TETRAHEDRON LETTERS Tetrahedron Letters 44 (2003) 3493–3496 Pergamon An efficient and facile synthesis of substituted cinnoline and benzo[h ]cinnoline derivatives Mohsen Abdel-Motaal Gomaa* Chemistry Department, Faculty of Science, Minia University, 61519 El -Minia, Egypt Received 4 February 2003; revised 27 February 2003; accepted 7 March 2003 Dedicated to Professor Dietrich Do ¨ pp on the occasion of his 65th birthday Abstract—New substituted 3-amino-5,7,8-trihalo-6-hydroxycinnoline-4-carbonitriles 7 and 8 and the 3-amino-5-chloro-6-hydroxy- benzo[h ]cinnoline-4-carbonitrile 9 were synthesized in two-steps starting from tetrahalo-1,4-benzoquinones or dichloro-1,4-naph- thoquinones, malononitrile and hydrazine. © 2003 Elsevier Science Ltd. All rights reserved. Cinnolines and their derivatives are widely used in pharmaceuticals and agrochemicals. Recently cinnoline derivatives have been patented as agrochemical and pharmaceutical drugs. In agrochemistry they act as microbicides, 1 pollen suppressants, 2–4 fungicides 5 and herbicides. 6,7 In the pharmaceutical field they are mainly patented as bactericides. 8–11 Hence the chemistry of cinnolines has received much attention and many methods for their synthesis have been developed. Cinnolines can be prepared by cyclization of monosub- stituted or 1,2-disubstituted benzenes. The second type of synthesis is the more general and is exemplified by the preparation of 3,4-disubstituted cinnolines (R 1 = aryl or alkyl) from diazotized 2-vinylaniline derivatives (Scheme 1). 12 The other type of synthesis is exemplified by acid catalyzed cyclization of benzil monophenylhydrazone (Scheme 2). 12 In 1997, Yoshida and co-workers reported a novel one-step synthesis of 3-aryl-4-cyanocinnolines from p - substituted acetophenone methylphenylhydrazones and tetracyanoethylene (TCNE). The reaction was per- formed in MeCN at 25°C for 5 days; the rationale of this novel reaction was not clarified. 13 This work describes the synthesis of polysubstituted cinnolines and benzo[h ]cinnoline in two steps starting from di- or tetrahalogenated p -quinones. Quinones 1–3 were added to 2–3 mmol equiv. of malo- nonitrile in boiling ethanol in the presence of traces of triethylamine to give the corresponding substitution products, the ylidenemalononitriles 4–6 in good yield 61–89% (Scheme 3) which were purified by recrystal- lization or by preparative thin-layer chromatography. The structures of products 4–6 were assigned on the basis of their spectral data. 14 IR spectra showed sharp Scheme 1. Keywords : benzoquinone; naphthoquinone; cyclohexadiene; cinnoline; benzo[h ]cinnoline. * Fax: +20-86-342601; e-mail: mohsengomaa@link.net 0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0040-4039(03)00686-5