Green procedure for the synthesis of phthalazino[2,3-b]phthalazine-5,7,12, 14-tetraones

Article abstract of DOI:10.1080/00397910701545247

Different novel phthalazino[2,3-b]phthalazine-5,7,12,14-tetraones were synthesized in a simple and environmentally benign method from the reaction of phthalic anhydrides with semicarbazide or thiosemicarbazide using montmorillonite K-10 clay as solid heterogeneous acidic catalyst and microwaves under solvent-free conditions in good yields and short reaction times. Products were characterized by the elemental analysis, IR, NMR, and mass spectrometry. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701545247

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Green Procedure for the Synthesis of
Phthalazino[2,3‐b]phthalazine‐5,7,12,14‐tetraon
Davood Habibi a , Nosratollah Mahmoudi b & Omid Marvi a
a Faculty of Chemistry, Bu‐Ali Sina University, Hamedan, Iran
b Department of Chemistry, Faculty of Sciences, University of Guilan, Iran
Version of record first published: 10 Sep 2007.
To cite this article: Davood Habibi , Nosratollah Mahmoudi & Omid Marvi (2007): Green Procedure for the
Synthesis of Phthalazino[2,3‐b]phthalazine‐5,7,12,14‐tetraones, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 37:18, 3165-3171
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Synthetic Communicationsw, 37: 3165–3171, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701545247
Green Procedure for the Synthesis of
Phthalazino[2,3-b]phthalazine-5,7,12,14-
tetraones
Davood Habibi
Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran
Nosratollah Mahmoudi
Department of Chemistry, Faculty of Sciences, University of Guilan, Iran
Omid Marvi
Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran
Abstract: Different novel phthalazino[2,3-b]phthalazine-5,7,12,14-tetraones were
synthesized in a simple and environmentally benign method from the reaction of
phthalic anhydrides with semicarbazide or thiosemicarbazide using montmorillonite
K-10 clay as solid heterogeneous acidic catalyst and microwaves under solvent-free
conditions in good yields and short reaction times. Products were characterized by
the elemental analysis, IR, NMR, and mass spectrometry.
Keywords: microwave, montmorillonite K-10 clay, phthalic anhydrides, semicarbazide,
solvent-free condition, thiosemicarbazide
In the past few decades, the synthesis of new heterocyclic compounds has
been a subject of great interest because of their wide applicability. Hetero-
cyclic compounds occur very widely in nature and are essential to life.
Nitrogen-containing heterocyclic molecules constitute the largest portion of
Received in the U.K. October 20, 2006
Address correspondence to Davood Habibi, Faculty of Chemistry, Bu-Ali Sina
University, Hamedan 6517838683, Iran. E-mail: dhabibi@basu.ac.ir
3165

