The synthesis of substituted imidazole derivatives (Scheme-1), and then recrystallized from ethylacetate to furnish (10a) as intermediate compound in quantitative yield (Table 3, Entry 1). Inspired by this result concentration of catalyst was optimized through the above reaction by using different concentrations 0.12, 0.25, 0.50, 0.75, 1.0, 1.12 and 1.25 g of RHA.SO3H at room temperature (Table 1, Entry 1-7), for 40 min to give the desired products (10a). Reusability was evaluated without loss of activity as shown in Table 2 and the reaction procedure was performed in absence of catalyst at the same conditions, a low yield is obtained which shows the value of the prescribed catalyst. The possible mechanism for synthesis of imidazoles (Scheme 2) depicted below. It involves condensation of dicarbonyl compound such as benzil with an aldehyde in presence of ammonium acetate which is good source of ammonia. Preasumably the aryl aldehyde and benzil are first activated by acid catalyst by nucleophilic attack on carbonyl groups. Other side the catalyst converts ammonium acetate to ammonia, which forms an intermediate with activated aldehyde. This intermediate reacted with activated benzil and then cyclization takes place to form substituted imidazoles. Table 4 indicates the comparison of the activity of different catalysts by considering the yield of the reaction. We observed that Rice Husk Ash. SO3H best give catalytic activity in terms of product yield, solvent and reaction time compared to other catalysts in the literature such as InCl3.3H2O, Clay, FeCl2, ZrCl4, L-proline, [H-Bim]BF4 and NiCl2.6H2O/Al2O3. Rice husk is an easily available and inexpensive catalyst, which makes this method green and mild. In addition, above catalyst is a renewable catalyst which follows one of the green chemistry principles regarding the maximum yield of renewable resources.
Table 1: Screening of Rice Husk Ash: SO3H for synthesis of compound (10a) at room temperature
Entry
|
Amount of Catalyst (g)
|
Time (h)
|
Yield (%)
|
1
|
0.12
|
1.4
|
70
|
2
|
0.25
|
1.2
|
75
|
3
|
0.50
|
0.40
|
87
|
4
|
0.75
|
0.30
|
82
|
5
|
1.00
|
0.30
|
84
|
6
|
1.12
|
0.25
|
84
|
7
|
1.25
|
0.25
|
82
|
Table 2: Reusability of catalyst (Rice Husk Ash: SO3H)
Reuse Cycle
|
Fresh
|
First
|
Second
|
Third
|
Time (h)
|
40
|
40
|
55
|
60
|
Yield (%)
|
87
|
87
|
82
|
81
|
Table 4: Comparison of the results of the present methods used for synthesis of imidazoles with the reported methods
S.No.
|
Catalyst
|
Solvent
|
Temperature (ºC)
|
Time (h)
|
Yield (%)
|
References
|
1
|
InCl3.3H2O
|
Methanol
|
RT
|
8.2
|
76
|
(8)
|
2
|
Clay
|
Solvent free
|
60
|
1.0
|
89
|
(9)
|
3
|
ZrCl4
|
Ethanol
|
RT
|
2.0
|
74
|
(10)
|
4
|
L-proline
|
Methanol
|
60
|
9.0
|
85
|
(11)
|
5
|
[H-Bim]BF4
|
-
|
100
|
1.0
|
82
|
(12)
|
6
|
NiCl2.6H2O/Al2O3
|
Ethanol
|
60
|
1.5
|
90
|
(13)
|
7
|
RiceHusk Ash.SO3H
|
Solvent Free
|
RT
|
0.40
|
87
|
Present work
|
Table 5: Herbicidal activity of substituted imidazoles (10a-10g)
Compounds
|
Growth Inhibition (%)
|
Root
|
Shoot
|
50 (µg/mL)
|
100 (µg/mL)
|
150 (µg/mL)
|
200 (µg/mL)
|
50
(µg/mL)
|
100
(µg/mL)
|
150
(µg/mL)
|
200
(µg/mL)
|
10a
|
41.05
|
58.93
|
68.01
|
81.00
|
47.98
|
51.05
|
67.06
|
89.11
|
10b
|
43.00
|
61.73
|
84.03
|
89.04
|
52.87
|
64.00
|
73.12
|
88.31
|
10c
|
37.91
|
52.74
|
63.91
|
93.00
|
34.16
|
51.04
|
78.00
|
87.00
|
10d
|
31.00
|
47.03
|
61.98
|
84.07
|
26.03
|
53.94
|
73.01
|
89.00
|
10e
|
a
|
a
|
a
|
a
|
a
|
a
|
a
|
a
|
10f
|
a
|
a
|
a
|
a
|
a
|
a
|
a
|
a
|
10g
|
7.65
|
19.87
|
46.02
|
75.79
|
17.48
|
38.01
|
59.00
|
64.62
|
