7736
R. Bernini et al. / Tetrahedron 62 (2006) 7733–7737
Mass spectra were recorded on a VG 70/250S spectrometer
with an electron beam of 70 eV. Melting points were deter-
mined on a Buchi SMP apparatus.
C, 63.2; H, 5.3; O, 31.5%]; n
(KBr): 1665, 2850,
max
ꢂ1
2920 cm . d (200 MHz, CDCl ) 2.00 (3H, d, J¼1.6 Hz,
H
3
CH ), 3.77 (3H, s, OCH ), 5.83 (1H, s, CH]COCH ),
3
3
3
6
CDCl ) 15.0, 56.3, 107.2, 133.8, 142.1, 158.0, 181.0,
.48 (1H, q, J¼1.6 Hz, CH]CCH ); d (200 MHz,
3
C
5
.1. Oxidation of phenols: general procedure
3
+
1
86.2; m/z 152 (M ).
The substrate (1.0 mmol) was solubilized in [bmim]BF
ꢀ
4
(
1 ml) at 25–60 C. Then, hydrogen peroxide (50% aqueous
5.1.9. 2,3-Dimethoxy-5-methyl-1,4-benzoquinone (19).
ꢀ
ꢀ
35
solution, 6–12 equiv) and methyltrioxorhenium (4–5%)
were added in several batches (2 equiv of H O and 1% of
Red solid; mp 57–59 C (lit. 59 C).
2
2
MTO) during the course of the experiment (6–24 h). Reac-
tions were monitored by thin layer chromatography and by
gas chromatography, using dodecane as an internal standard.
The GC analysis was performed using a CP-SIL 8 CB-MS
column (25 mꢁ0.25 mm and 0.25 mm film thickness) and
5.2. Assay of fungistatic activity of benzoquinone
derivatives
Ketoconazole is commercially available (Merck) and was
used as purchased. Antifungal activities were tested in
modified Sabouraud dextrose agar (Difco Lab.) against
ꢀ
36
an isothermal temperature profile of 60 C for 2 min, fol-
ꢀ
0 min. The injector temperature was 250 C. The oxidation
ꢀ
lowed by a 10 C/min temperature gradient to 250 C for
ꢀ
the following fungal strains: A. flavus, G. pannorum var.
pannorum, Fusarium sp., P. lilacinum, P. roseopurpureum,
T. koningii and Pestalotia sp. Stock solutions of quinones
2, 6, 9, 11, 15 and 19 were obtained in DMSO (5 mg/ml).
These compounds were tested in the 0.1–100 mg/ml range,
that was added to the modified Sabouraud dextrose agar.
The fungi were applied to the surface of the agar (inoculum
1
products were extracted with diethyl ether and the organic
layer was evaporated under vacuum. Benzoquinones were
purified by flash column chromatography on silica gel and
were identified by spectroscopic analysis, mass spectro-
metry and comparison with authentic commercial samples.
7
sizes approximately 1ꢁ10 conidia/ml). They were incu-
ꢀ
5
solid; mp 66–68 C (lit. 65–68 C).
.1.1. 2,6-Di-tert-butyl-1,4-benzoquinone (2). Orange
ꢀ
bated at 28 C up to a clearly visible growth on drug-free
30
ꢀ
control. MIC values were read after 24 h for P. roseopurpur-
eum and T. koningii and after 48 h for the A. flavus, G. pan-
norum var. pannorum, Fusarium sp., P. lilacinum and
Pestalotia sp.
3
1
5
.1.2. 2,6-Diisopropyl-1,4-benzoquinone (4). Yellow oil.
Found: C, 75.2; H, 8.0; O, 16.8. C H O requires C, 75.0;
[
H, 8.4; O, 16.6%]; nmax (KBr): 1605, 1650, 3050 cm
1
2 16 2
ꢂ1
.
dH (200 MHz, CDCl ) 1.14 (12H, d, 2CH(CH ) ), 3.08
3
3 2
(
CCH(CH ) ); d (200 MHz, CDCl ) 21.1, 27.0, 129.8,
2H, hept, J¼6.8 Hz, CH(CH ) ), 6.47 (2H, s, CH]
References and notes
3
2
3
2
C
3
+
1
55.3, 186.8, 188.6; m/z 192 (M ).
1. Lipshutz, B. H.; Mollard, P.; Pfeiffer, S. S.; Chrisman, W. J. Am.
Chem. Soc. 2002, 124, 14282–14283 and references therein.
2. (a) Rodriguez, J.; Quinoa, E.; Riguera, R.; Peters, B. M.; Abrell,
L. M.; Crews, P. Tetrahedron 1992, 48, 6667–6680; (b) Letcher,
R. M.; Wong, M. C. J. Chem. Soc., Perkin Trans. 1 1992, 3035–
3037; (c) Hakura, A.; Mochida, H.; Tsutsur, Y.; Yamatsu, K.
