Introduction

Benzimidazole incorporating structures are of immense importance pharmacologically due to their significant bioactivities like anti-HIV (Burkholder et al., 2001), anticancer (El-Naem et al., 2003), local anesthetic (Anisimova et al., 2002), antituberculosis (Foks et al., 2006), antifungal (Enguehard et al., 2000), anti-bacterial (Ramanatham et al., 2008), etc. Moreover, the SAR study interestingly evokes that the minor change in the structure of substituent group flanked between two nitrogen atoms of benzimidazole commonly results in the change of its bioactivity (Ge et al., 2007; Kazimierczuk et al., 2005). Literature survey manifests that the number of benzimidazole derivatives have been synthesized using various aldehydes and o-phenylenediamines but there is not a single report where tetrazolo[1,5-a]quinoline-4-carbaldehyde is used. As this heterocyclic aldehyde is conjugated with diverse biological activities (Bekhit et al., 2004), our research focus is concentrated at an efficient synthesis of new heterocyclic system incorporating above moieties together with an objective to gain more potent heterocycles.

There are two general methods for the synthesis of 2-substituted benzimidazoles. One is the coupling of o-phenylenediamines and carboxylic acids (Das and Thakuria, 2008) or their derivatives like imidates (Zarguil et al., 2008), orthoesters (Mohammadpoor-Baltork et al., 2008), and nitriles (Moskvichev et al., 2001), which often requires strong acidic conditions. Second method involves a two-step process that includes the oxidative cyclo-dehydrogenation of Schiff bases, which are often generated from the condensation of o-phenylenediamines and aldehydes. Various catalysts such as FeCl3·6H2O (Shen and Driver, 2008), I2 (Gogoi and Konwar, 2006), Air (Lin and Yang, 2005), KHSO4 (Ma et al., 2006), and Sc(OTf)3 (Itoh et al., 2004; Nagata et al., 2003) have been employed. Some of these methods suffer from one or more disadvantages such as high reaction temperature, prolonged reaction time, and tedious work-up process. Consequently, the discovery of mild and practicable routes for synthesis of 2-substituted benzimidazoles keeps on attracting much attention of researchers. p-TsOH has received considerable attention as an inexpensive and easily available catalyst of various organic reactions (Xiangming et al., 2007).

The conventional procedures are not found to be satisfactory with regard to operational simplicity, effectiveness, and yield. An alternative synthetic approach is microwave irradiation (Jing et al., 2006; Rao et al., 2004). In recent years, microwave irradiation has been demonstrated not only to dramatically accelerate many organic reactions, but also to improve yields and selectivity. Thus, the drive continues in search of an improved methodology and cleaner chemistry. Encouraged by their potential clinical applications and in continuation of our previous investigations on biologically active heterocycles including tetrazolo[1,5-a]quinoline (Ladani et al., 2009a, b, 2010; Mungra et al., 2009; Nirmal et al., 2009; Shah et al., 2009; Thakor et al., 2008; Thumar and Patel, 2009a, b), we report herein a microwave-assisted synthesis of 4-Benzimidazol-2-yl tetrazolo[1,5-a]quinoline catalyzed by an organocatalyst p-TsOH as a part of our search to design more biologically potent heterocyclic systems via combination of two therapeutically active moieties tetrazolo[1,5-a]quinoline and benzimidazole.

Results and discussion

Chemistry

The key intermediate, tetrazolo[1,5-a]quinoline-4-carbaldehyde 3a–d, was prepared by refluxing 2-chloro-3-formyl quinoline 2a–d, sodium azide, and acetic acid in ethanol for 3–4 h (Ladani et al., 2009a, b). The required 2-chloro-3-formyl quinoline 2a–d was prepared by Vilsmeier–Haack reaction of acetanilide 1a–d according to literature procedure (Meth-Cohn and Bramha, 1978).

