An Efficient and Convenient Approach to the Synthesis of Benzopyrans by a Three-Component Coupling of One-Pot Reaction

Abstract

A general and practical chemistry route to the synthesis of polyfunctionlized benzopyrans using tetrabutylammonium bromide (TBABr) as the catalyst (10 mol%) is described. This method provides several advantages such as neutral conditions, high yields and simple work-up procedure. In addition, water was chosen as a green solvent.

Key words

benzopyrans - tetrabutylammonium bromide - synthesis

References

• 1 Anastas P. Williamson T. Green Chemistry, Frontiers in Benign Chemical Synthesis and Procedures   Oxford Science Publications; Oxford: 1998. 
• 2 Wender PA. Handy SL. Wright DL. Chem. Ind. (London)  1997,  765 
• 3 Hudlicky T. Chem. Rev.  1996,  96:  3 
• 4a Foye WO. Prinicipi di Chimica Farmaceutica Piccin   Padova; Italy: 1991.  p.416 
• 4b Andreani LL. Lapi E. Boll. Chim. Farm.  1960,  99:  583 
• 4d Bonsignore L. Loy G. Secci D. Calignano A. Eur. J. Med. Chem.  1993,  28:  517 
• 5a Hatakeyama S. Ochi N. Numata H. Takano S. J. Chem. Soc., Chem. Commun.  1988,  1202 
• 5b Cingolant GM. Pigini M. J. Med. Chem.  1969,  12:  531 
• 6 O’Callaghan CN. Mc Murry TBH. J. Chem. Res., Synop.  1995,  214 
• 7 Ellis GP. The Chemistry of Heterocyclic Compounds, In Chromenes, Chromanes and Chromeones   Weissberger A. Taylor EC. Wiley; New York: 1977.  p.13 
• 8a Hafez EAA. Elnagdi MH. Elagamey AGA.
  El-Taweel FMAA. Heterocycles  1987,  26:  903 
• 8b Abdel Galil FM. Riad BY. Sherif SM. Elnagdi MH. Chem. Lett.  1982,  1123 
• 9 Mizuno N. Misono M. Chem. Rev.  1998,  98:  199 
• 10a Abdel-Larif FF. Indian J. Chem, Sect. B  1990,  29:  664 
• 10b Elagamey AGA. El-Taweel FMAA. Indian J. Chem., Sect. B  1990,  29:  885 
• 10c Kuthan J. Sebek P. Bohm S. Advances in Heterocyclic Chemistry   Katritzky AR. Academic Press, Inc.; New York: 1995. 
• 10d Bioxham J. Dell CP. Smith CW. Heterocycles  1994,  38:  399 
• 10e Elagamey AGA. Sawllim SZ.
  El-Taweel FMA. Elnagdi MH. Collect. Czech. Chem. Commun.  1988,  53:  1534 

