Supporting Information

Size: px

Start display at page:

Download "Supporting Information"

Deborah Lambert
5 years ago
Views:

1 Supporting Information Synthesis of N-Heteropolycyclic Compounds Including Quinazolinone Skeletons by Using Friedel-Crafts Alkylation Bu Keun Oh, Eun Bi Ko, Jin Wook Han* and Chang Ho Oh* Department of Chemistry, Hanyang University, Sungdong-Gu, Seoul , Korea Table of Contents 1. Typical experimental procedures from 5a to 1a Spectroscopic data of compounds 3c-e, 2a-e, 1a-e, 8a-b References H and 13 C NMR spectra of compounds 3c-e, 2a-e, 1a-e, 8a-b

2 2

3 1. Typical experimental procedures from 5a to 1a Synthesis of 2-amino-N-phenylbenzamide (6a). To a DCE solution (4 ml) of compound 2-aminobenzoic acid (4.8 g,.29 mol) was added a catalytic amount of DMF (.2 ml, 2.9 mmol) and oxalyl chloride (5. ml,.58 mol) at under Ar atmosphere. After the mixture was stirred for 2h at room temperature, the crude solution was evaporated under reduced pressure. The reaction mixture was redissolved in DCE (3 ml), pyridine (5.9 ml,.73 mol) and aniline (3. g,.32 mol) in DCE (1 ml) were added at. The mixture was stirred for 8h at RT under Ar atmosphere. After TCL analysis, the crude mixture was diluted with ethyl acetate, washed with 1N HCl, NaHCO 3, NaCl solution, and dried over anhydrous MgSO 4. The residue was recrystallized from ethyl acetate and hexane to give 2-nitro-N-phenylbenzamide (6.2 g, 88%) as a brown solid. Then, the solid (6.2 g, and.26 mol) and 1% Pd on charcoal (1 wt%) in methanol (5 ml) were stirred under H 2 (1 atm) atmosphere for 4h. After completion of reduction, Pd on charcoal was filtered off on celite, washed over and over with dichloromethane. The filtrate was concentrated under reduced pressure to afford 2-amino-N-phenylbenzamide (5.5 g, quantitative yield) as a white solid. Other substrate (6b) was synthesized to similar reaction conditions. Spectral data matches that previously reported. [1] 3

4 Synthesis of 2-acetamido-N-phenylbenzamide (7a). To a MC solution (5 ml) of 6 (5.5 g,.26 mol) was added triethylamine (7.3 ml,.52 mol) and acetic anhydride (4.9 ml,.52 mol) at under Ar atmosphere. The reaction mixture was stirred for 2h at 4. After TLC analysis, the crude was diluted with NH 4 Cl, extracted with dichloromethane, washed with NaHCO 3, NaCl solution, and dried over anhydrous MgSO 4. The organic phase was concentrated under reduced pressure, and the residue was recrystallized from ethyl acetate and hexane to give 2-acetamido-N-phenylbenzamide (6. g, 9%) as a white solid. Other substrate (7b) was synthesized to similar reaction conditions. Spectral data matches that previously reported. [2] Synthesis of 2-methyl-3-phenylquinazolin-4(3H)-one (4a). To a DCE solution (5 ml) of 7 (6.g,.24 mol) was added triethylamine (16.7 ml,.12 mol) and chlorotrimethylsilane (15.2 ml,.12 mol) at under Ar atmosphere. The reaction mixture was heated for 3h at 1. After TLC analysis, the crude was diluted with NH 4 Cl, extracted with ethyl acetate, washed with NaCl, and dried over MgSO 4. The organic phase was concentrated under reduced pressure, and the residue was recrystallized from ethyl acetate and hexane to give 2-methyl- 3-phenylquinazolin-4(3H)-one (5. g, 88%) as a white solid. Other substrate (4b) was synthesized to similar reaction conditions. Spectral data matches that previously reported. [3] 4

