The Journal of Organic Chemistry
Article
1JC−F = 272 Hz, CF ), 123.1 (C-8), 121.5 (C-4), 120.8 (q, J
3
= 3
(CDCl , 400 MHz): δ 10.11 (br, 1H, OH), 8.40 (d, J = 8.7 Hz, 1H,
3
C−F
3
Hz, C-7), 110.6 (C-2). The mother liquid was concentrated to give 2/
parts of 7-trifluoromethyl-1-naphthol (6i) and 1/3 parts of 6h.
H-1), 7.58 (d, J = 9.1 Hz, 1H, H-11), 7.46 (d, J = 2.6 Hz, 1H, H-4),
7.23 (dd, J = 8.7, 2.6 Hz, 1H, H-2), 6.80 (dd, J = 9.1, 2.7 Hz, 1H, H-
10), 6.64 (d, J = 2.7 Hz, 1H, H-8), 6.25 (s, 1H, H-6), 3.48 (q, J = 7.0
3
Further isolation of 6i by recrystallization was unsuccessful, and it was
1
13
1
used without further purification (0.78 g). H NMR (CDCl , 400
Hz, 4H, CH ), 1.16 (t, J = 7.0 Hz, 6H, CH ). C{ H} NMR (CDCl ,
3
2
3
3
MHz): δ 8.58 (dd, J = 1.8, 0.9 Hz, 1H, H-8), 7.91 (d, J = 8.7 Hz, 1H,
H-5), 7.67 (dd, J = 8.7, 1.8 Hz, 1H, H-6), 7.50 (d, J = 8.4 Hz, 1H, H-
101 MHz): δ 181.8 (C-5), 159.6 (C-3), 151.3 (C-6a), 150.0 (C-9),
145.9 (C-7a), 138.7 (C-12a), 132.9 (C-4a), 130.2 (C-11), 125.6 (C-
1), 124.0 (C-11a), 123.2 (C-12b), 120.0 (C-2), 110.0 (C-10), 109.9
(C-4), 104.5 (C-6), 95.9 (C-8), 44.3 (CH ), 12.3 (CH ). HRMS
4
5
1
7
), 7.44 (dd, J = 8.4, 7.3 Hz, 1H, H-3), 6.88 (dd, J = 7.3, 1.0 Hz, H-2),
.44 (s, 1H, OH). 1 C{ H} NMR (CDCl , 101 MHz): δ 152.0 (C-1),
3
1
3
2
3
2
+
+
35.9 (C-4a), 128.6 (C-5), 128.2 (C-3), 127.1 (q, J
= 34 Hz, C-
(ESI): calcd for C H N O [M + H] , m/z 335.1390, found: m/z
20 19 2 3
43,97
C−F
1
3
), 124.6 (q, J
= 272 Hz, CF ), 123.3 (C-8a), 122.1 (q, J = 3
335.1379. The data is in agreement with previous reports.
C−F
3
C−F
3
Hz, C-6), 120.6 (C-4), 120.1 (q, J
= 5 Hz, C-8), 109.8 (C-2).
7
9-Diethylamino-1-hydroxy-5H-benzo[a]phenoxazin-5-one (7c).
In a similar way, 1,5-dihydroxynaphthalene (6c, 2.40 g, 16.24
mmol) was mixed with 5-diethylamino-2-nitrosophenol hydrochloride
(1, 2.30 g, 10.50 mmol) to form 9-diethylamino-1-hydroxy-5H-
benzo[a]phenoxazin-5-one (7c), which was purified by flash
chromatography (0−20% EtOH in EtOAc) and crystallized from
C−F
4
8
-Trifluoromethyl-1-naphthol (6j). To a stirred solution of 2-
chlorobenzotrifluoride (1.45 mL, 11.1 mmol) in anhydrous THF (20
mL) at −78 °C was added dropwise a n-butyllithium solution (2.5 M
in hexanes, 4.43 mL, 11.1 mmol). The reaction mixture was stirred at
−
78 °C for 60 min, after which it was cannulated slowly through
Teflon tubing into a flask containing stirred furan (8.1 mL, 0.11 mol)
at 25 °C. The reaction mixture was stirred overnight and then
portioned between Et O (50 mL) and H O (50 mL). The organic
absolute EtOH in dark green crystals (1.70 g, 4.30 mmol). Yield: 47%.
