Microwave assisted, one-pot synthesis of 5-nitro- 2-aryl substituted-1H-benzimidazole libraries: Screening in vitro for antimicrobial activity

Figures & data

Scheme 1.  Synthesis of 5-nitro-2-aryl substituted phenoxymethyl-1H-benzimidazoles.

Table 1.  Comparison between microwave-assisted and thermal method synthesis of 5-nitro-2-aryl substituted phenoxymethyl-1H-benzimidazole libraries.

Compound	Phenoxy acetic Acid used	Mol. Formula	Conventional method			Microwave method
			Time (h)^a	Yield	M.P.	Time W/(min)^a	Yield	M. P.
1a	Unsubstituted	C14H11N3O3	3.35	58.40	219–221	400/2.5	87.86	218–220
1b	2-Methyl-	C15H13N3O3	3.20	67.59	89–91	400/3.0	88.55	88– 90
1c	3-Methyl-	C15H13N3O3	3.25	70.57	215–217	400/3.0	85.61	213–215
1d	4-Methyl-	C15H13N3O3	3.20	65.01	77–79	400/3.0	91.32	79–81
1e	2-Chloro-	C14H10N3O3Cl	3.50	74.70	187–189	400/3.5	85.24	185–187
1f	4-Chloro-	C14H10N3O3Cl	3.40	58.21	265–267	400/3.5	87.81	266–268
1g	2-Nitro-	C14H10N4O5	3.50	64.14	230–232	400/2.5	82.03	227–229
1h	4-Nitro-	C14H10N4O5	3.45	60.95	98–100	400/3.5	90.15	98–100
1i	2-Amino-	C14H12N4O3	3.15	63.97	215–217	400/3.0	83.08	216–218
1j	2,4-Dichloro-	C14H9N3O3Cl2	3.40	61.86	86–88	400/2.5	86.46	85–68

^aTime to finish the reaction monitored by TLC.

Figure 1.  Photographic comparison of compound 1h with standard for antibacterial activity in Staphylococcus aureus and antifungal activity in Penicillium.

A & B - Streptomycin (Standard) and Compound 1h for Staphylococcus aureus

C & D - Nystatin (Standard) and Compound 1h for Penicillium

A & C - c- control disc with DMSO, std- standard (Streptomycin-10mcg & Nystatin-100units)

B & D - a-1mcg, b-0.5mcg and c-0.25mcg

Figure 2.  Bar curves for comparison of antibacterial activity of compound 1h with Streptomycin standard.

Table 2.  The MIC values (μmoles/mL) of compounds 1a-1j for Antibacterial activity.

Compound	^cV. r. e.	^cS. a.	^cM.	^cB. s.	^cS. d.	^cE. c.
1a	≥3.71	0.445–0.929	1.858–3.71	≥3.71	1.858–3.71	1.858–3.71
1b	≥3.533	0.882–1.765	≥3.533	≥3.533	1.765–3.533	≥3.533
1c	≥3.533	0.423–0.882	1.765–3.533	≥3.533	1.765–3.533	≥3.533
1d	≥3.533	1.765–3.533	0.423–0.882	1.765–3.533	0.423–0.882	1.765–3.533
1e	1.64-3.29	0.823–1.64	1.64–3.29	≥3.29	1.64–3.29	≥3.29
1f	≥3.29	0.823–1.64	0.823–1.64	≥3.29	1.64–3.29	1.64–3.29
1g	≥3.182	0.381–0.795	≥3.182	≥3.182	1.59–3.182	≥3.182
1h	≥3.182	≤0.381	0.795–1.59	≥3.182	0.795–1.59	1.59–3.182
1i	≥3.521	0.88–1.76	≥3.521	≥3.521	1.76–3.521	≥3.521
1j	1.47-2.957	0.739–1.47	0.739–1.47	1.47–2.957	1.47–2.957	≥2.957
^bSD	0.85-1.71	≤0.85	≤0.85	0.85–1.71	1.71–3.43	≤0.85

^cV. r. e.- Vancomycin resistant enteroccoccus; ^cS. a.- Staphylococcus aureus; ^cM.- Micrococcus; ^cB. s.- Bacillus subtilis; ^cS. d.- Shigella dysentery; ^cE. c.- Escheria coli

^bSD–Streptomycin (Standard)

Figure 3.  Bar curves for comparison of antifungal activity of compound 1h with Nystatin standard.

Table 3.  The MIC values (μmoles/mL) of compounds 1a-1j Antifungal activity.

Compound	cC. a.	cA. n.	cP.
1a	≤0.4457	0.929–1.858	1.858–3.71
1b	0.8827–1.7655	1.858–3.71	>3.533
1c	≤0.4237	0.882–1.765	1.765–3.533
1d	0.423–0.882	0.423–0.882	0.882–1.765
1e	0.411–0.823	>3.29	1.64–3.29
1f	0.823–1.64	1.64–3.29	>3.29
1g	1.59–3.182	>3.182	>3.182
1h	0.381–0.795	≤0.381	1.59–3.182
1i	1.76–3.521	1.76–3.521	1.76–3.521
1j	0.739–1.47	1.47–2.957	0.739–1.47
^bSD	≤ 1.71	≤3.43	≤3.43

^cC. a.- Candida albicans; ^cA. n.- Aspergillus niger; ^cP.- Penicillium

^bSD–Nystatin (Standard)