Synthesis and tautomeric structure of 6-arylhydrazono 1H-pyrazolo[3′,4′:4,5]pyrimido[1,6-b][1,2,4]triazepines

Article abstract of DOI:10.1016/j.tet.2008.11.018

A simple synthetic strategy is described for synthesis of the hitherto unreported 6-arylhydrazono-1,3-diphenyl-7-methyl-1H-pyrazolo[3′,4′:4,5]pyrimido[1,6-b][1,2,4]triazepin-5(6H)-ones 5a-j. The acid dissociation constants were determined for the series p

Full text of DOI:10.1016/j.tet.2008.11.018

Tetrahedron 65 (2009) 644–647
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Tetrahedron
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Synthesis and tautomeric structure of 6-arylhydrazono 1H-pyrazolo[30,40:4,5]-
pyrimido[1,6-b][1,2,4]triazepines
*
Ahmad S. Shawali , Thoraya A. Farghaly
Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple synthetic strategy is described for synthesis of the hitherto unreported 6-arylhydrazono-1,3-
diphenyl-7-methyl-1H-pyrazolo[30,40:4,5]pyrimido[1,6-b][1,2,4]triazepin-5(6H)-ones 5a–j. The acid dis-
sociation constants were determined for the series prepared and were correlated by the Hammett
equation using the enhanced substituent constants. The results of such a correlation together with the
spectral data indicated that the studied compounds exist predominantly in the hydrazone tautomeric
form.
Received 17 September 2008
Received in revised form 19 October 2008
Accepted 6 November 2008
Available online 12 November 2008
Keywords:
Ó 2008 Elsevier Ltd. All rights reserved.
Azo-hydrazone tautomerism
Heterocycles
Pyrazolo[30,40:4,5]pyrimido[1,6-b]triazepine
1. Introduction
far studied were reported to be regioselective and lead to products
that result from nucleophilic attack of the ]NH and the N–NH2
In continuation of our studies on the synthesis and elucidation
of the tautomeric structures of arylazo heterocycles,1–8 we wish to
report herein the synthesis of a series of the title azo dyes, which
have not been reported hitherto. In addition it was thought in-
teresting to elucidate the actual tautomeric structure of such dyes
as they can have one or more of four possible tautomeric forms
(Fig. 1). The knowledge of the actual tautomeric form(s) of azo dyes
in solution and the solid phase is an important factor for their in-
dustrial and biological applications. Our interest in arylazo het-
erocycles is due to the fact that many of such dyes have found many
applications in industry including: hair dyeing, disperse dyes, ink-
jet inks, and laser material.9–15
groups at the ester and keto carbonyl groups of the keto ester, re-
spectively, to give the corresponding fused 2-oxo-1,2,4-triazepine
derivatives.17–21 The structure of the product 3 was confirmed by its
spectra (MS, 1H NMR, and IR) together with elemental analysis. The
1H NMR spectra revealed four characteristic signals near
d 2.31, 4.21,
7.43–8.75, 9.62 assignable to CH3, CH2, C6H5, and CH protons, re-
spectively. Its IR spectrum revealed band at 1716 (CO) cmꢀ1. Its
mass spectrum shows the molecular ion peak at m/z 368. A further
evidence for the assigned structure 3 is provided by its 13C NMR
spectrum, which revealed the signal for the ring carbonyl carbon at
d
173.85. This value suggests that the nitrogen atom adjacent to the
carbonyl carbon is sp2 hybridized.
In aqueous ethanol in the presence of sodium hydroxide, com-
pound 3 reacted with diazotized anilines and afforded the re-
spective arylazo derivatives 5 (Scheme 1). The assigned structure 5
was confirmed by an alternative synthesis of the products 5a, 5d,
and 5h as typical examples of the series prepared. Thus, treatment
of 1 with each of the compounds 6a, 6d, and 6h22 in dioxan in
presence of triethylamine gave the products 5a, 5d, and 5h that
proved identical in all respects (mp, mixed mp, IR, UV) with those
obtained above from the coupling of 3 with the respective di-
azotized anilines (Scheme 1). The mass spectra of the latter prod-
ucts revealed the molecular ion peaks at the expected m/z values
and their elemental analysis data were consistent with their
assigned structures. Their IR spectra showed, in each case, one
carbonyl band in the region 1708–1655 cmꢀ1 and one NH band in
the region 3433–3062 cmꢀ1. The observed wavenumber of the CO
stretching band in compounds 5 seems to result from the possible
2. Results and discussion
The
starting
1,3-diphenyl-7-methyl-1H-pyrazolo[30,40:4,5]
pyrimido[1,6-b][1,2,4]triazepin-5(6H)-one 3 has not been reported
hitherto. It was prepared in this study by condensation of ethyl
acetoacetate 2 with 5-amino-1,3-diphenyl-4,5-dihydro-4-imino-
1H-pyrazolo[3,4-d]pyrimidine 1.16 Although the reaction of 1 with
2 can lead to 3 and/or its isomer namely 1,3-diphenyl-5-methyl-
1H-pyrazolo[30,40:4,5]pyrimido[1,6-b]triazepin-7(8H)-one 4, the
latter isomeric structure was discarded (Scheme 1). This is because
reactions of ethyl acetoacetate with imino-aminoheterocycles thus
* Corresponding author. Tel.: þ20 235676609; fax: þ20 235727556.