11

General Procedure for the Preparation of Benzopyrans: A mixture of an aromatic aldehyde (1 mmol), malononitrile (1 mmol), phenol (1 mmol) and TBABr (10 mol%) in H₂O (20 mL) was stirred at refluxing for 6 h. The progress of the reaction was monitored by thin layer chromatograph. After completion of the reactions, the mixture was cooled to r.t. and extracted by Et₂O and EtOAc. The organic phase was collected and dried over anhyd Na₂SO₄. Then evaporate the solvent under reduced pressure and get the crude products. The crude products were purified by recrystallization by EtOH. Data of some compounds are shown below:
Compound 4a, 2-Amino-3-cyano-4-(phenyl)-4 H -benzo-chromene. Mp 210-211 °C (from EtOH): IR (KBr): ν_max = 3454, 3318, 3020, 2932, 2205, 1656, 1600, 1572, 1450, 1372, 1267, 1100, 1022, 811, 744 cm^-1. ¹H NMR: δ = 4.90 (s, 1 H, H-4), 7.10 (s 2 H, NH₂), 7.07-7.12 (m, 6 H, H-5, H-2′, H-3′, H-4′, H-5′, H-6′), 7.56-7.66 (m, 3 H, H-6, H-8, H-9), 7.94 (d, 1 H, J = 8.4 Hz, H-7 or H-10), 8.23 (d, 1 H, J = 8.4 Hz, H-10 or H-7). Anal. Calcd for C₂₀H₁₄N₂O: C, 80.54; H, 4.70; N, 9.39. Found: C, 80.40; H, 4.75; N, 9.37.
Compound 4c, 2-Amino-3-cyano-4-(3-chlorophenyl)-4 H -benzo-chromene. Mp 216-218 °C (from EtOH). IR (KBr): ν_max = 3455, 3340, 3023, 2930, 2210, 1645, 1600, 1580, 1470, 1378, 1266, 1030, 816, 750, 700 cm^-1. ¹H NMR: δ = 4.98 (s, 1 H, H-4), 7.24 (s, 2 H, NH₂), 7.12-7.38 (m, 4 H, H-4′, H-5′, H-6′, H-5), 7.23 (s, 1 H, H-2′), 7.56-7.66 (m, 3 H, H-6, H-8, H-9), 7.89 (d, 1 H, J = 8.4 Hz, H-7 or H-10), 8.26 (d, 1 H, J = 8.4 Hz, H-10 or H-7). Anal. Calcd for C₂₀H₁₃ClN₂O: C, 72.18; H, 3.91; N, 8.42. Found: C, 72.11; H, 4.01; N, 8.40.
Compound 4d, 2-Amino-3-cyano-4-(2-chlorophenyl)-4 H -benzo-chromene. Mp 236-237 °C (from EtOH). IR (KBr): ν_max = 3476, 3320, 2915, 2195, 1664, 1600, 1410, 1360, 1275, 1180, 1040, 805, 750 cm^-1. ¹H NMR: δ = 5.41 (s, 1 H, CH), 7.20 (s, 2 H, NH₂), 7.01 (d, 1 H, J = 8.4 Hz, H-5), 7.25-7.31 (m, 3 H, H-4′, H-5′, H-6′), 7.45 (d, 1 H, J = 8.4 Hz, H-3′), 7.56-7.67 (m, 3 H, H-6, H-8, H-9), 7.89 (d, 1 H, J = 8.4 Hz, H-7 or H-10), 8.24 (d, 1 H, J = 8.4 Hz, H-10 or H-7). Anal. Calcd for C₂₀H₁₃ClN₂O: C, 72.18; H, 3.91; N, 8.42. Found: C, 72.11; H, 4.00; N, 8.39.
Compound 4e, 2-Amino-3-cyano-4-(2,4-dichlorophenyl)-4 H -benzo-chromene. Mp 213-215 °C (from EzOH). IR (KBr): ν_max = 3454, 3336, 3030, 2186, 1667, 1600, 1572, 1466, 1378, 1200, 1050, 860, 811, 755 cm^-1. ¹H NMR δ = 5.47 (s, 1 H, H-4), 7.30 (s, 2 H, NH₂), 6.98 (d, 1 H, J = 8.4 Hz, H-6′), 7.60 (s, 1 H, H-3′), 7.39-7.59 (m, 2 H, H-5, H-5′), 7.69-7.89 (m, 3 H, H-6, H-8, H-9), 8.03 (d, 1 H, J = 8.4 Hz, H-7 or H-10), 8.25 (d, 1 H, J = 8.4 Hz, H-10 or H-7). Anal. Calcd for C₂₀H₁₂Cl₂N₂O: C, 65.39; H, 3.27; N, 7.63. Found: C, 65.23; H, 3.25; N, 7.60.