In the present study, all the 4-Benzimidazol-2-yl tetrazolo[1,5-a]quinoline 5a–p (Scheme 1; Table 1) were obtained in good yields by the p-toluenesulphonic acid catalyzed condensation reaction of various tetrazolo[1,5-a]quinoline-4-carbaldehyde 3a–d with o-phenylenediamine 4a–d in DMF under microwave irradiation as depicted in Scheme 1. The formation of compounds 5a–p may proceed via intramolecular oxidative cyclo-dehydrogenation of Schiff bases (Scheme 2) formed from the condensation of o-phenylenediamine 4a–d and tetrazolo[1,5-a]quinoline-4-carbaldehyde 3a–d. DMF was used as an energy transfer media, and the reaction mixture was irradiated in a microwave oven for 4 min. The reaction conditions were optimized. The course of reaction was followed by TLC, and maximum yield was obtained at (350 W) 50% microwave power level.

Scheme 1
scheme 1

Representative route for the synthesis of 4-benzimidazol-2-yltetrazolo[1,5-a]quinoline 5a–p; VHR Vilsmeier–Haack reaction

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Table 1 Antibacterial and antifungal activity of compounds 5a–p
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Scheme 2
scheme 2

Plausible mechanistic pathway for the synthesis of 4-benzimidazol-2-yltetrazolo[1,5-a] quinol me 5a–p involving intramolecular oxidative cyclo-dehydrogenation of Schiff base

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The identity of the product determined by 1H NMR, 13C NMR, FT-IR spectral data, and molecular weight of some selected compounds were confirmed by mass spectrometry. 1H NMR (DMSO-d 6) spectrum of 5a, molecule of interest, exhibited singlet peak at δ 11.79 ppm appeared for –NH– proton of benzimidazole ring. Aromatic protons as multiplets appeared at around δ 7.28–9.16 ppm. Moreover, it exhibited the absence of the aldehyde proton. The 13C NMR spectrum is in consonance with the structure assigned. In the 13C NMR spectra, signals around δ 115.48–145.86 ppm are attributed to aromatic carbons of compounds 5a. The IR spectrum of compound 5a exhibited characteristic absorption band at 3420 and 3015 cm−1 for cyclic –NH– of benzimidazole nucleus and aromatic C–H stretching, respectively. The mass spectra of compounds 5a and 5j, molecules of interest, detected the expected molecular ion signals corresponding to respective molecular formula, i.e., mass spectra of compound 5a (X = H, Y = H) and 5j (X = CH3, Y = OCH3) gave molecular ion peak at m/z 287 (M + 1) and m/z 331 (M + 1) corresponding to molecular formula C16H10N6 and C18H14N6O, respectively (Scheme 1). The obtained elemental analysis values are in good agreement with theoretical data. Similarly, all these compounds were characterized on the basis of spectral studies.

Antimicrobial activity

All the glass apparatus used were sterilized before use. Antimicrobial activity of all the synthesized compounds was carried out by broth microdilution method (NCCLS, 2002). Mueller–Hinton broth was used as nutrient medium to grow and dilute the compound suspension for the test bacteria and Sabouraud Dextrose broth used for fungal nutrition. Inoculum size for test strain was adjusted to 108 CFU [Colony Forming Unit] per milliliter by comparing the turbidity. The strains used for the activity were procured from [MTCC—Microbial Type Culture Collection] Institute of Microbial Technology, Chandigarh. Each synthesized compound was diluted obtaining 2000 μg/ml concentration, as a stock solution. The results are recorded in the form of primary and secondary screenings. The compounds 5a–p were screened for their antibacterial activity against Bacillus subtilis (MTCC 441), Clostridium tetani (MTCC 449), Streptococcus pneumoniae (MTCC 1936), Escherichia coli (MTCC 443), Salmonella typhi (MTCC 98), Vibrio cholerae (MTCC 3906) as well as for antifungal activity against Aspergillus fumigatus (MTCC 3008) and Candida albicans (MTCC 227) at concentrations of 1000, 500, and 250 μg/ml as primary screening. DMSO was used as vehicle to get desired concentrations of compounds to test upon microbial strains. The compounds found to be active in the primary screening were further screened in a second set of dilution at concentrations of 200, 100, 62.5, 50, 25, 12.5, and 6.25 μg/ml. Ten microliters suspension from each well was further inoculated and growth was noted after 24 and 48 h. The lowest concentration which showed no visible growth (turbidity) after spot subculture was considered as MIC for each compound. The standard drugs used for comparison in the present study were ampicillin, chloramphenicol, ciprofloxacin, norfloxacin, and gentamycin for evaluating antibacterial activity and griseofulvin and nystatin for antifungal activity.

