On the chemistry of 5-aryl-2-hydrazino-benzo[6,7]cyclohepta[1,2-o]pyrido[2, 3-e] pyrimidin-4-one

Article abstract of DOI:10.1002/hc.20248

Several pyrido[2,3-e]pyrimidine fused with other rings have been prepared by intramolecular cyclization of 5-(4-chlorophenyl)-2-hydrazino-benzo [6,7]cyclohepta-[1,2-b]pyrido[2,3-e]pyrimidine-4-one (1) with acids, carbon disulfide to form triazole derivati

Full text of DOI:10.1002/hc.20248

Heteroatom Chemistry
Volume 18, Number 1, 2007
On the Chemistry of 5-Aryl-2-hydrazino-
benzo[6,7]cyclohepta[1,2-b]pyrido[2,3-e]
pyrimidin-4-one
A. B. A. El-Gazzar, Kh. M. Abu-Zied, and N. Khir El-Din
Photochemistry Department (Heterocyclic Unit), National Research Center, Dokki, Giza, Egypt
Received 7 July 2005; revised 6 December 2005
tericide [4], and leishmanicide [5,6]. This aroused
ABSTRACT: Several pyrido[2,3-e]pyrimidine fused
considerable interest to design and synthesize com-
with other rings have been prepared by intramolecular
pounds that have profound leishmanicidal activity.
cyclization of 5-(4-chlorophenyl)-2-hydrazino-benzo
Thus, in continuation of our work on the synthesis of
[6,7]cyclohepta-[1,2-b]pyrido[2,3-e]pyrimidine-4-one
pyridopyrimidines [7] and pyridopyrimidines fused
(1) with acids, carbon disulfide to form triazole
with other ring systems [8–10] as a biologically ac-
derivatives (2,4), halo-ketones to give triazine deriva-
tive materials, we report in this paper the synthesis of
tive (5), ꢀ-ketoesters, ꢀ-cyanoesters, and ꢀ-diketones
new compounds derived from the biologically active
to yield 2-(1-pyrazolyl) derivatives (7,9,10), and
starting material.
aldehydes to form arylhydrazone derivatives (11a,b)
Heating under reflux the solution of 5-(4-chlo-
which cyclized to form triazoles (12a,b). Also, acyclic
rophenyl)-2-hydrazino-benzo-[6,7]cyclohepta[1,2-b]
N-nucleosides are prepared by heating under reflux 2-
pyrido[2,3-e]pyrimidine-4-one (1) with aliphatic
hydrazino-benzo[6,7]cyclohepta[1,2-b]pyrido[2,3-e]
acids, namely formic or acetic acid, resulted in the
pyrimidin-4-one (1) with xylose and glucose to give the
formation of 6-(4-chlorophenyl)-3-(un)substituted-
corresponding acyclic N-nucleosides (13a,b) which
1H-benzo[6,7] cyclohepta[1,2-b] pyrido[2,3-e][1,2,4]
are cyclized to afford the corresponding protected tetra
triazolo[2’,3’:5,6]pyrimidin-5(5H)-one (2a,b) (see
and penta–O-acetate C-nucleosides (14a,b). Deacety-
Scheme 1). Besides the correct values in elemental
lating of the latter nucleosides afforded the free acyclic
1
analysis, the IR and H-NMR spectra of 2a,b are in
ꢀ
C
C-nucleosides (15a,b).
2007 Wiley Periodicals, Inc.
agreement with the assigned structure. The 1H-NMR
(DMSO-d6) of 2a as an example showed signals at
δ 1.72–1.84 (m, 4H, 2CH2), 2.56 (m, 2H, CH2),
7.35–7.38 (d, 2H p-subs-phenyl), 7.54–7.57 (m, 1H,
disub-phenyl), 7.82–7.91 (m, 2H, disub-phenyl),
8.23–8.26 (d, 2H, p-subs-phenyl), 8.34–8.37 (m, 1H,
disubs-phenyl), 8.62 (s, 1H, triazole proton), and
13.02 (brs, 1H, NH, D2O exchangeable). The MS of
this compound showed molecular ion peak at m/z:
413 (M+) 100%, 415 (M+ + 1) 37%, 385 (M+ − CO)
56%. On the other hand, the 2-acetylhydrazino
derivative 3 was produced upon heating compound
1 with acetic acid for 2 h under reflux. The IR of
compound 3 showed the absorption of two carbonyl
bands at 1700 and 1689 cm−1. The MS of this
Heteroatom Chem 18:34–43, 2007; Published online in
Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.20248
INTRODUCTION
Pyrimidines, being an integral part of nucleic acids
and many chemotherapeutic agents, display a wide
range of pharmacological activities as phosphodi-
esterase inhibitor [1], fungicide [2], viricide [3], bac-
Correspondence to: Khir El-Din; e-mail: Nahid khaireldin@
hotmail.com.
c
ꢀ
2007 Wiley Periodicals, Inc.
34

On the Chemistry of 5-Aryl-2-hydrazino-benzo[6,7]cyclohepta[1,2-b]pyrido[2,3-e]pyrimidin-4-one 35
compound showed ion peaks at m/z: 445 (M+) 100%
phenyl), 8.40–8.42 (m, 1H, disubs-phenyl), and 11.09
(brs, 1H, NH, D2O exchangeable). The MS of this
compound showed ion peak at m/z: 445 (M+) 100%.
The cyclization of 2-hydrazino derivatives with
formic acid and/or carbon disulfide at N-3 nitrogen
atom producing the 1,2,4-triazolo pyrimidinone
was previously noted [11,12]. Also, the 2-hydrazino
derivative 1 was used for the preparation of pyrido-
pyrimidotriazine derivative 5. Thus, heating under
reflux compound 1 with chloroacetone in dry
xylene for 6 h yielded directly 3-methyl-7-(4-chloro-
phenyl)benzo[6,7]cyclohepta[1,2-b]pyrido[2,3-e][1,2,
4]triazino-[2’,3’:5,6]-pyrimidin-5(5H)-one (5).
Moreover, the 2-hydrazino derivative 1 reacted
with some ꢀ-ketoesters, ꢀ-cyanoesters, and ꢀ-
diketones to form 2-(1-pyrazolyl) derivatives. Thus,
when compound 1 was heated with ethyl acetoac-
etate in absolute ethanol, it gave the hydrazone
derivative 6, while the pyrazolyl derivative 7 was pro-
duced by heating 1 with ethyl acetoacetate under
reflux in ethanolic sodium ethoxide. Compound 6
and 446 (M+ + 1) 29%.
Similarly, the 2-hydrazino 1 reacted with car-
bon disulfide in ethanolic potassium hydroxide
solution to afford 3(3H)-thioxo-6-(4-chlorophenyl)
benzo[6,7]-cyclohepta[1,2-b]pyrido[2,3-e][1,2,4]tria-
zolo[2’,3’:5,6]pyrimidin-5(5H)-one (4). The IR spec-
–1
trum of 4 displayed absorption bands at 3400 cm
(NH) and 1686 cm−1 (CO). Its H-NMR spectrum
1
(DMSO-d6) showed signals at ꢁ 1.73–1.81 (m, 4H,
2CH2), 2.54 (m, 2H, CH2), 7.33–7.35 (d, 2H p-subs-
phenyl), 7.51–7.53 (m, 1H, disub-phenyl), 7.77–7.80
(m, 2H, disub-phenyl), 8.19–8.21 (d, 2H, p-subs-
SCHEME 1
Heteroatom Chemistry DOI 10.1002/hc

36 El-Gazzar, Abu-Zied, and El-Din
TABLE 1 Physical Data for the Products 2–15
Elemental Analyses Calcd./Found
Compound
2a
MP. ( ◦C)
Yield (%)
67
M.F. (M.Wt.)
