1 2 Diazole Synthesis Essay

Abstract

Microwave-assisted synthesis of some novel compounds, namely, 3-(2-methyl-1H-indol-3-yl)-6-aryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 5a,b was accomplished via bromination of 2-methyl-3-[4-(arylideneamino)-5-mercapto-4H-[1,2,4]triazol-3-yl]-1H-indoles 3a,b.Also, new [1,3,4]thiadiazoles 12a,b, [1,2,4]triazoles 15a,b and [1,3,4]oxadiazoles 19a,b, with indole moieties, were prepared by cyclization of 1-[(2-methyl-1H-indole)-3-carbonyl]thiosemicarbazides 8a,b under microwave irradiation using different reaction conditions. Moreover, reaction of acid hydrazide 7 with ethyl 2-(N-phenylhydrazono)-3-oxobutanoate (20) gave the respective phenylhydrazonopyrazole derivative 21 under the reaction conditions employed. The structures of the synthesized compounds were assigned based on elemental analyses and spectral data (IR, 1H-NMR, 13C-NMR, MS). The antifungal and antibacterial activities of the new products were also evaluated.

Keywords: [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles; diazoles; Schiff’s bases; microwave irradiation and antimicrobial activity[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles; diazoles; Schiff’s bases; microwave irradiation and antimicrobial activity

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MDPI and ACS Style

Gomha, S.M.; Riyadh, S.M. Synthesis under Microwave Irradiation of [1,2,4]Triazolo[3,4-b] [1,3,4]thiadiazoles and Other Diazoles Bearing Indole Moieties and Their Antimicrobial Evaluation. Molecules2011, 16, 8244-8256.

AMA Style

Gomha SM, Riyadh SM. Synthesis under Microwave Irradiation of [1,2,4]Triazolo[3,4-b] [1,3,4]thiadiazoles and Other Diazoles Bearing Indole Moieties and Their Antimicrobial Evaluation. Molecules. 2011; 16(10):8244-8256.

Chicago/Turabian Style

Gomha, Sobhi M.; Riyadh, Sayed M. 2011. "Synthesis under Microwave Irradiation of [1,2,4]Triazolo[3,4-b] [1,3,4]thiadiazoles and Other Diazoles Bearing Indole Moieties and Their Antimicrobial Evaluation." Molecules 16, no. 10: 8244-8256.

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Introduction

Selenium containing heterocyclic compounds are of interest due to their biological and synthetic applications. 1,2,3-Selenadiazoles and derivatives are well known and have attracted attention as versatile synthetic intermediates [1,2]. Many substituted 1,2,3-selenadiazoles and derivatives have been prepared to-date and some of them show high antibacterial activity [3,4,5,6]. The antifungal activity of other substituted 1,2,3-selenadiazoles has also been determined [6,7,8]. It has been found that the introduction of a 1,2,3-selenadiazole ring to molecules of known biological activity compounds changes their activities and in some cases leads to an increase in their biological activity [9]. Other heterocyclic compounds containing five membered rings like triazole, oxazole, pyrazoline, pyrazole and thiazole have been found to be biologically active substances [3, 11,12]. These ring systems are present in numerous antiparasitic, fungicidal, antihelminitic and antiinflammatory drugs.

β-Lactam antibiotics derivatized with a 1,2,3-thiadiazole-5-mercapto moiety have been found to be active against Gram-negative bacteria such as Pseudomonas aeruginosa. 4-Methyl-1,2,3-selena-diazole-5-carboxamides have been described to inhibit tumor cell colony formation [13,14]. In the area of antibacterial therapeutics, resistance to currently available drugs is progressively limiting their utility in treating bacterial infections. This problem can be solved by discovering novel pharmaceutical drugs that inhibit novel targets. Advances in molecular microbiology and genomics have led to the identification of numerous bacterial genes that are encoding for novel proteins, that could potentially serve as novel targets for antibacterial compounds. Regulatory proteins such as the two-component histidine kinases, involved in bacterial signal transduction, have recently gained considerable attention as one such class of potential targets [15].

As a continuation of our work on the synthesis of heterocyclic compounds containing 1,2,3-thiadiazoles and 1,2,3-selenadiazoles [16,17,18], we have set out to synthesize a new group of heterocyclic compounds containing 1,2,3-selenadiazole derivatives from the corresponding ketones 1a-d, respectively, hoping to obtain biologically active compounds with potential use in the manufacture of pharmaceutical drugs. In this paper we present new data on the antimicrobial activities of heterocyclic compounds containing 1,2,3-selenadiazole rings and the corresponding tosylhydrazones.

Results and Discussion

The target 1,2,3-selenadiazole derivatives 3a-d were prepared from the corresponding tosyl-hydrazones 2a-d as shown in Scheme 1. The synthetic procedure started from the commercially available polyketones 1a-d. They were transformed into the target heterocyclic compounds by the reaction of the tosylhydrazones with selenium dioxide, as previously described by Lalezari et. al. [19,20]. Compound 3e was prepared by reaction of 4-(1,2,3-selenadiazole-4-yl)phenol [16] and epichlorohydrin, as shown in Scheme 2.

Scheme 1.

Scheme 2.

The activity of these heterocyclic compounds and their tosylhydrazone precursors was tested against some human pathogenic microbes including Gram-positive (Staphylococcus aureus), Gram-negative (Escherichia coli, local resistant Pseudomonas aeruginosa and a reference Pseudomonasaeruginosa ATCC 27853) and Candida albicans by two methods, namely by the hole diffusion (see Table 1) and by the paper disk method (see Table 2).

From the results obtained from the two methods (Table 1 and Table 2), it was found that some of the tested heterocyclic compounds were highly active even at low concentrations (ie., at 0.005 g/mL or less). Both methods indicated that the sensitivity of the highly resistance Pseudomonas. aeruginosa and the sensitivity of a local, highly resistant clinical isolate, collected from King Abdullah Hospital at Jordan University of Science and Technology, to some of these heterocyclic compounds is high.

The extracts of compounds 3a, 3c and 3e in dimethyl sulfoxide (DMSO) are active against all the tested pathogens, with a (8-19 mm) inhibition zone diameter, when using the hole diffusion technique, as indicated in Table 1. Pseudomonas. aeruginosa, a local isolate highly resistant to all domestic antibiotics (amikacin, carbenicillin, cefoperazone, gentamicin, tobramycin), used in the clinical labs of King Abdullah Hospital was found to be more sensitive to compound 3e. This isolate was also sensitive to compounds 3a and 3c (at 0.01 g/mL) and to 3e (at 0.005 g/mL). The solvent showed no activity against any of the tested pathogens.

Table 1. Sensitivity of human pathogenic microbes to the new synthetic heterocyclic compounds using the hole method.

CompoundConc. (g/mL)Pathogens
AaBCDE
Tobramycin0.01015b 1322-14
0.005131117-8
2a0.010111212-9
0.0058108--
2b0.010131314-8
0.005889--
2c0.010-811--
0.005--8--
2d0.010-910-8
0.005--8--
3a0.01081210814
0.005-98-10
3b0.01091111-15
0.005-108-12
3c0.0108810814
0.005--9-10
3d0.010--8-8
0.005-----
3e0.0101313191015
0.00513-1499

Table 2. Sensitivity of human pathogenic microbes to the new synthetic heterocyclic compounds using the filter paper disk method.

CompoundConc. (g/mL)Pathogens
AaBCDE
Tobramycin0.01016b 1424-16
0.005101216-10
2a0.010101314-9
0.0058108--
2b0.010131415-8
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