One-pot synthesis of 2-substituted 4H-3,1-benzoxazin-4-one derivatives under mild conditions using iminium cation from cyanuric chloride/dimethylformamide as a cyclizing agent
© Shariat et al.; licensee Chemistry Central Ltd. 2013
Received: 27 January 2013
Accepted: 18 March 2013
Published: 27 March 2013
The derivatives of 2-substituted 4H-3,1-benzoxazin-4-one belong to a significant category of heterocyclic compounds, which have shown a wide spectrum of medical and industrial applications.
A new and effective one-pot method for the synthesis of 2-substituted 4H-3,1-benzoxazin-4-one derivatives is described in this paper. By using the iminium cation from a mixture of cyanuric chloride and dimethylformamide as a cyclizing agent, a series of 2-substituted 4H-3,1-benzoxazin-4-one derivatives was synthesized in high yield under mild conditions and simple workup.
The iminium cation from a mixture of cyanuric chloride and N,N-dimethylformamide is an effective cyclizing agent for the room temperature one-pot synthesis of 2-substituted 4H-3,1-benzoxazin-4-one derivatives in high yields through a cyclodehydration reaction. Furthermore, the method was performed under mild conditions characterized by simplified pathways and workup, minimized energy, and fewer reaction steps, compared with the previous methods. The proposed method, which is a simpler alternative than the published methods, is applicable for the synthesis of other 2-substituted 4H-3,1-benzoxazin-4-one derivatives.
The derivatives of 2-substituted 4H-3,1-benzoxazin-4-one belong to a significant category of heterocyclic compounds that have shown a wide spectrum of medical and industrial applications. Some of them are used as an elastase inhibitor [1–3], anti-neoplastic agent, enzyme inhibitor , protease inhibitor, and fungicidal . In addition, they are used as a starting material for the preparation of 2,3-disubstituted 4(3H)-quinazolinone derivatives, which are known to have medicinal properties.
Optimizing the previous methods or designing new routes according to the principles of green chemistry for the synthesis and workup of 4H-3,1-benzoxazin-4-one derivatives are essential given the increasing application of this group of fused heterocyclic compounds.
Green chemistry provides an interesting approach for the preparation and application of chemical compounds. This approach is presented as a set of twelve principles [13, 14]. From the standpoint of green chemistry, chemists should establish a group of parameters for the ideal chemical synthesis design . A simple pathway and workup, minimized energy, higher yield, lower reagent loss, and fewer reaction steps are among the important parameters in a green chemical pathway. Following this approach, the proposed method for the synthesis of 2-substituted-4H-3,1-benzoxazin-4-one derivatives under mild conditions is an attempt to design a greener reaction.
In this research, a series of 2-substituted-4H-3,1-benzoxazin-4-one derivatives was synthesized using the iminium cation from a mixture of cyanuric chloride and dimethylformamide as an effective cyclizing agent as well as the solvent as a catalyst, without the traditional heating or microwave irradiation.
Cyanuric chloride is a commercially available reagent that is commonly used by organic chemists. Numerous articles and reviews have reported various applications of cyanuric chloride in ordinary organic reactions. One of the common applications of cyanuric chloride is the conversion of carboxyl groups into active esters for the preparation of nitrile, acyl azide, ester, amide, and acyl chloride from carboxylic acid derivatives [15, 16]. Furthermore, cyanuric chloride is used to prepare alkyl chlorides from alcohols , amides from ketoximes , nitrile from aldoxime , isonitrile from formamide , disulfide from dimethylsulfoxide , and cyclic lactones . In addition, the mixture of cyanuric chloride and dimethylformamide is used as a new organic reagent for the conversion of a broad sequence of secondary and primary alcohols to the corresponding alkyl chlorides and iodides [23, 24]. Various ketoximes prepared from the related ketones undergo the Beckmann rearrangement upon reaction with a mixture of cyanuric chloride/dimethylformamide . Moreover, the mixture of cyanuric chloride/dimethylformamide is used for the conversion of β-amino alcohols to the corresponding chlorides .
