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DOI: 10.1055/s-2006-956450
A Novel Three-Component Reaction of Anilines, Formaldehyde and β-Diketones: Simple Synthesis of 3-Spirosubstituted 1,2,3,4-Tetrahydroquinolines
Publikationsverlauf
Publikationsdatum:
23. November 2006 (online)
Abstract
A new three-component reaction of cyclic β-diketones, formaldehyde and substituted anilines is described. The reaction provides a simple synthetic method for the one-pot preparation of 3-spirosubstituted 1,2,3,4-tetrahydroquinolines containing different substituents at the N-atom. This reaction also gives the opportunity to unite in one molecule the 1,2,3,4-tetrahydroquinoline, cyclic β-dicarbonyl, 2-azaspiro and some other (e.g., benzylic, bicyclic, adamantyl) fragments.
Key words
β-diketones - multicomponent reaction - Mannich reaction - azaspiro compounds - 1,2,3,4-tetrahydroquinolines
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References and Notes
General Procedure for Preparation of 1′,4′-dihydro-2
H
,2′
H
,6
H
-spiro[cyclohexane-1,3′-quinoline]-2,6-diones (4a-i).
A solution of amine 1 (2 mmol) and paraformaldehyde (8 mmol) in EtOH (25 mL) was prepared by gentle warming (2-3 min). Diketone 3 (2 mmol) was added to this solution in one portion and the mixture was heated under reflux for 5 min. After cooling to r.t. the colourless precipitate was filtered off, washed with EtOH (2 × 5 mL) and dried to give 4. The yields reported in Table
[1]
are unoptimised and additional crops of 4 could be obtained upon concentration of the mother liquors.
The N-monosubstituted anilines were prepared by reductive amination of the desired ketones with the corresponding primary anilines. Sodium triacetoxyborohydride was used as a reducing agent in the reaction as reported in ref. 5a.
7All new compounds gave satisfactory 500 MHz 1H NMR and 100 MHz 13C NMR and IR spectral data.
Selected Physical Data.
1′-(1,3-Benzodioxol-5-ylmethyl)-6′-methoxy-1′,4′-dihydro-2
H
,2′
H
,6
H
-spiro[cyclohexane-1,3′-quinoline]-2,6-dione (
4b).
Mp 148 °C. IR (KBr): 3439, 3404, 2931, 2904, 2830, 1726, 1701, 1504, 1489, 1444, 1242, 1151, 1036 cm-1. 1H NMR (CDCl3): δ = 1.82 (m, 1 H), 2.02 (m, 1 H), 2.60-2.75 (m, 4 H), 3.21 (s, 2 H), 3.46 (s, 2 H), 3.75 (s, 3 H), 4.30 (s, 2 H), 5.95 (s, 2 H), 6.55-6.63 (m, 2 H), 6.71-6.80 (m, 4 H). 13C NMR (CDCl3): δ = 19.05, 30.64, 37.86, 55.21, 56.25, 56.33, 67.07, 101.69, 108.37, 109.03, 113.10, 113.72, 115.39, 120.92, 123.33, 132.85, 139.13, 147.41, 148.70, 152.88, 206.33. MS (70 eV): m/z (%) = 135 (82), 252 (100), 393 (23) [M+], 394 (5) [M + H+]. Anal. Calcd for C23H23NO5: C, 70.21; H, 5.89; N, 3.56. Found: C, 70.21; H, 5.90; N, 3.57.
1′-(3,4-Dimethoxybenzyl)-6′-methoxy-4,4-dimethyl-1′,4′-dihydro-2
H
,2′
H
,6
H
-spiro[cyclohexane-1,3′-quinoline]-2,6-dione (
4g).
Mp 159 °C. IR (KBr): 2963, 2916, 2834, 1722, 1691, 1511, 1459, 1259, 1229, 1201, 1160, 1137, 1053, 1026 cm-1. 1H NMR (CDCl3): δ = 0.88 (s, 3 H), 1.05 (s, 3 H), 2.43 (d, J = 14.0 Hz, 2 H), 2.63 (d, J = 14.0 Hz, 2 H), 3.20 (s, 2 H), 3.41 (s, 2 H), 3.75 (s, 3 H), 3.85 (s, 3 H), 3.89 (s, 3 H), 4.31 (s, 2 H), 6.55-6.63 (m, 2 H), 6.76-6.86 (m, 4 H). 13C NMR (CDCl3): δ = 27.77, 29.99, 30.62, 31.51, 51.65, 55.51, 55.90, 56.24, 56.57, 56.65, 65.89, 66.51, 110.96, 111.83, 112.95, 113.64, 115.37, 119.98, 123.65, 131.53, 139.32, 148.83, 150.04, 152.93, 206.16. MS (70 eV): m/z (%) = 151 (100), 252 (63), 437 (12) [M+], 438 (3) [M + H+]. Anal. Calcd for C26H31NO5: C, 71.37; H, 7.14; N, 3.20. Found: C, 71.37; H, 7.14; N, 3.21.
