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 Palma; Jacqueline Jaimes Barajas; Vladimir V. Kouznetsov; Elena Stashenko; Ali Bahsas; Juan Amaro-Luis

doi:10.1055/s-2004-836026

LETTER

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 Palma^a, Jacqueline Jaimes Barajas^a, Vladimir V. Kouznetsov*^a, Elena Stashenko^a, Ali Bahsas^b, Juan Amaro-Luis^b
^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

Abstract

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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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References

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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).

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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-H_B), 4.95 (1 H, d, J = 14.8 Hz, 6-H_A), 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-H_B), 4.77 (1 H, d, J = 14.4 Hz, 6-H_A), 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-H_B), 4.71 (1 H, d, J = 14.6 Hz, 6-H_A), 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-H_B), 4.90 (1 H, d, J = 14.6 Hz, 6-H_A), 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.