Screening results displayed that compounds 5a–p exhibited good-to-moderate activity for all the bacterial strains, compared with other standard drugs. An examination of the data (Table 1) reveals that among the compounds 5a–p, compound 5e (X = H, Y = CH3) exhibited excellent activity against Bacillus subtilis and Clostridium tetani in comparison to standard antibiotic ampicillin. Compounds 5a (X = H, Y = H), 5k (X = Cl, Y = OCH3), 5n (X = CH3, Y = Cl), and 5o (X = Cl, Y = Cl) were found significantly active against Bacillus subtilis compared with ampicillin. Remaining compounds showed good-to-moderate activity against other bacteria in comparison to the rest of standard drugs.

None of the compounds was found sufficiently potent to inhibit Streptococcus pneumoniae. In case of Gram-negative bacteria Escherichia coli, compounds 5d (X = Br, Y = H) and 5e (X = H, Y = CH3) displayed comparable activity to the standard ampicillin, while 5b (X = CH3, Y = H) and 5o (X = Cl, Y = Cl) displayed significant activity. Compounds 5c (X = Cl, Y = H) and 5d (X = Br, Y = H) displayed comparable activity, while compound 5e (X = H, Y = CH3) showed significant activity against Gram-negative bacteria Salmonella typhi as compared to the standard ampicillin. None of the compounds was found sufficiently potent to inhibit Vibrio cholerae. The remaining compounds showed moderate activity against other bacteria when compared with the remaining standard drugs.

Antifungal study revealed that all the compounds have poor activity against Aspergillus fumigatus. As compared to the standard, griseofulvin, 5j (X = CH3, Y = OCH3), 5k (X = Cl, Y = OCH3), and 5n (X = CH3, Y = Cl) exhibited excellent activity against Candida albicans. Other compounds showed poor activity against the rest of the fungal species compared with the standard drugs nystatin and griseofulvin.

Experimental

All the reagents were obtained commercially and used with further purification. Solvents used were of analytical grade. All melting points were taken in open capillaries and were uncorrected. Thin-layer chromatography (TLC, on aluminum plates coated with silica gel 60 F254, 0.25 mm thickness, Merck) was used for monitoring the progress of all reactions, purity, and homogeneity of the synthesized compounds. Elemental analysis (% C, H, N) was carried out by Perkin-Elmer 2400 series-II elemental analyzer, and all compounds are within ±0.4% of theory specified. The IR spectra were recorded on a Shimadzu FTIR 8401 spectrophotometer using KBr discs, and only the characteristic peaks are reported in cm−1. 1H NMR and 13C NMR spectra were recorded in DMSO-d 6 on a Bruker Avance 400 MHz spectrometer using solvent peak as internal standard. Chemical shifts are reported in parts per million (ppm). Mass spectra were scanned on a Shimadzu LCMS 2010 spectrometer. Mode of ionization employed was ESI (electrospray ionization). The microwave oven used was specially modified by RAGA’s Electromagnetic systems.

Synthesis of the substituted tetrazolo[1,5-a]quinoline-4-carbaldehyde 3a–d

2-Chloro-3-formyl quinoline 2a–d (5 mmol), sodium azide (10 mmol), acetic acid (1 ml), and ethanol (10 ml) were charged in a 100-ml round bottom flask with mechanical stirrer and condenser. The reaction mixture refluxed for 3–4 h. After the completion of reaction (checked by TLC), the separated tetrazolo[1,5-a]quinoline-4-carbaldehyde 3a–d was filtered and washed with ethanol. The further purification was carried out by leaching in equal volume ratio of chloroform and methanol (10:10 ml) to obtain the pure solid sample.