Results and discussions
The positive charge, size, and planar skeleton of the iminium cation make it an easy target for the OH group, which could result in the production of activated ester in a short time with good yield. However, the stability of benzoxazin-4-one ring provides an appropriate condition for a mild cyclodehydration reaction as the result of the cyclization reaction and the role of dimethylformamide as a good living group in the cyclizing step.
In published papers and reviews, acetic anhydride is commonly used as a cyclizing agent for the synthesis of benzoxazin-4-one derivatives because it can be used in simpler conditions compared with the other known cyclizing agents. However, the use of this compound as a cyclizing agent has several disadvantages. For example, acetic anhydride normally works as a cyclizing agent through traditional heating or microwave irradiation. In addition, this compound is listed as a United State Drug Enforcement Administration (U. S. DEA List II precursor), and restricted in numerous countries. On the contrary, the iminium cation can be a good cyclizing agent in cyclodehydration reactions because it can be used at room temperature with commercially available cyanuric chloride and dimethylformamide.
The iminium cation obtained from a mixture of cyanuric chloride and N,N-dimethylformamide is an effective reagent for the room temperature one-pot synthesis of 2-substituted 4H-3,1-benzoxazin-4-one derivatives in high yields through cyclodehydration. The proposed method can be performed under mild conditions, with simplified pathways and workup, minimized energy, and fewer reaction steps, compared with the reported methods. Moreover, this method is applicable for the synthesis of other 2-substituted 4H-3,1-benzoxazin-4-one derivatives.
The structures of products 2a-i were confirmed by analysis using spectral data (1H-NMR, 13C-NMR, FT-IR and HRMS). All spectral data and spectrum are represented in Additional file 1. The FT-IR spectra were measured by using KBr pellets. The NMR spectra were recorded on 600 MHz spectrometer and chemical shifts are reported relative to TMS. The mass spectra were recorded using a TOF-Q instrument was operated in positive ion mode. The melting points were measured in open capillary tubes without correction. All commercial reagents were synthesis grade and were used as received without additional purification. The procedures for preparation and purification of reported products are the same.
Preparation of 2-phenyl-4H-3,1-benzoxazin-4-one (2a)
Benzoyl chloride (0.349 ml, 3 mmol) was added to a stirred solution of anthranilic acid (0.411 g, 3 mmol) and triethylamine (0.460 mL, 3.3 mmol) in chloroform (10 mL). The mixture was stirred at room temperature for 2 hours, then, a yellow light colour solution of Cyanuric chloride (0.553 g, 3 mmol) in DMF (5 mL) was added to the stirred mixture. After 4 hours, the solvent was evaporated in vacuum and the residual was poured into distilled water (20 mL) and ice. Then, the filtrated solids were washed with a saturated solution of NaHCO3 (10 mL, two times) and distilled water (two times, 25 mL each). The white precipitate was recrystallized from a 1:1 diethyl ether/ethanol mixture to give the fine needle crystal of 2a (0.578 gr, yield: 86%, mp: 123–124°C). IR (KBr): vmax/cm−1 1764, 1622, 1603, 1541, 1266, 1077. 1H-NMR (DMSO): δ ppm 8.20 (ddd, J = 7.2, 1.2, 0.6 Hz, 2H), 8.15 (ddd, J = 7.2, 1.2, 0.6 Hz 1H), 7.95 (tdd, J = 8.4, 7.2, 1.2 Hz, 1H), 7.59-7.73 (m, 5H). 13C-NMR (DMSO): 159.4, 156.8, 146.7, 137.3, 133.2, 130.5, 129.5, 129.1, 128.5, 128.3, 127.4, 117.4. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C14H10NO2 (224.0707); Found 224.0706.
Preparation of 2-(3,5-dinitrophenyl)-4H-3,1-benzoxazin-4-one (2b)
3,5-dinitrobenzoyl chloride (0.692 gr, 3 mmol) is used for preparation of 2b using the same procedure as 2a. The sea-urchin shaped crystal was prepared (0.839 gr, yield: 89%, mp: 236–238°C) from crystallization of the gray powder of 2b in 1:1 ether/ethanol. IR (KBr): vmax/cm−1 1776, 1622, 1603, 1541, 1473, 1266, 1077. 1H-NMR (DMSO): δ ppm 9.13 (dd, J = 1.8, 1.2 Hz, 2H), 9.04 (dd, J = 1.4, 1.2 Hz, 1H), 8.23 (ddd, J = 7.8, 1.2, 0.6 Hz, 1H), 8.02 (ddd, J =8.4, 7.8,1.2 Hz, 1H), 7.90 (ddd, J =7.8, 1.2, 0.6 Hz, 1H) and 7.73 (ddd, J = 8.4, 7.8,1.2 Hz, 1H). 13C-NMR (DMSO): 158.6, 153.6, 149.1, 145.9, 137.7, 133.7, 130.2, 128.8, 127.9, 127.6, 122.1, 117.8. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C14H8N3O6 (314.0408); Found 314.0390.
