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Synlett 2004(15): 2721-2724  
DOI: 10.1055/s-2004-836026
LETTER
© Georg Thieme Verlag Stuttgart · New York

New and Efficient Synthesis of 6,11-Dihydro-11-ethyl-5H-dibenz[b,e]azepine Derivatives Starting from N-Benzylanilines via Amino-Claisen and Friedel-Crafts Methodologies

Alirio Palmaa, Jacqueline Jaimes Barajasa, Vladimir V. Kouznetsov*a, Elena Stashenkoa, Ali Bahsasb, Juan Amaro-Luisb
a Laboratorio de Síntesis Orgánica Fina, Centro de Investigación en Biomoléculas, Escuela de Química, Universidad Industrial de Santander, A.A. 678, Bucaramanga, Colombia
Fax: +57(76)349069; e-Mail: kouznet@uis.edu.co;
b Laboratorio de RMN, Grupo de Productos Naturales, Departamento de Química, Universidad de los Andes, Mérida 5101, Venezuela
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Publication History

Received 4 May 2004
Publication Date:
25 November 2004 (online)

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Abstract

New and efficient synthesis of 6,11-dihydro-11-ethyl-5H-dibenz[b,e]azepine derivatives, using the key steps of BF3·OEt2-catalyzed aromatic amino-Claisen rearrangement and the intramolecular alkene Friedel-Crafts alkylation, is reported.

Key words

dibenz[b,e]azepine derivatives - amino-Claisen rearrangement - N-allylation - intramolecular alkene Friedel-Crafts ­alkylation

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24

Spectral Data for Selected Compounds 3. Compound 3b: 1H NMR (400 MHz, CDCl3): δ = 3.29 (2 H, d, J = 6.0 Hz, -CH2-), 4.10 (1 H, br s, NH), 4.34 (2 H, s, N-CH2-), 5.15 (2 H, m, =CH2), 5.95 (1 H, m, -CH=), 6.54 (1 H, d, J = 8.0 Hz, 6-H), 7.06 (1 H, d, J = 2.0 Hz, 3-H), 7.08 (1 H, dd, J = 8.0, 2.0 Hz, 5-H), 7.30-7.43 (5 H, m, H-phenyl). 13C NMR (100 MHz, CDCl3): δ = 36.1 (-CH2-), 48.2 (N-CH2-), 111.8 (6-C), 116.9 (=CH2), 122.0 (4-C), 125.2 (2-C), 127.3 (ortho-C), 127.4 (5-C), 128.7 (3-C), 129.0 (para-C), 129.5 (meta-C), 135.0 (-CH=), 139.0 (1′-C), 144.6 (1-C). MS (EI): m/z (%) = 257 (35Cl, 8) [M+], 242 (<1), 228 (1), 180 (11), 166 (26), 152 (11), 131 (40), 91 (100), 77 (10).
Compound 3c: 1H NMR (400 MHz, CDCl3): δ = 3.32 (2 H, d, J = 6.4 Hz, -CH2-), 4.06 (1 H, br s, NH), 4.34 (2 H, s, N-CH2-), 5.15 (2 H, m, =CH2), 5.97 (1 H, m, -CH=), 6.56 (1 H, dd, J = 9.0, 5.0 Hz, 6-H), 6.83 (1 H, d, J = 3.0 Hz, 3-H), 6.85 (1 H, dd, J = 9.0, 3.0 Hz, 5-H), 7.30-7.39 (5 H, m, H-phenyl). 13C NMR (100 MHz, CDCl3): δ = 36.2 (-CH2-), 48.7 (N-CH2-), 111.5 (d, J = 10.0 Hz. 6-C), 113.4 (d, J = 20.0 Hz, 3-C), 116.5 (d, J = 20.0 Hz, 5-C), 116.9 (=CH2), 125.3 (d, J = 10.0 Hz, 2-C), 127.2 (para-C), 127.5 (ortho-C), 128.5 (meta-C), 135.1 (-CH=), 139.3 (1′-C), 142.3 (1-C), 155.6 (d, J = 206.1 Hz, 4-C). MS (EI):
m/z (%) = 241 (28) [M+], 212 (8), 198 (4), 164 (9), 150 (66), 135 (17), 91 (100), 77 (6), 65 (21).
Compound 3d: 1H NMR (400 MHz, CDCl3): δ = 2.44 (3 H, s, 2-CH3), 3.29 (2 H, dt, J = 6.0, 1.6 Hz, -CH2-), 3.04 (1 H, br s, NH), 4.09 (2 H, s, N-CH2-), 5.05 (2 H, m, =CH2), 5.93 (1 H, m, -CH=), 6.95 (1 H, d, J = 8.0 Hz, 5-H), 7.07 (1 H, d, J = 8.0 Hz, 4-H), 7.33-7.40 (5 H, m, H-phenyl). 13C NMR (100 MHz, CDCl3): δ = 15.6 (2-CH3), 36.3 (-CH2-), 53.6 (N-CH2-), 116.9 (=CH2), 123.4 (4-C), 127.4 (ortho-C), 127.8 (5-C), 128.3 (para-C), 128.6 (meta-C), 129.4 (3-C), 130.4 (6-C), 133.7 (2-C), 136.5 (-CH=), 139.0 (1′-C), 147.4 (1-C). MS (EI): m/z (%) = 271 (35Cl, 11) [M+], 256 (2), 242 (4), 194 (7), 180 (33), 166 (18), 145 (46), 130 (14), 115 (8), 91 (100), 77 (8), 65 (22).