E-mail address: as_shawali@yahoo.com (A.S. Shawali).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.11.018

A.S. Shawali, T.A. Farghaly / Tetrahedron 65 (2009) 644–647
645
Table 1
Ar
Ar
UV spectra and acid dissociation constantsb of 6-arylahydrazono-1,3-diphenyl-7-
methyl-1H-pyrazolo[30,40:4,5]pyrimido[1,6-b][1,2,4]triazepin-5(6H)-ones 5a–j in
dioxan
O
NH
HO
N
N
N
N
N
CH3
CH3
Ph
Ph
Compd. No.
lmax (log
3
)
pKa (ꢂs)
sꢀ
x
N
N
N
N
4a
4b
4c
4da
4e
4f
4g
4h
4i
375 (4.80), 272 (5.16)
380 (4.58), 273 (4.63)
316 (4.08), 294 (4.05), 254 (4.61)
374 (4.47), 233 (5.40)
358 (4.91), 292 (4.74), 273 (4.80)
385 (4.96), 279 (5.35)
372 (4.62), 272 (5.03)
387 (5.00), 291 (4.57), 272 (4.83)
381 (4.59), 269 (5.08)
8.42 (0.02)
8.00 (0.03)
7.88 (0.04)
7.83 (0.05)
7.12 (0.02)
6.75 (0.02)
5.93 (0.02)
4.64 (0.03)
6.08 (0.05)
5.56 (0.02)
ꢀ0.27
ꢀ0.17
ꢀ0.07
0.0
0.23
0.37
0.71
1.28
N
N
N
N
N
Ph
N
Ph
5A
5B
Ar
N
Ar
N
O
N
N
O
0.68
0.84
N
H
4j
373 (4.54), 272 (4.97)
CH3
Ph
N
CH3
a
Solvent: lmax (log 3): acetic acid 380 (4.69), 273 (5.14); chloroform 379 (4.75),
N
Ph
N
N
N
H
204 (5.40); DMF 372 (4.54), 255 (5.40); ethanol 374 (4.52), 215 (5.00).
N
b
N
N
pKa in dioxan–water (4:1 v/v) solution at 25 ꢁC and
m¼0.10.
N
N
N
Ph
5D
Ph
5C
Hammett equation was examined.3–7 The acid dissociation con-
stants for the series 5a–j were determined potentiometrically at
25 ꢁC in 80% dioxan–water mixture (v/v). In all determinations the
Figure 1.
ionic strength
m was kept constant at 0.1. From the pH-titrant vol-
strong chelation with the hydrazone NH and conjugation with the
C]N double bond as required by the hydrazone form 5A (Fig. 1).23
These data seem to be consistent with tautomeric form 5A for the
compounds prepared (Fig. 1).
ume data, the acid dissociation constants of the compounds studied
were calculated (see Section 3) and the results are summarized in
Table 1. When the pKa values were plotted versus Hammett sub-
22
stituent constants sx
,
all the substituents fall on the correlation
The electronic absorption spectral data of the studied com-
pounds 5a–j are summarized in Table 1. As shown, each of com-
pounds 5 in dioxan exhibits two characteristic absorption bands in
the regions 387–316 and 294–233 nm. Such an absorption pattern is
similar to that of typical hydrazone chromophore.3,24 Furthermore,
the spectra of 5d, taken as a typical example of the series studied, in
solvents of different polarities showed little, if any, shift (Table 1).
This finding while it suggests that compounds 5 exist in one tauto-
meric form, it excludes the azo tautomeric forms 5B–D (Fig. 1).