Preparation of 2-(furan-2-yl)-4H-3,1-benzoxazin-4-one (2c)
For preparation of 2c, 2-Furoyl chloride was used by using the same procedure, as 2a. The product was isolated as a white crystalline solid (0.500 gr, yield: 78%, mp 106–108°C) . IR (KBr): vmax/cm−1 1753, 1683, 1604, 1557, 1256, 1011. 1H-NMR (DMSO, δ ppm): 8.12 (ddd, J = 7.8, 1.2, 0.6 Hz, 1H), 8.09 (dd, J = 0.6, 1.8 Hz, 1H), 7.93 (ddd, J = 0.6, 1.2, 7.8 Hz, 1H), 7.66 (ddd, J = 7.8, 1.2, 7.8 Hz, 1 H), 7.59 (ddd, J = 7.8, 1.2, 7.8 Hz, 1H), 7.45 (dd, J = 3.6, 0.6 Hz, 1H), 6.80 (dd, J = 1.8, 3.6 Hz, 1H). 13C-NMR (DMSO): 158.7, 149.6, 148.4, 146.7, 144.6, 137.4, 128.8, 128.6, 127.1, 117.5, 113.4. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C12H8NO3 (214.0499); Found 214.0497.
Preparation of 2-(furan-3-yl)-4H-3,1-benzoxazin-4-one (2d)
3-Furoyl chloride was used for preparation 2d and the product was isolated as a white crystalline solid (0.506 gr, yield: 79%, mp 89–91°C). IR (KBr): vmax/cm−1 1764, 1644, 1632, 1603, 1258, 1069. 1H-NMR (DMSO, δ ppm): 8.55 (dd, J = 1.8, 0.6 Hz, 1H), 8.16 (ddd, J = 7.8, 1.2, 0.6 Hz, 1H), 7.92 (ddd, J = 7.8, 1.2, 0.6 Hz, 1H), 7.89 (dd, J = 1.8, 1.2 Hz, 1H), 7.64 (ddd, J = 7.8, 1.2, 0.6 Hz, 1H), 7.59 (ddd, J = 7.4, 7.2, 1.2 Hz, 1 H), 7.00 (dd, J = 1.8, 0.6 Hz, 1 H). 13C-NMR (DMSO): 159.2, 153.5, 147.4, 146.7, 145.9, 137.4, 128.8, 128.6, 126.93, 119.8, 117.3, 109.2. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C12H8NO3 (214.0499); Found 214.0478.
Preparation of 2-(N-phthaloylmethyl)-4H-3,1-benzoxazin-4-one (2e)
Benzoxazinone 2e was prepared from phthalimidoacetyl chloride (0.671 gr, 3 mmol) the same procedure as above and product was collected as a light yellow crystalline solid (0.752 gr, yield: 82%, mp 261–263°C). IR (KBr): vmax/cm−1 1776, 1688, 1591, 1529, 1258, 1088. 1H-NMR (DMSO): δ ppm 7.89-8.08 (m, 5 H, Ar-H), 7.87 (ddd, J = 7.8, 1.2, 0.6 Hz 1H, Ar-H), 7.60 (ddd, J = 7.8, 1.2, 6.6 Hz, 1 H, Ar-H), 7.23 (ddd, J = 6.6, 7.2, 1.2 Hz, 1 H, Ar-H), 3.77 (s, 2 H, CH2). 13C-NMR (DMSO): 167.9, 167.8, 165.7, 138.6, 135.2, 134.2, 132.0, 131.0, 124.5, 124.4, 122.3, 119.8, 52.7. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C17H11N2O4 (307.0713); Found 307.0720.
