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Synlett 2009(9): 1485-1489  
DOI: 10.1055/s-0029-1216741
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

TDAE Strategy Using α-Diketones: Rapid Access to 2,3-Diphenylquinoline and Acenaphtho[1,2-b]quinoline Derivatives

Thierry Juspin, Thierry Terme, Patrice Vanelle*
Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, Universités d’Aix-Marseille I, II et III - CNRS, UMR 6264, Laboratoire Chimie Provence, 27 Boulevard J. Moulin, 13385 Marseille Cedex 05, France
Fax: +33(4)91794677; e-Mail: patrice.vanelle@pharmacie.univ-mrs.fr;
Further Information

Publication History

Received 8 February 2009
Publication Date:
04 May 2009 (online)

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Abstract

A series of new substituted diphenylquinolines and acenaphtho[1,2-b]quinolines was prepared in good yields according to a two-step synthesis using the TDAE methodology from substituted o-nitrobenzyl chlorides and α-diketones followed by a reduction-cyclization-dehydration step.

Key words

TDAE - α-diketone - o-nitrobenzyl chloride - diphenylquinoline - acenaphtho[1,2-b]quinoline

    References and Notes

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13

General Procedure for the Reaction of Nitrobenzyl Chloride 1, 6a-d and Naphthylene-1,2-dione (2) or Benzil (3) Using TDAE
Into a two-necked flask equipped with a SiO2 drying tube and a nitrogen inlet was added, under nitrogen at -20 ˚C, anhyd DMF (8 mL) soln of nitrobenzyl chlorides 1, 6a-d (0.2 g) and naphthylene-1,2-dione (2) or benzil (3, 3 equiv). The soln was stirred and maintained at this temperature for 30 min and then TDAE (1 equiv) was added dropwise (via a syringe). A red color immediately developed with the formation of a white fine precipitate. The soln was vigorously stirred at -20 ˚C for 1 h and then warmed up to 80 ˚C for 2 h. The turbid soln was filtered (to remove the octamethyl-oxamidinium dichloride) and diluted with toluene (50 mL). The organic soln was washed with H2O (3 × 50 mL) and dried over Na2SO4. Evaporation of the solvent left a brown oil as crude product. Purification by SiO2 [eluting with CH2Cl2 for compounds 4, 5, 7a-d and with a mixture of CH2Cl2-PE (6:4) for compounds 8a-d] and recristallization with i-PrOH gave the corresponding
α-hydroxyketones.
New Products
Compound 4: orange solid; mp 181.4 ˚C. ¹H NMR (200 MHz, CDCl3): δ = 2.34 (br s, 1 H), 3.23 (d, J AB = 13.1 Hz,
1 H), 3.49 (d, J AB = 13.1 Hz, 1 H), 7.18 (d, J = 8.8 Hz, 2 H), 7.30 (d, J = 8.0 Hz, 1 H), 7.58-7.74 (m, 2 H), 7.86-7.98 (m, 4 H), 8.10 (d, J = 8.0 Hz, 1 H). ¹³C NMR (50 MHz, CDCl3): δ = 44.1, 80.1, 121.2, 122.5, 122.9, 125.9, 128.5, 128.6, 130.1, 130.6, 131.3, 132.4, 137.8, 141.3, 142.6, 147.0, 204.3. Anal. Calcd for C19H13NO4: C, 71.47; H, 4.10; N, 4.39. Found: C, 71.17; H, 4.21; N, 4.28.
Compound 5: yellow solid; mp 167.3 ˚C. ¹H NMR (200 MHz, CDCl3): δ = 3.71 (d, J AB = 13.4 Hz, 1 H), 3.81 (d, J AB = 13.4 Hz, 1 H), 4.30 (br s, 1 H), 7,08 (d, J = 8.8 Hz, 2 H), 7.30-7.55 (m, 8 H), 7.62-7.67 (m, 2 H), 8.00 (d, J = 8.8 Hz, 2 H). ¹³C NMR (50 MHz, CDCl3): δ = 44.2, 81.9, 123.0, 125.7, 128.5, 129.2, 130.1, 131.5, 133.4, 134.0, 141.3, 143.2, 147.0, 200.0. Anal. Calcd for C21H17NO4: C, 72.61; H, 4.93; N, 4.03. Found: C, 72.01; H, 4.95; N, 3.99.

