Month 2018 Synthesis and Chemical Reactivity of the Novel 4-Hydroxy-6-methyl-2,5- dioxo-5,6-dihydro-2H-pyrano[3,2-c]quinoline-3-carboxaldehyde Magdy A. Ibrahim,* Hany M. Hassanin, Yassin Gabr, and Youssef A. Alnamer Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, 11711 Cairo, Egypt *E-mail: magdy_ahmed1977@yahoo.com Received May 26, 2018 DOI 10.1002/jhet.3353 Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com). Vilsmeier–Haack formylation of 3-(4-hydroxy-1-methy1-2-oxo-(1H)-quinolin-3-yl)-3-oxopropanoic acid (2) produced the novel 4-hydroxy-6-methyl-2,5-dioxo-5,6-dihydro-2H-pyrano[3,2-c]quinoline-3- carboxaldehyde (4). The chemical reactivity of carboxaldehyde 4 with a diversity of nitrogen nucleophilic reagents was studied, and a variety of products were obtained. Some 1,3,4-oxadiazolyl/1,3,4-thiadiazolyl/ benzothiazolyl linked pyrano[3,2-c]quinoline-2,5(6H)-dione were efficiently synthesized. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data. J. Heterocyclic Chem., 00, 00 (2018). INTRODUCTION Pyranoquinolinones constitute the parent ring structure of pyranoquinoline alkaloids, which occur in the plant family Rutaceae. These pyranoquinoline alkaloids have gained considerable importance due to their pharmaceutical activities like anti-coagulant [1], coronary constricting [2], and antifungal [3]. Pyrano[3,2-c] quinolinones were found to be active against certain immuno-reaction diseases, in particular against immediate hypersensitivity reactions (anaphylaxis) [4]. In turn, these pyranoquinolinones were used on wide range to obtain 4-hydroxyquinolin-2(1H)-ones and 3-acetyl-4- hydroxyquinolin-2(1H)-one derivatives [5,6]. Heating N-methylaniline with two equivalent diethylmalonate gave 4-hydroxy-6-methyl-2H-pyrano[3,2-c]quinoline-2,5 (6H)-dione (1) in one-pot double cyclocondensation process [7,8]. Warming pyranoquinoline-2,5(6H)- dione 1 in sodium hydroxide solution (1 N) at 40–50°C for 30 min afforded 3-(4-hydroxy-1-methy1-2-oxo-(1H)- quinolin-3-yl)-3-oxo-propanoic acid (2) (Scheme 1) [9]. Following our interest on the chemistry of pyrano[3,2-c] quinolinones [10–16], herein, we report the synthesis of the novel 4-hydroxy-6-methyl-2,5-dioxo-5,6-dihydro-2H- pyrano[3,2-c]quinoline-3-carboxaldehyde (4) as starting material and explored its chemical reactivity towards a variety of nitrogen nucleophilic reagents hoping to construct a novel series of substituted pyrano[3,2-c] quinoline-2,5(6H)-dione of potential biological activity. RESULTS AND DISCUSSION In the present work, the novel 4-hydroxy-6-methyl-2,5- dioxo-5,6-dihydro-2H-pyrano[3,2-c]quinoline-3-carboxald ehyde (4) was efficiently synthesized from Vilsmeier– Haack formylation of 3-(4-hydroxy-1-methy1-2-oxo- (1H)-quinolin-3-yl)-3-oxopropanoic acid (2) [17]. The reaction may proceed via formylation at the methylene carbon producing the non-isolable aldehyde 3, which underwent an intramolecular cyclodehydration leading to the novel aldehyde 4 (Scheme 1). Structure of carboxaldehyde 4 was deduced from its correct elemental analysis and spectral data. The IR spectrum of carboxaldehyde 4 showed characteristic absorption bands attributed to three carbonyl groups at 1745 (C═O α-pyrone ), 1685 (HC═O), and 1643 cm 1 (C═O quinolone ). The 1 H NMR spectrum of carboxaldehyde 4 showed characteristic singlet signal attributed to the aldehydic proton at δ 10.08, in addition to the aromatic benzo protons appeared at 7.60, 7.88, 8.00, and 8.21, as usual known pattern of quinolinone in which the chemical shift peaks are splitted into triplet, doublet, triplet, doublet in a consecutive order corresponding to protons at positions 9, 7, 8, and 10, respectively. The 13 C NMR spectrum showed four downfield signals at δ 161.0 (C-2 as C═O), 162.9 (C-5 as C═O), 173.7 (CH═O), and 184.9 (C-4 as C–OH). Furthermore, the mass spectrum of carboxaldehyde 4 revealed the molecular ion peak at m/z 271 and the base peak at m/z 243, assigned to (M + –CO). © 2018 Wiley Periodicals, Inc.