Month 2018 Rapid Synthesis of 2-Alkanol-substituted Pyrrolo[2,3-b]quinoxalines from Propargylic Alcohols via Copper-free Sonogashira Coupling Reaction at Room Temperature Mahsa Fakharian, a Ali Keivanloo, a * and Mohammad Reza Nabid b a Faculty of Chemistry, Shahrood University of Technology, Shahrood 36199-95161, Iran b Department of Chemistry and Petroleum Faculty of Sciences, Shahid Beheshti University, Tehran, Iran * E-mail: akeivanloo@yahoo.com; keivanloo@shahroodut.ac.ir Received December 27, 2017 DOI 10.1002/jhet.3165 Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com). A practical and efficient procedure is established for the synthesis of 2-alkanol-substituted pyrrolo[2,3-b] quinoxalines by the reaction of N-alkyl-3-chloroquinoxaline-2-amines with propargylic alcohols. The reaction is carried out in the absence of any copper salt but in the presence of a catalytic amount of Pd(PPh 3 ) 2 Cl 2 at room temperature. The Sonogashira coupling reaction step in this procedure is fast, produc- ing clean products with high yields without contamination by unwanted homocoupling Glaser reaction prod- ucts. The synthesized pyrroloquinoxaline derivatives are also screened against the three bacterial strains Micrococcus luteus, pseudomonas aeruginosa, and Bacillus subtilis. J. Heterocyclic Chem., 00, 00 (2018). INTRODUCTION Palladium-catalyzed Sonogashira reactions of terminal alkynes with aryl or vinyl halides have received continuing attention over the last few decades. These reactions have provided an influential tool for the construction of C─C bonds. The coupling products of these reactions are ubiquitous structural motifs, which have been widely used in diverse areas such as natural products, pharmaceuticals and agrochemicals, dyes, sensors, electronics, polymers, guest–host constructs and natural products, and the synthesis of heterocyclic compounds [1]. The traditional Sonogashira coupling reaction employs palladium catalyst with copper co- catalyst and an amine, as a base, in the presence of phosphine ligand [2]. However, the addition of copper, although beneficial in terms of increasing the reactivity of the system, has added some shortcomings such as the undesirable formation of alkyne homocoupling products through a copper-mediated Hay/Glaser reaction [3]. Quinoxaline and its derivatives are an important class of benzoheterocycles displaying a broad spectrum of biological activities that have made them common structures in pharmacologically active compounds [4–6]. They can act as antibacterial [7], antibiotic [8], anti- inflammatory [9], antimalarial [10], antiprotozoal [11], and kinase inhibitors [12]. Some studies have been carried out in order to explore the antitumoral properties of quinoxaline compounds [13]. In addition, the quinoxaline derivatives have also found applications in efficient electron luminescent materials [14], organic semiconductors [15], and chemically controllable switches [16], and building blocks for the synthesis of anion receptors [17], cavitands [18], and dehydoannulenes [19]. Pyrroloquinoxalines have proved to be a very attractive scaffold for medicinal chemists in the recent past. These compounds have been extensively studied as bioactive compounds, and many of them are known to be biologically and medicinally useful molecules such as anti- HIV agents, antimalarial agents, antagonist agents, anticancer agents, and poly(ADP-ribose) polymerase 1 inhibitors [20]. Additionally, pyrroloquinoxalines are important intermediates for the construction of 5-HT3 receptor agonists [21] and inhibitors of Akt kinase [22]. A few studies have been reported for the synthesis of pyrrolo[2,3-b]quinoxalines. Cacchi and co-workers have reported the synthesis of 2,3-disubstituted pyrrolo[2,3-b] quinoxalines via aminopalladation reductive elimination by the reaction of 2-alkynyl-3-trifluoroacetamidoquinoxalines with aryl and vinyl halides or triflates [23]. This methodology, however, requires protecting and de- protecting steps for cyclization processes. A more straightforward method was reported in 2012, which involved the reaction of N-alkyl/aryl-substituted 3- chloroquinoxalin-2-amines with terminal alkynes in toluene under Pd/C─Cu catalysis [24]. Recently, several research © 2018 Wiley Periodicals, Inc.