Tetrahedron Letters
3
compounds were prepared via the above procedure: (4a) Colourless oil. 1H
NMR (400 MHz, CDCl3): 7.30-7.16 (6H, m), 6.21 (1H, dd, J 3.3, 1.8
Hz), 6.12 (1H, br d, J 3.3 Hz), 5.02 (1H, dd, J 12.2, 7.6 Hz), 4.94 (1H, t, J
7.6 Hz), 4.81 (1H, dd, J 12.2, 7.6 Hz). 13C NMR (100 MHz, CDCl3):
151.8, 142.2, 136.7, 128.7, 127.7, 127.6, 110.2, 107.1, 77.57, 43.12. m/z
(EI): 217 (M+, 1%), 170 (100). C12H11NO3 (217.07): calcd. 217.0739,
found 217.0739. All data were in accordance with literature values.4,5 (4b)
1
Pale yellow oil. H NMR (400 MHz, CDCl3): 7.20 (1H, dd, J 1.8, 0.5
Hz), 7.15 (2H, d, J 8.5 Hz), 7.06 (2H, d, J 8.5 Hz), 6.15 (1H, dd, J 3.3, 1.8
Hz), 5.96 (H, br d, J 3.3 Hz), 4.99 (1H, dd, J 11.9, 7.6 Hz), 4.92 (1H, t, J
7.6 Hz), 4.79 (1H, dd, J 11.9, 7.6 Hz) . 13C NMR (100 MHz, CDCl3):
151.2, 142.5, 135.2, 133.7, 129.1, 129.0, 110.4, 107.3, 77.47, 42.6. m/z
(EI): 251 (M+, 1%), 204 (100). C12H10ClNO3 (251.03): calcd. C 57.3, H
4.0, N 5.6, found C 57.4, H 4.2, N 5.3. (4c) Colourless oil. 1H NMR (400
MHz, CDCl3): 7.31 (1H, d, J 2.0 Hz), 7.16 (2H, d, J 8.8 Hz), 6.83 (2H,
d, J 8.8 Hz), 6.25 (1H, dd, J 3.3, 2.0 Hz), 6.06 (1H, br d, J 3.3 Hz), 4.98
(1H, dd, J 12.3, 7.6 Hz), 4.90 (1H, t, J 7.6 Hz), 4.77 (1H, dd, J 12.3, 7.6
Hz), 3.70 (3H, s). 13C NMR (100 MHz, CDCl3): 159.0, 152.2, 142.2,
128.8, 128.6, 114.1, 110.2, 107.0, 77.9, 54.9, 42.5. m/z (EI): 247 (M+,
7%), 200 (100). C13H13NO4 (247.08): calcd. C 63.2, H 5.3, N 5.7, found C
63.3, H 5.4, N 5.5. (4d) Brown oil. 1H NMR (400 MHz, CDCl3): 7.32
(1H, dd, J 2.0, 0.8 Hz), 7.17 (1H, dd, J 4.5, 1.8 Hz), 6.95-6.87 (2H, m),
6.27 (1H, dd, J 3.3, 2.0, Hz), 6.16 (1H, ddd, J 3.3, 0.8, 0.8 Hz), 5.19 (1H,
t, J 7.8 Hz), 4.92 (1H, dd, J 12.8, 7.8 Hz),4.76 (1H, dd, J 12.8, 7.8 Hz).
13C NMR (100 MHz, CDCl3): 151.0, 142.4, 139.0, 126.9, 126.1, 125.3,
110.3, 107.4, 78.2, 38.4. m/z (EI): 223 (M+, 1%), 176 (100). C10H9NO3S
(223.03): calcd. 223.0303, found 223.0303. (4e) Brown oil. 1H NMR (400
MHz, CDCl3): 8.38 (1H, d, J 2.8 Hz), 7.64 (1H, dd, J 8.3, 2.8 Hz), 7.40
(1H, dd, J 2.0, 0.8 Hz), 7.34 (1H, d, J 8.3 Hz), 6.35 (1H, dd, J 3.3, 2.0 Hz),
6.17 (1H, d, J 3.3 Hz), 5.05 (1H, dd, J 12.3, 7.0 Hz), 4.96 (1H, app. t, J 7.6
Hz) 4.84 (1H, dd, J 12.3, 8.1 Hz). 13C NMR (100 MHz, CDCl3): 150.8,
149.8, 148.9, 142.8, 138.0, 131.5, 124.3, 110.4, 107.7, 76.8, 39.9. m/z
(EI): 207 (37Cl, M-HNO2, 31%), 206 (14), 205 (35Cl, M-HNO2, 100).