Compound 4f, 2-Amino-3-cyano-4-(4-nitrophenyl)-4 H -benzo-chromene. Mp 239-241 °C (from EtOH). IR (KBr): ν_max = 3460, 3335, 2196, 1665, 1600, 1575, 1536, 1500, 1346, 1270, 1195, 1100, 805, 770 cm^-1. ¹H NMR δ = 5.12 (s, 1 H, H-4), 7.29 (s, 2 H, NH₂), 7.05 (d, 1 H, J = 8.4 Hz, H-5), 7.51-7.72 (m, 3 H, H-6, H-8, H-9), 7.52 (d, 2 H, H-2′, H-6′), 7.90 (d, 1 H, J = 8.4 Hz, H-7 or H-10), 8.15 (d, 2 H, H-3′, H-5′), 8.27 (d, 1 H, J = 8.4 Hz, H-10 or H-7). Anal. Calcd for C₂₀H₁₃N₃O₃: C, 69.97; H, 3.79; N, 12.24. Found: C, 70.09; H, 3.99; N, 12.12.
Compound 4h, 2-Amino-3-cyano-4-(3,4-dioxymethyl-enephenyl)-4 H -benzo-chromene. Mp 242-244 °C (from EtOH). IR (KBr): ν_max = 3434, 3320, 2905, 2196, 1670, 1605, 1575, 1490, 1405, 1380, 1225, 1190, 1040, 790, 770 cm^-1. ¹H NMR δ = 4.88 (s, 1 H, H-4), 5.92 (s, 2 H, CH₂), 6.74-6.85 (m, 3 H, H-2′, H-5′, H-6′), 7.10-7.13 (m, 3 H, NH₂ + H-5), 7.55-7.65 (m, 3 H, H-6, H-8, H-9), 7.88 (d, 1 H, J = 8.4 Hz, H-7 or H-10), 8.22 (d, 1 H, J = 8.4 Hz, H-10 or H-7). Anal. Calcd for C₂₁H₁₄N₂O₃: C, 73.68; H, 4.09; N, 8.19. Found: C, 73.70; H, 4.00; N, 8.25.
Compound 4k, 2-Amino-3-cyano-4-(4-dimethylamino-phenyl)-4 H -benzo-chromene. Mp 203-205 °C (from EtOH). IR (KBr): ν_max = 3465, 3340, 3090, 2955, 2863, 2806, 2193, 1662, 1605, 1570, 1522, 1400, 1380, 1342, 1262, 1190, 1100, 800, 750 cm^-1. ¹H NMR δ = 2.84 [s, 6 H, N(CH₃)₂], 4.75 (s, 1 H, H-4), 7.03-7.10 (m, 3 H, H-5 or NH₂), 6.65 (d, 2 H, J = 8.4 Hz, H-2′, H-6′ or H-3′, H-5′), 7.06 (d, 2 H, J = 8.4 Hz, H-3′, H-5′ or H-2′, H-6′), 7.53-7.64 (m, 3 H, H-6, H-8, H-9), 7.88 (d, 1 H, J = 8.4 Hz, H-7 or H-10), 8.24 (d, 1 H, J = 8.4 Hz, H-10 or H-7). Anal. Calcd for C₂₂H₁₉N₃O: C, 77.42; H, 5.57; N, 12.32. Found: C, 77.36; H, 5.60; N, 12.23.
Compound 4n, 3-Amino-2-cyano-1-(4-nitrophenyl)-1 H -benzo-chromene. Mp 185-186 °C (from EtOH). IR (KBr): ν_max = 3430, 3325, 2190, 1650, 1610, 1582, 1540, 1502, 1340, 1244, 1200, 1070, 810 cm^-1. ¹H NMR δ = 5.45 (s, 1 H, H-4), 7.20 (s, 2 H, NH₂), 7.36-7.52 (m, 3 H, H-6, H-7, H-9 or H-10), 7.69-8.03 (m, 2 H, H-5 and H-8), 7.98 (d, 1 H, J = 9.2 Hz, H-10 or H-9), 7.44 (d, 2 H, H-2′ and H-6′), 8.15 (d, 2 H, H-3′ and H-5′). Anal. Calcd for C₂₀H₁₃N₃O₃: C, 69.97; H, 3.79; N, 12.24. Found: C, 70.10; H, 3.88; N, 12.08.
Compound 4o, 2-Amino-3-cyano-4-(dioxymethylene-phenyl)-4 H -benzo-chromene. Mp 250-252 °C (from EtOH). IR (KBr): ν_max = 3443, 3340, 3045, 2886, 2195, 1657, 1600, 1580, 1500, 1454, 1400, 1234, 1195, 1040, 811, 743 cm^-1. ¹H NMR δ = 5.25 (s, 1 H, H-4), 5.91 (s, 2 H, -OCH₂O-), 6.95 (s, 2 H, NH₂), 6.66-6.80 (m, 3 H, H-2′, H-5′, H-6′), 7.86-7.95 (m, 2 H, H-5 or H-8), 7.91 (d, 1 H, J = 8.0 Hz, H-9 or H-10), 7.20-7.49 (m, 3 H, H-6, H-7, H-10). Anal. Calcd for C₂₁H₁₄N₂O₃: C, 73.68; H, 4.09; N, 8.19; Found: C, 73.72; H, 3.99; N, 8.06.