Novel one-pot access to 2-formyl/acetyl-1-substituted pyrrolo[2,3- b ]quinoxalines under Sonogashira reaction conditions

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ORIGINAL PAPER

Novel one-pot access to 2-formyl/acetyl-1-substituted pyrrolo[2,3-b]quinoxalines under Sonogashira reaction conditions Ali Keivanloo • Mohammad Bakherad Mahrokh Rahmani • Amin Rahimi



Received: 18 February 2012 / Accepted: 22 November 2012 / Published online: 15 January 2013 Ó Springer-Verlag Wien 2013

Abstract A one-pot reaction of N-alkyl-3-chloroquinoxaline-2-amines with acetylenic alcohols in the presence of a Pd–Cu catalyst leads to the formation of 2-formyl/acetyl-N-substituted pyrrolo[2,3-b]quinoxalines in good to high yields. A possible mechanism for the conversion has also been proposed. Keywords Acetylenic alcohol  Pyrroloquinoxaline  Cross-coupling  Pd–Cu catalyst

Introduction Quinoxalines and their derivatives are a very important class of nitrogen-containing heterocycles showing various biological activities, and can act as antiviral, antibacterial, antibiotic, anti-inflammatory, and kinase inhibitors [1–7]. They are potential building blocks for the synthesis of organic semiconductors [8], electroluminescent materials [9], cavitands [10, 11], and dehydroannulenes [12]. Quinoxalines also serve as useful rigid subunits in macrocyclic receptors [13], for molecular recognition, and chemically controllable switches [14]. The Pd-catalyzed cross-coupling reactions of aryl halides or triflates with terminal alkynes, commonly referred to as Sonogashira reactions, are powerful, versatile, and popular tools for selective construction of new C–C bonds [15, 16]. This strategy with subsequent cyclization has been successfully utilized for the synthesis of carbocylic [17] and heterocyclic compounds alike [18–20]. A. Keivanloo (&)  M. Bakherad  M. Rahmani  A. Rahimi School of Chemistry, Shahrood University of Technology, Shahrood, Iran e-mail: [email protected]; [email protected]

We were intrigued by the prospect of applying this methodology to the synthesis of new heterocyclic compounds. Although a few methods have been reported [21, 22] for the synthesis of pyrrolo[2,3-b]quinoxalines, a survey of the literature showed that there are no references concerning the use of acetylenic alcohols as a starting material. In continuation of our recent studies [23–26] on the Pd-catalyzed reaction of acetylenes leading to new heterocyclic compounds, and in particular pyrrolo[2,3-b]quinoxalines [27], we decided to investigate the reaction of N-alkyl-3chloroquinoxaline-2-amines 1a–1h with acetylenic alcohols 2a, 2b in organic solvents.

Results and discussion When compounds 1a–1h were reacted with acetylenic alcohols 2a, 2b in dry morpholine in the presence of Pd(PPh3)2Cl2 and CuI at 70 °C, 2-formyl/acetyl-N-substituted pyrrolo[2,3-b]quinoxalines 3a–3l were obtained in moderate to good yields (Scheme 1). The reactions were carried out under an argon atmosphere, and solvents were degassed prior to use. We recently reported the synthesis of pyrrolo[2,3-b]quinoxaline-2-carbaldehydes from the reaction of N-alkyl-3chloroquinoxaline-2-amines with propargyl bromide [28]. In this article we report th