Glycerol: A more benign and biodegradable promoting medium for catalyst-free one-pot multi-component synthesis of triazolo[1,2-a]indazole-triones

Article abstract of DOI:10.1039/c5ra13805a

The one-pot three component synthesis of triazolo[1,2-a]indazole-triones was conducted successfully under catalyst-free conditions in glycerol as a benign, nontoxic and biodegradable promoting medium. A broad range of substrates including aromatic aldehyd

Full text of DOI:10.1039/c5ra13805a

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Glycerol: more benign and biodegradable promoting medium for
catalyst-free one-pot multi-component synthesis of triazolo[1,2-
a]indazole-triones
Received 00th January 20xx,
Accepted 00th January 20xx
Mohsen Shekouhya, Abdollah Masoudi Sarvestania, Soheila Khajeha, Ali Khalafi-Nezhad*, a
DOI: 10.1039/x0xx00000x
www.rsc.org/
The one-pot three component synthesis of triazolo[1,2-a]indazole-triones was conducted successfuly under catalyst-free
condition in glycerol as a benign, nontoxic and biodegradable promoting medium. A broad range of substrates including
aromatic aldehydes are condensed with carbonyl compounds possessing a reactive α-methylene group and urazole
derivatives. All reactions are completed in short times and the products are obtained in good to excellent yields.
Moreover, presented method was applied successfuly in large scale synthesis of titled compounds.
transition metal complexes are soluble in glycerol. Furthermore, it
also dissolves organic compounds that are poorly miscible in water.
Moreover, many hydrophobic solvents such as ethers and
hydrocarbons are immiscible in glycerol. This solubility profile
Introduction
makes the reaction products able to be separated from the reaction
medium with a simple extraction step. Moreover, the high boiling
point of glycerol (290 oC) is an important advantage and provides
higher temperature that making possible reaction that does not
proceed in low boiling point solvents. The non-toxicity of glycerol
(LD50= 12600 mg/Kg (oral rat)), its biodegradability and non-
flammability for which no special handling precautions or storage is
required makes it a worthy candidate for application in the
synthesis of pharmaceutically active ingredients in which the
toxicity and residue of solvents have to be carefully controlled.
Because of these unique properties, there is a large number of
reports on the application of glycerol as an efficient and convenient
solvent in organic transformations.10 More recently Hei et al.
demonstrated that glycerol is an effective promoting medium for
electrophilic activation of aldehydes and they showed that some
reactions which have been conventionally carried out using acid
catalysts, can be performed under catalyst-free conditions in the
presence of glycerol as a reaction medium.11
The growing awareness of the pressing need for more benign and
sustainable technologies has focused attention on the use of atom
efficient catalytic methodologies as well as the use of alternative
reaction media that circumvent the problems associated with many
of the traditional volatile organic solvents. Based on the Green
Chemistry protocols1a there are several issues that influence the
choice of a solvent as a benign and applicable reaction medium. It
should be relatively nontoxic and relatively nonhazardous and it
must be not flammable or corrosive. The solvent should also be
recoverable and should not be released to the environment.
Moreover, these green solvents have to be cheap and easy to
handle and recycle.1 During the past decade, various alternatives
have been reported to apply as a more benign reaction medium for
organic transformations.2-6 Various fascinating results of these
media are undeniable but, application of these alternatives is
combination with strict limitations such as need to very expensive
equipments7 or high prices and lack of data about the toxicity and
bio-compatibility8 of them or product separation for aqueous-based
processes.9 In fact, a global benign solvent doesn’t exist and the
scientific community is continuously searching for new sustainable
media in order to widen their use in organic processes.
Heterocyclic compounds are an important branch of chemicals
because they are the main building blocks of a large variety of
products, such as molecular materials, natural and biologically
active compounds and also in regularly marketed drugs. For that
reason, sustainable synthetic strategies have turned into a crucial
current research. From this viewpoint, one-pot procedures
involving multi-step transformations represent powerful
methodological means, which prevent the isolation (and
purification) of intermediates leading to selective and advantageous
processes.12a-c Two important classes of heterocyclic compounds
are triazoles and indazoles. The main reason of interest on
indazoles is its distribution in the structure of natural products.
