162.2 (C-7), 166.1 (C-2); HRMS m/z282.0883 (M
C
),
C
17
H
14
O
4
requires 282.0892. Anal. Calcd for C
17
H
14
O
4
:C,
72.33%; H, 5.00%. Found: C, 72.16%; H, 4.82%.
4.1.2. 7-Benzyloxy-4-hydroxy-8-methyl-3-nitrochromen-
2-one (14). Concentrated sulphuric acid (1.61 ml,
22.1 mmol) and concentrated nitric acid (1.00 ml,
18.4 mmol) were mixed slowly at 0 8C and then added,
over a period of 15 min, to 13 (2.08 g, 7.4 mmol) suspended
in CHCl
3
. After an additional 1 h, the solvent was
evaporated under reduced pressure and 1 M HCl (30 ml)
was added. The yellow solid was filtered, rinsed well
with methanol, and crystallized from glacial acetic acid
to give 14 (2.23 g, 93%) as yellow plates: mp 205–208 8C;
IR n
max
(KBr pellet)/cm
K1
1325 and 1530 (NO stretch),
1754 (C]O stretch), 3540 (OH stretch);
1
HNMR
(300 MHz, DMSO-d
6
)d2.18 (s, 3H, ArCH
3
), 5.07 (br,
1H, –OH), 5.22 (s, 2H, –CH
2
C
6
H
5
), 7.06 (d, 1H, H-6, JZ
9.0 Hz), 7.30–7.48 (m, 5H, –CH
2
C
6
H
5
), 7.77 (d, 1H, H-5,
JZ9.0 Hz);
13
C NMR (75.5 MHz, DMSO-d
6
)d8.2
(ArCH
3
), 69.9 (–CH
2
C
6
H
5
), 108.1 (C-6), 112.2 (C-3),
113.9 (C-4a), 119.5 (C-8), 123.9 (C-5), 127.3, 127.8,
128.5, 136.8 (–CH
2
C
6
H
5
), 151.3 (C-8a), 157.0 (C-4),
159.7 (C-7), 166.4 (C-2). Anal. Calcd for C
17
H
13
NO
6
:C,
62.39%; H, 4.00%; N, 4.28%. Found: C, 62.14%; H, 3.88%;
N, 4.31%.
4.1.3. N-(7-Benzyloxy-4-hydroxy-8-methyl-2-oxo-(2H)-
chromen-3-yl)-acetamide (15). Compound 14 (1.00 g,
3.1 mmol) and Zn (1.00 g, 15.5 mmol) were refluxed in
acetic acid (10 ml) for 1 h, in which time the solution turned
deep purple and then colourless. The Zn salts were filtered
and rinsed well with hot acetic acid. The filtrate was cooled
to room temperature, allowing the amide to precipitate. The
product was filtered and crystallized with ethyl acetate to
yield 15 (0.87 g, 86%) as colourless crystals: mp 240–
243 8C; IR n
max
(CH
2
Cl
2
)/cm
K1
1500 (aromatic C]C),
1572 (amide I), 1598 (aromatic C]C), 1632 (amide II),
1686 (C]O stretch), 3288 (NH stretch), 3500 (OH stretch);
1
H NMR (300 MHz, CDCl
3
)d2.11 (s, 3H, –NHCOCH
3
),
2.23 (s, 3H, ArCH
3
), 5.24 (s, 2H, –CH
2
C
6
H
5
), 7.16 (d, 1H,
H-6, JZ9.0 Hz), 7.38–7.48 (m, 5H, –CH
2
C
6
H
5
), 7.68
(d, 1H, H-5, JZ9.0 Hz), 9.42 (s, 1H, –NH), 12.2 (br, 1H,
–OH);
13
C NMR (75.5 MHz, CDCl
3
)d8.1 (ArCH
3
), 22.6
(–NHCOCH
3
), 69.9 (–CH
2
C
6
H
5
), 101.4 (C-3), 108.9 (C-6),
109.7 (C-4a), 112.5 (C-8), 121.7 (C-5), 127.3, 127.9, 128.4,
136.7 (–CH
2
C
6
H
5
), 150.1 (C-8a), 157.4 (C-4), 158.9 (C-7),
160.3 (C-2), 171.2 (–COCH
3
). Anal. Calcd for C
19
H
17
NO
5
:
C, 67.25%; H, 5.05%; N, 4.13%. Found: C, 67.27%; H,
4.94%; N, 4.07%.