3166
D. Habibi, N. Mahmoudi, and O. Marvi
chemical entities, which are part of many natural products, fine chemicals, and
biologically active pharmaceuticals and are vital for enhancing the quality of
life.[1–4] In this connection, various studies on fused nitrogen heterocycles
have been reported,[5–13] but a limited number of phthalazino[2,3-b]phthala-
zine-5,7,12,14-tetraone derivatives have been synthesized.[14–17] Most of
these procedures involve the use of corrosive reagents such as polyphosphoric
and acetic acids, and the reported yields are far from satisfactory. Therefore,
the use of inexpensive and environmentally safe solid acids would extend the
scope of these transformations.
Recently, the use of solid acidic catalysts such as clays, zeolites, and ion-
exchange resins has received much interest in different areas of organic
synthesis because of their environmental compatibility, reusability, greater
selectivity, noncorrosiveness, low cost, and ease of handling. Particularly,
the clay catalysts make the reaction process more convenient, economic,
and environmentally benign and act as both Brønsted and Lewis acids in
their natural and ion-exchanged forms, enabling them to function as
efficient catalysts for various transformations.[18]
Montmorillonite clays have been used as catalysts for a number of organic
reactions and offer several advantages over classical acids: strong acidity,
noncorrosive properties, recyclability, cheapness, mild reaction conditions,
high yields and selectivity, and ease of setup and workup.[19–23]
In the past few years, a growing interest has been shown in the use of
microwave irradiation in organic synthesis.[24–26] Microwave-assisted
organic reactions constitute an emerging technology that makes experimen-
tally and industrially important organic syntheses more effective and more
ecofriendly than the conventional reactions.[27–29] In addition, microwave-
mediated solvent-free synthesis offers advantages for reducing hazardous
explosions and the removal of the high boiling solvents from the reaction
mixtures.[30,31]
RESULTS AND DISCUSSION
In continuation of our study with microwaves on solid surfaces,[32–34] herein
we describe a convenient and simple method to synthesize some of the new
phthalazino[2,3-b]phthalazine-5,7,12,14-tetraones from the reaction of
different substituted phthalic anhydrides as well as either semicarbazide or
thiosemicarbazide reacted for the appropriate time under solvent-free con-
ditions and microwave irradiation on montmorillonite K-10 clay (Scheme 1).
The polarity of the carbonyl group of semicarbazide is greater than its
thio-carbonyl analogs in thiosemicarbazide, so the –NH2 group of thiosemi-
carbazide is a better nucleophile than the –NH2 group of semicarbazide and
hence the more yields will be obtained.
The nature of the substituents on the aromatic ring of phthalic anhydride
has different influences. For instance, presence of electron-withdrawing

Phthalazino[2,3-b]phthalazine-5,7,12,14-tetraones
3167
Scheme 1. Synthesis of phthalazino[2,3-b]phthalazine-5,7,12,14-tetraones.
groups such as chlorine, nitro, and fluorine, which increase the polarity of the
carbonyl group inductively, gives high yields of products as well as short
reaction times compared to those of the unsubstituted rings.
IR spectral evaluations of the obtained compounds showed that in the
cases of c, e, h, and j, 1,11-disubstituted compound is a real product (and
not 1,8-), whereas in the cases of d and i, 2,10-disubstituted compound (and
not 2, 9-) was obtained.
The use of clay as an efficient heterogeneous acidic catalyst as well as
microwave irradiation offer high yields of products compared to the conven-
tional procedures, probably due to the more molecular interactions. The
related comparative data have been shown in the typical procedure section.[17]
All attempts to prepare the products in the absence of montmorillonite
K-10 clay failed (despite 20 min of irradiation at 1808C, 900 W). So, the
role of montmorillonite K-10 clay as a solid catalyst in this reaction is
important and essential.
In summary, we have described a new, simple, and highly efficient
procedure for the synthesis of phthalazino[2,3-b]phthalazine-5,7,12,14-
tetraone compounds using montmorillonite K-10 clay. The catalyst is inex-
pensive, nontoxic, and reusable, which makes the process convenient and
economically viable. The recyclability of the K-10 clay, which is another
advantage of our method, has been explained in the footnote of Table 1.
EXPERIMENTAL
Melting points were measured on an Electro-thermal 9100 apparatus. The IR
spectra were obtained on a Perkin-Elmer FT IR GX instrument in KBr
1
discs. The H NMR and 13C NMR spectra were recorded on a FT-NMR
Jeol FX 90Q spectrometer using TMS as internal standard (d/ppm). Mass
spectra were measured with GCMS-Agilent 5973 N instrument. Elemental
analyses were performed using a Heraeus CHN-Rapid analyzer. Chemicals
were purchased from the Aldrich, Merck, and Fluka chemical companies
and used without further purification. The chemical composition (average