C
H
N
304–307
decom.
269–271
decom.
310–312
melted
342–345
decom.
323–325
decom.
271–273
melted
329–331
decom.
296–298
decom.
282–285
decom.
339–341
decom.
301–303
melted
293–295
melted
285–287
melted
263–265
melted
329–331
decom.
341–343
decom.
182–184
decom.
171–173
decom.
62–64
C23H16N5ClO
(413.85)
66.75
66.72
67.36
67.29
64.64
64.59
61.94
61.87
67.94
67.89
65.17
65.20
66.45
66.43
63.16
63.09
65.61
65.58
63.76
63.73
69.30
69.25
64.55
64.50
70.79
70.81
69.02
69.04
71.09
71.11
71.49
71.39
60.50
60.61
59.41
59.33
59.87
59.89
57.86
57.78
60.73
60.68
59.63
59.43
3.90
3.86
4.24
4.25
4.52
4.54
3.62
3.71
4.56
4.52
5.08
5.11
4.29
4.31
3.81
3.77
4.34
4.29
4.07
4.09
4.74
4.71
4.21
4.17
4.51
4.48
4.63
4.59
4.11
4.09
4.40
4.51
4.89
4.90
4.98
4.99
4.59
4.62
4.81
4.84
4.53
4.50
4.65
4.67
16.92
16.85
16.37
16.35
15.71
15.67
15.71
15.65
15.85
15.74
13.57
13.54
14.90
14.78
16.11
16.02
16.23
16.19
17.85
17.78
14.97
14.81
13.94
13.89
14.24
14.17
13.42
13.39
14.29
14.23
13.90
13.67
13.07
12.98
12.37
12.34
9.97
2b
63
C
24H18N5ClO
(427.87)
3
72
C
24H20N5ClO2
(445.89)
4
65
C
23H16N5ClOS
(445.91)
5
54
C
25H20N5ClO
(441.90)
6
79
C
C
28H26N5ClO3
(515.98)
26H20N5ClO2
(469.91)
7
48
8a
63
C
32H23N7Cl O2
(608.46)2
33H26N7ClO3
(604.04)
8b
59
C
9
61
C
25H19N6ClO2
(470.90)
10a
10b
11a
11b
12a
12b
13a
13b
14a
14b
15a
15b
78
C
27H22N5ClO
(467.94)
75
C
C
27H21N5Cl O
(502.39) 2
69
C
29H22N5ClO
(491.96)
76
30H24N5ClO2
(521.98)
55
C
29H20N5ClO
(489.94)
57
C
C
C
C
30H22N5ClO2
(503.97)
27H26N5O5Cl
(536.02)
28H28N5ClO6
(565.99)
35H32N5ClO9
(702.10)
69
76
52
melted
58–60
melted
161–163
decom.
143–145
decom.
10.01
9.29
9.32
13.12
13.09
12.42
12.39
63
C
38H36N5ClO11
(754.16)
48
C
27H24N5ClO5
(533.95)
56
C
28H26N5ClO6
(563.98)
1H-NMR spectrum of 7 showed no signals corre-
sponding to ethyl group protons (cf. Experimental).
Compound 7 was coupled with aromatic diazonium
salts to afford the corresponding azo derivatives
8a,b. The IR spectra of 8a displayed absorption
bands around 3450 cm−1 (OH), 3180 cm−1 (NH), and
1671 cm−1 (CO). The 1H-NMR spectrum (DMSO-d6)
of 8a, as an example, showed signals at δ 1.72 ppm
(m, 4H, 2CH2), 2.34 (s, 3H, CH3), 2.58 (m, 2H, CH2),
7.33–7.35 (two d, 4H p-subs-phenyl), 7.51–7.53 (m,
1H, disub-phenyl), 7.77–7.80 (m, 2H, disub-phenyl),
8.19–8.21 (d, 2H, p-subs-phenyl), 8.23–8.26 (d, 2H,
could be converted to 7 upon heating with ethanolic
sodium ethoxide solution. The H-NMR spectrum
1
(CDCl3) of 6 showed signals at δ 1.30 ppm (t, 3H,
CH3), 1.71 (m, 4H, 2CH2), 2.00 (s, 3H, CH3), 2.60 (m,
2H, CH2), 3.31 (s, 2H, CH2), 4.19 (q, 2H, CH2), 7.33–
7.35 (d, 2H p-subs-phenyl), 7.51–7.53 (m, 1H, disub-
phenyl), 7.77–7.80 (m, 2H, disub-phenyl), 8.19–8.21
(d, 2H, p-subs-phenyl), 8.40–8.42 (m, 1H, disubs-
phenyl), 9.51 (brs, 1H, NH, D2O exchangeable), and
10.06 (brs, 1H, NH, D2O exchangeable). And its IR
spectrum displayed absorption bands at 3279, 3206
cm−1 2(NH), 1741 and 1686 cm−1 2(CO). Also, the
Heteroatom Chemistry DOI 10.1002/hc

On the Chemistry of 5-Aryl-2-hydrazino-benzo[6,7]cyclohepta[1,2-b]pyrido[2,3-e]pyrimidin-4-one 37
p-subs-phenyl), 8.40–8.42 (m, 1H, disubs-phenyl),
12a,b displayed absorption bands around 3370
cm−1 (NH) and 1685 (C O). The 1H-NMR spectrum
(DMSO-d6) of 12a, as an example, showed signals
at δ 1.70 ppm (m, 4H, 2CH2), 2.53 (m˜ , 2H, CH2),
7.20–7.28 (d, 2H p-subs-phenyl), 7.43–7.47 (m, 4H,
1H for disub-phenyl + 3H for phenyl), 7.61–7.70 (m,
4H, 2H for disub-phenyl + 2H for phenyl), 8.21–8.25
(d, 2H, p-subs-phenyl), 8.36–8.40 (m, 1H, disubs-
phenyl), and 10.65 (brs, 1H, NH, D2O exchangeable).
According to the Shishoo synthesis of hydrazi-
nopyrimidine [13] derivatives and Elgazzar for C-nu-
cleoside synthesis [8], the reaction of compound
1 with some penta monosaccharides, namely,
D-xylose or D-glucose in dry dioxane in the pres-
ence of catalytic amounts of pipridine, yielded the
corresponding 2-(glucosylhydrazon)-5-(4-chlorop-
henyl)benzo[6,7]cyclohepta[1,2-b]pyrido[2,3-e]pyri-
midin-4-one (13a,b). The spectral data besides the
correct values in elemental analyses support the
open chain nature of the sugar residue in 13a,b.
