One-pot, four-component synthesis of 2H-indazolo[2,1-b
reaction mass was cooled to 25 °C, then the solid residue was dissolved in hot EtOH
and the catalyst was filtered off. The filtrate solution was concentrated and the solid
crude product was purified by recrystallization in aqueous EtOH (25 %).
The desired pure products were characterized by comparison of their physical data
(melting points, IR, 1H and 13C NMR) with those of known compounds [9–11, 18].
Results and discussion
To choose optimum conditions, first we tried to prepare 2H-indazolo[2,1-b]phthal-
azine-trione from the reaction of benzaldehyde (1 mmol), dimedone (1 mmol)
phthalic anhydride (1 mmol) and hydrazinium hydroxide (1.2 mmol) as a model
under solvent-free conditions at different temperatures (60, 70, 75, 80, 90 °C) in the
presence of cellulose-SO3H (0.05 g, 2.5 mol%). The best result was obtained at 80 °C.
Next, the model was examined with different amounts of cellulose-SO3H (0.05, 0.06,
0.07, 0.08, 0.09 g) at 80 °C. The highest yield and short reaction time was obtained at
80 °C and 0.08 g (4 mol%) of the catalyst.
Using these optimized reaction conditions, the scope and efficiency of these
procedures were explored for the synthesis of a wide variety of substituted
2H-indazolo[2,1-b]phthalazine-triones. Interestingly, a variety of aldehydes includ-
ing ortho-, meta-, and para- substituted aryl aldehydes participated well in this
reaction and gave the 2H-indazolo[2,1-b]phthalazine-trione derivatives in good to
excellent yield (Table 1). As can be seen from Table 1, both aromatic aldehydes
carrying electron-donating or electron-withdrawing substituents act well in these
reaction conditions. Aliphatic aldehydes such as n-heptanal and n-octanal were
intact in the mentioned reaction (Table 1, Entries 13, 14).
According to a literature survey [11], the suggested mechanism for the formation
of the products is shown in Scheme 2. First, the reaction occurs via initial
nucleophilic addition of phthalic anhydride (1) to hydrazinium hydroxide (2) and
followed by dehydration to form phthalhydrazide in the absence of the catalyst
under thermal solvent-free conditions. Next, intermediate (6) was formed by
standard Knoevenagel condensation of aldehyde (4) and dimedone (5) in the
presence of cellulose-SO3H. Subsequent Michael addition of the phthalhydrazide
(3) to (6) in the presence of the catalyst followed by cyclization affords the
corresponding product (7) (Scheme 2).
In order to show the accessibility of the present work (4-CRs) in comparison
with the three-component reported results in the literature such as H2SO4 [18],
PMA-SiO2 [11], Mg(HSO4)2 [9] and TMSCl [19], we summarize some of the
results for the preparation of 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione in
Table 2, which shows that cellulose-SO3H is the most efficient catalyst reaction
time and temperature, and exhibits broad applicability in terms of the obtained
yield.
We also studied the reusability of the catalysts in the reaction of benzaldehyde,
dimedone, phthalic anhydride, and hydrazinium hydroxide under solvent-free
conditions at 80 °C. In this procedure, after completion of the reaction, the reaction
mixture was cooled to room temperature, and the crude solid was dissolved in hot
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