5 Synthesis of (E)-3-phenyl-2-strylquinazolin-4(3H)-one (3a). A General procedure To a glacial acetic acid (8 ml) of 4a (5 mg, 2.1 mmol) was added benzaldehyde (.3 ml, 3.2 mmol) and sodium acetate (34 mg, 4.2 mmol) at under Ar atmosphere. The reaction mixture was refluxed for 8h at 15. After completion of reaction, the mixture was cooled to, poured into crushed ice, and the separated precipitate was filtered off. The solid state was washed with water, and recrystallized from ethyl acetate and hexane to give (E)-3-phenyl-2-strylquinazolin-4(3H)-one (51 mg, 75%) as a white solid. Other substrates (3b-e) were synthesized to similar reaction conditions. Spectral data of 3a-b matches that previously reported. [4] Synthesis of 5-phenyl-5,6-dihydro-12H-quinolino[2,1-b]quinazolin-12-one (2a). A General procedure To a DCE solution (4 ml) of 3a (32 mg, 1. mmol) was added trifluoromethanesulfonic acid (.4 ml, 5. mmol) at under Ar atmosphere. The reaction mixture was heated for 8h at 1. After TLC analysis, the crude mixture was diluted with H 2 O, extracted with ethyl acetate, washed with NaHCO 3, NaCl solution, dried over anhydrous MgSO 4, and concentrated under reduced pressure. The concentrated residue was purified by flash silica gel chromatography by using a 1:2 mixture of ethyl acetate and hexane to give 5-phenyl-5H-quinolino[2,1-b]quinazolin-12(6H)-one (23 mg, 71%) as a white solid. Other substrates (2b-e) were synthesized to similar reaction conditions. Synthesis of 5-phenyl-12H-quinolino[2,1-b]quinazolin-12-one (1a). A General procedure To a benzene solution (2 ml) of 2a (15 mg,.46 mmol) was added 2,3-dichloro-5,6-dicyano-1,4- benzoquinone (16 mg,.69 mmol) at under Ar atmosphere. The reaction mixture was heated for 1h at 1. After TLC analysis, the crude mixture was diluted with H 2 O, extracted with ethyl acetate, washed with NaHCO 3, NaCl solution, dried over MgSO 4, and concentrated under reduced 5

6 pressure. The concentrated residue was purified by flash silica gel chromatography by using a 1:4 mixture of ethyl acetate and hexane to give 5-phenyl-12H-quinolino[2,1-b]quinazolin-12-one (12 mg, 78%) as a white solid. Other substrates (1b-e) were synthesized to similar reaction conditions. 2. Spectroscopic data of compounds 3c: Yellow solid; M.P ; 1 H NMR (4 MHz, CDCl 3 ) δ 8.31 (d, J 6

7 = 8. Hz, 1H), 7.9 (d, J = 16. Hz, 1H), (m, 2H), (m, 3H), (m, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 7.2 Hz, 2H), 7.17 (d, J = 8.4 Hz, 2H), 6.37 (d, J = 15.6 Hz, 1H); 13 C NMR (1 MHz, CDCl 3 ) δ , , , 138.6, , , , , 13.8, , , , 127.4, 127.3, , , 121.6, 12.63, 12.61; IR (NaCl, Cm -1 ) 359, 1681, 1632, 1548; HRMS (ESI) Calcd for (C 22 H 14 N 2 O + Na) + requires m/z , found m/z d: Yellow solid; M.P ; 1 H NMR (4 MHz, CDCl 3 ) δ 7.9 (d, J = 15.6 Hz, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.67 (d, J = 2.8 Hz, 1H), (m, 3H), 7.4 (dd, J = 8.4 Hz, 2.4 Hz, 1H), (m, 7H), 6.37 (d, J = 15.6 Hz, 1H), 3.93 (s, 3H); 13 C NMR (1 MHz, CDCl 3 ) δ , 158.5, , , , , , 13.1, 13.8, 13.2, , , , , , , 128.8, , 125.5, , 12.1, 16.63, 55.96; IR (NaCl, Cm -1 ) 363, 285, 1673, 1616, 1487; HRMS (ESI) Calcd for (C 23 H 18 N 2 O 2 + Na) + requires m/z , found m/z e: Yellow solid; M.P ; 1 H NMR (4 MHz, CDCl 3 ) δ 7.82 (d, J = 15.6 Hz, 1H), 7.72 (d, J = 9.2 Hz, 1H), 7.66 (d, J = 2.4 Hz, 1H), (m, 3H), (m, 3H), 7.32 (d, J = 7.2 Hz, 2H), 7.15 (d, J = 8.8 Hz, 2H), 6.34 (d, J = 16. Hz, 1H), 3.92 (s, 3H); 13 C NMR (1 MHz, CDCl 3 ) δ , , , , , , , 132.9, 13.5, 129.5, , , , 125.9, , , 12.73, 16.69, 55.98; IR (NaCl, Cm -1 ) 377, 2842, 1671, 1616, 1488; HRMS (ESI) Calcd for (C 23 H 17 BrN 2 O 2 + Na) + requires m/z , found m/z 7

