A Facile Access to the 1,5-Dihydro- and 1,3,4,5-Tetrahydro-benzo[b]azepin-2-one Ring Systems via a New Ring Enlargement

Abstract

Synthesis of a 1,5-dihydro-benzo[b]azepin-2-one is reported. The key reaction is a silver nitrate-induced rearrangement of N-benzyl quinolinium bromide. Its reduction leads to the 1,3,4,5-tetrahydro-benzo[b] azepin-2-one ring system found in several pharmacological important compounds.

Key words

quinolinium salt - silver nitrate - 1,5-dihydro-benzo[b]azepin-2-one - 1,3,4,5-tetrahydro-benzo[b] azepin-2-one - ring enlargement

References

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9

Spectral Data for Compound 5:
IR (KBr): 1659, 1615, 1595 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 3.40 (s, 3 H, OCH ₃), 4.82 (br s, 1 H, CHOCH₃), 5.08 and 5.40 (AB system, J = 15.2 Hz, 2 H, NCH ₂), 5.84 (d, J = 11.2 Hz, 1 H, COCH=CH), 6.51 (dd, J = 11.2 and 4.0 Hz, 1 H, COCH=CH), 7.05-7.45 (m, 9 H, Ar). ¹³C NMR (50 MHz, CDCl₃): δ = 52.4, 57.7, 77.2, 121.3, 122.6, 123.1, 125.7, 127.3, 127.4, 127.5 (2 C), 128.5 (2 C), 137.7, 138.3 (2 quaternary carbons), 146.1, 166.5. MS: m/z (relative intensity) = 279(8) [M⁺], 264(19), 246(30), 91(100), 65(18). HRMS (SIMS) calcd for C₁₈H₁₇NO₂ + H: 280.1338; found: 280.1342.

12

For a close example of Beckmann rearrangement, see ref. [2b]

13

Spectral Data for Compounds 9 and 10:
9: IR (KBr): 1667 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 1.70-1.90 (m, 1 H, CH ₂CHOCH₃), 2.15-2.35 (m, 2 H, CH ₂CO), 2.45-2.65 (m, 1 H, CH ₂CHOCH₃), 3.06 (s, 3 H, OCH ₃), 4.01 (dd, J = 10.4 and 6.8 Hz, 1 H, CHOCH₃), 4.63 and 5.37 (AB system, J = 14.4 Hz, 2 H, NCH ₂), 7.10-7.35 (m, 9 H, Ar). ¹³C NMR (50 MHz, CDCl₃): δ = 31.8, 35.4, 51.3, 57.6, 77.5, 123.3, 124.6, 126.7, 127.5, 128.1, 128.5 (4 C; the ortho and meta carbons of the phenyl ring are identical), 135.9, 137.6, 140.5, 172.6. MS: m/z (relative intensity) = 281(24) [M⁺], 194(58), 130(100), 91(90), 65(22). HRMS (SIMS) calcd for C₁₈H₁₉NO₂ + H: 282.1494; found: 282.1491.
10: IR (KBr): 1674 cm^-1; ¹H NMR (200 MHz, CDCl₃): δ = 2.00-2.20 (m, 1 H of the CH₂CH₂ motif), 2.30-2.60 (m, 3 H of the CH₂CH₂ motif), 3.32 (s, 3 H, OCH ₃), 3.70-3.85 (m, 1 H, CHOCH₃), 4.90 and 5.24 (AB system, J = 14.8 Hz, 2 H, NCH ₂), 7.05-7.30 (m, 9 H, Ar). ¹³C NMR (50 MHz, CDCl₃): δ = 27.8, 36.2, 51.8, 57.9, 78.1, 123.1, 126.7, 127.5, 127.8, 128.3 (2 C), 128.5 (2 C), 129.1, 136.1, 137.6, 140.7, 171.6. MS: m/z (relative intensity) = 281(96) [M⁺], 132(79), 118(76), 91(100), 65(20). HRMS (SIMS) calcd for C₁₈H₁₉NO₂ + H: 282.1494; found: 282.1495.