Subscribe to RSS
DOI: 10.1055/s-2006-932452
A New Approach to the Preparation of 1,3,4-Triarylpyrroles
Publication History
Publication Date:
06 February 2006 (online)

Abstract
A class of 1,3,4-triaryl-2,5-dihydropyrroles were synthesized using the McMurry coupling reaction as the key step. The non-catalytic photoconversion of 1,3,4-triaryl-2,5-dihydropyrroles furnished 1,3,4-triarylpyrroles in good yields (63-89%). It was found that the photoconversion was facile and very reliable; the solvent was found to play an important role.
Key words
1,3,4-triaryl-2,5-dihydropyrrole - 1,3,4-triarylpyrrole - photoconversion - McMurry reaction
- 1
Amima R.Evan T.Aknin N.Kashman Y. J. Nat. Prod. 2000, 63: 832 -
2a
Unverferth K.Engel J.Hofgen N.Rostock A.Gunther R.Lankau HJ.Menzer M.Rolfs A.Liebscher L.Muller B. J. Med. Chem. 1998, 41: 63 -
2b
Dannhardt G.Kiefer W.Kramer G.Maehrlein S.Nowe U.Fiebich B. Eur. J. Med. Chem. 2000, 35: 499 -
3a
Jacobi PA.Coults LD.Guo JS.Leung SL. J. Org. Chem. 2000, 65: 205 -
3b
Boger DL.Boyce CW.Labrili MA.Sehon CA.Jin Q. J. Am. Chem. Soc. 1999, 121: 54 -
4a
Holland GFU. inventors; Patent 4,282,242. ; Chem. Abstr. 1981, 95, 187068e -
4b
Koho KT. inventors; (Nippon Soda Co., Ltd.) JP 81 79,672. ; Chem. Abstr. 1981, 95, 187069f -
4c
Bettarini F,Meazza G,Castoro P, andPortoso D. inventors; Patent PCT Int. Appl. WO 02 70476. ; Chem. Abstr. 2002, 137, 232545 -
4d
Umio S, andKariyone K. inventors; JP 68 14,699. ; Chem. Abstr. 1969, 70, 87560z - 5
Shiraishi H.Nishitani T.Nishihara T.Sakaguchi S.Ishii Y. Tetrahedron 1999, 55: 13957 - 6
Zelikin A.Shastri VR.Langer R. J. Org. Chem. 1999, 64: 3379 - 7
Liu J.-H.Chan H.-W.Wong HN. J. Org. Chem. 2000, 65: 3274 -
8a
Airaksinen AJ.Ahlgren M.Vepsalainen J. J. Org. Chem. 2002, 67: 5019 -
8b
Smith ND.Huang D.Cosford NDP. Org. Lett. 2002, 4: 3537 - 9
Dieter RK.Yu H. Org. Lett. 2001, 3: 3855 - 10
Verniest G.De Kimpe N. Synlett 2003, 2013 -
11a
Balme G. Angew. Chem. Int. Ed. 2004, 43: 6238 -
11b
Dhawan R.Arndtsen BA. J. Am. Chem. Soc. 2004, 126: 468 -
12a
De Kimpe N.Tehrani KA.Stevens C.De Cooman P. Tetrahedron 1997, 53: 3693 -
12b
Tehuani KA.Borremans D.De Kimpe N. Tetrahedron 1999, 55: 4133 -
12c
Verniest G.Claessens S.De Kimpe N. Tetrahedron 2005, 61: 4631 -
12d
Verniest G.Claessens S.Bombeke F.Van Thienen T.De Kimpe N. Tetrahedron 2005, 61: 2879 -
12e
Keppens M.De Kimpe N.Fonck G. Synth. Commun. 1996, 26: 3097
References and Notes
1a-f; General Procedure 2-Bromoacetophenone or 2-bromoacetone derivative (20 mmol), Na2CO3 (20 mmol), and p-anisidine (10 mmol) or aniline derivatives (10 mmol) were dissolved in EtOH (95 %; 20 mL). The mixture was stirred for 0.5 h at ambient temperature followed by heating to reflux for 4 h. The reaction mixture was cooled and diluted with H2O. The solid was obtained and purified by recrystallization from EtOH. To a suspension of Zn powder (0.3 mol) in THF (350 mL) under nitrogen flux was added TiCl4 (10 mL) at 0 °C by syringe. The mixture was then refluxed for 1 h. To the mixture was added the solid (15 mmol) obtained above in THF (250 mL) very slowly at ambient temperature. The reaction mixture was stirred for another 24 h in darkness then quenched with K2CO3 (40%; 80 mL). The solid was filtered and washed with Et2O (50 mL). The combined organic phases were concentrated to 50 mL under reduced pressure. H2O (50 mL) was then added to the residue. The product was extracted with Et2O (50 mL) and dried over MgSO4. After evaporation of the solvent, the crude product was purified by flash column chromatography. For 1f 2-bromoacetonephenone was treated with p-anisidine first, followed by reaction with 3-(2,5-dimethyl)-1′-bromoacetylthiophene. 