One-pot synthesis of aliphatic and aromatic 2H-indazolo[2,1-b]phthalazine- triones catalyzed by N-halosulfonamides under solvent-free conditions

Article abstract of DOI:10.1016/j.tet.2011.01.024

N, N, N′, N′-Tetrabromobenzene-1,3-disulfonamide and poly(N-bromo-N-ethylbenzene-1,3-disulfonamide) were used as efficient catalysts for the one-pot synthesis of aliphatic and aromatic 2H-indazolo[2,1-b] phthalazine-triones in excellent yields from aldehy

Full text of DOI:10.1016/j.tet.2011.01.024

Tetrahedron 67 (2011) 1930e1937
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Tetrahedron
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One-pot synthesis of aliphatic and aromatic 2H-indazolo[2,1-b]phthalazine-triones
catalyzed by N-halosulfonamides under solvent-free conditions
,
a
a
a
Ramin Ghorbani-Vaghei a , Rahman Karimi-Nami , Zahra Toghraei-Semiromi , Mostafa Amiri ,
*
Mehdi Ghavidel b
a Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, 65174, Hamedan, Iran
b Department of Chemistry, Urmia University, Urmia 57154, Iran
a r t i c l e i n f o
a b s t r a c t
N, N, N0, N0-Tetrabromobenzene-1,3-disulfonamide and poly(N-bromo-N-ethylbenzene-1,3-disulfonamide)
were used as efficient catalysts for the one-pot synthesis of aliphatic and aromatic 2H-indazolo[2,1-b]
phthalazine-triones in excellent yields from aldehydes, phthalhydrazide, and dimedone at 80e100 ꢀC
under solvent-free conditions.
Article history:
Received 26 August 2010
Received in revised form 14 December 2010
Accepted 6 January 2011
Available online 14 January 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Indazolo[2,1-b]phthalazine-trione
Multicomponent reaction
Phthalhydrazide
Dimedone
Solvent-free
TBBDA
PBBS
1. Introduction
Amongst a large variety of heterocyclic compounds, heterocycles
containing phthalazine moiety are of interest because they show
The development of simple synthetic routes for complex organic
molecules from readily available reagents is an important task in
organic synthesis.1 Multi-component reactions (MCRs) are signifi-
cant tools for the rapid and efficient synthesis of a wide variety
of organic molecules.2 These reactions have been investigated
extensively in organic and diversely oriented synthesis; primarily
due to their ability to generate complex molecular functionality
from simple starting materials via one-pot reaction.
Organic reactions under solvent-free conditions have attracted
much interest from chemists particularly from the viewpoint of
green chemistry. Green chemistry approaches are significant due to
the reduction in byproducts, a reduction in produced waste, and
reduction of energy cost. The possibility of performing multicom-
ponent reactions under solvent-free conditions with a heteroge-
neous catalyst could enhance their efficiency from an economic as
well as ecological point of view.3
some pharmacological and biological activities.4e6 Phthalazine de-
rivatives were reported to possess anticonvulsant,7 cardiotonic,8 and
vasorelaxant activities.9 Thus, the synthesis of phthalazine is an im-
portant and useful task in organic chemistry. In recent years, p-TSA,10
H2SO4 in watereethanol or ionic liquid,11 and silica supported poly-
phosphoric acid,12 have been utilized for this synthesis.
2. Results and discussion
In a continuation of our interest in the application of N, N, N0, N0-
tetrabromobenzene-1,3-disulfonamide [TBBDA] and poly(N-
bromo-N-ethylbenzene-1,3-disulfonamide) [PBBS],13 in organic
synthesis,13e21 we wish to report here a facile and improved pro-
tocol for preparation of aliphatic and aromatic 2H-indazolo[2,1-b]
phthalazine-triones from phthalhydrazide, dimedone, and various
aliphatic and aromatic aldehydes in the presence of TBBDA and
PBBS as catalysts under solvent-free conditions (Scheme 1).
The advantages of TBBDA and PBBS are as follows:
The synthesis of new heterocyclic compounds has always been
a subject of great interest due to their wide applicability. Heterocyclic
compounds occur very widely in nature and are essential to life.
1. The preparation of TBBDA and PBBS are easy.
2. TBBDA and PBBS are stable under atmospheric conditions for
two months.
* Corresponding author. Tel./fax: þ98 811 8257407; e-mail address: rgvaghei@
yahoo.com (R. Ghorbani-Vaghei).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.01.024

R. Ghorbani-Vaghei et al. / Tetrahedron 67 (2011) 1930e1937
1931
O
NH
NH
O
R
O
O
O
TBBDA, PBBS
Solvent-free,
N
O
N
80-100 ( C)
O
O
R
H
R = aryl, alkyl
Br
Br N
Br
N Br
Br
Br
N
N
(
)
CH2CH2
S
S
S
S
n
O O
O O
O O
O O
TBBDA
PBBS
Scheme 1. Three-component synthesis of indazolo[2,1-b]phthalazine-triones derivatives.
