4
Tetrahedron
C.; Simard, J.; Merand, Y.; Belanger, A.; Labrie, C.; Labrie, F. J.
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General procedure for the synthesis of 2-methoxy-6-nitro-2,3-
diphenyl-2H-1-benzopyran (7): To
a
mixture of 5-
nitrosalicylaldehyde (0.334 g, 2.0 mmol), diphenylacetylene
(0.178 g, 1.0 mmol) and trimethyl orthoformate (0.212 mL, 2.0
mmol) in toluene under nitrogen, trifluoromethanesulfonic acid
(0.0176 mL, 20 mol%) was added. After being stirred at reflux for
15 h, methanol (5.0 mL, 0.12 mol) was added. Then the reaction
mixture was quenched with H2O. The organic layer was separated
and the aqueous layer was extracted with ethylacetate. The
combined organic layer were washed with brine, dried over
MgSO4, and filtered. The filtrate was concentrated in vacuo. The
resulting residue was purified by column chromatography on silica
gel (hexane / ethylacetate = 100 : 1 to 20 : 1) to afford product 7.
1
It was identified by H NMR, 13C NMR, COSY, HMBC, HSQC,
IR, and HRMS. Yield 52%, yellow solid. IR (neat): 3063, 2839,
1511, 1480, 1446, 1336, 1249, 1181, 1125, 1107, 1087, 1016, 987,
962, 903, 827, 772, 748, 697, 595, 566 cm-1. 1H NMR (300 MHz,
CDCl3): δ 8.17 (d, J = 2.6 Hz, 1H), 8.11 (dd, J = 2.6, 9.0 Hz, 1H),
7.44-7.55 (m, 2H), 7.31-7.35 (m, 2H), 7.17-7.31 (m, 7H), 7.15 (s,
1H), 7.00 (d, J = 9.0 Hz, 1H), 3.44 (s, 3H). 13C NMR (125 MHz,
CDCl3): δ 157.3, 142.0, 140.7, 136.3, 134.7, 128.3, 128.1, 127.8,
126.5, 125.5, 124.7, 122.9, 119.7, 115.8, 105.2, 51.2. HRMS
(ESI+): m/z calcd for C21H13NO3 ([M-OMe]+): 327.0895, found:
327.0911.
Scheme 4 Plausible mechanism for the synthesis of 2,3-diaryl-
2H-1-benzopyrans from various salicylaldehydes and
diarylacetylenes
10. Rubin, M.; Trofimov, A.; Gevorgyan, V. J. Am. Chem. Soc. 2005,
127, 10243−10249.
In summary, we have developed a regioselective one-pot
synthesis of 2,3-diaryl-2H-1-benzopyrans from easily available
various diarylacetylenes and salicylaldehydes via Brønsted acid-
catalyzed [4+2] cycloaddition. Electron withdrawing or electron
donating substituted aryl groups of diarylacetylenes induced the
high regioselectivities by which 2-(electron-rich aryl)-3-
(electron-poor aryl)-2H-1-benzopyrans were obtained. The
substitution of methoxy group of the product by various
nucleophiles led to 2-substituted 2,3-diaryl-2H-1-benzopyrans or
4-substituted 2,3-diaryl-4H-1-benzopyran skelton according to
HSAB principle. Thus, the present reactions provide versatile
access to functionalized 2,3-diaryl-2H-1-benzopyrans that would
11. For 2D NMR spectral data of product 7, see supplementary data.
12. (a) A. Kumar, S. Thadkappaly and R. S. Menon, J. Org. Chem.,
2015, 80, 11048-11056; (b) C. Fichtner, G. Remennikov, H. Mayr,
Eur. J. Org. Chem. 2001, 4451-4456; (c) Chen, W.; Xie, Z.;
Zheng, H.; Lou, H.; Liu, L. Org. Lett. 2014, 16, 5988-5991.
13. General procedure for the synthesis of 6-nitro-2,3-diphenyl-2-
isopropoxy-2H-1-benzopyran (10): To 2-methoxy-6-nitro-2,3-
diphenyl-2H-chromene (7), (0.359 g, 1.0 mmol) in toluene under
nitrogen, TfOH (0.018 mL, 20 mol%) was added and heated to 60
°C. Then 2-propanol (0.771 mL, 10 mmol) was added. After being
stirred at 60 °C for 5 h, the reaction mixture was quenched with
H2O. The organic layer was separated and the aqueous layer was
extracted with ethylacetate. The combined organic layer was
washed with brine, dried over MgSO4, and filtered. The filtrate
was concentrated in vacuo. The resulting residue was purified by
column chromatography on silica gel (hexane / ethylacetate = 100
: 1 to 20 : 1) to afford 6-nitro-2,3-diphenyl-2-isopropoxy-2H-1-
benzopyran (10) (0.157 g, 41%) as a yellow solid. IR (neat): 3066,
2971, 1634, 1612, 1578, 1516, 1480, 1448, 1334, 1257, 1233,
1178, 1091, 1072, 1042, 1019, 971, 926, 910, 877, 833, 808, 757,
750, 695, 650, 589, 571 cm-1. 1H NMR (300 MHz, CDCl3): δ 8.16
(s, 1H), 8.07 (dd, J = 2.6, 8.7 Hz, 1H), 7.47-7.63 (m, 2H), 7.32-
7.40 (m, 2H), 7.17-7.32 (m, 6H), 7.16 (s, 1H), 6.91 (d, J = 9.0 Hz,
1H), 4.01-4.16 (m, 1H), 1.26 (d, J = 6.0 Hz, 3H), 0.99 (d, J = 6.0
Hz, 3H). 13C NMR (126 MHz, CDCl3): δ 156.9, 141.7, 141.5,
136.4, 135.7, 128.6, 128.1, 128.0, 126.4, 125.3, 123.8, 122.8,
119.8, 115.9, 105.4, 68.2, 24.5, 23.3. HRMS (ESI+): m/z calcd
for C24H22NO4 ([M+H]+): 388.1549, found: 388.1551.
be
a useful tool for the synthesis of biologically and
photochemically active molecules.
References and notes
1.
(a) Saeed, A.; Sharma, A. P.; Durani, N.; Jain, R.; Durani, S.;
Kapil, R. S. J. Med. Chem. 1990, 33, 3210-3216; (b) Sharma, A.
P.; Saeed, A.; Durani, S.; Kapil, R. S. Structureactivity J. Med.
Chem. 1990, 33, 3216-3222; (c) Sharma, A. P.; Saeed, A.; Durani,
S.; Kapil, R. S. J. Med. Chem. 1990, 33, 3222-3229; (d) Gauthier,
S.; Cloutier, J.; Dory, Y. l.; Favre, A.; Failhot, J. C.; Ouellet, A.;
Schwerdtfeger, Y.; Rand, C.; Martel, J.; Simard, F.; Labrie J.
Enzyme Inhib. Med. Chem. 2005, 20, 165-177; (e) Gauthier, S.;
Caron, B.; Cloutier, J.; Dory, Y. L.; Favre, A.; Larouche, D.;
Mailhot, J.; Ouellet, C.; Schwerdtfeger, A.; Leblanc, G.; Martel,
14. (a) Coefficient values calculated by using Winmostar version
6.015 (MOPAC PM3) are shown in supplementary data. (b) N.
Senda, Idemitsu Tech. Rep., 2006, 49, 106-111.