Mutat. Res. 1994, 347, 37–43; (d) Lund, A. K.; Adsernen, A.;
Nyman, U. Phytomedicine 1998, 5, 199–203; (e) Gonzalez-
Ibarra, M.; Farfan, N.; Trejo, C.; Uribe, S.; Lotina-Hennsen,
B. J. Agric. Food Chem. 2005, 53, 3415–3420.
5
mp 27–29 C (lit. 29 C).
.1.3. 2,3,5-Trimethyl-1,4-benzoquinone (6). Yellow solid;
ꢀ
32
ꢀ
5
.1.4. 2-tert-Butyl-5-methyl-1,4-benzoquinone (9). Yellow
oil. [Found: C, 74.5; H, 7.7; O, 17.8. C H O requires C,
1
1 14 2
7
3
1
4.1; H, 7.9; O, 18.0%]; n
060 cm . d (200 MHz, CDCl ) 1.19 (9H, s, C(CH ) ),
(KBr): 1605, 1650, 2960,
max
ꢂ1
H
3
3 3
.96 (3H, d, J¼1.5 Hz, CH ), 6.46 (1H, q, J¼1.5 Hz,
3
CH]CCH ), 6.52 (1H, s, CH]CC(CH ) ); d (200 MHz,
3
3. (a) Nishina, A.; Uchibori, T. Agric. Biol. Chem. 1991, 55,
2395–2398; (b) Meazza, G.; Dayan, F. E.; Wedge, D. E.
J. Agric. Food Chem. 2003, 51, 3824–3828.
3 3
C
CDCl ) 14.9, 29.1, 131.5, 135.9, 144.1, 156.0, 187.8,
3
+
1
88.9; m/z 178 (M ).
4
. (a) Schudel, P.; Mayer, H.; Isler, O. The Vitamins; Sebrell,
W. H., Harris, R. S., Eds.; Academic: New York, NY, 1972;
Vol. 5, p 165; (b) Yamada, S.; Takeshita, T.; Tanaka, J.
J. Synth. Org. Chem. Jpn. 1982, 40, 268–270.
5.1.5. 2-tert-Butyl-6-methyl-1,4-benzoquinone (11). Yel-
low oil. [Found: C, 74.5; H, 7.6; O, 17.9. C H O requires
1
1 14 2
C, 74.8; H, 7.4; O, 17.8%]; n
3
(KBr): 1600, 1650, 2960,
060 cm . d (200 MHz, CDCl ) 1.10 (9H, s, C(CH ) ),
max
ꢂ1
5. Quideau, S.; Pouysegu, L. Org. Prep. Proced. Int. 1999, 31,
617–668 and references therein.
6. Brimble, M. A.; Duncalf, L. J.; Phytion, S. J. J. Chem. Soc.,
Perkin Trans. 1 1997, 1399–1401.
H
3
3 3
1
and CH]CC(CH ) ); d (200 MHz, CDCl ) 16.1, 28.7,
.91 (3H, d, J¼1.3 Hz, CH ), 6.41 (2H, m, CH]CCH
3
3
3
3
C
3
+
1
31.3, 131.9, 147.6, 156.2, 187.6, 188.6; m/z 178 (M ).
7
8
. McKillop, A.; Perry, D. H.; Edwards, M.; Antus, S.; Farkas, L.;
Nogrady, M.; Taylor, E. C. J. Org. Chem. 1976, 41, 282–287
and references therein.
. Kato, N.; Sugaya, T.; Mimura, T.; Ikuta, M.; Kato, S.; Kuge, Y.;
Tomioka, S.; Kasai, M. Synthesis 1997, 625–627; Tohma, H.;
Morioka, H.; Harayama, Y.; Hashizume, M.; Kita, T.
Tetrahedron Lett. 2001, 42, 6899–6901.
5
1
.1.6. 1,4-Naphthoquinone (13). Yellow solid; mp 118–
ꢀ
33
ꢀ
21 C (lit. 119–120 C).
5.1.7. 2-Methoxy-5-methyl-1,4-benzoquinone (15). Yel-
ꢀ
low solid; mp 172–173 C (lit. 170–171 C).
ꢀ
34
5.1.8. 2-Methoxy-6-methyl-1,4-benzoquinone (17). Yel-
low oil. [Found: C, 63.8; H, 5.0; O, 31.2. C H O requires
9. Land, T. Comprehensive Organic Chemistry; Stoddart, J. F.,
Ed.; Pergamon: Oxford, 1979; Vol. 1, p 1216.
2
1
8
8 3