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Synlett 2009(11): 1795-1799  
DOI: 10.1055/s-0029-1217367
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

One-Pot, Three-Component Synthesis of a Library of New Pyrrolo[1,2-a]quinoline Derivatives

Emilian Georgescua, Mino R. Caira*b, Florentina Georgescua, Bogdan Drăghicic, Marcel M. Popac, Florea Dumitrascuc
a Oltchim Research Center, St. Uzinei 1, 240050 Ramnicu Valcea, Romania
b Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
Fax: +27(21)6897499; e-Mail: Mino.Caira@uct.ac.za;
c Centre of Organic Chemistry ‘C. D. Nenitzescu’, Romanian Academy, Spl. Independentei 202B, Bucharest 060023, Romania
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Publication History

Received 2 February 2009
Publication Date:
12 June 2009 (online)

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Abstract

The synthesis of a library of pyrrolo[1,2-a]quinoline derivatives 4-33 was performed by an efficient one-pot, three-component reaction from quinolines 1a-c, 2-bromoacetophenones 2 and non-symmetrical acetylenic dipolarophiles 3a-c in 1,2-epoxypropane as both reaction medium and HBr scavenger. As this approach was unsuccessful in the case of DMAD, a different method was used for the synthesis of pyrrolo[1,2-a]quinolines 35-44. The structural features of the cycloadducts 19 and 44 were investigated by X-ray analysis.

Key words

1,3-dipolar cycloaddition - N-ylide - pyrrolo[1,2-a]quinoline - multicomponent reaction

    References and Notes

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9

Synthesis of Pyrrolo[1,2- a ]quinolines 4-33; General Procedure: Quinoline 1 (5 mmol), phenacyl bromide 2 (5 mmol) and non-symmetrical acetylene 3 (ethyl propiolate, 3-butyn-2-one or benzoylacetylene; 7 mmol) in 1,2-epoxy-propane (40 mL) were stirred at room temperature for 30 h. The solvent was partly removed by evaporation, then methanol (10 mL) was added and the mixture was left overnight at room temperature. The solid was filtered, washed with a mixture of MeOH-Et2O (1:1) and recrystallised from CHCl3-MeOH. Ethyl 1-(4-Methyl-benzoyl)-7-methyl-pyrrolo[1,2- a ]quinoline-3-carboxy-late (19): Yellow crystals with mp 173-175 ˚C were obtained by recrystallization from CHCl3-MeOH. Yield: 54%; Anal. Calcd for C24H21NO3: C, 77.61; H, 5.70; N, 3.77. Found: C, 77.91; H, 5.94; N, 3.98. FT-IR: 1617, 1654, 1704, 2976 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 1.39 (t, J = 7.1 Hz, 3 H, MeCH2), 2.47 (s, 3 H, MeAr), 2.50 (s, 3 H, 7-Me), 4.39 (q, J = 7.1 Hz, 2 H, CH2), 7.35-7.38 (m, 3 H, H-8, H-3′, H-5′), 7.57 (d, J = 2.1 Hz, 1 H, H-6), 7.62 (s, 1 H, H-2), 7.60 (d, J = 9.3 Hz, 1 H, H-5), 7.87 (d, J = 8.9 Hz, 1 H, H-9), 7.95 (d, J = 8.8 Hz, 2 H, H-2′, H-6′), 8.23 (d, J = 9.3 Hz, 1 H, H-4). ¹³C NMR (75 MHz, CDCl3): δ = 14.5 (MeCH2), 20.8, 21.6 (7-Me, MeAr), 59.9 (OCH2), 107.4 (C-3), 117.6 (C-4), 119.9 (C-9), 125.1, 128.0, 131.4, 135.9, 139.7 (C-1, C-3a, C-5a, C-9a, C-7), 128.3 (C-6), 129.4 (C-5), 128.6 (C-8), 129.1 (C-3′, C-5′), 129.9 (C-2), 130.2 (C-2′, C-6′), 135.1 (C-1′), 143.4 (C-4′), 164.1 (COO), 184.8 (COAr).

10

Synthesis of Pyrrolo[1,2- a ]quinolines 35-44; General Procedure: Quaternary salt 34a-j (5 mmol) and DMAD or DEAD (7 mmol) in 1,2-epoxypropane (40 mL) were stirred at room temperature for 24 h. The solvent was partly removed by evaporation, then methanol (10 mL) was added and the mixture was left overnight at room temperature. The solid was filtered, washed on filter with a mixture of MeOH-Et2O (1:1) and recrystallised from CHCl3-MeOH. Dimethyl 1-(3-Bromobenzoyl)-7-methylpyrrolo[1,2- a ]quinoline-2,3-dicarboxylate (39): Yellow crystals with mp 192-194 ˚C were obtained by recrystallization from MeOH-CHCl3. Yield: 44%. Anal. Calcd for C23H18BrNO3: C, 63.32; H, 4.16; Br, 18.31; N, 3.21. Found: C, 63.44; H, 4.39; Br, 18.66; N, 3.56. FT-IR: 1617, 1654, 1704, 2976 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 2.54 (s, 3 H, 7-Me), 3.50, 3.90 (s, 6 H, 2-CO2Me, 3-CO2Me), 7.27 (dd, J = 8.8, 2.1 Hz, 1 H, H-8), 7.36 (t, J = 7.8 Hz, 1 H, H-5′), 7.51 (d, J = 8.9 Hz, 1 H, H-9), 7.57 (d, J = 2.1 Hz, 1 H, H-6), 7.58 (d, J = 9.3 Hz, 1 H, H-5), 7.73-7.77 (m, 1 H, H-4′), 7.84-7.87 (m, 1 H, H-6′), 8.15 (t, J = 2.0 Hz, 1 H, H-2′), 8.23 (d, J = 9.3 Hz, 1 H, H-4). ¹³C NMR (75 MHz, CDCl3): δ = 20.9 (7-Me), 51.7, 52.8 (CO2CH3), 105.5 (C-3), 117.7 (C-4), 118.8 (C-9), 122.7 (C-3′), 125.3, 127.2, 128.8, 131.2, 135.7, 140.3 (C-1, C-3a, C-5a, C-9a, C-7, C-2), 128.4 (C-6), 128.5 (C-2′), 128.9 (C-5), 130.2 (C-5′), 130.4 (C-8), 132.7 (C-2′), 136.5 (C-4′), 139.5 (C-1′), 163.5, 165.1 (2 × COO), 185.7 (COAr).

11

X-ray crystal data for 19: C24H21NO3; yellow plate; M = 371.42; triclinic; P(-1); a = 9.3086 (5) Å, b = 10.4631 (5) Å, c = 10.9389 (5) Å, α = 91.153 (2)˚, β = 112.900(3)˚, γ = 104.195 (3)˚; V = 943.48 (7) ų; Z = 2; T = 173 (2) K; F 000  = 392; R1 = 0.0428, wR2 = 0.1170. The CCDC deposition number: 718544.

12

X-ray crystal data for 44: C28H27NO7; pale-yellow plate; M = 489.51; triclinic; P(-1); a = 7.5730 (3) Å, b = 13.0161 (3) Å, c = 13.4416 (6) Å, α = 97.269 (2)˚, β = 104.946 (2)˚, γ = 102.512 (3)˚; V = 1226.13 (8) ų; Z = 2; T = 173 (2) K; F 000  = 516; R1 = 0.0414, wR2 = 0.1132. The CCDC depo-sition number: 718545.