Table 1. Yields and reaction times of compounds a–j
Yield (%)b
Recovered
Optimum
time (min)
Entry
Anhydride
Reagent
Compounda
Fresh clay
clay
1
2
Phthalic anhydride
Tetrachloro-phthalic
anhydride
Semicarbazide
Semicarbazide
a
7.0
3.5
61
73
54
64
b
3
4
5
6
7
3-Nitro-phthalic anhydride
4-Nitro-phthalic anhydride
3-Fluoro-phthalic anhydride
Phthalic anhydride
Semicarbazide
Semicarbazide
c
d
e
f
5.5
5.0
6.0
5.0
3.0
69
67
65
67
82
60
57
58
61
77
Semicarbazide
Thiosemicarbazide
Thiosemicarbazide
Tetrachloro-phthalic
anhydride
g
8
9
3-Nitro-phthalic anhydride
4-Nitro-phthalic anhydride
3-Fluoro-phthalic anhydride
Thiosemicarbazide
Thiosemicarbazide
Thiosemicarbazide
h
i
4.0
3.5
4
74
73
70
58
56
64
10
j
aCompound a ¼ f is known and its spectra and physical data has been reported in the literature.[17]
bYields are after recrystallization. The applied K-10 clay was filtered off after completion of the reaction, washed with methanol, and dried in
vacuum to be reused in the subsequent reactions, which showed gradual decrease in the activity.
Notes: a ¼ f) Phthalazino[2,3-b]phthalazine-5,7,12,14-tetraone. b ¼ g) 1,2,3,4,8,9,10,11-Octachlorophthalazino[2,3-b]phthalazine-5,7,12,14-
tetraone c ¼ h) 1,11-Dinitrophthalazino[2,3-b]phthalazine-5,7,12,14-tetraone d ¼ i) 2, 9-Dinitrophthalazino[2,3-b]phthalazine-5,7,12,14-tetraone
e ¼ j) 1,11-Difluorophthalazino[2,3-b]phthalazine-5,7,12,14-tetraone.

Phthalazino[2,3-b]phthalazine-5,7,12,14-tetraones
3169
value) of the applied montmorillonite K-10 clay [surface area: 200 m2/g; pH:
2.5–3.5) is 73.0% SiO2, 14.0% Al2O3, 2.7% Fe2O3, 0.2% CaO, 1.1% MgO,
0.6% Na2O, and 1.9% K2O.
General Procedure for the Synthesis of Phthalazino[2,3-
b]phthalazine-5,7,12,14-tetraones
In a typical experiment, phthalic anhydride (2.2 mmol, 0.330 g), thiosemicar-
bazide (1 mmol, 0.091 g), and montmorillonite K-10 clay (1 g) are mixed,
ground properly, placed in a septum-capped microwave tube, and irradiated
at 1808C (900 W) for a certain period of time (5 min). After completion of
the reaction, which was monitored by thin-layer Chromatography (TLC)
using n-hexane–acetone as eluent, the mixture was allowed to cool to the
room temperature. The resulting product was extracted into dichloromethane
(2 ꢀ 20 mL) and filtered off, and the solvent was removed by rotary. The
obtained product [(phthalazino[2,3-b]phthalazine-5,7,12,14-tetraone (f)] was
washed with distilled water very well, dried in an oven, and recrystallized
from acetic acid. Mp ꢀ 3408C, 67% yield, 0.195 g (with fresh K-10 clay)
and 61% yield, 0.178 g (with recovered K-10 clay) (lit.: mp 343–3448C,
55% yield, reaction time 1.5 h using poly-phosphoric acid[17]). The solid
clay portion was washed with methanol and dried at 1208C under reduced
pressure to be reused in the subsequent reactions, which showed gradual
decrease in the activity (Table 1). The physical as well as the spectral data
of known compound (a ¼ f) was found to be identical with the authentic
sample. Unknown compounds (b 5 g, c 5 h, d ¼ i, and e ¼ j) were charac-
terized by the elemental analysis, IR, NMR, and mass spectrometry.
Data
Phthalazino[2,3-b]phthalazine-5,7,12,14-tetraone (entries
1
and 6,
Table 1, a 5 f). Mp 332–3368C. m/z: 292 (Mþ). IR (KBr) n: 3092.7,
1
1853.5, 1792.6, 1763.5, 1686.4, 1597.4, 1471.3, 1258.7, 1109.8, 907.2. H
NMR (DMSO-d6) d: 7.81–7.98 (8H, m, Ar). 13C NMR (DMSO-d6) d:
123.0, 129.3, 134.8, 168.9. Anal. calcd. for C16H8N2O4 (%): C, 65.76; H,
2.76; N, 9.58. Found: C, 65.12; H, 2.60; N, 9.48.
1,2,3,4,8,9,10,11-Octachlorophthalazino[2,3-b]phthalazine-5,7,12,14-
tetraone (entries 2 and 7, Table 1, b 5 g). Mp 317–3218C. m/z: 568 (Mþ).
IR (KBr) n: 1846.7, 1835.4, 1775.7, 1757.76, 1373.9, 1299.3, 1233.8, 923.3.
13C NMR (DMSO-d6) d: 170.24, 139.92, 135.46, 127.41. Anal. calcd. for
C16Cl8N2O4 (%): C, 33.80; N, 4.92. Found: C, 33.67; N, 4.53.
1,11-Dinitrophthalazino[2,3-b]phthalazine-5,7,12,14-tetraone (entries 3
and 8, Table 1, c 5 h). Mp 271–2748C. m/z: 382 (Mþ). IR (KBr) n:
3172.9, 3026.24, 2922.0, 1669.9, 1654.7, 1618.0, 1603.3, 1578.1, 1560.2,

