The Journal of Organic Chemistry
Note
MHz, CDCl3) δC = 185.0, 138.7, 133.9, 131.9, 126.4 pm; MS (EI) m/
z 158 (M+, 100%), 130 (27), 104 (31), 102 (31), 76 (21).
Scheme 1. Large-Scale Reaction
5-Hydroxy-1,4-naphthalenedione (Juglone) (2):15 orange solid;
21.6 mg, 83% yield, (without further purification), Rf = 0.41 (hexane/
ethyl acetate 4:1); 1H NMR (400 MHz, CDCl3) δH = 11.93 (s, 1H),
7.70−7.63 (m, 2H), 7.31 (dd, J = 7.4, 2.2 Hz, 1H), 6.98 (s, 2H) ppm;
13C{1H} NMR (101 MHz, CDCl3) δC = 190.3, 184.3, 161.4, 139.6,
138.6, 136.6, 131.7, 124.52, 119.18, 114.97 ppm; MS (EI) m/z 174
(M+, 100%), 173 (25), 120 (19), 118 (29), 92 (16), 63 (13).
Benzoquinone (3):17 dark brown solid; purification by preparative
1
TLC (hexane/ethyl acetate 9:1), Rf = 0.36, 10.1 mg, 62% yield; H
NMR (400 MHz, CDCl3) δH = 6.81 (s, 4H) ppm; 13C{1H} NMR
(101 MHz, CDCl3) δC = 187.2, 136.5 ppm; MS (EI) m/z 108 (M+,
100%), 82 (32), 80 (25), 54 (55), 53 (14), 52 (16).
UHP as a source of H2O2 and HFIP as a solvent and reaction
promoter, and its success relies on the electrophilic activation
of H2O2 by means of the fluorinated alcohol. The whole
process can be considered as environmentally benign since it
avoids the use of metal and/or organic oxidants. In addition, it
has a high atom economy, and the only byproducts and waste
formed (H2O and urea) are considered biodegradable. In the
majority of cases, the yields obtained vary from moderate to
high. Although there is not a clear trend in reactivity, it can be
asserted that naphthalene derivatives and highly substituted
electron-rich arenes seem to perform better under the reaction
conditions described. Additionally, it was observed that
quinones bearing electron-donating substituents on both
double bonds were obtained with higher yields.
3,5-Dimethyl-p-benzoquinone (4):9h dark orange solid; purifica-
tion by preparative TLC (hexane/ethyl acetate 9:1), Rf = 0.46, 13.7
mg, 67% yield; 1H NMR (400 MHz, CDCl3) δH = 6.60 (q, J = 1.6 Hz,
2H), 2.04 (s, 3H), 2.04 (s, 3H) ppm; 13C{1H} NMR (101 MHz,
CDCl3) δC = 188.1, 145.8, 133.4, 15.5 ppm; MS (EI) m/z 136 (M+,
100%), 108 (63), 107 (29), 96 (24), 80 (21), 79 (60), 77 (12), 68
(88).
2,3,5-Trimethyl-p-benzoquinone (6):9h yellow oil, purification by
preparative TLC (hexane/ethyl acetate 9:1), Rf = 0.57, 17.1 mg, 76%
yield; 1H NMR (400 MHz, CDCl3) δH = 6.75−6.40 (m, 1H), 2.06 (d,
J = 1.6 Hz, 3H), 2.05 (t, J = 1.1 Hz, 3H), 2.03 (t, J = 1.1 Hz, 3H)
ppm; MS (EI) m/z 150 (M+, 100%), 122 (32), 121 (17), 107 (47),
79 (31), 68 (22), 54 (12).
2,6-Dimethoxy-p-benzoquinone (9):16 ochre-orange solid, purifi-
cation by preparative TLC (hexane/ethyl acetate 4:1), Rf = 0.15, 22.0
mg, 87% yield; 1H NMR (300 MHz, CDCl3) δH = 5.88 (s, 2H), 3.84
(s, 6H) ppm; 13C{1H} NMR (101 MHz, CDCl3) δC = 186.9, 176.6,
157.4, 107.4, 56.4 ppm; MS (EI) m/z 168 (M+, 74%), 138 (23), 125
(15), 97 (13), 80 (36), 69 (100), 59 (13), 53 (22).
EXPERIMENTAL SECTION
General Remarks. All reagents and solvents were obtained
commercially and used without further purification.
■
NMR spectra were performed on a Bruker AV-300 or Bruker AV-
400 (Bruker Corporation) using CDCl3 as a solvent and TMS as an
internal standard unless otherwise stated.
Low-resolution mass spectra (MS) were recorded in the electron
impact mode (EI, 70 eV, He as carrier phase) using an Agilent GC/
MS 5973 Network Mass Selective Detector spectrometer apparatus
equipped with an HP-5MS column (Agilent technologies, 30 m ×
0.25 mm) and giving fragment ions in m/z with relative intensities
(%) in parentheses. Low-resolution electron impact (EI) mass spectra
were obtained at 70 eV on an Agilent GC/MS-5973N apparatus
equipped with an HP-5MS column (Agilent technologies, 30 m ×
0.25 mm).
