DMAP-Catalyzed Domino Reactions of α-Chloroaldoxime O-Methanesulfonates and 2-Aminobenzoic Acids for the Synthesis of Quinazolinediones

Abstract

Quinazolinedione derivatives were obtained from 2-aminobenzoic acids and bench-stable α-chloroaldoxime O-methanesulfonates via DMAP-catalyzed domino reactions under mild reaction conditions in one-pot fashion. Chemical transformations involved nucleophilic substitution, Tiemann rearrangement, and cyclic urea formation. The strength of nitrogen nucleophile of 2-aminobenzoic acids and the high level of carbon electrophile of α-chloroaldoxime O-methanesulfonates were crucial for the reaction outcome. An application to synthesize a quinazolinedione building block was introduced.

Key words

quinazolinediones - cylic ureas - organocatalysis - intramolecular C–N amide bond formation - Tiemann rearrangement

• References and Notes

• 1a Rivero I, Espinoza K, Somanathan R. Molecules 2004; 9: 609
• 1b Fakhraian H, Heydary M. J. Heterocycl. Chem. 2014; 51: 151
• 1c Jin H.-Z, Du J.-L, Zhang W.-D, Chen H.-S, Lee J.-H, Lee J.-J. J. Asian Nat. Prod. Res. 2007; 9: 685
• 1d Charoensutthivarakul S, Lohawittayanan D, Kanjanasirirat P, Jearawuttanakul K, Seemakhan S, Borwornpinyo S, Phanchana M. Molbank 2022; 2022: M1358
• 1e Hamiaux C, Larsen L, Lee HW, Luo Z, Sharma P, Hawkins BC, Perry NB, Snowden KC. Biochem. J. 2019; 476: 1843
• 2 Abdelmonsef AH, Mosallam AM. J. Heterocycl. Chem. 2020; 57: 1
• 3 Ismail MA. H, Barker S, Abou El Ella DA, Abouzid KA. M, Toubar RA, Todd MH. J. Med. Chem. 2006; 49: 1526
• 4a Ellsworth EL, Tran TP, Hollis Showalter HD, Sanchez JP, Watson BM, Stier MA, Singh R. J. Med. Chem. 2006; 49: 6435
• 4b Jiang Z.-Y, Hong WD, Cui X.-P, Gao H.-C, Wu P.-P, Chen Y.-S, Shen D, Yang Y, Zhang B.-J, Taylor MJ, Ward SA, O’Neill PM, Zhao S.-Q, Zhang K. RSC Adv. 2017; 7: 52227
• 5 Bouchut A, Rotili D, Pierrot C, Valente S, Lafitte S, Schultz J, Hoglund U, Mazzone R, Lucidi A, Fabrizi G, Pechalrieu D, Arimondo PB, Skinner-Adams TS, Chua MJ, Andrews KT, Mai A, Khalife J. Eur. J. Med. Chem. 2019; 161: 277
• 6 Crespo I, Giménez-Dejoz J, Porté S, Cousido-Siah A, Mitschler A, Podjarny A, Pratsinis H, Kletsas D, Parés X, Ruiz FX, Metwally K, Farrés J. Eur. J. Med. Chem. 2018; 152: 160
• 7a Gheidari D, Mehrdad M, Maleki S. Appl. Organomet. Chem. 2022; 36: e6631
• 7b Wu X, Yu Z. Tetrahedron Lett. 2010; 51: 1500
• 7c Duangjan C, Rukachaisirikul V, Saithong S, Kaeobamrung J. Tetrahedron Lett. 2018; 59: 3537
• 7d Larksarp C, Alper H. J. Org. Chem. 2000; 65: 2773
• 7e Willis MC, Snell RH, Fletcher AJ, Woodward RL. Org. Lett. 2006; 8: 5089
• 7f Beutner GL, Hsiao Y, Razler T, Simmons EM, Wertjes W. Org. Lett. 2017;  19: 1052
• 7g Wang P.-X, Wang Y.-N, Lin Z.-Y, Li G, Huang H.-H. Synth. Commun. 2018; 48: 1183
• 8a Roopan SM, Maiyalagan T, Khan FN. Can. J. Chem. 2008; 86: 1019
• 8b Yoo E, Salunke DB, Sil D, Guo X.-Q, Salyer AC. D, Hermanson AR, Kumar M, Malladi SS, Balakrishna R, Thompson WH. J. Med. Chem. 2014; 57: 7955
• 8c Koay N, Campeau L.-C. J. Heterocycl. Chem. 2011; 48: 473
• 8d Li Z, Huang H, Sun H, Jiang H, Liu H. J. Comb. Chem. 2008; 10: 484
• 9 Chen H, Li P, Qin R, Yan H, Li G, Huang H. ACS Omega 2020; 5: 9614
