Synthesis of pyranopyrazoles with sodium lactate catalyst Section A-Research paper Eur. Chem. Bull. 2019, 8(6), 207-211 207 ONE POT SYNTHESIS OF PYRANOPYRAZOLES USING SODIUM LACTATE AS AN EFFICIENT CATALYST J. P. Sonar, [a] S. D. Pardeshi, [a] S. A. Dokhe, [a] G. M. Bhavar, [a] S. U. Tekale, [c] A. M. Zine [b] and S. N. Thore [c]* Keywords: catalyst; green synthesis; one pot; pyranopyrazole; sodium lactate. An efficient one pot synthesis of pyranopyrazoles has been achieved by the four-component condensation of hydrazine hydrate, ethyl acetoacetate, aldehydes and malononitrile using sodium lactate as a catalyst in aqueous ethanolic medium under reflux condition. The method is simple and green to afford pyranopyrazoles in a short time. It provides a new base catalyst that readily gives product from moderate to excellent yields. * Corresponding Authors Fax: +91 240 2367301 E-Mail: snthore@rediffmail.com [a] Department of Chemistry, Vinayakrao Patil Mahavidyalaya, Vaijapur, Aurangabad-423701, Maharashtra, India. [b] Department of Chemistry, Majalgaon Arts, Science and Commerce College, Majalgaon, Dist. Beed- 431131, Maharashtra, India. [c] Department of Chemistry, Deogiri College, Station Road, Aurangabad- 431 005, Maharashtra, India. Introduction Addition of three or more starting materials in one pot and their transformation to final product without isolation of intermediate provides a significant tool for organic synthesis. After the Strecker’s amino acid synthesis, many successful attempts were made for organic transformations such as the synthesis of pyranopyrazoles which is one of themost important heterocycles of great biological significance. Pyranopyrazolescaffolds are reported for various biological activities such as analgesic, anti-inflammatory, 1 anti- bacterial, 2 anti-microbial, 3 andantitumor activity. 4 Many methods are reported for the synthesis of pyranopyrazoles involving the use of three or four component condensation using CeCl3, 5 InCl3, 6 La(NO3)3, 7 ionic liquids such as [(CH2)4SO3HMIM][HSO4], 8 [H- NMP][MeSO3], 9 cetyltrimethylammonium chloride, 10 amino acids such as glycine, 11 L-tyrosine, 12 nano-particles such as CuI, 13 Fe3O4, 14 Fe3O4@SiO2, 15 1,3,5-triazine-2,4,6- triamine modified nano rice husk silica, 16 MgO, 17 ZnO, 18,19 and vitamin B1 on silica coated ferrite (Fe2O3@SiO2) nanoparticles. 20 Some heterogeneous catalysts like cerium (IV) carboxymethylcellulose, 21 acidic montmorillonite K-10 clay 22 are also documented for the one pot synthesis of pyranopyrazoles. Organic acids catalysing the synthesis of these heterocycles include citric acid, 23 and L-Proline. 24 Pyranopyrazoles can also be synthesized by using organic base catalysts like triethyl amine, 25-27 triethanol amine, 28 piperazine, piperidine, pyrrolidine and morpholine, 29 salts like ammonium chloride, 30 and sodium benzoate. 31 However many of these methods have several drawbacks such as costly catalysts, harsh reaction condition and poor yields. In addition, the problem of waste remains an environmental question. In the present work, we report sodium lactate as a new environmentally benign base catalyst for the four-component synthesis of pyranopyrazoles from hydrazine hydrate, ethyl acetoacetate, malononitrile and various aldehydes (Scheme1). Scheme 1. Four component pyranopyrazole synthesis. Experimental Melting points were recorded in open capillaries and are uncorrected. Structures of the synthesized products were assigned on the basis of spectral analysis. IR spectra were recorded on Shimadzu IR Affinity 1 spectrophotometer using KBr pellets. 1 H NMR spectra were recorded in DMSO-d6 on a BRUKER AVANCE II 400 MHz spectrometer and the chemical shifts were expressed in ppm relative to TMS. Mass spectra were recorded on a Macro mass spectrometer by Electron Spray technique. Sodium lactate (60 %) solution was purchased from Loba Chemicals Pvt. Ltd. Progress of the reaction was monitored on silica pre-coated TLC plates in 40 % ethyl acetate: n-hexane. General procedure A mixture of ethyl acetoacetate (1 mmol), hydrazine hydrate (1 mmol) and sodium actate solution (10 mol %) was mixed thoroughly. To it 40 % aqueous ethanol (5 mL) was added followed by aldehyde (1 mmol) and malononitrile (1mmol) and the resulting mixture was stirred for a while and then refluxed for appropriate time (Table 1). After completion of reaction, as monitored by TLC, the reaction mixture was allowed to cool and poured onto 50 g O N N H CN NH 2 + CH 2 (CN) 2 N 2 H 4. H 2 O O COOEt Sodium Lactate (10 mol%) Ethanol -water (4:6) (1) (2) (3) 5(a-l) Ar-CHO 4(a-l) Ar + +