To provide further evidence for the assignment of the tauto-
meric structure 5A for the products prepared 5, their acid dissoci-
ation constants, pKa’s, were determined and their correlation by the
line except the substituents with ꢀR effect, namely the p-NO2, p-
CH3CO, and p-EtOCO groups, which are capable of direct interaction
with the negatively charged reaction site. However, when the pKa
data were plotted versus sxꢀ constants,22 better correlation was
obtained. The equation of the regression line obtained is:
pKa [ 7:701L2:445sLx ; r [ 0:996; s [ 0:04
This excellent correlation indicates that the parameter rꢀ in the
Humffray–Ryan equation:25 pKa¼pKaoþ
r
{
sxþrꢀ
(
sꢀx ꢀsx)}, which
gives the contribution of the resonance effect of the substituent
varied, is close to unity for the series 5a–j studied.
The foregoing linear correlation between pKa values and sxꢀ
constants and the values of
dence that the studied compounds 5 exist predominantly in the
r
and rꢀ found to provide further evi-
NH
Ph
hydrazone form 5A. This is because the values of
r (2.445) and
NH2
rꢀ¼1.00 are similar to those reported for ionization of phenols
N
CH3COCH2COOEt
N
(r
¼2.67; rꢀ¼1.00) and anilinium ions (
r
¼2.77; rꢀ¼1.00) in 50%
+
N
Ph
N
ethanol–water mixture.26–28 This finding indicates that the negative
charge in the anion formed by deprotonation of 5 is largely localized
on the N-atom adjacent to the benzene bearing the substituent.
Thus, it is not unreasonable to conclude that the observed linear
correlation of the dissociation constants with the enhanced Ham-
mett substituent constant indicates that the hydrazone tautomeric
form 5A prevails under the conditions of the measurement of pKa’s.
In conclusion, we have encountered a novel series of 6-arylhy-
drazono-1,3-diphenyl-7-methyl-1H-pyrazolo[30,40:4,5]pyrimido[1,6-b]
[1,2,4]triazepin-5(6H)-ones 5 and both their spectral data and LFER
correlations of their acidity constants indicate collectively that such
compounds exist predominantly in the hydrazone tautomeric form 5A.
2
1
O
H3C
N
N
CH3
O
Ph
Ph
N
N
N
N
H
N
N
N
Ph
N
N
Ph
N
3
4
Ar
NH
O
N
N
CH3
COCH3
Ph
N
1
Et3N
N
+
3. Experimental
3.1. General
N
Ar
N
H
COOEt
N
N
Ph
N
6
5
Melting points were determined on a Gallenkamp apparatus. IR
spectra were recorded in potassium bromide using Perkin–Elmer
FTIR 1650 and Pye-Unicam SP300 infrared spectrophotometers. 1H
NMR and 13C NMR spectra were recorded in deuterated dimethyl
sulfoxide using a Varian Gemini 300 NMR spectrometer. Mass
Ar = X C6H4
X : a, 4-OCH3; b, 4-CH3; c, 3-CH3; d, H; e, 4-Cl; f, 3-Cl;
g, 3-NO2; h, 4-NO2; i, 4-COCH3; j, 4-EtOCO
Scheme 1.

646
A.S. Shawali, T.A. Farghaly / Tetrahedron 65 (2009) 644–647
spectra were recorded on a GCMS-QP 1000 EX Shimadzu and GCMS
5988-A HP spectrometers. Electronic absorption spectra were
recorded on Perkin–Elmer Lambada 40 spectrophotometer. Ele-
mental analyses were carried out using German made Elementar
vario LIII CHNS analyzer at the Microanalytical Laboratory of Cairo
University, Giza, Egypt. 5-Amino-1,3-diphenyl-4,5-dihydro-4-imino-1H-
pyrazolo[3,4-d]pyrimidine 116 and ethyl 2-arylhydrazonoacetoacetate
622 were prepared as previously described.
3.3.4. 6-(4-Methylphenylhydrazono)-1,3-diphenyl-7-methyl-1H-
pyrazolo[30,40:4,5]pyrimido[1,6-b][1,2,4]triazepin-5(6H)-one (5b)
Orange solid, (0.82 g, 70%), mp 248–250 ꢁC (ethanol). 1H NMR
(DMSO-d6)
ArH), 7.15 (d, J¼9 Hz, 2H, ArH), 7.34–7.76 (m, 10H, ArH), 8.23 (s, 1H,
pyrimidine-H), 10.35 (s, 1H, NH); 13C NMR (DMSO-d6)
193.01,
d
2.28 (s, 3H, CH3), 2.49 (s, 3H, CH3), 7.01 (d, J¼9 Hz, 2H,
d
164.68, 157.75, 156.25, 146.70, 139.36, 137.87, 135.83, 134.54, 130.31,
129.72, 129.28, 128.30, 127.73, 127.61, 125.86, 123.24, 121.99, 121.84,
119.91, 21.31, 14.44; IR (KBr) nmax 3301, 1666 cmꢀ1. MS m/z (%) 488
(Mþþ2, 34), 487 (Mþþ1, 96), 486 (Mþ, 100), 444 (59), 368 (38), 367
(42), 341 (24), 338 (30), 106 (32), 91 (40), 77 (27). Anal. Calcd for
C28H22N8O (486.54): C, 69.12; H, 4.56; N, 23.03. Found: C, 69.02; H,
4.31; N, 23.16%.