Various alkaloids such as Nigellicine, Nigeglanine, and Nigellidine
Glycerol is
a
non-volatile, inflammable, very cheap and
biodegradable material that is produced as a by-product during the
biodiesel synthesis. This compound introduces a unique solubility
profile. Most of inorganic salts, acids, bases, enzymes and many
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are indazoles.12d Moreover there are various kinds of tetrazole-
contained chemicals that are used as antifungal drugs such as
CHO
O
HN
HN
N
fluconazole13a isavuconazole13b itraconazole13c voriconazole13d
, , , ,
O
pramiconazole13e, ravuconazole13f, and posaconazole13f. In addition,
epoxiconazole13g, triadimenol13h, propiconazole13i, metconazole13j
cyproconazole13g tebuconazole13k flusilazole13l
and
O
(3a)
(1a)
Various Condition
-2 H2O
O
N
,
O
N
,
,
N
paclobutrazol13m are the other triazole-contained chemicals that are
used as plant protection fungicides. Triazolo[1,2-a]indazole-triones
and their derivatives are a class of very useful compounds that their
chemical structures consist of indazole and triazole backbones at
the same time. They have been widely used as medicine
intermediates because of their biological and pharmacological
properties.13n However there are only a few reported methods for
the synthesis of these compounds such as application of p-
toluenesulfunic acid (PTSA)14, sulfonated polyrthyene glycol (PEG-
(4a)
O
O
(2b)
Scheme 2. The one-pot three component condensation reaction of
benzaldehyde (1a), dimedone (2a) and N-phenyl urazole (3a) under
various conditions.
Only a trace amount of products were detected in toluene, DMF,
DMSO, ethyl acetate and in neat conditions (Table 1, entries
1,2,5,6,13). While the reaction proceeded sluggishly in ethanol, a
huge improvement was observed in polyethylene glycol and
ethylene glycol (Table 1, entries 3,4,7). Although water was proved
to be capable of promoting the reaction, in this case, a gummy solid
was obtained which makes the separation of products very hard
(Table 1, entry 14). Inspired by the observed determinant effect of
alcoholic solvents on the reaction, we then investigated the
efficiency of glycerol as a solvent for this reaction. As we expected,
the reaction proceeded very well, and 94% yield was obtained
under identical conditions (Table 1, entry 12). As shown in Table 1,
the best results were obtained at 100 °C in the presence of glycerol
(1 mL). Interestingly, all starting materials are soluble in glycerol, so
at the start of the reaction, a solution, which seemed to be nearly
transparent, was observed. All obtained products were found to be
insoluble in glycerol, so with progress of the reaction, wrought
products sediment slowly from the reaction mixture.
OSO3H)15, melamine trisulfonic acid (MTSA)16, tungstosilicic acid17
silica nanoparticles prepared from rice husk18
quinuclidine
stabilized on FeNi3 nanoparticles19, camphor-10-sulfonic acid20
ZrOCl2.8H2O21 and sulfamic acid.22
Despite the available
,
,
,
methodologies, there still exists a demand for devising a more
efficient and environmentally benign procedure which allows the
ready synthesis of these polycyclic systems.
Based on the above facts we herein report a catalyst-free one-pot
three component synthesis of triazolo[1,2-a]indazole-triones in
glycerol as a biodegradable and benign solvent (Scheme 1). To the
best of our knowledge this is the first report of catalyst-free
synthesis of triazolo[1,2-a]indazole-triones.
O
CHO
R1
HN
HN
R3
N
O
R1
O
(3)
Glycerol / 100 o
-2 H2O
C
O
(1)
Table 1. The catalyst-free condensation reaction between
benzaldehyde (1a, 1 mmol), dimedone (2b, 1 mmol) and N-phenyl
urazole (3a, 1 mmol) under various conditions
R2
R2
N
O
N
N
R3
(4a-w)
O
R2
R2
O
Temp
(oC)
100
100
Reflux
100
100
Reflux
100
r.t.
