Synthesis and antimicrobial activity of some imidazothiazole derivatives of benzofuran

Sheelavanth Shankerrao; Yadav D. Bodke; S. Santoshkumar

doi:10.1016/j.arabjc.2012.10.018

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Original article

10 (

1_suppl

); S554-S558

doi:

10.1016/j.arabjc.2012.10.018

Synthesis and antimicrobial activity of some imidazothiazole derivatives of benzofuran

Sheelavanth Shankerrao^{^a}, Yadav D. Bodke^{^a,⁎}, S. Santoshkumar^{^b}

a Department of P.G. Studies and Research in Industrial Chemistry, School of Chemical Science, Jnana Sahyadri, Kuvempu University, Shankaraghatta 577 451, Shivamogga, Karnataka, India

b Department of P.G. Studies and Research in Pharmaceutical Chemistry, Kuvempu University, P.G. Centre, Kadur 577 548, Chikkamagaluru Dt., Karnataka, India

⁎Corresponding author. Tel.: +91 9449140275. ydbodke@gmail.com (Yadav D. Bodke)

Received: 2012-3-26, Accepted: 2012-10-31, Published: 2012-02-01

Disclaimer:
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.

Peer review under responsibility of King Saud University.

Abstract

A series of 6-(1-benzofuran-2-yl)-3-phenyl imidazo[2,1-b][1,3]thiazole (5a–f) and 3,6-bis (1-benzofuran-2-yl)imidazo[2,1-b][1,3]thiazole (6a–d) derivatives are synthesized by the reaction of 1-(1-benzofuran-2-yl)-2-bromoethanones (2a–b) with 4-phenyl-1,3-thiazol-2-amines (4a–c) and 4-benzofurano-1,3-thiazol-2-amines (3a–b) respectively. The structures of newly synthesized compounds are characterized by IR, ¹H NMR and mass spectroscopic studies and were screened for their antimicrobial activities. The preliminary results revealed that some of the compounds exhibited promising antimicrobial activities.

Keywords

Anhydrous aluminum chloride

1-(1-Benzofuran-2-yl)-2-bromoethanone

Imidazothiazoles

Antibacterial

Antifungal

Show Related Articles from PubMed

1 Introduction

Oxygen containing heterocycles are essential structural units for medicinal chemists. Among the various heterocyclic compounds, benzofuran derivatives occur predominately in nature appreciable to their stability and ease of generation. Especially benzofuran with its substituent(s) at C-2 and/or C-3 have attracted a strong interest due to their widespread in a large number of natural products and for their pronounced biological activities such as antimicrobial (Abdel-Aziz and Mekawey, 2009; Koca et al., 2005; Manna and Agrawal, 2009; Abdel-Wahab et al., 2009 ), anti-inflammatory (Jadhav et al., 2008) antioxidant (Chandrashekar et al., 2012; Gilbert et al., 2009), anticancer (Galal et al., 2009; Chen et al., 2009), etc. On the other hand, imidazothiazoles, a bicyclic (5,5)-fused system with one bridgehead nitrogen atom possesses different biological activities such as antipsychotic (Cole et al., 2007), anthelmintic, anti-inflammatory (Powers et al., 1981), anticoccidial (Scribner et al., 2008), antitumor (Andreani et al., 2006; Andreani et al., 2008; Andreani et al., 2005 ), etc. An imidazothiazole derivative, Levamisole (the levo isomer of tetramisole) is a broad spectrum anthelmintic, belonging to a general class of agents called biologic response modifiers and has been originally designed for anthelmintic properties and also possesses immuno-modulating and immuno-stimulating properties (Kamal et al., 2005). Our research group reported the synthesis of a series of novel bicyclic benzofuran heterocycles containing bridgehead nitrogen atom, imidazo[2,1-b][1,3,4]thiadiazoles and screened for antimicrobial activities (Venkatesh and Bodke, 2010). The scattered reports on biological importance of both benzofuran and imidazothiazole derivatives have speculated us to design the molecules which encompass both benzofurans and imidazothiazole together in one molecule (see Scheme 1).