Preparation of 2-(4-bromophenyl)-4H-3,1-benzoxazin-4-one (2f)
Final product was isolated as a crystalline solid (0.802 gr, yield: 89%, mp: 184–185°C). IR (KBr): vmax/cm−1 1762, 1619, 1602, 1586, 1256, 1067. 1H-NMR (DMSO): δ ppm 8.16 (ddd, J = 7.2, 1.2, 0.6 Hz, 1H), 8.11 (ddd, J = 6.6, 1.8, 0.6 Hz, 2H), 7.96 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H), 7.81 (ddd, J = 6.0, 1.2, 0.6 Hz, 2H), 7.73 (ddd, J = 8.4, 1.2, 0.6 Hz, 1H) and 7.64 (ddd, J = 7.8, 7.2, 0.6 Hz, 1H). 13C-NMR (DMSO): 159.2, 156.2, 154.1, 137.4, 132.6, 130.2, 129.8, 129.2, 128.6, 127.4, 127.1, 117.5. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C14H9BrNO2 (301.9811); Found 301.9807.
Preparation of 2-(styryl)-4H-3,1-benzoxazin-4-one (2g)
The product was collected as a yellow crystalline solid (0.600 gr, yield: 80%, mp: 148–149°C). IR (KBr): vmax/cm−1 1761, 1635, 1592, 1566, 1251, 1040. 1H-NMR (DMSO): δ ppm 7.78 (d, J = 16.2 Hz, 1H), 7.59 - 8.16 (m, 9H, Ar-H), 7.01 (d, J = 16.2 Hz, 1H). 13C-NMR (DMSO): 159.2, 157.3, 147.1, 141.6, 137.3, 134.9, 130.8, 129.4, 128.9, 128.7, 128.5, 127.1, 119.7, 117.3. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C16H12NO2 (250.0863); Found 250.0851.
Preparation of 2-(diphenylamino)-4H-3,1-benzoxazin-4-one (2h)
The result was isolated as a crystalline solid (83% yield, 0.780 gr, mp: 167–168°C). IR (KBr): vmax/cm−1 1745, 1619, 1582, 1489, 1267, 1072. 1H-NMR (DMSO): δ ppm 7.93 (ddd, J = 8.4, 1.8, 0.6 Hz, 1H), 7.69 (ddd, J = 8.4, 7.2, 1.8 Hz, 1H), 7.42-7.45 (m, 8 H, Ar-H), 7.29 - 7.32 (m, 2H, Ar-H), 7.26 (ddd, J = 7.8, 7.2, 0.6 Hz, 1H), 7.16 (ddd, J = 7.8, 1.2, 0.6 Hz, 1H). 13C-NMR (DMSO): 159.4, 153.1, 150.1, 142.7, 137.2, 128.5, 129.7, 128.0, 127.2, 125.1, 124.9, 114.1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C20H15N2O2 (315.1128); Found 315.1131.
Preparation of 2-(4-nitrophenyl)-4H-3,1-benzoxazin-4-one (2i)
The procedure 2a was used for synthesis and workup of 2-(4-nitrophenyl)-4H-3,1-benzoxazin-4-one and the final product was gathered as a yellow wish crystalline solid (0.779 gr, yield: 86%, mp: 202–204). IR (KBr): vmax/cm−1 1766, 1607, 1589, 1522, 1493, 1251, 1082. 1H-NMR (DMSO): δ ppm 8.43 (ddd, J = 6.6, 1.8, 0.6 Hz, 2 H), 8.39 (ddd, J = 0.6, 7.8, 1.1 Hz, 1H), 8.18 (ddd, J = 0.6, 7.2, 1.2 Hz, 2H), 8.00 (ddd, J = 7.8, 1.2, 0.6 Hz, 1H), 7.71 (ddd, J = 8.4, 1.2, 7.2 Hz, 1H), 7.30 (ddd, J = 7.2, 7.8, 0.6 Hz, 1H). 13C-NMR (DMSO): 159.0, 156.2, 150.3, 146.7, 137.4, 136.4, 130.1, 129.8, 128.6, 127.2, 125.4, 119.1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C14H9N2O4 (269.0557); Found 269.0554.
