214
Ferreira, Kaiser, and Ferreira
KBr pellets on a Perkin-Elmer model 1420 FT-IR Spectrophotometer. NMR spectra were
determined on a Varian Unity Plus VXR (300 MHz) instrument in CDCl3 solutions. The
chemical shift data are reported in δ (ppm) units downfield from tetramethylsilane, used as
an internal standard; coupling constants (J) are given in Hertz and refer to apparent peak
multiplicities. High resolution mass spectra (HRMS) were recorded on an MICROMASS
Q-TOF MICRO Mass spectrometer using ESI-TOF (electrospray ionization-time of flight).
The isobutylene gas used in the experiments can be obtained from commercial sources or
21
may be generated in situ by dehydration of tert-butanol under acid catalysis.
β-Lapachone (2)
To a stirred solution of lawsone (4) (0.456 g, 2 mmols) and paraformaldehyde (0.480 g,
6 mmols) in dry dioxane (50 mL) isobutylene gas was bubbled during 18 h. The resulting
1
suspension was stirred at reflux. The progress of the reaction was followed by thin layer
chromatography (hexane:ethyl acetate 1:1). Upon consumption of the starting material (ca.
48 hours), the mixture was cooled to room temperature and then concentrated sulfuric acid
(15 mL) was added and kept stirring for 30 min. The mixture was poured onto ground ice
forming a dark orange solid. This solid was collected, dissolved in CH2Cl2 (50 mL) and
washed with saturated aqueous NaHCO3 (3 × 50 mL). The organic layer was dried over
sodium sulfate, filtered, concentrated under reduced pressure and dried under vacuum to
◦
22
◦
give 2 (0.291 g, 60% yield) as an orange solid, mp. 153–155 C, lit. 153–155 C. IR (film):
1
−1
1
760 cm (C = O); H NMR (300 MHz, CDCl3,): δ (J in Hz): 1.47 (6H, s), 1.85 (2H, t,
J = 6.8), 2.57 (2H, t, J = 6.8), 7.50 (1H, ddd, J = 8.7, 7.5, 1.2), 7.64 (1H, ddd, J = 9.0,
13
7
.5, 1.4), 7.80 (1H, ddd, J = 7.5, 1.4, 0.4), 8.05 (1H, ddd, J = 7.5, 1.4, 0.4); C NMR (75
MHz. CDCl3) δ: 16.3, 26.9, 31.8, 79.5, 112.9, 124.3, 128.7, 130.6, 130.8, 132.8, 135.0,
62.2, 178.7, 180.0. HRMS (ESI): Calcd for C15H14O3: 242.0943. Found: 242.0956.
1
nor-β-Lapachone (3)
To a stirred solution of lawsone (4) (0.456 g, 2 mmols) and cerium (IV) ammonium ni-
trate (2.74 g, CAN, 5 mmols) in dry acetonitrile (50 mL) was bubbled during 5 h with
isobutylene gas and the resulting suspension was stirred at room temperature. The progress
of the reaction was followed by thin layer chromatography (hexane:ethyl acetate 1:1).
Upon consumption of the starting material (ca. 5 h), concentrated sulfuric acid (10 mL)
was added and the mixture was kept stirring for 30 min. The mixture was poured onto
ground ice forming a dark orange solid. This solid was collected, dissolved in CH2Cl2 (50
mL) and washed with saturated aqueous NaHCO3 (3 × 50 mL) and saturated aqueous
NH4Cl (3 × 50mL). The organic layer was dried over sodium sulfate, filtered, concen-
trated under reduced pressure and dried under vacuum. Compound 3 (0.387 g, 80% yield)
◦
23
◦
−1
was obtained as an orange solid, mp. 168–170 C, lit. 170–171 C. IR (film) 1779 cm
(
1
C=O); H NMR (300 MHz, CDCl3,): δ (J in Hz): 1.53 (6H, s), 2.87 (2H, s), 7.50 (1H, ddd,
J = 9.0, 7.3, 1.7), 7.56 (1H, ddd, J = 9.0, 7.3, 2.0), 7.57 (1H, ddd, J = 7.3, 2.0, 0.8), 8.01
13
(
1H, ddd, J = 7.3, 2.0, 0.8); C NMR (75 MHz. CDCl3): δ 28.1, 39.0, 93.5, 114.7, 124.3,
1
2
27.6, 129.0, 130.6, 131.6, 134.2, 168.6, 175.4, 181.0. HRMS (ESI): Calcd for C14H12O3:
28.0786. Found: 228.0866.