Ito et al.
6
.90 (dd, J ) 12.0, 1.5 Hz, 1H, H-4), 6.29 (d, J ) 12.3 Hz, 1H,
δ 194.4, 152.3, 134.0, 129.6, 129.4, 125.8, 99.5, 63.9 (OCD
3
peak
OD, a
mixture of 2 and hemiketal 5a and 5b) for 5b δ 193.7, 153.8, 138.9,
127.1, 127.0, 121.8, 99.5, 64.0, (OCD peak overlapping with
solvent peak). LR-MS m/z 150 (M - Me, 42), 137 (13), 122 (15),
106 (12), 80 (80). Anal. Calcd for C NO : C, 58.18; H, 4.27; N,
8.48. Found: C, 58.04; H, 4.48; N, 8.29.
1
3
13
H-7), 6.18 (d, J ) 12.0 Hz, 1H, H-3). C NMR (75 MHz, DMSO-
overlapping with solvent peak). C NMR (75 MHz, CD
3
1
3
d
[
6
) δ 185.4, 183.8, 152.0, 139.3, 130.0, 127.8, 123.9. C NMR
75 MHz, CD OD, a mixture of 1 and hemiketal 4a and 4b] only
assignable signals for 4b δ 193.8, 153.5, 140.2, 135.6, 126.0, 121.8,
9.5, (OCD peak overlapping with solvent peak). LR-MS m/z 151
3
3
+
9
3
8
H
7
3
+
(
M , 48), 134 (8), 123 (22), 95 (14), 80 (30), 65 (100).
Potassium Salt of “5-Nitrosotropolone”. To an ethanol solution
of “5-nitrosotropolone” 1 was added 1 equiv of potassium hydroxide
Cyclohepta-3,6-diene-1,2,5-trione-5-O-methyloxime-2-dimeth-
yl Ketal (6). A solution of 2 (47 mg, 0.285 mmol), orthoformic
acid trimethyl ester (0.3 mL, 2.85 mmol), and a catalytic amount
of p-toluenesulfonic acid (TsOH) in CH Cl (3 mL) was stirred at
in ethanol and the mixture was evaporated at room temperature to
-1
give a brown precipitate. IR (KBr) (cm ) 1611, 1584, 1470, 1322.
2
2
1
H NMR (500 MHz, DMSO-d
6
) δ 8.20 (dd, J ) 12.0, 1.5 Hz, 1H,
room temperature for 16 h. The mixture was poured into saturated
H-6), 6.76 (dd, J ) 12.5, 1.5 Hz, 1H, H-4), 6.46 (d, J ) 12.0 Hz,
aqueous sodium hydrogen carbonate (NaHCO ) and extracted with
3
1
3
1
H, H-7), 6.07 (d, J ) 12.5 Hz, 1H, H-3). C NMR (75 MHz,
CHCl . The organic layer was washed with brine, dried over sodium
3
DMSO-d ) δ 184.5, 181.0, 164.1, 146.7, 119.0, 118.0, 117.5.