Synthesis of substituted 4-benzimidazol-2-yl tetrazolo[1,5-a]quinoline 5a–p

Tetrazolo[1,5-a]quinoline-4-carbaldehyde 3a–d (5 mmol) and o-phenylenediamine 4a–d (5 mmol) were thoroughly mixed in DMF (10 ml) and then p-TsOH (1 mmol) was added to it. The mixture was irradiated for 240 s at 350 W of output power. After the completion of reaction (checked by TLC), the solution was cooled to room temperature. The reaction mixture was added dropwise with vigorous stirring into a previously chilled solution of Na2CO3 (2 mmol) in H2O (30 ml). The separated precipitates of 4-Benzimidazol-2-yl tetrazolo[1,5-a]quinoline 5a–p were filtered, thoroughly washed well with water, dried, and recrystallized from chloroform. The physicochemical and spectral properties of all the newly synthesized compounds 5a–p are presented below.

4-(1H-benzo[d]imidazol-2-yl)tetrazolo[1,5-a]quinoline (5a)

Yield 76%, m.p. 239°C, Anal. Calcd. for C16H10N6 (286.29 gm/mol): C 67.12, H 3.52, N 29.35% Found: C 67.23, H 3.66, N 29.12%. IR (KBr, cm−1): 3420 (cyclic –NH), 3015 (ArC–H). 1H NMR (400 MHz, DMSO-d 6): δ 11.79 (s, 1H, NH), 7.28–9.16 (m, 9H, Ar–H). 13C NMR (400 MHz, DMSO-d 6) δ: 115.48, 116.69, 123.30, 124.38, 128.95, 129.05, 130.50, 130.85, 132.27, 132.59, 132.65, 145.73, 145.86 (Ar–C), MS: (M + 1) 287.

4-(5-methyl-1H-benzo[d]imidazol-2-yl)tetrazolo[1,5-a]quinoline (5b)

Yield 71%, m.p. 216°C, Anal. Calcd. for C17H12N6 (300.32 gm/mol): C 67.99, H 4.03, N 27.98% Found: C 67.86, H 4.13, N 27.86%. IR (KBr, cm−1): 3305 (cyclic –NH), 3000 (ArC–H). 1H NMR (400 MHz, DMSO-d 6): δ 12.35 (s, 1H, NH), 2.49 (s, 3H, CH3), 7.14–8.52 (m, 8H, Ar–H). 13C NMR (400 MHz, DMSO-d 6) δ: 21.90 (CH3), 113.58, 114.58, 115.19, 116.36, 117.09, 121.47, 121.58, 124.64, 126.74, 131.33, 145.71, 145.95, 147.98, 149.69, 158.08, 159.26 (Ar–C).

4-(5-chloro-1H-benzo[d]imidazol-2-yl)tetrazolo[1,5-a]quinoline (5c)

Yield 68%, m.p. 219°C, Anal. Calcd. for C16H9N6Cl (320.74 gm/mol): C 59.92, H 2.83, N 26.20% Found: C 59.73, H 2.68, N 26.12%. IR (KBr, cm−1): 3410 (cyclic –NH), 3005 (ArC–H). 1H NMR (400 MHz, DMSO-d 6): δ 11.71 (s, 1H, NH), 7.38–9.27 (m, 8H, Ar–H). 13C NMR (400 MHz, DMSO-d 6) δ: 114.83, 116.99, 118.67, 123.80, 124.77, 126.07, 127.95, 129.05, 130.53, 130.59, 131.28, 132.51, 132.99, 141.51, 145.47, 146.98 (Ar–C).

4-(5-Bromo-1H-benzo[d]imidazol-2-yl)tetrazolo[1,5-a]quinoline (5d)

Yield 74%, m.p. 200°C, Anal. Calcd. for C16H9N6Br (365.19 gm/mol): C 52.62, H 2.48, N 23.01% Found: C 52.73, H 2.54, N 23.16%. IR (KBr, cm−1): 3420 (cyclic –NH), 3025 (ArC–H). 1H NMR (400 MHz, DMSO-d 6): δ 11.84 (s, 1H, NH), 7.45–9.39 (m, 8H, Ar–H). 13C NMR (400 MHz, DMSO-d 6) δ: 113.46, 114.97, 117.77, 122.85, 124.65, 126.72, 127.05, 129.73, 130.43, 130.37, 131.21, 132.69, 132.91, 140.57, 144.40, 145.16 (Ar–C).