3. After completion of the reaction, the catalysts are recovered
and can be reused several times without decreasing the yield.
in Scheme 2 can be suggested for the conversion of the phthalhy-
drazide, dimedone, and various aliphatic and aromatic aldehydes to
2H-indazolo[2,1-b]phthalazine-triones.10
Initially, we decided to explore the role of our catalyst in ethanol
and ethanolewater as solvent system for the synthesis of 3,3-
dimethyl-13-phenyl-3,4-dihydro-1H-indazolo[1,2-b]phthalazine-
1,6,11(2H,13H)-trione (Table 2, entry 1) used as a model compound.
In the absence of catalyst, no phthalazine was observed, even after
prolonged reaction time. Since, the synthesis of phthalazine failed
in the absence of catalyst, the effect of catalyst was also investigated
in various conditions, and the results are presented in Table 1.
With respect to the solvent system, the best results were achieved
using ethanol (Table 1, entry 2). In recent years, the synthesis of
compounds under solvent-free is an important task in heterocyclic
synthesis. Therefore,wedecidedtotestthissolvent-freereactionwith
various ratios of catalysts. We found that the reaction was rapid and
gave excellent yields of the products when using N, N, N0, N0-tetra-
bromobenzene-1,3-disulfonamide [TBBDA] (10 min, 89%, entry 7).
3. Conclusion
In summary, we have developed a new facile protocol for the
synthesis of new aliphatic and aromatic indazolo[2,1-b]phthala-
zine-triones derivatives from the reaction of aldehydes, phthalhy-
drazide and dimedone compounds using TBBDA and PBBS under
solvent-free conditions.
4. Experimental
4.1. General
All commercially available chemicals were obtained from Merck
and Fluka companies, and used without further purification unless
Table 1
Reaction times and yields in various conditions
Entry
Solvent
Amount of catalyst[TBBDA (g)]
Temperature (ꢀC)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
Ethanol
Ethanol
Ethanol
Ethanolewater
Ethanolewater
Solvent-free
Solvent-free
Solvent-free
0.05 g
0.1 g
0.1 g
0.05 g
0.07 g
0.02 g
0.05 g
0.07 g
87
87
rt
100
100
100
100
100
120
90
90
120
120
30
61%
70%
d
60%
65%
80%
89%
89%
10
10
These results encouraged us to investigate the scope and gener-
ality of this new protocol for various aliphatic and aromatic aldehydes
under optimized conditions. As shown in Table 2, a series of aliphatic
and aromatic aldehydes containing either electron-withdrawing or
electron-donating substituents successfully react with phthalhy-
drazide and dimedone afforded good to high yields of products with
high purity, at 80e100 ꢀC under solvent-free conditions. It is note-
worthy that there are no reports of the synthesis of 2H-indazolo[2,1-
b]phthalazine-triones from aliphatic aldehydes.10e12
otherwisestated.Nuclearmagneticresonance1Hand13CNMRspectra
(Sharif University and Urmia University) were recorded on Bruker
Avance 300 and 500 MHz FT NMR spectrometers. Infrared (IR) spec-
troscopy was conducted on a Perkin Elmer GX FT-IR spectrometer.
Mass spectra were recorded on a Shimadzu QP 1100 BX Mass Spec-
trometer. Elemental analyses (C, H, N) were performed with a Heraeus
CHN-O-Rapid analyzer (University of Tarbiatmoallem, Tehran).
4.2. Typical procedure for the preparation of 3,4-dihydro-3,3-
dimethyl-13-phenyl-2H-indazolo[2, 1-b]phthalazine-1,6,11
(13H)-trione (Table 2, entry 1)
The nature and electronic properties of the aldehyde substrates
affect the conversion rate and yield. Aromatic aldehydes (Table 2,
entries 1e12) react faster and in higher yield than the aliphatic
aldehydes (Table 2, entries 13e20).
A mixture of dimedone (0.28 g, 2 mmol), phthalhydrazide
(0.32 g, 2 mmol), benzaldehyde (0.24 g, 2.2 mmol), and TBBDA
(0.05 g) or PBBS (0.1 g) was heated at 100 ꢀC for 10 min. After
It is likely that these reagents release Brþ in situ, which can act
as an electrophilic species.13ꢁ21 Therefore, the mechanism shown

1932
R. Ghorbani-Vaghei et al. / Tetrahedron 67 (2011) 1930e1937
Table 2
Synthesis of indazolo[2,1-b]phthalazine-triones
Entry
Substrate
Producta
TBBDA Time (min)/yield (%)
PBBS Time (min)/yield (%)
O
H
O
O
O
1
10
89
25
65
N
N
O
O
Cl
O
H
2
10
87
25
67
N
N
Cl
H
O
O2N
O
O
3
10
91
25
66
O
N
N
NO2
H
O
O
Me
O
4
15
84
45
60
O
N
N
Me
O
Me
O
H
O
O
Me
O
O
Me
5
15
87
25
67
Me
Me
O
N
N
O
O
O
Me
Cl
O
Cl
H
O
O
O
Cl
6
10
89
25
70
N
N
O
Cl
O
NO2
H
O
O
7
10
91
25
65
O
N
N
NO2
O
O
8
10
89
45
59
H
O
N
N
O

R. Ghorbani-Vaghei et al. / Tetrahedron 67 (2011) 1930e1937
1933
Table 2 (continued )
Entry
Substrate
Producta
TBBDA Time (min)/yield (%)
PBBS Time (min)/yield (%)
O
H
O
O
9
15
10
10
10
80
81
86
84
60
25
25
30
51
75
87
55
N
N
O
Cl
O
O
Cl
H
O
10
11
12
N
N
Cl
Cl
O
Me
O
S
H
O
O
O
N
N
Me
S
OH
O
O
H
O
N
N
OH
O
O
H
O
O
N
N
13
14
60
60
59
58
130
130
45
O
O
O
O
N
N
45
H
O
O
O
15
60
61
150
43
O
N
N
H
O
H
O
O
90
61
O
16
30
75
O
N
N
(continued on next page)

1934
R. Ghorbani-Vaghei et al. / Tetrahedron 67 (2011) 1930e1937
Table 2 (continued )
Entry
Substrate
Producta
TBBDA Time (min)/yield (%)
PBBS Time (min)/yield (%)
SMe
O
O
O
N
N
17
60
71
60
60
MeS
H
O
O
O
18
19
60
60
51
51
150
130
40
O
N
N
H
O
O
O
O
N
N
40
H
O
O
O
O
O
N
N
20
60
59
130
48
H
a
Known products were characterized from their physical properties, by comparison with authentic samples, and by spectroscopic methods.