6
sulfate (Na SO ), and evaporated in vacuo. The residue was flash-
2
4
Cyclohepta-3,6-diene-1,2,5-trione-5-(O-methyloxime) (Tropo-
quinone-5-O-methyl oxime, 2). A solution of “5-nitrosotropolone”
chromatographed [silica gel, ethyl acetate-hexane (1:6)] to give a
1
mixture of ketals 6a and 6b (48 mg, 80%, ca. 1:2.5, based on H
1
(2.77 g, 18.3 mmol), potassium carbonate (K
2
CO
3
) (5.05 g, 36.6
NMR integration). Mp 62-64 °C (a mixture of 6a and 6b). IR
-1
mmol), 18-crown-6 (0.69 g, 1.84 mmol), and methyl iodide (5.7
mL, 91.5 mmol) in acetonitrile (MeCN) (80 mL) was heated at 60
(KBr) (cm ) 1691, 1036. UV data: see the Supporting Information,
1
13
Table S1. H and C NMR spectra were determined in CDCl
3
and
1
°
C for 5 h, then cooled to room temperature and filtered. The filtrate
was concentrated in vacuo. The residue was flash-chromatographed
silica gel, ethyl acetate-hexane (1:3)] to give methyl oxime 2 (0.77
CD OD. H NMR (300 MHz, CDCl3, a mixture of 6a and 6b) for
3
6a δ 7.37 (dd, J ) 12.9, 1.8 Hz, 1H, H-6), 6.49 (dd, J ) 12.0, 1.8
Hz, 1H, H-4), 6.23 (d, J ) 12.9 Hz, 1H, H-7), 5.97 (d, J ) 12.0
[
1
g, 26%). Mp 123-125 °C, yellow prisms (recryst from methylene
chloride-hexane). IR (KBr) (cm ) 1662, 1643, 1619, 1314, 1037.
Hz, 1H, H-3), 4.08 (s, 3H, NOMe), 3.30 (s, 6H, OMe × 2). H
-
1
NMR (300 MHz, CDCl3, a mixture of 6a and 6b) for 6b δ 6.88
(dd, J ) 12.0, 1.5 Hz, 1H, H-4), 6.77 (dd, J ) 12.3, 1.5 Hz, 1H,
H-6), 6.19 (d, J ) 12.3 Hz, 1H, H-7), 6.02 (d, J ) 12.0 Hz, 1H,
1
UV data: see the Supporting Information, Table S1. H NMR
spectra were determined in various deuterated solvents (DMSO-
1
d
6
, DMF-d
DMSO-d
dd, J ) 12.6, 1.0 Hz, 1H, H-4), 7.10 (d, J ) 12.6, 1.0 Hz, 1H,
H-6), 6.60 (d, J ) 12.6 Hz, 1H, H-3), 6.57 (d, J ) 12.6 Hz, 1H,
7
, CD
and CD
3
CN, CD
3
OD, and D
2
H-3), 4.08 (s, 3H, NOMe), 3.29 (s, 6H, OMe × 2). H NMR (300
1
OD. H NMR (300 MHz, DMSO-d
3
MHz, CD OD, a mixture of 6a and 6b) for 6a δ 7.36 (dd, J )
6
3
(
12.9, 1.5 Hz, 1H, H-6), 6.51 (dd, J ) 12.0, 1.5 Hz, 1H, H-4), 6.23
(d, J ) 12.9 Hz, 1H, H-7), 5.96 (d, J ) 12.0 Hz, 1H, H-3), 4.06 (s,
1
1
H-7), 4.16 (s, 3H, NOMe). H NMR (300 MHz, DMF-d
7
7
3H, NOMe), 3.24 (s, 6H, OMe × 2). H NMR (300 MHz, CD
3
OD,
.85-7.50 (m, 1H, H-4), ca. 7.30-7.05 (m, 1H, H-6), 6.68 (d, J
a mixture of 6a and 6b) for 6b δ 6.91 (dd, J ) 11.9, 1.5 Hz, 1H,
H-4), 6.77 (dd, J ) 12.5, 1.5 Hz, 1H, H-6), 6.16 (d, J ) 12.5 Hz,
1H, H-7), 6.02 (d, J ) 11.9 Hz, 1H, H-3), 4.06 (s, 3H, NOMe),
3.23 (s, 6H, OMe × 2). C NMR (75 MHz, CDCl3, a mixture of
6a and 6b) for 6a δ 191.6, 151.1, 130.8, 129.5, 129.1, 123.7, 102.7,
63.4, 50.3. C NMR (75 MHz, CDCl3, a mixture of 6a and 6b)
)
12.6 Hz, 1H, H-3), 6.65 (d, J ) 12.6 Hz, 1H, H-7), 4.23 (s, 3H,
1
NOMe). H NMR (300 MHz, CD
3
CN) δ 7.63 (dd, J ) 12.9, 2.1
1
3
Hz, 1H, H-4), 7.09 (dd, J ) 12.9, 2.1 Hz, 1H, H-6), 6.55 (d, J )
1
NOMe). H NMR [300 MHz, CD
hemiketals 5a and 5b in a ratio of ca. 1:0.7:4 (based on H NMR
2.9 Hz, 1H, H-7), 6.54 (d, J ) 12.9 Hz, 1H, H-3), 4.17 (3H, s,
1
13
3
OD, a mixture of 2 and
1
for 6b δ 191.1, 152.6, 136.0, 133.2, 126.8, 122.0, 102.6, 63.6, 50.3.
