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N. Zanatta et al.
LETTER
(10) Nenajdenko, V. G.; Statsuk, A. V.; Balenkova, E. S. Chem.
Heterocycl. Compd. 2003, 5, 598.
(11) Peng, W.-M.; Zhu, S.-Z. J. Fluorine Chem. 2002, 116, 81.
(12) Matsumoto, N.; Takahashi, M. Tetrahedron Lett. 2005, 46,
5551.
(25) Synthesis of N-Substituted 3-Trifluoroacetyl Pyrroles 5 –
General Procedure
To a solution of 3-trifluoroacetyl-4,5-dihydrofuran 1 (0.50 g,
3.0 mmol) in CH2Cl2 (5 mL), amines 2a,b (approx. 6.0
mmol), amines 2c–r (3.0 mmol), and amines 2s–u (1.5
mmol) were added under magnetic stirring, and the reaction
was stirred for 30 min at r.t. After this period, PCC (4.5
mmol) in CH2Cl2 (5 mL) was added, and the reaction
mixture was refluxed for 3 h. For amines 2a,b, before the
addition of PCC, the reaction was extracted with CH2Cl2
(3 × 15 mL) and dried with MgSO4. The solvent was
evaporated by rotary evaporator, and the reaction residue
was treated with 1 M solution of NaOH and extracted with
Et2O (3 × 50 mL). The combined organic layers were
washed with 1 M NaOH solution (2 × 50 mL) and distilled
H2O (1 × 50 mL). The organic phase was dried with anhyd
MgSO4, evaporated, and purified by column
(13) (a) Okada, E.; Masuda, R.; Hojo, M.; Yoshida, R.
Heterocycles 1992, 34, 1435. (b) Elguero, R.; Jacquier, B.;
Shimizu, B. Bull. Soc. Chim. Fr. 1967, 2996. (c) Elguero,
R.; Jacquier, B.; Shimizu, B. Bull. Soc. Chim. Fr. 1970,
1585. (d) Shaitanova, E. N.; Gerus, I. I.; Kukhar, V. P.
Tetrahedron Lett. 2008, 49, 1184.
(14) Jones, R. A.; Bean, G. P. In The Chemistry of Pyrroles;
Academic Press: London, 1977 and references cited therein.
(15) (a) Pavri, N. P.; Trudell, M. L. J. Org. Chem. 1997, 62,
2649. (b) Chen, N.; Lu, Y.; Gadamasetti, K.; Hurt, C. R.;
Norman, M. H.; Fotsch, C. J. Org. Chem. 2000, 65, 2603.
(c) Marcotte, F.-A.; Rombouts, F. J. R.; Lubell, W. D.
J. Org. Chem. 2003, 68, 6984. (d) Kagoshima, H.;
Akiyama, T. J. Am. Chem. Soc. 2000, 122, 11741.
(e) Wasserman, H. H.; Power, P.; Petersen, A. K.
Tetrahedron Lett. 1996, 37, 6657.
chromatography using basic alumina (60 g) with a plug of
active charcoal and eluted with Et2O (50 mL).
(26) Spectroscopic Data of Selected Compounds
1-Methyl-3-trifluoroacetylpyrrole (5b)
(16) (a) Nunomoto, S.; Kawakami, Y.; Yamashita, Y.; Takeuchi,
H.; Egushi, S. J. Chem. Soc., Perkin Trans. 1 1990, 111.
(b) Bourak, M.; Gallo, R. Heterocycles 1990, 31, 401.
(17) For recent examples, see: (a) Salamone, S. G.; Dudley,
G. B. Org. Lett. 2005, 7, 4443. (b) Song, G.; Wang, B.;
Wang, G.; Kang, Y.; Yang, T.; Yang, L. Synth. Commun.
2005, 35, 1051. (c) Dieltiens, N.; Stevens, C. V.; De Vos,
D.; Allaert, B.; Drozdzak, R.; Verpoort, F. Tetrahedron Lett.
2004, 45, 8995. (d) Tracey, M. R.; Hsung, R. P.; Lambert,
R. H. Synthesis 2004, 918. (e) Wang, B.; Gu, Y.; Luo, C.;
Yang, T.; Yang, L.; Suo, J. Tetrahedron Lett. 2004, 45,
3417. (f) Dhawan, R.; Arndtsen, B. A. J. Am. Chem. Soc.
2004, 126, 468. (g) Abdelrazek, F. Synth. Commun. 2005,
35, 2251. (h) Delayen, A.; Goossens, L.; Houssin, R.;
Henichart, J. P. Heterocycles 2005, 65, 1673.
1H NMR (200 MHz, CDCl3): d = 7.4 (s, 1 H), 6.7 (s, 1 H),
6.6 (s, 1 H), 3.7 (s, 1 H). 13C NMR (100 MHz, CDCl3):
d = 175.0 (q, 2JCF = 35.3 Hz), 130.1, 124.3, 117.8, 116.9 (q,
1JCF = 288.7 Hz), 110.9, 36.8. GC-MS (IE, 70eV): m/z (%) =
117 (68) [M+], 108 (100), 80 (30). ESI-HRMS: m/z calcd for
C6H4F3NO [M + H]+: 178.0479; found: 178.0471.
1-(Ethan-1-ol-2-yl)-3-trifluoroacetylpyrrole (5g)
1H NMR (400 MHz, CDCl3): d = 7.5 (s, 1 H), 6.7 (m, 2 H),
4 (t, 1 H, J = 9.2 Hz), 3.9 (t, 1 H, J = 9.2 Hz). 13C NMR (100
MHz, CDCl3): d = 175.4 (q, 2JCF = 35.7 Hz), 130.1, 123.8,
117.8, 116.9 (q, 1JCF = 288.8 Hz), 110.9, 61.8, 52.5. GC-MS
(IE, 70eV): m/z (%) = 207 (25) [M+], 138 (100), 94 (57).