completion of the reaction [TLC acetone/n-hexane (3:10)]. The re-
action mixture was cooled, filtered and washed with acetone
(15 mL). Removal of the solvent under reduced pressure gave the
catalyst. The crude product was recrystallized from ethyl acetate/n-
hexane (1:3) to afford the pure product (0.33 g, 89%) as a yellow
powder. Mp 206e208 ꢀC (204e206 ꢀC)10; [found: C, 74.10; H, 5.24;
N, 7.30. C23H20N2O3 requires C, 74.18; H, 5.41; N, 7.52%]; Rf (23%
acetone/n-hexane) 0.34; IR (KBr) (vmax, cmꢁ1) 2957, 1663, 1575; dH
(300 MHz, CDCl3) 1.22 (6H, s, 2Me), 2.34 (2H, s, CH2C), 3.21e3.46
(2H, AB system, J 18.9 Hz, CHaHbCO), 6.45 (1H, s, CHN), 7.28e8.37
(9H, m, Ph); dC (300 MHz, CDCl3); 28.4, 28.7, 34.7, 38.0, 50.9, 64.9,
118.6, 127.0, 127.1, 127.7, 127.9, 128.6, 128.7, 128.8, 128.9, 129.1, 133.5,
134.5,136.4,150.8,154.3,156.0,192.1; MS, m/z (%): 372 (Mþ,10), 295
(100), 128 (15), 104 (50), 76 (50).
O
HO
4.2.1. 13-(4-chlorophenyl)-3,3-dimethyl-3,4-dihydro-2H-indazolo[1,2-
b]phthalazine-1,6,11(13H)-trione (Table 2, entry 2). Yellow powder
(87%); mp 262e264 ꢀC (262e264 ꢀC)10; [found: C, 67.91; H, 4.77; N,
6.75. C23H19ClN2O3 requires C, 67.90; H, 4.71; N, 6.89%]; Rf (23%
acetone/n-hexane) 0.25; IR (KBr) (vmax, cmꢁ1) 2958, 2932, 1687,
1654, 1623; dH (300 MHz, CDCl3) 1.21 (6H, s, 2Me), 2.34 (2H, s,
CH2C), 3.21e3.44 (2H, AB system, J 19.2 Hz, CHaHbCO), 6.42 (1H, s,
CHN), 7.29e7.38 (4H, dd, J 8.4 Hz ArCl), 7.85e8.38 (4H, m, Ph); dC
(300 MHz, CDCl3); 28.4, 28.7, 34.7, 38.0, 50.9, 64.3118.6, 127.0, 127.1,
127.7, 127.9, 128.6, 128.7, 128.8, 128.9, 129.1, 133.5, 134.5, 136.4, 150.8,
154.3, 156.0, 192.1; MS, m/z (%): 406 (Mþ, 6), 295 (100), 130 (15), 104
(50), 76 (56).
Br
[TBBDA]
O
O
R
R
H
[TBBDA]
+
O
O
O
HN
HN
O
H
R
R
O
O
O
N
NH
[TBBDA]
O
Br
[TBBDA]
4.2.2. 3,3-Dimethyl-13-(3-nitrophenyl)-3,4-dihydro-2H-indazolo
[1,2-b]phthalazine-1,6,11(13H)-trione (Table 2, entry 3). Yellow
powder (91%); mp 268e271 ꢀC (270e272 ꢀC)10; [found: C, 65.86; H,
4.54; N, 9.93. C23H19N3O5 requires C, 66.18; H, 4.56; N, 10.07%]; Rf
(23% acetone/n-hexane) 0.24; IR (KBr) (vmax, cmꢁ1) 2973, 1684,
1661, 1625; dH (300 MHz, CDCl3) 1.23 (6H, s, 2Me), 2.35 (2H, s,
CH2C), 3.24e3.47 (2H, AB system, J 18.9 Hz, CHaHbCO), 6.53 (1H, s,
CHN), 7.53e8.4 (8H, m, Ph); dC (300 MHz, CDCl3); 28.4, 28.7, 34.7,
38.0, 50.8, 64.1, 117.1, 121.5, 123.7, 127.7, 128.2, 128.6, 128.9, 129.6,
O
O
R
O
N
N
Scheme 2. Suggested mechanism for synthesis of indazolo[2,1-b]phthalazine-triones
derivatives.