15

New Products
Compound 7a: yellow solid; mp 150.7 ˚C. ¹H NMR (200 MHz, CDCl3): δ = 2.54 (br s, 1 H), 3.44 (d, J AB = 13.8 Hz, 1 H), 3.88 (d, J AB = 13.8 Hz, 1 H), 7.16 (d, J = 6.9 Hz, 1 H), 7.37-7.45 (m, 2 H), 7.49-7.61 (m, 2 H), 7.70-7.77 (m, 1 H), 7.86-7.97 (m, 3 H), 8.12 (d, J = 8.1 Hz, 1 H). ¹³C NMR (50 MHz, CDCl3): δ = 40.2, 80.0, 120.8, 122.5, 125. 0, 125.7, 128.2, 128.5, 128.6, 130.1, 130.2, 130.6, 132.2, 132.4, 134.3, 138.4, 140.8, 150.2, 204.1. Anal. Calcd for C19H13NO4: C, 71.47; H, 4.10; N, 4.39. Found: C, 71.28;
H, 4.17; N, 4.35.
Compound 7b: brown solid; mp 128.8 ˚C. ¹H NMR (200 MHz, CDCl3): δ = 2.41 (s, 3 H), 2.87 (br s, 1 H), 3.43 (d, J AB = 13.7 Hz, 1 H), 3.87 (d, J AB = 13.7 Hz, 1 H), 7.20 (d, J = 7.4 Hz, 2 H), 7.27 (s, 1 H), 7.54-7.62 (m, 1 H), 7.70-7.78 (m, 1 H), 7.84-7.88 (m, 2 H), 7.90-7.98 (m, 1 H), 8.13 (d, J = 8.0 Hz, 1 H). ¹³C NMR (50 MHz, CDCl3): δ = 21.3, 40.5, 80.0, 120.7, 122.5, 125.2, 125.6, 128.5, 128.6, 128.8, 130.2, 130.3, 130.6, 132.1, 134.9, 138.6, 140.8, 143.6, 147.8, 204.1. Anal. Calcd for C20H15NO4: C, 72.06; H, 4.54; N, 4.20. Found: C, 71.85; H, 4.54; N, 4.15.
Compound 7c: yellow solid; mp 215.5 ˚C. ¹H NMR (200 MHz, CDCl3): δ = 3.25 (br s, 1 H), 3.45 (d, J AB = 13.7 Hz, 1 H), 3.92 (s, 3 H), 3.93 (s, 3 H), 3.94 (d, J AB = 13.7 Hz, 1 H), 6.82 (s, 1 H), 7.23-7.30 (m, 1 H), 7.55 (s, 1 H), 7.53-7.64 (m, 1 H), 7.72-7.79 (m, 1 H), 7.87-7.98 (m, 2 H), 8.14 (d, J = 8.0 Hz, 1 H). ¹³C NMR (50 MHz, CDCl3): δ = 40.6, 56.3, 56.4, 80.2, 108.2, 115.5, 120.7, 122.5, 125.1, 125.7, 128.4, 128.5, 130.2, 130.6, 132.1, 138.7, 140.8, 142.3, 147.9, 152.2, 204.3. Anal. Calcd for C21H17NO6: C, 66.49; H, 4.52; N, 3.69. Found: C, 66.25; H, 4.57; N, 3.56.
Compound 7d: brown solid; mp 151.3 ˚C. ¹H NMR (200 MHz, CDCl3): δ = 2.43 (br s, 1 H), 3.45 (d, J AB = 13.8 Hz, 1 H), 3.75 (d, J AB = 13.8 Hz, 1 H), 6.12 (s, 2 H), 6.92 (s, 1 H), 7.30 (d, J = 6.8 Hz, 1 H), 7.47 (s, 1 H), 7.56-7.64 (m, 1 H), 7.71-7.79 (m, 1 H), 7.87-7.98 (m, 2 H), 8.13 (d, J = 8.1 Hz, 1 H). ¹³C NMR (50 MHz, CDCl3): δ = 40.8, 80.0, 102.9, 105.8, 112.7, 120.4, 122.5, 125.6, 127.2, 128.4, 128.6, 130.1, 130.5, 132.1, 138.7, 140.6, 143.8, 147.1, 151.1, 204.1. Anal. Calcd for C20H13NO6: C, 66.12; H, 3.61; N, 3.86. Found: C, 66.24; H, 3.71; N, 3.74.
