902
X. Zhang, J. Shi / Tetrahedron 67 (2011) 898e903
1H NMR: (500 MHz, CDCl3):
d
¼2.40 (s, 3H), 6.36 (t, J¼2.0 Hz,
6.78 (dd, J¼1.5, 8.0 Hz, 1H), 7.05 (t, J¼2.0 Hz, 2H), 7.18 (t, J¼2.0 Hz,
1H) ppm.
2H), 7.09 (t, J¼2.0 Hz, 2H), 7.25 (s, 2H), 7.31 (d, J¼8.5 Hz,
2H) ppm.
3.2. General procedure for preparation of N-acyl pyrrole 5aee
3.1.4. 1-(2-Tolyl)-1H-pyrrole (3d). Yellowish oil;13 Rf 0.79 (100%
petroleum ether); 1H NMR (500 MHz, CDCl3):
d
¼2.25 (s, 3H),
A Schlenk reaction tube was charged with primary aromatic
amide (5.0 mmol), 2,5-dimethoxytetrahydrofuran (6.0 mmol), MgI2
etherate (10% mmol), and acetonitrile (10 mL). The reaction mix-
ture was stirred at 80 ꢀC for several hours and then concentrated in
vacuo. The residue was purified by flash column chromatography
on a silica gel to give the desired product.
6.36 (t, J¼2.0 Hz, 2H), 6.83 (t, J¼2.0 Hz, 2H), 7.28e7.33 (m,
4H) ppm.
3.1.5. 1-(2,6-Diisopropylphenyl)-1H-pyrrole (3e). White crystalline
solid;21 mp 62.2e63.0 ꢀC; Rf 0.84 (100% petroleum ether); 1H NMR
(500 MHz, CDCl3):
2H), 6.31 (t, J¼2.0 Hz, 2H), 6.63 (t, J¼2.0 Hz, 2H), 7.21 (d, J¼8.0 Hz,
2H), 7.38 (t, J¼8.0 Hz, 1H) ppm.
d
¼1.123 (s, 6H), 1.137 (s, 6H), 2.401e2.456 (m,
The physical and spectra data of the compounds 5aee are as
follows.
3.2.1. 1-Benzoyl-1H-pyrrole (5a). Yellowish oil;13 Rf 0.65 (10% EtOAc
3.1.6. 1-(4-Bromophenyl)-1H-pyrrole (3f). White solid;13 mp
96.0e97.0 ꢀC; Rf 0.68 (100% petroleum ether); 1H NMR (500 MHz,
in petroleum ether); 1H NMR (500 MHz, CDCl3):
d
¼6.35 (t,
J¼2.5 Hz, 2H), 7.29 (t, J¼2.5 Hz, 2H), 7.51 (t, J¼7.5 Hz, 2H), 7.60 (d,
CDCl3):
d
¼6.38 (t, J¼2.0 Hz, 2H), 7.01 (t, J¼2.0 Hz, 2H), 7.28 (d,
J¼7.5 Hz, 1H), 7.74e7.76 (m, 2H) ppm.
J¼9.0 Hz, 2H), 7.55 (t, J¼7.0 Hz, 2H) ppm.
3.2.2. 1-(4-Methylbenzoyl)-1H-pyrrole (5b). Yellowish oil;13 Rf 0.70
3.1.7. 1-(4-Fluorophenyl)-1H-pyrrole (3g). Pale yellowish solid;22
mp 50.6e51.7 ꢀC; Rf 0.68 (100% petroleum ether); 1H NMR
(CDCl3, 500 MHz):
7.15 (t, J¼8.5 Hz, 2H), 7.36e7.39 (m, 2H) ppm.
(10% EtOAc in petroleum ether); 1H NMR (500 MHz, CDCl3):
(s, 3H), 6.33 (t, J¼2.5 Hz, 2H), 7.29 (dd, J¼2.5, 4.0 Hz, 4H), 7.65 (d,
J¼8.5 Hz, 2H) ppm.
d¼2.44
d¼6.38 (t, J¼2.0 Hz, 2H), 7.05 (t, J¼2.0 Hz, 2H),
3.2.3. 1-(2-Methoxybenzoyl)-1H-pyrrole (5c). Yellowish oil; Rf 0.55
3.1.8. 1-(2,4-Difluorophenyl)-1H-pyrrole (3h). Pale yellowish oil;23
Rf 0.33 (100% petroleum ether); 1H NMR (CDCl3, 500 MHz):
(10% EtOAc in petroleum ether); 1H NMR (500 MHz, CDCl3):
d¼3.81
(s, 3H), 6.28 (t, J¼2.5 Hz, 2H), 7.02e7.08 (m, 2H), 7.17 (s, 2H), 7.39
(dd, J¼2.0, 8.0 Hz, 1H), 7.47e7.51 (m, 1H). 13C NMR (125 MHz,
d¼6.34 (t, J¼2.0 Hz, 2H), 6.91e6.99 (m, 4H), 7.31e7.36 (m, 1H) ppm.
CDCl3):
132.29, 156.79, 166.35 ppm.
d
¼55.78, 111.50, 113.06, 120.49, 120.61, 123.66, 129.22,
3.1.9. 1-(3-Trifluoromethylphenyl)-1H-pyrrole (3i). White solid;11
mp 49.7e50.0 ꢀC; Rf 0.67 (100% petroleum ether); 1H NMR
(CDCl3, 500 MHz):
3.2.4. 1-(4-Fluorobenzoyl)-1H-pyrrole (5d). Yellowish oil;27 Rf 0.70
d¼6.38 (t, J¼2.0 Hz, 2H), 7.11 (t, J¼2.0 Hz, 2H),
(10% EtOAc in petroleum ether); 1H NMR (500 MHz, CDCl3):
d
¼6.35
7.48e7.58 (m, 3H), 7.63 (s, 1H) ppm.
