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

Alexander V. Butin; Fatima A. Tsiunchik; Vladimir T. Abaev; Valery E. Zavodnik

doi:10.1055/s-2008-1072720

LETTER

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

Alexander V. Butin*^a, Fatima A. Tsiunchik^a, Vladimir T. Abaev^b, Valery E. Zavodnik^c
^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

Abstract

Alle Artikel dieser Rubrik

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

Volltext

Referenzen

References and Notes

<A NAME="RD33807ST-1">1</A> Kobayashi G. Furukawa S. Matsuda Y. Natsuki R. Yakugaku Zasshi 1969, 89: 58 ; Chem. Abstr. 1969, 70, 96665

<A NAME="RD33807ST-2">2</A> Levy J. Royer D. Guilhem J. Cesario M. Pascard C. Bull. Soc. Chim. Fr. 1987, 193

<A NAME="RD33807ST-3">3</A> Olesen PH. Hansen JB. Engelstoft M. J. Heterocycl. Chem. 1995, 32: 1641

<A NAME="RD33807ST-4">4</A> Smitrovich JH. Davies IV. Org. Lett. 2004, 4: 533

<A NAME="RD33807ST-5">5</A> Engqvist R. Javaid A. Bergman J. Eur. J. Org. Chem. 2004, 2589

<A NAME="RD33807ST-6">6</A> Appukkuttan P. Van der Eycken E. Dehaen W. Synlett 2005, 127

<A NAME="RD33807ST-7">7</A> Majumdar KC. Alam S. J. Chem. Res., Synop. 2006, 289

<A NAME="RD33807ST-8A">8a</A> Kanbe K. Okamura M. Hattori S. Naganawa H. Hamada M. Okami Y. Takeuchi T. Biosci. Biotech. Biochem. 1993, 57: 632

<A NAME="RD33807ST-8B">8b</A> Kanbe K. Naganawa H. Nakamura KT. Okami Y. Takeuchi T. Biosci. Biotech. Biochem. 1993, 57: 636

<A NAME="RD33807ST-9">9</A> Pedras MSC. Suchy M. Bioorg. Med. Chem. 2006, 14: 714

<A NAME="RD33807ST-10A">10a</A> Abaev VT. Gutnov AV. Butin AV. Zavodnik VE. Tetrahedron 2000, 56: 8933

<A NAME="RD33807ST-10B">10b</A> Butin AV. Abaev VT. Mel’chin VV. Dmitriev AS. Tetrahedron Lett. 2005, 46: 8439

<A NAME="RD33807ST-10C">10c</A> Butin AV. Smirnov SK. Tetrahedron Lett. 2005, 46: 8443

<A NAME="RD33807ST-10D">10d</A> Mel’chin VV. Butin AV. Tetrahedron Lett. 2006, 47: 4117

<A NAME="RD33807ST-10E">10e</A> Butin AV. Smirnov SK. Stroganova TA. J. Heterocycl. Chem. 2006, 43: 623

<A NAME="RD33807ST-10F">10f</A> Abaev VT. Dmitriev AS. Gutnov AV. Podelyakin SA. Butin AV. J. Heterocycl. Chem. 2006, 43: 1195

<A NAME="RD33807ST-10G">10g</A> Butin AV. Mel’chin VV. Abaev VT. Bender W. Pilipenko AS. Krapivin GD. Tetrahedron 2006, 62: 8045

<A NAME="RD33807ST-10H">10h</A> Butin AV. Smirnov SK. Stroganova TA. Bender W. Krapivin GD. Tetrahedron 2007, 63: 474

<A NAME="RD33807ST-10I">10i</A> Stroganova TA. Butin AV. Vasilin VK. Nevolina TA. Krapivin GD. Synlett 2007, 1106

<A NAME="RD33807ST-10J">10j</A> Butin AV. Dmitriev AS. Kostyukova ON. Abaev VT. Trushkov IV. Synthesis 2007, 2208

<A NAME="RD33807ST-10K">10k</A> Dmitriev AS. Abaev VT. Bender W. Butin AV. Tetrahedron 2007, 63: 9437

<A NAME="RD33807ST-11A">11a</A> Friedmann A. Gattermann L. Ber. Dtsch. Chem. Ges. 1892, 25: 3525

<A NAME="RD33807ST-11B">11b</A> Tust K. Gattermann L. Ber. Dtsch. Chem. Ges. 1892, 25: 3528

