moiety
(Scheme 4).
Next, we examined the reactions of bis-enaminones 4 with some C-nucleohiles.
In our hands, reaction of malononitrile with each of the enaminones 4a–c in reflux-
ing glacial acetic acid in the presence of ammonium acetate gave rise to a single
product that proved to be the corresponding 3,4-bis(5-cyano-6-oxo-1H-pyridin-2-
yl)-1-aryl-5-methylpyrazole 16 (Scheme 5). The structures of the latter products were

POLYAZA-3,4-BIS(HETARYL) PYRAZOLES
5
Scheme 4.
Scheme 5.

6
A. S. SHAWALI AND A. J. M. HABOUB
compatible with their spectral and elemental analytical data. Thus, their IR spectra
showed the presence of NH, CN, and CO group stretching bands near t 3310, 2221,
and 1658 cmꢀ1, respectively. The 1H NMR spectra revealed two doublet signals near
d 8.29 (d, 2H, J ¼ 8 Hz, pyridine-H-3) and 8.19 (2H, 2H, J ¼ 8 Hz, pyridine-H-4). In
addition, the spectra showed a singlet at d 12.5 due to the NH proton resonance. To
account for the formation of 16, it is suggested by analogy to reactions of malononi-
trile with mono-enaminones, that reaction of 4 with malononitrile starts with a
Michael addition to yield the respective adduct 14, followed by tandem in situ cycli-
zation and elimination of dimethylamine to give the iminopyran 15 as intermediate.
The latter isomerizes through Dimroth-type rearrangement under the reaction
conditions to afford 16 as end product.
The assigned structure 16 is further evidenced by an alternative synthesis of 16a
as an example of the series prepared. Thus, reaction of 4a with cyanoacetamide in
refluxing dry toluene afforded a product that proved identical in all respects with
that one obtained from reaction of 4a with malononitrile.
When a mixture of ethyl acetoacetate and each of the bis-enaminone 4a–c
was refluxed for 30 h in glacial acetic acid in the presence of ammonium acetate,
it yielded, in each case, a single product. Both elemental analyses and spectral
data (see Experimental) indicate that the products isolated are the respective 3,4-bis
[5-ethoxycarbonyl-6-methyl-pyrid-2-yl]-1-aryl-5-methylpyrazole 21a-c (Scheme 6).
Ethyl benzoyl acetate reacted similarly with each of 4a–c under the same reaction
Scheme 6.

POLYAZA-3,4-BIS(HETARYL) PYRAZOLES
7
conditions and afforded the respective 3,4-bis[5-ethoxycarbonyl-6-phenyl-pyrid-
2-yl]-1-aryl-5-methylpyrazoles 22a–c (Scheme 6). A reaction pathway that accounts
for the formation of the products 21 and 22 is depicted in Scheme 6. It involves initial
addition of the active methylene moiety to the activated double bond of 4 to afford
17(18) as intermediates that undergo elimination of dimethylamine to afford 19(20),
which in turn condenses with ammonium acetate to yield the respective
1
3,4-bis(pyridine-6-yl)pyrazoles 21(22) as end products (Scheme 3). The H NMR
spectra of both compounds 21 and 22 revealed, in addition to the characteristic sig-
nals for the protons of the aryl and COOCH2CH3 groups, signals at d 7.5–7.8
(d, J ¼ 9 Hz, 2H, pyridine-H-3) and 8.2–8.3 (d, J ¼ 9 Hz, 2H, pyridine-H-4), Com-
punds 21 also, exhibit, in each case, two singlet signals near d 2.88 (s, 6H, 2CH3)
and 2.79 (s, 3H, pyrazole-5-CH3).
CONCLUSION
The results of the present work indicate that the studied bis-enaminones
are useful precursors for the synthesis of different functionalized
3,4-bis-(hetaryl)pyrazoles through their reactions with the N- and C-nucleophiles.
In addition, they indicate that the studied reactions are regiospecific as they yielded,
in each case, one product. The ter-heterocycles prepared are expected to be of
pharmacological interest.
EXPERIMENTAL
Melting points were determined on an electrothermal Gallenkamp apparatus.
Solvents were generally distilled and dried by standard literature procedures prior to
use. The IR spectra were measured on a Pye-Unicam SP300 instrument in potassium
bromide discs. The 1H NMR spectra were recorded on a Varian Mercury
VXR300-MHz spectrometer and the chemical shifts d are downfield from tetra-
methylsilane (TMS) as an internal standard. The mass spectra were recorded on
GCMS-Q1000-EX Shimadzu and GCMS 5988-A HP spectrometers, and the ioniz-
ing voltage was 70 eV. Elemental analyses were carried out by the Microanalytical
Center of Cairo University, Giza, Egypt. Compounds 3 and 4 were prepared as
previously described.[7]
Synthesis of 3,4-Bis(isoxazol-3-yl)-1-aryl-5-methylpyrazoles (6a–c)
To a solution of the appropriate bis-enaminone 4 (2 mmol) in absolute ethanol
was added 0.27 g, 4 mmol of hydroxylamine hydrochloride in the presence of anhy-
drous potassium carbonate (0.5 g). The reaction mixture was then refluxed for 5 h.
The solid formed was collected by filtration and crystallized from ethanol to give
the respective compound 6. Compounds 6a–c together with their physical constants
are listed.