4-(1H-benzo[d]imidazol-2-yl)-7-methyltetrazolo[1,5-a]quinoline (5e)

Yield 84%, m.p. 234°C, Anal. Calcd. for C17H12N6 (300.32 gm/mol): C 67.99, H 4.03, N 27.98% Found: C 67.80, H 4.14, N 28.10%. IR (KBr, cm−1): 3320 (cyclic –NH), 3005 (ArC–H). 1H NMR (400 MHz, DMSO-d 6): δ 12.52 (s, 1H, NH), 2.56 (s, 3H, CH3), 7.14–8.48 (m, 8H, Ar–H). 13C NMR (400 MHz, DMSO-d 6) δ: 23.94 (CH3), 109.39, 111.56, 114.14, 117.22, 117.97, 120.08, 121.59, 124.73, 125.80, 130.27, 141.81, 146.20, 148.01 (Ar–C).

4-(5-Methyl-1H-benzo[d]imidazol-2-yl)-7-methyltetrazolo[1,5-a]quinoline (5f)

Yield 69%, m.p. 242°C, Anal. Calcd. for C18H14N6 (314.34 gm/mol): C 68.78, H 4.49, N 26.74% Found: C 68.68, H 4.40, N 26.66%. IR (KBr, cm−1): 3340 (cyclic –NH), 3005 (ArC–H). 1H NMR (400 MHz, DMSO-d 6): δ 12.54 (s, 1H, NH), 2.39 (s, 3H, CH3), 2.54 (s, 3H, CH3), 7.11–8.56 (m, 7H, Ar–H). 13C NMR (400 MHz, DMSO-d 6) δ: 21.90 (CH3), 22.36 (CH3), 109.48, 111.57, 114.67, 117.91, 117.93, 121.85, 123.54, 124.36, 125.00, 133.22, 145.97, 145.39, 146.58, 148.12, 158.00, 159.37 (Ar–C).

4-(5-Chloro-1H-benzo[d]imidazol-2-yl)-7-methyltetrazolo[1,5-a]quinoline (5g)

Yield 64%, m.p. 212°C, Anal. Calcd. for C17H11N6Cl (334.76 gm/mol): C 60.99, H 3.31, N 25.10% Found: C 61.12, H 3.43, N 25.33%. IR (KBr, cm−1): 3320 (cyclic –NH), 3025 (ArC–H). 1H NMR (400 MHz, DMSO-d 6): δ 12.18 (s, 1H, NH), 2.48 (s, 3H, CH3), 7.29–8.68 (m, 7H, Ar–H). 13C NMR (400 MHz, DMSO-d 6) δ: 22.94 (CH3), 111.65, 112.68, 114.44, 115.19, 117.00, 122.36, 123.98, 124.36, 125.90, 134.16, 145.90, 145.99, 146.50, 149.98, 157.08, 158.29 (Ar–C).

4-(5-Bromo-1H-benzo[d]imidazol-2-yl)-7-methyltetrazolo[1,5-a]quinoline (5h)

Yield 73%, m.p. 238°C, Anal. Calcd. for C17H11N6Br (379.21 gm/mol): C 53.84, H 2.92, N 22.16% Found: C 53.77, H 2.80, N 22.13%. IR (KBr, cm−1): 3340 (cyclic –NH), 3005 (ArC–H). 1H NMR (400 MHz, DMSO-d 6): δ 11.96 (s, 1H, NH), 2.41 (s, 3H, CH3), 7.34–8.53 (m, 7H, Ar–H). 13C NMR (400 MHz, DMSO-d 6) δ: 22.94 (CH3), 110.01, 112.78, 114.08, 115.63, 117.40, 120.36, 122.91, 124.82, 125.00, 133.30, 143.85, 145.15, 146.18, 149.90, 158.16, 159.36 (Ar–C).