a: no growth inhibition
Table 6: Antifungal activity of substituted imidazoles (10a-10g)
Compounds
|
Growth inhibition (%)
|
Fungi
|
Rhizoctonia solani
|
Aspergillus niger
|
50 µg/mL
|
100 µg/mL
|
150 µg/mL
|
200 µg/mL
|
50 µg/mL
|
100 µg/mL
|
150 µg/mL
|
200 µg/mL
|
10a
|
40.00
|
49.55
|
58.61
|
70.00
|
42.10
|
51.52
|
62.00
|
71.12
|
10b
|
42.01
|
51.10
|
60.01
|
70.08
|
40.21
|
48.64
|
58.72
|
69.61
|
10c
|
a
|
a
|
26.00
|
49.00
|
38.11
|
47.00
|
58.64
|
70.72
|
10d
|
30.05
|
39.78
|
48.56
|
59.61
|
39.88
|
49.55
|
60.02
|
71.75
|
10e
|
35.08
|
46.00
|
55.12
|
65.88
|
a
|
a
|
a
|
a
|
10f
|
39.56
|
48.61
|
57.85
|
68.72
|
41.00
|
52.85
|
61.00
|
71.89
|
10g
|
41.56
|
52.00
|
61.12
|
71.01
|
39.79
|
49.85
|
58.12
|
70.12
|
a: no growth inhibition
Characterization data of some selected compounds
2-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazoles (10a): yellow solid. m.p: 229-230 ºC; 1H NMR (400 Hz, CDCl3): δ 3.88 (s, 3H, OCH3), 7.09-7.37 (m, Ar-H); 7.54-8.87 (m, ArH); 11.76 (s, 1H, NH); IR (νmax cm-1) (neat): 3297 (NH), 3062 (C=CH), 1587 (C=C, aromatic), 1183 (OCH3)
2-(4-chlorophenyl)-4,5-diphenyl-1H-imidazoles (10b): pale yellow solid. m.p: 229-230 ºC; 1H NMR (400 Hz, CDCl3): δ 7.61-7.85 (m, Ar-H); 7.43-8.81 (m, Ar-H); 11.62 (s, 1H, NH) IR (νmax cm-1) (neat): 3320 (NH), 3064 (C=CH), 1590 (C=C, aromatic), 1450 (C=N), 751(C-Cl)
2-(4-methylphenyl)-4,5-diphenyl-1H-imidazoles (10c): pale yellow solid. m.p: 233-235 ºC; 1H NMR (400 Hz, CDCl3): δ 2.52 (s, 3H, CH3); 7.28-7.85(d, 4H); 8.09-8.64(m, Ar-10H); 11.62(s, 1H, NH); IR (νmax cm-1) (neat): 3321 (NH), 3057 (C=CH), 1589 (C=C, aromatic), 1452 (C=N)
2-(2-chlorophenyl)-4,5-diphenyl -1H-imidazoles (10d): pale yellow solid. m.p: 195-197 ºC; 1H NMR (400 Hz, CDCl3): δ 6.83-7.61 (m, 4H, Ar-H); 8.40-8.86 (m, Ar-H); 11.00(s, 1H, NH) IR (νmax cm-1) (neat): 3318 (NH), 3066 (C=CH), 1592 (C=C, aromatic), 1449 (C=N), 753 (C-Cl)
Herbicidal assay
All synthesized compounds (10a-10g) were tested for herbicidal activities against Raphanus sativus L. at various concentrations 200, 150, 100 and 50 µg/mL as shown in Table 5 and Figs 8-9. Results were recorded in the form of primary screening. Synthesized compounds were diluted to 1000 µg/mL concentration as a stock solution. Herbicidal activities of synthesized compounds were evaluated against Raphanus sativus L. by inhibitory effect of the compounds on the growth of weed roots and shoots. The percentage of inhibition of growth was calculated from the mean differences between treated and control. From the herbicidal activity results, we identified that compound 10c was exhibited maximum percentage growth inhibition i.e. 93.00 against Raphanus sativus L. (root) whereas compound 10a was exhibited maximum percentage growth inhibition i.e. 89.11 against Raphanus sativus L. (shoot) respectively at 200 µg/mL concentration. The compound 10e and 10f show no growth inhibition at all the concentration.
Antifungal activity
All synthesized compounds (10a-10g) were tested for their in vitro antifungal activity against Rhizoctonia solani and Aspergillus niger. The percentage growth inhibition of compounds against R. Solani and A.niger was presented in Table 5. From the fungicidal activity results, we concluded that compounds 10g and 10f was found to be most likely against R. solani and A. niger respectively. The growth inhibition may be attributed to substitution of hydroxy group on phenyl ring. The graphical representation of antifungal activity of all synthesized compounds (10a-10g) against Rhizoctonia solani and Aspergillus niger were shown in Figs 10-11.