R. Ghorbani-Vaghei et al. / Tetrahedron 67 (2011) 1930e1937
1935
133.9, 134.2, 134.7, 138.4, 148.5, 150.8, 154.3, 155.9, 192.1; MS, m/z
128.7, 129.0, 129.6, 133.2, 133.4, 133.5, 133.6, 134.5, 150.8, 154.2,
(%): 417 (Mþ, 6), 295 (100), 162 (70), 104 (90), 76 (56).
156.1, 192.1; MS, m/z (%): 422 (Mþ, 5), 295 (100), 104 (40), 76 (56).
4.2.8. 3,3-Dimethyl-13-(naphthalen-1-yl)-3,4-dihydro-1H-indazolo
[1,2-b]phthalazine-1,6,11(2H,13H)-trione (Table 2, entry 9). Yellow
powder (80%); mp 261e263 ꢀC; [found: C, 76.19; H, 5.19; N, 6.53.
C27H22N2O3 requires C, 76.76; H, 5.25; N, 6.63%]; Rf (23% acetone/n-
hexane) 0.28; IR (KBr) (vmax, cmꢁ1) 2961, 1655, 1626; dH (300 MHz,
CDCl3) 1.20 (3H, s, Me), 1.23 (3H, s, Me), 2.29 (2H, s, CH2C),
3.27e3.53 (2H, AB system, J 19.2 Hz, CHaHbCO), 7.10 (1H, s, CHN),
7.38e7.87 (7H, m, naphthayl) 8.18e8.41 (4H, m, Ph); dC (300 MHz,
CDCl3); 28.4, 28.7, 34.6, 38.1, 50.9, 65.1, 119.9, 122.8, 125.1, 125.8,
126.5, 127.7 (2C), 128.0 (2C), 129.0, 129.6, 130.9, 133.5 (2C), 133.8,
134.5, 150.6, 154.1, 155.2, 156.2, 192.0; MS, m/z (%): 422 (Mþ, 30),
295 (100), 239 (25), 127 (70), 104 (90), 76 (65), 41 (35).
4.2.3. 3,3-Dimethyl-13-(4-methylphenyl)-3,4-dihydro-2H-indazolo
[2,1-b]phthalazine-1,6,11(13H)-trione (Table 2, entry 4). Yellow pow-
der (84%); mp 226e228 ꢀC (227e229 ꢀC)10; [found: C, 74.32; H, 5.77;
N, 7.23. C24H22N2O3 requires C, 74.61; H, 5.69; N, 7.25%]; Rf (23%
acetone/n-hexane) 0.34; IR (KBr) (vmax, cmꢁ1) 2958, 1668, 1630; dH
(300 MHz, CDCl3) 1.21 (6H, s, 2Me), 2.3 (3H, s, CH3), 2.34 (2H, s,
CH2C), 3.20e3.45 (2H, AB system, J 18.9 Hz, CHaHbCO), 6.42 (1H, s,
CHN), 7.13e7.32 (4H, dd, J 7.8 Hz, ArMe) 7.83e8.37 (4H, m, Ph); dC
(300 MHz, CDCl3); 21.2, 28.4, 28.7, 34.6, 38.0, 50.9, 64.8, 118.7, 127.0
(2), 127.7, 127.9, 128.9, 129.2, 129.4, 133.41, 133.45, 134.4, 138.4, 148.5,
150.7, 154.2, 156.0, 192.1; MS, m/z (%): 386 (Mþ, 15), 295 (100), 141
(15), 104 (45), 76 (46).
4.2.9. 13-(2,3-Dichlorophenyl)-3,3-dimethyl-3,4-dihydro-1H-indazolo
[1,2-b]phthalazine-1,6,11(2H,13H)-trione (Table 2, entry 10). Yellow
powder (81%); mp 266e268 ꢀC; [found: C, 62.42; H, 3.99; N, 6.40.
C23H18N2O3Cl2 requires C, 62.60; H, 4.1; N, 6.36%]; Rf (23% acetone/
n-hexane) 0.15; IR (KBr) (vmax, cmꢁ1) 2967,1664,1627; dH (300 MHz,
CDCl3) 1.21 (6H, s, 2Me), 2.33 (2H, s, CH2C), 3.21e3.44 (2H, AB
system, J 19.2 Hz, CHaHbCO), 6.7 (1H, s, CHN), 7.21e8.39 (7H, m, Ph);
dC (300 MHz, CDCl3); 28.4, 28.7, 34.6, 38.0, 50.8, 64.4, 118.7, 127.5
(2C), 127.7 (2C), 128.1, 128.5, 129.0, 130.7 (2C), 133.7, 134.1, 134.6,
152.1, 154.3, 156.1, 192.0; MS, m/z (%): 441 (Mþ, 5), 405 (20), 295
(100), 239 (15), 130 (20), 104 (80), 76 (65), 41 (20).