3,4-Bis(isoxazol-3-yl)-1-phenyl-5-methylpyrazole (6a). Red crystals, yield
0.43 g (75%), mp 176–178 ꢁC; IR (KBr) nmax=cmꢀ1 1598 (C N). 1H NMR
=
(DMSO-d6) d 3.58 (s, 3H, CH3), 6.81 (d, J ¼ 7 Hz, 2H, isoxazole-H), 7.6–7.7
(m, 5H, ArH), 8.42 (d, J ¼ 7 Hz, 7 Hz, isoxazole-H); MS m=z (%) 292 (Mþ, 6), 291

8
A. S. SHAWALI AND A. J. M. HABOUB
(8), 278 (14), 277 (19), 276 (22), 248 (14), 130 (10), 118 (21), 93 (17), 89 (16), 77 (100),
68 (13), 51 (70). Anal. calcd. for C16H12N4O2(292.29): C, 65.75; H, 4.14; N, 19.17.
Found: C, 66.15; H, 4.35; N, 19.45%.
3,4-Bis(isoxazol-3-yl)-1-(p-tolyl)-5-methylpyrazoles (6b). Pale brown
crystals, yield 0.48 g (80%), mp 210–212 ꢁC, IR (KBr) nmax=cmꢀ11588 (C N). H
1
=
NMR (DMSO-d6) d 2.43 (s, 3H, CH3), 3.52 (s, 3H, CH3), 6.83 (d, J ¼ 7 Hz, 7H,
isoxazole-H), 7.10 (d, J ¼ 6 Hz, 2H, ArH), 7.45 (d, J ¼ 6 Hz, 2H, ArH), 8.42 (d,
J ¼ 7 Hz, 2H, isoxazole-H); 13C NMR (DMSO-d6) d 12.1, 24.0, 103.0, 108.4,
120.5, 129.7, 129.8, 136.0, 137.0, 138.8, 148.7, 150.3, 158.5, 162.0; MS m=z (%)
308 (Mþ þ 2, 3), 307 (Mþ þ 1, 9), 306 (Mþ, 26), 289 (30), 290 (42), 276 (15), 262
(22), 154 (12), 149 (14), 132 (23), 106 (13), 91 (60), 77 (28), 67 (13), 65 (100), 51
(55). Anal. calcd. for C17H14N4O2 (306.33): C, 66.66; H, 4.61; N, 18.28. Found: C,
67.00; H, 4.82; N, 18.40%.
3,4-Bis(isoxazol-3-yl)-1(p-anisyl)-5-methylpyrazoles (6c). Pale brown
crystals, yield 0.51 g (80%), mp 180–182 ꢁC: IR (KBr) nmax=cmꢀ1 1598 (C N),
=
1
1251 (C-O-C). H NMR (DMSO-d6) d 3.53 (s, 3H, CH3), 3.86 (s, 3H, OCH3),
6.83 (d, J ¼ 7 Hz, 2H, isoxazole-H), 7.30 ꢀ 7.42 (m, 4H, ArH), 8.42 (d, J ¼ 7 Hz,
2H, isoxazole-H); MS m=z (%) 324 (Mþ þ 2, 4), 323 (Mþ þ 1, 9), 322 (Mþ, 12),
306 (100), 292 (12), 282 (22), 237 (13), 236 (24), 207 (12), 196 (11), 172 (11), 133
(13), 123 (22), 116 (22), 108 (23), 103 (16), 98 (19), 92 (33), 84 (20), 77 (80), 67
(31), 64 (74), 51 (20). Anal. calcd. for C17H14N4O3(322.33): C, 63.35; H, 4.38; N,
17.38. Found: C, 63.50; H, 4.45; N, 17.70%.
Alternate Synthesis of 3,4-Bis[(3-isoxazol-3-yl)-1-(4-tolyl)]-5-methyl-
pyrazole (6b)
Hydroxylamine hydrochloride (20 mmol) and potassium carbonate (0.5 g) were
added to a solution of 3b (2.56 g, 10 mmol) in absolute ethanol (20 ml). The mixture
was then refluxed for 7 h. The precipitate formed was filtered and crystallized from
ethanol to afford compound 9b as a pale orange solid, yield (2.23 g, 78%), mp
144–146 ꢁC, IR (KBr) nmax=cmꢀ1 3340, 3272 (OH), 1590 (C N). 1H NMR
=
(DMSO-d6) d 2.22 (s, 3H, CH3), 2.38 (s, 3H, Ar-CH3), 3.23 (s, 3H, CH3), 4.40
(br, 2H, 2OH), 7.32–7.42 (m, 4H, Ar-H); MS m=z (%) 286 (Mþ, 0.4) 132 (10), 91
(89), 84 (65), 76 (32), 64 (100). Anal. calcd. for C15H18N4O2 (286.32): C, 62.92; H,
6.34; N, 19.57. Found: C, 63.10; H, 6.50; N, 19.72%.
A mixture of compound 9b (1.43 g, 5 mmol) and DMF-DMA (1.19 g, 10 mmol)
was refluxed for 20–30 h and then left to cool. Methanol was added to the cold mix-
ture. The resulting solid was collected by filtration, washed with methanol, dried,
and finally crystallized from ethanol to afford the respective 6b (1.31 g, 86%), mp
210–212 ꢁC, which was found identical in all respective to that compound produced
from reaction of compound 4b with hydroxylamine hydrochloride.