In the present work, we have synthesized a series of 6-(1-benzofuran-2-yl)-3-phenylimidazo[2,1-b][1,3]thiazole (5a–f) and 3,6-bis(1-benzofuran-2-yl)imidazo[2,1-b][1,3]thiazole (6a–d) derivatives and structures of these new compounds were supported by the spectral data. All the synthesized compounds were evaluated for antimicrobial activity by the agar well diffusion method against one Gram-positive bacterial strain (Staphylococcus aureus), three Gram-negative bacterial strains (Pseudomonas Aeruginosa, Kleibsella Pneumonia, Escherichia Coli) and two fungal strains (Aspergillus Niger, Candida albicans). Ampicillin and Flucanozole were used as standard drugs for antibacterial and antifungal activity respectively and dimethyl formamide is used as solvent control.

2 Experimental

All the chemicals used were of analytical grade. Melting points were determined in open capillary and are uncorrected. Purity of the compounds was checked by TLC on silica gel. The IR spectra were recorded on a Nicolet-Impact-410 FT-IR spectrometer, using KBR pellets. ¹H NMR spectra were recorded on a Bruker supercon FT NMR (400 MHz) spectrometer in CDCl₃ or DMSO-d₆ using TMS as an internal standard. The chemical shifts were expressed in δ units. Mass spectra were recorded on a JEOL SX 102/DA-6000 (10 kV) FAB mass spectrometer.

2.1

2.1 General procedure for the synthesis of compounds 2(a–b)

Substituted 2-acetyl benzofuran (0.01 mol) 1(a–b) was dissolved in diethyl ether and catalytic amount of anhydrous AlCl₃ was added. The reaction flask was kept in ice bath with stirring and bromine (0.01 mol) was added to this solution drop by drop for about 15–20 min. After complete addition, stirring was continued for another 10 min. The solid mass separated was filtered and washed with water and followed by pet ether to get compounds 2(a–b).

2.1.1

2.1.1 1-(1-Benzofuran-2-yl)-2-bromoethanone 2(a)

White crystalline solid (ethanol), yield 80%, mp 90–92 °C, (lit. mp 89 °C). ¹H NMR (DMSO-d₆, 400 MHz): 8.098 (s, 1H), 8.074 (s, 1H), 7.883–7.911 (t, J = 11.2, 1H), 7.575–7.617 (m, 1H), 7.394–7.431 (t, 1H), 4.836 (s, 2H) MS: m/z = 238.1 (M+), 240.1 (M + 2).

2.1.2

2.1.2 2-Bromo-1-(5-bromo-1-benzofuran-2-yl) ethanone 2(b)

White solid (ethanol), yield 76%, mp 140–143 °C, (lit. mp 140 °C). ¹H NMR (DMSO-d₆, 400 MHz): 8.098 (s, 1H), 8.074 (s, 1H), 7.88–7.91 (t, 1H), 7.575–7.617 (m, 1H), 4.836 (s, 2H). MS: m/z = 316.2 (M + 1), 318.2 (M + 2), 320.2 (M + 4).

2.2

2.2 General procedure for the synthesis of compounds 5(a–f) & 6(a–d)

A mixture of 1-(1-benzofuran-2-yl)-2-bromoethanone (0.01 mol) 2a and 4-phenyl-1,3-thiazol-2-amines 4a, (0.01 mol) was refluxed in ethanol (25 ml) for 10 h. The progress of reaction was monitored by TLC (mobile phase: ethyl acetate−hexane, 2:8). After completion of the reaction, the reaction mixture was cooled to room temperature and poured to cold water with stirring. The resulting clear solution was neutralized with 5% aqueous sodium bicarbonate solution; the separated solid mass was filtered and washed with water. The resulting compound was recrystallized from ethanol to get pure compound 5a.

Compounds 5(b–f) were prepared by a similar method. Compounds 6(a–d) were prepared by the reaction of 1-(1-benzofuran-2-yl)-2-bromoethanones 2(a–b) and 4-(1-benzofuran-2-yl)-1,3-thiazol-2-amines 3(a–b) using the above method.