4.2.4. 3,3-Dimethyl-13-(3,4,5-trimethoxyphenyl)-3,4-dihydro-2H-in-
dazolo[1,2-b]phthalazine-1,6,11(13H)-trione (Table 2, entry 5). Yellow
powder (87%); mp 234e236 ꢀC (232e234 ꢀC)12; [found: C, 67.46; H,
5.65; N, 5.93. C26H26N2O6 requires C, 67.52; H, 5.62; N, 6.06%]; Rf
(23% acetone/n-hexane) 0.39; IR (KBr) (vmax, cmꢁ1) 2958, 2838,
1655, 1627; dH (300 MHz, CDCl3) 1.23 (6H, s, 2Me), 2.36 (2H, s,
CH2C), 3.20e3.45 (2H, AB system, J 19.1 Hz, CHaHbCO), 3.8 (9H, s,
3OCH3), 6.39 (1H, s, CHN), 6.63 (2H, s, Ar) 7.85e8.38 (4H, m, Ph); dC
(300 MHz, CDCl3); 28.1, 28.9, 34.6, 38.0, 50.9, 56.2, 60.7, 64.9, 104.6,
118.3, 127.7 (2C), 128.0 (2C), 128.9, 129.0, 131.7, 133.6, 134.6 (2C),
138.3, 150.8, 153.3, 154.5, 156.1, 192.1; MS, m/z (%): 462 (Mþ, 23),
295 (100), 273 (100), 104 (50), 76 (25).
4.2.10. 3,3-Dimethyl-13-(4-(methylthio)phenyl)-3,4-dihydro-1H-
indazolo[1,2-b]phthalazine-1,6,11(2H,13H)-trione (Table 2, entry
11). Yellow powder (86%); mp 229e231 ꢀC; [found: C, 68.77; H,
5.29; N, 6.63. C24H22N2O3S requires C, 68.9; H, 5.30; N, 6.7%]; Rf
(23% acetone/n-hexane) 0.27; IR (KBr) (vmax, cmꢁ1) 2959, 1663,
1628; dH (300 MHz, CDCl3) 1.21 (6H, s, 2Me), 2.34 (2H, s, CH2C),
2.42 (3H, s, SMe), 3.21e3.45 (2H, AB system, J 18.6 Hz, CHaHbCO),
6.4 (1H, s, CHN), 7.10e7.35 (4H, dd, J 8.4 Hz, ArS), 7.84e7.88 (2H, m,
Ph), 8.25e8.37 (2H, m, Ph); dC (300 MHz, CDCl3); 15.5, 28.4, 28.7,
34.6, 38.0, 50.9, 64.6, 118.3, 126.6(2C), 127.6 (2C), 127.7, 127.9, 128.9,
129.0, 133.0, 133.5, 134.5, 139.2, 150.9, 154.3, 156.0, 192.1; MS, m/z
(%): 418 (Mþ, 6), 295 (100), 104 (50), 76 (60), 43 (49).
4.2.5. 13-(2,4-Dichlorophenyl)-3,3-dimethyl-3,4-dihydro-2H-in-
dazolo[1,2-b]phthalazine-1,6,11(13H)-trione (Table 2, entry 6). Yellow
powder (89%); mp 219e221 ꢀC (219e221 ꢀC)12; [found: C, 61.98;
H, 4.04; N, 6.31. C23H18N2O3Cl2 requires C, 62.60; H, 4.10; N,
6.35%]; Rf (23% acetone/n-hexane) 0.32; IR (KBr) (vmax, cmꢁ1
)
2967, 1664, 1627; dH (300 MHz, CDCl3) 1.21 (3H, s, Me), 1.23 (3H, s,
Me), 2.33 (2H, s, CH2C), 3.20e3.44 (2H, AB system, J 19.2 Hz,
CHaHbCO), 6.64 (1H, s, CHN), 7.26e8.4 (7H, m, Ph); dC (300 MHz,
CDCl3); 28.4, 28.7, 34.6, 38.0, 50.8, 63.5, 118.1, 127.6, 127.7 (2C),
128.1, 128.6, 129.0, 131.1, 131.7, 133.2, 133.7, 134.6, 135.1, 152.0,
154.3, 156.1, 192.1; MS, m/z (%): 440 (Mþ, 5), 295 (100), 104 (46),
76 (46).
4.2.11. 13-(3-Hydroxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-indazolo
[1,2-b]phthalazine-1,6,11(2H,13H)-trione (Table 2, entry 12). Yellow
powder (84%); mp 268e270 ꢀC; [found: C, 70.93; H, 5.32; N, 7.03.