Compounds 10a–c and 11–c
To a solution of 4 (0.70 g, 2 mmol) in absolute ethanol (20 ml) was added 10 ml
of hydrazine hydrate. The mixture was refluxed for 5 h and then cooled. The precipi-
tate formed was filtered off and crystallized from ethanol to give the respective

POLYAZA-3,4-BIS(HETARYL) PYRAZOLES
9
compound ter-pyrazole derivatives 10a–c. When this procedure was repeated using
phenylhydrazine in lieu of hydrazine hydrate, the respective ter-pyrazoles 11a–c were
obtained.
3,4-Bis[1H-pyrazol-3-yl]-5-methyl-1-phenyl-1H-pyrazole
(10a). White
crystals, yield 0.49 g (85%), mp 246–248 ꢁC: IR (KBr) nmax=cmꢀ1 3318 (NH), 1593
(C N). 1H NMR (DMSO-d6) d 3.35 (s, 3H, CH3), 6.41 (d, J ¼ 7 Hz, 2H,
=
Pyrazole-H4), 7.60 (s, 5H, ArH), 7.82 (d, J ¼ 7 Hz, 2H, Pyrazole-H5), 13.11
(s, D2O exchangeable, 2H, NH); MS m=z (%), 292 (Mþ þ 2, 2), 291 (Mþ þ 1, 16),
290 (Mþ, 81), 289 (43), 262 (11), 118 (12), 77 (100), 64 (10), 51 (55). Anal. calcd.
for C16H14N6(290.33): C, 66.19; H, 4.86; N, 28.95. Found: C, 66.40; H, 4.98; N,
29.31%.
3,4-Bis[1H-pyrazol-3-yl]-5-methyl-1-(4-tolyl)-1H-pyrazole (10b). White
crystals, yield 0.49 g (79%), mp 264–264 ꢁC; IR (KBr) nmax=cmꢀ1 3435 (NH), 1595
(C N). 1H NMR (DMSO-d6) d 2.39 (s, 3H, CH3), 3.35 (s, 3H, CH3), 6.42
=
(d, J ¼ 7 Hz, 2H, Pyrazole-H4), 7.38–7.45 (m, 4H, ArH), 7.66 (d, J ¼ 7 Hz, 2H,
Pyrazole-H5), 12.98 (s, D2O exchangeable, 2H, 2NH); 13C NMR (DMSO-d6) d
11.5, 24.0, 103.0, 108.4, 120.5, 129.7, 129.9, 130.05, 136.03, 137.0, 138.8, 146.0,
148.0; MS m=z (%) 305 (Mþ þ 1, 20), 304 (Mþ, 83), 303 (45), 130 (19), 117 (14),
104 (11), 91 (86), 77 (18), 65 (100), 51 (65). Anal. calcd. for C17H16N6 (304.36): C,
67.09; H, 5.30; N, 27.61. Found: C, 67.40; H, 5.51; N, 27.90%.
3,4-Bis[1H-pyrazol-3-yl]-5-methyl-1-(4-anisyl)-1H-pyrazole (10c). White
crystals, yield 0.48 g (82%), mp 250–252 ꢁC: IR (KBr) nmax=cmꢀ1 3430 (NH), 1589
1
=
(C N), 1251 (C-O-C). H NMR (DMSO-d6) d 3.34 (s, 3H, CH3), 3.83 (s, 3H,
OCH3), 6.39 (d, J ¼ 7 Hz, 2H, Pyrazole-H4), 7.81 (d, J ¼ 7 Hz, 2H, ArH), 7.48
(d, J ¼ 8 Hz, 2H, ArH), 7.81 (d, J ¼ 7 Hz, 2H, Pyrazole-H5), 13.09 (s, D2O exchange-
able, 2H, 2NH); MS m=z (%) 321 (Mþ þ 1, 24), 320 (Mþ, 78), 160 (14), 115 (21), 103
(24), 94 (19), 92 (42), 77 (100), 65 (25), 51 (42). Anal. calcd. for C17H16N6O (320.36):
C, 63.74; H, 5.03; N, 26.23. Found: C, 64.00; H, 5.36; N, 26.54%.
3,4-Bis[1-phenyl-1H-pyrazol-3-yl]-5-methyl-1-phenyl-1H-pyrazole (11a).
Yellow crystals, yield 0.68 g (75%), mp 218–220 ꢁC; IR (KBr) nmax=cmꢀ1 1593
(C N). 1H NMR (DMSO-d6) 3.46 (s, 3H, CH3), 6.83 (d, J ¼ 7 Hz, 2H,
=
Pyrazole-H4), 7.58 (m, 15H, ArH), 8.35 (d, J ¼ 7 Hz, 2H, Pyrazole-H5); MS m=z
(%) 442 (Mþ, 4), 118 (17), 92 (10), 77 (100), 51 (65). Anal. calcd. for C28H22N6
(442.53): C, 76.00; H, 5.01; N, 18.99. Found: C, 76.49; H, 5.38; N, 18.65%.
3,4-Bis[1-phenyl-1H-pyrazol-3-yl]-5-methyl-1-(4-tolyl)-1H-pyrazole (11b).
