Diels-Alder Reactions of (E)-2-Styrylquinolin-4(1H)-ones with N-Methylmaleimide: New Syntheses of Acridin-9(10H)-ones

Abstract

New syntheses of acridin-9(10H)-ones were developed. One involves a two-step transformation, namely the Diels-Alder ­reactions of (E)-1-methyl-2-styrylquinolin-4(1H)-ones with N-methylmaleimide in refluxing toluene, followed by oxidation of the formed adducts. The second consists in an one-pot procedure using 1,2,4-trichlorobenzene as solvent at 180 ˚C. The effect of microwave irradition and Lewis acid catalysts in these cycloaddition ­reactions was also investigated.

(E)-2-styrylquinolin-4(1H)-ones - acridin-9(10H)-ones - Diels-Alder reactions - N-methylmaleimide - NMR

References and Notes

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7

General Procedure for the Diels-Alder Reaction of ( E )-1-Methyl-2-styrylquinolin-4(1 H )-ones 1a-c with N -Methylmaleimide in Toluene under Classical Heating Conditions
A mixture of the appropriate (E)-1-methyl-2-styrylquinolin-4 (1H)-one 1a-c (0.096 mmol) and N-methylmaleimide (32.0 mg, 0.29 mmol) in toluene (25 mL) was stirred at 120 ˚C under N₂ atmosphere. An extra excess of N-methylmale-imide (32.0 mg, 0.288 mmol) was added after a reaction time of 48 h. After 72 h the reaction mixture was concentrated, taken in CH₂Cl₂ and purified by TLC using a 5:1 mixture of CH₂Cl₂-acetone as eluent. The adducts 3a-c were obtained in moderate yields (3a: 18.60 mg, 52%; 3b: 15.80 mg, 41%; 3c: 13.28 mg, 34%) as a yellow solid, and some starting material was recovered (1a: 3.26 mg, 13%; 1b: 4.20 mg, 15%; 1c: 3.69 mg, 13%). Also, traces of compounds 4a-c were found.

8

Physical Data of 2,6-Dimethyl-4-phenyl-4,5,6,11b-tetrahydro-1 H -pyrrolo[3,4- a ]acridine-1,3,11(2 H ,3a H )-trione (3a)
Mp 283-284 ˚C. ^¹H NMR (300.13 MHz, CDCl₃): δ = 2.76 (3 H, s, 2-NCH₃), 3.04 (1 H, dd, J = 16.2, 10.0 Hz, H-5 _cis ), 3.24 (1 H, dd, J = 16.2, 3.6 Hz, H-5 _trans ), 3.41-3.55 (2 H, m, H-3a, 4-H), 3.79 (3 H, s, 6-NCH₃), 5.01 (1 H, d, J = 8.6 Hz, H-11b), 7.21-7.24 (2 H, m, H-3′,5′), 7.30-7.35 (3 H, m, H-2′,4′,6′), 7.41 (1 H, ddd, J = 7.8, 7.7, 0.7 Hz, H-9), 7.51 (1 H, d, J = 8.2 Hz, H-7), 7.69 (1 H, ddd, J = 8.2, 7.7, 1.7 Hz, H-8), 8.56 (1 H, dd, J = 7.8, 1.7 Hz, H-10). ^¹³C NMR (75.47 MHz, CDCl₃): δ = 24.6 (2-NCH₃), 30.2 (C-5), 34.6 (6-NCH₃), 39.1 (C-11b), 41.2 (C-4), 44.4 (C-3a), 112.6 (C-11a), 115.2 (C-7), 123.7 (C-9), 125.5 (C-10a), 127.4 (C-10), 127.6 (C-4′), 127.8 (C-3′,5′), 128.5 (C-2′,6′), 132.4 (C-8), 139.1 (C-1′), 141.3 (C-6a), 150.2 (C-5a), 175.78, 175.82 and 173.3 (C-1, C-3 and C-11). ESI(+)-MS: m/z (%) = 373 (100) [M + H]⁺, 395 (16) [M + Na]⁺. HRMS (EI): m/z calcd for C₂₃H₂₀N₂O₃: 372.1474; found: 372.1472.

9

Physical Data of 2,6-Dimethyl-4-phenyl-1 H -pyrrolo[3,4- a ]acridine-1,3,11(2 H ,6 H )-trione (4a)
Mp 353-354 ˚C. ^¹H NMR (300.13 MHz, CDCl₃): δ = 3.18 (3 H, s, 2-NCH₃), 3.95 (3 H, s, 6-NCH₃), 7.38 (1 H, dd, J = 7.9, 7.6 Hz, H-9), 7.51-7.54 (3 H, m, H-7, H-3′,5′), 7.57-7.61 (3 H, m, H-2′,4′,6′), 7.76 (1 H, s, H-5), 7.77 (1 H, ddd, J = 7.8, 7.7, 1.6 Hz, H-8), 8.56 (1 H, dd, J = 7.9, 1.6 Hz, H-10). ^¹³C NMR (75.47 MHz, CDCl₃): δ = 24.3 (2-NCH₃), 35.4 (6-NCH₃), 114.8 (C-7), 118.9 (C-11a), 121.5 (C-5), 122.8 (C-9), 123.5 (C-3a), 125.0 (C-10a), 128.1 (C-3′,5′), 128.3 (C-10), 129.1 (C-4′), 129.3 (C-2′,6′), 134.2 (C-8), 134.9 (C-11b), 136.5 (C-1′), 142.1 (C-6a), 143.8 (C-4), 146.7 (C-5a), 165.2 and 166.9 (C-1 and C-3), 176.2 (C-11). ESI(+)-MS: m/z (%) 369 (100) [M + H]⁺. HRMS-ESI(+): m/z calcd for C₂₃H₁₇N₂O₃ [M + H]⁺: 369.1239; found: 369.1234.

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15

Physical Data of ( Z )-1-Methyl-2-styrylquinolin-4(1 H )-one
^¹H NMR (300.13 MHz, CDCl₃): δ = 3.94 (3 H, s, 1-NCH₃), 6.93 (1 H, s, H-3), 7.37-7.54 (7 H, m, H-6, H-8, H-3′,4′,5′, H-α and H-β), 7.71 (1 H, dt, J = 7.8, 1.6 Hz, H-7), 7.98 (2 H, dd, J = 7.7, 1.6 Hz, H-2′,6′), 8.69 (1 H, dd, J = 8.1, 1.6 Hz, H-5).

16

The configuration cis and trans of H-5 is established by the position relative to H-4.