C23H20N2O4 requires C, 71.1; H, 5.19; N, 7.2%]; Rf (23% acetone/n-
hexane) 0.16; IR (KBr) (vmax, cmꢁ1): 3357, 2954, 2895, 1663; dH
(300 MHz, CDCl3) 1.21 (6H, s, 2Me), 2.32(2H, s, CH2C), 3.21e3.44
(2H, AB system, J 18 Hz, CHaHbCO), 5.97 (1H, b, OH), 6.41 (1H, s,
CHN), 6.71e7.19 (4H, m, ArOH), 7.84e7.90 (2H, m, Ph), 8.27e8.38
(2H, m, Ph); dC (300 MHz, CDCl3); 28.5, 28.6, 34.6, 38.0, 50.9, 64.7,
114.6, 115.9, 118.5, 118.6, 127.7, 128.0 (2), 128.9, 129.9, 133.6, 134.6,
137.9, 151.0, 154.0, 156.1, 192.3; MS, m/z (%): 388 (Mþ, 6), 295 (60),
104 (100), 76 (90), 65(60), 41 (46).
4.2.6. 3,3-Dimethyl-13-(4-nitrophenyl)-3,4-dihydro-2H-indazolo
[1,2-b]phthalazine-1,6,11(13H)-trione (Table 2, entry 7). Yellow pow-
der (91%); mp 222e225 ꢀC (223e225 ꢀC)10; [found: C, 66.13; H, 4.56;
N, 9.95. C23H19N3O5 requires C, 66.18; H, 4.58; N, 10.07%]; Rf (23%
acetone/n-hexane) 0.24; IR (KBr) (vmax, cmꢁ1) 2971, 2958, 1694,
1660; dH (300 MHz, CDCl3) 1.19 (3H, s, Me),1.26 (3H, s, Me), 2.34 (2H,
s, CH2C), 3.20e3.44 (2H, AB system, J 19.2 Hz, CHaHbCO), 6.51 (1H, s,
CHN), 7.25 and 8.18 (4H, dd, J 11.1 Hz, ArNO2), 7.86e7.9 (2H, m, Ph),
8.25e8.38 (2H, m, Ph); dC (300 MHz, CDCl3); 28.3, 28.7, 34.7, 38.0,
50.8, 64.1, 117.3, 124.0, 127.7, 128.0, 128.2, 128.6, 128.9, 133.9, 134.8,
143.4, 147.9, 135.1, 151.6, 154.5, 155.9, 192.0; MS, m/z (%): 417
(Mþ, 10), 295 (100), 104 (48), 76 (50).
4.3. Typical procedure for the preparation of 13-ethyl-3,3-
dimethyl-3,4-dihydro-1H-indazolo[1,2-b]phthalazine-1,6,11
(2H,13H)-trione (Table 2, entry 13)
4.2.7. 3,3-Dimethyl-13-(naphthalen-2-yl)-3,4-dihydro-2H-indazolo
[1,2-b]phthalazine-1,6,11(13H)-trione (Table 2, entry 8). Yellow
powder (89%); mp 251e253 ꢀC (251e252 ꢀC)11; [found: C, 76.31; H,
5.12; N, 6.35. C27H22N2O3 requires C, 76.76; H, 5.25; N, 6.63%]; Rf
(23% acetone/n-hexane) 0.26; IR (KBr) (vmax, cmꢁ1) 2956, 1665,
1619; dH (300 MHz, CDCl3) 1.22 (6H, s, 2Me), 2.33 (2H, s, CH2C),
3.24e3.50 (2H, AB system, J 18.6 Hz, CHaHbCO), 6.62 (1H, s, CHN),
7.45e8.38 (11H, m, Ph); dC (300 MHz, CDCl3); 28.4, 28.7, 34.6, 38.1,
50.9, 65.1, 118.6, 124.2, 126.2, 126.3, 126.8, 127.6, 127.7, 127.9, 128.2,
A mixture of dimedone (0.28 g, 2 mmol), phthalhydrazide
(0.32 g, 2 mmol), propanal (0.14 g, 2.2 mmol), and TBBDA (0.05 g) or
PBBS (0.1 g) was heated at 80 ꢀC for 60 min. After completion of the
reaction by TLC [chamber containing iodine crystals and acetone/n-
hexane (1:3.5)], the reaction mixture was cooled, and was acetone
added to it (15 mL). The insoluble phthalhydrazide was removed by
filtration and washed with acetone (15 mL). Removal of the solvent
under reduced pressure gave the catalyst. The crude product was

1936
R. Ghorbani-Vaghei et al. / Tetrahedron 67 (2011) 1930e1937
purified by [TLC using acetone/n-hexane (3:10)] as eluent to afford
the pure product. Yellow powder (59%); mp 145e147 ꢀC; [found: C,
70.02; H, 6.34; N, 8.47. C19H20N2O3 requires C, 70.35; H, 6.21; N,
8.64%]; Rf (23% acetone/n-hexane) 0.49; IR (KBr) (vmax, cmꢁ1) 2961,
1664, 1622; dH (300 MHz, CDCl3) 0.72e0.77 (3H, t, Me), 1.23 (3H, s,
Me), 1.44 (3H, s, Me), 2.07e2.17 (1H, m, CH), 2.39 (2H, m, CH), 2.39
(2H, s, CH2C) 2.51e2.59 (1H, m, CH), 3.11e3.39 (2H, AB system, J
18 Hz, CHaHbCO), 5.72e5.73 (1H, m, CHN), 7.83e7.93 (2, m, Ph),
8.31e8.39 (2H, m, Ph); dC (300 MHz, CDCl3); 7.2, 22.1. 28.3, 28.8,
34.4, 38.1, 51.0, 63.5, 117.6, 127.5, 127.8, 128.9, 129.0, 133.4, 134.4,
151.8, 155.3, 156.4, 193.0; MS, m/z (%): 325 (5), 324 (Mþ, 3), 295 (80),
130 (20), 104 (43), 76 (50).