The authors thank the technical assistants and coordinators of the analytical laboratories of Faculty of Science and Technology (FST), University Kebangsaan Malaysia (UKM).
- Peet NP, Angelastro MR, Burkhart JP: Novel orally-active elastase inhibitors. Book Novel orally-active elastase inhibitors. 1997, Munich, Germany: European Patent Office, EP Patent 0,529,568Google Scholar
- Colson E, Wallach J, Hauteville M: Synthesis and anti-elastase properties of 6-amino-2-phenyl-4<i>H</i>−3, 1-benzoxazin-4-one aminoacyl and dipeptidyl derivatives. Biochimie. 2005, 87: 223-230. 10.1016/j.biochi.2004.10.015.View ArticleGoogle Scholar
- Oshida J, Kawabata H, Kato Y, Kokubo M, Uejima Y, Sato O, Fujii K: 4H-3, 1-benzoxazin-4-one compound and elastase inhibitor composition containing the same. Book 4H-3, 1-benzoxaz-4-one compound and elastase hibitor composition contag the same. 1992, EP Patent 0,466,944Google Scholar
- Krantz A, Spencer R, Tam T: 4H-3, 1-benzoxazin-4-ones and related compounds and use as enzyme inhibitors. Book 4H-3, 1-benzoxaz-4-ones and related compounds and use as enzyme hibitors. 1987, U.S. Patent and Trademark Office: Washington, DC, U.S. Patent No. 4,657,893Google Scholar
- Besson T, Rees CW, Cottenceau G, Pons AM: Antimicrobial evaluation of 3, 1-benzoxazin-4-ones, 3, 1-benzothiazin-4-ones, 4-alkoxyquinazolin-2-carbonitriles and < i > N</i > −arylimino-1, 2, 3-dithiazoles. Bioorg Med Chem Lett. 1996, 6: 2343-2348. 10.1016/0960-894X(96)00423-4.View ArticleGoogle Scholar
- Connolly DJ, Cusack D, O'Sullivan TP, Guiry PJ: Synthesis of quinazolinones and quinazolines. Tetrahedron. 2005, 61: 10153-10202. 10.1016/j.tet.2005.07.010.View ArticleGoogle Scholar
- Elgohary AMF, Hassan MM, Abass M: Synthesis of some quinazolin-4-one derivatives carrying ibuprofenyl moiety and their antiinflammatory activity. Der Pharma Chemica. 2011, 3: 1-12.Google Scholar
- Azarifar D, Sheikh D: Ultrasound-Promoted Catalyst-Free Synthesis of 2,2′-(1,4-Phenylene)bis[1-acetyl-1,2-dihydro-4H-3,1-benzoxazin-4-one] Derivatives. Helv Chim Acta. 2012, 95: 1217-1225. 10.1002/hlca.201100481.View ArticleGoogle Scholar
- Alagarsamy V: Synthesis and pharmacological investigation of some novel 2-methyl-3-(substituted methylamino)-(3H)-quinazolin-4-ones as histamine H1-receptor blockers. Die Pharmazie - An International Journal of Pharmaceutical Sciences. 2004, 59: 753-755.Google Scholar
- Kurihara M, Saito H, Nukada K, Yoda N: Cyclopolycondensation. XII. Polymerization mechanism of polybenzoxazinones in polyphosphoric acid medium. J Polym Sci [A1]. 1969, 7: 2897-2914.View ArticleGoogle Scholar
- Papadopoulos EP, Torres CD: Convenient preparation of N-substituted 2-amino-4H–3, l-benzoxazin-4-ones and 3-substituted 2,4(1H,3H)-quinazolinediones. J Heterocycl Chem. 1982, 19: 269-272. 10.1002/jhet.5570190209.View ArticleGoogle Scholar
- Eissa AMF, El-Sayed R: Synthesis and evaluation of condensed and noncondensed heterocyclic compounds of industrial application. J Heterocycl Chem. 2006, 43: 1161-1168. 10.1002/jhet.5570430505.View ArticleGoogle Scholar
- Anastas P, Eghbali N: Green chemistry: principles and practice. Chem Soc Rev. 2010, 39: 301-312. 10.1039/b918763b.View ArticleGoogle Scholar