8 a: White solid; M.P ; 1 H NMR (4 MHz, CDCl 3 ) δ 8.34 (d, J = 7.2 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), (m, 1H), 7.59 (d, J = 8. Hz, 1H), 7.46 (t, J = 8. Hz, 1H), (m, 1H), (m, 4H), 7.17 (d, J = 7.6 Hz, 2H), 7.6 (d, J = 7.6 Hz, 1H), (m, 1H), (m, 2H); 13 C NMR (1 MHz, CDCl 3 ) δ 16.8, 153.4, , , , , 129.2, , , , , , 126.8, 12.73, , 122.9, 41.48, 4.52; IR (NaCl, Cm -1 ) 36, 1683, 1594; HRMS (ESI) Calcd for (C 22 H 16 N 2 O + Na) + requires m/z , found m/z b: Yellow solid; M.P ; 1 H NMR (4 MHz, CDCl 3 ) δ 8.34 (d, J = 8. Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), (m, 1H), 7.59 (d, J = 8. Hz, 1H), 7.46 (t, J = 7.6 Hz, 1H), 7.4 (t, J = 7.2 Hz, 1H), 7.24 (d, J = 7.6 Hz, 1H), 7.8 (d, J = 8.4 Hz, 3H), 6.82 (d, J = 8.4 Hz, 2H), (m, 1H), 3.75 (s, 3H), (m, 2H); 13 C NMR (1 MHz, CDCl 3 ) δ 16.82, , , , , 134.7, , , , 129.2, , , , , , 127.3, , 126.8, , , 122.7, , 55.3, 4.69; IR (NaCl, Cm -1 ) 363, 2836, 1683, 1594; HRMS (ESI) Calcd for (C 23 H 18 N 2 O 2 + Na) + requires m/z , found m/z c: White solid; M.P ; 1 H NMR (4 MHz, CDCl 3 ) δ 8.33 (d, J = 8. Hz, 1H), 8.28 (d, J = 8. Hz, 1H), 7.73 (t, J = 7.2 Hz, 1H), 7.58 (d, J = 8. Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H), (m, 3H), 7.27 (t, J = 8. 8