128.3, 129.3, 133.9, 134.9, 152.3, 155.4, 156.5, 193.4; MS, m/z (%):
371 (Mþ, 3), 349 (90), 295 (25), 273 (20), 217 (20), 161 (20), 41 (20).
4.3.5. 13-Hexyl-3,3-dimethyl-3,4-dihydro-1H-indazolo[1,2-b]phtha-
lazine-1,6,11(2H,13H)-trione (Table 2, entry 18). Yellow powder
(51%); mp 82e85 ꢀC; [found: C, 72.11; H, 7.42; N, 7.41. C23H28N2O3
requires C, 72.6; H, 7.42; N, 7.36%]; Rf (23% acetone/n-hexane) 0.54;
IR (KBr) (vmax, cmꢁ1) 2959, 2927, 1656, 1625; dH (500 MHz, CDCl3)
0.83e0.85 (3H, t, Me), 1.12e1.14 (2H, m, CH2R), 1.17e1.34 (12H, m,
2Me, 3CH2), 2.12e2.13 (1H, m, CH), 2.44e2.46 (2H, dd, CH2C),
2.47e2.50 (1H, m, CH), 3.15e3.39 (2H, AB system, J 19.2 Hz,
CHaHbCO), 5.74e5.73 (1H, m, CHN), 7.88e7.93 (2H, m, Ph),
8.37e8.41 (2H, m, Ph); dC (500 MHz, CDCl3); 14.3, 22.9, 23.7, 28.8,
29.2, 29.3, 29.7, 32.0, 34.9, 38.5, 51.4, 63.3, 117.7, 127.9, 128.3, 129.4,
133.8, 134.8, 152.0, 155.0, 156.5, 193.4; MS, m/z (%): 379 (Mþ, 6), 295
(25), 273 (20), 178 (90), 104 (40), 76 (30), 41 (90).
4.3.1. 3,3-Dimethyl-13-propyl-3,4-dihydro-1H-indazolo[1,2-b]phtha-
lazine-1,6,11(2H,13H)-trione (Table 2, entry 14). Yellow powder (58%);
mp 136e138 ꢀC; [found: C, 70.79; H, 6.61; N, 8.23. C20H22N2O3
requires C, 71.0; H, 6.55; N, 8.3%]; Rf (23% acetone/n-hexane) 0.31;
IR (KBr) (vmax, cmꢁ1) 2955, 1715, 1656, 1625; dH (500 MHz, CDCl3)
0.87e0.90 (3H, t, Me), 1.13e1.18 (2H, m, CH2R), 1.21 (3H, s, Me),
1.25 (3H, s, Me), 2.06e2.13 (1H, m, CH), 2.36e2.47 (3H, m, CH,
CH2C), 3.13e3.37 (2H, AB system, J 19 Hz, CHaHbCO), 5.71 (1H, m,
CHN), 7.87e7.92 (2H, m, Ph), 8.34e8.39 (2H, m, Ph); dC (500 MHz,
CDCl3); 14.1, 17.1, 28.9, 29.1, 32.0, 34.9, 38.4, 51.4, 63.2, 117.7, 127.9,
128.2, 129.3, 129.4, 133.8, 134.8, 152.0, 155.1, 156.5, 193.4; MS, m/z
(%): 338 (Mþ, 3), 295 (100), 273 (20), 239 (25) 104 (80), 76 (60),
41 (60).
4.3.6. 13-Isopropyl-3,3-dimethyl-3,4-dihydro-1H-indazolo[1,2-b]
phthalazine-1,6,11(2H,13H)-trione (Table 2, entry 19). Yellow pow-
der (51%); mp 132e134 ꢀC; [found: C, 70.53; H, 6.49; N, 8.17.
C20H22N2O3 requires C, 71.0; H, 6.55; N, 8.3%]; Rf (23% acetone/n-
hexane) 0.33; IR (KBr) (vmax, cmꢁ1) 2958, 2935, 1681, 1659; dH
(500 MHz, CDCl3) 0.96e0.97 (3H, d, Me), 1.06e1.08 (3H, d, Me) 1.21
(3H, s, Me), 1.28 (3H, s, Me), 2.36e2.48 (2H, AB system, J 15 Hz,
CHaHbC), 2.71e2.74 (1H, m, CH), 3.11e3.34 (2H, AB system, J 20 Hz,
CHaHbCO), 5.65 (1H, m, CHN), 7.87e7.95 (2, m, Ph), 8.35e8.41 (2H,
m, Ph); dC (500 MHz, CDCl3); 18.5, 18.8, 28.7, 29.2, 31.7, 34.6, 38.5,
51.5, 67.54, 117.5, 127.5, 128.0, 128.3, 129.2, 129.5, 133.8, 134.9, 152.8,
155.6, 156.5, 193.3; MS, m/z (%): 338 (Mþ, 3), 339 (5), 295 (100), 104
(25), 76 (25), 41 (25).