Moreover, the IR (KBr) spectrum for 13a displayed
absorption bands at 3430 cm−1 (broad, OH), 3221
(NH), and 1687 (C O). Its NMR spectrum of
compound 13a, as an example, showed signals
at δ 1.67 (m, 4H, 2CH2), 2.55 (m, 2H, CH2), 3.31
(m, 2H, CH2), 3.53 (m, 4OH, D2O exchangeable,
OH-2ꢁ, OH-5’), 4.21 (q, 1H, J = 6 Hz, H-4ꢁ), 4.45 (m,
2H, H-5ꢁꢁ), 4.61 (d, 1H, J = 5 Hz, H-3’), 5.76 (dd,
1H, J = 7 Hz, H-2ꢁ), 7.29 (d, 1H, J = 4 Hz, H-1ꢁ),
7.35–7.37 (d, 2H, p-subs-phenyl), 7.50–7.53 (m, 1H,
disub-phenyl), 7.76–7.80 (m, 2H, disub-phenyl),
8.18–8.21 (d, 2H, p-subs-phenyl), 8.39–8.42 (m,
1H, disub-phenyl), and 11.25 (brs, 1H, NH, D2O ex-
changeable). The MS of the latter compound showed
ion peak at m/z: 536 (M+) 100%. The hydrazone
derivatives 13a,b were stirred at room tempera-
ture in acetic anhydride-pyridine (1:1) mixture to
afford the corresponding 3-(2ꢁ,3ꢁ,4ꢁ,5ꢁ-O-tetraacetyl-
glycosyl)- or 3-(1ꢁ,2ꢁ,3ꢁ,4ꢁ,5ꢁ-O-pentaacetyl-glucosyl)-
6-(4-chlorophenyl)benzo[6,7]-cyclohepta[1,2-b]pyr-
ido [2,3-e][1,2,4]triazolo[2ꢁ,3ꢁ:5,6]pyrimidin-5(5H)-
one(14a,b) (Scheme 3). The spectral data besides
the correct values in elemental analyses support
9.21 (brs, 1H, NH, D2O exchangeable), and 13.02
(brs, 1H, OH, D2O exchangeable). Its mass spec-
trum showed the molecular ion peak at m/z 608
(M+), 100%. Similarly, the 2-hydrazino deriva-
tive 1 reacted with ethyl cyanoacetate in ethanolic
sodium ethoxide solution afforded the 2-(3-amino-5-
hydroxy-4H-pyrazol-l-yl) derivative 9. The IR spec-
trum of 9 displayed absorption bands at 3340 cm−1
(NH2), 3260 cm−1 (NH), and 1687 cm−1 (CO). Its
1H-NMR spectrum (DMSO-d6) showed signals at δ
1.73–181 (m, 4H, 2CH2), 2.54 (m, 2H, CH2), 5.02
(brs, 2H, NH2, D2O exchangeable), 7.23–7.35 (d,
2H p-subs-phenyl), 7.50–7.53 (m, 1H, disub-phenyl),
7.71–7.74 (m, 2H, disub-phenyl), 8.0 (s, 1H, pyrazole
proton), 8.20–8.24 (d, 2H, p-subs-phenyl), 8.39–8.42
(m, 1H, disubs-phenyl), and 9.68 (brs, 1H, NH, D2O
exchangeable).
When equimolar amounts of 1 and pentane-
2,4-dione or 3-chloro-pentane-2,4-dione were heated
under ruflux in absolute ethanol, the 2-pyrazolyl-
pyrido[2,3-e]pyrimidinone 10a,b was obtained in
1
good yield. The H-NMR spectrum (DMSO-d6) of
10a, as an example, showed signals at δ 1.68 ppm (m,
4H, 2CH2), 2.55 (m˜ , 2H, CH2), 2.61 (s, 3H, CH3), 6.20
(s, 1H, CH), 7.21–7.30 (d, 2H p-subs-phenyl), 7.47–
7.51 (m, 1H, disub-phenyl), 7.69–7.72 (m, 2H, disub-
phenyl), 8.21–8.25 (d, 2H, p-subs-phenyl), 8.36–8.40
(m, 1H, disubs-phenyl), and 11.70 (brs, 1H, NH, D2O
exchangeable). Its IR spectrum displayed absorp-
tion bands at 3139 cm−1 (NH) and 1688 cm−1 (CO).
Its mass spectrum showed the molecular ion peak at
m/z 467.
The interaction of 1 with a proper aldehyde in
boiling dioxane in the presence of catalytic amounts
of piperidine afforded the arylhydrazone derivatives
11a,b(see Scheme 2) which could be cyclized into
the 3-aryl-benzo[6,7]cyclohepta[1,2-b]pyrido[2,3-e]
[1,2,4]-triazolo[2ꢁ,3ꢁ:5,6]pyrimidin-5(5H)-ones (12a,
b). Compounds 11a,b gave compatible spectral and
analytical data (experimental). The IR spectra of
1
the structure. The H-NMR spectrum of compound
14a, as an example, showed signals at δ 1.69 (m, 4H,
2CH2), 1.94 (s, 3H, CH3), 2.11 (s, 3H, CH3), 2.14 (s,
3H, CH3), 2.20 (s, 3H, CH3), 2.60 (m, 2H, CH2), 3.22
(m, 2H, CH2), 4.65 (m, 1H, H-3ꢁ), 5.23 (m, 2H, H-4ꢁ),
5.44 (m, 1H, H-2ꢁ), 5.75 (m, 1H, H-1ꢁ), 7.29–7.31 (d,
2H p-subs-phenyl), 7.46-7.52 (m, 1H, disub-phenyl),
7.74–7.79 (m, 2H, disub-phenyl), 8.20–8.23 (d, 2H,
p-subs-phenyl), 8.38–8.41 (m, 1H, disub-phenyl),
and 10.11 (brs, NH, D2O exchangeable).
Deprotection of the protected acyclic-C-nucleo-
sides 14a,b could be achieved by treatment with
SCHEME 2
Heteroatom Chemistry DOI 10.1002/hc

38 El-Gazzar, Abu-Zied, and El-Din
on Finnigan SSQ 7000 spectrometer. All reactions
were followed up by TLC. The starting 2-hydrazino
derivative was prepared according to El-Gazzar et al.
[7].
6-(4-Chlorophenyl)benzo[6,7]cyclohepta[1,2-
b]pyrido[2,3-e][1,2,4]triazolo[2ꢁ,3ꢁ:5,6]-
pyrimidin-5(5H)-one 2a
A mixture of compound 1 (4.03 g, 0.01 mol) and
formic acid (10 mL) was heated under reflux for
5 h. The reaction mixture was allowed to cool to
room temperature and poured onto water. The solid
product so precipitated was filtered off and recrystal-
lized from dioxane to produce 2a as colorless crys-
tals. IR spectrum (KBr) (cm−1): 3224 (NH), 2921
(CH aliphatic), and 1689 (CO). 1H-NMR (DMSO-
d6) δ (ppm): 1.72–1.84 (m, 4H, 2CH2), 2.56 (m,
2H, CH2), 7.35–7.38 (d, 2H p-subs-phenyl), 7.54–
7.57 (m, 1H, disub-phenyl), 7.82–7.91 (m, 2H, disub-
phenyl), 8.23–8.26 (d, 2H, p-subs-phenyl), 8.34–
8.37 (m, 1H, disubs-phenyl), 8.62 (s, 1H, triazole
proton), and 13.02 (brs, 1H, NH, D2O exchange-
able). MS (m/z): 413 (M+) 100%, 415 (M+ + 1)
37%.
