PAPER 436 Solvent-Free Synthesis of 6-Arylbenzimidazo[1,2-c]quinazolines under Microwave Irradiation Solvent-Free Synthesis of 6-Arylbenzimidazo[1,2-c]quinazolines Hernán Pessoa-Mahana,* a C. David Pessoa-Mahana, b Ricardo Salazar, a Jaime A. Valderrama, c Edmundo Saez, b Ramiro Araya-Maturana a a Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233, Santiago 1, Chile Fax +56(2)6782868; E-mail: hpessoa@ciq.uchile.cl b Departamento de Farmacia, Pontificia Universidad Católica de Chile, Casilla 306, Santiago, Chile c Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago, Chile Received 16 October 2003; revised 9 December 2003 SYNTHESIS 2004, No. 3, pp 0436–0440xx.xx.2004 Advanced online publication: 26.01.2004 DOI: 10.1055/s-2004-815924; Art ID: M04503SS.pdf © Georg Thieme Verlag Stuttgart · New York Abstract: The syntheses of 2-(2-nitrophenyl)-1-benzoyl-1H-benz- imidazole derivatives 5–9 and their reduction to the corresponding 2-benzimidazoylbenzamides 10–13 are described. Compounds 10– 13 were cleanly and efficiently converted to the corresponding 6- arylbenzimidazo[1,2-c]quinazolines 17–20 by microwave activa- tion using SiO 2 -MnO 2 as solid inorganic support. Key words: benzimidazoles, heterocyclization, microwaves, benz- imidazoquinazolines, solvent-free reactions The synthesis of compounds belonging to benzimida- zo[1,2-c]quinazoline series 1,2 constitutes an important area of research due to their interesting DNA binding properties. 3–5 In a previous paper we reported that the re- action of 1-acetyl-2-(2-nitrophenyl)benzimidazole (1) with iron in acetic acid–ethanol–water afforded a mixture of benzimidazoquinazoline 2 and 2-arylbenzimidazole 3 (Figure 1). 6 The formation of compounds 2 and 3 was in- terpreted assuming the participation of an dihydrobenzim- idazoquinazoline intermediate. In continuation of our work, we wish to report a novel and interesting approach for the synthesis of 6-arylbenzimida- zo[1,2-c]quinazolines 17–20 as sole products, using mi- crowave activation on the precursor N-[2-(1H- benzimidazol-2-yl)phenyl]benzamides 10–13. Com- pounds 10–13 were obtained from the corresponding 5–9 benzoylbenzimidazole derivatives under reductive condi- tions. The starting benzimidazole 4 required for the study was prepared from o-nitrobenzaldehyde by using our previ- ously reported procedure. 6 Compound 4 was reacted with a range of 4-substituted benzoyl chlorides at 0 °C in THF using triethylamine for trapping the hydrogen chloride (Equation 1). This treatment provided the corresponding amides 5–9 in good yields (Table 1). The numbering of the general formulas of compounds 5–9, 10–13, and 17– 20 in Equations 1–3 does not follow IUPAC rules, but makes interpretation of NMR spectra easier. Equation 1 Amides 5–9 were subjected to reduction with iron in ace- tic acid–ethanol–water solution at 45–50 °C (Equation 2). This afforded the corresponding rearranged products 10– Table 1 1-Benzoylbenzoimidazoles 5–9 Prepared by Reaction of 4 with Benzoyl Chlorides Product R Yield (%) 5 H 76 6 Cl 92 7 F 91 8 MeO 86 9 NO 2 77 N N H O 2 N N N NO 2 R O 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 4 5-9 COCl R Figure 1 Compounds 1–3 N N N H N N N CH 3 N Ac O 2 N NHAc 1 2 3