One-Step Synthesis of [1,2]Diazepino[4,5-b]indole Derivatives from the Reaction
of Pyranoindolones with Methylhydrazine

Dimitra Hatzimimikou; Despina Livadiotou; Constantinos A. Tsoleridis; Julia Stephanidou-Stephanatou

doi:10.1055/s-2008-1078511

LETTER

One-Step Synthesis of [1,2]Diazepino[4,5-b]indole Derivatives from the Reaction of Pyranoindolones with Methylhydrazine

Dimitra Hatzimimikou, Despina Livadiotou, Constantinos A. Tsoleridis, Julia Stephanidou-Stephanatou*
Department of Chemistry, Laboratory of Organic Chemistry, University of Thessaloniki, 54124 Thessaloniki, Greece
Fax: +30(2310)997679; e-Mail: ioulia@chem.auth.gr;

Abstract

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Abstract

The synthesis of a number of [1,2]diazepino[4,5-b]indoles in good yields by a one-step sequence from the reaction of pyranoindolones with methylhydrazine is described. The observed regioselectivity of the reaction is explained considering several reaction paths.

Keywords

diazepinoindoles - pyranoindolones - methylhydrazine - bisnucleophiles

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References

References and Notes

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All melting points were determined on a Büchi apparatus and are uncorrected. The ^¹H NMR and ^¹³C NMR spectra were recorded on a Bruker AM300 spectrometer in CDCl₃ with TMS as internal standard. All coupling constants are given in Hz and chemical shifts are given in ppm.
Typical Experimental Procedure for the Preparation of 4e: To a stirred and refluxing solution of pyranoindolone 3e (1.5 mmol) in bromobenzene (15 mL), methylhydrazine (Fluka, purum; 3.0 mmol) was added and refluxing was continued for 20 min. The solvent was distilled off under reduced pressure to yield the corresponding crude product, which was purified by silica gel chromatography using petroleum ether-EtOAc (5:1) as eluent, to give 1-ethyl-3,10-dimethyl-5,10-dihydro[1,2]diazepino[4,5-b]indol-4(3H)-one (4e). Yield: 73%; yellow crystals; mp 104-106 ˚C (ethanol). IR (nujol): 1651 cm^-¹. ^¹H NMR: δ = 1.16 (t, J = 7.4 Hz, 3 H, 1-Me), 2.92 (q, J = 7.4 Hz, 2 H, 1-CH₂), 3.33 (s, 3 H, 3-Me), 3.51 (br s, 2 H, C-5), 3.82 (s, 3 H, 10-Me), 7.19 (ddd, J = 1.0, 7.0, 8.0 Hz, 1 H, C-7),^¹4 7.35 (ddd, J = 0.75, 1.0, 8.0 Hz, 1 H, C-9), 7.37 (ddd, J = 1.2, 7.0, 8.0 Hz, 1 H, C-8), 7.70 (ddd, J = 0.75, 1.2, 8.0 Hz, 1 H, C-6). ^¹³C NMR: δ =12.4 (1-Me), 30.3 (1-CH₂), 32.19 (C-5), 32.2 (10-Me), 38.2 (3-Me), 109.9 (C-9), 117.8 (C-5a), 119.7 (C-6), 120.3 (C-7), 124.6 (C-5b), 125.0 (C-8), 130.2 (C-10a), 140.1, (C-9a), 158.8 (C-1), 168.9 (C=O). EIMS: m/z (%) = 255 (71) [M⁺], 240 (10), 226 (100), 212 (5), 168 (20), 143 (6). Anal. Calcd for C₁₅H₁₇N₃O (255.31): C, 70.56; H, 6.71; N, 16.46. Found: C, 70.76; H, 6.83; N, 16.68.

Selected data for compound 5d. ^¹H NMR: δ = 2.27 (s, 3 H, 1′-Me), 3.16 (s, 3 H, 3′-Me), 3.73 (s, 3 H, 1-Me), 3.77 (s, 2 H, 3-CH₂), 7.16 (ddd, J = 0.9, 7.1, 7.95 Hz, 1 H, C-5),^¹4 7.27 (ddd, J = 1.2, 7.1, 8.2 Hz, 1 H, C-6), 7.27 (ddd, J = 0.65, 0.9, 8.2 Hz, 1 H, C-7), 7.70 (ddd, J = 0.65, 1.2, 7.95 Hz, 1 H, C-4), 7.92 (br s, 1 H, N-3′), 8.05 (br s, 1 H, OH). ^¹³C NMR: δ = 16.7 (1′-Me), 32.1 (1-Me), 33.6 (3-CH₂), 37.5 (3′-Me), 108.3 (C-3), 109.4 (C-7), 119.8 (C-4), 120.5 (C-5), 123.6 (C-6), 127.2 (C-3a), 138.0 (C-7a), 138.3 (C-1′), 172.2 (C=O). EIMS: m/z (%) = 255 (71) [M⁺], 226 (100). Anal. Calcd for C₁₅H₁₇N₃O (255.31): C, 70.56; H, 6.71; N, 16.46. Found: C, 70.76; H, 6.83; N, 16.68.

The multiplicities and chemical shifts of the aromatic protons have been confirmed after simulation with the program SpinWorks, version 2.5, available from
ftp://davinci.chem.umanitoba.ca.