Time
(h)
12
12
12
4
12
12
4
Yield
(%)a
Trace
Trace
51
Entry
Solvent (1 mL)
(2)
Scheme 1. The catalyst-free one-pot three component synthesis of
triazolo[1,2-a]indazole-triones in glycerol as a biodegradable and
benign solvent.
1
2
3
4
5
6
7
8
DMF
DMSO
Ethanol
Poly ethylene glycol 400
Toluene
80
Trace
Trace
82
Ethyl acetate
Ethylene glycol
Glycerol
Results and discussion
8
33
Initially, the reaction between benzaldehyde (1a), dimedone (2b)
and N-phenyl urazole (3a) was investigated in different solvents
under catalyst-free conditions at various temperatures (Scheme 2),
and the results are listed in Table 1.
9
Glycerol
Glycerol
Glycerol
Glycerol
50
60
80
8
6
4
4
8
8
8
8
71
78
86
94
Trace
69
91
93
93
10
11
12
13
14
14
16
17
18
19
100
100
100
100
100
100
100
100
-
Water
Choline chloride/Glycerol 1:1
Choline chloride/Glycerol 1:2
Choline chloride/Glycerol 1:3
Et2(EtOH)NClb/Glycerol 1:2
Et2(EtOH)NCl/Glycerol 1:3
8
8
8
83
86
a Isolated yields. b N,N-diethylenethanol ammonium chloride.
2 | J. Name., 2012, 00, 1-3
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Table 2. The catalyst-free one-pot three-component synthesis of triazolo[1,2-a]indazole-triones in glycerol at 100 oC.
1 mmol Scale
25 mmol Scale
Entry
R1
R2
R3
Product
(m.p. oC)
Ti
me
(h)
Yield
(%)a
A. E.
(%)b
Time
(h)
Yield
(%)a
A. E.
(%)b
191-192 (190-
192)15
1
2
C6H5
p-Br-C6H4
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4a
4b
4c
4d
4e
4f
4
4
6
4
6
3
6
6
3
3
3
3
6
6
94
94
92
92
91
92
90
90
94
93
91
93
90
91
86
87
85
84
83
84
82
83
86
85
83
86
82
84
7
7
90
91
89
90
88
90
90
88
91
92
90
89
83
85
82
84
82
83
81
82
82
81
84
84
82
82
76
78
183-184 (185-
187)15
170-172 (172-
174)15
3
m-Br-C6H4
p-Cl-C6H4
10
7
170-171 (173-
175)15
4
179-180, (177-
178)15
5
o-Cl-C6H4
8
104-106, (105-
10815
6
p-F-C6H4
6
166-167 (163-
164)15
7
p-CH3-C6H4
p-CH(CH3)2-C6H4
p-NO2-C6H4
m-NO2-C6H4
p-CN-C6H4
p-CF3-C6H4
m-OCH3-C6H4
2-Naphthyl
4g
4h
4i
10
10
6
162-164 (164-
166)15
8
173-174 (175-
177)15
9
132-135 (131-
133)15
10
11
12
13
14
4j
7
240-241 (240-
242)15
4k
4l
7
186-188 (184-
186)15
6
104-106 (106-
107)15
4m
4n
10
10
140-141 (139-
142)15
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226-228 (225-
15b
4-OH-C6H3
C6H5
4o
7
6
8
6
6
6
5
5
5
90
90
91
89
92
90
90
91
92
82
82
83
80
84
78
82
83
84
12
9
83
88
90
84
88
87
85
89
89
76
80
82
76
80
75
78
81
81
CH3
CH3
CH3
H
C6H5
C6H11
C6H11
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
228)15
114-116 (112-
16
17
18
19
20
21
22
23
4p
114)15
170-172 (167-
m-OC6H4-C6H4
4q
9
169)15
C6H5
4r
4s
198-199
205-207
202-204
206-208
251-253
183-185
8
p-Cl-C6H4
p-CH3-C6H4
p-NO2-C6H4
p-CN-C6H4
m-NO2-C6H4
19
10
7
H
4t
H
4u
4v
4w
H
7
H
7
H
a Isolated yields. b Atom economy.