2.2.1

2.2.1 6-(1-Benzofuran-2-yl)-3-phenyl imidazo [2,1-b][1,3]thiazole (5a)

Yellow solid (ethanol), yield 55%, mp 102–105 °C, ¹H NMR (DMSO-d₆, 400 MHz): 8.36 (s, 1H), 8.18 (s, 1H), 8.16 (s, 1H), 7.941 (d, J = 1.6 Hz, 1H), 7.89 (s, 1H), 7.85–7.87 (m, 2H), 7.58–7.62 (t, 1H), 7.49–7.52 (t, 1H), 7.45–7.48 (t, 2H), 7.32 (s, 1H). ¹³C NMR (CDCl₃, 100.5 MHz): 102.6(1C), 107.6(1C), 111.5(1C), 115.9(1C), 120.9(1C), 122.1(1C), 123.3(1C), 123.8(1C), 124.6(1C), 127.8(2C), 128.4(1C), 129.3(2C), 133.2(1C), 136.0(1C), 150.1(1C), 155.3(2C). MS: m/z = 317.3 (M + 1).

2.2.2

2.2.2 6-(5-Bromo-1-benzofuran-2-yl)-3-phenylimidazo [2,1-b][1,3]thiazole (5b)

Yellow solid (ethanol), yield 62%, mp 120–124 °C, ¹H NMR (DMSO-d₆, 400 MHz): 8.36 (s, 1H), 8.18 (s, 1H), 7.94–7.95 (d, J = 3.6 Hz, 1H), 7.86 (s, 1H), 7.86–7.88 (m, 2H), 7.60–7.63 (t, 1H). 7.48–7.49 (t, 1H), 7.47–7.51 (t, 2H), 7.29 (s, 1H). ¹³C NMR (CDCl₃, 100.5 MHz): 102.6(1C), 107.6(1C), 111.5(1C), 114.0(1C), 116.8(1C), 121.0(1C), 122.5(1C), 123.7(1C), 124.6(1C), 127.8(2C), 128.4(1C), 129.3(2C), 133.2(1C), 136.0(1C), 150.1(1C), 154.3(1C) 155.6(1C). MS: m/z = 394.3 (M+), 396.3 (M + 2).

2.2.3

2.2.3 6-(1-Benzofuran-2-yl)-3-(4-methylphenyl) imidazo[2,1-b][1,3]thiazole (5c)

Brown solid (ethanol), yield 65%, mp 95–98 °C, ¹H NMR (DMSO-d₆, 400 MHz): 8.34 (s, 1H), 8.19 (s, 1H), 8.12 (s, 1H), 7.94 (d, J = 1.6 Hz, 1H), 7.89 (s, 1H), 7.85–7.87 (m, 2H), 7.48–7.49 (t, 1H), 7.43–7.46 (t, 2H), 7.30 (s, 1H). 2.59 (s, 3H, CH₃). ¹³C NMR (CDCl₃, 100.5 MHz): 102.6(1C), 107.6(1C), 111.5(1C), 115.9(1C), 120.9(1C), 122.1(1C), 123.3(1C), 123.8(1C), 124.6(1C), 127.4(2C), 129.5(2C), 133.2(1C), 136.1(1C), 138.4(1C), 150.1(1C), 155.3(2C). 24.2(1C, CH₃) MS: m/z = 331.0 (M + 1).

2.2.4

2.2.4 6-(5-Bromo-1-benzofuran-2-yl)-3-(4-methylphenyl) imidazo [2,1-b][1,3]thiazole(5d)

Brown solid (ethanol), yield 59%, mp 110–113 °C, ¹H NMR (DMSO-d₆, 400 MHz): 8.36 (s, 1H), 8.18 (s, 1H), 7.94 (d, J = 3.6 Hz, 1H), 7.86 (s, 1H), 7.86–7.88 (m, 2H), 7.48–7.497 (t, 1H), 7.47–7.51 (t, 2H), 7.34 (s, 1H), 2.6 (s, 3H, CH₃). ¹³C NMR (CDCl₃, 100.5 MHz): 102.6(1C), 107.6(1C), 111.5(1C), 115.9(1C), 116.4(1C), 120.9(1C), 122.1(1C), 123.3(1C), 123.8(1C), 127.4(2C), 129.5(2C), 133.2(1C), 136.1(1C), 138.4(1C), 150.1(1C), 154.3(1C), 155.3(1C), 24.2(1C, CH₃) MS: m/z = 331.0 (M + 1), 332.0 (M + 2). MS: m/z = 409.3 (M+), 411.1 (M + 2).

