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Synlett 2009(5): 843-847  
DOI: 10.1055/s-0028-1087955
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

One-Pot Synthesis of Isoindolo[2,1-a]quinolin-11-ones by Cyclocondensation of 3-Hydroxy-2-arylisoindol-1-ones with 1,3-Dicarbonyls

Yuehua Zhou, Lingfeng Qian, Wei Zhang*
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China
Fax: +86(931)8625657; e-Mail: zhangwei6275@lzu.edu.cn;
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Received 20 September 2008
Publikationsdatum:
26. Februar 2009 (online)

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Abstract

Isoindolo[2,1-a]quinolin-11-ones have been synthesized by one-pot reaction of 3-hydroxy-2-arylisoindol-1-ones with 1,3-dicarbonyls via coupling of N-acyliminium ion intermediates with 1,3-dicarbonyls and subsequent intramolecular Friedel-Crafts reactions catalyzed by H3PO4-P2O5 or H3PO4-H2SO4.

Key words

2,3-dihydro-3-hydroxy-2-arylisoindol-1-one - 1,3-dicarbonyls - 6a,11-dihydroisoindolo[2,1-a]quinolin-11-ones - N-acyl-iminium ions - Friedel-Crafts reaction

    References and Notes

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8

Typical Experimental ProcedureMethod A
To a stirred mixture of 3-hydroxy-2-phenylisoindol-1-one (1a, 1.0 mmol), ethyl acetoacetate (2b, 1.2 mmol) and H3PO4 (2 mL), P2O5 (2 g) was added at one portion at r.t. After the solid was dissolved completely the mixture was stirred at r.t. or heated at 60 ˚C for 6-24 h (TLC control). The reaction was quenched by crashed ice and the solution was extracted with CH2Cl2 (2 × 10 mL).The organic phase was washed with sat. aq NaHCO3 (10 mL) and H2O, respectively and dried with anhyd Na2SO4, concentrated at reduced pressure to furnish the crude products 3a which was purified by silica gel column chromatography using EtOAc-hexane (1:9) as eluents and further purified by recrystallization from EtOH.
Method B
The procedure is similar to method A, only P2O5 was replaced by H2SO4 (2 mL, 98%) which was added dropwise into the mixture of 1a (1.0 mmol), 2a (1.2 mmol), and H3PO4 (2 mL).
Selected Spectroscopic Data
Compound 3a: colorless needles; mp 124-126 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 1.33 (t, 3 H, J = 7.5 Hz, CH3), 2.21 (s, 3 H, CH3), 4.35 (q, 2 H, J = 7.5 Hz, OCH2), 5.92 (s, 1 H, H-6a), 7.23 (t, 1 H, J = 7 8 Hz), 7.42-7.60 (m, 5 H), 7.96 (d, 1 H, J = 7.2 Hz H-10), 8.05 (d, 1 H, J = 7 8 Hz H-1). ¹³C NMR (75 MHz, CDCl3): δ = 14.2 (CH3), 15.6 (CH3), 58.7 (OCH2), 61.0 (C-6a), 122.0 (CH), 123.7 (CH), 124.3 (CH), 125.0 (CH), 125.2 (CH), 126.8 (C), 127.5 (C), 128.9 (CH), 129.7(CH), 132.0 (C), 132.5 (CH), 133.7 (C), 134.7 (C), 140.7 (C), 166.5 (CO), 166.9 (CO). MS (EI): m/z (%) = 319 (18) [M+], 304 (8), 290 (30), 274 (4), 262 (6), 246 (99), 86 (100). Anal. Calcd (%) for C20H17NO3: C, 75.22; H, 5.37; N 4.39 Found: C, 75.13; H, 5.45; N 4.25.
