A new series of 2-pyrazolin-1-ylthiazoles 8a–d and 13–16 was synthesized by cyclization of N-thiocarboxamide-2-pyrazoline with different haloketones and 2,3-dichloroquinoxaline. The structures of the new compounds were confirmed by elemental analyses as well as NMR, IR, and mass spectral data. The newly synthesized compounds were evaluated for their antimicrobial activities, and also their minimum inhibitory concentration (MIC) against most of test organisms was performed. Amongst the tested ones, compound 8c displayed excellent antimicrobial activity. 1. Introduction Pyrazolines are nitrogen-containing heterocyclic compounds, well known for their pronounced biological activity. These biological activities include antibacterial [1], antifungal [2], herbicidal [3], and insecticidal activities [4]. It was demonstrated that the combination of pyrazole with azole ring, linked to each by one sigma bond, led to more biologically active targets; for example, pyrazolylthiazoles showed excellent antimicrobial activities [5]. Continuing our work in this research field [6–9] and in an attempt to identify new and potent antimicrobial agents, we tried here to generate new benzofuryl 2-pyrazolin-1-ylthiazoles as antimicrobial agents using simple methods. 2. Results and Discussion 2.1. Chemistry The starting pyrazoline-1-carbothioamide 5 was prepared by treatment of 2-acetylbenzofuran 1 with equivalent of 4-flurobenzaldehyde 2 in the presence of 10% alcoholic NaOH in 90% ethanol with stirring at room temperature to give chaconne 3. Reaction of chalcone 3 with equivalent amount of thiosemicarbazide was performed in ethanol in the presence of 2.5 equivalent of sodium hydroxide to the target precursor 5. The resulting pyrazoline-1-carbothioamide 5 was cyclized to the corresponding 2-(3-(benzofuran-2-yl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-methyl-5-(p-subs.phenyldiazenyl)thiazole derivatives 8a–d by reaction with hydrazonoyl halides 6a–d in anhydrous ethanol and in the presence of an equivalent of triethylamine (Scheme 1). Scheme 1 The reaction product structures were elucidated by means of NMR, MS spectroscopy, and elemental analyses (Table 1). Table 1: Characteristic data of the synthesized compounds. For example, 1H NMR spectra of 8a–d contained two doublet-doublet and one triplet signals due to the presence of CH2 adjacent asymmetric carbon. The mass spectra of 8a–d showed the molecular ion peaks at m/z 481, 499, 515 and 561, respectively in agreement with the calculated masses. The reaction between pyrazoline-1-carbothioamide 5 and the equivalent amount
References
[1]
H. Patel, V. Ugale, A. Ingale, and S. Bari, “Synthesis and antimicrobial evaluation of pyrazo-thiazoles,” Letters in Drug Design & Discovery, vol. 9, pp. 840–847, 2012.
[2]
C.-Y. Zhang, X.-H. Liu, B.-L. Wang, S.-H. Wang, and Z.-M. Li, “Synthesis and antifungal activities of new pyrazole derivatives via 1,3-dipolar cycloaddition reaction,” Chemical Biology and Drug Design, vol. 75, no. 5, pp. 489–493, 2010.
[3]
T. D. Sherman, M. V. Duke, R. D. Clark, E. F. Sanders, H. Matsumoto, and S. O. Duke, “Pyrazole phenyl ether herbicides inhibit protoporphyrinogen oxidase,” Pesticide Biochemistry and Physiology, vol. 40, no. 3, pp. 236–245, 1991.
[4]
H. Song, Y. Liu, L. Xiong, Y. Li, N. Yang, and Q. Wang, “Design, synthesis, and insecticidal activity of novel pyrazole derivatives containing α-hydroxymethyl-N-benzyl carboxamide, α-chloromethyl-N-benzyl carboxamide, and 4,5-dihydrooxazole moieties,” Journal of Agricultural and Food Chemistry, vol. 60, no. 6, pp. 1470–1479, 2012.
[5]
B. F. Abdel-Wahab, A. Sediek, H. A. Mohamed, and G. E. A. Awad, “Novel 2-pyrazolin-1-ylthiazoles as potential antimicrobial agents,” Letters in Drug Design & Discovery, vol. 10, no. 2, pp. 111–118, 2013.
[6]
B. F. Abdel-Wahab, E. Abdel-Latif, H. A. Mohamed, and G. E. A. Awad, “Design and synthesis of new 4-pyrazolin-3-yl-1,2,3-triazoles and 1,2,3-triazol-4-yl-pyrazolin-1-ylthiazoles as potential antimicrobial agents,” European Journal of Medicinal Chemistry, vol. 52, pp. 263–268, 2012.
[7]
B. F. Abdel-Wahab, R. E. Khidre, and G. E. A. Awad, “Regioselective synthesis and antimicrobial activities of some novel aryloxyacetic acid derivatives,” European Journal of Medicinal Chemistry, vol. 50, pp. 55–62, 2012.
[8]
B. F. Abdel-Wahab, H. A. Mohamed, A. A. Farahat, and K. M. Dawood, “Synthetic accesses to azolylthiazoles,” Heterocycles, vol. 83, no. 12, pp. 2731–2767, 2011.
[9]
R. E. Khidre, B. F. Abdel-Wahab, and F. A.-R. Badria, “New quinoline-based compounds for analgesic and anti-inflammatory evaluation,” Letters in Drug Design & Discovery, vol. 8, no. 7, pp. 640–648, 2011.
[10]
P. H. Richter, M. Elsner, and B. Vogt, “Preparation of benzo[b]furan-derived ketone amidinohydrazone class-III antiarrhythmic agents,” European Patent Applications, EP 778274, 1997.
[11]
L. Czollner, G. Szilagyi, J. Lango, and J. J. Janaky j., “Synthesis of new 1,5-diphenyl-3-1H-1,2,4-triazoles substituted with H-,alkyl, or carboxyl groups at C-3,” Archiv der Pharmazie, vol. 323, no. 4, pp. 225–227, 1990.
[12]
R. L. Shriner and J. Anderson, “Derivatives of coumaran. VI. Reduction of 2-acetobenzofuran and its derivatives,” Journal of the American Chemical Society, vol. 61, no. 10, pp. 2705–2708, 1939.
[13]
C. F. Koelsch, “Bromination of 3-acetocoumarin,” Journal of the American Chemical Society, vol. 72, no. 7, pp. 2993–2995, 1950.
[14]
V. S. H. Krishnan, K. S. Chowdary, and P. K. Dubey, “Studies in the syntheses of s-triazolo[4,3-a] quinoxalines,” Indian Journal of Chemistry B, vol. 38, no. 1, pp. 45–51, 1999.
[15]
C. Perez, M. Pauli, and P. Bazevque, “An antibiotic assay by the agar well diffusion method,” Acta Biologica et Medica Experimentalis, vol. 15, pp. 113–115, 1990.
[16]
A. C. Scott, “Laboratory control of antimicrobial therapy,” in Mackie and MacCartney Practical Medical Microbiology, J. G. Collee, J. P. Duguid, A. G. Fraser, and B. P. Marmion, Eds., vol. 2, pp. 161–181, Churchill Livingstone, Edinburgh, Scotland, 13th edition, 1989.