3.2. 1,3-Diphenyl-7-methyl-1H-pyrazolo[30,40:4,5]pyrimido-
[1,6-b][1,2,4]triazepin-5(6H)-one (3)
A mixture of 1 (3.01 g, 10 mmol) and ethyl acetoacetate 2 (2.0 g,
15 mmol) was heated to reflux for 30 h, then cooled. The oil residue
was treated with methanol. The solid formed was collected by fil-
tration and crystallized from N,N-dimethylformamide to give
compound 3 as pale yellow solid, (1.29 g, 35%). Mp >300 ꢁC. 1H
3.3.5. 6-(3-Methylphenylhydrazono)-1,3-diphenyl-7-methyl-1H-
pyrazolo-[30,40:4,5]pyrimido[1,6-b][1,2,4]triazepin-5(6H)-one (5c)
Red solid, (0.61 g, 50%), mp 242–244 ꢁC (ethanol). 1H NMR
(DMSO-d6)
ArH), 8.50 (s, 1H, pyrimidine-H), 11.18 (s, 1H, NH); 13C NMR (DMSO-
d6) 195.42, 164.72, 161.67, 152.20, 149.58, 147.00, 139.49, 139.32,
d 2.46 (s, 3H, CH3), 2.52 (s, 3H, CH3), 7.38–8.27 (m, 14H,
NMR (DMSO-d6)
10H, Ar–H), 9.62 (s, 1H, pyrimidine-H); 13C NMR (DMSO-d6)
173.85, 148.40, 140.53, 137.91, 129.28, 128.74, 127.66, 127.31,
d 2.31 (s, 3H, CH3), 4.21 (s, 2H, CH2), 7.43–8.75 (m,
d
d
137.99, 136.24, 134.74, 133.19, 129.24, 129.19, 128.31, 128.18, 128.06,
127.04, 124.74, 123.96, 122.91, 114.93, 24.73, 20.37; IR (KBr) nmax
3417, 1681 cmꢀ1. MS m/z (%) 487 (Mþþ1, 1), 486 (Mþ, 1), 369 (1),
368 (1), 187 (2), 146 (64), 131 (16), 120 (2), 105 (100), 104 (86), 77
(53). Anal. Calcd for C28H22N8O (486.54): C, 69.12; H, 4.56; N, 23.03.
Found: C, 69.30; H, 4.19; N, 22.95%.
122.46, 122.38, 120.79, 120.70, 120.66, 120.56, 115.16, 29.81, 19.80;
IR (KBr) nmax 1716 (CO) cmꢀ1. MS m/z (%) 369 (Mþþ1, 4), 368 (Mþ,
32), 350 (13), 281 (58), 228 (21), 187 (17), 152 (30), 126 (100), 116
(43), 111 (60), 102 (44), 91 (78), 77 (17). Anal. Calcd for C21H16N6O
(368.40): C, 68.47; H, 4.38; N, 22.81. Found: C, 68.24; H, 4.13; N,
22.62%.
3.3.6. 1,3-Diphenyl-7-methyl-6-(phenylhydrazono)-1H-pyrazolo-
[30,40:4,5]pyrimido[1,6-b][1,2,4]triazepin-5(6H)-one (5d)
1
3.3. 6-Arylhydrazono-1,3-diphenyl-7-methyl-1H-pyrazolo-
[30,40:4,5] pyrimido[1,6-b][1,2,4]triazepin-5(6H)-ones (5a–j)
Orange solid, (0.80 g, 68%), mp 228–230 ꢁC (dioxan–ethanol). H
NMR (DMSO-d6)
d
2.63 (s, 3H, CH3), 7.76–7.79 (m,15H, ArH), 8.24 (s,1H,
194.10, 164.69,
pyrimidine-H), 10.35 (s, 1H, NH); 13C NMR (DMSO-d6)
d
3.3.1. Method A
157.75, 156.25, 146.70, 139.36, 137.87, 136.25, 135.83, 134.54, 130.31,
129.72, 128.30, 127.61, 125.86, 121.99, 120.23, 119.21, 118.67, 116.31,
14.45; IR (KBr) nmax 3240, 1708 cmꢀ1. MS m/z (%) 474 (Mþþ2, 17), 473
(Mþþ1, 66), 472 (Mþ, 80), 429 (33), 367 (40), 340 (35), 338 (33), 286
(14), 127 (15), 92 (32), 77 (100). Anal. Calcd for C27H20N8O (472.51): C,
68.63; H, 4.27; N, 23.71. Found: C, 68.42; H, 4.06; N, 23.50%.