Compound 3c: colorless needles; mp 151-153 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 1.33 (t, 3 H, J = 7.2 Hz, CH3), 2.17 (s, 3 H, CH3), 4.35 (q, 2 H, J = 7.5 Hz, OCH2), 5.90 (s, 1 H, H-6a), 7.39 (dd, 1 H, J = 7.5, 1.5 Hz), 7.42 (d, 1 H, J = 1.5 Hz, H-4), 7.52-7.60 (m, 3 H), 7.94 (d, 1 H, J = 7.5 Hz, H-1), 8.00 (d, 1 H, J = 8.1 Hz, H-10). ¹³C NMR (75 MHz, CDCl3): δ = 14.2 (CH3), 15.6 (CH3), 58.5 (OCH2), 61.2 (C-6a), 123.1 (CH), 123.7 (CH), 124.4 (CH), 125.2 (CH), 128.0 (C), 129.0 (CH), 129.4 (CH), 130.4 (C), 131.7 (C), 132.5 (C), 132.7 (CH), 133.1 (C), 140.5 (C), 166.5 (CO), 166.7 (CO). MS (EI): m/z (%) = 355 (8) [M + 2+], 353 (25 [M+], 340 (20), 338 (62), 326 (31), 324 (87), 310 (28), 296 (5), 282 (29), 280 (100). Anal. Calcd (%) for C20H18ClNO3: C, 67.90; H, 4.56; N, 3.96 Found: C, 67.83; H, 4.63; N, 4.07.
Compound 3f: colorless needles; 141-143 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 2.09 (s, 3 H, CH3), 2.16 (s, 3 H, CH3), 2.39 (s, 3 H, CH 3), 5.80 (s, 1 H, H-6a), 7.23 (s, 1 H, H-4), 7.26 (t, 1 H, J = 6.0 Hz), 7.41 (d, 1 H, J = 7.2 Hz, H-2), 7.50-7.59 (m, 3 H), 7.95 (d, 2 H, J = 8.7 Hz, H-1, H-10). ¹³C NMR (75 MHz, CDCl3): δ = 15.6 (CH3), 21.2 (CH3), 32.8 (CH3), 58.5 (C-6a), 121.5 (CH), 123.7 (CH), 124.3 (CH), 125.2 (CH), 127.2 (C), 128.9 (CH), 129.1 (C), 130.1 (CH), 132.1 (C), 132.2 (C), 132.4 (CH), 134.5 (C), 134.8 (C), 140.1 (C), 166.1 (CO), 204.6 (CO). MS (EI): m/z (%) = 303 (16) [M+], 302 (10), 288 (36), 260 (62), 246 (18), 230 (5), 217 (13), 43 (100). Anal. Calcd (%) for C20H17NO2: C, 79.18; H, 5.65; N, 4.62 Found: C, 79.12; H, 5.74; N, 4.55.
Compound 3g: colorless needles; 156-158 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 1.94 (s, 3 H, CH3), 6.06 (s, 1 H, H-6a), 7.22-7.54 (m, 9 H), 7.80 (d, 2 H, J = 7.8 Hz, H-2¢), 7.90 (d, 1 H, J = 6.9 Hz, H-10), 8. 16 (d, 1 H, J = 7.5 Hz, H-1). ¹³C NMR (75 MHz, CDCl3): δ = 16.4 (CH3), 59.2 (C-6a), 121.7 (CH), 124.0 (2 CH), 124.8 (CH), 125.0 (CH), 127.6 (C), 128.7 (CH), 128.9 (2 CH), 129.2 (2 CH), 129.6 (CH), 131.3 (C), 131.7 (C), 131.9 (C), 132.3 (CH), 134.1 (CH), 134.7 (C), 136.8 (C), 140.1 (C), 166.5 (CO), 196.9 (CO). MS: m/z (%) = 351 (37) [M+], 350 (14), 336 (25), 246 (79), 105 (100), 77 (89). Anal. Calcd (%) for C24H17NO2: C, 82.03; H, 4.88; N, 3.99 Found: C, 81.94; H, 4.84; N, 4.07.
Compound 3j: colorless needles; 131-132 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 1.49-1.75 (m, 2 H), 1.81-1.85 (m, 2 H), 2.16-2.31 (m, 2 H), 2.54-2.62 (m, 2 H), 5.40 (s, 1 H, NCH), 7.22 (t, 1 H, J = 8.7 Hz), 7.30-7.35 (m, 2 H), 7.49-7.61 (m, 2 H), 7.67 (d, 1 H, J = 7.8 Hz), 7.95 (d, 1 H, J = 6.5 Hz), 8.05 (d, 1 H, J = 6.9 Hz). ¹³C NMR (75 MHz CDCl3): δ = 22.0 (CH2), 22.2 (CH2), 22.4 (CH2), 27.5 (CH2), 60.8 (NCH), 121.3 (CH), 122.7 (CH), 124.0 (CH), 124.7 (CH), 127.3 (CH), 127.6 (C), 128.4 (CH), 129.2 (C), 130.4 (C), 131.5 (CH), 132.4 (C), 133.6 (C), 141.2 (C), 165.6 (NCO). MS (EI): m/z (%) = 287 (86) [M+], 286 (67), 270 (4), 258 (100), 232 (10), 216 (11). Anal. Calcd (%) for C20H17NO: C, 83.60; H, 5.96; N, 4.87 Found: C, 83.67; H, 6.02; N, 4.74.