25

NMR and Analytical Data for Compounds 4.
Compound 4a: IR (KBr): 3405 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.91 (3 H, t, J = 7.4 Hz, 13-H), 2.17 (2 H, m, 12-H), 3.69 (1 H, t, J = 7.3 Hz, 11-H), 4.00 (1 H, d, J = 14.8 Hz, 6-HB), 4.95 (1 H, d, J = 14.8 Hz, 6-HA), 6.50 (1 H, d, J = 8.0 Hz, 4-H), 6.67 (1 H, td, J = 8.0, 1.0 Hz, 2-H), 6.96 (1 H, td, J = 8.0, 1.0 Hz, 3-H), 7.12 (1 H, dd, J = 8.0, 1.0 Hz, 1-H), 7.19-7.30 (4 H, m, 7-H-10-H). 13C NMR (100 MHz, CDCl3): δ = 13.0 (13-C), 31.6 (12-C), 51.1 (6-C), 54.8 (11-C), 117.9 (4-C), 118.2 (2-C), 127.2 (3-C), 127.6-129.5 (7-C-10-C), 130.2 (11a-C), 130.8 (1-C), 136.5 (6a-C), 142.1 (10a-C), 146.2 (4a-C). MS (EI): m/z (%) = 223 (14) [M+], 194 (100), 178 (8), 165 (11), 116 (10), 96 (10). Anal. Calcd for C16H17N: C, 86.06; H, 7.67; N, 6.27. Found: C, 86.13; H, 7.81; N, 6.14.
Compound 4b: IR (KBr): 3406 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.91 (3 H, t, J = 7.3 Hz, 13-H), 2.14 (2 H, m, 12-H), 3.63 (1 H, t, J = 7.7 Hz, 11-H), 4.17 (1 H, d, J = 14.4 Hz, 6-HB), 4.77 (1 H, d, J = 14.4 Hz, 6-HA), 6.40 (1 H, d, J = 8.5 Hz, 4-H), 6.91 (1 H, dd, J = 8.5, 2.3 Hz, 3-H), 7.10 (1 H, d, 2.3 Hz, 1-H), 7.12-7.34 (4 H, m, 7-H-10-H). 13C NMR (100 MHz, CDCl3): δ = 13.3 (13-C), 31.5 (12-C), 49.5 (6-C), 51.5 (11-C), 119.4 (4-C), 122.9 (2-C), 127.4 (3-C), 127.4-128.7 (7-C-10-C), 129.1 (11a-C), 130.7 (1-C), 136.5 (6a-C), 142.0 (10a-C), 145.1 (4a-C). MS (EI): m/z (%) = 257 (35Cl, 17) [M+], 228 (100), 193 (46), 165 (17), 115 (6), 89 (5). Anal. Calcd for C16H16ClN: C, 74.56; H, 6.26; N, 5.43. Found: C, 74.38; H, 6.49; N, 5.35.
Compound 4c: IR (KBr): 3429 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.91 (3 H, t, J = 7.1 Hz, 13-H), 2.18 (2 H, m, 12-H), 3.76 (1 H, t, J = 7.6 Hz, 11-H), 4.20 (1 H, d, J = 14.6 Hz, 6-HB), 4.71 (1 H, d, J = 14.6 Hz, 6-HA), 6.49 (1 H, dd, J = 8.0, 5.0 Hz, 4-H), 6.72 (1 H, ddd, J = 8.0, 3.0 Hz, 3-H), 6.82 (1 H, dd, J = 10.0, 3.0 Hz, 1-H), 7.13-7.22 (4 H, m, 7-H-10-H). 13C NMR (100 MHz, CDCl3): δ = 12.9 (13-C), 30.8 (12-C), 49.7 (6-C), 53.1 (11-C), 113.7 (d, J = 20 Hz, 3-C), 116.7 (d, J = 20 Hz, 1-C), 119.5 (d, J = 10 Hz, 4-C), 126.8 (8-C), 127.4 (9-C), 128.2 (7-C), 129.1 (10-C), 130.0 (11a-C), 136.5 (6a-C), 141.3 (10a-C), 142.5 (4a-C), 156.4 (d, J = 230 Hz, 2-C). MS (EI): m/z (%) = 241 (17) [M+], 212 (100), 196 (15), 183 (17), 165(10), 116 (9). Anal. Calcd for C16H16FN: C, 79.64; H, 6.68; N, 5.80.Found: C, 79.70; H, 6.80; N, 5.65.
Compound 4d: IR (KBr): 3446 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.96 (3 H, t, J = 7.4 Hz, 13-H), 2.20 (3 H, s, 4-CH3), 2.23 (2 H, m, 12-H), 3.84 (1 H, t, J = 7.6 Hz, 11-H), 4.09 (1 H, br s, N-H), 4.3 (1 H, d, J = 14.6 Hz, 6-HB), 4.90 (1 H, d, J = 14.6 Hz, 6-HA), 6.78 (1 H, d, J = 8.3 Hz, 2-H), 6.92 (1 H, d, J = 8.3 Hz, 1-H), 7.18-7.29 (4 H, m, 7-H-10-H). 13C NMR (100 MHz, CDCl3): δ = 11.9 (13-C), 13.3 (4-CH3), 29.9 (12-C), 48.0 (6-C), 52.5 (11-C), 117.5 (3-C), 120.3 (2-C), 124.9 (4-C), 125.9 (9-C), 126.5 (7-C), 127.0 (8-C), 127.7 (10-C), 127.8 (1-C), 131.8 (11a-C), 135.3 (6a-C), 140.9 (10a-C), 144.4 (4a-C). MS (EI): m/z (%) = 271 (35Cl, 13) [M+], 242 (100), 227 (6), 207 (31), 191 (10), 178 (11), 165 (8), 152 (6), 139 (2), 89 (4). Anal. Calcd for C17 H18ClN: C, 75.13; H, 6.68; N, 5.15. Found: C, 75.29; H, 6.83; N, 5.08.