To a stirred solution of compound 3 (0.92 g, 2.5 mmol) in eth-
anol (20 mL) was added sodium hydroxide (0.1 g, 2.5 mmol) and
the mixture was cooled in an ice bath to 0–5 ꢁC. To the resulting
solution, while being stirred, was added dropwise over a period of
20 min a solution of the appropriate arenediazonium chloride,
prepared as usual by diazotizing the respective aniline (2.5 mmol)
in hydrochloric acid (6 M, 1.5 mL) with sodium nitrite (1 M, 2.5 mL).
The whole mixture was then left in a refrigerator overnight. The
precipitated solid was filtered, washed with water and finally
crystallized from ethanol to give the respective hydrazone 5.
3.3.7. 6-(4-Chlorophenylhydrazono)-1,3-diphenyl-7-methyl-1H-
pyrazolo[30,40:4,5]pyrimido[1,6-b][1,2,4]triazepin-5(6H)-one (5e)
Orange solid, (0.90 g, 71%), mp >300 ꢁC (dioxan). 1H NMR
(DMSO-d6)
ArH), 7.53 (d, J¼8 Hz, 2H, ArH), 8.05 (d, J¼8 Hz, 2H, ArH), 8.22 (s, 1H,
pyrimidine-H), 9.89 (s, 1H, NH); 13C NMR (DMSO-d6)
193.43,
d 2.57 (s, 3H, CH3), 7.36–7.48 and 7.58–7.69 (m, 10H,
3.3.2. Method B
d
A mixture of 1 (0.76 g, 2.5 mmol) with ethyl 2-arylhydrazono-3-
oxobutanoate 6 (5 mmol) in dioxan (30 mL) and triethylamine
(0.35 mL) was heated to reflux for 10 h, then cooled. The solid
formed was collected by filtration and crystallized from the
appropriated solvent to give the corresponding compounds 5a, 5d,
and 5h, which were found identical in all respects with that pro-
duced by method A.
162.33, 151.34, 149.12, 147.32, 141.37, 138.12, 132.09, 131.36, 129.26,
129.13, 128.95, 128.68, 128.19, 127.30, 127.24, 126.75, 121.78, 117.63,
116.64, 13.82; IR (KBr) nmax 3394,1705 cmꢀ1. MS m/z (%) 508 (Mþþ2,
33), 507 (Mþþ1, 38), 506 (Mþ, 100), 367 (30), 339 (40), 302 (62),
287 (48), 198 (51), 111 (3), 77 (20). Anal. Calcd for C27H19ClN8O
(506.96): C, 63.97; H, 3.78; N, 22.10. Found: C, 63.69; H, 3.61; N,
21.95%.
3.3.3. 6-(4-Methoxyphenylhydrazono)-1,3-diphenyl-7-methyl-1H-
pyrazolo[30,40:4,5]pyrimido[1,6-b][1,2,4]triazepin-5(6H)-one (5a)
Red solid, (0.78 g, 62%), mp 210–212 ꢁC (ethanol–dioxan). 1H
3.3.8. 6-(3-Chlorophenylhydrazono)-1,3-diphenyl-7-methyl-1H-
pyrazolo[30,40:4,5]pyrimido[1,6-b][1,2,4]triazepin-5(6H)-one (5f)
Dark red solid, (0.72 g, 57%), mp 150–152 ꢁC (ethanol). 1H NMR
NMR (DMSO-d6)
d
2.32 (s, 3H, CH3), 3.85 (s, 3H, OCH3), 7.08 (d,
(DMSO-d3)
1H, pyrimidine-H), 11.10 (s, 1H, NH); 13C NMR (DMSO-d6)
193.00, 160.12, 159.29, 156.39, 155.00, 149.62, 145.29, 140.26,
d 2.34 (s, 3H, CH3), 7.39–8.02 (m, 14H, ArH), 9.01 (s
J¼8 Hz, 2H, ArH), 7.38–7.59 (m, 10H, ArH), 7.80 (d, J¼8 Hz, 2H, ArH),
8.34 (s, 1H, pyrimidine-H), 11.0 (s, 1H, NH); 13C NMR (DMSO-d6)
d
d
193.60, 164.05, 159.82, 152.30, 147.71, 144.88, 140.09, 137.50,
139.11, 137.53, 131.09, 130.33, 129.60, 128.40, 128.21, 127.45,
124.63, 122.05, 121.40, 119.44, 118.05, 115.26, 13.21; IR (KBr) nmax
3433, 1680 cmꢀ1. MS m/z (%) 508 (Mþþ2, 34), 507 (Mþþ1, 83),
506 (Mþ, 100), 491 (31), 481 (23), 479 (30), 368 (30), 339 (57),
338 (30), 312 (43), 286 (78), 77 (57). Anal. Calcd for C27H19ClN8O
(506.96): C, 63.97; H, 3.78; N, 22.10. Found: C, 63.76; H, 3.52; N,
22.40%.