- Poliakoff M, Anastas P: Green chemistry: a principal stance. Nature. 2001, 413: 257-258. 10.1038/35095133.View ArticleGoogle Scholar
- Bandgar B, Pandit S: Synthesis of acyl azides from carboxylic acids using cyanuric chloride. Tetrahedron Lett. 2002, 43: 3413-3414. 10.1016/S0040-4039(02)00508-7.View ArticleGoogle Scholar
- Venkataraman K, Wagle D: Cyanuric chloride: a useful reagent for converting carboxylic acids into chlorides, esters, amides and peptides. Tetrahedron Lett. 1979, 20: 3037-3040. 10.1016/S0040-4039(00)71006-9.View ArticleGoogle Scholar
- Hamon F, Prié G, Lecornué F, Papot S: Cyanuric chloride: an efficient reagent for the Lossen rearrangement. Tetrahedron Lett. 2009, 50: 6800-6802. 10.1016/j.tetlet.2009.09.115.View ArticleGoogle Scholar
- Maia A, Albanese DCM, Landini D: Cyanuric chloride catalyzed Beckmann rearrangement of ketoximes in biodegradable ionic liquids. Tetrahedron. 2012, 68: 1947-1950. 10.1016/j.tet.2011.12.051.View ArticleGoogle Scholar
- Akhlaghinia B, Roohi E: Efficient method for tetrahydropyranylation of phenols and alcohols using 2, 4, 6-trichloro [1,3,5] triazine. Turk J Chem. 2007, 31: 83-88.Google Scholar
- Porcheddu A, Giacomelli G, Salaris M: Microwave-assisted synthesis of isonitriles: a general simple methodology. J Org Chem. 2005, 70: 2361-2363. 10.1021/jo047924f.View ArticleGoogle Scholar
- De Luca L, Giacomelli G, Porcheddu A: A mild and efficient alternative to the classical swern oxidation. J Org Chem. 2001, 66: 7907-7909. 10.1021/jo015935s.View ArticleGoogle Scholar
- Venkataraman K, Wagle DR: Cyanuric chloride, a useful reagent for macrocyclic lactonization. Tetrahedron Lett. 1980, 21: 1893-1896. 10.1016/S0040-4039(00)92809-0.View ArticleGoogle Scholar
- Hullio AA, Mastoi GM: Application of multipurpose dimethylformamide-like task specific ionic liquid as a recyclable reagent for direct iodination of alcohols. Iranian Journal of Catalysis. 2011, 1 (2): 79-86.Google Scholar
- De Luca L, Giacomelli G, Porcheddu A: Beckmann rearrangement of oximes under very mild conditions. J Org Chem. 2002, 67: 6272-6274. 10.1021/jo025960d.View ArticleGoogle Scholar
- De Luca L, Giacomelli G, Porcheddu A: An efficient route to alkyl chlorides from alcohols using the complex TCT/DMF. Org Lett. 2002, 4: 553-555. 10.1021/ol017168p.View ArticleGoogle Scholar
- Thilagavathy R, Kavitha HP, Arulmozhi R, Vennila JP, Manivannan V: 2-Phenyl-4H-3,1-benzoxazin-4-one. Acta Crystallogr Sect E- Struct Rep. 2009, 65: o127-10.1107/S1600536808042050.View ArticleGoogle Scholar
- Khajavi MS, Shariat SM: A New Synthesis of 2-Substituted 4H-3,1-Benzoxazin-4-ones by Cyanuric Chloride Cyclodehydration of N-Benzoyl- and N-Acylanthranilic Acids. Heterocycles. 2005, 65: 1159-1165. 10.3987/COM-05-10364.View ArticleGoogle Scholar
- Bain DI, Smalley R: Synthesis of 2-substituted-4H-3, 1-benzoxazin-4-ones. J Chem Soc C. 1968, 0: 1593-1597.View ArticleGoogle Scholar
- Jagani CL, Vanparia SF, Patel TS, Dixit RB, Dixit BC: A comparative study of solution phase as well as solvent free microwave assisted syntheses of 3-benzothiazole/isoxazole substituted 2-styryl-4 (3H)-quinazolinones. Arkivoc. 2012, 6: 281-294.Google Scholar
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