D. Wischang, J. Hartung / Tetrahedron 67 (2011) 4048e4054
4053
for pentane/acetone¼5:1 (v/v). 1H NMR (CDCl3, 600 MHz)
d
4.78
150 MHz) d 95.5, 101.0, 113.6, 120.5, 124.9. MS (EI) m/z 172 (97), 170
(dd, 2H, J¼4.5, 1.8 Hz), 5.30 (dd, 1H, J¼10.5, 1.0 Hz), 5.39 (dd, 1H,
(100), 145 (9), 143 (10), 91 (21), 64 (57). 3,4,5-Tribromo-1H-pyrrole-
J¼17.2, 1.5 Hz), 5.95e6.02 (m, 1H), 6.92 (d, 1H, J¼2.8 Hz), 9.82 (br s,
2-carbonitrile ð4e3;4;5ꢁBr Þ. 1H NMR (DMSO-d6, 600 MHz)
d 14.10 (br
102.0, 103.5, 108.2, 109.0,
3
1H, NH). 13C NMR (CDCl3, 150 MHz)
d
65.8, 100.9, 107.4, 118.3, 119.0,
s, 1H, NH). 13C NMR (DMSO-d6, 150 MHz)
d
123.8, 131.8, 159.6. MS (EI) m/z 311 (35), 309 (74), 307 (38), 294 (6),
292 (11), 290 (6), 254 (52), 252 (100), 250 (52), 230 (20), 228 (20),
226 (14), 224 (26), 222 (14), 199 (21), 197 (44), 195 (23), 149 (71),
144 (24), 142 (24). Anal. Calcd for C8H7Br2NO2 (308.96): C, 31.10; H,
2.28; N, 4.53; Found: C, 31.37; H, 2.33; N, 4.56. Prop-2-enyl 3,4,5-
111.9. MS (EI) m/z 332 (30), 330 (93), 328 (100), 326 (33), 251 (13),
249 (27), 247 (12), 224 (9), 222 (19), 220 (9), 172 (10), 170 (10). Anal.
Calcd for C5H3BrN2 (169.99)/C5HBr3N2 (328.78) (53/47): C, 24.50; H,
0.85; N, 11.42; Found: C, 24.22; H, 0.89; N, 11.23. 558 U0T mgꢁ1, not
detected UTfinal mgꢁ1, pHfinal 7.0.
tribromo-1H-pyrrole-2-carboxylate ð4b3;4;5ꢁBr Þ. 1H NMR (CDCl3,
3
600 MHz)
d
4.85 (d, 2H, J¼5.6 Hz), 5.31 (dd, 1H, J¼10.6, 0.8 Hz), 5.47
4.2.6. Bromination of methyl 1-ethylpyrrole-2-carboxylate (1f).
According to general method in Section 4.2. Yield: 134 mg, yellowish
liquid; 90/10-mixture of 1f/2f4-Br-isomers. Methyl 4-bromo-1-ethyl-
(dd, 1H, J¼17.2, 1.3 Hz), 5.95e6.04 (m, 1H), 10.22 (br s, 1H, NH). 13C
NMR (CDCl3, 150 MHz) d 66.2, 105.7, 106.7, 107.2, 119.0, 122.0, 131.5,
159.0. MS (EI) m/z 341 (22), 399 (64), 387 (65), 385 (23), 334 (33),
332 (96), 330 (100), 328 (37), 310 (22), 308 (49), 306 (32), 292 (18),
290 (34), 288 (16), 279 (14), 277 (40), 275 (40), 273 (13), 198 (26),
196 (51), 194 (25). 611 U0T mgꢁ1, 6 UfTinal mgꢁ1, pHfinal 6.6.
pyrrole-2-carboxylate (2f4-Br).1H NMR (CDCl3, 600 MHz)
d 1.39 (t, 3H,
J¼7.2Hz), 3.81(s, 3H), 4.35 (q, 2H, J¼7.1Hz), 6.83(d,1H, J¼1.8 Hz), 6.90
(d, 1H, J¼1.8 Hz). MS (EI) m/z 233 (97), 231 (100), 218 (27), 216 (29),
202 (55), 200 (61), 173 (41), 171 (38), 146 (12), 144 (12), 120 (26), 93
(24). 611 UT0 mgꢁ1, 53 UTfinal mgꢁ1, pHfinal 6.0.