Analytical TLC was performed on Merck silica gel plates, and the
spots were visualized with UV light at 254 nm. Flash chromatography
employed Merck silica gel 60 (0.040−0.063 mm). Silica gel 60 F254
containing gypsum was employed for preparative layer chromatog-
raphy.
General Procedure for the HFIP-UHP Oxidation of Electron-Rich
Arenes. In a capped tube, onto the corresponding arene (0.15 mmol),
HFIP (150−200 μL) and UHP (7.5 equiv) were added in one
portion. The reaction was then stirred at 45 °C (sand bath) for 24−45
h, until the reaction was judged to be completed by GC−MS. After
this time, the reaction mixture was filtered over a silica/Celite plug,
then the solvent was evaporated, and the crude material was directly
purified by flash chromatography or preparative TLC.
For the large-scale synthesis, the general procedure was adapted: In
a round-bottomed flask, 1-naphthol (6 mmol, 0.864 g), UHP (7.5
equiv, 4.2 g), and 3 mL of HFIP were added in one portion. After
heating the reaction at 45 °C (sand bath) for 30 h, the crude mixture
was filtered over a silica/Celite plug, then the solvent was evaporated,
the residue was directly purified by flash chromatography to yield
naphthoquinone (1) with a 73% yield (0.692 g).
2,5-Dimethoxy-p-benzoquinone (13):16 brown solid; purification
by preparative TLC (hexane/ethyl acetate 9.0/1.0), Rf = 0.32, 16.8
mg, 67% yield; 1H NMR (300 MHz, CDCl3) δH = 5.89 (s, 2H), 3.87
(s, 6H) ppm; 13C{1H} NMR (126 MHz, CDCl3) δC = 181.7, 159.6,
105.5, 56.6 ppm; MS (EI) m/z 168 (M+, 13%), 155 (74), 153 (30),
149 (60), 139 (56), 127 (26), 122 (15), 112 (16), 95 (35), 69 (100),
59 (17), 53 (22).
3,4-Dimethoxyphenol (14):14 brown solid; purification by flash
chromatography (hexane/ethyl acetate 4:1), Rf = 0.18, 20.3 mg, 88%
1
yield; H NMR (400 MHz, CDCl3) δH = 6.74 (d, J = 8.6 Hz, 1H),
6.49 (d, J = 2.8 Hz, 1H), 6.37 (dd, J = 8.6, 2.8 Hz, 1H), 3.83 (s, 3H),
3.82 (s, 3H) ppm; 13C{1H} NMR (101 MHz, CDCl3) δC = 150.2,
149.8, 143.0, 112.4, 105.8, 100.6, 56.6, 55.8 ppm; MS (EI) m/z 154
(M+, 100%), 139 (71), 111 (40), 93 (17), 69 (12), 65 (12), 55 (11).
4-Methoxyphenol (15):14 white solid; 17.9 mg, 96% yield (without
1
further purification), Rf = 0.23 (hexane/ethyl acetate 4:1); H NMR
(300 MHz, CDCl3) δH = 6.79 (s, 4H), 5.15 (s, 1H), 3.77 (s, 3H)
ppm; 13C{1H} NMR (75 MHz, CDCl3) δC = 153.6, 149.5, 116.1,
114.9, 55.8 ppm; MS (EI) m/z 124 (M+, 99%), 109 (100), 8 (42), 53
(14).
2-Methoxyphenol (16):14 white solid; 17.0 mg, 91% yield (without
1
further purification), Rf = 0.35 (hexane/ethyl acetate 4:1); H NMR
(300 MHz, CDCl3) δH = 7.05−6.84 (m, 4H), 5.71 (s, 1H), 3.91 (s,
3H) ppm; 13C{1H} NMR (75 MHz, CDCl3) δC = 146.6, 145.7, 121.5,
120.2, 114.6, 110.7, 55.8 ppm; MS (EI) m/z 124 (M+, 93%), 109
(100), 81 (50).
Benzoic Acid (17):14 white solid; 17.0 mg, 93% yield (without
Spectroscopic and analytical data for isolated compounds are given
below:
1
further purification), Rf = 0.38 (hexane/ethyl acetate 3:2); H NMR
Naphthoquinone (1):9h brown solid; purification by preparative
TLC (hexane/ethyl acetate 8.5/1.5), Rf = 0.38, 20.5 mg, 87% yield;
1H NMR (300 MHz, CDCl3) δH = 8.11 (dd, J = 5.8, 3.3 Hz, 2H),
(300 MHz, CDCl3) δH = 12.02 (s, 1H), 8.21−8.10 (m, 2H), 7.70−
7.59 (m, 1H), 7.51 (ddt, J = 8.2, 6.8, 1.0 Hz, 2H) ppm; 13C{1H}
NMR (75 MHz, CDCl3) δC = 172.5, 133.8, 130.2, 129.3, 128.5 ppm;
MS (EI) m/z 122 (M+, 90%), 105 (100), 77 (62), 51 (22), 50 (13).
7.79 (dd, J = 5.8, 3.3 Hz, 2H), 7.01 (s, 2H) ppm; 13C{1H} NMR (75
D
J. Org. Chem. XXXX, XXX, XXX−XXX