Brown crystals, yield 0.77 g (78%), mp 242–244 ꢁC; IR (KBr) nmax=cmꢀ1 1596 (C C).
=
1H NMR (DMSO-d6) d 2.52 (s, 3H, CH3), 3.31 (s, 3H, CH3), 7.23ꢀ 7.62 (m, 14H,
ArH), 6.73 (d, J ¼ 7 Hz, 2H, Pyrazole-H4), 8.35 (d, J ¼ 8 Hz, 2H, Pyrazole-H5); MS
m=z (%) 459 (Mþ þ 3, 2), 458 (Mþ þ 2, 8), 456 (Mþ, 100), 313 (12), 192 (11), 153 (12),
140 (15), 115 (15), 103 (17), 90 (38), 77 (32), 64 (17). Anal. calcd. for C29H24N6
(456.55): C, 76.30; H, 5.30; N, 18.41. Found: C, 76.70; H, 5.70; N, 18.77%.
3,4-Bis[1-phenyl-1H-pyrazol-3-yl]-5-methyl-1-(4-anisyl)-1H-pyrazole (11c).
Pale brown crystals, yield 0.80 g (85%), mp 230–232 ꢁC; IR (KBr) nmax=cmꢀ1 1599
1
=
=
(C N), 1599 (C C), 1250 (C-O-C). H NMR (DMSO-d6) d 3.31 (s, 3H, CH3),

10
A. S. SHAWALI AND A. J. M. HABOUB
3.84 (s, 3H, OCH3), 6.82 (d, J ¼ 7 Hz, 2H, Pyrazole-H4), 7.13ꢀ7.67 (m, 14H, ArH),
8.30 (d, J ¼ 7 Hz, 2H, Pyrazole-H5); MS m=z (%) 474 (Mþ þ 2, 3), 472 (Mþ, 12), 167
(18), 147 (25), 140 (12), 131 (13), 118 (15), 92 (77), 76 (40), 65 (100), 50 (17). Anal.
calcd. for C29H24N6O (472.55); C: 73.71; H, 5.12; N, 17.78. Found; C: 74.20; H, 5.47;
N, 18.05%.
Synthesis of 3,4-Bis([1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-1-aryl-
5-methylpyrazoles (12a–c)
3-Amino-1,2,4-triazole (0.77 g, 4 mmol), was added to a solution of 4 (0.70 g,
2 mmol) in acetic acid (20 ml). The mixture was refluxed for 6 h and then cooled.
The solid that deposited after cooling was filtred and crystallized from ethanol–diox-
ane to give the respective product 12.
3,4-Bis([1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-1-phenyl-5-methylpyrazole
(12a). Orange solid, yield 0.60 g (77%), mp 238–240 ꢁC; IR (KBr) nmax=cmꢀ1 1617
(C N). 1H NMR (DMSO-d6) d 3.38 (s, 3H, CH3), 7.65 (s, 5H, Ar-H), 7.80
=
(d, J ¼ 9 Hz, 2H, pyrimidine-H), 8.79 (s, 2H, triazole H), 9.27 (d, J ¼ 9 Hz, 2H,
pyrimidine-H). MS m=z (%) 394 (Mþ, 10), 83 (21), 68 (11), 56 (16), 46 (100). Anal.
calcd. for C20H14N10 (394.39): C, 60.91; H, 3.58; N, 35.51. Found: C, 61.15; H, 3.71;
N, 35.85.
3,4-Bis([1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-1-(p-tolyl)-5-methylpyrazole
(12b). Yellow solid, yield 0.61 g (75%), mp 266–268 ꢁC; IR (KBr) nmax=cmꢀ1 1609
1
=
(C N). H NMR (DMSO-d6) d 2.44 (s, 3H, Ar-CH3), 3.37 (s, 3H, CH3), 7.46
(d, J ¼ 9 Hz, 2H, Ar-H), 7.58 (d, J ¼ 9 Hz, 2H, Ar-H), 7.79 (d, J ¼ 9 Hz, 2H,
pyrimidine-H), 8.79 (s, 2H, triazole H), 9.27 (d, J ¼ 9 Hz, 2H, pyrimidine-H). MS
m=z (%) 408 (Mþ, 12), 332 (13), 256 (30), 241 (100), 223 (11), 170 (34), 155 (19),
143 (12), 130 (40), 104 (42), 91 (57), 83 (64), 76 (22), 64 (54), 57 (34), 45 (63). Anal.
calcd. for C21H16N10 (408.42): C, 61.76; H, 3.95; N, 34.29. Found: C, 62.01; H, 3.84;
N, 34.51%.
3,4-Bis([1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-1-(p-anisyl)-5-methylpyrazole
(12c). Pale brown solid, yield 0.67 g (80%), mp 254–256 ꢁC; IR (KBr) nmax=cmꢀ1
1687, 1617 (C N). 1H NMR (DMSO-d6) d 3.38 (S, 3H, CH3), 3.84 (S, 3H,
=
OCH3), 7.42 (d, J ¼ 9 Hz, 2H, Ar-H), 7.59 (d, J ¼ 9 Hz, 2H, Ar-H), 7.79 (d, J ¼ 9 Hz,
2H, pyrimidine-H), 8.79 (s, 2H, triazole H), 9.27 (d, J ¼ 9 Hz, 2H, pyrimidine-H).