4.2.3. Bromination of pentyl 1H-pyrrole-2-carboxylate (1c). According
to general method in Section 4.2. For isomer separation see also the
Supplementary data. Yield: 353 mg, dark yellow oil; 49/12/39-mix-
4.3. Synthesis of methyl 4,5-dibromopyrrole-2-carboxylate
ð3a4;5ꢁBr
Þ
2
ture of 2c4ꢁBr=2c5ꢁBr=3c4;5ꢁBr -isomers. Pentyl 4-bromo-1H-pyr-
2
role-2-carboxylate (2c4-Br). 1H NMR (CDCl3, 600 MHz)
d 0.92 (t, 3H,
A solution of H2O2 (2.0 mL, 0.825 M) and NaBr (169.8 mg,
1.65 mmol) inMES-buffer (500 mM, pH6.2)wasaddedwitha syringe
J¼7.1 Hz), 1.35e1.41 (m, 4H), 1.72e1.74 (m, 2H), 4.26 (t, 2H, J¼6.8 Hz),
6.88e6.89 (m, 1H), 6.93e6.94 (m, 1H), 9.23 (br s, 1H, NH). 13C NMR
pump (20 h, 1.67
mL/min) to a solution of substrate 1a (0.75 mmol)
(CDCl3, 150 MHz) d 14.1, 22.5, 28.3, 28.7, 65.1, 97.9, 116.8, 122.6, 123.5,
and VBrPO(AnI) (125.6
m
L, 34.6 UT, 0.063 mmol%) in MES-buffer
160.6. MS (EI) m/z 261(22), 259 (20), 189 (100), 187 (100), 173 (94),
171 (92), 146 (19), 144 (19), 93 (8), 65 (25). Pentyl 5-bromo-1H-pyr-
t
(500 mM, pH 6.2, 10.0 ml) and BuOH (3.3 mL). The reaction mix-
ture was stirred at 23 ꢀC for 1 day. The aqueous layer was extracted
with Et2O (3ꢃ20 mL). Combined organic extracts were dried
(MgSO4). The solvent was removed underreduced pressure (14 mbar,
40 ꢀC) to afford a product mixture, which was analyzed by 1H NMR
and GC, using pentachlorobenzene (1H NMR) as an internal standard
in comparison to spectral data from authenticreferences. For spectral
data see Section 4.2.1. 611 U0T mgꢁ1, 279 UfTinal mgꢁ1, pHfinal 6.9.
role-2-carboxylate (2c5-Br). 1H NMR (CDCl3, 600 MHz)
d 0.92 (t, 3H,
J¼7.0 Hz), 1.36e1.39 (m, 4H), 1.71e1.73 (m, 2H), 4.26 (t, 2H, J¼6.7 Hz),
6.21e6.22 (m, 1H), 6.82e6.83 (m, 1H), 9.25 (br s,1H, NH). MS (EI) m/z
261 (15), 259 (15),189 (100),187 (100),173 (85),171 (89),146 (17),144
(12), 93 (8), 65 (22). Pentyl 4,5-dibromo-1H-pyrrole-2-carboxylate
ð3c4;5ꢁBr Þ. 1H NMR (CDCl3, 600 MHz)
d
0.92 (t, 3H, J¼7.0 Hz),
2
1.36e1.39 (m, 4H), 1.71e1.73 (m, 2H), 4.26 (t, 2H, J¼6.7 Hz), 6.88 (d,
1H, J¼2.8 Hz), 9.50 (br s, 1H, NH). MS (EI) m/z 341 (10), 339 (21), 337
(11), 271 (51), 269 (100), 267 (53), 253 (55), 251 (99), 249 (54), 226
(7), 224 (15), 222 (7). 13C NMR (CDCl3, 150 MHz; mixture of
Acknowledgements
This work was supported by the Deutsche Bundesstiftung
Umwelt (grant 20008/982; scholarship for D.W.) and NanoKat. The
study is part of the Ph.D. thesis of D.W. We express our gratitude to
Ms. Madlen Radlow and Ms. Astrid Hoppe for technical assistance.