The model reaction was also examined in the presence of various 2. As it is shown in Table 2, all reactions proceeded efficiently and
glycerol-based eutectic solvents as another green reaction media23 the desired products were produced in good to excellent yields in
at 100 oC (Table 1, entries 14-19) and in all cases high yields of relatively short reaction times without formation of any by-
products were obtained. However, glycerol was selected as the best products. Aromatic aldehydes having electron withdrawing groups
promoting medium for this reaction because it is a readily available (Table 2, entries 6, 9, 10, 11, 12, 21, 22, 23) reacted at faster rates
material and there is no need to a pre-treatment step as this is compared with those that substituted with electron releasing
necessary for the production of eutectic systems.
groups (Table 2, entries 8, 13, 17, 20). The reactivity of aliphatic
aldehydes was also investigated with the condensation of
butyraldehyde with dimedone and N-phenylurazole and
unfortunately only a mixture of starting materials and unknown
products was obtained even after a long time (24h).
It should be noted that the synthesis of triazolo[1,2-a]indazole-
triones via a one-pot three component condensation reaction
between aldehydes, carbonyl compounds possessing a reactive α-
methylene group and urazoles are generally carried out in the
presence of various acids or metal-containing catalysts with the aid Due to the high hydrophilicity of glycerol, separation of the
of organic solvents. Obviously, these reported methods not only products from the reaction mixture could be realized by adding
generate a lot of organic or inorganic wastes during the work-up water at 100 °C. This simple procedure allows easy scale up of our
procedure, but also suffer from the difficulty of removing trace methodology. In another study, to recognize the applicability of our
amounts of residue metal species from the product when it is method at large scales, we examined reactions in scales of 25 mmol
applied in pharmaceutical synthesis. Particularly, in the case of solid and the obtained results are summarized in Table 2. As shown in
acids, a large amount of organic solvent has to be used for the Table 2, the reactions were successfully performed at large scales
separation and recovery of the catalyst owing to the fact that both without significant loss of yield.
the catalyst and the product are solid. Performing the model
reaction in glycerol not only offers a high reaction yield, but also
In another study phthalhydrazide (
of N-phenyl urazole in one-pot condensation with benzaldehyde
1a, 1 mmol) and dimedone (2b, 1 mmol) under optimized reaction
condition (Scheme 3) and desired product ( ) was obtained as a
5, 1 mmol) was applied instead
avoids the generation of toxic wastes, the use of large amount of
organic solvents or catalysts and tedious post-treatment. Therefore,
our system is an attractive strategy for the synthesis of the target
compound from the viewpoint of green synthesis. With these
results in hand, we then investigated the substrate scopes and
limitations of the synthesis of triazolo[1,2-a]indazole-triones in
glycerol as a promoting medium, and the results are listed in Table
(
6
white powder after 4h in 90% yield. Moreover, this reaction was
applied in 25 mmol scale and desired product was obtained after 8
h in 85% yield. These results demonstrate the efficiency of glycerol
4 | J. Name., 2012, 00, 1-3
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as
ARTICLE
a
promoting medium for the synthesis of indazolo[2,1- sustainability due to the avoidance of a quenching step, reduced
b]phthalazine-triones as the other important derivatives of reliance on toxic organic solvents, and minimization of waste.
indazoles. Besides, these results approve the efficiency of glycerol
as a promoting medium in such multi component reactions that are
Experimental
conducted through an intramolecular cyclocondensation reaction.
O
CHO
All chemicals were purchased from Merck or Fluka Chemical
O
HN
HN
1
Companies. The H NMR (250 MHz) and 13C NMR (62.5 MHz) were
O
Glycerol (1 mL) / 100 oC / 4h
-2 H2O
N
run on a Bruker Avance DPX-250, FT-NMR spectrometer (δ in ppm).
O
N
(5)
(1a)
Microanalysis was performed on
a
PerkineElmer 240-B
O
microanalyzer. Melting points were recorded on a Büchi B-545
apparatus in open capillary tubes. The progress of the reaction and
the purity of compounds were monitored by TLC analytical silica gel
plates (Merck 60 F250).