MS m=z (%) 424 (Mþ, 10), 272 (13), 257 (30), 214 (11), 223 (11), 147 (19), 121
(18), 103 (12), 91 (21), 83 (39), 68 (45), 56 (30), 45 (100). Anal. calcd. for
C21H16N10O (424.42): C, 59.43; H, 3.80; N, 33.00. Found: C, 59.69; H, 3.92;
N, 33.25%.
Preparation of compounds 16, 21, and 22
Malononitrile (0.26 g, 4 mmol) was added to a solution of 4 (0.70 g, 2 mmol) in
glacial acetic acid in the presence of ammonium acetate (0.5 g). The reaction mixture
refluxed for 25 h, and then cooled. The reaction was followed by thin-layer chroma-
tagraphy (TLC). The reaction mixture was poured into cold water while being

POLYAZA-3,4-BIS(HETARYL) PYRAZOLES
11
stirred. The solid product that precipitated was filtered off and crystallized from
ethanol to give the respective compound 16.
When this procedure was repeated using ethyl acetoacetate and ethyl benzoyl
acetate in lieu of malononitrile, the respective products 21 and 22 were produced,
respectively.
3,4-Bis[5-cyano-6-oxo-1H-pyrid-2-yl]-5-methyl-1-phenyl-1H-pyrazole
(16a). Orange crystals, yield 0.55 g (70%), mp 234–236 ꢁC; IR (KBr) nmax=cmꢀ1
1
=
3336 (NH), 2213 (CN), 1675 (C O). H NMR (DMSO-d6) d 3.31 (s, 3H, CH3),
7.65 (s, 5H, ArH), 7.94 (d, J ¼ 9 Hz, 2H, Pyridine-H), 8.67 (d, J ¼ 9 Hz, 2H,
Pyridine-H), 13.12 (s, 2H, 2NH); MS m=z (%) 394 (Mþ, 6), 328 (10), 118 (10), 91
(12), 77 (100), 66 (18), 51 (54). Anal. calcd. for C22H14N6O2 (394.39): C, 67.00; H,
3.58; N, 21.31. Found: C, 67.48; H, 3.82; N, 21.44%.
3,4-Bis[5-cyano-6-oxo-1H-pyrid-2-yl]-5-methyl-1-(4-tolyl)-1H-pyrazole
(16b). Yellow solid, yield 0.60 g (74%), mp 272–274 ꢁC: IR (KBr) nmax=cmꢀ1 3350
1
=
(NH), 2210 (CN), 1670 (C O). H NMR (DMSO-d6) d 2.43 (s, 3H, CH3) 3.30
(s, 3H, CH3), 7.43–7.69 (2 d, J ¼ 8 Hz, 2H, ArH), 7.95 (d, J ¼ 9 Hz, 2H, Pyridine-H),
8.65 (d, J ¼ 9 Hz, 2H, Pyridine-H), 12.95 (s, 2H, 2NH); 13C NMR (DMSO-d6) d
11.3, 24.0, 100.3, 103.0, 106.2, 108.4, 115.8, 120.5, 129.7, 129.90, 136.53, 136.56,
137.0, 140.8, 156.03, 156.06, 161.5; MS m=z (%) 408 (Mþ, 2), 360 (72), 342 (90),
314 (60), 298 (16), 287 (41), 258 (12), 244 (19), 216 (14), 190 (11), 177 (12), 164
(22), 155 (10), 149 (15), 127 (45), 114 (61), 103 (58), 91 (96), 76 (48), 64 (100), 50
(38). Anal. calcd. for C23H16N6O2 (408.41): C, 67.64; H, 3.94; N, 20.58. Found: C,
68.00; H, 4.31; N, 20.76%.
3,4-Bis[5-cyano-6-oxo-1H-pyrid-2-yl]-5-methyl-1-(4-anisyl)-1H-pyrazole
(16c). Yellow crystals, yield 0.67 g (80%), mp 265–267 ꢁC; IR (KBr) nmax=cmꢀ1 3338
1
=
(NH), 2208 (CN), 1667 (C O), 1250 (C-O-C). H NMR (DMSO-d6) d 3.31 (s, 3H,
CH3) 3.85 (s, 3H, OCH3), 7.14 (d, J ¼ 8 Hz, 2H, ArH), 7.72 (d, J ¼ 8 Hz, 2H, ArH),
7.94 (d, J ¼ 9 Hz, 2H, Pyridine-H), 8.59 (d, J ¼ 9 Hz, 2H, Pyridine-H), 13.07 (s, 2H,
2NH); MS m=z (%) 424 (Mþ, 0.6), 376 (81), 358 (100), 348 (10), 330 (56), 315 (22),
303 (47), 287 (24), 277 (10), 258 (25), 243 (16), 234 (12), 216 (23), 204 (16), 191 (25),
178 (30), 165 (30), 157 (13), 151 (32), 147 (24), 128 (49), 115 (54), 107 (69), 95 (10), 90
(75), 76 (73), 63 (59), 50 (30). Anal. calcd. for C23H16N6O3 (424.41): C, 65.09; H,
3.80; N, 19.80. Found: C, 65.40; H, 3.92; N, 20.22%.