3170
D. Habibi, N. Mahmoudi, and O. Marvi
1
1560.8, 1491.6, 1336.5, 1298.2, 825.6. H NMR (DMSO-d6) d: 7.92–8.63
(6H, m, Ar). 13C NMR (DMSO-d6) d: 167.71, 167.43, 148.45, 136.85,
133.39, 132.70, 132.52, 129.61. Anal. calcd. for C16H6N4O8 (%): C, 50.26;
H, 1.57; N, 14.56. Found: C, 50.14; H, 1.38; N, 14.33.
2,9-Dinitrophthalazino[2,3-b]phthalazine-5,7,12,14-tetraone (entries
4
and 9, Table 1, d 5 i). Mp 263–2678C. m/z: 382 (Mþ). IR (KBr) n:
3106.3, 3006.5, 1641.8, 1626.7, 1598.7, 1539.9, 1466.6, 1355.1, 1188.4,
1
1061.3, 791.9. H NMR (DMSO-d6) d: 8.36–8.94 (6H, m, Ar). 13C NMR
(DMSO-d6) d: 162.52, 162.43, 154.81, 137.78, 134.66, 133.19, 129.26,
122.34. Anal. calcd. for C16H6N4O8 (%): C, 50.26; H, 1.57; N, 14.56.
Found: C, 50.09; H, 1.29; N, 14.25.
1, 11-Difluorophthalazino[2,3-b]phthalazine-5,7,12,14-tetraone (entries 5
and 10, Table 1, e 5 j). Mp 298–3028C. m/z: 328 (Mþ). IR (KBr) n:
3021.9, 2921.0, 1671.2, 1664.3, 1618.1, 1603.1, 1577.8, 1572.2, 1560.2,
1
1491.3, 1336.6, 1299.7, 825.8. H NMR (DMSO-d6) d: 7.82–8.27 (6H, m,
Ar). 13C NMR (DMSO-d6) d: 175.27, 163.66, 163.32, 163.08, 136.42,
136.27, 130.52. Anal. calcd. for C16H6 F2N2O4 (%): C, 58.53; H, 1.82; N,
8.53. Found: C, 58.34; H, 1.69; N, 8.21.
ACKNOWLEDGMENTS
Financial support from the Bu-Ali Sina University, Hamedan, Iran, is grate-
fully appreciated.
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