Compound 8a: white solid; mp 128.2 ˚C. ¹H NMR (200 MHz, CDCl3): δ = 3.83 (d, J AB = 14.0 Hz, 1 H), 4.10 (d, J AB = 14.0 Hz, 1 H), 4.60 (br s, 1 H), 6.69-6.74 (m, 1 H), 7.24-7.48 (m, 10 H), 7.76-7.82 (m, 3 H). ¹³C NMR (50 MHz, CDCl3): δ = 40.9, 83.1, 124.6, 125.4, 127.8, 128.2, 128.8, 130.4, 130.6, 132.1, 132.8, 133.3, 134.4, 141.3, 151.4, 200.1. Anal. Calcd for C21H17NO4: C, 72.61; H, 4.93; N, 4.03. Found: C, 72.20; H, 4.86; N, 4.05.
Compound 8b: white solid; mp 119.2 ˚C. ¹H NMR (200 MHz, CDCl3): δ = 2.16 (s, 3 H), 3,74 (d, J AB = 14.0 Hz, 1 H), 4.08 (d, J AB = 14.0 Hz, 1 H), 4.71 (br s, 1 H), 7.07-7.14 (m, 2 H), 7.30-7.37 (m, 4 H), 7.39-7.48 (m, 4 H), 7.72 (d, J AB = 8.4 Hz, 1 H), 7.80 (m, 2 H). ¹³C NMR (50 MHz, CDCl3): δ = 21.1, 41.1, 83.1, 124.8, 125.4, 128.0, 128.1, 128.3, 128.7, 130.4, 130.6, 132.8, 134.0, 134.5, 141.4, 143.2, 149.0, 200.1. Anal. Calcd for C22H19NO4: C, 73.12; H, 5.30; N, 3.88. Found: C, 72.82; H, 5.20; N, 3.88.
Compound 8c: yellow solid; mp 128.0 ˚C. ¹H NMR (200 MHz, CDCl3): δ = 3.47 (s, 3 H), 3.59 (d, J AB = 14.2 Hz, 1 H), 3.90 (s, 3 H), 4.20 (d, J AB = 14.2 Hz, 1 H), 4.91 (br s, 1 H), 5.90 (s, 1 H), 7.29-7.52 (m, 8 H), 7.44 (s, 1 H), 7.86-7.90 (m, 2 H). ¹³C NMR (50 MHz, CDCl3): δ = 41.8, 55.8, 56.2, 83.5, 107.9, 114.7, 125.5, 125.9, 127.9, 128.0, 128.8, 130.6, 132.7, 134.5, 141.5, 143.4, 147.6, 152.0, 200.2. Anal. Calcd for C23H21NO6: C, 67.80; H, 5.20; N, 3.44. Found: C, 67.70; H, 5.15; N, 3.44.
Compound 8d: yellow solid; mp 137.5 ˚C. ¹H NMR (200 MHz, CDCl3): δ = 3.63 (d, J AB = 14.2 Hz, 1 H), 4.13 (d, J AB = 14.2 Hz, 1 H), 4.80 (br s, 1 H), 6.00 (d, J = 4.3 Hz, 2 H), 6.17 (s, 1 H), 7.25-7.34 (m, 4 H), 7.31 (s, 1 H), 7.38-7.43 (m, 2 H), 7.48-7.51 (m, 2 H), 7.84 (d, J = 7.2 Hz, 2 H). ¹³C NMR (50 MHz, CDCl3): δ = 41.5, 83.3, 102.7, 105.5, 111.8, 125.2, 127.7, 128.0, 128.1, 128.8, 130.4, 132.7, 134.4, 141.4, 145.1, 146.7, 150.9, 200.0. Anal. Calcd for C22H17NO6: C, 67.51; H, 4.38; N, 3.58. Found: C, 67.14; H, 4.42; N, 3.54.