SCHEME 3
ethanolic sodium hydroxide solution (25%) at room
temperature for 24 h. The deprotected acyclic-C-
nucleosides, mainly 3-xylosyl and 3-glucosyl-6-(4-ch-
lorophenyl)benzo[6,7]cyclohepta[1,2-b]pyrido[2,3-e]
[1,2,4]triazolo[2ꢁ,3ꢁ:5,6]pyrimidin-5(5H)-ones (15a,b)
were obtained (Scheme 3). The IR (KBr) for com-
pound 15b, as an example, displayed absorption
bands around 3439, 3465 (hydroxyl groups) and
3262 (NH) cm−1 and revealed the absence of any
absorption in the carbonyl region except that of the
3-Methyl-6-(4-chlorophenyl)benzo
[6,7]cyclohepta-[1,2-b]pyrido[2,3-e][1,2,4]
triazolo-[2ꢁ,3ꢁ:5,6]pyrimidin-5(5H)-one 2b
A mixture of compound 1 (4.03 g, 0.01 mol) and
glacial acetic acid (30 mL) was refluxed for 5 h.
The reaction mixture was allowed to cool to room
temperature and poured into water. The precipitate
was collected by filtration, dried, and recrystallized
from acetic acid to produce 2b as colorless crystals.
IR spectrum (KBr) (cm−1): 3277 (NH), 2985 (CH
1
carbonyl pyrimidone. Also, its H-NMR spectrum
showed signals at δ 1.67 (m, 4H, 2CH2), 2.59 (m,
2H, CH2), 3.12 (m, 5H, 5OH, D2O exchangeable),
3.31 (m, 2H, CH2), 3.37 (m, 1H, H-3ꢁ), 3.77 (m,
2H, H-5ꢁ, H-5ꢁꢁ), 4.25 (m, 1H, H-2ꢁ), 4.60 (m, 1H,
H-1ꢁ), 7.32–7.36 (d, 2H p-subs-phenyl), 7.51–7.55
(m, 1H, disub-phenyl), 7.75–7.78 (m, 2H, disub-
phenyl), 8.21–8.32 (d, 2H, p-subs-phenyl), 8.40–8.45
(m, 1H, disub-phenyl), and 10.35 (brs, NH, D2O
exchangeable).
1
aliphatic), 1681 (CO). H-NMR (DMSO-d6) δ (ppm):
1.73–181 (m, 4H, 2CH2), 2.41 (s, 3H, CH3), 2.56 (m,
2H, CH2), 7.31–7.35 (d, 2H, p-subs-phenyl), 7.45–
7.47 (m, 1H, disub-phenyl), 7.86–7.90 (m, 2H, disub-
phenyl), 8.25–8.27 (d, 2H, p-subs-phenyl), 8.32–8.35
(m, 1H, disub-phenyl), and 12.34 (brs, 1H, NH, D2O
exchangeable).
EXPERIMENTAL
2-(Acetylhydrazone)-5-(4-chlorophenyl)benzo
[6,7]cyclohepta[1,2-b]pyrido[2,3-e]-pyrimidin-4-
one 3
All melting points are uncorrected. Microanalysis
was carried out at the Microanalytical units, Na-
tional Research Center and Faculty of Science, Cairo
University. IR spectra were registered on a FT/IR-300
E Jasco using KBr disks. H-NMR spectra were mea-
sured in DMSO or CDCl3, using JEOL-JNM-Ex270
NMR spectrometer. The mass spectra were recorded
A mixture of compound 1 (4.03 g, 0.01 mol) and
glacial acetic acid (30 mL) was refluxed for 2 h. The
reaction mixture was allowed to cool to room tem-
perature and poured into water. The precipitate was
1
Heteroatom Chemistry DOI 10.1002/hc

On the Chemistry of 5-Aryl-2-hydrazino-benzo[6,7]cyclohepta[1,2-b]pyrido[2,3-e]pyrimidin-4-one 39
collected by filtration, dried, and recrystallized from
2-Ethylacetoacetatehydrazon-3H-5-(4-
chlorophenyl)benzo[6,7]cyclohepta[1,2-b]-
pyrido[2,3-e]pyrimidin-4-one 6
acetic acid to produce 3 as colorless crystals. IR
spectrum (KBr) (cm−1): 3287 (NH), 3215 (NH), 2985
1
(CH aliphatic), 1700 (CO), and 1689 (CO). H-NMR
A mixture of compound 1 (4.03 g, 0.01 mol) and
ethyl acetoacetate (1.30 g, 0.01 mol) was heated un-
der reflux in absolute ethanol for 5 h. The reaction
mixture was allowed to cool to room temperature
and poured into water. The precipitate so formed
was collected by filtration, dried, and recrystallized
from ethanol to produce 6 as colorless crystals. IR
spectrum (KBr) (cm−1): 3279 (NH), 3206 (NH), 2975
(DMSO-d6) δ (ppm): 1.70–1.83 (m, 4H, 2CH2), 2.66
(s, 3H, CH3), 2.54 (m, 2H, CH2),7.31–7.33 (d, 2H p-
subs-phenyl), 7.58–7.60 (m, 1H, disub-phenyl), 7.81–
7.84 (m, 2H, disub-phenyl), 8.34–8.36 (d, 2H, p-subs-
phenyl), 8.41–8.44 (m, 1H, disubs-phenyl), and two
bands at 12.18 (brs, 1H, NH) and 13.17 (brs, 1H, NH,
D2O exchangeable).
1
(CH aliphatic), 1741 (CO), and 1643 (CO). H-NMR
(CDCl3) δ(ppm): ꢁ 1.25 (t, 3H, CH3), 1.72–1.84 (m,
4H, 2CH2), 2.00 (s, 3H, CH3), 2.58 (m, 2H, CH2),
3.35 (s, 2H, CH2), 4.15 (q, 2H, CH2), 7.15–7.25 (d,
2H, p-sub-phenyl), 7.25–7.30 (m, 1H, disub-phenyl),
7.30–7.35 (m, 2H, disub-phenyl), 7.40–7.50 (d, 2H, p-
sub-phenyl), 8.20–8.30 (m, 1H, disub-phenyl), 9.80–
10.40 (brs, 1H, NH, D2O exchangeable), and 11.15
(brs, NH, D2O exchangeable).
3(3H)-Thioxo-6-(4-chlorophenyl)benzo
[6,7]cyclohepta[1,2-b]pyrido[2,3-e][1,2,4]-
triazolo[2ꢁ,3ꢁ:5,6]pyrimidin-5(5H)-one 4
To a warmed ethanolic sodium hydroxide solution
(prepared by dissolving sodium hydroxide (0.40 g,
0.01 mol) in ethanol (50 mL)), compound 1 (4.03 g,
0.01 mol) and carbon disulfide (10 mL) was added.
The mixture was heated on a water bath at 80oC un-
der reflux for 10 h, then it was poured into water,
neutralized by diluted acetic acid, and the formed
precipitate was filtered off. The product was re-
crystallized from dioxane to produce 4 as yellow
crystals. IR spectrum (KBr) (cm−1): 3404 (NH),
3122 (NH), 2929 (CH aliphatic), and 1664 (CO). 1H-
NMR (DMSO-d6δ 1.73–1.81 (m, 4H, 2CH2), 2.54 (m,
2H, CH2), 7.33–7.35 (d, 2H, p-subs-phenyl), 7.51–
7.53 (m, 1H, disub-phenyl), 7.77–7.80 (m, 2H, disub-
phenyl), 8.19–8.21 (d, 2H, p-subs-phenyl), 8.40–
8.42 (m, 1H, disub-phenyl), and 11.09 (brs, 1H,
NH, D2O exchangeable). MS (m/z): 445 (M+)
100%.