O
(6) 90%
O
(2b)
Scheme 3. The one-pot three component condensation reaction of
benzaldehyde 1a 1mmol), dimedone 2a mmol) and
, 1 mmol) in the presence of glycerol (1 mL) at
General procedure for the synthesis of triazolo[1,2-a]indazole-
trione derivatives
(
,
(
, 1
phthalhydrazide (
5
100 oC.
To a mixture of aldehyde (1 mmol), carbonyl compound possessing
a reactive α-methylene group (1 mmol) and urazole (1 mmol) in a
10 mL round-bottomed flask connected to a reflux condenser, was
added glycerol (1 mL), and the resulting mixture was stirred in an
oil-bath (100 °C). The progress nof the reaction was monitored by
TLC using EtOAc/n-hexane (1:5) as an eluent. After completion of
the reaction, warm water (5 mL) was added. Glycerol dissolved in
the water and the insoluble crude products were isolated by simple
filtration. The crude products were dissolved in warm EtOH (6 mL)
and were allowed to stand at room temperature for 5-6 h. The
crystalline solids were collected and dried.
It is well known that presented method for the synthesis of titled
compounds is a multi-component approach that is established
based on electrophilic alkylation of aldehydes with a nucleophile
with the aid of an intramolecular condensation that is fully studied
in the literature.24 Moreover, the mechanism of condensation of
aldehydes, reactive carbonyl compounds possessing a α-methylene
group and urazoles in the presence of various catalytic systems is
fully described.14, 15 However, in this work, any kind of catalyst was
not applied and the reaction was just preceded in the presence of
glycerol as a benign reaction medium. As it has been mentioned by
Safaei et al.25, it may be speculated that the polar amphoteric
hydroxyl groups of the glycerol facilitate the interaction of weak
acidic and basic components due to the stabilization of the
corresponding transition states and intermediates by hydrogen
bonding. Moreover, we think that hydrogen bonding between polar
parts of electrophiles and nucleophiles may lead to the increase in
their nucleophilicity as well as electrophilicity. So, in addition to its
unique properties a benign and non-hazardous reaction medium,
glycerol can act as an activator in this reaction.
General procedure for the large scale synthesis of triazolo[1,2-
a]indazole-trione derivatives
To a mixture of aldehyde (25 mmol), carbonyl compound possessing
a reactive α-methylene group (25 mmol) and urazole (25 mmol) in a
100 mL round-bottomed, two necked flask fitted with an efficient
mechanical stirrer and a reflux condenser, was added glycerol (25
mL), and the resulting mixture was stirred in an oil-bath (100 °C).
The progress of the reaction was monitored by TLC using EtOAc/n-
hexane (1 : 5) as an eluent. After completion of the reaction, warm
water (25 mL) was added. Glycerol dissolved in the water and the
insoluble crude products were isolated by simple filtration. The
crude products were dissolved in warm EtOH or (30 mL) and were
allowed to stand at room temperature for 24 h.
Conclusion
In summary, a highly efficient, catalyst-free and more benign
procedure was reported for one-pot three component synthesis of
triazolo[1,2-a]indazole-triones using glycerol as an inexpensive,
biodegradable and commercially available promoting medium. This
method avoids the use of hazardous catalysts or solvents. The
promising points for the presented methodology are large-scale
availability, high efficiency, high yields of products, short reaction
times, facile work up and product isolation and finally, agreement
with green chemistry protocols, that making it a useful and
attractive process for the synthesis of triazolo[1,2-a]indazole-trione
derivatives. Compared with previously reported systems composed
of acid or base catalysts and organic solvents, application of glycerol
as a solvent not only makes the product separation much easier,
but also shows higher environmental compatibility and
Selected Spectral Data:
6,7-dihydro-2,9-diphenyl-[1,2,4]triazolo[1,2-a]indazole-
1,3,8(2H,5H,9H)-trione (4r)
White powder, υmax (KBr) 3050, 2965, 1720, 1655, 1610, 1375 cm-1.