1′-Cyclododecyl-6′-methoxy-1′,4′-dihydro-2
H
,2′
H
,6
H
-spiro[cyclohexane-1,3′-quinoline]-2,6-dione (
4i).
Mp 186 °C. IR (KBr): 3431, 2937, 2925, 2859, 1717, 1692, 1611, 1580, 1505, 1256, 1239, 1052 cm-1. 1H NMR (CDCl3): δ = 1.30-1.50 (m, 20 H), 1.59-1.70 (m, 2 H), 1.74-1.88 (m, 1 H), 2.06-2.18 (m, 1 H), 2.62-2.67 (m, 2 H), 2.81-2.87 (m, 2 H), 3.15 (s, 2 H), 3.35 (s, 2 H), 3.74 (s, 3 H), 3.88 (t, J = 5.8 Hz, 1 H), 6.68 (br s, 2 H), 6.37 (s, 1 H). 13C NMR (CDCl3): δ = 18.31, 22.47, 22.60, 23.01, 23.77, 23.97, 26.42, 29.65, 37.22, 48.07, 50.91, 55.42, 65.98, 111.58, 112.12, 115.02, 123.10, 138.75, 151.28, 205.74. Anal. Calcd for C27H39NO3: C, 76.20; H, 9.24; N, 3.29. Found: C, 76.21; H, 9.22; N, 3.28.
1′-(5,5,6-Trimethylbicyclo[2.2.1]hept-2-yl)-6′-methyl-1′,4′-dihydro-2
H
,2′
H
,6
H
-spiro[cyclohexane-1,3′-quinoline]-2,6-dione (
4j).
Mp 156 °C. IR (KBr): 3407, 2964, 2893, 2865, 2833, 1728, 1702, 1619, 1505, 1416, 1265, 1170, 1019, 819, 812 cm-1. 1H NMR (CDCl3): δ = 0.87 (s, 3 H), 0.91 (s, 3 H), 1.03 (d, J = 7.5 Hz, 3 H), 1.31 (dd, J = 1.1, 10.3 Hz, 1 H), 1.49 (dt, J = 3.6, 13.0 Hz, 1 H), 1.70 (d, J = 3.7 Hz, 1 H), 1.75-1.95 (m, 3 H), 2.00 (dq, J = 1.1, 7.4 Hz, 1 H), 2.05-2.13 (m, 1 H), 2.16 (d, J = 2.0 Hz, 1 H), 2.26 (s, 3 H), 2.51 (dt, J = 5.3, 15.5 Hz, 1 H), 2.72 (dt, J = 5.3, 15.5 Hz, 1 H), 2.81-2.97 (m, 2 H), 2.88 (d, J = 11.0 Hz, 1 H), 2.91 (d, J = 13.0 Hz, 1 H), 3.16 (d, J = 13.0 Hz, 1 H), 3.36 (dt, J = 3.9, 9.7 Hz, 1 H), 3.71 (d, J = 11.0 Hz, 1 H), 6.61 (d, J = 8.0 Hz, 1 H), 6.85 (s, 1 H), 6.97 (d, J = 8.0 Hz, 1 H). 13C NMR (CDCl3): δ = 15.81, 17.96, 20.50, 24.72, 26.31, 32.46, 34.84, 35.80, 37.03, 37.40, 37.88, 39.67, 48.17, 49.38, 49.93, 60.55, 71.76, 114.87, 125.63, 127.47, 127.86, 128.07, 146.13, 205.77, 206.23. Anal. Calcd for C25H33NO2: C, 79.11; H, 8.76; N, 3.69. Found: C, 79.10; H, 8.74; N, 3.70.
1′-(2-Adamantyl)-6′-methyl-4,4-dimethyl-1′,4′-dihydro-2
H
,2′
H
,6
H
-spiro[cyclohexane-1,3′-quinoline]-2,6-dione (
4k).
Mp 205 °C. IR (KBr): 3440, 2919, 2900, 2862, 1725, 1695, 1502, 1248, 1155, 819, 519 cm-1. 1H NMR (CDCl3): δ = 0.94 (s, 3 H), 1.07 (s, 3 H), 1.56 (d, J = 12.5 Hz, 2 H), 1.75 (s, 2 H), 1.83-1.96 (m, 6 H), 2.06 (d, J = 12.5 Hz, 2 H), 2.24 (s, 3 H), 2.28 (br s, 2 H), 2.56 (d, J = 14.0 Hz, 2 H), 2.80 (d, J = 14.0 Hz, 2 H), 3.05 (s, 2 H), 3.51 (s, 3 H), 6.56 (d, J = 8.0 Hz, 1 H), 6.88 (s, 1 H), 6.93 (d, J = 8 Hz, 1 H). 13C NMR (CDCl3): δ = 20.45, 27.02, 27.51, 28.02, 29.00, 29.77, 30.65, 32.26, 34.37, 37.57, 37.59, 46.18, 51.21, 60.98, 69.57, 114.64, 125.76, 127.58, 127.84, 128.30, 144.59, 206.01. Anal. Calcd for C27H35NO2: C, 79.96; H, 8.70; N, 3.45. Found: C, 80.00; H, 8.73; N, 3.42.