2-(3-Methyl-5-oxo-4H-pyrazol-1-yl)-3H-5-(4-
chlorophenyl)benzo[6,7]cyclohepta[1,2-
b]pyrido[2,3-e]pyrimidin-4-one 7
Method A. A solution of compound 1 (4.03 g,
0.01 mol) and ethyl acetoacetate (1.30 g, 0.01mol)
in sodium ethoxide solution (prepared by dissolv-
ing sodium metal (0.23 g , 0.01 mol) in absolute
ethanol (30 mL)) was heated under reflux for 5 h.
The reaction mixture was allowed to cool to room
temperature, poured into water, and neutralized by
diluted acetic acid solution. The solid product so
precipitated was filtered off, dried, and recrystallized
from dimethylformamide to produce 7 as colorless
crystals.
3-Methyl-7-(4-chlorophenyl)benzo
Method B. A solution of compound 6 (5.15 g,
0.01 mol) was heated under reflux with sodium
ethoxide solution (prepared by dissolving sodium
metal (0.23 g, 0.01 mol) in absolute ethanol (30
mL)) for 5 h. The reaction mixture was allowed
to cool to room temperature then poured into wa-
ter and neutralized by diluted acetic acid solution.
The precipitate formed was collected by filtration,
dried, and recrystallized from dimethylformamide
to produce 7 as colorless crystals. IR spectrum
(KBr) (cm−1): 3446 (OH), 2922 (CH aliphatic), and
1654 (CO) .1H-NMR (CDCl3-TFA) (ppm): ꢁ 1.73–
1.86 (m, 4H, 2CH2), 2.50 (s, 3H, CH3), 2.55–2.70
(m, 2H, CH2), 3.45 (s, 2H, CH2), 7.15–7.25 (d,
2H, p-sub-phenyl), 7.25–7.30 (m, 1H, disub-phenyl),
7.35–7.40 (m, 2H, disub-phenyl), 7.45–7.50 (d, 2H,
[6,7]cyclohepta[1,2-b]pyrido[2,3-e][1,2,4]-
triazin[2ꢁ,3ꢁ:5,6]pyrimidin-5(5H)-one 5
A mixture of compound 1 (4.03 g, 0.01 mol) and
chloroacetone (0.93 g, 0.01 mole) was heated under
reflux for 6 h in dry xylene (30 mL). The solid product
precipitated was filtered off and recrystallized from
dioxane to produce 5 as yellow crystals. IR spec-
trum (KBr) (cm−1): 3373 (NH), 2918 (CH aliphatic),
and 1688 (CO).1H-NMR (DMSO-d6) δ (ppm): 1.71–
1.83 (m, 4H, 2CH2), 2.05 (s, 3H, CH3), 2.56 (m, 2H,
CH2), 4.80 (s, 2H, CH2), 7.20–7.30 (d, 2H, p-sub-
phenyl), 7.35–7.40 (m, 1H, disub-phenyl), 7.45–7.55
(m, 4H, 2H, disub-phenyl + 2H p-sub-phenyl), 8.25–
8.40 (m, 1H, disub-phenyl), and 11.05 (brs, NH, D2O
exchangeable). MS (m/z): 441 (M+).
Heteroatom Chemistry DOI 10.1002/hc

40 El-Gazzar, Abu-Zied, and El-Din
p-sub-phenyl), 8.35–8.45 (m, 1H, disub-phenyl), and
14.3 (brs, NH, D2O exchangeable). MS (m/z): 469
(M+).
etate (1.13 g, 0.01 mol). The heating was continued
for 5 h. The reaction mixture was allowed to cool
to room temperature, poured into water, and neu-
tralized by diluted acetic acid solution. The solid
product so precipitated was filtered off, dried, and
recrystallized from dimethylformamide to produce
9 as yellow crystals. IR spectrum (KBr) (cm−1): 3340
(NH2), 3260 (NH), and 1687 (CO). Its 1H-NMR spec-
trum (DMSO-d6) (ppm): δ 1.73–181 (m, 4H, 2CH2),
2.54 (m, 2H, CH2), 5.02 (brs, 2H, NH2, D2O exchange-
able), 7.23–7.35 (d, 2H p-subs-phenyl), 7.50–7.53 (m,
1H, disub-phenyl), 7.71–7.74 (m, 2H, disub-phenyl),
8.0 (s, 1H, pyrazole proton), 8.20–8.24 (d, 2H, p-subs-
phenyl), 8.39–8.42 (m, 1H, disub-phenyl), 9.68 (brs,
1H, NH, D2O exchangeable).
Synthesis of the adducts 8a,b
General Procedure. To an ice-cold solution of the
appropriate aromatic amine (0.01 mol) in concen-
trated hydrochloric acid (3 mL) was added dropwise
a solution of sodium nitrite (1.03 g, 0.01 mol) dis-
solved in the least amount of water, in an ice bath at
−5◦C. This previously prepared diazonium salt was
added dropwise to a mixture of 7 (4.69 g, 0.01 mol)
and anhydrous sodium acetate in ethanol. The re-
action mixture was allowed to stand overnight at
room temperature, then it was poured into water.
The formed solid was filtered off, washed with wa-
ter, dried and recrystallized from dioxane to produce
8a,b, respectively.
2-(3,5-Dimethyl-pyrazol-1-yl)-3H-5-(4-
chlorophenyl)benzo[6,7]cyclohepta[1,2-b]
pyrido[2,3-e]pyrimidin-4-one 10a,b
Preparation of 8a. From 4-chloroaniline (1.27 g,
0.01 mol), 8a was obtained as dark yellow crystals.
IR (KBr) (cm−1): 3450 (OH), 3180 (NH), and 1671
General Procedure. A mixture of compound 1
(4.03 g, 0.01 mol) and the appropriate ꢀ-diketone
(0.01 mol) was heated under reflux in absolute
ethanol (30 mL) for 5 h. The reaction mixture was al-
lowed to cool to room temperature. The precipitate
solid was collected by filtration, dried, and crystal-
lized from dioxane to produce 10a,b, respectively.
1
(CO). The H-NMR spectrum (DMSO-d6) (ppm): δ
1.72 (m, 4H, 2CH2), 2.34 (s, 3H, CH3), 2.58 (m, 2H,
CH2), 7.33–7.35 (two d, 4H, p-subs-phenyl), 7.51–
7.53 (m, 1H, disub-phenyl), 7.77–7.80 (m, 2H, disub-
phenyl), 8.19–8.21 (d, 2H, p-subs-phenyl), 8.23–8.26
(d, 2H, p-subs-phenyl), 8.40–8.42 (m, 1H, disub-
phenyl), 9.21 (brs, 1H, NH, D2O exchangeable), and
13.02 (brs, 1H, OH, D2O exchangeable). Its mass
spectrum showed the molecular ion at peak m/z 608
(M+), 100%.
