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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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Publication History

Received 20 September 2008
Publication Date:
26 February 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

  • 1a Ishihara Y. Kiyota Y. Goto G. Chem. Pharm. Bull.  1990,  38:  3024 
    Search in Google Scholar
  • 1b Sui Z. Altom J. Nguyen VN. Fernandez J. Bernstein JI. Hiliard JJ. Barrett JF. Podlogar BL. Ohemeng KA. Bioorg. Med. Chem.  1998,  6:  735 
    Search in Google Scholar
  • 1c Goto G, and Ishihara Y. inventors; JP  02042078.  ; Application: JP 88-193656 19880802
  • 2a Kouznetsov VV. Cruz UM. Zubkov FI. Nikitina EV. Synthesis  2007,  375 
  • 2b Zubkov FI. Boltukhina EV. Turchin KF. Borisov RS. Varlamov AV. Tetrahedron  2005,  61:  4099 
    Search in Google Scholar
  • 2c Mamane V. Fort Y. Tetrahedron Lett.  2006,  47:  2337 
    Search in Google Scholar
  • 2d Hamersak Z. Litvic M. Sepac D. Lesac A. Raza Z. Sunjic V. Synthesis  2002,  2174 
  • 2e Kim G. Keum G. Heterocycles  1997,  45:  1979 
    Search in Google Scholar
  • 2f Epsztajn J. Jozwiak A. Koluda P. Sadokierska I. Wilkowska ID. Tetrahedron  2000,  56:  4837 
    Search in Google Scholar
  • 2g Epsztajn J. Grzelak R. Jozwiak A. Synthesis  1996,  1212 
  • 2h Kumar P. Dinesh CU. Pandey B. Tetrahedron Lett.  1994,  35:  9229 
    Search in Google Scholar
  • 3 Bonnett R. North SA. Adv. Heterocycl. Chem.  1981,  29:  341 
    Search in Google Scholar
  • 4a Zhang W. Zhen A. Liu Z. Yang L. Liu ZL. Tetrahedron Lett.  2005,  46:  5691 
    Search in Google Scholar
  • 4b Zhang W. Huang L. Wang J. Synthesis  2006,  2053 
  • 5a Kleber C. Andrade Z. Matos RAF. Synlett  2003,  1189 
  • 5b Kraus GA. Neuenschwander K. Tetrahedron Lett.  1980,  21:  3841 
    Search in Google Scholar
  • 6 Lübbers T. Angehrn P. Gmünder H. Herzig S. Bioorg. Med. Chem. Lett.  2007,  17:  4708 
    CrossrefSearch in Google Scholar
  • 7a Maryanoff BE. Zhang HC. Cohen JH. Turchi IJ. Maryanoff CA. Chem. Rev.  2004,  104:  1431 
    Search in Google Scholar
  • 7b Speckamp WN. Hiemstra H. Tetrahedron  1985,  41:  4367 
    Search in Google Scholar
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