4-(1H-Benzo[d]imidazol-2-yl)-7-methoxytetrazolo[1,5-a]quinoline (5i)

Yield 79%, m.p. 213°C, Anal. Calcd. for C17H12N6O (316.32 gm/mol): C 64.55, H 3.82, N 26.57% Found: C 64.68, H 3.94, N 26.40%. IR (KBr, cm−1): 3325 (cyclic –NH), 3015 (ArC–H). 1H NMR (400 MHz, DMSO-d 6): δ 12.12 (s, 1H, NH), 3.84 (s, 3H, OCH3), 7.24–8.39 (m, 8H, Ar–H). 13C NMR (400 MHz, DMSO-d 6) δ: 57.08 (OCH3), 110.10, 112.50, 114.21, 116.20, 117.17, 121.02, 121.65, 123.73, 125.23, 131.98, 140.12, 145.24, 147.56 (Ar–C).

4-(5-Methyl-1H-benzo[d]imidazol-2-yl)-7-methoxytetrazolo[1,5-a]quinoline (5j)

Yield 64%, m.p. 204°C, Anal. Calcd. for C18H14N6O (330.34 gm/mol): C 65.44, H 4.27, N 25.44% Found: C 65.12, H 4.36, N 25.56%. IR (KBr, cm−1): 3300 (cyclic –NH), 3010 (ArC–H). 1H NMR (400 MHz, DMSO-d 6): δ 12.61 (s, 1H, NH), 2.43 (s, 3H, CH3), 3.91 (s, 3H, OCH3), 7.04–8.99 (m, 7H, Ar–H). 13C NMR (400 MHz, DMSO-d 6) δ: 21.90 (CH3), 56.34 (OCH3), 110.36, 111.50, 115.65, 117.86, 117.99, 121.00, 121.51, 124.84, 125.78, 131.27, 145.01, 145.29, 146.58, 147.89, 158.99, 159.10 (Ar–C), MS: (M + 1) 331.

4-(5-Chloro-1H-benzo[d]imidazol-2-yl)-7-methoxytetrazolo[1,5-a]quinoline (5k)

Yield 66%, m.p. 222°C, Anal. Calcd. for C17H11N6OCl (350.76 gm/mol): C 58.21, H 3.16, N 23.96% Found: C 58.12, H 3.22, N 23.86%. IR (KBr, cm−1): 3340 (cyclic –NH), 3015 (ArC–H). 1H NMR (400 MHz, DMSO-d 6): δ 12.69 (s, 1H, NH), 3.79 (s, 3H, OCH3), 7.16–8.46 (m, 7H, Ar–H). 13C NMR (400 MHz, DMSO-d 6) δ: 56.34 (OCH3), 109.12, 111.65, 115.94, 117.00, 117.94, 121.84, 122.52, 124.26, 126.71, 130.15, 145.98, 147.29, 148.50, 149.09, 157.35, 156.17 (Ar–C).

4-(5-Bromo-1H-benzo[d]imidazol-2-yl)-7-methoxytetrazolo[1,5-a]quinoline (5l)

Yield 69%, m.p. 243°C, Anal. Calcd. for C17H11N6OBr (395.21gm/mol): C 51.66, H 2.81, N 21.26% Found: C 51.49, H 2.92, N 21.20%. IR (KBr, cm−1): 3335 (cyclic –NH), 3005 (ArC–H). 1H NMR (400 MHz, DMSO-d 6): δ 12.52 (s, 1H, NH), 3.84 (s, 3H, OCH3), 7.20–8.41 (m, 7H, Ar–H). 13C NMR (400 MHz, DMSO-d 6) δ: 56.49 (OCH3), 110.84, 113.67, 115.90, 117.52, 117.90, 121.00, 122.57, 123.23, 126.35, 133.48, 145.08, 146.24, 148.41, 149.82, 156.35, 158.23 (Ar–C).

4-(1H-Benzo[d]imidazol-2-yl)-7-chlorotetrazolo[1,5-a]quinoline (5m)

Yield 66%, m.p. 242°C, Anal. Calcd. for C16H9N6Cl (320.74 gm/mol): C 59.92, H 2.83, N 26.20% Found: C 59.99, H 2.74, N 26.16%. IR (KBr, cm−1): 3335 (cyclic –NH), 3005 (ArC–H). 1H NMR (400 MHz, DMSO-d 6): δ 11.84 (s, 1H, NH), 7.22–8.56 (m, 8H, Ar–H). 13C NMR (400 MHz, DMSO-d 6) δ: 110.45, 111.92, 113.24, 115.27, 117.28, 120.98, 121.66, 123.70, 125.25, 132.47, 142.56, 146.72, 149.92 (Ar–C).