17

General Procedure for the Reduction-Cyclization-Double Dehydration Step
In a two-necked flask a soln of the appropriate starting material (7a-d, 8a-d) in glacial AcOH (20 mL) was heated at 120 ˚C and then iron powder (14 equiv or 28 equiv) was added. After 2 h or 48 h of reaction, the mixture was filtered on Celite® and the solvent evaporated under reduced pressure. After neutralization with an aq soln of Na2CO3 and extraction with CH2Cl2 (3 × 50 mL), the combined organic layers were washed with H2O and dried over Na2SO4. Evaporation of the solvent left a viscous liquid as crude product. Purification by SiO2 chromatography [eluting with CH2Cl2 for compounds 9a-d, 10c,d and with a mixture of CH2Cl2-PE (7/3) for compounds 10a,b] and recrystalli-zation with i-PrOH gave the corresponding 2,3-diphenyl-quinoline or acenaphto[1,2-b]quinoline derivatives.
New Products
Compound 9c: orange solid; mp 276.6 ˚C. ¹H NMR (200 MHz, CDCl3): δ = 4.01 (s, 3 H), 4.07 (s, 3 H), 7.08 (s, 1 H), 7.56 (s, 1 H), 7.60-7.78 (m, 2 H), 7.85-7.97 (m, 3 H), 8.29 (s, 1 H), 8.38 (d, J = 6.8 Hz, 1 H). ¹³C NMR (50 MHz, CDCl3): δ = 56.0, 56.2, 106.3, 107.9, 113.8, 119.7, 121.3, 122.6, 126.3, 126.8, 128.1, 128.4, 129.9, 130.4, 133.5, 134.2, 138.9, 143.4, 149.5, 152.2. Anal. Calcd for C21H15NO2: C, 80.49; H, 4.82; N, 4.47. Found: C, 79.46;
H, 4.85; N, 4.35.
Compound 9d: yellow solid; mp 237.7 ˚C. ¹H NMR (200 MHz, CDCl3): δ = 6.11 (s, 2 H), 7.11 (s, 1 H), 7.55 (s, 1 H), 7.62-7.79 (m, 2 H), 7.87-7.98 (m, 3 H), 8.29 (s, 1 H), 8.38 (d, J = 6.9 Hz, 1 H). ¹³C NMR (50 MHz, CDCl3): δ = 101.8, 104.0, 106.3, 119.8, 121.2, 124.1, 126.6, 126.9, 128.1, 128.3, 128.5, 130.0, 130.5, 133.6, 134.3, 135.3, 145.5, 147.7, 150.4, 158.1. Anal. Calcd for C20H11NO2: C, 80.80; H, 3.73; N, 4.71. Found: C, 79.36; H, 3.80; N, 4.56.
Compound 10b: white solid; mp 123.5 ˚C. ¹H NMR (200 MHz, CDCl3): δ = 2.57 (s, 3 H), 7.21-7.31 (m, 8 H), 7.41-7.48 (m, 2 H), 7.55-7.62 (m, 2 H), 8.09-8.16 (m, 2 H). ¹³C NMR (50 MHz, CDCl3): δ = 21.6, 126.2, 127.1, 127.2, 127.8, 127.9, 128.2, 128.9, 129.7, 130.0, 132.0, 134.5, 136.7, 137.1, 140.0, 140.2, 145.7, 157.3. HRMS (EI):
m/z calcd for C22H17N: 296.1434; found: 296.1433.
Compound 10d: white solid; mp 159.3 ˚C. ¹H NMR (200 MHz, CDCl3): δ = 6.13 (s, 2 H), 7.11 (s, 1 H), 7.19-7.32
(m, 8 H), 7.40-7.45 (m, 2 H), 7.56 (s, 1 H), 8.00 (s, 1 H). ¹³C NMR (50 MHz, CDCl3): δ = 102.0, 102.4, 105.0, 124.5, 127.2, 128.0, 128.3, 129.7, 130.1, 132.9, 137.5, 137.6, 138.7, 139.5, 144.5, 148.4, 151.4, 155.3. Anal. Calcd for C22H15NO2: C, 81.21; H, 4.65; N, 4.30. Found: C, 80.74; H, 4.77; N, 4.15.