2-(3,5-Dimethyl-pyrazol-1-yl)-3H-5-(4-chlorophe-
nyl)benzo[6,7]cyclohepta[1,2-b]-pyrido[2,3-e]pyrimi-
din-4-one 10a. Obtained from compound 1 (4.03
g, 0.01 mol) and pentane-2,4-dione (1.00 g, 0.01
mol), the product was recrystallized from dioxane
to produce 10a as pale yellow crystals. IR spectrum
(KBr) (cm−1): 3239 (NH), 2917 (CH aliphatic),
Preparation of 8b. From 4-methoxyaniline
(1.13 g, 0.01 mol), 8b was obtained as orange
crystals. IR (KBr) (cm−1): 3398 (OH), 3230 (NH),
1
and 1686 (CO). The H-NMR spectrum (DMSO-d6)
(ppm): δ 1.68 (m, 4H, 2CH2), 2.5 5 (m˜ , 2H, CH2),
2.61 (s, 3H, CH3), 2.98 (s, 3H, CH3), 6.20 (s, 1H,
CH), 7.21–7.30 (d, 2H p-subs-phenyl), 7.47–7.51 (m,
1H, disub-phenyl), 7.69–7.72 (m, 2H, disub-phenyl),
8.21–8.25 (d, 2H, p-subs-phenyl), 8.36–8.40 (m,
1H, disubs-phenyl), and 11.70 (brs, 1H, NH, D2O
1
and 1681 (CO). The H-NMR spectrum (DMSO-d6)
(ppm): δ 1.70 ppm (m, 4H, 2CH2), 2.31 (s, 3H, CH3),
2.56 (m, 2H, CH2), 4.20 (s, 3H, OCH3) 7.34–7.36
(two d, 4H, p-subs-phenyl), 7.51–7.54 (m, 1H,
disub-phenyl), 7.79–7.81 (m, 2H, disub-phenyl),
8.21–8.24 (d, 2H, p-subs-phenyl), 8.33–8.36 (d, 2H,
p-subs-phenyl), 8.42–8.45 (m, 1H, disub-phenyl),
and 9.56 (brs, 1H, NH, D2O exchangeable). 13.22
(brs, 1H, OH, D2O exchangeable).
exchangeable).
Its mass spectrum showed the
molecular ion peak at m/z 467.
2-(4-Chloro-3,5-dimethyl-pyrazol-1-yl)-3H-5-(4-ch-
lorophenyl) benzo[6,7]cyclohepta-[1,2-b]pyrido[2,3-
e]pyrimidin-4-one 10b. Obtained from compound
1 (4.03 g, 0.01 mol) and 3-chloropentane-2,4-dione
(1.34 g, 0.01 mol). The product was recrystallized
from dioxane to produce 10b as orange crystals.
IR spectrum (KBr) (cm−1): 3254 (NH), 2914 (CH
2-(3-Amino-5-oxo-4H-pyrazol-1-yl)-3H-5-(4-
chlorophenyl)benzo[6,7]cyclohepta[1,2-
b]pyrido[2,3-e]pyrimidin-4-one 9
To a warmed ethanolic sodium ethoxide solution
(prepared by dissolving sodium metal (0.23 g,
0.01 mol) in absolute ethanol (30 mL)) was added
compound 1 (4.03 g, 0.01 mol) and ethyl cyanoac-
1
aliphatic), and 1694 (CO). The H-NMR spectrum
(DMSO-d6) (ppm): δ 1.73 (m, 4H, 2CH2), 2.52 (m,
2H, CH2), 2.64 (s, 3H, CH3), 2.92 (s, 3H, CH3),
Heteroatom Chemistry DOI 10.1002/hc

On the Chemistry of 5-Aryl-2-hydrazino-benzo[6,7]cyclohepta[1,2-b]pyrido[2,3-e]pyrimidin-4-one 41
7.19–7.27 (d, 2H, p-subs-phenyl), 7.44–7.50 (m, 1H,
disubs-phenyl), 10.60 (brs, 1H, NH, D2O exchange-
able), and 12.90 (brs, 1H, NH, D2O exchangeable).
Mass spectrum showed the molecular ion peak at
m/z 521.
disub-phenyl), 7.67–7.67 (m, 2H, disub-phenyl),
8.15–8.22 (d, 2H, p-subs-phenyl), 8.38–8.41 (m,
1H, disub-phenyl), and 11.40 (brs, 1H, NH, D2O
exchangeable).
Its mass spectrum showed the
molecular ion peak at m/z 502.
3-Aryl-6-(4-chlorophenyl)benzo[6,7]cyclohepta-
[1,2-b]pyrido[2,3-e][1,2,4]triazolo-[2ꢁ,3ꢁ:5,6]
pyrimidin-5(5H)-ones 12a,b
2-(Arylmethylenehydrazone)-5-(4-chlorophenyl)-
benzo[6,7]cyclohepta[1,2-b]pyrido[2,3-
e]pyrimidin-4-one 11a,b
General Procedure. A mixture of compound
(11a or 11b) (10 mmol), anhydrous sodium acetate
(1.64 g, 20 mmol), and bromine (1.60 g, 10 mmol)
was heated gently in glacial acetic acid (30 mL) in wa-
ter bath at 80◦C for long time (under TLC control).
The reaction mixture was allowed to cool to room
temperature, poured into water (100 mL), and the
solid so-formed was collected by filtration and crys-
tallized from appropriate solvents, to produce 12a,b,
respectively.
General Procedure. A mixture of compound 1
(4.03 g, 0.01 mol) and the appropriate aromatic
aldehyde (0.01 mol), dioxane (30 mL), and a cat-
alytic amount of piperidine was heated under reflux
for 6 h. The reaction mixture was allowed to cool
to room temperature, then it was poured into wa-
ter. The formed precipitate was filtered off, washed
with water, dried and recrystallized from dimethyl-
formamide to produce 11a,b.
3-Phenyl-6-(4-chlorophenyl)benzo[6,7]cyclohepta
[1,2-b]pyrido[2,3-e][1,2,4]triazolo-[2ꢁ,3ꢁ:5,6]pyrimid-
in-5(5H)-ones 12a. Obtained from compound 11a
(4.91 g, 10 mmol). The product was recrystallized
from dimethylformamide to produce 12a as orange
powder. IR spectrum (KBr) (cm−1): 3370 (NH) and
1685 (C O). The 1H-NMR spectrum (DMSO-d6)
(ppm): δ 1.70 (m, 4H, 2CH2), 2.54 (m, 2H, CH2),
7.20–7.28 (d, 2H, p-subs-phenyl), 7.43–7.47 (m, 4H,
1H for disub-phenyl + 3H for phenyl), 7.61–7.70 (m,
4H, 2H for disub-phenyl + 2H for phenyl), 8.21–8.25
(d, 2H, p-subs-phenyl), 8.36–8.40 (m, 1H, disub-
phenyl), and 10.65 (brs, 1H, NH, D2O exchangeable).
Mass spectrum showed the molecular ion peak at
m/z 489.
2-(Phenylmethylenehydrazone)-5-(4 -chlorophen-
yl)-benzo[6,7]cyclohepta[1,2-b]-pyrido[2,3-e]pyrimid-
in-4-one 11a. Obtained from benzaldehyde (1.06 g,
0.01 mol). The product was recrystallized from
dimethylformamide to produce 11a as pale yellow
crystals. IR spectrum (KBr) (cm−1): 3326 2 (NH),
1
2914 (CH aliphatic), and 1686 (CO). The H-NMR
spectrum (DMSO-d6) (ppm): δ 1.68 (m, 4H, 2CH2),
2.59 (m˜ , 2H, CH2), 7.19–7.25 (d, 2H, p-subs-phenyl),
7.40–7.47 (m, 4H, 1H for disub-phenyl + 3H for
phenyl), 7.64–7.70 (m, 4H, 2H for disub-phenyl + 2H
for phenyl), 8.19–8.23 (d, 2H, p-subs-phenyl), 8.29
(s, 1H, methylenic proton), 8.37–8.42 (m, 1H, disub-
phenyl), and 11.25 (brs, 1H, NH, D2O exchange-
able), 13.05 (brs, 1H, NH, D2O exchangeable).
