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Synlett 2008(8): 1145-1148  
DOI: 10.1055/s-2008-1072720
LETTER
© Georg Thieme Verlag Stuttgart · New York

A New Simple Route to the Thieno[2,3-b]indole Ring System

Alexander V. Butin*a, Fatima A. Tsiunchika, Vladimir T. Abaevb, Valery E. Zavodnikc
a Research Institute of Heterocyclic Compounds Chemistry, Kuban State University of Technology, Moskovskaya st. 2, Krasnodar 350072, Russian Federation
Fax: +7(861)2596592; e-Mail: alexander_butin@mail.ru; e-Mail: av_butin@yahoo.com;
b North-Ossetian State University, Vatutina st. 46, Vladikavkaz 362025, Russian Federation
c Karpov Institute of Physical Chemistry, Vorontsovo pole st. 10, Moscow 103064, Russian Federation
Further Information

Publication History

Received 22 October 2007
Publication Date:
16 April 2008 (online)

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Abstract

A simple and effective method has been elaborated for the synthesis of thieno[2,3-b]indole ring system. It is based on the electrophilic recyclization of 2-alkyl-5-(2-isothiocyanoaryl)furans in the presence of anhydrous AlCl3.

Key words

furan - ring opening - ring closure - fused-ring system - thieno[2,3-b]indole

    References and Notes

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    Compounds 3 were prepared using the Meerwein method. For a typical procedure, see ref. 16b.
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    Compounds 4 were synthesized according to the reported procedure, see ref. 17b.
    General Procedure for the Preparation of Compounds 4a-e
    To a cooled (0-5 °C) solution of compound 3 (17 mmol) in THF (120 mL), anhyd AlCl3 (4.5 g, 34 mmol) and NaBH4 (1.3 g, 34 mmol) were added portionwise under stirring. The resulting suspension was stirred at 0-5 °C for 20 min and then brought to reflux. After 1-2 h when the starting compound 3 vanished (TLC monitoring), the reaction mixture was cooled and poured into H2O (400 mL). The organic layer was separated and the water layer was extracted with EtOAc (3 × 50 mL). The combined organic layers were dried over anhyd Na2SO4, treated with activated charcoal, and the solvent evaporated under the reduced pressure. The residue 4 was used in the next step without further purification.
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18

General Procedure for the Preparation of Compounds 5a-e
To an ethanolic solution (50 mL) of compound 4 (6 mmol), Raney Ni (1.5 g) and hydrazine hydrate (2.5 mL) were added and the reaction mixture was refluxed for 1-2 h. After completion of the reaction (TLC monitoring), the catalyst was filtered off and the filtrate was evaporated under reduced pressure. The residue was dissolved in benzene-PE (1:1), filtered through a pad of silica gel, and the solvent evaporated under reduced pressure. The residue 5 was used in the next step without further purification.
WARNING: Care should be taken when handling benzene as a solvent due to its carcinogenic properties.

19

General Procedure for the Preparation of Compounds 6a-e
A solution of thiophosgene (0.5 mL, 6.5 mmol) in CH2Cl2 (10 mL) and NaHCO3 (1.3 g, 15.5 mmol) in H2O (50 mL) were simultaneously added at r.t. to a stirred solution of compound 5 (5 mmol) in CH2Cl2 (15 mL). When the reaction had finished (TLC monitoring), the mixture was poured into H2O (200 mL) and stirred for 6 h. The organic layer was separated and water layer was extracted with CH2Cl2 (2 × 50 mL). The combined organic layers were dried over anhyd Na2SO4, the dried extract was reduced to the half of its volume, and PE was added until the solution became cloudy. The solution was filtered through a pad of silica gel, evaporated to one third of its volume, and left to allow crystallization of the compounds 6.
Selected Analytical Data of 6e
Mp 85-86 °C. IR: νmax = 2136, 1616, 1600, 1568, 1548, 1496, 1296, 1200, 1176, 1032, 976, 880, 804, 788 cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.37 (s, 3 H, CH3), 3.80 (s, 3 H, OCH3), 6.10 (d, J = 3.3 Hz, 1 H, HFur), 6.67 (d, J = 3.3 Hz, 1 H, HFur), 6.78 (d, J = 2.6 Hz, 1 H, HAr), 6.84 (dd, J = 2.6, 8.8 Hz, 1 H, HAr), 7.62 (d, J = 8.8 Hz, 1 H, HAr). 13C NMR (75 MHz, CDCl3): δ = 13.8, 55.6, 108.0, 109.0, 112.4, 114.6, 120.5, 126.2, 127.3, 134.7, 148.0, 152.0, 158.7. MS: m/z (%) = 245 (85) [M+], 230 (37), 212 (23), 202 (29), 188 (32), 171 (20), 160 (17), 159 (19), 127 (13), 116 (13), 115 (26), 76 (14), 59 (23), 43 (38). Anal. Calcd for C13H11NO2S: C, 63.65; H, 4.52; N, 5.71. Found: C, 63.86; H, 4.38; N, 5.79.

20

General Procedure for the Preparation of Compounds 8a-e
Aluminum chloride (1.6 g, 12 mmol) was added to a solution of compound 6 (6 mmol) in 1,2-dichloroethane (30 mL). The reaction mixture was stirred for 30 min at 50 °C (TLC monitoring), then poured into H2O (200 mL) and extracted with CH2Cl2 (2 × 40 mL). The combined extracts were dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was crystallized from the appropriate solvent: benzene-PE for 8a; benzene for 8b; EtOH for 8c; EtOAc-PE for 8d; EtOH for 8e.
WARNING: Care should be taken when handling benzene as a solvent because of its carcinogenic properties.
Selected Analytical Data of 8e
Mp 225-226 °C. IR: νmax = 1628, 1608, 1584, 1508, 1480, 1472, 1400, 1280, 1236, 1196, 1156, 1092, 1024, 936, 824, 808 cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.53 (s, 3 H, CH3), 3.81 (s, 3 H, OCH3), 6.81 (dd, J = 2.3, 8.6 Hz, 1 H, HAr), 7.04 (d, J = 2.3 Hz, 1 H, HAr), 7.73 (d, J = 8.6 Hz, 1 H, HAr), 8.29 (s, 1 H, HTh), 11.86 (s, 1 H, NH). 13C NMR (75 MHz, CDCl3): δ = 25.7, 55.3, 96.1, 109.2, 115.9, 120.1, 124.7, 126.2, 135.8, 143.5, 146.6, 156.8, 190.5. MS: m/z (%) = 245 (85) [M+], 231 (22), 230 (100), 203 (11), 202 (57), 188 (13), 187 (18), 160 (17), 159 (16), 158 (17), 115 (11), 69 (18), 57 (12). Anal. Calcd for C13H11NO2S: C, 63.65; H, 4.52; N, 5.71. Found: C, 63.69; H, 4.41; N, 5.77.

21

Crystal Data of Compound 8a
C12H9NOS, orthorhombic, space group Pbca; a = 11.982(2) Å, b = 10.837(2) Å, c = 15.752(3) Å, V = 2045.4(6) Å3, Z = 8, D calcd = 1.398 Mg/m3, F(000) = 896; 1797 reflections collected, 1797 unique (R int = 0.0000); final R indices (935 observed collections I > 2σI): R 1 = 0.0309, wR 2 = 0.0924; final R indices (all data): R 1 = 0.0859, wR 2 = 0.1005. Crystallographic data (excluding structure factors) for the structure in this article have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 657300. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44 (1223)336033 or e-mail: deposit@ccdc.cam.ac.uc]. Each request should be accompanied by the complete citation of this paper.