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).

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.