4.3.2. 3,3-Dimethyl-13-pentyl-3,4-dihydro-1H-indazolo[1,2-b]phthala-
zine-1,6,11(2H,13H)-trione (Table 2, entry 15). Yellow powder (61%);
mp 138e140 ꢀC; [found: C, 71.90; H, 7.47; N, 7.55. C22H26N2O3 re-
quires C, 72.1; H, 7.15; N, 7.64%]; Rf (23% acetone/n-hexane) 0.53; IR
(KBr) (vmax, cmꢁ1) 2953, 2929, 1656, 1620; dH (500 MHz, CDCl3)
0.81e0.83 (3H, t, Me), 1.11e1.17 (2H, m, CH2R), 1.22e1.28 (10H, m,
2Me, 2 CH2), 2.09e2.15 (1H, m, CH), 2.37e2.44 (2H, dd, CH2C),
2.45e2.50 (1H, m, CH), 3.14e3.38 (2H, AB system, J 19 Hz, CHaHbCO),
5.72e5.73 (1H, m, CHN), 7.87e7.94 (2H, m, Ph), 8.35e8.4 (2H, m, Ph);
dC (500 MHz, CDCl3); 14.3, 22.8, 23.3, 28.8, 29.2, 29.7, 31.7, 34.9, 38.5,
51.4, 63.3, 117.7, 127.9, 128.3, 129.3, 129.4, 133.8, 134.8, 152.0, 155.1,
156.5,193.4; MS, m/z (%): 366 (Mþ, 4), 295 (100), 273 (20),104 (50), 76
(40), 41 (90).
4.3.7. 13-Isobutyl-3,3-dimethyl-3,4-dihydro-1H-indazolo[1,2-b]
phthalazine-1,6,11(2H,13H)-trione (Table 2, entry 20). Yellow pow-
der (59%); mp 135e137 ꢀC; [found: C, 70.73; H, 7.16; N, 7.63.
C21H24N2O3 requires C, 71.56; H, 6.86; N, 7.95]; Rf (23% acetone/n-
hexane) 0.45; IR (KBr) (vmax, cmꢁ1) 2958, 2871, 1664, 1630; dH
(500 MHz, CDCl3) 0.86e0.87 (3H, d, Me), 0.93e0.94 (3H, d, Me),1.20
(3H, s, Me), 1.25 (3H, s, Me), 1.69e1.75 (1H, m, CH), 2.01e2.05 (1H,
m, CH), 2.14e2.19 (1H, m, CH), 2.35e2.45 (2H, AB system, J 15 Hz,
CHaHbC), 3.14e3.36 (2H,AB system, J 19 Hz, CHaHbCO), 5.7 (1H, m,
CHN), 7.86e7.93 (2H, m, Ph), 8.34e8.39 (2H, m, Ph); dC (500 MHz,
CDCl3); 23.1, 24.0, 25.3, 28.9, 29.0, 34.8, 38.5, 39.9, 51.5, 62.3, 118.7,
127.9, 128.3, 129.8, 129.5, 133.8, 134.8, 151.8, 155.3, 156.6, 193.3; MS,
m/z (%): 352 (Mþ, 3), 353 (5), 331 (10), 295 (75), 273 (90), 217 (25)
104 (25), 76 (25), 41 (75).
4.3.3. 3,3-Dimethyl-13-phenethyl-3,4-dihydro-1H-indazolo[1,2-b]
phthalazine-1,6,11(2H,13H)-trione (Table 2, entry 16). Yellow pow-
der (75%); mp 171e173 ꢀC; [found: C, 74.91; H, 6.27; N, 7.04.
C25H24N2O3 requires C, 75.0; H, 6.0; N, 7.0%]; Rf (23% acetone/n-
hexane) 0.5; IR (KBr) (vmax, cmꢁ1) 2961, 1712, 1655, 1630; dH
(300 MHz, CDCl3) 1.15 (3H, s, Me), 1.25 (3H, s, Me), 2.27e2.28 (2H,
dd, CH2C), 2.41e2.69 (3H, m, CH, CH2), 2.91e3.05 (1H, m, CH),
3.09e3.25 (2H, AB system, J 19.2 Hz, CHaHbCO), 5.73 (1H, m, CHN),
6.69e7.04 (5H, m, ArH), 7.81e7.95 (2H, m, Ph) 8.23e8.26 (2H, m,
Ph); dC (500 MHz, CDCl3); 28.6, 28.7, 29.3, 29.4, 30.5, 34.7, 38.4, 51.2,
62.8, 116.9, 125.9, 127.7, 128.0, 128.3, 128.5, 128.8, 129.1, 129.2, 133.6,
134.6, 141.0, 152.3, 155.0, 156.5, 193.6; MS, m/z (%): 400 (Mþ, 5), 295
(100), 239 (20), 104 (80), 76 (70), 41 (20).
Acknowledgements
We are thankful to Bu-Ali Sina University, Center of Excellence
and Development of Chemical Methods (CEDCM) for financial
support
References and notes
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