<A NAME="RD33807ST-11C">11c</A> Jagodzinski T. Synthesis 1988, 717

<A NAME="RD33807ST-11D">11d</A> Jagodzinski T. Jagodzinska E. Jabzonsky Z. Tetrahedron 1986, 42: 3683

<A NAME="RD33807ST-11E">11e</A> Papadopoulos EP.
J. Org. Chem. 1976, 41: 962

<A NAME="RD33807ST-11F">11f</A> Looney-Dean V. Lindamood BS. Papadopoulos EP. Synthesis 1984, 68

<A NAME="RD33807ST-11G">11g</A> Deck LM. Turner SD. Deck JA. Papadopoulos EP. J. Heterocycl. Chem. 2001, 38: 343

<A NAME="RD33807ST-11H">11h</A> Naik PU. Nara SJ. Harjani JR. Salunkhe MM. Can. J. Chem. 2003, 81: 1057

<A NAME="RD33807ST-12A">12a</A> Gittos MW. Robinson MR. Verge JP. Davies RV. Iddon B. Suschitzky H. J. Chem. Soc., Perkin Trans. 1 1976, 33

<A NAME="RD33807ST-12B">12b</A> Davies RV. Iddon B. Paterson T. Pickering MW. Suschitzky H. Gittos M. J. Chem. Soc., Perkin Trans. 1 1976, 138

<A NAME="RD33807ST-12C">12c</A> Davies RV. Iddon B. Suschitzky H. Pickering MW. Gallagher PT. Gittos MW. Robinson MD. J. Chem. Soc., Perkin Trans. 1 1977, 2357

<A NAME="RD33807ST-12D">12d</A> Molina P. Alcantara J. Lopez-Leonardo C. Tetrahedron 1996, 52: 5833

<A NAME="RD33807ST-12E">12e</A> Duceppe JS. Gauthier J. J. Heterocycl. Chem. 1984, 21: 1685

<A NAME="RD33807ST-13">13</A> Jagodzinski TS. Dziembowska TM. Szczodrowska B. Bull. Soc. Chim. Belg. 1989, 98: 327

<A NAME="RD33807ST-14A">14a</A> Butin AV. Abaev VT. Stroganova TA. Gutnov AV. Molecules 1997, 2: 62

<A NAME="RD33807ST-14B">14b</A> Abaev VT. Tsiunchik FA. Gutnov AV. Butin AV. J. Heterocycl. Chem. 2008, 45: 475

<A NAME="RD33807ST-15">15</A> Abaev VT. Tsiunchik FA. Gutnov AV. Butin AV. Tetrahedron Lett. 2006, 47: 4029

Compounds 3 were prepared using the Meerwein method. For a typical procedure, see ref. 16b.
General Procedure for the Arylation Reaction
A mixture of substituted 2-nitroaniline (0.3 mol), H₂O (400 mL) and 36% HCl (200 mL) was stirred for 30 min at 80 °C. The solution was then cooled to 0 °C to -10 °C. The resulting suspension of aniline hydrochloride was treated with NaNO₂ (25 g, 0.36 mol) in H₂O (120 mL). The resulting solution of the diazonium salt was stirred for 40 min at 0 °C to -5 °C and filtered. A solution of furfural or 2-acetylfuran (0.3 mol) in acetone (150 mL) was added, followed by CuCl₂ (8 g, 0.06 mol) in H₂O (100 mL). The reaction mixture was stirred for 12 h at r.t. When the reaction was complete, the resulting precipitate was filtered off and crystallized from EtOH-acetone; yields of 5-arylfurfurals 3a,c-e: 45-53%; yield of 2-acetyl-5-phenylfuran (3b): 41%.

<A NAME="RD33807ST-16B">16b</A> Janda L. Voticky Z. Chem. Zvesti 1984, 38: 507

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.

<A NAME="RD33807ST-17B">17b</A> Ono A. Suzuki N. Kamimura J. Synthesis 1987, 736

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.

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: ν_max = 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, H_Fur), 6.67 (d, J = 3.3 Hz, 1 H, H_Fur), 6.78 (d, J = 2.6 Hz, 1 H, H_Ar), 6.84 (dd, J = 2.6, 8.8 Hz, 1 H, H_Ar), 7.62 (d, J = 8.8 Hz, 1 H, H_Ar). 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.

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: ν_max = 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, H_Ar), 7.04 (d, J = 2.3 Hz, 1 H, H_Ar), 7.73 (d, J = 8.6 Hz, 1 H, H_Ar), 8.29 (s, 1 H, H_Th), 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.

Crystal Data of Compound 8a
C₁₂H₉NOS, orthorhombic, space group P_bca; 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.