3,4-Bis[5-ethoxycarbonyl-6-methyl-pyrid-2-yl]-5-methyl-1-phenyl-1H-
pyrazole (21a). Reddish crystals, yield 0.72 g (75%), mp 254 ꢁC; IR (KBr) nmax
=
cmꢀ1 1715 (C O), 1582 (C N). 1H NMR (DMSO-d6) d 1.22 (t, J ¼ 7 Hz, 6H,
2CH3), 2.51 (s, 6H, CH3), 3.32 (s, 3H, CH3), 4.27 (q, J ¼ 7 Hz, 4H, 2 OCH2), 7.61
(s, 5H, ArH), 7.95 (d, J ¼ 9 Hz, 2H, Pyridine-H), 8.69 (d, J ¼ 9 Hz, 2H, Pyridine-H);
MS m=z (%) 484 (Mþ, 11), 483 (19), 334 (22), 280 (14), 279 (22), 254 (14), 253 (16),
236 (11), 215 (19), 194 (39), 188 (16), 163 (16), 132 (22), 118 (36), 104 (36), 91 (41), 84
(25), 79 (25), 77 (100), 70 (28), 57 (44). Anal. calcd. for C28H28N4O4 (484.55): C,
69.41; H, 5.82; N, 11.56. Found: C, 69.80; H, 6.02; N, 11.88%.
=
=
3,4-Bis[5-ethoxycarbonyl-6-methyl-pyrid-2-yl]-5-methyl-1-(4-tolyl)-1H-
pyrazole (21b). Orange solid, yield 0.79 g (80%), mp. 298–300 ꢁC, IR (KBr)

12
A. S. SHAWALI AND A. J. M. HABOUB
1
max=cmꢀ1 1715 (C O). H NMR (DMSO-d6) d 1.22 (t, J ¼ 7 Hz, 6H, 2CH3), 2.50
=
n
(s, 3H, Ar-CH3), 2.72 (s, 6H, CH3), 3.32 (s, 3H, CH3), 4.35 (q, J ¼ 7 Hz, 4H,
2OCH2), 7.40–7.64 (m, 4H, ArH), 7.94 (d, J ¼ 9Hz, 2H, Pyridine-H), 8.71
(d, J ¼ 9 Hz, 2H, Pyridine-H); MS m=z (%) 498 (Mþ, 0.53), 387 (11), 289 (27), 265
(22), 193 (14), 171 (11), 165 (11), 149 (14), 141 (15), 132 (25), 122 (12), 115 (29),
105 (51), 97 (28), 91 (87), 81 (22), 76 (52), 69 (42), 63 (80), 56 (45), 45 (100). Anal.
calcd. for C29H30N4O4 (498.57): C, 69.86; H, 6.06; N, 11.24. Found: C, 70.20; H,
6.40; N, 11.53%.
3,4-Bis[5-ethoxycarbonyl-6-methyl-pyrid-2-yl]-5-methyl-1-(4-anisyl)-1H-
pyrazole (21c). Pale brown crystals, yield 0.88 g (86%), mp 280–282 ꢁC; IR (KBr)
1
max=cmꢀ1 1720 (C O), 1250 (C-O-C). H NMR (DMSO-d6) d 1.07 (t, J ¼ 7 Hz,
=
n
6H, 2CH3), 2.49 (s, 6H, 2CH3), 3.31 (s, 3H, CH3), 3.85 (s, 3H, OCH3), 4.25
(q, J ¼ 7 Hz, 4H, 2OCH2), 7.13–7.56 (m, 4H, ArH), 7.95 (d, J ¼ 9 Hz, 2H,
Pyridine-H), 8.70 (d, J ¼ 9 Hz, 2H, Pyridine-H); 13C NMR (DMSO-d6) d 11.4,
12.8, 18.0, 55.9, 60.3, 107.6, 114.2, 115.0, 119.3, 120.46, 120.50, 120.53, 120.56,
129.3, 132.0, 136.0, 137.8, 147.7, 156.03, 156.06, 158.2, 162.0, 166.5; MS m=z (%)
514 (Mþ, 0.50), 375 (11), 334 (58), 306 (40), 281 (36), 278 (14), 179 (12), 165 (22),
157 (10), 148 (39), 138 (14), 131 (15), 122 (42), 115 (22), 103 (69), 91 (90), 76 (99),
63 (100), 54 (63), 50 (77). Anal. calcd. for C29H30N4O5 (514.57): C, 67.69; H, 5.88;
N, 10.89. Found: C, 67.25; H, 6.20; N, 11.12%.
3,4-Bis[5-ethoxycarbonyl-6-phenyl-pyrid-2-yl]-5-methyl-1-phenyl-1H-
pyrazole (22a). Yellow solid, yield 0.96 g (79%), mp 232–234 ꢁC; IR (KBr)
max=cmꢀ1 1710 (C O). 1H NMR (DMSO-d6) d 1.22 (t, J ¼ 7 Hz, 6H, 2CH3),
=
n
3.52 (s, 3H, CH3), 4.29 (q, J ¼ 7 Hz, 2H, 2 OCH2), 7.58 (s, 15H, ArH), 7.98
(d, J ¼ 9 Hz, 2H, Pyridine-H), 8.28 (d, J ¼ 9Hz, 2H, Pyridine-H); MS m=z (%) 608
(Mþ, 17), 527 (12), 347 (44), 335 (12), 214 (47), 187 (44), 185 (12), 176 (17), 160
(29), 145 (18), 144 (18), 132 (32), 118 (35), 104 (32), 91 (38), 78 (44), 77 (82), 69
(32), 65 (64), 60 (47), 51 (100). Anal. calcd. for C38H32N4O4 (608.69): C, 74.98;
H, 5.30; N, 9.20. Found: C, 75.33; H, 5.40; N, 9.56%.