2.2.5

2.2.5 6-(1-Benzofuran-2-yl)-3-(4-fluorophenyl)imidazo[2,1-b][1,3]thiazole (5e)

Yellow solid (ethanol), yield 56%, mp 97–100 °C, ¹H NMR (DMSO-d₆, 400 MHz): 8.34 (s, 1H), 8.19 (s, 1H), 8.12 (s, 1H), 7.94–7.94 (d, J = 1.6 Hz, 1H), 7.89 (s, 1H), 7.85–7.87 (m, 2H), 7.48–7.49 (t, 1H), 7.43–7.46 (t, 2H), 7.30 (s, 1H). ¹³C NMR (CDCl₃, 100.5 MHz): 102.6(1C), 107.6(1C), 111.5(1C), 115.9(1C), 116.4(2C), 120.9(1C), 122.1(1C), 123.3(1C), 123.8(1C), 124.6(1C), 129.5(2C), 133.2(1C), 136.1(1C), 138.4(1C), 155.3(2C), 162.0 (1C). MS: m/z = 335.3 (M + 1), 336.3 (M + 1).

2.2.6

2.2.6 6-(5-Bromo-1-benzofuran-2-yl)-3-(4-fluorophenyl)imidazo[2,1-b][1,3]thiazole (5f)

Yellow solid (ethanol), yield 60%, mp 123–127 °C, ¹H NMR (DMSO-d₆, 400 MHz): 8.36 (s, 1H), 8.18 (s, 1H), 7.94 (d, J = 3.6 Hz, 1H), 7.86 (s, 1H), 7.86–7.88 (m, 2H), 7.48–7.49 (t, 1H), 7.47–7.51 (t, J = 16, 2H), 7.34 (s, 1H). ¹³C NMR (CDCl₃, 100.5 MHz): 102.6(1C), 107.6(1C), 111.5(1C), 115.9(1C), 116.0(2C), 116.6(1C), 122.1(1C), 123.3(1C), 123.8(1C), 124.6(1C), 129.1(2C), 133.2(1C), 136.1(1C), 138.4(1C), 154.2(1C), 155.3(1C), 162.0(1C). MS: m/z = 412.2 (M+), 414.2 (M + 2).

2.2.7

2.2.7 3,6-Bis (1-benzofuran-2-yl)imidazo[2,1-b][1,3]thiazole (6a)

Yellow solid (ethanol), yield 64%, mp 104–107 °C, ¹H NMR (DMSO-d₆, 400 MHz): 7.91 (s, 1H), 7.80–7.85 (m, 3H), 7.71–7.73 (d, J = 8.4 Hz, 1H), 7.530–7.569 (t, 1H), 7.360–7.398 (t, 2H), 7.165–7.210 (t, 2H), 7.053 (s, 2H), 6.98 (s, 1H). ¹³C NMR (CDCl₃, 100.5 MHz): 102.7(2C), 107.6(1C), 111.3(2C), 119.2(1C), 119.9(2C), 123.3(1C), 123.8(2C), 124.2(2C), 125.4(2C), 133.0(1C), 147.8(1C), 151.4(2C), 155.6(2C). MS: m/z = 357.0 (M + 1).

2.2.8

2.2.8 6-(1-Benzofuran-2-yl)-3-(5-bromo-1-benzofuran-2-yl) imidazo[2,1-b][1,3]thiazole (6b)

Yellow solid (ethanol), yield 56%, mp 114–116 °C, ¹H NMR (DMSO-d₆, 400 MHz): 7.91 (s, 1H), 7.80–7.85 (m, 3H), 7.71–7.73 (d, J = 8.4 Hz, 1H), 7.36–7.39 (t, 2H), 7.16–7.21 (t, 2H), 7.053 (s, 2H), 6.98 (s, 1H). ¹³C NMR (CDCl₃, 100.5 MHz): 102.7(2C), 107.6(1C), 111.5(1C), 113.7(1C), 116.5(1C), 119.9(1C), 120.4(1C), 122.3(1C), 123.1(1C), 123.8(1C), 124.2(1C), 124.7(1C), 126.2(1C), 129.1(1C), 136.0(1C), 147.8(1C), 149.4(2C), 154.1(1C), 155.6(1C). MS: m/z = 434.2 (M+), 436.2 (M + 2).