4-(5-Methyl-1H-benzo[d]imidazol-2-yl)-7-chlorotetrazolo[1,5-a]quinoline (5n)

Yield 72%, m.p. 205°C, Anal. Calcd. for C17H11N6Cl (334.76 gm/mol): C 60.99, H 3.31, N 25.10% Found: C 60.82, H 3.46, N 25.30%. IR (KBr, cm−1): 3315 (cyclic –NH), 3020 (ArC–H). 1H NMR (400 MHz, DMSO-d 6): δ 12.25 (s, 1H, NH), 2.41 (s, 3H, CH3), 7.34–8.65 (m, 7H, Ar–H). 13C NMR (400 MHz, DMSO-d 6) δ: 22.63 (CH3), 109.27, 111.78, 114.04, 115.23, 117.70, 122.33, 123.98, 124.84, 125.94, 133.10, 143.97, 145.09, 146.43, 149.00, 154.74, 157.38 (Ar–C).

4-(5-Chloro-1H-benzo[d]imidazol-2-yl)-7-chlorotetrazolo[1,5-a]quinoline (5o)

Yield 64%, m.p. 229°C, Anal. Calcd. for C16H8N6Cl2 (355.18 gm/mol): C 54.11, H 2.27, N 23.66% Found: C 54.00, H 2.21, N 23.48%. IR (KBr, cm−1): 3305 (cyclic –NH), 3010 (ArC–H). 1H NMR (400 MHz, DMSO-d 6): δ 12.36 (s, 1H, NH), 7.48–8.82 (m, 7H, Ar–H). 13C NMR (400 MHz, DMSO-d 6) δ: 110.95, 111.45, 113.14, 115.00, 119.78, 122.30, 123.98, 125.65, 125.90, 132.18, 142.94, 144.16, 146.38, 149.95, 153.12, 156.30 (Ar–C).

4-(5-Bromo-1H-benzo[d]imidazol-2-yl)-7-chlorotetrazolo[1,5-a]quinoline (5p)

Yield 73%, m.p. 236°C, Anal. Calcd. for C16H8N6ClBr (399.63 gm/mol): C 48.09, H 2.02, N 21.03% Found: C 48.22, H 1.98, N 21.16%. IR (KBr, cm−1): 3315 (cyclic –NH), 3015 (ArC–H). 1H NMR (400 MHz, DMSO-d 6): δ 12.48 (s, 1H, NH), 7.40–8.89 (m, 7H, Ar–H). 13C NMR (400 MHz, DMSO-d 6) δ: 111.15, 111.95, 112.20, 115.47, 119.71, 123.34, 123.90, 125.12, 125.96, 131.63, 141.35, 144.00, 145.30, 148.03, 152.39, 157.43 (Ar–C).

Conclusion

Rapid, simple, and efficient method has been developed for the synthesis of some new tetrazolo[1,5-a]quinoline-based benzimidazole derivatives under the microwave irradiation conditions in the presence of an organocatalyst p-TsOH. This synthetic strategy allows the construction of relatively complicated nitrogen containing heterocyclic system as well as the introduction of various heteroaromatic substitutions in between two nitrogen atoms of benzimidazole scaffold. It can be concluded from Table 1 that compound 5e having a methyl group at 7-position of tetrazolo[1,5-a]quinoline nucleus and unsubstituted fused phenyl ring of benzimidazole is highly active against Bacillus subtilis and Clostridium tetani. It is worth mentioning that minor changes in molecular configuration of these compounds profoundly influence the bioactivity. Further work to intensify the potency of this series by changing molecular configuration of cyclic –NH– of benzimidazole nucleus is in progress at our laboratory. The present study throws light on the identification of this new structural class as antimicrobials which can be of interest for further detailed preclinical investigations.