3,4-Bis[5-ethoxycarbonyl-6-phenylpyrid-2-yl]-5-methyl-1-(4-tolyl)-1h-
pyrazole (22b). Yellow crystals, yield 0.95 g (77%), mp > 300 ꢁC; IR (KBr)
max=cmꢀ1 1710 (C O); 1H NMR (DMSO-d6) d 1.22 (t, J ¼ 7 Hz, 6H, 2CH3),
=
n
2.41 (s, 3H, Ar-CH3), 3.31 (s, 3H, CH3), 4.25 (q, J ¼ 7 Hz, 4H, 2 OCH2),
7.43–7.51 (m, 14 H, ArH), 7.94 (d, J ¼ 9 Hz, 2H, Pyridine-H), 8.24 (d, J ¼ 9 Hz,
2H, Pyridine-H); MS m=z (%) 623 (Mþ þ 1, 0.08), 622 (Mþ, 0.08), 376 (17), 347
(19), 317 (23), 288 (23), 272 (11), 236 (12), 229 (18), 220 (26), 183 (15), 178 (14),
165 (22), 153 (31), 141 (46), 131 (36), 120 (19), 115 (52), 103 (90), 89 (80), 76 (97),
63 (100). Anal. calcd. for C39H34N4O4 (622.71): C, 75.22; H, 5.50; N, 9.00. Found:
C, 75.33; H, 5.78; N, 9.40%.
3,4-Bis[5-ethoxycarbonyl-6-phenylpyrid-2-yl]-5-methyl-1-(4-anisyl)-1H-
pyrazole (22c). Pale brown solid, yield 0.99 g (78%), mp 282–284 ꢁC, IR (KBr)
1
max=cmꢀ1 1710 (C O), 1251 (C-O-C). H NMR (DMSO-d6) d 1.22 (t, J ¼ 7 Hz,
=
n
6H, 2CH3), 3.3 (s, 3H, CH3), 3.84 (s, 3H, OCH3), 4.28 (q, J ¼ 7 Hz, 4H, 2OCH2),
7.13–7.56 (s, 14H, ArH), 7.93 (d, J ¼ 9 Hz, 2H, Pyridine-H), 8.35 (d, J ¼ 9 Hz, 2H,
Pyridine-H); 13C NMR (DMSO-d6) d 11.3, 12.8, 55.9, 60.3, 107.7, 114.6, 119.3,

POLYAZA-3,4-BIS(HETARYL) PYRAZOLES
13
120.5, 127.53, 127.56, 132.0, 135.0, 138.8, 147.7, 156.03, 156.06, 158.2, 166.3; MS m=z
(%) 638 (Mþ, 0.5), 148 (12), 104 (22), 90 (61), 76 (78), 62 (100). Anal. calcd. for
C39H34N4O5 (638.71): C, 73.34; H, 5.37; N, 8.77. Found: C, 73.68; H, 5.16; N, 8.98%.
Alternate Synthesis of 16b
Cyanoacetamide (0.33 g, 4 mmol) was added to a solution of 4b (0.73 g, 2
mmole) in dry toluene, and the mixture was refluxed for 12 h and then cooled.
The solid so formed was filtered off and crystallized from ethanol to give compound
16b (0.61 g, 85%), mp 272–274 ꢁC, which proved identical in all respects (mp, mixed
mp, and spectral data) with 16b.
REFERENCES
1. (a) Abu Shanab, F. A.; Sherif, S. M.; Mousa, S. A. Dimethylformamide dimethyl acetal as
a building block in heterocyclic synthesis. J. Heterocycl. Chem. 2009, 46, 801–82; (b)
Riyadh, S. M.; Abdelhamid, I. A.; Al-Matar, H. M.; Hilmy, N. M.; Elnagdi, M. H. Enam-
ines as precursors to polyfunctional heteroaromatic compounds: A decade of development.
Heterocycles 2008, 75, 1849–1905; (c) Edafiogho, I. O.; Kombian, S. B.; Ananthalakshmi,
K. V. V.; Salama, N. N.; Eddington, N. D.; Wilson, T. L.; Alexander, M. S.; Jackson, P. L.;
Hanson, C. D.; Scott, K. R. Exploring additional therapeutic activities. J. Pharm. Sci.
2007, 96, 2509–2531; (d) Svete J. Utilisation of chiral enaminones and azomethine imines
in the synthesis of functionalised pyrazoles. Arkivoc 2006, 1, 35–56; (e) Palmieri, G.;
Cimarelli, C. Chemo- and stereoselective reduction of enaminones for the preparation of
biologically active compounds. Arkivoc 2006, 6, 104–126; (f) Negri, G.; Kascheres, C.;
Kascheres, A. J. Recent development in preparation reactivity and biological activity of
enaminoketones and enaminothiones and their utilization to prepare heterocyclic com-
pounds. J. Heterocycl. Chem. 2004, 41, 461–491; (g) Stanovnik, B.; Svete, J. Synthesis of
heterocycles from alkyl 3-(dimethylamino)propenoates and related enaminones. Chem.
