Molecular Diversity of Three-Component Reactions
Typical Procedure for the Preparation of Pyrrolo[1,2-a]Benzimid-
azoles 4a–4l and 5a–5k by Three-Component Reactions: A mixture
of α-phenacyl or p-nitrobenzyl bromide (2.0 mmol) and N-benzyl-
benzimidazole (2.0 mmol, 0.439 g) in acetonitrile (20 mL) was
stirred at room temperature for 8 h and then the aromatic aldehyde
(2.0 mmol), malononitrile or ethyl cyanoacetate (2.0 mmol), and
triethylamine (2.0 mmol) were added and the mixture was stirred
at 50 °C for 36 h. Water (50 mL) was added and the mixture was
extracted with dichloromethane (40 mL). After removing the sol-
vent the resulting crude product was purified by thick-layer
chromatography with a mixture of light petroleum and ethyl acetate
(3:1, v/v) as developing reagent to give the product for analysis.
ate. A series of unusual charge-separated zwitterionic salts
and functionalized pyrrolo[1,2-a]benzimidazoles were con-
veniently prepared in high yields. An unprecedented re-
gioselectivity in the prepared functionalized pyrrolo[1,2-a]-
benzimidazoles was also observed. Prominent among the
advantages of this new method are novelty, operational sim-
plicity, and good yields. Further expansion of the reaction
scope and synthetic applications of this methodology are in
progress in our laboratory.
Experimental Section
4a: Pale-yellow solid, yield 58%, m.p. 184–186 °C. IR (KBr): ν =
˜
3063, 2225, 1613, 1474, 1395, 1364, 1324, 1274, 1236, 1203, 1161,
1119, 1078, 1025, 976, 861 cm–1. 1H NMR (600 MHz, CDCl3): δ =
8.77 (d, J = 8.4 Hz, 1 H, ArH), 7.91 (d, J = 7.8 Hz, 2 H, ArH),
7.62 (t, J = 7.2 Hz, 1 H, ArH), 7.54 (t, J = 7.8 Hz, 2 H, ArH), 7.41
(t, J = 7.2 Hz, 1 H, ArH), 7.37 (s, 5 H, ArH), 7.31 (t, J = 7.8 Hz,
1 H, ArH), 7.28 (s, 1 H, ArH), 7.25–7.21 (m, 3 H, ArH), 6.87 (d, J
= 7.2 Hz, 2 H, ArH), 5.24 (s, 2 H, CH2) ppm. 13C NMR (150 MHz,
CDCl3): δ = 183.2, 138.7, 137.8, 134.9, 132.5, 130.3, 130.1, 129.5,
128.9, 128.4, 128.2, 128.0, 126.9, 126.4, 125.8, 121.4, 117.7, 109.8,
106.1, 47.5 ppm. MS (ESI): m/z = 452.17. C31H21N3O (451.53):
calcd. C 82.45, H 4.69, N 9.31; found C 82.36, H 4.91, N 8.97.
Typical Procedure for the Preparation of Zwitterionic Salts 2a–2k
by Three-Component Reactions Involving α-Phenacyl Bromide: A
mixture of α-phenacyl bromide (2.0 mmol) and N-benzylbenzimid-
azole (2.0 mmol, 0.439 g) in acetonitrile (20 mL) was stirred at
room temperature for 8 h and then the aromatic aldehyde
(2.0 mmol), cyclic 1,3-dicarbonyl compound (2.0 mmol), and tri-
ethylamine (2.0 mmol) were added. The mixture was stirred at
room temperature overnight. After adding water (50 mL), the re-
sulting yellow precipitate was collected by filtration and washed
with acetonitrile and ethanol to give the pure product for analysis.
2a: Pale-yellow solid, yield 74%, m.p. 178–180 °C. IR (KBr): ν =
˜
5a: Orange solid, yield 60%, m.p.182–184 °C. IR (KBr): ν = 3060,
˜
3107 (w), 3055 (m), 2971 (w), 1683 (s), 1581 (vs), 1491 (m), 1450
(m), 1389 (s), 1260 (m), 1111 (m), 751 (m) cm–1. 1H NMR
(600 MHz, [D6]DMSO): δ = 10.45 (s, 1 H, ArH), 8.12 (s, 1 H,
ArH), 7.96 (s, 1 H, ArH), 7.88 (s, 3 H, ArH), 7.63 (s, 1 H, ArH),
7.55 (s, 1 H, ArH), 7.51 (s, 4 H, ArH), 7.38 (s, 5 H, ArH), 7.04 (s,
2 H, CH, ArH), 6.95 (s, 1 H, ArH), 5.95–5.77 (m, 2 H, CH2),
4.93 (d, J = 3.6 Hz, 1 H, CH), 1.01 (s, 6 H, CH3) ppm. 13C NMR
(150 MHz, [D6]DMSO): δ = 166.6, 143.6, 133.7, 131.6, 130.4,
129.0, 128.8, 128.2, 127.6, 127.4, 126.9, 126.8, 126.6, 126.5, 124.6,
114.0, 113.9, 62.0, 56.0, 47.6, 18.5 ppm. MS (ESI): m/z = 559.9.
C35H30N2O5 (558.63): calcd. C 75.25, H 5.41, N 5.01; found C
75.48, H 5.75, N 4.67.
