A Convenient Synthesis of 5- and 8- Nitroquinazoline-2,4-dione Derivatives D. Aziane [a,b], M. Soukri [a,c], A. El Hakmaoui [a], S. Lazar [a], E. M. Essassi [b], G. Guillaumet * [c] and M. Akssira * [a] [a] Laboratoire de Chimie Bioorganique et Analytique, FST-Université Hassan II - Mohammedia, BP 146, 20650 Mohammedia, Maroc [b] Laboratoire de Chimie Hétérocyclique, FS-Université Mohamed V, Rabat, Maroc [c] Institut de Chimie Organique et Analytique, UMR CNRS 6005, Université d’Orléans, BP 6759, 45067 Orléans cedex 2, France Received April 9, 2001 3-Nitrophthalic acid 1 was converted selectively to the two regioisomeric monoesters 2 and 3, which were subsequently transformed via Curtius rearrangement to the corresponding 5- and 8-nitroquinazoline-2,4- diones 4 and 5, respectively. The reduction of the nitro group produced 5- and 8-aminoquinazoline-2,4- diones 6 and 7, respectively, in good yields. The condensation of compounds 7b and 7c with carbon disulfide in pyridine afforded tricyclic derivatives 9, which are analogues of the HIV-1 reverse transcriptase inhibitor 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one (TIBO). J. Heterocyclic Chem., 39, 271 (2002). Quinazolines are important medicinal agents and pharmacological tools that have been applied to a variety of therapeutic areas [1]. In particular, quinazoline-2,4- diones form an interesting class of heterocycles with broad synthetic applications in medicinal chemistry as starting materials for biologically active compounds [2]. Additionally, some quinazoline-2,4-diones derivatives have been reported to exhibit anticonvulsant activity against electroshock [3], to possess sedative and hypo- tensive properties [4], and also to cause vasodilatation [5] in animals. They are also characterized as phospho- diesterase (PDE) inhibitors with antiinflammatory activity in vivo [6], and more recently as potent fibrinogen receptor antagonists [7]. Thus, several synthetic pathways for the preparation of these heterocyclic compounds have been described [8], most of them start from derivatives of anthranilic acid. We have also shown [9] previously that the phthalic anhydride can be a versatile starting material for the synthesis of quinazoline-2,4-diones. In the present work, we describe a convenient and regioselective synthesis of the two regioisomeric 5- and 8-nitroquinazoline-2,4- diones 4 and 5 starting from commercially available 3-nitrophthalic acid 1. In fact, the key intermediates, Mar-Apr 2002 271