Rev. 2004, 104, 2433–2480; (h) Elassar, A. A.; El-Khair, A. A. Recent developments in
the chemistry of enaminones. Tetrahedron 2003, 59, 8463–8480; (i) Kascheres, C. M. The
chemistry of enaminones, diazocarbonyls, and small rings: Our contribution. J. Braz.
Chem. Soc. 2003, 14, 945–969; (j) Lui, P.; Greenhill, J. V. Enaminones in heterocyclic
Synthesis. Adv. Heterocycl. Chem. 1996, 67, 207–343.
2. (a) Hassanien, A. A. 2,6-Bis [3-N,N-dimethylamino-1-oxopropen-1-yl]pyridine as a
building block in heterocyclic synthesis: synthesis of 2,20:60,200-terpyridines and 2,6-bis
[pyrazolyl, isoxazolyl, diazepinyl, pyrazolo[5,1-a]pyrimidinyl and pyrazolo-[4,3-
d]pyridazinyl]pyridines. J. Chem. Res. 2004, 536–540; (b) Pleier, A. K.; Glas, H.; Grosche,
M.; Sirsch, P.; Thiel, W. R. Microwave-assisted synthesis of 1-aryl-3-dimethylaminopro-
2-enones: A simple and rapid access to 3(5)-arylpyrazoles. Synthesis 2001, 1, 55–62;
(c) Bejan, E.; Haddou, H. A.; Daran, J. C.; Balavoine, G. G. A. The reaction of enami-
nones with carboxamidines: A convenient route for the synthesis of polyaza heterocycles.
Synthesis 1996, 4, 1012–1018.
3. (a) Shawali, A. S.; Farghaly, T. A.; Al-Dahshoury, A. R. Synthesis reactions and antitumor
activity of new b-aminovinyl 3-pyrazolyl ketones. Arkivoc 2009, 14, 88–99; (b) Shawali, A.
S. Synthesis, reactions, and antitumour screening of new enaminones. J. Chem. Res. 2010,
630–634; (c) Shawali, A. S.; Sherif, S. M.; Darwish, M. A. A.; El-merzabani, M. M. Syn-
thesis and antitumor screening of new 1,7-diphenyl-3-(1,3-disubstituted-1H-pyrazole-4-car-
bonyl) [1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones. Arch. Pharm. Res. 2010, 33, 55–60;
(d) Shawali, A. S.; Sherif, S. M.; Darwish, M. A. A.; El-merzabani, M. M. Synthesis

14
A. S. SHAWALI AND A. J. M. HABOUB
and antitumor activity of novel pyrazolylenaminone and bis(pyrazolyl)ketones via
hydrazonoyl halides. J. Heterocycl. Chem. 2009, 46, 548–551; (e) Shawali, A. S.; Farghaly,
T. A.; Al-Dahshoury, A. R. An efficient synthesis of functionalized 3-(hetaryl)pyrazoles.
Arkivoc 2010, 9, 19–30.
4. Kleemann, J.; Engel, B.; Kutscher, R. Pharmaceutical Substances; Thieme: New York,
1999; pp. 1785–1787.
5. Bruno, O.; Ranise, A.; Bondavalli; Schenone, P.; D’Amico, M.; Filippelli, A.; Felippelli,
W.; Rossi, S. 3,5-Diphenyl-1H-pyrazole derivatives, XI: N-aryl-5(3)-phenyl-4-
(3,5-diphenyl-1-pyrazolyl)-3(5)-pyrazole amines, 5-substituted 4,5-dihydro-3-phenyl-4-(3,
5-diphenyl-1-pyrazolyl)-1H-pyrazoles and 2,6-disubstituted 1,6-dihydro-4- phenyl-5-(3,5-
diphenyl-1-pyrazolyl)pyrimidines with antipyretic, anti-inflammatory, and other activities.
Farmaco. 1993, 48, 949–966.
6. Cuadro, A. M.; Elguero, J.; Navarro, P. Binuclear pyrazoles, I: Synthesis and cytotoxic
activity of 1,10-dibenzyl and 1,10-dihydroxymethyl 4,40 bispyrazoles. Chem. Pharm. Bull.
1985, 33, 2535–2540.
7. Shawali, A. S.; Haboub, A. J. M. Reaction of hydrazonoyl halides with bis-enaminones: A
convenient route for synthesis of novel polyaza-terheterocycles. J. Heterocycl. Chem. 2011,
in press.
8. Farag, A. M.; Mayhoub, A. S.; Barakat, S. E.; Bayomi, A. H. Synthesis of new
N-phenylpyrazole derivatives with potent antimicrobial activity. Bioorg. Med Chem.
2008, 16, 4569–4578.
9. Salgado, A.; Varela, C.; Collazo, A. M. G.; Pevarello, P. Differentiation between
[1,2,4]triazolo[1,5-a]pyrimidine and [1,2,4]triazolo[4,3-a]-pyrimidine regioisomers by
1H–15N HMBC experiments. Mag. Reson. Chem. 2010, 48, 614–622.