LPDE-Catalyzed Intramolecular Cyclization of Arylimines: A Facile Synthesis of Tetrahydrochromanoquinolines

Abstract

Lithium perchlorate in diethyl ether (LPDE) is found to catalyze an intrarmolecular cyclization of aldimines derived from aromatic amines and O-prenyl derivatives of salicylaldehydes to afford the corresponding tetrahydrochromano[4,3-b]quinoline derivatives in excellent yields with moderate diastereoselectivity.

Key words

LPDE - aldimines - intramolecular cyclization - acridines

References

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12

Experimental procedure: Method I: A mixture of prenyl derivative of salicylaldimine (5 mmol) and 5 M lithium perchlorate in diethyl ether (5 mL) was stirred at ambient temperature for an appropriate time (Table). After completion of the reaction, as indicated by TLC, the reaction mixture was quenched with water (15 mL) and extracted with diethyl ether (2 × 15 mL). The combined organic layers were dried over anhydrous Na₂SO₄, concentrated in vacuo and purified by column chromatography on silica gel (Merck, 100-200 mesh ethyl acetate-hexane, 0.5:9.5) to afford pure product.
Method II: A mixture of prenyl derivative of salicylaldimine (5 mmol) and Amberlyst 15 (1.5 g) in acetonitrile (10 mL) was stirred at ambient temperature for an appropriate time (Table). After completion of the reaction, as indicated by TLC, the reaction mixture was filtered and washed with ethyl acetate (2 × 10 mL) The combined organic layers were dried over anhydrous Na₂SO₄, concentrated in vacuo and purified by column chromatography on silica gel (Merck, 100-200 mesh ethyl acetate-hexane, 0.5:9.5) to afford pure product. The ion-exchange resin Amberlyst 15 was washed with methanol and reused in subsequent reaction without apparent loss of activity.
Spectral data for product 2b: Solid, mp146-147 °C; ¹H NMR (CDCl₃): δ 1.27 (s, 3 H), 1.50 (s, 3 H), 1.98 (dt, 1 H, J = 10.8, 3.5 Hz), 3.90 (brs, NH), 3.95 (t, 1 H, J = 10.8 Hz), 4.27 (dd, 1 H, J = 10.8, 3.5 Hz), 4.60 (d, 1 H, J = 3.5 Hz), 6.38 (d, 1 H, J = 8.0 Hz), 6.85-7.0 (m, 3 H), 7.05 (d, 1 H, J = 2.1 Hz), 7.10 (d, 2 H, J = 8.0 Hz); ¹³C NMR (CDCl₃, proton decoupled): δ 25.4, 33.5, 40.1, 45.9, 63.3, 114.4, 116.8, 117.7, 120.4, 121.4, 122.5, 123.4, 124.5, 125.5, 127.1, 127.7, 128.2, 129.3, 129.4, 129.6, 138.9, 153.7; IR (KBr): 3381, 3087, 3030, 2960, 2933, 2891, 1697, 1574, 1499, 1478, 1329, 1245, 1059, 1030, 972 cm^-1; EIMS : m/z 299 M⁺, 284, 254, 178, 168, 131, 117, 77. 3b: Oil, ¹H NMR (CDCl₃): δ 1.20 (s, 3 H), 1.45 (s, 3 H), 2.05 (dt, 1 H, J = 11.2, 3.3 Hz), 3.95 (t, 1 H, J = 11.2 Hz), 4.05 (brs, NH), 4.43 (d, 1 H, J = 11.2 Hz), 4.60 (dd, 1 H, J = 11.2, 3.3 Hz), 6.40 (d, 1 H, J = 8.0 Hz), 6.95-7.05 (m, 3 H), 7.10-7.25 (m, 3 H).
2e: Solid, mp130-131 °C; ¹H NMR (CDCl₃): δ 1.38 (s, 3 H), 1.45 (s, 3 H), 1.95 (dt, 1 H, J = 10.8, 3.5 Hz), 2.15 (s, 3 H), 3.60 (brs, NH), 3.80 (d, 1 H, J = 10.8 Hz), 4.20 (dd, 1 H, J = 10.8, 3.5 Hz), 4.60 (d, 1 H, J = 3.5 Hz), 6.55 (t, 1 H, J = 7.8 Hz), 6.80-6.98 (m, 3 H), 7.05 (d, 1 H, J = 8.0 Hz), 7.20 (m, 2 H); EIMS: m/z 281 M⁺, 265, 235, 149, 132, 116, 78; IR (KBr): 3392, 3225, 3028, 2988, 2831, 1651, 1568, 1488, 1274, 1181, 1048, 917 cm^-1.
3e: Solid, mp122-123 °C; ¹H NMR (CDCl₃): δ 1.20 (s, 3 H), 1.40 (s, 3 H), 2.05 (dt, 1 H, J = 11.0, 3.0 Hz), 2.20 (s, 3 H), 3.95 (d, 1 H, J = 11.0 Hz), 4.05 (brs, NH), 4.40 (d, 1 H, J = 11.0 Hz), 4.50 (dd, 1 H, J = 11.0, 3.0 Hz), 6.70 (t, 1 H, J = 7.8 Hz), 6.85-7.05 (m, 3 H), 7.20 (m, 2 H), 7.40 (d, 1 H, J = 8.0 Hz).
2g: Solid, mp122-124 °C; ¹H NMR (CDCl₃): δ 1.30 (s, 3 H), 1.42 (s, 3 H), 1.90 (dt, 1 H, J = 11.0 and 3.3 Hz), 2.10 (s, 3 H), 3.60 (brs, NH), 3.70 (d, 1 H, J = 11.0 Hz), 4.18 (dd, 1 H, J = 11.0, 3.3 Hz), 4.50 (d, 1 H, J = 3.3 Hz), 5.0 (s, 2 H), 6.38 (d, 1 H, J = 8.0 Hz), 6.70-6.90 (m, 5 H), 7.25-7.35 (m, 5 H); ¹³C NMR (CDCl₃): δ 20.6, 25.6, 33.2, 33.9, 40.9, 46.3, 63.6, 70.9, 113.5, 115.2, 116.5, 117.3, 124.4, 126.0, 126.8, 127.4, 127.8, 128.5, 137.2, 138.0, 148.0, 152.6; IR (KBr): 3395, 3168, 2855, 1655, 1598, 1460, 1275, 1182, 1048, 920 cm^-1.