Synthesis and Antimicrobial Activity of New 3 H -Chromeno[2,3- d ]pyrimidine Derivatives
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ynthesis and Antimicrobial Activity of New 3H-Chromeno[2,3-d]pyrimidine Derivatives A. H. Moustafaa,*, S. M. Mohammeda, E. A. Abd El-Salama, and H. A. El-Sayeda a
Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, 44519 Egypt *e-mail: [email protected] Received June 12, 2020; revised July 30, 2020; accepted August 14, 2020
Abstract—Some new fused chromenopyrimidines have been synthesized and evaluated for their antimicrobial activity based on the precursor 4H-chromene-3-carbonitrile. Heterocyclization of 4H-chromene-3-carbonitrile derivative results in pyrimidine, pyrimidinone, pyrimidinedithione, and iminopyrimidine derivatives. Acetylated N-aminochromeno[2,3-d]pyrimidine derivative has been introduced into SN2/heterocyclization reaction with formation of 2-substituted pyrimidinone derivatives. 4H-Chromene-3-carbonitrile propargylation followed by the “click reaction” has resulted in chromene linked 1,2,3-triazole. Some newly synthesized compounds demonstrate significant antimicrobial activity. Keywords: chromene, pyrimidine, intramolecular cyclization, 1,2,3-triazole, antimicrobial activity
DOI: 10.1134/S1070363220080277 INTRODUCTION Many natural chromene derivatives exhibit diverse pharmacological properties including pronounced antibacterial activity [1–5]. Some compounds that included 4H-chromene scaffold acted as fluorescence markers [6–8], which makes those particularly valuable in synthesis of bioactive products including such nitrogen containing heterocyclic compounds as pyrimidines and triazoles that demonstrate, among variable others, antibacterial [9], antimicrobial [10] and antiviral [11] activities. RESULTS AND DISCUSSION 4H-Сhromene-3-carbonitrile 1 was synthesized by heating a mixture of resorcinol with 4-chlorobenzaldehyde
and malononitrile in presence of piperidine as a catalyst in absolute ethanol (Scheme 1). Interaction of 1 with an excess of triethyl orthoformate in acetic anhydride led to the intermediate 2. The latter compound reacted with hydrazine hydrate to afford 4-imino-4,5-dihydro-3H-chromeno[2,3-d]pyrimidin8-ol (3), which was acetylated with acetic anhydride to give acetamide derivative 4 (Scheme 2). Formation of compound 2 was confirmed by its IR spectrum that revealed absence of NH2 bands and presence of the carbonyl band at 1740 cm–1. In 1H NMR spectrum of compound 2 the proton N–CHO signal was measured at 12.53 ppm. IR spectrum of compound 3 demonstrated NH2 band at 3210 cm–1 and no band of C≡N. In 1H NMR spectrum of compound 4 the methyl CH3–C=O
Scheme 1. Synthesis of 2-Amino-4-aryl-7-hydroxy-4H-chromene-3-carbonitriles.
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SYNTHESIS AND ANTIMICROBIAL ACTIVITY
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Scheme 2. Synthesis of 3H-chromeno[2,3-d]pyrimidine derivatives.
and lactam NH–C=O protons signals were recorded at 2.28 and 12.51 ppm, respectively. Refluxing of the initial compound 1 with carbon disulphide and chloroacetyl chloride led to dithione pyrimidine derivative 5 and 2-chloromethyl pyrimidinone 6, respectively (Scheme 2). Their structures were confirmed by IR and 1H NMR
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