2.2.9

2.2.9 3-(1-Benzofuran-2-yl)-6-(5-bromo-1-benzofuran-2-yl)imidazo[2,1-b][1,3]thiazole (6c)

Yellow solid (ethanol), yield 67%, mp 94–97 °C, ¹H NMR (DMSO-d₆, 400 MHz): 7.88 (s, 1H), 7.81–7.85 (m, 3H), 7.73 (d, J = 10 Hz, 1H), 7.36–7.39 (t, 2H), 7.16–7.21 (t, 2H), 7.053 (s, 2H), 6.98 (s, 1H). ¹³C NMR (CDCl₃, 100.5 MHz): 102.7(2C), 107.6(1C), 111.5(1C), 113.7(1C), 116.5(1C), 119.9(1C), 120.4(1C), 122.3(1C), 123.1(1C), 123.8(1C), 124.2(1C), 124.7(1C), 126.2(1C), 129.1(1C), 136.0(1C), 147.8(1C), 149.4(2C), 154.1(1C), 155.6(1C). MS: m/z = 434.2 (M+), 436.2 (M + 2).

2.2.10

2.2.10 3,6-Bis (5-bromo-1-benzofuran-2-yl)imidazo[2,1-b][1,3]thiazole (6d)

Yellow solid (ethanol), yield 61%, mp 103–106 °C, ¹H NMR (DMSO-d₆, 400 MHz): 7.98 (s, 1H), 7.81–7.85 (m, 2H), 7.75 (d, J = 10.8 Hz, 1H), 7.36–7.39 (t, 2H), 7.16–7.21 (t, 2H), 7.053 (s, 2H), 6.98 (s, 1H). ¹³C NMR (CDCl₃, 100.5 MHz): 102.7(2C), 107.5(1C), 113.3(2C), 116.4(2C), 120.1(1C), 122.8(1C), 124.1(2C), 126.2(2C), 129.4(2C), 136.3(1C), 146.0(1C), 147.8(2C), 155.6(2C). MS: m/z = 514.1 (M+), 516.1 (M + 2). 518.1 (M + 4).

2.3

2.3 Antimicrobial activity

All the newly synthesized compounds were dissolved in dimethyl formamide (DMF) to prepare stock solution at the concentration of 1 mg/mL. The antimicrobial activity was carried out by the agar-well diffusion method which is a simple susceptibility screening method (Bayrak et al., 2009). Each microorganism was suspended in nutrient broth and diluted approximately colony forming unit (cfu) per mL. They were ‘flood-inoculated' onto the surface of nutrient agar and then dried. Five-millimeter diameter wells were cut from the agar using a sterile cork-borer; 50 μL and 100 μL of the test compound solution were delivered into the wells. The plates were incubated for 32 h at 35 °C. Antimicrobial activity was evaluated by measuring the zone of inhibition against the test organisms.

3 Result and discussion

3.1

3.1 Chemistry

Earlier the key intermediates 1-(1-benzofuran-2-yl)-2-bromoethanone 2(a–b) were synthesized in our laboratory by the bromination of 2-acetyl benzofuran using bromine in acetic acid which was a more tedious method (Venkatesh and Bodke, 2010). In the present work we have synthesized the key intermediate more efficiently using catalytic amount of AlCl₃ in non aqueous solvent diethyl ether by direct addition of bromine to accomplish product within 30 min with about 96% of purity. The structure was confirmed by spectral analysis and by comparing the melting points with the literature value. The reaction of 1-(1-benzofuran-2-yl)-2-bromoethanones 2(a–b) with thiourea in ethanol furnished 4-(1-benzofuran-2-yl)-1,3-thiazol-2-amines 3(a–b). Substituted 4-phenyl-1,3-thiazol-2-amines 4(a–c) were prepared by the literature method (Siddiqui et al., 2006).