Compound 5: colorless needles; 172-174 ˚C. ¹H NMR (300 MHz CDCl3): δ = 2.20 (s, 3 H, CH3), 2.73 (dd, 1 H, J = 18.6, 9.6 Hz, CHH), 3.15 (dd, 1 H, J = 18.0, 2.4 Hz, CHH), 5.83 (dd, 1 H, J = 9.6, 2.4 Hz CH), 7.49 (d, 1 H, J = 7.5 Hz, C-5), 7.64 (t, 1 H, J = 7.2 Hz, ArH), 7.55 (t, 1 H, J = 7.2 Hz, ArH), 7.88 (d, 2 H, J = 8.7 Hz, H-2′), 7.92 (d, 1 H, J = 7.8 Hz, H-7), 8.30 (d, 2 H, J = 9.0 Hz, H-3′). ¹³C NMR (75 MHz, CDCl3): δ = 30.7 (CH3), 46.2 (CH2), 55.7 (C-3), 121.2 (2 C), 122.8 (CH), 124.5 (CH), 124.9 (2 C), 129.1 (CH), 130.1 (C), 133.3 (CH), 142.6 (C), 143.8 (C), 144.8 (C), 167.1 (NCO), 205.6 (CO). MS (EI): m/z (%) = 310 (11) [M+], 293 (10), 281 (7), 267 (27), 253 (44), 234 (18), 43 (100). Anal. Calcd (%) for C17H14N2O4: C, 65.80; H, 4.55; N, 9.03 Found: C, 65.75; H, 4.62; N, 9.02.
Compound 6b: mixture of cis- and trans-isomers (30:70). ¹H NMR (300 MHz, CDCl3): δ (trans-isomer) = 1.48 (d, 3 H, J = 7.8 Hz, CH3), 1.78 (dt, 1 H, J = 9.3, 3.3 Hz, CHH), 2.30 (dd, 1 H, J = 12.9, 1.2 Hz, CHH), 2.33 (s, 3 H, CH3), 3.18 (t, 1 H, J = 6.6 Hz, CH), 4.78 (d, 1 H, J = 12.3, Hz NCH), 7.06 (s, 1 H, H-4), 7.11 (d, 1 H, J = 8.4 Hz, H-2), 7.48-7.51 (m, 2 H), 7.57 (d, 1 H, J = 7.5 Hz), 7.92 (d, 1 H, J = 8.4 Hz), 8.46 (d 1 H, J = 8.1 Hz); δ (cis-isomer) = 1.42 (d 3 H, J = 6.9 Hz, CH3), 2.35 (s 3 H, CH3), 2.60 (dt 1 H, J = 13 5, 1 2 Hz, CHH), 3 21 (t 3 H, J = 6 9 Hz, CH3), 4 70 (dd 1 H, J = 12 3, 2.4 Hz, NCH), 7.11 (d, 1 H, J = 8.4 Hz, H-2), 7.18 (s, 1 H, H-4), 7.48-7.51 (m, 2 H), 7.59 (d, 1 H, J = 6.9 Hz), 7.92 (d, 1 H, J = 8.4 Hz), 8.44 (d, 1 H, J = 7.8 Hz). ¹³C NMR (75 MHz, CDCl3): δ (trans-isomer) = 21.0, 24.5, 30.8, 34.8, 54.2 (NCH), 120.1 (CH), 121.7 (CH), 124.1 (CH), 127.6 (CH), 128.3 (CH), 129.6 (CH), 131.0 (C), 131.8 (CH), 132.8 (C), 133.4 (C), 144.6 (C), 165.9 (NCO); δ (cis-isomer) = 20.9, 21.1, 31.4, 37.5, 58.7, 120.0 (CH), 121.7 (CH), 124.1 (CH), 127.6 (CH), 128.4 (CH), 129.6 (CH), 131.0 (C), 131.8 (CH), 132.9 (C), 133.4 (C), 144.6 (C), 165.9 (NCO). MS (EI): m/z = 263 (87) [M+], 248 (100), 232 (16), 220 (17), 115 (25), 77 (38).

9

(9) Crystal Data for Compound 3c
Formula: C20H16ClNO3; Mr = 353.79 monoclinic; a = 9.3133(17) Å, b = 7.3351(14) Å, c = 24.716(5) Å, β = 96.800(3)˚; space group P2(1)/n; V = 1676.6(5) ų; colorless plates ρ = 1.402 g cm-³, T = 296(2) K, space group P2(1)/c Z = 4, µ(Mo Ka) = 0.71073 mm-¹, c max = 25.82˚, 3217 reflections collected 2045 unique (R int = 0.1585) which was used in all calculations. Final wR (F2) = 0.0830 (all data); CCDC No: 695063