Month 2017 Synthesis and Antioxidant Evaluation of Quinoxalino[2 0 ,3 0 :5,6][1,3,4] thiadiazino[2,3-b]quinazolin-15-ones: Derivatives of a Novel Ring System Mahsa Mousavi, Mehdi Bakavoli,* Ali Shiri, and Hossein Eshghi Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad 91775-1436, Iran * E-mail: mbakavoli@um.ac.ir; mbakavoli@yahoo.com Received July 31, 2017 DOI 10.1002/jhet.3078 Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com). Quinoxalino[2 0 ,3 0 :5,6][1,3,4]thiadiazino[2,3-b]quinazolin-15-one, a novel fused heterocyclic system, was synthesized from a one-pot condensation reaction of 2,3-dichloroquinoxaline and 3-amino-2-thioxo-2,3- dihydroquinazolin-4(1H)-one under mild condition. Derivatization was performed on treatment of the titled compound with several alkyl bromides. In vitro antioxidant activity of the synthesized compounds was evaluated. J. Heterocyclic Chem., 00, 00 (2017). INTRODUCTION Quinazolines and quinoxalines are pharmacologically important motifs possessing a wide range of biological and pharmaceutical activities. Quinoxalines are core units in a number of medicines with diverse properties like anticancer [1], antibacterial [2], antiviral [3], anti-HIV [4], and anti-inflammatory [5]. Moreover, scientists have already determined many therapeutic activities of quinazolines including antibacterial [6], antivirus [7], anti-cytotoxin [8], anticancer [9], antimalarial [10], anti- spasm [11], anti-inflammation [12], and others. From the synthetic point of view, treatment of 4-amino-1, 2,4-triazole-3-thiols with 2,3-dichloroquinoxalines in refluxing ethanol [13,14] or in the presence of sodium acetate under microwave irradiation [15] can afford the bioactive [1,2,4]triazolo-thiadiazino[5,6-b]quinoxalines. Thiadiazino[2,3-b]quinazolin-6-ones can also be obtained from hetrocyclization of substituted quinazolines [16] through a simple nucleophilic substitution reaction. A literature survey disclosed that there are few examples available on antioxidant evaluation of these bioactive skeletons [17,18]. Obviously, combination of two or more moieties into one can result in discovery of new bioactive molecules with improved biological activities. In this regard and in continuation of our previous research in this field [19,20], we wish to report the combination of quinazoline and quinoxaline moieties via formation of a thiadiazine core to afford a novel pentacyclic ring system. Antioxidant activity of the new system and its derivatives was evaluated. RESULTS AND DISCUSSION Chemistry. As illustrated in Scheme 1, a synthetic pathway was designed for preparation of the desired pentacyclic compound (3) and its derivatives 4(a–f). 2,3- Dichloroquinoxaline (1) was conveniently synthesized according to the previously published procedure [21]. 3-Amino-2-thioxo-2,3-dihydroquinazolin-4(1H )-one (2) was prepared from the reaction of methyl 2- isothiocyanatobenzoate with hydrazine hydrate in diethyl ether [22]. Reaction of compound 1 with 2, in a mixture of dimethylformamide (DMF)/K 2 CO 3 at 80°C, afforded the 13H,15H-quinoxalino [2 0 ,3 0 ,5,6] [1,3,4] thiadiazino[2,3-b]quinazolin-15-one (3), as the novel pentacyclic system. In 1 H NMR spectral analysis, emerging a D 2 O-exchangeable signal at δ = 7.96 ppm for NH group and a set of multiplet signals at δ = 6.74–8.02 ppm belonging to the aromatic C-H bonds properly implies to the formation of 3. Moreover, detecting a molecular ion peak at m/z = 319 (M + ), along with the complimentary results of micro analytical data, confirms the synthesis of the titled ring system. Further treatment of compound 3 with various alkylbromides in a mixture of DMF/ K 2 CO 3 at 80°C, furnished the substituted derivatives 4(a–f). Structural characterization of the newly synthesized derivatives 4(a–f) was fully accomplished through the experimental spectroscopic and elemental analysis data. As an example, 1 H NMR spectrum of compound 4a shows a triplet signal at δ = 1.36 ppm, a quartet signal at δ = 4.23 ppm, and multiplet signals at δ = 7.03–8.1 ppm © 2017 Wiley Periodicals, Inc.