131.04, 130.79, 129.82, 128.23, 128.09, 127.57, 127.47, 127.41, 125.66,
121.32, 119.35, 116.20, 67.09, 13.21; IR (KBr) nmax 3395, 1658 cmꢀ1
.
MS m/z (%) 504 (Mþþ2, 36), 503 (Mþþ1, 51), 502 (Mþ, 51), 369 (52),
368 (81), 299 (14), 196 (17), 141 (4), 102 (25), 90 (89), 77 (85), 76
(100). Anal. Calcd for C28H22N8O2 (502.54): C, 66.92; H, 4.41; N,
22.30. Found: C, 66.60; H, 4.21; N, 22.17%.

A.S. Shawali, T.A. Farghaly / Tetrahedron 65 (2009) 644–647
647
3.3.9. 6-(3-Nitrophenylhydrazono)-1,3-diphenyl-7-methyl-1H-
pyrazolo[30,40:4,5]pyrimido[1,6-b][1,2,4]triazepin-5(6H)-one (5g)
Dark yellow solid, (0.66 g, 51%), mp 296–298 ꢁC (dioxan). 1H
and the titroprocessor were calibrated with standard Beckman
buffer solutions of pH 4.01 and 7.00. The pH meter reading B
recorded in dioxan–water solution was converted to hydrogen ion
concentration [Hþ] by means of the relation of van Uitert and
Haas28 namely:
NMR (DMSO-d6)
d
2.42 (s, 3H, CH3), 7.34–7.83 (m, 14H, ArH), 8.23 (s
191.95,
1H, pyrimidine-H), 11.09 (s, 1H, NH); 13C NMR (DMSO-d6)
d
165.38, 159.15, 156.85, 151.31, 149.70, 145.31, 140.10, 139.23, 137.53,
131.11, 130.75, 129.78, 128.02, 127.50, 127.47, 123.56, 122.31, 121.48,
119.65, 118.21, 116.30, 14.16; IR (KBr) nmax 3301, 1655 cmꢀ1. MS m/z
(%) 519 (Mþþ2, 4), 518 (Mþþ1, 6), 517 (Mþ, 7), 369 (1), 260 (83), 232
(6), 218 (16), 208 (19), 142 (96), 132 (22), 121 (10), 106 (100), 105
(97), 77 (52). Anal. Calcd for C27H19N9O3 (517.51): C, 62.67; H, 3.70;
N, 24.36. Found: C, 62.45; H, 3.61; N, 24.45%.
Llog½HDꢃ [ BDlog UH
where log UH is the correction factor for the solvent composition
and ionic strength used for which B is read. The value of log UH
was found to be 0.48. A carbonate-free sodium hydroxide titrant
was prepared and standardized against potassium hydrogen phtha-
late solution.
The experimental procedure followed in the determination of
pKa values and their calculations, by the method of least squares,
fromthe titrant volume-pH data using the relation: pKa¼pHiꢀlog Vi/
(VeꢀVi), is similar to that previously described.4,6,29 In this equation,
pHi is the corrected pH value of the solution when the volume of the
added titrant is Vi and Ve is the volume of the titrant at the equiva-
lence point. The calculations of the pKa values were carried out using
computer program MINIQUAD-75.30 The pKa values obtained were
reproducible to within ꢂ0.02 pKa unit. The results are summarized
in Table 1.