• 10a Yamamoto Y, Mizuno H, Tsuritani T, Mase T. J. Org. Chem. 2009; 74: 1394
• 10b Yamamoto Y, Mizuno H, Tsuritani T, Mase T. Tetrahedron Lett. 2009; 50: 5813
• 11 Kaeobamrung J, Lanui A, Mahawong S, Duangmak W, Rukachaisirikul V. RSC Adv. 2015; 5: 58587
• 12a Doleschall G, Lempert K. Tetrahedron Lett. 1963; 12: 781
• 12b Nakajima N, Ikada Y. Bioconjugate Chem. 1995; 6: 123
• 12c Wertjes W, Ayers S, Gao Q, Simmons E, Beutner G. Synthesis 2018; 50: 4453
• 13 Byrne FP, Jin S, Paggiola G, Petchey TH. M, Clark JH, Farmer TJ, Thomas J, Hunt AJ, Robert MC, Sherwood J. Sustainable Chem. Processes 2016; 4: 7
• 14 Duangjan C, Rukachaisirikul V, Kaeobamrung J. Tetrahedron Lett. 2020; 61: 152330
• 15 Alternative amidoxime rearrangement: Lin C.-C, Hsieh T.-H, Liao P.-Y, Liao Z.-Y, Chang C.-W, Shih Y.-C, Yeh W.-H, Chien T.-C. Org. Lett. 2014; 16: 892
• 16 Scarborough RM, Huang W, Pandey A, Bauer SM, Zhang X, Jia ZJ. WO2005032488, 2005
• 17 Magnus NA, Confalone PN, Storace L, Patel M, Wood CC, Davis WP, Parsons JrR. L. J. Org. Chem. 2003; 68: 754
• 18 General Procedure: Synthesis of QuinazolinedionesTo a round-bottom flask was added 2-(benzylamino)benzoic acid 2 (1.0 mmol) as a solid, α-chloroaldoxime O-methanesulfonate 1 (1.2 mmol), K₃PO₄ (3.0 mmol), DMAP (0.5 mmol), and t-BuOH (5.0 mL). Then H₂O (2.0 mmol) was added to the reaction mixture. The reaction mixture was allowed to stir at room temperature for 15–18 h. After completion of reaction, the reaction mixture was quenched with sat. NH₄Cl and extracted with EtOAc. The combined organic layers were washed with sat. NaCl (brine), dried over anhydrous Na₂SO₄, filtered, and concentrated. The residue was purified by column chromatography (4:1, hexanes/EtOAc) to provide the corresponding quinazolinedione.
• 19 Analytical Data for 1-Benzyl-3-phenylquinazoline-2,4(1H,3H)-dione (3a)Prepared according to general procedure from N-(methylsulfonyloxy)benzimidoyl chloride (1a) and 2-(benzylamino)benzoic acid (2a) yielding 3a in 242.81 mg (74 %) as a white solid. ¹H NMR (300 MHz, CDCl₃): δ = 8.31 (d, J = 7.8 Hz, 1 H), 7.65–7.47 (m, 4 H), 7.42–7.24 (m, 9 H), 5.44 (s, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 161.9, 151.6, 140.3, 135.6, 129.4, 129.0, 128.8, 128.5, 127.8, 127.1, 123.5, 115.9, 114.9, 47.6. IR (thin film): ν = 1704, 1656, 1349, 1317, 1330, 760, 702, 691, 672 cm^–1. HRMS (ESI-TOF): m/z [M + Na]⁺ calcd for C₂₁H₁₆N₂O₂Na: 351.1104; found: 351.1105.
• 20 Analytical Data for 1-Benzyl-3-(4-nitrophenyl)quinazoline-2,4(1H,3H)-dione (3b)Prepared according to general procedure from N-(methylsulfonyloxy)-4-nitrobenzimidoyl chloride (1b) and 2-(benzylamino)benzoic acid (2a) yielding 3b in 305.95 mg (82 %) as a white solid. ¹H NMR (300 MHz, CDCl₃): δ = 8.33 (d, J = 8.7 Hz, 2 H), 8.20 (dd, J = 8.1, 1.5 Hz, 1 H), 7.59 (t, J = 1.8 Hz, 1 H), 7.48 (d, J = 9.0 Hz, 2 H), 7.33–7.16 (m, 7 H), 5.34 (s, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 161.4, 150.9, 147.7, 141.2, 140.2, 136.0, 135.2, 130.1, 129.4, 129.1, 128.0, 126.7, 126.4, 124.6, 123.7, 115.8, 114.9, 113.4, 47.6. IR (thin film): ν = 1704 1663 1344 1310 1478 860 752 699 688 cm^–1. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₁H₁₆N₃O₄: 374.1135; found: 374.1136.