1
H NMR (DMSO/CDCl , 400 MHz): δ 13.12 (br, 1H, OH), 7.69 (d,
3
2
2
J = 7.9 Hz, 1H, H-4), 7.58 (d, J = 9.0 Hz, 1H, H-11), 7.53 (t, J = 7.9
Hz, 1H, H-3), 7.22 (d, J = 7.9 Hz, 1H, H-2), 6.75 (dd, J = 9.0, 2.7 Hz,
1H, H-10), 6.58 (d, J = 2.7 Hz, 1H, H-8), 6.30 (s, 1H, H-6), 3.51 (q, J
layer was isolated, washed with H O (50 mL) and brine (50 mL),
2
dried over Na SO , and concentrated under reduced pressure. The
2
4
residue was purified by flash chromatography (0−5% EtOAc in
hexanes) to afford 1,4-epoxy-1,4-dihydro-5-(trifluoromethyl)-
13
1
=
7.1 Hz, 4H, CH ), 1.24 (t, J = 7.1 Hz, 6H, CH ). C{ H} NMR
2
3
(
6
DMSO/CDCl , 101 MHz): δ 182.1 (C-5), 159.0 (C-1), 151.4 (C-
a), 150.7 (C-9), 146.5 (C-7a), 141.5 (C-12a), 132.0 (C-4a), 131.3
3
naphthalene (5j) as a colorless oil (1.31 g, 6.18 mmol). Yield: 56%.
1
H NMR (CDCl , 400 MHz): δ 7.39 (d, J = 6.8 Hz, 1H, H-7), 7.18
3
(
(
(
3
C-3), 129.2 (C-2), 121.2 (C-11a), 120.1 (C-11), 116.8 (C-4), 114.2
(
d, J = 6.8 Hz, 1H, H-5), 7.09 (t, J = 6.8 Hz, 1H, H-6), 7.07 (dd, J =
C-12b), 110.0 (C-10), 106.2 (C-6), 96.5 (C-8), 44.7 (CH ), 12.4
2
5
6
1
6
.6, 1.8 Hz, 1H, vinyl CH), 7.05 (dd, J = 5.6, 1.8 Hz, 1H, vinyl CH),
.00 (d, J = 1.8 Hz, 1H, allyl CH), 5.78 (d, J = 1.8 Hz, 1H, allyl CH).
,4-Epoxy-1,4-dihydro-5-(trifluoromethyl)naphthalene (5j, 1.30 g,
.13 mmol) was dissolved in a HCl solution (1.25 M in EtOH, 25
+
+
CH ). HRMS (ESI): calcd for C H N O [M + H] , m/z
3
20 19
2
3
35.1390, found: m/z 335.1406. The data is in agreement with
37,87
previous reports.
-Bromo-9-diethylamino-5H-benzo[a]phenoxazin-5-one (7e). In
3
mL, 31.3 mmol) and stirred at 50 °C (DrySyn heating block) for 20 h.
The mixture was evaporated to dryness to give 8-trifluoromethyl-1-
a similar way, 7-bromo-1,3-naphthalenediol (12e, 150 mg, 0.63
mmol) was mixed with 5-diethylamino-2-nitrosophenol hydrochloride
naphthol (6j), which crystallized from pentanes in colorless needles
(
1, 145 mg, 0.63 mmol) to obtain 3-bromo-9-diethylamino-5H-
1
(
1.12 g, 5.27 mmol). Yield: 86%. H NMR (CDCl , 400 MHz): δ
3
benzo[a]phenoxazin-5-one (7e), which crystallized from hexanes in
7
.99 (d, J = 8.2 Hz, 1H, H-7), 7.96 (d, J = 7.5 Hz, 1H, H-4), 7.53 (dd,
J = 8.2, 1.2 Hz, 1H, H-5), 7.47 (t, J = 8.2 Hz, 1H, H-6), 7.42 (t, J =
.5 Hz, 1H, H-3), 7.01 (dd, J = 7.5, 1.2 Hz, 1H, H-2), 5.50 (s, 1H,
1
dark green crystals (143 mg, 0.36 mmol). Yield: 57%. H NMR
(
CDCl , 400 MHz): δ 8.48 (d, J = 8.5 Hz, 1H, H-1), 8.42 (d, J = 2.1
3
7
Hz, 1H, H-4), 7.78 (dd, J = 8.5, 2.1 Hz, 1H, H-2), 7.57 (d, J = 9.1 Hz,
13
1
OH). C{ H} NMR (CDCl , 101 MHz): δ 150.6 (C-1), 136.5 (C-
3
1
1
=
H, H-11), 6.67 (dd, J = 9.1, 2.7 Hz, 1H, H-10), 6.44 (d, J = 2.7 Hz,
4
1
1
a), 133.6 (q, J = 2 Hz, C-6), 127.1 (C-5), 126.4 (q, J = 8 Hz, C-7),
H, H-8), 6.36 (s, 1H, H-6), 3.47 (q, J = 7.1 Hz, 4H, CH ), 1.27 (t, J
2
25.0 (q, J = 272 Hz, CF ), 124.5 (C-3), 124.2 (q, J = 32 Hz, C-8),
13
1
3
7.1 Hz, 6H, CH3). C{ H} NMR (CDCl , 101 MHz): δ 182.2 (C-
3
22.5 (C-4), 120.5 (C-8a), 114.2 (C-2).