Mass spectrum showed the molecular ion peak at
m/z 491.
3-(4-Methoxyphenyl)-6-(4-chlorophenyl)benzo[6,7]
cyclohepta[1,2-b]pyrido[2,3-e]-[1,2,4]triazolo[2ꢁ,3ꢁ:5,6]
pyrimidin-5(5H)-ones 12b. Obtained from com-
pound 11b (5.21g, 10 mmol). The product was
recrystallized from dimethylformamide to produce
12b as yellow powder. IR spectrum (KBr) (cm−1):
2-(4-Methoxyphenylmethylenehydrazone)-5-(4-ch-
lorophenyl)benzo[6,7]cyclohepta-[1,2-b]pyrido[2,3-e]
pyrimidin-4-one 11b . Obtained from 4-methoxybe-
nzaldehyde (1.36 g, 0.01 mol). The product was
crystallized from dimethylformamide to produce
11b as yellow crystals. IR spectrum (KBr) (cm−1):
3312 2(NH), 2934 (CH aliphatic), and 1692 (CO).
The 1H-NMR spectrum (DMSO-d6) (ppm): δ 1.71 (m,
4H, 2CH2), 2.54 (m, 2H, CH2), 3.97 (s, 3H, OCH3),
7.09–7.14 (d, 2H, p-subs-phenyl), 7.18–7.23 (d, 2H
p-subs-phenyl), 7.39–7.44 (m, 1H, disub-phenyl),
7.56–7.67 (m, 4H, 2H for disub-phenyl + 2H for
p-subs-phenyl), 8.20–8.23 (d, 2H, p-subs-phenyl),
8.37 (s, 1H, methylenic proton), 8.45–8.50 (m, 1H,
1
3354 (NH) and 1687 (C O). The H-NMR spectrum
(DMSO-d6) (ppm): δ 1.72 (m, 4H, 2CH2), 2.53 (m, 2H,
CH2), 3.39 (s, 3H, OCH3), 7.07–7.12 (d, 2H, p-subs-
phenyl), 7.22–7.27 (d, 2H p-subs-phenyl), 7.40–7.45
(m, 1H, disub-phenyl), 7.59–7.68 (m, 4H, 2H for
disub-phenyl + 2H for p-subs-phenyl), 8.20–8.23
(d, 2H, p-subs-phenyl), 8.39–8.42 (m, 1H, disubs-
phenyl), and 10.24 (brs, 1H, NH, D2O exchangeable).
Mass spectrum showed the molecular ion peak
at m/z 503.
Heteroatom Chemistry DOI 10.1002/hc

42 El-Gazzar, Abu-Zied, and El-Din
pyridine (20 ml: 20 ml) was stirred at room tem-
perature for 24 h, poured into water (100 mL). The
reaction mixture was then extracted with chloro-
form several times, and after the removal of chlo-
roform under reduced pressure the formed crystals
were recrystallized from the proper solvent to pro-
duce 14a,b, in good yields.
2-(Glycosylhydrazon)-5-(4-chlorophenyl)benzo
[6,7]cyclohepta[1,2-b]pyrido[2,3-e]-pyrimidin-4-
one 13a,b
General Procedure. A solution of compound 1
(10 mmol) and xylose or glucose (10 mmol) in dry
dioxane in the presence of catalytic amounts of
pipridine was refluxed for 6 h, poured into water
(100 mL), and neutralized with hydrochloric acid.
The solid that was separated filtered, washed with
ethanol, dried, and crystallized from the proper sol-
vent to produce 13a,b in good yields.
3-(2ꢁ,3ꢁ,4ꢁ,5ꢁ-O-tetraacetyl-xylosyl)-6-(4-chlorophe-
nyl)benzo[6,7]cyclohepta-[1,2-b]pyrido[2,3-e][1,2,4]
triazolo[2ꢁ,3ꢁ:5,6]pyrimidin-5(5H)-one 14a. Obtain-
ed from compound 13a (3.82 g, 10 mmol). The
compound was obtained as white crystals, which
was crystallized from ethanol. IR (KBr) (cm−1):
3220 (NH), 1751–1729 (4 C O, acetyl) 1681 (C O,
pyrimidone). 1H-NMR (CDCl3) (ppm): δ 1.69 (m,
4H, 2CH2), 1.94 (s, 3H, CH3), 2.11 (s, 3H, CH3),
2.14 (s, 3H, CH3), 2.20 (s, 3H, CH3) 2.60 (m, 2H,
CH2), 3.22 (m, 2H, CH2), 4.65 (m, 1H, H-3ꢁ), 5.23
(m, 2H, H-4ꢁ), 5.44 (m, 1H, H-2ꢁ), 5.75 (m, 1H,
H-1ꢁ), 7.29–7.31 (d, 2H p-subs-phenyl), 7.46–7.52
(m, 1H, disub-phenyl), 7.74–7.79 (m, 2H, disub-
phenyl), 8.20–8.23 (d, 2H, p-subs-phenyl), 8.38–8.41
(m, 1H, disubs-phenyl), and 10.11 (brs, NH, D2O
exchangeable). MS (m/z): 702 (M+) 100%.
2-(Xylosylhydrazon)-5-(4-chlorophenyl)benzo
[6,7]cyclohepta[1,2-b]pyrido[2,3-e]pyr-imidin-4-
one 13a
Obtained from D-xylose (1.50 g, 10 mmol). The com-
pound was obtained as white powder, crystallized
from dioxane. IR (KBr) (cm−1): 3430 (broad, OH),
3221 (NH), 1687 (C O). 1H-NMR (DMSO-d6) (ppm):
δ 1.67 (m, 4H, 2CH2), 2.55 (m, 2H, CH2), 3.31 (m,
2H, CH2), 3.53 (m, 4OH, D2O exchangeable, OH-2ꢁ,
OH-5ꢁ), 4.21 (q, 1H, J = 6 Hz, H-4ꢁ), 4.45 (m, 2H, H-
5ꢁꢁ), 4.61 (d, 1H, J = 5 Hz, H-3ꢁ), 5.76 (dd, 1H, J = 7
Hz, H-2ꢁ), 7.29 (d, 1H, J = 4 Hz, H-1ꢁ), 7.35–7.37 (d,
2H p-subs-phenyl), 7.50–7.53 (m, 1H, disub-phenyl),
7.76–7.80 (m, 2H, disub-phenyl), 8.18–8.21 (d, 2H, p-
subs-phenyl), 8.39–8.42 (m, 1H, disubs-phenyl), and
11.25 (brs, 1H, NH, D2O exchangeable). MS (m/z):
536 (M+) 100%.
