1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 z Catalysis Sustainable and Eco-Friendly Method for the Synthesis of Some Bioactive Derivatives of Biscoumarin and Pyrano [3,2-c]Chromene-3-Carbonitrile Using Taurine, as the Catalyst Nader Daneshvar, [a] Omid Goli-Jolodar, [b] Reyhaneh Karimi-Chayjani, [a] Mohaddeseh Safarpoor Nikoo Langarudi, [b] and Farhad Shirini* [a, b] Coumarin is a bio-organic compound which exists in some plants. Coumarin by its own or its derivatives are important compounds in the medicinal chemistry, agrochemistry fra- grance and food chemistry. Bis(4-hydroxycoumarin) derivatives are the most famous species of these compounds. Also, pyrano [3,2-c]chromene-3-carbonitrile derivatives which contain a moi- ety of 4-hydroxycoumarin have a wide range of biological activities. Taurine, the semi-essential β-amino acid in the organs of living creatures especially human and animals, is used as a green bio-organic catalyst to promote the formation of biscoumarin and pyrano[3,2-c]chromene-3-carbonitrile deriva- tives via a Knoevenagel-Micheal reaction in aqueous media. Using this method, the requested products are obtained in high yields during acceptable reaction times and the catalyst can be recycled with high efficiency. In fact, in this study, a bio- organic reagent is used as the catalyst to promote the synthesis of bioactive compounds in the greenest conditions possible. Introduction Heterocyclic compounds are common structures in bioactive and natural compounds thus new designing of new structures and methods are very important for their synthesis. [1] One of the most important of these compounds is coumarin or 2H- chromen-2-one that was isolated for the first time from tonka bean and sweet clover in 1820 by A. Vogel who at first mistook coumarin with benzoic acid. [2] Also at the same time, a French scientist, N. Guibourt, isolated this compound and realized that it is not benzoic acid then he named it coumarin. [3] In 1835, A. Guillemette, another French chemist, proved that Vogel and Guibourt both had isolated the same compound. [4] In 1868, and for the first time, W. Perkin reported the synthesis of coumarin in the laboratory. [5] Coumarins are a part of 1,2-benzopyrones which are found in the higher plants. [6] These compounds have many applica- tions such as the industries. [7] These compounds like the other types of benzopyrans stimulate the macrophages that lead to a decrease in the amount of extracellular protein and thus the edematous fluids. [8] Coumarin has also antifungal anti-tumor and anti-tubercular activities. [9–10] Though coumarin is not anticoagulant by its own, it changes into 4-hydroxycoumarin in a fungal metabolism (also is not anti-coagulant) and in the presence of natural formaldehyde converts into dicoumarol that is an anticoagu- lant. [11] [a] Dr. N. Daneshvar, R. Karimi-Chayjani, Prof. F. Shirini Department of Chemistry, University Campus 2, University of Guilan, Rasht, Iran E-mail: ndxdaneshvar@gmail.com [b] Dr. O. Goli-Jolodar, Dr. M. S. Nikoo Langarudi, Prof. F. Shirini Department of Chemistry, College of Sciences, University of Guilan, Rasht, 41335–19141, Iran Fax: + 98 131 3233262 E-mail: shirini@guilan.ac.ir Supporting information for this article is available on the WWW under https://doi.org/10.1002/slct.201803210 Table 1. Typical optimization of the conditions for the preparation of bis (4-hydroxycoumarin) derivatives. a Entry Catalyst (mmol) Solvent Temp. Time (min.) Yield (%) 1 - - 100 °C 150 Trace 2 0.24 - 100 °C 120 Trace 3 0.24 CHCl 3 Reflux 120 Trace 4 0.24 EtOH RT 120 20 b 5 0.24 EtOH Reflux 120 45 b 6 0.24 CH 3 CN Reflux 120 40 b 7 0.16 H 2 O RT 120 35 b 8 0.24 H 2 O RT 120 60 b 9 0.16 H 2 O 75 °C 120 75 b 10 0.16 H 2 O Reflux 110 84 c 11 0.20 H 2 O Reflux 45 94 c 12 0.24 H 2 O Reflux 45 91 c 13 0.20 H 2 O/EtOH (3:1) Reflux 65 88 c a Reaction conditions: 4-chlorobenzaldehyde (1.0 mmol), 4-hydroxycou- marin (2.0 mmol), solvent (3 mL) and required amount of the catalyst. b The reaction was not completed. c The yields are related to the isolated products. Full Papers DOI: 10.1002/slct.201803210 1562 ChemistrySelect 2019, 4, 1562–1566 © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim