Send Orders for Reprints to reprints@benthamscience.net Current Microwave Chemistry, 2014, 1, 41-46 41 Microwave Assisted Synthesis of New Pyrrolopyridazine Derivatives with Acetophenone Skeleton. Part V Gheorghita Zbancioc 1 , Costel Moldoveanu 1 , Ana Maria Zbancioc 2 and Ionel I. Mangalagiu 1 * 1 "Al. I. Cuza” University of Iasi, Faculty of Chemistry, Bd. Carol 11, 700506 Iasi, Romania; 2 University of Medicine and Pharmacy “Grigore T. Popa” Iasi, Str. Universitatii 16, 700115 Iasi, Romania Abstract: A comprehensive comparative study, microwave (MW) versus conventional thermal heating (TH), for synthe- sis of fused pyrrolopyridazine derivatives with dihydroxyacetophenone is described. The reaction pathway is efficient and straight applicable, involving a Huisgen [3 + 2] dipolar cycloaddition of pyridazinium ylides to activated Z-alkynes sym- metrical or unsymmetrical substituted. Under MW irradiation the consumed energy decreases considerably, the amount of used solvent also decreases (at least three-fold less comparative with conventional TH), and the reaction conditions are milder. Consequently these reactions could be considered environmentally friendly. It is also to be pointed out that under MW irradiation the yields are higher and the reaction time decreased substantially (from hours to minutes) comparative with conventional TH. A feasible explication for the MW efficiency in Huisgen [3+2] dipolar cycloaddition reactions was furnished. The regiochemistry studies indicate that the reactions occur highly regiospecific (a single regioisomer being formed), under charge control. Keywords: Environmentally friendly methods, cycloaddition, microwave, pyridazine, dihydroxyacetophenone, pyrrolopyridaz- ine, regiochemistry, regiospecific, ylides, Z-alkynes. INTRODUCTION Within the past decade, microwave (MW) assisted reac- tions have gained popularity as a widely accepted method in organic synthesis [1-7]. More than 200.000 papers and 250.000 patents have been published in the area of MW as- sisted reactions since the first reports on the use of MW heat- ing to accelerate organic chemical transformations by the groups of Gedye and Giguere/Majetich in 1986. During the time, MW irradiation became in organic chemistry a powerful tool offering a versatile and facile pathway in a large variety of syntheses. Among the numer- ous advantages presented by MW, several are of particular interest: rapid energy transfer, faster reactions and substan- tial decreases of reaction time, less energy consumer, less byproducts, improved yields and high purity of the com- pounds, lower costs and simplicity in handling and process- ing [1-11]. In recent years, azaheterocycles and especially pyridazine derivatives have been reported to display a large variety of applications in the fields of medicinal chemistry (these in- cluding antimicrobials, anticancer, anti-HIV, etc.) [12-16], opto-electronics (fluorescent materials, organic semiconduc- tors, etc.) [17, 18], agriculture (herbicides or growth factors for plants) [19, 20], etc. On the other hand, synthesis of func- tionalized acetophenone derivatives is currently experiencing a renewed interest as highly valuable compounds for medici- nal chemistry [21-23], etc. *Address correspondence to this author at the "Al. I. Cuza” University of Iasi, Faculty of Chemistry, Bd. Carol 11, 700506 Iasi, Romania; Tel: +40 +232201343; Fax: +40+ 232 201313; E-mail: ionelm@uaic.ro A simple and flexible method to generate fused azahet- erocycles derivatives, involves a Huisgen [3+2] cycloaddi- tion of cycloimmonium ylides to various symmetric and non- symmetric dipolarophiles (activated alkenes and alkynes) [24-29]. In continuing our efforts of using MW irradiation in or- ganic chemistry [17, 21, 23-25, 30-34], and in order to syn- thetise new fused azaheterocycles with acetophenone skele- ton, we wish to report herein an efficient environmentally friendly method of synthesis of fused azaheterocycles with dihydroxyacetophenone skeleton under MW irradiation. MATERIALS AND METHODS All the reagents and solvents were purchased from com- mercial sources and used without further purification. Melt- ing points were recorded on a MEL-TEMP II apparatus in open capillary tubes and are uncorrected. Infrared (IR) data were recorded as films on potassium bromide (KBr) pellets on a FT-IR Shimadzu Prestige 8400s spectrophotometer. The NMR spectra were recorded on a Bruker Avance 3 spectrometer operating at 500 MHz for 1 H and 125 MHz for 13 C. The following abbreviations were used to designate chemical shift multiplicities: s = singlet, d = doublet, t = triplet, m = multiplet. Chemical shifts were reported in delta () units, part per million (ppm) and coupling constants (J) in Hz. The microanalyses were in satisfactory agreement with the calculated values: C, ±0.15; H, ±0.10; N, ±0.30. Flash chromatography was performed with Aldrich 230-400 mesh silica gel. Analytical thin-layer chromatography was performed with commercial silica gel plates 60 F 254 (Merck) and visualized with UV light. For the microwave irradiation we used a 800 W STAR SYSTEM-2 monomode reactor (CEM Corporation). The system is comprised of two 2213-3364/14 $58.00+.00 © 2014 Bentham Science Publishers