2-Aminothiazoles are known to react with 2-halo ketones to form imidazo[2,1-b]thiazoles through cyclization involving the 2-imino, carbonyl functions (El-Taweel and Elnagdi, 2000; Burger and Ullyot, 1947; Toan and Tefas, 1962 ). The title compounds 5(a–f) and 6(a–d) were synthesized by reacting 1-(1-benzofuran-2-yl)-2-bromoethanones 2(a–b) as a haloketone with 4-phenyl-1,3-thiazol-2-amines 4(a–c) and 4-(1-benzofuran-2-yl)-1,3-thiazol-2-amines 3(a–b) derivatives respectively. The structures of these compounds were confirmed by spectral data. The chemical structures of all synthesized compounds were further confirmed by ¹H and ¹³C NMR spectral data. In the 1H NMR spectra of compounds 5c and 5d, we found a singlet at ∂2.6 ppm corresponding to three methyl protons and the multiplet in the range of ∂6.70–8.37 ppm due to aromatic protons. The resonance of different carbons at ∂115.79–157.48 ppm was attributed to aromatic carbons. On varying the substitution on the same carbon the shift in the resonance frequency was observed. For example when C–H in compound 6a (∂123.3 ppm) was replaced with C–Br, 6b (∂116.5 ppm), upfield shift of ∂6.8 ppm was observed. Further the structures of the new compounds were supported by mass spectral analysis.

3.2

3.2 Anti microbial activity

All the synthesized compounds were screened for their antibacterial and antifungal activities at two different concentrations and the results are shown in Table 1. The results revealed that most of the synthesized compounds showed variable degrees of inhibition against the tested microorganisms.

Table 1 Antimicrobial activity data (Zone of inhibition in mm).

Comp. no.	S. aureus		K. pneumona		P. aeruginosa		E. Coli		A. Niger		T. viradae
	50 μL	100 μL	50 μL	100 μL	50 μL	100 μL	50 μL	100 μL	50 μL	100 μL	50 μL	100 μL
5a	12	16	09	16	08	12	12	16	10	12	07	09
5b	20	27	16	22	18	25	15	18	19	22	15	19
5c	20	24	06	09	12	19	10	12	22	26	24	26
5d	18	22	12	18	–	08	15	22	14	20	23	25
5e	14	17	06	16	12	14	18	20	06	12	14	20
5f	18	22	–	10	14	18	16	20	08	12	14	20
6a	08	10	13	18	–	–	–	–	14	16	13	18
6b	23	28	13	18	18	24	12	16	08	10	08	12
6c	15	23	06	14	12	18	16	20	06	08	12	16
6d	18	22	12	18	–	12	15	22	23	26	21	25
Ampicillin	24	30	28	32	20	28	28	31	–	–	–	–
Flucanozole	–	–	–	–	v	–	–	–	28	34	28	30

3.2.1

3.2.1 Antibacterial activity

Compounds 5b and 6b showed an excellent effect at both the tested concentrations against S. aureus, P. aeruginosa and Enterococcus feltis, whereas the same compounds revealed moderate activity against Klbesilla pneumona and E. coli (Table 1). Compounds 5e and 5f showed excellent activity against S. aureus and E. coli. On the other hand, compounds 5a, 5c, 6c and 6d displayed moderate activity against all bacterial species.

3.2.2

3.2.2 Antifungal activity

Antifungal activity was carried against two human pathogen fungal species A. Niger and Trichoderma Virdae. The results obtained from the present study recorded a remarkable difference in the antifungal effect of all tested compounds at both the concentrations (Table 1). Compounds 5b, 5c and 6d showed excellent activities against both the tested organisms whereas compounds 5d and 6a showed moderate activity and compounds 5a, 5e, 5f, 6b and 6d showed weak antifungal activity against both the tested organisms.

Acknowledgements

The authors are thankful to authorities, Dept. of Industrial Chemistry, Kuvempu University, Shivamogga, for providing laboratory facilities to carry out the research work. One of the authors (S. Sheelavanth) is thankful to DST – Govt. of India, for awarding Inspire fellowship.

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Manna K., Agrawal Y.K., . Bioorg. Med. Chem. Lett.. 2009;19:2688.
Powers L.J., Fogt S.W., Ariyan Z.S., Rippin D.J., Heilman R.D., . J. Med. Chem.. 1981;24:604.
Scribner A., Meitz S., Fisher M., Wyvratt M., Leavitt P., Liberator P., Gurnett A., Brown C., Mathew J., Thompson D., Schmatz D., Biftu T., . Bioorg. Med. Chem. Lett.. 2008;18:5263.
Siddiqui H.L., Iqbal A., Ahmad S., Weaver G.W., . Molecules. 2006;11:206.
Toan, L.Q., Tefas, D., Farmazia, 1962. (Bucharest), 10, No. 1, 10. Chem. Abstr. 1963, 58, 3408.
Venkatesh K.B., Bodke Y.D., . Curr. Chem. Biol.. 2010;4:145.