3.3.10. 6-(4-Nitrophenylhydrazono)-1,3-diphenyl-7-methyl-1H-
pyrazolo[30,40:4,5]pyrimido[1,6-b][1,2,4]triazepin-5(6H)-one (5h)
Orange solid, (0.88 g, 68%), mp 268–270 ꢁC (dioxan). 1H NMR
(DMSO-d6)
J¼7 Hz, 2H, ArH), 8.74 (d, J¼7 Hz, 2H, ArH), 9.77 (s 1H, pyrimidine-H),
11.74 (s, 1H, NH); 13C NMR (DMSO-d6)
194.05, 162.50, 154.49,
d 2.49 (s, 3H, CH3), 7.40–8.29 (m, 10H, ArH), 8.60 (d,
d
152.83, 146.70, 140.50, 137.66, 130.81, 129.15, 129.07, 128.62, 128.49,
127.63,127.20,125.52,123.19,122.24,120.60,114.72,114.34, 25.52; IR
(KBr) nmax 3433,1693 cmꢀ1. MS m/z (%) 518 (Mþþ1,18), 517 (Mþ, 67),
516 (35), 367 (36), 339 (25), 338 (43), 312 (13), 287 (11),154 (11),127
(17), 116 (15), 77 (100), 76 (34). Anal. Calcd for C27H19N9O3 (517.51):
C, 62.67; H, 3.70; N, 24.36. Found: C, 62.41; H, 3.29; N, 24.16%.
References and notes
1. Shawali, A. S.; Elsheikh, S.; Parkanyi, C. J. Heterocycl. Chem. 2003, 40, 207.
2. Shawali, A. S.; Abdallah, M. A.; Mosselhi, M. N.; Mohamed, Y. F. Z. Naturforsch.
2002, 57B, 552.
3. Shawali, A. S.; Abdelkader, M. H.; Eltalbawy, F. M. A. Tetrahedron 2002, 58,
2875.
4. Mosselhi, M. N.; Abdallah, M. A.; Mohamed, Y. F.; Shawali, A. S. Phosphorus,
Sulfur Silicon Relat. Elem. 2002, 177, 487.
5. Shawali, A. S.; Zeid, I. F.; Abdelkader, M. H.; Eltalbawy, F. M. A. J. Chin. Chem. Soc.
2001, 48, 65.
6. Mosselhi, M. A. N.; Abdallah, M. A.; Riyadh, S. M.; Harhash, A. E.; Shawali, A. S.
J. Prakt. Chem. 1998, 340, 160.
7. Shawali, A. S.; Harb, N. M. S.; Badahdah, K. O. J. Heterocycl. Chem. 1985, 22,
1397.
8. (a) Shawali, A. S.; Mosselhi, M. N.; Farghaly, T. A. J. Chem. Res. 2007, 479; (b)
Shawali, A. S.; Sherif, S. M.; Farghaly, T. A.; Shehata, M. R.; Darwish, M. A. A.
J. Chem. Res. 2007, 44.
3.3.11. 6-(4-Acetylphenylhydrazono)-1,3-diphenyl-7-methyl-1H-
pyrazolo[30,40:4,5]pyrimido[1,6-b][1,2,4]triazepin-5(6H)-one (5i)
Red solid, (0.72 g, 56%), mp 118–120 ꢁC (ethanol). 1H NMR
(DMSO-d6)
2H, ArH), 7.56–8.00 (m, 10H, ArH), 8.20 (d, J¼7 Hz, 2H, ArH), 8.68 (s,
1H, pyrimidine-H), 13.56 (s, 1H, NH); 13C NMR (DMSO-d6)
194.50,
d
2.50 (s, 3H, CH3), 2.64 (s, 3H, COCH3), 7.41 (d, J¼7 Hz,
d
194.41, 168.00, 149.90, 144.65, 129.89, 129.77, 129.57, 129.20, 128.99,
128.88, 128.74, 128.51, 128.19, 127.85, 126.97, 123.01, 122.75, 120.65,
120.63, 113.61, 25.68, 14.00; IR (KBr) nmax 3062, 1678 cmꢀ1. MS m/z
(%) 515 (Mþþ1, 3), 514 (Mþ, 6), 342 (33), 325 (100), 324 (11), 272 (12),
104 (4), 98 (54), 84 (18), 77 (45). Anal. Calcd for C29H22N8O2 (514.55):
C, 67.69; H, 4.31; N, 21.78. Found: C, 67.51; H, 4.03; N, 21.64%.
9. Tao, J.; Mao, G.; Daehne, L. J. Am. Chem. Soc. 1999, 121, 3475.
10. Navarro, A.; Sanz, F. Dyes Pigm. 1999, 40, 131.
11. Karpicz, R.; Gulbinas, V.; Undzenas, A. J. Chin. Chem. Soc. 2000, 47, 589.
12. Isak, S. J.; Eyring, E. M.; Spikes, J. D.; Meekins, P. A. J. Photochem. Photobiol., A
2000, 134, 77.