2214, 1593, 1516, 1483, 1451, 1390, 1344, 1264, 1222, 1161, 1136,
1
1074, 1028, 973, 857 cm–1. H NMR (600 MHz, CDCl3): δ = 8.43
(d, J = 8.4 Hz, 2 H, ArH), 7.97 (d, J = 9.0 Hz, 2 H, ArH), 7.56 (t,
J = 8.4 Hz, 1 H, ArH), 7.43 (t, J = 7.2 Hz, 2 H, ArH), 7.38 (t, J
= 7.2 Hz, 2 H, ArH), 7.33 (t, J = 7.2 Hz, 2 H, ArH), 7.25–7.21 (m,
4 H, ArH), 7.10 (t, J = 7.8 Hz, 1 H, ArH), 6.94 (d, J = 6.0 Hz, 2
H, ArH), 5.20 (s, 2 H, CH2) ppm. 13C NMR (150 MHz, CDCl3):
δ = 147.0, 139.4, 138.7, 136.8, 135.7, 135.3, 130.9, 129.8, 128.9,
128.5, 127.9, 127.5, 126.5, 125.4, 124.4, 120.2, 112.8, 110.4, 101.3,
47.6 ppm. MS (ESI): m/z = 469.68. C30H20N4O2 (468.51): calcd. C
76.91, H 4.30, N 11.96; found C 76.83, H 4.77, N 11.64.
CCDC-820013 (for 3a), -85392 (for 4c), -85394 (for 4i), -85393 (for
5c), and -85395 (for 5h) contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Typical Procedure for the Preparation of Zwitterionic Salts 3a–3h
by Three-Component Reactions Involving Ethyl α-Bromoacetate: A
mixture of ethyl α-bromoacetate (2.0 mmol) and N-benzylbenz-
imidazole (2.0 mmol, 0.439 g) in acetonitrile (20 mL) was stirred at
room temperature for 8 h and then the aromatic aldehyde
(2.0 mmol), cyclic 1,3-dicarbonyl compound (2.0 mmol), and tri-
ethylamine (2.0 mmol) were added and the mixture was stirred at
room temperature overnight. After adding water (50 mL), the re-
sulting yellow precipitate was collected by filtration and washed
with acetonitrile and ethanol to give the pure product for analysis.
Supporting Information (see footnote on the first page of this arti-
cle): Yields, characterization data, and spectra for all compounds.
Acknowledgments
This work was financially supported by the National Natural Sci-
ence Foundation of China (NSFC) (grant number 20972132 and
21172189).
3a: White solid, yield 75%, m.p. 208–210 °C. IR (KBr): ν = 3439
˜
(m), 3113 (w), 2989 (m), 1740 (s), 1594 (vs), 1488 (m), 1450 (m),
1392 (s), 1262 (m), 1202 (m), 1112 (m), 1031 (w), 864 (m), 748
(s) cm–1. 1H NMR (600 MHz, [D6]DMSO): δ = 10.29 (s, 1 H,
ArH), 7.99 (d, J = 7.2 Hz, 1 H, ArH), 7.89 (d, J = 8.4 Hz, 1 H,
ArH), 7.65 (t, J = 7.8 Hz, 1 H, ArH), 7.60 (t, J = 6.6 Hz, 3 H,
ArH), 7.50 (d, J = 7.2 Hz, 2 H, ArH), 7.39–7.35 (m, 3 H, ArH),
7.29 (t, J = 7.2 Hz, 2 H, ArH), 7.22 (t, J = 7.2 Hz, 1 H, ArH), 6.73
(d, J = 12.6 Hz, 1 H, CH), 5.90 (d, J = 9.0 Hz, 1 H, CH2), 5.79 (d,
J = 15.0 Hz, 1 H, CH2), 4.83 (d, J = 15.6 Hz, 1 H, CH), 3.88–3.84
(m, 2 H, CH2), 1.01 (s, 6 H, CH3), 0.81 (t, J = 6.6 Hz, 3 H,
CH3) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 168.8, 164.9,
133.8, 128.9, 128.8, 128.0, 127.8, 126.8, 126.4, 113.8, 99.2, 72.0,
61.5, 56.0, 49.9, 25.2, 25.1, 18.5, 13.3 ppm. MS (ESI): m/z = 527.4.
C31H30N2O6 (526.59): calcd. C 70.71, H 5.74, N 5.32; found C
70.53, H 6.18, N 5.44.
[1] a) F. Kröhnke, W. Zecher, J. Curtze, D. Drechsler, K. Pfleghar,
K. E. Schnalke, W. Weis, Angew. Chem. 1962, 74, 811; Angew.
Chem. Int. Ed. Engl. 1962, 1, 626–632; b) F. Kröhnke, Angew.
Chem. 1963, 75, 181; Angew. Chem. Int. Ed. Engl. 1963, 2, 225–
238; c) F. Kröhnke, Synthesis 1976, 1–24.
[2] a) S. Yamada, J. Yamamoto, E. Ohta, Tetrahedron Lett. 2007,
48, 855–858; b) S. Kojima, K. Hiroikea, K. Ohkata, Tetrahe-
dron Lett. 2004, 45, 3565–3568; c) S. Kojima, K. Fujitomo, Y.
Shinohara, M. Shimizu, K. Ohkata, Tetrahedron Lett. 2000,
41, 9847–9851; d) N. N. Vo, C. J. Eyermann, C. N. Hodge, Tet-
rahedron Lett. 1997, 38, 7951–7954.
[3] a) O. Tsuge, S. Kanemasa, S. Takenaka, Bull. Chem. Soc. Jpn.
1985, 58, 3137–3157; b) F. Neve, A. Crispini, S. Campagna,
Eur. J. Org. Chem. 2011, 7194–7198
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