4.1.4. 7-Benzyloxy-2,6-dimethylchromeno[3,4-d]oxazol-
4-one (16). Amide 15 (2.06 g, 6.1 mmol), pyridine
(1.72 ml, 18.3 mmol) and POCl
3
(2.96 ml, 30.4 mmol)
were suspended in tetrahydrofuran (50 ml) and refluxed
for 10 min. After cooling to room temperature, the mixture
was filtered, the excess solvent evaporated under vacuum
and the remaining slurry azeotroped with toluene (!3) to
remove traces of pyridine. The product was crystallized
with ethyl acetate to yield 16 (1.70 g, 87%) as colourless
crystals: mp 206–207 8C; IR n
max
(CH
2
Cl
2
)/cm
K1
1503,
1605 (aromatic C]C), 1647 (coumarin C]C), 1748 (C]O
stretch);
1
H NMR (400 MHz, CDCl
3
)d2.33 (s, 3H, ArCH
3
),
2.56 (s, 3H, –CH
3
), 5.10 (s, 2H, –CH
2
C
6
H
5
), 6.88 (d, 1H,
H-8, JZ8.8 Hz), 7.29–7.34 (m, 5H, –CH
2
C
6
H
5
), 7.48 (d,
1H, H-9, JZ8.8 Hz);
13
C NMR (100 MHz, CDCl
3
)d8.8
(ArCH
3
), 14.1 (–CH
3
), 70.79 (–CH
2
C
6
H
5
), 105.1 (C-9a),
108.9 (C-8), 115.8 (C-6), 118.9 (C-9), 122.4 (C-3a), 127.1,
128.2, 128.7, 136.3 (–CH
2
C
6
H
5
), 152.1 (C-5a), 156.2
(C-1a), 156.3 (C-7), 159.3 (C-4), 162.6 (C-2). Anal. Calcd
for C
19
H
15
NO
4
: C, 71.02%; H, 4.71%; N, 4.36%. Found: C,
70.96%; H, 4.56%; N, 4.34%.
4.1.5. 2,6-Dimethyl-7-hydroxychromeno[3,4-d]oxazol-4-
one (17). 10% Pd/C (0.50 g, 0.05 mmol) was added to
compound 16 (0.15 g, 0.5 mmol) in a mixture of THF
(10 ml) and CH
2
Cl
2
(5 ml) and the solution stirred for 3 h at
room temperature in an atmosphere of H
2
using a balloon.
The excess solvent was evaporated after removing the Pd/C
by filtration (rinsing with hot methanol). The product was
recrystallized with methanol to yield 17 (0.08 g, 74%) as
colourless crystals: mp 330–332 8C (decomp.) (lit.
25
mp
295–303 8C (decomp.) from water/dimethylformamide); IR
n
max
(CH
2
Cl
2
)/cm
K1
1503, 1584, 1604 (aromatic C]C),
1647 (coumarin C]C), 1749 (C]O stretch), 3150 (OH
stretch);
1
H NMR (400 MHz, CDCl
3
)d2.17 (s, 3H, ArCH
3
),
2.59 (s, 3H, –CH
3
), 6.91 (d, 1H, H-8, JZ8.4 Hz), 7.48
(d, 1H, H-9, JZ8.4 Hz), 10.55 (s, 1H, –OH);
13
C NMR
(100 MHz, CDCl
3
)d9.0 (ArCH
3
), 14.4 (CH
3
), 103.5
(C-9a), 112.5 (C-6), 113.3 (C-8), 119.8 (C-9), 120.8 (C-3a),
152.8 (C-5a), 156.2 (C-1a), 157.0 (C-7), 159.5 (C-4), 163.0
(C-2). Anal. Calcd for C
12
H
9
NO
4
: C, 62.34%; H, 3.92%; N,
6.06%. Found: C, 62.13%; H, 3.99%; N, 5.98%.
4.1.6. Dimethyl (2-acetamido)phenyl phosphate (20).
2-Acetamidophenol (0.20 g, 1.32 mmol) was suspended in
THF (10 ml). Pyridine (0.43 ml, 5.29 mmol) and POCl
3
(0.25 ml, 2.65 mmol) were added and the mixture refluxed
for 1 h. Methanol was added and the reaction mixture was
refluxed for a further 20 min before being diluted with water
and the aqueous phase extracted with ethyl acetate (!1).
The combined organic extracts were dried over anhydrous
magnesium sulphate, filtered and evaporated under reduced
pressure. The crude product (0.44 g) was purified by column
chromatography (10 g silica, 50% ethyl acetate/hexane) to
afford 20 (0.06 g, 18%) as colourless crystals: mp 65–67 8C;
IR n
max
(CH
2
Cl
2
)/cm
K1
1637 (C]O);
1
H NMR (400 MHz;
DMSO-d
6
)d2.05 (3H, s, –NHCOCH
3
), 3.79 (6H, d,
J
HP
Z11.2 Hz, –OCH
3
), 7.16 (2H, m, Ar-H), 7.27 (1H, m,
Ar-H), 7.69 (1H, d, JZ6.4 Hz, Ar-H), 9.40 (1H, s,
–NHCOCH
3
);
13
C NMR (100 MHz, DMSO-d
6
)d24.1
(–NHCOCH
3
), 55.7 (d, J
CP
Z6Hz, 2!–OCH
3
), 120.6,
125.7, 126.0, 126.2 (aromatics), 130.1 (C-2), 143.1 (C-1),
169.1 (C]O);
31
P NMR (300 MHz, DMSO-d
6
)d0.87
(PO(OCH
3
)
2
OR).
Acknowledgements
This work was supported by the National Research
Foundation (NRF) as well the Equity Development
Programme of the Department of Chemistry, University of
Cape Town.
D. W. Gammon et al. / Tetrahedron 61 (2005) 10683–10688 10687