1a: 1H NMR: δ = 7.30-7.19 (m, 12 H), 6.66 (d, 3 H, J = 7.6 Hz), 4.57 (s, 4 H). MS (EI): m/z = 297 (M+, 100). HRMS: m/z calcd for C22H19N [M+]: 297.3991; found: 297.4056. 1b: 1H NMR: δ = 7.30-7.27 (m, 10 H), 6.88 (d, 2 H, J = 8.8 Hz), 6.63-6.60 (d, 2 H, J = 8.9 Hz), 4.54 (s, 4 H), 3.69 (s, 3 H). MS (EI): m/z = 327 (M+, 100). HRMS: m/z calcd for C23H21NO [M+]: 327.4259; found: 327.6128. 1c: 1H NMR: δ = 7.30-7.27 (m, 10 H), 7.22 (d, 2 H, J = 8.2 Hz), 6.67 (d, 2 H, J = 8.8 Hz), 4.57 (s, 4 H). MS (EI): m/z = 330 (M+ - 1, 99), 138 (100). HRMS: m/z calcd for C22H18ClN [M+]: 331.8542; found: 332.0014. 1d: 1H NMR: δ = 6.92 (d, 2 H, J = 9.0 Hz), 6.57 (d, 2 H, J = 6.0 Hz), 5.87 (s, 2 H), 4.35 (s, 4 H), 3.79 (s, 3 H), 2.24 (s, 6 H), 2.06 (s, 6 H). MS (EI): m/z = 363 (M+, 100). HRMS: m/z calcd for C23H25NO3 [M+]: 363.5225; found: 363.5249. 1e: 1H NMR: δ = 7.93 (d, 4 H, J = 9.0 Hz), 7.28 (d, 4 H, J = 9.0 Hz), 6.93 (d, 2 H, J = 9.0 Hz), 6.68 (d, 2 H, J = 9.0 Hz), 4.64 (s, 4 H), 3.79 (s, 3 H), 2.41 (s, 6 H), 2.06 (s, 6 H). MS (EI): m/z = 517 (M+, 52), 119 (100). HRMS: m/z calcd for C33H31N3O3 [M+]: 517.6259; found: 517.6164. 1f: 1H NMR: δ = 7.30-7.25 (m, 5 H), 6.88 (d, 2 H, J = 9.0 Hz), 6.68 (s, 1 H), 6.62 (d, 2 H, J = 9.0 Hz), 4.59 (t, 2 H, J = 4.5 Hz), 4.36 (t, 2 H, J = 4.5 Hz), 3.71 (s, 3 H), 2.41 (s, 3 H), 1.95 (s, 3 H). MS (EI): m/z = 361 (M+, 100). HRMS: m/z calcd for C23H23NOS [M+]: 361.5067; found: 361.5095.
142a-f; General Procedure A solution of 1,3,4-trisubstituted 2,5-dihydropyrroles (0.5 mmol) in CH2Cl2 (100 mL) was irradiated with UV light (high-pressure Hg lamp, 500 W) until the starting material was no longer detected by TLC. After the solvent was evaporated the crude product were purified by column chromatography (EtOAc-PE). 2a: 1H NMR: δ = 7.71 (d, 2 H, J = 7.7 Hz), 7.53 (d, 2 H, J = 7.4 Hz), 7.48 (s, 2 H), 7.34-7.21 (m, 11 H). MS (EI): m/z = 295 (M+, 100). HRMS: m/z calcd for C22H17N [M+]: 295.3833; found: 295.4122. 2b: 1H NMR: δ = 7.57 (d, 2 H, J = 9.0 Hz), 7.32-7.17 (m, 12 H), 7.05 (d, 2 H, J = 8.8 Hz), 3.81 (s, 3 H). MS (EI): m/z = 325 (M+, 100). HRMS: m/z calcd for C23H19NO [M+]: 325.4101; found: 325.4708. 2c: 1H NMR: δ = 7.72 (d, 2 H, J = 8.8 Hz), 7.52 (d, 2 H, J = 8.7 Hz), 7.46 (s, 2 H), 7.31-7.20 (m, 8 H). MS (EI): m/z = 329 (M+, 100). HRMS: m/z calcd for C22H16ClN [M+]: 329.8384; found: 329.9123. 2d: 1H NMR: δ = 7.36 (d, 2 H, J = 8.8 Hz), 6.98 (d, 2 H, J = 9.0 Hz), 6.94 (s, 2 H), 5.86 (s, 2 H), 3.85 (s, 3 H), 2.25 (s, 6 H), 2.18 (s, 3 H). MS (EI): m/z = 361 (M+, 100). HRMS: m/z calcd for C23H23NO3 [M+]: 361.4387; found: 361.4401. 2e: 1H NMR: δ = 7.96 (d, 4 H, J = 9.0 Hz), 7.45 (d, 2 H, J = 9.0 Hz), 7.32 (s, 2 H), 7.27 (d, 4 H, J = 8.9 Hz), 7.00 (d, 2 H, J = 8.9 Hz), 3.85 (s, 3 H), 2.41 (s, 6 H), 2.12 (s, 6 H). MS (EI): m/z = 515 (M+, 65), 119 (100). HRMS m/z calcd for C33H29N3O3 [M+]: 515.6106; found: 515.6164. 2f: 1H NMR: δ = 7.43-7.30 (m, 6 H), 7.25-7.23 (m, 2 H), 7.02-7.00 (m, 3 H), 6.57 (s, 1 H), 3.87 (s, 3 H), 2.45 (s, 3 H), 2.22 (s, 3 H). MS (EI): m/z = 359 (M+, 100). HRMS: m/z calcd for C23H21NOS [M+]: 359.4909; found: 359.4972.