1H NMR (250 MHz, CDCl3): δ (ppm) 1.65-1.82 (m, 2H), 1.89-1.98 (m,
2H), 2.01-2.81 (m, 2H), 6.22 (s, 1H,), 7.40-7.50 (m, 10H). 13C NMR
(62.5 MHz, CDCl3): δ (ppm) 21.4, 21.9, 34.3, 64.4, 120.0, 123.4,
126.4, 127.5, 127.9, 128.52, 128.59, 132.9, 135.0, 137.0, 150.8,
152.0, 192.0. Anal. Calcd for C21H17N3O3: C, 70.18; H, 4.77; N, 11.69
%. Found: C, 71.21; H, 4.72; N, 11.73 %.
9-(4-chlorophenyl)-6,7-dihydro-2-phenyl-[1,2,4]triazolo[1,2-
a]indazole-1,3,8(2H,5H,9H)-trione (4s)
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White powder, υmax (KBr) 3050, 2950, 1665, 1615, 1200 cm-1. 1H 7.5 Hz, 1H), 8.37 (dd, J= 6.0, 3.5 Hz, 1H). 13C NMR (62.5 MHz, CDCl3):
NMR (250 MHz, CDCl3): δ (ppm) 2.15-2.25 (m, 2H), 2.42-2.47 (m, δ (ppm) 28.9, 29.1, 35.0, 38.4, 65.3, 119.0, 127.5, 128.1, 128.4,
2H), 2.99-3.06 (m, 2H), 6.16 (s, 1H), 7.32-7.48 (m, 9H). 13C NMR 129.11, 129.14, 129.4, 129.5, 133.9, 134.9, 136.8, 151.2, 154.7,
(62.5 MHz, CDCl3): δ (ppm) 21.9, 22.6, 34.6, 64.8, 119.1, 122.6, 156.4, 192.5. Anal. Calcd for C23H20N2O3: C, 74.18; H, 5.41; N, 7.52%.
126.6, 127.8, 128.8, 129.4, 132.1, 132.2, 133.9, 136.5, 150.6, 152.5, Found: C, 74.29; H, 5.38; N, 7.63%.
192.0. Anal. Calcd for C21H16ClN3O3: C, 64.05; H, 4.09; N, 10.67%.
Found: C, 64.10; H, 4.16; N, 10.55 %.
Acknowledgements
6,7-dihydro-2-phenyl-9-
p-tolyl-[1,2,4]triazolo[1,2-a]indazole-
1,3,8(2 ,5 ,9 )-trione (4t)
H
H
H
The authors gratefully appreciate the Shiraz University
Research Councils for the financial support of this work.
White powder, υmax (KBr) 3060, 2940, 1670, 1620, 1210 cm-1. 1H
NMR (250 MHz, CDCl3): δ (ppm) 1.28 (s, 3H), 1.70 (m, 2H), 1.89 (m,
2H), 2.53 (m, 2H), 6.20 (s, 1H), 7.20 (d, J= 8.0 Hz, 2H), 7.35 (d, J= 8.0
Hz, 2H), 7.40-7.48 (m, 1H), 7.55-7.59 (m, 4H). 13C NMR (62.5 MHz,
CDCl3): δ (ppm) 20.9, 21.8, 22.7, 66.9, 121.9, 126.5, 127.8, 129.1,
130.2, 130.3, 132.5, 133.7, 136.5, 136.7, 153.8, 154.5, 190.5. Anal.
Calcd for C22H19N3O3: C, 70.76; H, 5.13; N, 11.25%. Found: C, 70.64;
H, 5.19; N, 11.12 %.
Notes and references
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and Practice, Oxford University Press, Oxford, 1998; (b) C.
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123.
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6,7-dihydro-9-(4-nitrophenyl)-2-phenyl-[1,2,4]triazolo[1,2-
a
]indazole-1,3,8(2H,5H,9H)-trione (4u)
4- J. Chen, S. K. Spear, J. G. Huddleston and R. D. Rogers, Green
Chem. 2005, , 64.
5- J. F. Brennecke, Chem. Ind. 1996, 831.