(t, J¼2.5 Hz, 2H), 7.19 (t, J¼8.5 Hz, 2H), 7.26 (t, J¼2.5 Hz, 2H), 7.78
3.1.10. 1-(2-Nitrophenyl)-1H-pyrrole (3j). Yellowish oil;15 Rf 0.38
(dd, J¼5.5, 8.5 Hz, 2H) ppm.
(10% EtOAc in petroleum ether); 1H NMR (500 MHz, CDCl3):
3.2.5. 1-(2-Chlorobenzoyl)-1H-pyrrole (5e). Yellowish oil;15 Rf 0.60
d
¼6.37 (t, J¼2.0 Hz, 2H), 6.80 (t, J¼2.0 Hz, 2H), 7.48 (dd, J¼5.0,
(10% EtOAc in petroleum ether); 1H NMR (500 MHz, CDCl3):
J¼2.5 Hz, 2H), 7.12 (s, 2H), 7.37e7.40 (m, 1H), 7.45e7.50 (m, 3H) ppm.
d
¼6.33 (t,
8.0 Hz, 2H), 7.65 (dd, J¼1.5, 8.0 Hz, 1H), 7.86 (dd, J¼2.0, 7.0 Hz,
1H) ppm.
3.1.11. 1-(4-Nitrophenyl)-1H-pyrrole (3k). Yellowish solid;15 mp
183.1e184.4 ꢀC; Rf 0.50 (10% EtOAc in petroleum ether); 1H NMR
3.3. General procedure for crossover reaction
(500 MHz, CDCl3):
d
¼6.45 (t, J¼2.0 Hz, 2H), 7.20 (t,
A
Schlenk reaction tube was charged with each amine
J¼2.0 Hz, 2H), 7.54 (dd, J¼9.0, 7.0 Hz, 2H), 8.33 (dd, J¼2.0, 7.0 Hz,
(5.0 mmol), 2,5-dimethoxytetrahydrofuran (6.0 mmol), MgI2
etherate (10% mmol), and acetonitrile (10 mL). The reaction mix-
ture was stirred at 80 ꢀC for several hours and then concentrated in
vacuo. Flash column chromatography afforded the desired prod-
ucts. The ratio of each product was determined by column chro-
matography isolation or GC analysis.
2H) ppm.
3.1.12. 1-(3-Nitro-4-aminophenyl)-1H-pyrrol (3l). Red-brown solid;24
mp 178.8e179.7 ꢀC; Rf 0.42 (17% EtOAc in petroleum ether); 1H NMR
(500 MHz, CDCl3):
J¼9.0 Hz, 1H), 7.02(t, J¼2.0 Hz, 2H), 7.48 (dd, J¼2.0, 6.5 Hz, 1H), 8.16
(d, J¼3.0 Hz, 1H) ppm.
d
¼6.11 (s, 2H), 6.36 (t, J¼2.0 Hz, 2H), 6.91 (d,
Acknowledgements
3.1.13. 1-(2-Pyridinyl)-1H-pyrrol (3m). Yellowish oil;14 Rf 0.33 (2.5%
Financial support from the Zhejiang Province Natural Science
Foundation of China (Project Y4100692).
EtOAc in petroleum ether); 1H NMR (500 MHz, CDCl3):
d¼6.36 (s,
2H), 7.10 (t, J¼6.0 Hz, 1H), 7.32 (d, J¼8.0 Hz, 2H), 7.52 (s, 2H), 7.74 (t,
J¼8.0 Hz, 1H), 8.43 (d, J¼4.0 Hz, 1H) ppm.
Supplementary data
3.1.14. 1-(4-Aminophenyl)-1H-pyrrol (3n). Pale yellowish solid;25
mp 155.5e156.5 ꢀC; Rf 0.32 (17% EtOAc in petroleum ether); 1H
Supplementary data associated with this article can be found in
NMR (500 MHz, CDCl3):
6.5 Hz, 2H), 6.97 (t, J¼2.0 Hz, 2H), 7.18 (dd, J¼2.0, 6.5 Hz, 2H), 8.16
(d, J¼3.0 Hz, 1H) ppm.
d
¼6.30 (t, J¼2.0 Hz, 2H), 6.72 (dd, J¼2.0,
References and notes
1. (a) Jones, R. A.; Bean, G. P. The Chemistry of Pyrroles; Academic: London, 1977;
(b) Lipshutz, B. H. Chem. Rev. 1986, 86, 795; (c) Jacobi, P. A.; Coults, L. D.; Guo, J.
3.1.15. 1-(3-Aminophenyl)-1H-pyrrol (3o). Yellowish oil;26 Rf 0.33
€
S.; Leung, S. I. J. Org. Chem. 2000, 65, 205; (d) Furstner, A. Angew. Chem. 2003,
(17% EtOAc in petroleum ether); 1H NMR (500 MHz, CDCl3):
(t, J¼2.0 Hz, 2H), 6.55 (dd, J¼2.0, 8.0 Hz, 1H), 6.70 (t, J¼2.0 Hz, 1H),
d
¼6.32
115, 3706; (e) Muchowski, J. M. Adv. Med. Chem. 1992, 1, 109; (f) Aydogan, F.;
Basarir, M.; Yolacana, C.; Demirb, A. S. Tetrahedron 2007, 63, 9746; (g) Pridmore,