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Synlett 2004(12): 2239-2241  
DOI: 10.1055/s-2004-831295
LETTER
© Georg Thieme Verlag Stuttgart · New York

An Efficient Synthesis of Substituted Pyrroles with the Aid of a Low-Valent Titanium Reagent

Daqing Shi*a-c, Chuling Shia, Xiangshan Wanga,b, Qiya Zhuanga,b, Shujiang Tua,b, Hongwen Huc
a Department of Chemistry, Xuzhou Normal University, Xuzhou 221116, P. R. China
b The Key Laboratory of Biotechnology for Medical Plants of Jiangsu Province, Xuzhu 221116, P. R. China
c Department of Chemistry, Nanjing University, Nanjing 210093, P. R. China
Fax: +86(516)3403164; e-Mail: dqshi@263.net;
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Publication History

Received 7 June 2004
Publication Date:
06 August 2004 (online)

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Abstract

A short and efficient synthesis of substituted pyrroles was accomplished in good yields via the novel coupling cyclization reaction of 1,3-diketones with imines or oximes promoted by TiCl4/Zn system.

Key words

pyrrole - low-valent titanium reagent - synthesis

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The general procedure is represented as follows: TiCl4 (1.65 mL, 15 mmol) was added dropwise using a syringe to a stirred suspension of Zn powder (1.95 g, 30 mmol) in freshly distilled dry THF (20 mL) at r.t. under a N2 atmosphere. The mixture was refluxed for 2 h. The suspension of low-valent titanium reagent formed was cooled to r.t. and a solution of 1,3-diketone(1) (5 mmol) and imine 2 (5 mmol) in THF (5 mL) was added carefully. The reaction mixture was stirred for 4 h at r.t. On completion of the reaction most of the solvent was removed in vacuo. The residue was poured into 5% HCl (100 mL) and extracted with CHCl3 (4 × 30mL). The combined organic layer was washed with H2O (4 × 30 mL), dried (Na2SO4), and the solvent was removed to give the crude product, which was purified by column chromatography [silica gel, acetone-petroleum ether (bp 60-90ºC), 1:6] to give pure 3.

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Typical data for representative compounds: Compound 3a, 1,2,3,5-tetraphenylpyrrole: mp 202-204 °C. IR: νmax = 3050, 1600, 1495, 1450, 1370, 1075, 1030, 915, 760, 695 cm-1. 1H NMR (400 MHz, CDCl3): = 6.71 (1 H, s, C4-H), 6.98-6.99 (2 H, m, ArH), 7,03-7.05 (2 H, m, ArH), 7.11-7.26 (16 H, m, ArH). MS: m/z (%) = 371 (100). Anal. Calcd for C28H21N: C, 90.53; H, 5.70; N, 3.77%. Found: C, 90.56; H, 5.59; N, 3.74%. Compound 5a, 3,5-diphenyl-2-(3′,4′-dimethoxy-phenyl)pyrrole: mp 184-185 °C. IR: νmax = 3350, 3030, 1600, 1515, 1495, 1460, 1245, 1220, 1140, 1025, 855, 815, 760, 695 cm-1. 1H NMR (400 MHz, CDCl3): δ = 3.66 (6 H, s, 2 × CH3O), 6.47 (1 H, s,C4-H), 6.87-7.40 (13 H, m, ArH), 8.43 (1 H, s, NH). MS: m/z (%) = 355 (100), 340 (22). Anal. Calcd for C24H21NO2: C, 81.10; H, 5.96; N, 3.94%. Found: C, 81.28; H, 5.82; N, 3.85%.

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X-Ray data for 3g: C28H19Cl2N; M = 440.34, colorless block crystals, 0.54 × 0.50 × 0.50 mm, monoclinic, space group P21/c, a = 9.952 (2), b = 9.863 (2), c = 23.460 (6) Å, β = 99.62 (2)°, V = 2270.4 (9) Å3, Z = 4, Dc = 1.288 gcm-3. F(000) = 912, µ(MoKα) = 0.301 mm-1. Intensity data were collected on a Siemens P4 diffractometer with graphite monochromated MoKα radiation (λ = 0.71073 Å), using scan mode with 1.76°<q<25.50°. 4205 unique reflections were measured and 2267 reflections with I>2σ(I) were used in the refinement. The structure was solved by direct methods and expanded using Fourier techniques. The final refinement was converged to R = 0.0387 and wR = 0.0793.