C. Commandeur, J.-C. Florent, P. Rousselle, E. Bertounesque
SHORT COMMUNICATION
55.3 (C-15), 55.1 (C-15Ј), 33.7 (C-16), 33.6 (C-16Ј), 16.5 (C-14Ј),
containing compounds, such as 4g and 17, will be subjected
to the intermolecular Diels–Alder reaction to create spiro
compounds.
15.3 (C-14) ppm. IR (film): ν = 2924, 2853, 1720, 1611, 1467, 1233,
˜
1208, 1165, 761 cm–1. MS (ESI–): m/z = 292.1 [M – H]–, 293.1
[M]–. HRMS (ESI+): calcd. for C19H18NO2 [M + H]+ 292.1338;
found 292.1337.
Supporting Information (see footnote on the first page of this arti-
Experimental Section
cle): Experimental procedures and full spectroscopic data for all
1
new compounds. Copies of the H and 13C NMR spectra.
General Procedure for the Synthesis of Pyranoacridines: To a solu-
tion of 1-hydroxy-3-methoxy-10-methylacridone (5; 300 mg,
1.18 mmol) in anhydrous THF (15 mL, 0.08 m) at 0 °C and under
an argon atmosphere was added dropwise the Grignard reagent in
dry Et2O or THF (2.9 mL, 2.9 mmol, 2.5 equiv.). During the ad-
dition of the Grignard reagent, a color change from yellow to
orange-red was observed. The reaction mixture was stirred at room
temperature for 2–4 h. Then, water was added at 0 °C, and the
reaction mixture was stirred for 5 min. The purple reaction mixture
was then diluted with ethyl acetate and icy brine. Rapid extraction
with ethyl acetate, drying over MgSO4, filtration, and concentra-
tion gave the crude product as a dark red-purple oil. Certain pyrano-
acridines appeared to have low stability on silica, and in such cases,
the yields were determined by 1H NMR spectroscopy by using
pentachloroethane (PCE, 20 μL) as internal standard.[20]
Acknowledgments
This work was supported by the Agence Nationale de la Recherche
(Grant ANR-08-PCVI-0031-CHEMISPIKE), Centre National de
la Recherche Scientifique (CNRS) and Institut Curie.
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26.
2,2-Dimethyl-5-methoxy-7-methylpyrano[2,3,4-kl]acridine (4c): This
compound was prepared according to the general procedure start-
ing from 5 (100 mg, 0.39 mmol) and was obtained as a light-brown
residue (113 mg, 0.38 mmol, Ͼ 95%). 1H NMR (400 MHz,
CDCl3): δ = 7.49 (dd, J = 8.0, 1.6 Hz, 1 H, 11-H), 7.12 (ddd, J =
8.0, 7.2, 1.6 Hz, 1 H, 9-H), 6.81 (m, 2 H, 8-H, 10-H), 5.98 (d, J =
2.4 Hz, 1 H, 4-H or 6-H), 5.94 (d, J = 2.4 Hz, 1 H, 6-H or 4-H),
5.40 (s, 1 H, 1-H), 3.67 (s, 3 H, 12-H), 3.23 (s, 3 H, 13-H), 1.37 (s,
6 H, 14-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 161.3 (C-5),
153.6 (C-3a), 140.1 and 140.0 (C-6a, C-7a), 128.9 (C-9), 124.1 (C-
11a), 122.6 (C-11), 120.3 (C-10), 119.7 (C-11b), 113.5 (C-8), 109.1
(C-1), 102.5 (C-11c), 93.8 and 92.3 (C-4, C-6), 77.1 (C-2), 55.2 (C-
12), 33.4 (C-13), 27.7 (C-14) ppm. IR (ATR): ν = 2935, 1744, 1606,
˜
1561, 1468, 1327, 1310, 1190, 1151, 1091, 1053, 818, 757 cm–1. MS
(ESI+): m/z = 294.1 [M + H]+. HRMS (ESI+): calcd. for
C19H20NO2 [M + H]+ 294.1494;, found 294.1504.
9-(But-3-en-2-ylidene)-9,10-dihydro-3-methoxy-10-methylacridin-1-
ol (4g): This compound was prepared according to the general pro-
cedure starting from 5 (149 mg, 0.58 mmol) and commercially
available crotylmagnesium bromide. Purification by flash
chromatography on silica gel (pentane/ethyl acetate, 1:1) led to 4g
as an inseparable mixture of regioisomers with E/Z = 1.5:1, as de-
termined by 1H NMR spectroscopy (157.9 mg, 0.54 mmol, 92%).
1H NMR (300 MHz, CDCl3): δ = 7.40 (2*dd, J = 7.6, 1.5 Hz, 1 H,
8-H, 8Ј-H), 7.31–7.25 (m, 1 H, 6-H, 6Ј-H), 7.14 (dd, J = 17.8,
10.9 Hz, 0.4 H, 12Ј-H), 7.06 (2*dd, J = 7.5, 1.0 Hz, 1 H, 7-H, 7Ј-
H), 6.98 (dd, J = 8.2, 0.9 Hz, 1 H, 5-H, 5Ј-H), 6.62 (dd, J = 17.3,
10.8 Hz, 0.6 H, 12-H), 6.31 (d, J = 2.3 Hz, 0.6 H, 2-H), 6.21 (d, J
= 2.3 Hz, 0.6 H, 4-H), 6.19 (d, J = 2.3 Hz, 0.4 H, 2Ј-H), 6.06 (d, J
= 2.3 Hz, 0.4 H, 4Ј-H), 5.51 (dd, J = 17.3, 1.3 Hz, 0.6 H, 13-HE),
5.41 (dd, J = 17.3, 1.4 Hz, 0.4 H, 13-HЈE), 5.32 (dd, J = 10.8,
1.3 Hz, 0.6 H, 13-HZ), 5.19 (dd, J = 10.9, 1.4 Hz, 0.4 H, 13-HЈZ),
3.83 (s, 1.8 H, 15-H), 3.82 (s, 1.2 H, 15Ј-H), 3.39 (s, 1.8 H, 16-H),
3.38 (s, 1.2 H, 16Ј-H), 2.16 (s, 1.8 H, 14-H), 2.00 (s, 1.2 H, 14Ј-H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 160.4 (C-3), 160.3 (C-3Ј),
152.5 (C-1, C-1Ј), 145.9 (C-4aЈ), 145.7 (C-4a), 143.3 (C-10a), 143.2
(C-10aЈ), 137.4 (C-12), 136.8 (C-12Ј), 128.6 (C-11Ј), 128.5 (C-8Ј),
128.0 (C-8), 127.3 (C-11), 127.2 (C-6), 127.1 (C-6Ј), 126.32 (C-9),
126.27 (C-9Ј), 125.8 (C-8a), 125.4 (C-8aЈ), 119.9 (C-7Ј), 119.8 (C-
7), 116.0 (C-13), 114.5 (C-13Ј), 112.1 (C-5Ј), 112.0 (C-5), 106.1 (C-
9aЈ), 105.5 (C-9a), 93.6 (C-2), 93.5 (C-2Ј), 92.1 (C-4), 91.7 (C-4Ј),
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[10] Yields in parentheses were determined by 1H NMR spectro-
scopic analysis of the crude mixture after workup by using a
known amount of pentachloroethane as an internal standard.
No starting material was recovered.
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