2c5ꢁBr=3c4;5ꢁBr
) d 14.1, 22.5, 28.2, 28.5, 28.6, 65.0, 65.4, 100.8, 104.8,
2
106.8, 112.8, 116.7, 117.8, 124.3, 124.4, 159.9, 160.4. 611 U0T mgꢁ1
,
32 UfTinal mgꢁ1, pHfinal 6.4.
4.2.4. Bromination of 1H-pyrrole-2-carboxamide (1d). According to
general method in Section 4.2. Yield: 262 mg, colorless semi-solid;
59/24/17-mixture of 2d4ꢁBr=2d5ꢁBr=3d4;5ꢁBr2-isomers. 4-Bromo-
1H-pyrrole-2-carboxamide (2d4-Br).39 1H NMR (DMSO-d6,
Supplementary data
Instrumentation, reagent specification, details about steady
state kinetic data and analysis, experimental procedures, spectral
and analytical data of new compounds. Supplementary data related
600 MHz)
d 6.83e6.84 (m, 1H), 6.96e6.97 (m, 1H), 7.09 (br s, 1H,
NH2), 7.57 (br s, 1H, NH2) 11.76 (br s, 1H, NH). MS (EI) m/z 190 (97),
188 (97), 173 (100), 171 (100), 146 (21), 144 (21), 119 (20), 117 (20),
109 (15), 64 (58). 5-Bromo-1H-pyrrole-2-carboxamide (2d5-Br).40
1H NMR (DMSO-d6, 600 MHz)
d 6.11e6.12 (m, 1H), 6.74e6.75 (m,
References and notes
1H), 7.00 (br s, 1H, NH2), 7.45 (br s, 1H, NH2) 12.15 (br s, 1H, NH). MS
(EI) m/z 190 (100), 188 (100), 173 (95), 171 (95), 146 (23), 144 (23),
119 (33), 117 (33), 64 (71). 4,5-Dibromo-1H-pyrrole-2-carboxamide
1. Walsh, C. T.; Garneau-Tsodikova, S.; Howard-Jones, A. R. Nat. Prod. Rep. 2006, 23,
517e531.
2. Schroif-Gregoire, C.; Travert, N.; Zaparucha, A.; Al-Mourabit, A. Org. Lett. 2006,
8, 2961e2964.
ð3d4;5ꢁBr Þ.41 1H NMR (DMSO-d6, 600 MHz)
d 6.92 (s, 1H), 7.20 (br s,
1H, NH2), 7.58 (br s, 1H, NH2), 12.64 (br s, 1H, NH). MS (EI) m/z 270
2
3. Trost, B. M.; Dong, G. J. Am. Chem. Soc. 2006, 128, 6054e6055.
€
(32), 268 (67), 266 (33), 253 (52), 251 (100), 249 (45), 226 (5), 224
(8), 222 (5), 199 (6), 197 (12), 195 (5), 173 (5), 171 (5). 611 U0T mgꢁ1
,
ꢀ
5. Podgorsek, A.; Zupan, M.; Iskra, J. Angew. Chem., Int. Ed. 2009, 48, 8424e8450.
41 UfTinal mgꢁ1, pHfinal 6.6.
6. Pavlinac, J.; Zupan, M.; Laali, K. K.; Stavber, S. Tetrahedron 2009, 65, 5625e5662.
7. Rothenberg, G.; Clark, J. H. Green Chem. 2000, 2, 248e251.
8. Forenza, S.; Minale, L.; Riccio, R.; Fattorusso, E. J. Chem. Soc., Chem. Commun.
1971, 1129e1130.
4.2.5. Bromination of 1H-pyrrole-2-carbonitrile (1e). According to
general method in Section 4.2. For isomer separation see also the
Supplementary data. Yield: 333 mg, rose solid; 53/47-mixture of
9. Hoffmann, H.; Lindel, T. Synthesis 2003, 1753e1783.
10. Maass, O.; Hiebert, P. G. J. Am. Chem. Soc. 1924, 46, 290e308.
11. Vilter, H. Vanadium and its role in Life In. Metal Ions in Biological Systems; Sigel,
H., Sigel, A., Eds.; Dekker: New York, NY, 1995; Vol. 31, pp 325e362.
12. Butler, A.; Walker, J. V. Chem. Rev. 1993, 93, 1937e1944.
13. de Boer, E.; Wever, R. J. Biol. Chem. 1988, 263, 12326e12332.
2e4ꢁBr=4e3;4;5ꢁBr -isomers.
4-Bromo-1H-pyrrole-2-carbonitrile
(2e4-Br). 1H NMR (DMSO-d6, 600 MHz)
7.05e7.06 (m, 1H),
7.33e7.34 (m, 1H), 12.69 (br s, 1H, NH). 13C NMR (DMSO-d6,
3
d