9 Hz, 1H), (m, 3H), 4.3 (t, 6. Hz, 1H), (m, 2H); 13 C NMR (1 MHz, CDCl 3 ) δ 16.72, , , , , , , , , , , , , , , , 122.1, , 4.98, 4.37; IR (NaCl, Cm -1 ) 364, 1686, 1595; HRMS (ESI) Calcd for (C 22 H 15 BrN 2 O + Na) + requires m/z , found m/z d: White solid; M.P ; 1 H NMR (4 MHz, CDCl 3 ) δ 8.3 (d, J = 8. Hz, 1H), 7.71 (d, J = 2.8 Hz, 1H), 7.52 (d, J = 9.2 Hz, 1H), 7.41 (t, J = 7.2 Hz, 1H), (m, 2H), (m, 3H), 7.17 (d, J = 7.2 Hz, 2H), 7.6 (d, J = 7.2 Hz, 1H), (m, 1H), 3.93 (s, 3H), (m, 2H); 13 C NMR (1 MHz, CDCl 3 ) δ 16.74, , , 14.94, , , 134.5, 129.3, , , , , , , 124.4, , 17.13, 55.93, 41.63, 4.34; IR (NaCl, Cm -1 ) 363, 2851, 168, 149; HRMS (ESI) Calcd for (C 23 H 18 N 2 O 2 + Na) + requires m/z , found m/z e: White solid; M.P ; 1 H NMR (4 MHz, CDCl 3 ) δ 8.3 (d, J = 8. Hz, 1H), 7.7 (d, J = 2.4 Hz, 1H), 7.52 (d, J = 9.2 Hz, 1H), (m, 3H), 7.32 (dd, J = 8. Hz, 2. Hz, 1H), 7.27 (d, J = 15.2 Hz, 1H), 7.8 (d, J = 7.6 Hz, 1H), 7.4 (d, J = 7.6 Hz, 2H), (m, 1H), 3.93 (s, 3H), (m, 2H); 13 C NMR (1 MHz, CDCl 3 ) δ 16.66, , 15.55, 14.86, , , , , 129.6, , , , , 124.8, , , , 17.16, 5.95, 41.17, 4.24; IR (NaCl, Cm -1 ) 362, 2837, 168, 149; HRMS (ESI) Calcd for (C 23 H 17 BrN 2 O 2 + Na) + requires m/z , found m/z

10 1a: Whit solid; M.P ; 1 H NMR (4 MHz, CDCl 3 ) δ 9.55 (d, J = 8.8 Hz, 1H), 8.47 (d, J = 7.6 Hz, 1H), (m, 1H), 7.75 (d, J = 8. Hz, 1H), (m, 2H), (m, 6H), 7.41 (t, J = 7.6 Hz, 1H), 7.22 (s, 1H); 13 C NMR (1 MHz, CDCl 3 ) δ , 147.8, , , 136.9, 135.8, , , 129.1, 129.5, , , , , , 126.8, , , 12.15; IR (NaCl, Cm -1 ) 36, 1683, 1544; HRMS (ESI) Calcd for (C 22 H 14 N 2 O + H) + requires m/z , found m/z b: Yellow solid; M.P ; 1 H NMR (4 MHz, CDCl 3 ) δ 9.53 (d, J = 8.8 Hz, 1H), 8.47 (d, J = 7.6 Hz, 1H), 7.82 (t, J = 6.8 Hz, 1H), (m, 2H), 7.62 (t, J = 7.2 Hz, 1H), (m, 3H), 7.41 (t, J = 8. Hz, 1H), 7.2 (s, 1H), 7.7 (d, J = 8.4 Hz, 2H), 3.91 (s, 3H); 13 C NMR (1 MHz, CDCl 3 ) δ , 16.36, , 147.6, , , , 13.44, , , , 127.4, , , , , , , 12.7, , 55.55; IR (NaCl, Cm -1 ) 367, 2853, 1685, 1546; HRMS (ESI) Calcd for (C 23 H 17 N 2 O 2 + H) + requires m/z , found m/z c: Yellow solid; M.P ; 1 H NMR (4 MHz, CDCl 3 ) δ 9.55 (d, J = 8.4 Hz, 1H), 8.47 (d, J = 7.6 Hz, 1H), 7.83 (t, J = 7.6 Hz, 1H), 7.75 (d, J = 8. Hz, 1H), 7.68 (d, J = 8.4 Hz, 2H), (m, 2H), 7.53 (d, J = 7.6 1

