Month 2014 Site- and Regioselectivity of the Reaction of Hydrazonoyl Chlorides with Perimidine Ketene Aminal. Antimicrobial Evaluation of the Products Thoraya A. Farghaly * and Huda K. Mahmoud Chemistry Department, Faculty of Science, University of Cairo, Giza 12613, Egypt *E-mail: thoraya-f@hotmail.com Received July 2, 2012 DOI 10.1002/jhet.1985 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). Reaction of hydrazonoyl chlorides with perimidine ketene aminal derivative in dioxane in the presence of triethylamine afforded either pyrrolo[1,2-a]perimidines or pyrazolyl perimidines depending on the type of hydrazonoyl chloride used. The reaction was found to be site- and regioselective according to the suggested mechanism. The structure of the newly synthesized compounds was established on the basis of spectral data and elemental analyses. In addition, the antimicrobial activity of the newly synthesized compounds was evaluated, and the results showed moderate activity of all compounds against the bacterial species. J. Heterocyclic Chem., 00, 00 (2014). INTRODUCTION Hydrazonoyl halides have been widely employed in the synthesis of heterocyclic derivatives [1–3]. Reaction of heterocyclic ketene aminal I, which are the cyclic enediamine analogues bearing secondary amino group(s), with nitrilimine II led to the formation of pyrazole III [4–6] (Fig. 1). Such results were considered to indicate that reaction of nitrilimine with ketene aminal is 1,3-cycloaddition condensation and stepwise reaction. In addition, perimidines and their deriva- tives have found a variety of applications ranging from dye- stuffs [7–11] to fluorescent molecular sensors [12]. Their biological activity as antimicrobial and antifungal agents, DNA-binding properties, and antitumor activity of various perimidines have been studied [8–10,13–15]. Also, they are found to have the thermochromic properties and EPR spectra of perimidine (diazaphenalenyl) radicals [12,14–16]. On the basis of the above findings and in continuation of our recent work in the utility of hydrazonoyl halides in synthesis of heterocyclic systems with remarkable biological importance [17–20], we report herein a study to investigate the site- and regioselectivity of the reaction of hydrazonoyl chlorides with perimidine ketene aminal. Also, antimicrobial activity of the newly synthesized compounds was evaluated. RESULTS AND DISCUSSION Barchet et al. [21] have reported that reaction of 1,8-diamino-naphthalene 1 with ethyl benzoylacetate 2 afforded diazocine derivative 4 (Scheme 1). How- ever, 2-(benzoylmethylene)-1,2-dihydro-perimidine (3) has been previously reported from the reaction of the corresponding diketone or 3,3-dichloro-acryloyl chloride with 1,8-diamino-naphthalene [22,23]. Recently [24], compound 3 was prepared by the reaction of 1,8-diamino-naphthalene 1 with ethyl benzoylacetate 2 under reflux for 6 h in xylene in the presence of P-toluenesulfonic acid (PTSA catalytic amount) in good yields (56–73%). In this work, we report here a new approach for the preparation of 3. Thus, fusion of 1 with ethyl benzoylacetate 2 without solvent for 15 min afforded compound 3 in very good yield (90%). The structure assignment of 3 was confirmed using X-ray crystallographic analysis [25] (Fig. 2 and Table 1). Reaction of compound 3 with N-aryl 2-oxo-2- phenylaminoethane-hydrazonoyl chlorides 5a–h in diox- ane solution under reflux in the presence of triethylamine as a basic catalyst can be afforded theoretically one or more of seven products 6–12, but this reaction afforded only a single product as evidenced by TLC (Scheme 2). It afforded products 7a–h. The structure of compounds 7 was established on the basis of spectral data and elemental analysis. The mass spectra of all derivatives 7a–h revealed in each case a molecular ion peak corresponding to elimi- nation of HCl and water molecules. 1 H NMR spectra of compounds 7 indicated the presence of two singlet signals at d 10.66–10.43 and 10.94–10.75 ppm for the two NH groups. In addition, the IR spectra revealed the presence of absorption bands at 3409–3188, 3200–3128, and 1659–1627 cm 1 characteristic for two NH and amidic CO groups. On the basis of the above data, products 8, 9, 11, and 12 were discarded. This result indicated that reaction of ketene aminal 3 with N-aryl 2-oxo-2- phenylaminoethane-hydrazonoyl chlorides 5a–h proceeded via intermediate 6 rather than 10. On the other hand, when the reaction of compound 3 was repeated with ethyl (N-arylhydrazono)-chloroacetates © 2014 HeteroCorporation