May-Jun 2007 Reaction of Phthalaldehydic Acid with Different Substituted Aniline as well as Hydrazine Derivatives 617 Sherine N. Khattab * , Seham Y. Hassan, Ayman El-Faham, Abdel Moneim M. El Massry and Adel Amer Department of Chemistry, Faculty of Science, University of Alexandria, Alexandria 21321, Egypt *Corresponding author: Phone: +20-12-3140924, e-mail address: ShKh2@link.net Received June 30, 2006 NH 2 X O H HO O Benzene/PTS X N O H N X HO O CHO OH O MeOH Ar-NH-NH 2 N N Ar O MeOH N NH O OH Ar Benzene/PTS N N N N H O DMF 6 4 1a 1b 17 15 14 Phthalaldehydic acid 1 is often represented as having two tautomeric forms 1a and 1b. The reaction of phthalaldehydic acid with different aryl amine and heterocyclic aryl hydrazine derivatives afforded different products depending on the reaction conditions such as solvent and temperature. J. Heterocyclic Chem., 44, 617 (2007). INTRODUCTION Phthalaldehydic acid 1 (namely, 2-formyl benzoic acid) and its derivatives represent an important member in aromatic hydrocarbon, chemistry for their wide usages in the preparation of 3-substituted phthalides [1- 4], heterobicyclic, tricyclic and tetracyclic systems [5-7], in addition to their broad spectrum of biological activities [8,9]. Reported among these activities, were anorexic, anti HIV, anti-inflammatory, analgesic or anti- allergic effects [8, 10-12]. Some have been used in therapy, in particular as nootropic agents [13]. Derivatives of phthalaldehydic acid 1 also show activities as hypnotics, sedatives, muscle relaxants [14], and the non-nucleosidic HIV-reverse transcriptase inhibitors [8,15]. Also related compounds are important herbicides for bud growth inhibition [16,17] and plant regulation [18]. The bi-functionality at ortho-position of this molecule gives it the ability for introducing hetero- cycle moieties. Several procedures have been applied in that aspect [5-7, 19a]. Our interest was focused on studying the reaction of phthalaldehydic acid with different aryl amine and hetero- cyclic aryl hydrazine derivatives in various solvents. The change of solvent had a great effect on the type of products obtained. The microbiological activity of the obtained compounds was also evaluated. RESULTS AND DISCUSSION Chemistry. Phthalaldehydic acid 1 is often represented as having an aldehyde and an acid group 1a. However, the tautomeric structure 3-hydroxy phthalide form 1b was suggested by Racine in 1886 [20]. On the basis of spectroscopic evidence, 1 exists in both the open 1a and ring form 1b depending upon the solvent and temperature [19]. At 500 MHz 1 is shown to exist in the two tautomeric forms 1a and 1b in CDCl 3 by exhibiting both the CH hydrogen at  6.65 ppm and CHO hydrogen at  10.58 ppm. Examination of the influence of acid such as p- toluenesulfonic acid on this equilibrium revealed a complete shift to the cyclic form 1b by displaying the CH at  6.01 ppm and no aldehydic hydrogen was detected.