Novel Microwave-assisted [3+3] Cyclocondensations with 1-Cyanomethylene Tetrahydroisoquinoline

Péter  Nemes; Zoltán  Vincze; Barbara  Balázs; Gábor  Tóth; Pál  Scheiber

doi:10.1055/s-2003-36796

LETTER

Novel Microwave-assisted [3+3] Cyclocondensations with 1-Cyanomethylene Tetrahydroisoquinoline

Péter Nemes*^a, Zoltán Vincze^a, Barbara Balázs^b, Gábor Tóth^b, Pál Scheiber^a
^a Department of Chemistry, Faculty of Veterinary Science, Szent István University, H-1400 Budapest, P.O.Box 2, Hungary
Fax: 36(1)478 4268; e-Mail: pnemes@univet.hu;
^b Technical Analytical Research Group, Institute for General and Analytical Chemistry, Technical University, H-1111 Budapest, Szent Gellért tér 4, Hungary

Abstract

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Abstract

α,β-Unsaturated aldehydes and ketones react with 1-cyanomethylene-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline in microwave-enhanced reactions affording regioselectively 6,7-dihydro-4H-benzo[a]quinolizines and 6,7-dihydro-2H-benzo[a]quinolizines, respectively.

Key words

β-enaminonitriles - [3+3] cyclisations - Michael additions - microwave heating - benzo[a]quinolizines

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References

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Experimental procedure: 2.4 mmol (520 mg) of 1 was mixed with 3.2 mmol of the carbonyl compound, and the reaction mixture was irradiated in an open vessel for 4 minutes in a Synthewave S402 (Prolabo) monomode, focused MW (2,45 GHz) reactor with continuous rotation. During the irradiation, the temperature of the reaction mixture (measured by infrared thermometry) raised linearly and reached its maximum between 140-170 °C depending on the enone after ca. 180 seconds. The oily mixture was then cooled and the product was either crystallised from an appropriate solvent (EtOH) or purified by flash chromatography. Yield: 72-85%.

