An Efficient Synthesis of 1-(1-Benzyl-1H-benzo[D]imidazol-2-yl)-3-alkylureas using Nano- γ-Fe₂O₃

E. Janardhan¹, M. Maheshwar Reddy¹, P. Venkat Reddy¹, M. Ranadheer Kumar², S. Ramu³

¹Sreenidhi Institute of Science and Technology, Yamnampet, Ghatkesar, Hyderabad-501301 Telangana, India

²Kakatiya Institute of Technology and Science, Yerragattu, Hanamkonda, Warangal-506015 Telangana, India

³Rishitha Biosciences, North Hastinapuram, LB Nagar, Hyderabad, 500 074, Telangana, India

*Corresponding Author E-mail: janardhanphy@yahoo.com

ABSTRACT:

Nano- γ-Fe₂O₃ particles are considered to be attractive as catalysts for their greater reactivity, due to high surface area, recovered easily from the reaction mixture and reusable for further reaction, therefore the method being more efficient.

Compounds 1-5 are reacted with amines to give 1-(1-benzyl-1H-benzo[d]imidazol-2-yl)-3-alkylureas. The structures of the compounds were confirmed by IR, ¹HNMR Spectra and elemental analysis.

Scheme

Ar= Phenyl, 2-ChloroPhenyl, 3-ChloroPhenyl, 4-ChloroPhenyl, 4-MethylPhenyl; R=Phenyl

Nano- γ-Fe₂O₃was applied as an efficient, green, heterogeneous and reusable catalyst at ambient temperature; some advantages of the catalyst are clean reaction, simple purification, and high yield. The antibacterial activity of all the substituted derivatives were determined against four bacteria strains such as Staphylococcus aureus, E.coli, Salmonella typhi, Bacillus subtilis. The newly prepared compounds for antibacterial activity were screened through agar-cup method. Their antibacterial activities are investigated and reported in this paper. The prepared derivatives were growth inhibitory towards all the bacteria. In the synthesized compounds some compounds showed moderate to good activity while some were found to be inactive.

KEYWORDS:Nano- γ-Fe₂O₃; Amine, Heterogeneous catalyst; alkylurea

INTRODUCTION:

Heterocyclic compounds containing nitrogen occurred widely in roast food and drugs and posses different pharmacological properties due to oxidation of nitrogen in molecule¹.The studies recently carried out in many laboratories dealt mainly with the synthesis of 2-Aminobezimidazole derivatives exhibiting antilipidemic or platelet antiaggregatory activity²,antimicrobial³, antiinflammatory and analgesic properties⁴, anti-HIV and antitumer activity⁵, antiallergic⁶, immunosupperssive and antiviral activity⁷. The functional group plays an important role in organic and medicinal chemistry; many biologically active compounds either contain the urea functionality⁸ or are synthesized from urea containing starting materials⁹. In view of the biological activity of imidazole systems we undertook the synthesis of 1-(1-Benzyl-1h-benzo[d]imidazol-2-yl)-3-alkylureas.

Hence, herein we report an easy and efficient method for the alkylureas of various amines using Fe₂O₃ nanoparticle. To the best of our knowledge, the use of Nano- γ-Fe₂O₃for the alkylureas of amine in water has not been reported.

EXPERIMENTAL:

The IR spectra were recorded on Brucher-IFS-66 FTIR instrument. NMR spectra were recorded on Varian Gemini 200 M Hz instrument using tetramethylsilane as an internal standard in DMSO-d₆. Chemical shifts are expressed in ppm. The purity of the compounds was checked by TLC and spots were visualized in iodine vapour.

1-(1-Benzyl-1H-benzo[d]imidazol-2-yl)-3-phenylurea(6):

A mixture of compound 3a (0.01 mole) and amine (0.01 mole) were dissolved in DCM (30 ml) and Et₃N was added at 0-5⁰C. the mixture was stirred at RT. Reaction was monitored by TLC. After the completion of reaction solvent is evaporated to get crude product, which was purified by column chromatography, eluted with 50 % Ethylacetate.

IR: 3337.48 cm^-1 (NH), 2934.83 cm^-1 (CH), 1626.40 cm^-1 (C=O); ¹HNMR (DMSO-d₆): 5.28 (s, 2H), 6.80 (d, 1H), 6.86 (d, 1H), 7.02-7.18 (m, 4H), 7.20-7.38( m, 9H), 7.88 (brs, 1H); Mass: 358 (M+1) );Yield 66%.

1-(1-(2-Chlorobenzyl)-1H-benzo[d]imidazol-2-yl)-3-phenylurea (7):

¹HNMR (DMSO-d₆): 5.28 (s, 2H), 6.80 (d, 1H), 6.86 (d, 1H), 7.02-7.20 (m, 4H), 7.22-7.40 (m, 8H), 7.89 (brs, 1H); Mass: 392 (M+1) );Yield 71%.

1-(1-(3-Chlorobenzyl)-1H-benzo[d]imidazol-2-yl)-3-phenylurea (8):

¹HNMR (DMSO-d₆): 5.29 (s, 2H), 6.82 (d, 1H), 6.88 (d, 1H), 7.02-7.20 (m, 4H), 7.22-7.39 (m, 8H), 7.90 (brs, 1H); Mass: 392 (M+1) );Yield 68%.

1-(1-(4-Chlorobenzyl)-1H-benzo[d]imidazol-2-yl)-3-phenylurea (9):

¹HNMR (DMSO-d₆): 5.28 (s, 2H), 6.82 (d, 1H), 6.88 (d, 1H), 7.04-7.22 (m, 4H), 7.24-7.40 (m, 8H), 7.88 (brs, 1H); Mass: 392 (M+1) );Yield 65%.

1-(1-(4-Methylbenzyl)-1H-benzo[d]imidazol-2-yl)-3-phenylurea (10):

¹HNMR (DMSO-d₆): 2.32 (s, 3H), 5.22 (s, 2H), 6.80 (d, 1H), 6.86 (d, 1H), 7.04-7.38 (m, 4H), 7.20-7.38 (m, 8H), 7.88 (brs, 1H); Mass: 372 (M+1) );Yield 70%.

Table -1 Antibacterial screening data of the compounds 6-10

Compound	*S.aureus*	E. *coli*	*Salmonella typhi*	*Bacillus subtilis*
6	4	3	1	2
7	19	15	9	8
8	10	11	5	4
9	18	15	7	9
10	10	17	8	9
Control (Chloramphenicol)	19	23	24	18

RESULTS AND DISCUSSION:

The antibacterial activity of all the substituted urea derivatives were determined against four bacteria strains. The newly prepared compounds for antibacterial activity were screened through agar-cup method. Their antibacterial activities are reported in Table-1. Perusal of the above Table-1 reveals that the derivatives were growth inhibitory towards all the bacteria. In the synthesized compounds some compounds showed moderate to good activity while some were found to be inactive. 7 and 9 were as good as the standard drug chloramphenicol towards S.aureus.

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