Appendix A

Supplementary data

Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.arabjc.2012.10.018.

Appendix A

Supplementary data

Supplementary data 1

Supplementary data 1 Supplementary material.

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Introduction

Experimental

General procedure for the synthesis of compounds 2(a–b)
General procedure for the synthesis of compounds 5(a–f) & 6(a–d)
Antimicrobial activity

Result and discussion

Chemistry
Anti microbial activity

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[13] Gilbert D.W.F.K., Christian D.F., Jean H.D., Ghislain W.F., Dawe A., Angèle N.T., Merhatibeb B., Paul F.M., Bonaventure T.N., Berhanu M.A., . Phytochemistry. 2009;70:216.

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[15] Kamal A., Ramesh Khanna G.B., Krishnaji T., Ramu R., . Bioorg. Med. Chem. Lett.. 2005;15:613.

[16] Koca M., Servi S., Kirilmis C., Ahmedzade M., Berna Özbek C.K., Ötük G., . Euro J. Med. Chem.. 2005;40:1351.

[17] Manna K., Agrawal Y.K., . Bioorg. Med. Chem. Lett.. 2009;19:2688.

[18] Powers L.J., Fogt S.W., Ariyan Z.S., Rippin D.J., Heilman R.D., . J. Med. Chem.. 1981;24:604.

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[21] Toan, L.Q., Tefas, D., Farmazia, 1962. (Bucharest), 10, No. 1, 10. Chem. Abstr. 1963, 58, 3408.

[22] Venkatesh K.B., Bodke Y.D., . Curr. Chem. Biol.. 2010;4:145.

Synthesis and antimicrobial activity of some imidazothiazole derivatives of benzofuran

Abstract

Keywords

Anhydrous aluminum chloride

1-(1-Benzofuran-2-yl)-2-bromoethanone

Imidazothiazoles

Antibacterial

Antifungal

1 Introduction

2 Experimental

2.1 General procedure for the synthesis of compounds 2(a–b)

2.1.1 1-(1-Benzofuran-2-yl)-2-bromoethanone 2(a)

2.1.2 2-Bromo-1-(5-bromo-1-benzofuran-2-yl) ethanone 2(b)

2.2 General procedure for the synthesis of compounds 5(a–f) & 6(a–d)

2.2.1 6-(1-Benzofuran-2-yl)-3-phenyl imidazo [2,1-b][1,3]thiazole (5a)

2.2.2 6-(5-Bromo-1-benzofuran-2-yl)-3-phenylimidazo [2,1-b][1,3]thiazole (5b)

2.2.3 6-(1-Benzofuran-2-yl)-3-(4-methylphenyl) imidazo[2,1-b][1,3]thiazole (5c)

2.2.4 6-(5-Bromo-1-benzofuran-2-yl)-3-(4-methylphenyl) imidazo [2,1-b][1,3]thiazole(5d)

2.2.5 6-(1-Benzofuran-2-yl)-3-(4-fluorophenyl)imidazo[2,1-b][1,3]thiazole (5e)

2.2.6 6-(5-Bromo-1-benzofuran-2-yl)-3-(4-fluorophenyl)imidazo[2,1-b][1,3]thiazole (5f)

2.2.7 3,6-Bis (1-benzofuran-2-yl)imidazo[2,1-b][1,3]thiazole (6a)

2.2.8 6-(1-Benzofuran-2-yl)-3-(5-bromo-1-benzofuran-2-yl) imidazo[2,1-b][1,3]thiazole (6b)

2.2.9 3-(1-Benzofuran-2-yl)-6-(5-bromo-1-benzofuran-2-yl)imidazo[2,1-b][1,3]thiazole (6c)

2.2.10 3,6-Bis (5-bromo-1-benzofuran-2-yl)imidazo[2,1-b][1,3]thiazole (6d)

2.3 Antimicrobial activity

3 Result and discussion

3.1 Chemistry

3.2 Anti microbial activity

3.2.1 Antibacterial activity

3.2.2 Antifungal activity

Acknowledgements

References

Appendix A

Supplementary data

Appendix A

Supplementary data

Supplementary data 1

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