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Table 1 Optimization of various reaction conditionsa

From: A green protocol ball milling synthesis of dihydropyrano[2,3-c]pyrazole using nano-silica/aminoethylpiperazine as a metal-free catalyst

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Entry

Conditions

Time (min)

Yield (%)b

Solvent/ Temp. (°C)/ (Catalyst (g))

1

-/ r. t./ (Nano-SiO2/AEP (0.01))

60

49

2

-/ r. t./ (Nano-SiO2/AEP (0.02))

60

53

3

-/ r. t./ (Nano-SiO2/AEP (0.03))

45

68

4

-/ r. t./ (Nano-SiO2/AEP (0.035))

25

87

5

-/ r. t./ (Nano-SiO2/AEP (0.04))

5

95

6

-/ r. t./ (Nano-SiO2/AEP (0.05))

30

90

7c

-/ 80/ (Nano-SiO2/AEP (0.04))

80

68

8c

-/ 70/ (Nano-SiO2/AEP (0.04))

70

73

9c

-/ 50/ (Nano-SiO2/AEP (0.04))

35

89

10c

H2O/ r. t./ (Nano-SiO2/AEP (0.04))

120

50

11c

EtOH/ r. t./ (Nano-SiO2/AEP (0.04))

120

49

12c

H2O/EtOH/r. t./(Nano-SiO2/AEP (0.04))

120

70

13c

MeOH/ r. t./ (Nano-SiO2/AEP (0.04))

120

67

14c

CH3CN/ r. t./ (Nano-SiO2/AEP (0.04))

120

56

15

-/ r. t./ -

120

Trace

16

-/ r.t./ (Nano-SiO2 (0.04))

120

Trace

17

-/ r.t./ (Nano-SC (0.04))

120

Trace

  1. Bold values indicate the modified condition for synthesis of pyranopyrazole
  2. aReaction conditions: ethylacetoacetate (1 mmol), hydrazine hydrate (1.5 mmol), malononitrile (1 mmol), and 4-nitrobenzaldehyde (1 mmol) were milled in a 10 mL stainless steel milling vial with two balls at 20 Hz. bIsolated yield. cNormal stirring condition