3-(1ꢁ,2ꢁ,3ꢁ,4ꢁ,5ꢁ-O-Pentaacetyl-glucosyl)-6-(4-chlo-
rophenyl)benzo[6,7]cyclohepta-[1,2-b]pyrido[2,3-e][1,
2,4]triazolo[2ꢁ,3ꢁ:5,6]pyrimidin-5(5H)-one 14b. Ob-
tained from compound 13b (4.12 g, 10 mmol). The
compound was obtained as white powder, which
was crystallized from ethanol. IR (KBr) (cm−1):
3310 (NH), 1743–1720 (5 C O, acetyl) 1689 (C O,
pyrimidone). 1H-NMR (CDCl3) (ppm): δ 1.70 (m,
4H, 2CH2), 1.84 (s, 3H, CH3), 1.90 (s, 3H, CH3),
2.10 (s, 3H, CH3), 2.35 (s, 3H, CH3), 2.44 (s, 3H,
CH3), 2.57 (m, 2H, CH2), 3.36 (m, 2H, CH2), 4.67
(m, 1H, H-4ꢁ), 5.26 (d, 1H, J = 10.6 Hz, H-3ꢁ), 5.40
(m, 2H, H2ꢁ, 5ꢁ), 5.62 (s, 1H, H-2ꢁ), 5.73 (s, 1H,
H-1ꢁ), 7.30–7.32 (d, 2H, p-subs-phenyl), 7.44–7.49
(m, 1H, disub-phenyl), 7.69–7.73 (m, 2H, disub-
phenyl), 8.22–8.25 (d, 2H, p-subs-phenyl), 8.39–8.42
(m, 1H, disubs-phenyl), 10.55 (brs, 1H, NH, D2O
exchangeable). MS (m/z): 754 (M+) 100%.
2-(Glucosylhydrazon)-5-(4-chlorophenyl)benzo[6,7]
cyclohepta-[1,2-b]pyrido[2,3-e]pyrimidin-4-one 13b.
Obtained from D-glucose (1.80 g, 10 mmol). The
compound was obtained as white powder, crystal-
lized from dioxane. IR (KBr) (cm−1): 3450 (broad,
1
OH), 3217 (NH), 1688 (C O). H-NMR (DMSO-d6)
(ppm): δ 1.67 (m, 4H, 2CH2), 2.56 (m, 2H, CH2), 3.25
(m, 2H, CH2), 3.61 (m, 5H, 5OH, D2O exchangeable
OH-2ꢁ-OH-6ꢁ), 4.24 (m, 1H, CH, H-3ꢁ), 4.36 (m, 2H,
CH2, H2-6ꢁ), 4.53 (m, 2H, 2CH, H-3ꢁ, and H-4ꢁ), 5.22
(dd, 1H, CH, J = 7.5 Hz, H-2ꢁ), 7.35–7.37 (d, 2H,
p-subs-phenyl), 7.43–7.47 (m, 1H, disub-phenyl),
7.53 (d, 1H, J = 7.5, H-1ꢁ), 7.77–7.80 (m, 2H,
disub-phenyl), 8.19–8.23 (d, 2H, p-subs-phenyl),
8.40–8.42 (m, 1H, disubs-phenyl), 10.12 (brs, 1H,
NH, D2O exchangeable), and 11.85 (brs, 1H, NH,
D2O exchangeable). MS (m/z): 565 (M+) 100%.
3-(Glycosyl)-6-(4-chlorophenyl)benzo[6,7]
cyclohepta-[1,2-b]pyrido[2,3-e][1,2,4]tri-azolo
[2ꢁ,3ꢁ:5,6]pyrimidin-5(5H)-ones 15a,b
General Procedure. A solution of compounds
14a,b (10 mmol) in methanolic ammonia solution
(25%, 50 mL) was stirred at room temperature for 24
h, then neutralized with hydrochloric acid solution
(under pH control). The excess of methanol was re-
moved under reduced pressure, whereby a solid was
precipitated. The precipitate so formed was filtered
3-(O-Acetylglycosyl)-6-(4-chlorophenyl)benzo
[6,7]cyclohepta[1,2-b]pyrido[2,3-e]-[1,2,4]triazolo
[2ꢁ,3ꢁ : 5,6]pyrimidin-5(5H)-ones 14a,b.
General Procedure. A solution of compounds
13a,b (10 mmol) in a mixture of acetic anhydride-
Heteroatom Chemistry DOI 10.1002/hc

On the Chemistry of 5-Aryl-2-hydrazino-benzo[6,7]cyclohepta[1,2-b]pyrido[2,3-e]pyrimidin-4-one 43
off, wash with cold water, dried and was recrystal-
lized from the proper solvent to produce the com-
CONCLUSION
The present investigation offers rapid and ef-
fective new procedures for the synthesis of the
C-nucleosides systems. Furthermore, the prepared
new ring systems and C-nucleoside are interesting
for biological activity studies. The latter will be pub-
lished elsewhere.
pounds 15a,b, in good yield.
3-Xylosy-6-(4-chlorophenyl)benzo[6,7]cyclohepta-
[1,2-b]pyrido[2,3-e][1,2,4]tri-azolo[2ꢁ,3ꢁ:5,6]pyrimid-
in-5(5H)-one 15a. Obtained from compound 14a
(2.74 g, 5 mmol). The compound was obtained as
white powder, which was crystallized from ethanol.
IR (KBr) (cm−1): 3431–3460 (broads band OH),
3210 (NH), 1681 (C O, pyrimidone). 1H-NMR
(CDCl3) (ppm): δ 1.71 (m, 4H, 2CH2), 2.57 (m, 2H,
CH2), 4.40 (m, 4H, 4OH, D2O exchangeable, OH-1ꢁ,
OH-4ꢁ), 4.65 (m, 1H, H-3ꢁ), 4.88 (m, 2H, H2–4ꢁ),
5.10 (m, 1H, H-2ꢁ), 7.29–7.32 (d, 2H p-subs-phenyl),
7.43–7.48 (m, 1H, disub-phenyl), 7.70–7.74 (m, 2H,
disub-phenyl), 8.23–8.26 (d, 2H, p-subs-phenyl),
8.40–8.41 (m, 1H, disubs-phenyl), and 9.20 (brs,
NH, D2O exchangeable).
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3-Glucosyl-6-(4-chlorophenyl)benzo[6,7]cyclohe-
pta[1,2-b]pyrido[2,3-e][1,2,4]tri-azolo[2ꢁ,3ꢁ:5,6]pyrim-
idin-5(5H)-one 15b. Obtained from compound 14b
(3.10 g, 5 mmol). The compound was obtained as
white crystals, which was crystallized from ethanol.
IR (KBr) (cm−1): 3439, 3465 (broads band OH), 3262
(NH), 1689 (C O, pyrimidone). 1H-NMR (CDCl3)
(ppm): δ 1.67 (m, 4H, 2CH2), 2.59 (m, 2H, CH2),
3.12 (m, 5H, 5OH, D2O exchangeable), 3.31 (m, 2H,
CH2), 3.37 (m, 1H, H-3ꢁ), 3.77 (m, 2H, H-5ꢁ, H-5ꢁꢁ),
4.25 (m, 1H, H-2ꢁ), 4.60 (m, 1H, H-1ꢁ), 7.32–7.36 (d,
2H p-subs-phenyl) 7.51–7.55 (m, 1H, disub-phenyl),
7.75–7.78 (m, 2H, disub-phenyl), 8.21–8.32 (d, 2H,
p-subs-phenyl), 8.40–8.45 (m, 1H, disubs-phenyl),
10.35 (brs, NH, D2O exchangeable).
Heteroatom Chemistry DOI 10.1002/hc