1
3
integration)] for 2 δ 7.70 (dd, J ) 12.9, 1.5 Hz, 1H, H-4), 7.16
C NMR (75 MHz, CD OD, a mixture of 6a and 6b) for 6a δ
3
13
(
dd, J ) 12.9, 1.5 Hz, 1H, H-6), 6.60 (d, J ) 12.9 Hz, 1H, H-7),
193.1, 152.4, 131.9, 130.6, 130.4, 124.6, 104.0, 63.9, 50.5. C NMR
(75 MHz, CD OD, a mixture of 6a and 6b) for 6b δ 192.7, 153.9,
137.2, 134.4, 127.9, 123.1, 104.0, 64.0, 50.5. LR-MS m/z 196 (M
- Me, 42), 180 (100), 152 (33), 132 (40), 120 (27), 106 (18).
4
HRMS Calcd for C10H13NO 211.0844, found 211.0855.
1
6
.59 (d, J ) 12.9 Hz, 1H, H-3), 4.21 (s, 3H, NOMe). H NMR
300 MHz, CD OD, a mixture of 2 and hemiketals 5a and 5b in a
ratio of ca. 1:0.7:4 (based on H NMR integration)] for 5a δ 7.46
dd, J ) 12.9, 1.5 Hz, 1H, H-6), 6.44 (dd, J ) 12.0, 1.5 Hz, 1H,
H-4), 6.28 (d, J ) 12.9 Hz, 1H, H-7), 6.02 (d, J ) 12.0 Hz, 1H,
3
+
[
3
1
(
Ketalization of the Methyl Oxime 2 to Form Monoethylene
Ketal 7. A solution of 2 (121 mg, 0.73 mmol), ethylene glycol (44
1
H-3), 4.06 (s, 3H, NOMe). H NMR [300 MHz, CD
3
OD, a mixture
of 2 and hemiketals 5a and 5b in a ratio of ca. 1:0.7:4 (based on
µL, 0.80 mmol), and a catalytic amount of TsOH in CHCl
was heated at reflux for 3 h. The mixture was poured into saturated
aqueous NaHCO and extracted with CHCl . The organic layer was
washed with brine, dried over Na SO , and evaporated in vacuo.
