Synthesis of 2,4-Diaryl-3H-1-benzazepines

Keith Ramig; Shaan Alli; Myra Cheng; Richard Leung; Rabail Razi; Michelle Washington; Linas V. Kudzma

doi:10.1055/s-2007-991095

LETTER

Synthesis of 2,4-Diaryl-3H-1-benzazepines

Keith Ramig*^a, Shaan Alli^a, Myra Cheng^a, Richard Leung^a, Rabail Razi^a, Michelle Washington^a, Linas V. Kudzma^b
^a Department of Natural Sciences, Baruch College, 17 Lexington Ave., New York, NY 10010, USA
Fax: +1(646)6606201; e-Mail: keith_ramig@baruch.cuny.edu;
^b Baxter Anesthesia and Critical Care, 95 Spring St., New Providence, NJ 07974, USA

Abstract

Alle Artikel dieser Rubrik

Abstract

Treatment of 2-fluoroaniline and some derivatives with aryl methyl ketones under acid catalysis gives the title compounds.

Key words

amines - annulations - bicyclic compounds - heterocycles - ketones

Volltext

Referenzen

References and Notes

1 Kudzma L. Synthesis 2003, 1661

2 Brooke GM. Matthews RS. J. Fluorine Chem. 1988, 40: 109

3 Sudo K. Miyazaki Y. Kojima N. Kobayashi M. Suzuki H. Shintani M. Shimizu Y. Antiviral Res. 2005, 65: 125

4 Seto M. Miyamoto N. Aikawa K. Aramaki Y. Kanzaki N. Iizawa Y. Baba M. Shiranishi M. Bioorg. Med. Chem. 2005, 13: 363

5 Qadir M. Priestley RE. Rising TWDF. Gelbrich T. Coles SJ. Hursthouse MB. Sheldrake PW. Whittall N. Hii KK. Tetrahedron Lett. 2003, 44: 3675

6

Typical Procedure
A solution of 6.7 mmol of the 2-fluoroaniline, 6.7 mmol of the aryl methyl ketone, and 40 mg of PTSA in 30 mL of toluene or xylenes in a Dean-Stark apparatus was heated at reflux until the initially formed imine was converted into benzazepine, as judged by silica gel TLC. After cooling, the solution was washed with 5% NaHCO₃ solution and dried over MgSO₄. Removal of the solvent under reduced pressure gave dark oil or solid, which was triturated with EtOAc-hexanes to isolate a first crop of benzazepine. Additional product can be obtained by taking a second crop, or purification by silica gel chromatography, eluting with EtOAc-hexanes. Analytically pure samples can be obtained by recrystallization from EtOAc-hexanes.
2,4-Bis(4-methoxyphenyl)-3 H -1-benzazepine (2a)
Mp 159-160 °C. ¹H NMR (300 MHz, CDCl₃): δ = 7.86 (d, 2 H, J = 9 Hz), 7.56-7.15 (m, 4 H), 7.49 (d, 2 H, J = 9 Hz), 6.98 (s, 1 H), 6.91 (d, 2 H, J = 9 Hz), 6.85 (d, 2 H, J = 9 Hz), 3.82 (s, 3 H), 3.78 (s, 3 H), 3.32 (br s, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 161.30, 159.43, 156.30, 146.88, 134.37, 132.63, 130.88, 130.45, 129.70, 128.08, 127.90, 126.61, 125.29, 123.53, 114.12, 113.84, 55.32, 55.31, 33.67. Anal. Calcd for C₂₄H₂₁NO₂ (355.43): C, 81.10; H, 5.96; N, 3.94. Found: C, 80.95; H, 6.17; N, 3.78.
2,4-Bis(3-methoxyphenyl)-3 H -1-benzazepine (2b)
Mp 109-110 °C. ¹H NMR (300 MHz, CDCl₃): δ = 7.60-7.20 (m, 9 H), 7.08 (s, 1 H), 7.05-6.85 (m, 3 H), 3.79 (s, 3 H), 3.70 (s, 3 H), 3.36 (br s, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.96, 159.79, 157.13, 146.90, 141.47, 139.72, 134.83, 130.52, 130.13, 129.76, 129.48, 127.96, 127.00, 126.84, 123.97, 120.48, 119.37, 117.02, 113.64, 112.53, 112.48, 55.28, 55.19, 34.36. HRMS (EI): m/z calcd for C₂₄H₂₂NO₂ [M + H⁺]: 356.1645; found: 356.1644.
2,4-Bis(4-methylphenyl)-3 H -1-benzazepine (2c)
Mp 147-149 °C. ¹H NMR (300 MHz, CDCl₃): δ = 7.79 (d, 2 H, J = 6 Hz), 7.56 (dd, 1 H, J = 8, 1 Hz), 7.49-7.43 (m, 3 H), 7.37 (td, 1 H, J = 8, 2 Hz), 7.23-7.13 (m, 5 H), 7.05 (s, 1 H), 3.36 (br s, 2 H), 2.37 (s, 3 H), 2.34 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 157.04, 146.95, 140.32, 137.68, 137.12, 135.50, 134.84, 130.47, 129.68, 129.42, 129.21, 128.03, 127.94, 126.71, 126.69, 126.02, 123.69, 33.67, 21.29, 21.15. HRMS (EI): m/z calcd for C₂₄H₂₂N [M + H⁺]: 324.1746; found: 324.1749.
2,4-Bis(4-trifluoromethylphenyl)-3 H -1-benzazepine (2d)
Mp 142-143 °C. ¹H NMR (300 MHz, CDCl₃): δ = 7.95 (d, 2 H, J = 6 Hz), 7.64-7.25 (m, 10 H), 7.13 (s, 1 H), 3.39 (br s, 2 H). ¹⁹F NMR (300 MHz, CDCl₃): δ = -63.05 (s), -63.35 (s). ¹³C NMR (75 MHz, CDCl₃): δ = 155.45, 146.75, 143.08 (q, J = 3 Hz), 141.19 (q, J = 3 Hz), 133.06, 132.00 (q, J = 129 Hz), 130.75, 130.07 (q, J = 129 Hz), 129.05, 128.81, 128.27, 128.17, 127.76, 127.05, 125.96 (q, J = 15 Hz), 125.65 (q, J = 15 Hz), 124.72, 124.11 (q, J = 1083 Hz), 123.96 (q, J = 1083 Hz), 33.60. Anal. Calcd for C₂₄H₁₅NF₆ (431.37): C, 66.82; H, 3.50; N, 3.25. Found: C, 66.61; H, 3.82; N, 3.12.

2,4-Bis(2-naphthyl)-3 H -1-benzazepine (2e) Mp 177-179 °C. ¹H NMR (300 MHz, DMSO-d ₆): δ = 8.70 (s, 1 H), 8.49 (s, 1 H), 8.19-7.88 (m, 8 H), 7.72-7.32 (m, 9 H), 3.66 (br s, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 157.08, 147.05, 137.12, 135.49, 134.87, 134.18, 133.50, 132.94, 130.64, 129.64, 128.93, 128.51, 128.28, 128.26, 128.21, 128.06, 127.65, 127.57, 127.35, 127.13, 127.09, 126.49, 126.30, 126.28, 125.86, 125.21, 124.91, 124.05, 33.88. Anal. Calcd for C₃₀H₂₁N (395.49): C, 91.11; H, 5.35; N, 3.54. Found: C, 90.81; H, 5.54; N, 3.44.