13. Bhaskar, M.; Gnanamani, A.; Ganeshjeevan, R. J.; Chandraskar, R.; Sadulla, S.;
Radhakrishnan, G. J. Chromatogr., A 2003, 1018, 117.
14. Dakiky, M.; Nemcova, I. Dyes Pigm. 2000, 44, 181.
15. Nagoka, K. Jpn. Kokai Tokyo 09,222,710; Chem. Abstr. 1997, 127, 301208g.
16. Shawali, A. S.; Fahmi, A. A.; Albar, H. A.; Hassaneen, H. M.; Abdelhamid, H. A.
J. Chem. Res., Synop. 1994, 6; J. Chem. Res., Miniprint 1994, 1040.
17. Taha, M. A. J. Indian Chem. Soc. 2005, 82, 76.
3.3.12. 6-(4-Ethoxycarbonylphenylhydrazono)-1,3-diphenyl-4-
methyl-1H-pyrazolo[30,40:4,5]pyrimido[1,6-b][1,2,4]triazepin-
5(6H)-one (5j)
Red solid, (0.58 g, 42%), mp 158–160 ꢁC (ethanol). 1H NMR
(DMSO-d6)
d
1.37 (t, J¼7 Hz, 3H, CH3), 2.48 (s, 3H, CH3), 4.35 (q,
J¼7 Hz, 2H, CH2), 7.45–7.62 (m, 10H, ArH), 7.99 (d, J¼8 Hz, 2H, ArH),
8.32 (d, J¼8 Hz, 2H, ArH), 8.65 (s 1H, pyrimidine-H), 10.75 (s, 1H,
NH); 13C NMR (DMSO-d6)
d 193.49, 162.34, 157.00, 151.37, 151.09,
149.80, 144.00, 141.41, 138.08, 132.05, 131.51, 129.17, 129.01, 128.70,
128.24, 127.22, 126.85, 123.12, 121.86, 117.67, 116.67, 61.10, 25.35,
13.83; IR (KBr) nmax 3386, 1720, 1680 cmꢀ1. MS m/z (%) 545 (Mþþ1,
7), 544 (Mþ, 15), 434 (23), 395 (40), 368 (24), 351 (23), 325 (34), 287
(53), 271 (33), 142 (27), 116 (22), 103 (40), 92 (23), 77 (100). Anal.
Calcd for C30H24N8O3 (544.58): C, 66.17; H, 4.44; N, 20.58. Found: C,
66.21; H, 4.19; N, 20.77%.
18. Essassi, E. M.; Lavergne, J. P.; Viallefont, Ph. J. Heterocycl. Chem. 1975, 12, 661.
19. Hassan, Kh. M.; Ahmed, R. A.; Abdel-Hafez, Sh. H.; Abdel-Azim, M. A. Phos-
phorus, Sulfur Silicon Relat. Elem. 2006, 181, 481.
20. Romano, C.; De La Cuesta, E.; Avendano, C.; Florencio, F.; Sainz-Aparicio, J.
Tetrahedron 1988, 44, 7185.
21. Baraldi, P. G.; El-Kashef, H.; Farghaly, A.; Vanelle, P.; Fruttarolo, F. Tetrahedron
2004, 60, 5093.
22. Karci, F.; Demircali, A. Dyes Pigm. 2007, 74, 288.
23. Jones, R.; Ryan, A. J.; Sternhell, S.; Wright, S. E. Tetrahedron 1963, 19, 1497.
24. Shawali, A. S.; Khattab, S. A.; Farag, A. M. J. Chem. Eng. Data 1977, 22, 104.
25. Johnson, C. D. The Hammett Equation; Cambridge University: London, 1973;
pp 1–24.
3.4. pKa Determination of compounds 5a–j
26. Shawali, A. S.; Hassaneen, H. M.; Hanna, M. A. Heterocycles 1981, 15, 697.
27. Elhilaly, A. E.; Shawali, A. S.; Madkour, M. A. Inorg. Chim. Acta 1979, 36, 179.
28. van Uitert, L. G.; Haas, C. G. J. Am. Chem. Soc. 1953, 75, 451.
29. Albert, A.; Serjeant, E. P. The Determination of Ionization Constants; Chapman
and Hall: London, 1971; pp 9–39.
The acid dissociation constants of compounds 5 were de-
termined potentiometrically in 80% dioxan–water mixtures at
25ꢂ0.1 ꢁC and ionic strength (KNO3) of 0.1. A Meetrohm 686
titroprocessor equipped with 665 Dosimat was used. The electrode
30. Gans, P.; Sabatini, A.; Vacca, A. Inorg. Chim. Acta 1976, 18, 237.