3
(5 mL)
1
H NMR integration)] for 5b δ: 6.87 (dd, J ) 12.0, 1.8 Hz, 1H,
H-4), 6.85 (dd, J ) 12.6, 1.8 Hz, 1H, H-6), 6.23 (d, J ) 12.6 Hz,
3
3
1
1
H, H-7), 6.08 (d, J ) 12.0 Hz, 1H, H-3), 4.06 (s, 3H, NOMe). H
2
4
NMR [300 MHz, D
2
O, a mixture of 2 and hydrate 11a and 11b in
Theresiduewasflash-chromatographed[silicagel,ethylacetate-hexane
1
a ratio of ca. 1:0.2:0.5 (based on H NMR integration)] for 2 δ:
(1:4)] to give a mixture of 7a and 7b (67 mg, 44%, ca. 1:5, based
1
7
1
1
.68 (dd, J ) 13.1, 1.8 Hz, 1H, H-4), 7.14 (dd, J ) 12.9, 1.8 Hz,
on H NMR integration). Mp 70-72 °C [a mixture of 7a and 7b,
-1
H, H-6), 6.60 (d, J ) 12.9 Hz, 1H, H-7), 6.58 (d, J ) 13.1 Hz,
yellow prisms (recryst from ether-hexane)]. IR (KBr) (cm ) 1675,
1
1
H, H-3), 4.13 (s, 3H, NOMe). H NMR [300 MHz, D
2
O, a mixture
1036, 1009. H NMR (300 MHz, CDCl3, a mixture of 7a and 7b)
of 2 and hydrate 11a and 11b in a ratio of ca. 1:0.2:0.5 (based on
H NMR integration)] for 11a δ 7.47 (dd, J ) 12.9, 1.5 Hz, 1H,
H-6), 6.38 (dd, J ) 12.0, 1.5 Hz, 1H, H-4), 6.34 (d, J ) 12.9 Hz,
for 7a δ 7.46 (dd, J ) 12.6, 1.8 Hz, 1H, H-6), 6.49 (dd, J ) 12.3,
1.5 Hz, 1H, H-4), 6.29 (d, J ) 12.6 Hz, 1H, H-7), 6.14 (d, J )
12.3 Hz, 1H, H-3), ca. 4.10-3.92 (m, 8H), 4.08 (s, 3H, NOMe).
1
1
1
1
H, H-7), 6.11 (d, J ) 12.0 Hz, 1H, H-3), 3.99 (s, 3H, NOMe). H
H NMR (300 MHz, CDCl3, a mixture of 7a and 7b) for 7b δ 6.94
NMR [300 MHz, D
2
O, a mixture of 2 and hydrate 11a and 11b in
(dd, J ) 12.3, 1.5 Hz, 1H, H-4), 6.86 (dd, J ) 12.6, 1.8 Hz, 1H,
H-6), 6.26 (d, J ) 12.6 Hz, 1H, H-7), 6.23 (d, J ) 12.3 Hz, 1H,
1
a ratio of ca. 1:0.2:0.5 (based on H NMR integration)] for 11b δ
1
3
6
1
1
1
.87 (dd, J ) 12.5, 1.5 Hz, 1H, H-6), 6.81 (dd, J ) 12.2, 1.5 Hz,
H-3), ca. 4.10-3.92 (m, 8H), 4.08 (s, 3H, NOMe). C NMR (75
MHz, CDCl3, a mixture of 7a and 7b) for 7a δ 190.4, 152.1, 137.0,
H, H-4), 6.29 (d, J ) 12.5 Hz, 1H, H-7), 6.17 (d, J ) 12.2 Hz
H, H-3), 3.99 (s, 3H, NOMe). 13C NMR (75 MHz, DMSO-d
) δ
133.3, 127.0, 121.0, 106.5, 65.6, 63.6. C NMR (75 MHz, CDCl3,
13
6
1
3
85.0, 183.5, 151.4, 137.5, 131.5, 129.1, 123.6, 64.3. C NMR
OD, a mixture of 2 and hemiketal 5a and 5b) for 2
a mixture of 7a and 7b) for 7b δ 191.2, 150.7, 130.0, 129.7, 129.2,
+
(
75 MHz, CD
δ 186.6, 185.2, 152.8, 139.9, 131.9, 129.6, 125.5, 65.2. C NMR
75 MHz, CD OD, a mixture of 2 and hemiketal 5a and 5b) for 5a
3
124.1, 106.5, 65.6, 63.5. LR-MS m/z 209 (M , 5), 194 (60), 178
1
3
(100), 150 (26), 134 (83), 106 (43), 98 (36), 80 (73), 52 (37). HRMS
Calcd for C10H11NO : 209.0687, found 209.0714.
4
(
3
1
280 J. Org. Chem. Vol. 74, No. 3, 2009