ESI-HRMS: m/z calcd for C9H8F3NO [M + H]+: 208.0585;
found: 208.0576.
1-(2,2-Dimethyl-etan-1-ol-2-yl)-3-trifluoroacetylpyrrole
(5k)
(18) Black, B. C.; Hollingworth, R. M.; Ahammadsahib, K. Y.;
Kukel, C. D.; Donovan, S. Pestic. Biochem. Physiol. 1994,
50, 115.
1H NMR (400 MHz, CDCl3): d = 7.6 (s, 1 H), 6.9 (m, 1 H),
6.7 (m, 2 H), 3.6 (s, 2 H), 1.5 (s, 6 H). 13C NMR (100 MHz,
CDCl3): d = 175.4 (q, 2JCF = 35 Hz), 127.5, 121, 117.3,
116.9 (q, 1JCF = 289 Hz), 110.5, 70.4, 60.2, 24.5. GC-MS (IE
70eV): m/z (%) = 235 (30) [M+], 204 (97), 94 (100). ESI-
HRMS: m/z calcd for C10H12F3NO2 [M + H]+: 236.0898;
found: 236.0891.
(19) Unpublished results: compound 5f exhibited activity against
H37Rv and RMPr (MIC = 12.5 mg/mL) and INHr (MIC = 50
mg/mL); 5h exhibited activity against H37Rv and RMPr
(MIC = 12.5 mg/mL) and INHr (MIC = 25.0 mg/mL); 5l
exhibited activity against H37Rv (MIC = 6.25 mg/mL) and
RMPr and INHr (MIC = 12.5 mg/mL); 5m exhibited activity
against H37Rv and RMPr (MIC = 6.25 mg/mL) and INHr
(MIC = 12.5 mg/mL).
1-(Ethan-2-dimethylamino-1-yl)-3-trifluoroacetyl-
pyrrole (5q)
1H NMR (400 MHz, CDCl3): d = 7.55 (s, 1 H), 6.74 (m, 2
H), 4.01 (t, 2 H, J = 3.2 Hz) 2.67 (t, 2 H, J = 3.1 Hz), 2.27 (s,
6 H). 13C NMR (100 MHz, CDCl3): d = 175.2 (q, 2JCF = 35
Hz), 129.6, 123.5, 117.8, 116.9 (q, 1JCF = 288 Hz), 110.7,
59.6, 48.5, 45.4. GC-MS (IE, 70eV): m/z (%) = 235 (100)
[MH+], 165 (20). ESI-HRMS: m/z calcd for C10H13F3N2O
[M + H]+: 235.1058; found: 235.1058.
(20) Colla, A.; Martins, M. A. P.; Clar, G.; Krimmer, S.; Fisher,
P. Synthesis 1991, 483.
(21) (a) Corey, E. J.; Sugs, J. W. Tetrahedron Lett. 1975, 32,
2647. (b) Hunsen, M. Tetrahedron Lett. 2005, 46, 1651.
(c) Dugger, R. W.; Ragan, J. A.; Brown, D. H. Org. Process
Res. Dev. 2005, 9, 253. (d) Rauter, A. D.; Piedade, F.;
Almeida, T.; Ramalho, R.; Ferreira, M. J.; Resende, R.;
Amado, J.; Perreira, H.; Justino, J.; Neves, H.; Silva, F. V.
M.; Canda, T. Carbohydr. Res. 2004, 339, 1889. (e) Li,
S. H.; Li, T. S. Steroids 1998, 63, 76. (f) Rauter, A. P.;
Fernandes, A. C.; Czernecki, S.; Valery, J. M. J. Org. Chem.
1996, 61, 3594. (g) Rauter, A.; Ferreira, M.; Borges, C.;
Duarte, T.; Piedade, F.; Silva, M.; Santos, H. Carbohydr.
Res. 2000, 325, 1.
1,2-Bis-3-trifluoroacetylpyrrole-1-yl-ethane (5s)
1H NMR (400 MHz, CDCl3): d = 7.14 (s, 1 H), 6.77 (s, 1 H),
6.50 (m, 1 H), 4.30 (s, 2 H). 13C NMR (100 MHz, CDCl3):
d = 175.2 (q, 2JCF = 35 Hz), 128.8, 122.8, 118.8, 116.7 (q,
1JCF = 288 Hz), 111.9, 52.1. GC-MS (IE, 70eV): m/z (%) =
352 (31) [M+], 283 (100), 176 (26), 107 (25). ESI-HRMS:
m/z calcd for C14H10F6N2O2 [M + H]+: 367.0881; found:
367.0876.
(22) Choudary, B. M.; Prosad, A. D.; Bhuma, V.; Swapna, V.
J. Org. Chem. 1992, 57, 5841.
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(24) Aydin, F.; Turunc, E. J. Serb. Chem. Soc. 2007, 72, 129.
(27) Zanatta, N.; Barichello, R.; Pauletto, M. M.; Bonacorso,
H. G.; Martins, M. A. P. Tetrahedron Lett. 2003, 44, 961.
(28) Zanatta, N.; Schneider, M. F. M.; Schneider, P. H.; Wouters,
A. D.; Bonacorso, H. G.; Martins, M. A. P.; Wessjohann,
L. A. J. Org. Chem. 2006, 71, 6996.
Synlett 2009, No. 5, 755–758 © Thieme Stuttgart · New York