11 Hz, 1H), (m, 3H), 7.19 (s, 1H); 13 C NMR (1MHz, CDCl 3 ) δ , , , , , , 134.9, , 13.71, , , , , , , , , , 122.7, 12.19; IR (NaCl, Cm -1 ) 366, 1682, 1549; HRMS (ESI) Calcd for (C 22 H 14 BrN 2 O + H) + requires m/z , found m/z d: Yellow solid; M.P ; 1 H NMR (4 MHz, CDCl 3 ) δ 9.6 (d, J = 8.8 Hz, 1H), 7.84 (d, J = 2.4 Hz, 1H), 7.7 (d, J = 8.4 Hz, 1H), (m, 2H), 7.53 (s, 5H), 7.45 (dd, J = 8.8 Hz, 2.8 Hz, 1H), 7.41 (t, J = 7.6 Hz, 1H), 7.2 (s, 1H), 3.99 (s, 3H); 13 C NMR (1 MHz, CDCl 3 ) δ , , 146.5, , , 137.2, , , 129.5, , , , , , , , , 122.2, 12.8, 16.4, 55.99; IR (NaCl, Cm -1 ) 371, 285, 168, 1487; HRMS (ESI) Calcd for (C 23 H 17 N 2 O 2 + H) + requires m/z , found m/z e: Yellow solid; M.P ; 1 H NMR (4 MHz, CDCl 3 ) δ 9.6 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 2.8 Hz, 1H), (m, 3H), (m, 2H), (m, 4H), 7.17 (s, 1H), 3.99 (s, 3H); 13 C NMR (1 MHz, CDCl 3 ) δ , , , , , , , , 13.72, , , , , , , , 123.3, , 12.87, 16.45, 55.98; IR (NaCl, Cm -1 ) 372, 285, 1671, 1485; HRMS (ESI) Calcd for (C 23 H 16 BrN 2 O 2 + H) + requires m/z , found m/z

12 8a: Yellow solid; M.P ; 1 H NMR (4 MHz, CDCl 3 ) δ 9.55 (d, J O N N 8a = 8.4 Hz, 1H), 8.48 (d, J = 8. Hz, 1H), 7.83 (t, J = 7.6 Hz, 1H), 7.76 (s, 2H), 7.74 (s, 2H), (m, 5H), 7.52 (t, J = 7.6 Hz, 1H), 7.44 (t, J = 7.2 Hz, 1H), 7.31 (d, J = 8. Hz, 2H), 7.28 (s, 1H), 2.44 (s, 3H); 13 C NMR (1 MHz, CDCl 3 ) δ , , , , , , , 135.4, , , , , , , 127.8, , , , , , , 12.11, 21.29; IR (NaCl, Cm -1 ) 366, 2858, 168, 1487; HRMS (ESI) Calcd for (C 29 H 21 N 2 O + H) + requires m/z , found m/z b: White solid; M.P ; 1 H NMR (4 MHz, CDCl 3 ) δ 9.56 (d, O N N 8b J = 8.8 Hz, 1H), 8.49 (d, J = 8.4 Hz, 1H), 7.84 (t, J = 8. Hz, 1H), (m, 2H), (m, 2H), 7.65 (t, J = 7.6 Hz, 1H), (m, 6H), (m, 3H), 7.32 (t, J = 6.8 Hz, 1H), 7.27 (s, 1H), 7.23 (d, J = 6. Hz, 1H); 13 C NMR (1 MHz, CDCl 3 ) δ 162.9, , 147.1, , , , , , , 13.1, , , 128.9, , , , , , 126.8, , , , , , 122.1, 12.16; IR (NaCl, Cm -1 ) 327, 1682, 1544, 1468; HRMS (ESI) Calcd for (C 3 H 2 N 2 O + H) + requires m/z , found m/z References [1] (a) Shaterian, H. R.; Oveisi, A. R.; Honarmand, M. Synthetic Comm. 21, 4, (b) J. Med. Chem. 213, 56,

13 [2] Hesp, K. D.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 211, 133, [3] (a) Xu, L.; Jiang, Y.; Ma, D. Org. Lett. 212, 14, (b) J. Med. Chem. 1972, 15, [4] Trashakhova, T. V.; Nosova, E. V.; Valova, M. S.; Slepukhin, P. A.; Lipunova, G. N.; Charushin, V. N. Russ. J. Org. Chem. 211, 47,

14 4. 1 H and 13 C NMR Spectra of compounds 14

p-toluenesulfonic Acid-Mediated 1,3-Dipolar Cycloaddition of

Supporting Information for: p-toluenesulfonic Acid-Mediated 1,3-Dipolar Cycloaddition of Nitroolefins with NaN 3 for Synthesis of 4-Aryl-NH-1,2,3-triazoles Xue-Jing Quan, Zhi-Hui Ren, Yao-Yu Wang, and