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All isolated compounds were fully characterised by ¹H and ¹³C NMR analysis. Representative data are given as follows: 4b: ¹H NMR δ = 7.88 (s, 1 H, H-11), 7.37 (d, 1 H, J = 1.8 Hz, 4-furanyl), 6.64 (s, 1 H, H-8), 6.32 (dd, 1 H, 4-furanyl), 6.30 (d, 1 H, 4-furanyl), 6.28 (d, 1 H, H-2), 5.28 (dd, 1 H, H-3), 5.20 (d, 1 H, H-4), 3.94 (s, 3 H, 9-MeO), 3.90 (s, 3 H, 10-MeO), 3.41 (m, 1 H, H-6), 3.40 (m, 1 H, H-6), 2.89 (dd, 1 H, H-7), 2.74 (dt, 1 H, H-7); ¹³C NMR δ = 153.7 (4-furanyl), 150.6 (C-9), 150.2 (C-11b), 147.3 (C-10), 142.6 (4-furanyl), 129.5 (C-7a), 125.5 (C-2), 123.6 (1-CN), 121.0 (C-11a), 111.0 (C-11), 110.5 (4-furanyl), 110.1 (C-3), 110.0 (C-8), 108.5 (4-furanyl), 74.9 (C-1), 57.6 (C-4), 56.2 (9-MeO), 56.0 (10-MeO), 48.0 (C-6), 29.4 (C-7). 3 (R⁴ = 2-furanyl, R¹, R², R³ = H): ¹H NMR δ = 7.87 (s, 1 H, H-11), 7.39 (d, 1 H, J = 2.0 Hz, 2-furanyl), 6.65 (s, 1 H, H-8), 6.34 (dd, 1 H, 2-furanyl), 6.18 (d, 1 H, 2-furanyl), 6.09 (d, 1 H, H-4), 4.87 (dd, 1 H, H-3), 4.53 (d, 1 H, H-2), 3.93 (s, 3 H, 9-MeO), 3.90 (s, 3 H, 10-MeO), 3.52 (m, 1 H, H-6), 3.42 (m, 1 H, H-6), 2.90 (m, 1 H, H-7), 2.76 (m, 1 H, H-7); ¹³C NMR δ = 157.6 (2-furanyl), 150.5 (C-9), 147.4 (C-10), 146.3 (C-11b), 142.1 (2-furanyl), 130.7 (C-4), 130.0 (C-7a), 123.3 (1-CN), 120.1 (C-11a), 111.3 (C-11), 110.3 (C-8), 110.4 (2-furanyl), 105.5 (2-furanyl), 100.4 (C-3), 73.6 (C-1), 56.3 (9-MeO), 56.0 (10-MeO), 48.8 (C-6), 36.2 (C-2), 29.4 (C-7). 5a: ¹H NMR δ = 8.11 (d, 2 H, H-2′′), 8.09 (d, 1 H, J = 8.4 Hz, H-4), 7.82 (d, 1 H, J = 8.4 Hz, H-5), 7.51 (t, 1 H, H-4′′), 7.50 (t, 2 H, H-3′′), 7.22 (s, 1 H, H-5′), 7.02 (s, 1 H, H-2′), 6.68 (dd, 1 H, J = 11.0; 17.4 Hz, CH=), 5.64 (d, 1 H, J = 17.4 Hz, CH ₂=), 5.20 (d, 1 H, J = 11.0 Hz, CH ₂=), 4.00 (s, 3 H, 4′-MeO), 3.95 (s, 3 H, 3′-MeO); ¹³C NMR δ = 161.9 (C-2), 159.6 (C-6), 150.4 (C-4′), 148.8 (C-3′), 141.7 (C-4), 137.6 (C-1′′), 134.3 (CH=), 130.8 (C-3′′), 130.1 (C-6′), 129.3 (C-1′), 129.2 (C-4′′), 127.7 (C-2′′), 118.0 (C-5), 117.6 (3-CN), 114.7 (CH₂=), 112.9 (C-2′), 108.8 (C-5′), 108.3 (C-3), 56.3 (3′-MeO), 56.2 (4′-MeO). 6 E: ¹H NMR δ = 7.94 (s, 1 H, H-8), 7.43 (d, 2 H, Ph), 7.31 (t, 2 H, Ph), 7.20 (t, 1 H, Ph), 6.86 (d, 1 H, H-3′), 6.81 (d, 1 H, H-2′), 6.70 (s, 1 H, H-5), 5.41 (s, 1 H, H-2), 3.98 (s, 3 H, 7-MeO), 3.93 (s, 3 H, 6-MeO), 3.41 (t, 2 H, H-3), 2.83 (dd, 2 H, H-4); ¹³C NMR δ = 151.6 (C-1), 151.0 (C-6), 147.4 (C-7), 137.7 (Ph), 131.2 (C-4a), 128.6 (Ph), 127.0 (C-3′), 126.9 (Ph), 126.0 (Ph), 122.0 (1′-CN), 120.5 (C-8a), 120.3 (C-2′), 111.9 (C-8), 110.6 (C-5), 76.9 (C-1′), 56.3
(7-MeO), 56.0 (6-MeO), 39.6 (C-3), 29.9 (C-4). 6 Z: ¹H NMR δ = 7.30 (d, 2 H, Ph), 7.27 (t, 2 H, Ph), 7.18 (s, 1 H, H-8), 7.13 (t, 1 H, Ph), 7.11 (d, 1 H, H-2′), 6.78 (s, 1 H, H-5), 6.61 (d, 1 H, H-3′), 5.80 (s, 1 H, H-2), 3.96 (s, 3 H, 7-MeO), 3.83 (s, 3 H, 6-MeO), 3.40 (t, 2 H, H-3), 2.83 (dd, 2 H, H-4); ¹³C NMR δ = 151.6 (C-1), 151.0 (C-6), 147.2 (C-7), 138.1 (Ph), 131.8 (C-4a), 128.6 (Ph), 123.4 (C-2′), 126.2 (Ph), 125.3 (Ph), 122.0 (1′-CN), 120.6 (C-8a), 123.7 (C-3′), 113.2 (C-8), 110.8 (C-5), 77.2 (C-1′), 56.3 (7-MeO), 56.0 (6-MeO), 39.6 (C-3), 30.1 (C-4).