7
White powder, υmax (KBr) 3050, 2960, 1650, 1610, 1200 cm-1. 1H
NMR (250 MHz, CDCl3): δ (ppm) 2.06-2.29 (m, 2H), 2.31-2.37 (m,
2H), 2.88-2.95 (m, 2H), 6.18 (s, 1H), 7.33-7.42 (m, 5H), 7.66 (dd, J=
8.75, 3.75 Hz, 2H), 8.13 (dd, J= 8.75, 3.75 Hz, 2H). 13C NMR (62.5
MHz, CDCl3): δ (ppm) 21.3, 22.0, 34.8, 63.5, 119.5, 122.5, 124.4,
126.4, 127.9, 128.6, 132.8, 135.6, 135.9, 143.7, 150.9, 151.5, 192.0.
Anal. Calcd for C21H16N4O5: C, 62.37; H, 3.99; N, 13.86%. Found: C,
62.42; H, 3.85; N, 13.93 %.
6- I. T. Horváth, Acc. Chem. Res. 1998, 31, 641.
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and Practice, Oxford University Press, USA, 2003.
4-(1,2,3,5,6,7,8,9-octahydro-1,3,8-trioxo-2-phenyl-
[1,2,4]triazolo[1,2-a]indazol-9-yl)benzonitrile (4v)
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White powder, υmax (KBr) 3040, 2950, 2250, 1650, 1620, 1200 cm-1.
1H NMR (250 MHz, CDCl3): δ (ppm) 1.70 (m, 2H), 1.81 (m, 2H), 2.52
(m, 2H), 6.31 (s, 1H), 7.43-7.52 (br, 5H), 7.70 (d, J= 7.5 Hz, 2H), 8.01
(d, J= 7.5 Hz, 2H). 13C NMR (62.5 MHz, CDCl3): δ (ppm) 21.5, 22.9,
36.8, 67.3, 112.0, 119.5, 121.7, 125.8, 128.5, 129.0, 130.6, 131.7,
132.5, 137.8, 140.9, 151.6, 153.0, 192.0. Anal. Calcd for C22H16N4O3:
C, 68.74; H, 4.20; N, 14.58%. Found: C, 68.68; H, 4.29; N, 14.66%.
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6,7-dihydro-9-(3-nitrophenyl)-2-phenyl-[1,2,4]triazolo[1,2-
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a
]indazole-1,3,8(2H,5H,9H)-trione (4w)
White powder, υmax (KBr) 3050, 2970, 1670, 1610, 1220 cm-1. 1H
NMR (250 MHz, CDCl3): δ (ppm) 1.76 (m, 2H), 1.88 (m, 2H), 2.59 (m,
2H), 6.30 (s, 1H), 7.44-7.58 (m, 5H), 7.63 (t, J= 7.5 Hz, 1H), 7.95 (d,
J= 7.0 Hz, 1H), 8.20 (d, J= 7.0 Hz, 1H), 8.34 (s, 1H). 13C NMR (62.5
MHz, CDCl3): δ (ppm) 21.7, 22.9, 36.7, 67.0, 121.9, 122.6, 125.5,
128.5, 129.1, 129.8, 130.5, 132.7, 134.1, 137.6, 146.5, 152.7, 152.9,
191.7. Anal. Calcd for C21H16N4O5: C, 62.37; H, 3.99; N, 13.86%.
Found: C, 62.44; H, 4.11; N, 13.74%.
3,4-dihydro-3,3-dimethyl-13-phenyl-2H-indazolo[1,2-
b]phthalazine-1,6,11(13H)-trione (6)
White powder, υmax (KBr) 3045, 2985, 1665, 1620, 1210 cm-1. 1H
NMR (500 MHz, CDCl3): δ (ppm) 1.23 (s, 6H), 2.36 (Distorted AB
System, 2H), 3.26 (AB System, J= 19.0 Hz, 1H), 3.44 (AB System, J=
19.0 Hz, 1H), 6.47 (s, 1H), 7.30 (d, J= 6.0 Hz, 1H), 7.36 (t, J= 7.5 Hz,
2H), 7.44 (d, J= 7.0 Hz, 2H), 7.86 (dd, J= 6.0, 3.5 Hz, 2H), 8.29 (t, J=
6 | J. Name., 2012, 00, 1-3
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