C11H9ClN2O3 (252.03): calcd. 252.0302, found 252.0301. (4f) Colourless
oil. 1H NMR (400 MHz, CDCl3): 7.40 (1H, dd, J 2.0, 0.8 Hz), 7.2-7.0
(4H, m), 6.23 (1H, dd, J 3.3, 2.0 Hz), 6.05 (1H, d, J 3.3 Hz), 4.98 (1H,
app. t, J 7.4 Hz), 4.89 (1H, dd, J 11.8, 8.1 Hz), 4.82 (1H, dd, J 11.8, 7.0
Hz), 2.26 (3H, s). 13C NMR (100 MHz, CDCl3): 152.1, 142.2, 137.6,
133.7, 129.5, 127.5, 110.2, 107.0, 77.8, 42.9, 20.8. m/z (EI): 231 (M+,
1%), 184 (100). C13H13NO3 (231.09): calcd. C 67.52, H 5.67, N 6.06,
found C 67.50, H 5.95, N 6.07. Calcd. 231.0895, found C 231.0895. (4g)
Pale yellow oil. 1H NMR (400 MHz, CDCl3): 7.34 (1H, d, J 2.0 Hz),
7.29 (1H, dd, J 2.0, 0.8 Hz), 7.14 (1H, dd, J 8.5, 2.0 Hz), 7.04 (1H, d, J 8.5
Hz), 6.24 (1H, dd, J 3.3, 2.0 Hz), 6.12 (1H, d, J 3.3 Hz), 5.35 (1H, dd, J
8.8, 7.0 Hz), 4.87 (1H, dd, J 13.3, 8.8 Hz), 4.72 (1H, dd, J 13.3, 7.0 Hz).
13C NMR (100 MHz, CDCl3): 150.0, 142.8, 134.4, 134.2, 133.0, 129.8,
129.7, 127.7, 110.5, 108.1, 75.8, 39.2. m/z (EI): 285 (35Cl,35Cl, M+, <1%),
238 (100). C12H9Cl2NO3 (285.00): calcd. 284.9959, found 284.9959. (5)
Figure 1. Products from 2-methylfuran and 2,5-dimethylfuran
In conclusion, 5 M lithium perchlorate in diethyl ether is a
versatile Lewis acid catalyst for the mild, and high-yielding
Friedel-Crafts alkylation of furans.
methylfuran react exclusively at C2 or C5, whilst 2,5-
dimethylfuran reacts more slowly at C3. Work is
Furan and 2-
continuing on the application of this technique to the
synthesis of more complex heterocyclic systems, and
agents of biological interest.
Acknowledgements
We gratefully acknowledge financial support of this work
by Bayer AG, Leverkusen. We are indebted to Dr. G.
Remberg, University of Göttingen, for high resolution mass
spectra.
References
1
Sargent, M.V., Dean, F.M., in "Comprehensive Heterocyclic
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4 Richter, H. Ph.D. Thesis, 1998, Technical University of Clausthal.
5 Xing, J.; Chen, G.; Liao, J.; Cao, P. Eur. J. Org. Chem, 2012, 1230 –
1236.
1
Pale yellow oil. H NMR (400 MHz, CDCl3): 7.28-7.18 (5H, m), 5.92
(1H, br d, J 3.1, Hz), 5.82 (1H, dq, J 3.1, 1.0 Hz), 4.93 (1H, dd, J 11.9, 7.6
Hz), 4.86 (1H, app. t, J 7.5 Hz), 4.73 (1H, dd, J 11.9, 7.2 Hz), 2.15 (3H, s).
13C NMR (100 MHz, CDCl3): 151.9, 149.9, 136.9, 128.7, 127.7, 127.6,
107.7, 106.1, 77.7, 43.3, 13.1. m/z (EI): 231 (M+, 3%), 184 (100).
C13H13NO3 (231.09): calcd. C 67.52, H 5.67, N 6.06, found C 67.38, H
5.80, N 5.77. Calcd. 231.0895, found C 231.0895. (6) Pale yellow oil. 1H
NMR (200 MHz, CDCl3): 7.5-7.0 (5H, m, ArH), 5.86 (1H, s), 4.84 (1H,
dd, J 11.8, 8.0 Hz), 4.75 (1H, dd, J 11.8, 8.0 Hz), 4.66 (1H, br t, J 8.0 Hz),
2.13 (6H, s). 13C NMR (50 MHz, CDCl3) 150.1, 146.5, 139.14, 128.7,
127.2, 127.1, 117.3, 104.7, 79.1, 40.1, 13.2, 11.2. m/z (EI): 245 (M+,
72%), 155 (100). C14H15NO3 (245.11): calcd. 245.1052, found 245.1052.
16 Hashmi, A.; Stephen K.; Haeffner, T.; Yang, W.; Pankajakshan, S.;
Schaefer, S.; Schultes, L.; Rominger, F.; Frey, W. Chem. Eur. J. 2012, 18,
10480-10486.
6
Campbell, M.M.; Cosford, N.; Zongli, L.; Sainsbury, M.
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14 As with all acid-catalysed reactions of furans, some polymerisation
occurs in these reactions. Polymeric material accounts for the remainder
of material not converted into product.
15 General Procedure: To a mixture of the nitrostyrene (1.5 mmol) and
furan (1 ml) was added a solution of LiClO4 in Et2O (5 M, 1.5 ml). The
mixture was stirred at room temperature until GC analysis of small
aliquots worked up as below indicated complete conversion of the starting
styrene. The mixture was then partitioned between Et2O (10 ml) and H2O
(10 ml). The organic layer was washed with saturated NaCl solution,
dried over anhydrous Na2SO4, filtered and evaporated. The residues were
purified where necessary by column chromatography (50 g, SiO2) in
CH2Cl2:petroleum ether (1:1) to >95% purity by 1H NMR. The following