Electrocyclization Reactions of Annulated 1,2-Diazahepta-2,4-dien-6-ynyl Anions

Abstract

Hydrazones 12a,b,f furnish annulated indenone derivatives (6-azafulvenes) 13a-d upon deprotonation with t-BuOK in DMF at 50 °C. In contrast, deprotonation of a similar N-methyl ­hydrazone 12d unexpectedly leads to the isoquinoline derivative 15. Mechanisms for both transformations are proposed, supported by quantum chemical density functional theory (DFT) and ab initio calculations.

anionic electrocyclic reactions - indenes - heterocycles - hydrazones - quinolines - 6-azafulvenes

References and Notes

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7

Preparation of 1-[2-(Hex-1-ynyl)benzylidene]-2-phenyl-hydrazine (12a): A mixture of 2-(1-hexynyl)benz-aldehyde (0.93 g, 5.00 mmol) and phenylhydrazine (0.54 g, 5.00 mmol) in anhyd CH₂Cl₂ (20 mL) was stirred in the presence of molecular sieves (4 Å) at r.t. for 16 h. Molecular sieves were removed by filtration through Celite and washed with CH₂Cl₂ (20 mL). The solvent was removed in vacuo to afford the hydrazone 12a (1.10 g, 4.00 mmol, 80%) as a yellow oil. The obtained hydrazone was pure enough to be used without further purification. FTIR (film): 3313 (br, w), 2931 (s), 2871 (s), 2862 (m), 2225 (m), 1575 (m), 1494 (s), 1448 (m), 1257 (s), 1145 (m) cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.98 (t, J = 7.3 Hz, 3 H), 1.47-1.68 (m, 4 H), 2.48 (t, J = 7.4 Hz, 2 H), 6.87 (tt, J = 7.3, 1.2 Hz, 1 H), 7.11-7.14 (m, 2 H), 7.19 (dd, J = 7.4, 1.4 Hz, 1 H), 7.25-7.30 (m, 3 H), 7.38 (dm, J = 7.8 Hz, 1 H), 7.72 (br s, 1 H, NH), 8.04 (dm, J = 8.0 Hz, 1 H), 8.19 (s, 1 H, CH=N). ¹³C NMR (100 MHz, CDCl₃): δ = 13.7, 19.4, 22.2, 30.9, 78.1, 95.7, 112.8, 120.2, 122.4, 124.5, 127.8, 127.9, 129.3, 132.6, 136.0, 136.1, 144.6. HRMS (ESI): m/z calcd for C₁₉H₂₀N₂H: 277.1705; found: 277.1699. Anal. Calcd for C₁₉H₂₀N₂: C, 82.57; H, 7.29; N, 10.14. Found: C, 82.87; H, 7.48; N, 9.57.

8

Preparation of 1-(2-Butyl-1 H -inden-1-ylidene)-2-phenylhydrazine (13a): Hydrazone 12a (0.28 g, 1.00 mmol) was added under argon to the solution of t-BuOK (0.22 g, 2.00 mmol) in DMF (5 mL) and the mixture was stirred at 50 °C until all starting hydrazone had disappeared (approx. 5 h, TLC monitoring). H₂O (20 mL) was added and the mixture was extracted with Et₂O (3 × 20 mL). The combined organic extracts were dried with MgSO₄ and the residue was purified by flash chromatography (Et₂O-pentane-Et₃N, 0.5:10:0.2) giving 13a (0.07 g, 0.25 mmol, 25%) as a yellowish oil. FTIR (film): 2956 (s), 2927 (s), 1600 (s), 1566 (s), 1504 (s), 1494 (s), 1255 (s), 1207 (s), 1168 (s), 1151 (w), 1122 (m), 1093 (w) cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 1.00 (t, J = 7.1 Hz, 3 H), 1.43-1.52 (m, 2 H), 1.68-1.75 (m, 2 H), 2.66-2.69 (m, 2 H), 6.56 (s, 1 H), 7.03 (tt, J = 7.3, 1.0 Hz, 1 H), 7.17-7.40 (m, 7 H), 7.68 (d, J = 7.2 Hz, 1 H), 8.92 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 14.1, 22.7, 26.2, 31.4, 113.6, 121.0, 121.8, 122.7, 124.9, 126.1, 127.4, 128.8, 129.4, 143.9, 144.0, 144.1, 144.3. HRMS (ESI): m/z calcd for C₁₉H₂₀N₂H: 277.1705; found: 277.1699. Anal. Calcd for C₁₉H₂₀N₂: C, 82.57; H, 7.29; N, 10.14. Found: C, 82.64; H, 7.54; N, 9.62.

9

CCDC 658782 contains the supplementary crystallographic data of picrate 13d·2,4,6-(O ₂ N) ₃ C ₆ H ₂ ( OH). These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: [phone], E-mail: [e-mail]].

10

Preparation of 3-Butylisoquinoline (15): Hydrazone 12d (0.21 g, 1.00 mmol) was added under argon to the solution of t-BuOK (0.22 g, 2.00 mmol) in DMF (5 mL) and the mixture was stirred at r.t. until all starting hydrazone had disappeared (approx. 0.5 h, TLC monitoring). H₂O (20 mL) was added and the mixture was extracted with Et₂O (3 × 20 mL). The combined organic extracts were dried with MgSO₄ and the residue was purified by flash chromatography (tert-butyl methyl ether) giving 15 (0.09 g, 0.47 mmol, 47%) as a yellow oil. All spectroscopic and physical data were in accordance with published data (see ref. 11).

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17b

Details of the quantum chemical calculations may be obtained from E.-U. Würthwein upon request.

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