Design and Synthesis of Fused and Spiro Pyrazole Derivatives
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esign and Synthesis of Fused and Spiro Pyrazole Derivatives M. G. Assya,*, W. Shehtaa, and E. F. Abdelrahmana a
Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, 44519 Egypt *e-mail: [email protected] Received January 19, 2020; revised January 25, 2020; accepted January 29, 2020
Abstract—Condensation of 5-methyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one with p-hydroxybenzaldehyde in alcoholic sodium hydroxide yielded (Z)-4-(4-hydroxybenzylidene)-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol3-one which was treated with acetylacetone, hydrazine hydrate, ethyl cyanoacetate, and ethyl acetoacetate to afford pyranopyrazole, pyrazolopyrazole, pyrazolopyridine, and 6-aminopyrazolopyridine derivatives, respectively. 5-Methyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one was also reacted at the enamino carbon atom with 2,4-dichlorobenzoyl isothiocyanate, thiosemicarbazide, and hydrazine hydrate to produce pyrazolooxazine, pyrazolopyrazole, and spiro[pyrazole-3,3′-pyrazolo[3,4-c]pyrazole] derivatives. Keywords: pyranopyrazole, pyrazolopyrazole, pyrazolopyridine, pyrazolooxazine
DOI: 10.1134/S1070428020070192 INTRODUCTION Pyrazolone derivatives constitute a significant class of heterocyclic compounds found in many drugs and synthetic products [1, 2]. These compounds exhibits analgesic [3], antitubercular [4], antifungal, antibacterial [5], anti-inflammatory [6], antioxidant, and antitumor activities [7]. A survey of literature on antimicrobial studies revealed that the presence of pyrazole ring in any molecule plays a significant role in improving the activity [8–11]. This gave an extraordinary impulse to look forward potential pharmacologically active drugs carrying pyrazole substituents. On the basis of this view, our study reports on the synthesis of some new fused pyrazole derivatives such as pyranopyrazole, pyrazolopyrazole, pyrazolopyridine, and pyrazolooxazine. RESULTS AND DISCUSSION 5-Methyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one (3) was synthesized by the reaction of ethyl acetoacetate with phenylhydrazine. The condensation of 3 with p-hydroxybenzaldehyde in basic medium afforded pyrazolone 4 due to activation of the 5-methyl group via protonation of endocyclic nitrogen atom. The reaction of 3 with the same aldehyde in acidic medium yielded pyrazolone 5 [12, 13] (Scheme 1). The IR spectrum of 4 contained absorption bands at 3178 and 1654 cm–1 due to NH and C=O groups. The 1H NMR of 4 showed singlets at δ 10.83 and 10.59 ppm for OH
and NH protons. Also, two doublets were observed at δ 6.89–7.08 ppm with J = 8 Hz, which were assigned to the cis-CH=CH protons. The 13C NMR spectrum showed a signal at δC 163.06 ppm for the carbonyl carbon. The mass spectrum of 4 showed the molecular ion peak at m/z 278.32 and the base peak at m/z 77. The IR spectrum of 5 displayed OH stretching band at 3411 cm –1 and carbonyl band at 1650 cm –1 . Its 1 H NMR spectrum showed singlets at δ 10.84 and 2.49 ppm corresponding to the OH and CH3 protons. In the 13CNMR spectrum of 5, the carbonyl carbon nucleus resonated at δ C 163.06 pp
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