5), 152.3 (C-6a), 151.1 (C-9), 146.9 (C-7a), 138.9 (C-12a), 134.3
9
-Diethylamino-2-hydroxy-5H-benzo[a]phenoxazin-5-one (7a).
(
(
9
C-2), 133.0 (C-4a), 131.3 (C-11), 130.8 (C-3), 128.6 (C-4), 125.6
C-1), 125.2 (C-11a), 124.9 (C-12b), 110.1 (C-10), 105.6 (C-6),
To a solution of 1,6-naphthalenediol (6a, 1.00 g, 6.24 mmol) in
anhydrous DMF (25 mL) was added 5-diethylamino-2-nitrosophenol
hydrochloride (1, 1.44 g, 6.24 mmol). This reaction mixture was
stirred at 100 °C (DrySyn heating block) for 16 h and concentrated
under reduced pressure. The crude product was purified by flash
chromatography (0−50% EtOAc in hexanes) to obtain 9-
diethylamino-2-hydroxy-5H-benzo-[a]phenoxazin-5-one (7a), which
was purified by flash chromatography (0−50% EtOH in EtOAc) and
6.3 (C-8), 45.2 (CH ), 12.6 (CH ). HRMS (ESI): calcd for
2 3
+
+
79
81
C H BrN O [M + H] , m/z 397.0546 ( Br), 399.0526 ( Br),
found: m/z 397.0540 ( Br), 399.0524 ( Br).
2
0
18
2
2
7
9
81
3
-Cyano-9-diethylamino-5H-benzo[a]phenoxazin-5-one (7f). To
a solution of 9-diethylamino-3-(((trifluoromethyl)sulfonyl)oxy)-5H-
benzo[a]phenoxazin-5-one (7p, 200 mg, 0.43 mmol) in toluene/
EtOH (25 mL, 4:1) were added CuCN (192 mg, 2.14 mmol), SPhos
(14 mg, 34 μmol), Pd (dba) (16 mg, 17 μmol), and Na CO (2.0 M,
crystallized from absolute EtOH in dark green crystals (1.51 g, 4.51
1
2
3
2
3
mmol). Yield: 72%. H NMR (CDCl , 400 MHz): δ 10.41 (s, 1H,
3
5
.0 mL, 10.0 mmol). The reaction mixture was flushed with N and
2
OH), 7.96 (d, J = 8.5 Hz, 1H, H-4), 7.87 (d, J = 2.5 Hz, 1H, H-1),
stirred at 80 °C (DrySyn heating block) overnight. This resulted in a
purple precipitate of crude 3-cyano-9-diethylamino-5H-benzo[a]-
phenoxazin-5-one (7f), which was filtered off, extracted with acetone
(100 mL), concentrated under reduced pressure, and recrystallized
7
6
6
6
.54 (d, J = 9.0 Hz, 1H, H-11), 7.08 (dd, J = 8.5, 2.5 Hz, 1H, H-3),
.76 (dd, J = 9.0, 2.6 Hz, 1H, H-10), 6.60 (d, J = 2.6 Hz, 1H, H-8),
.13 (s, 1H, H-6), 3.47 (q, J = 6.9 Hz, 4H, CH ), 1.16 (t, J = 6.9 Hz,
2
H, CH3). 13C{ H} NMR (CDCl , 101 MHz): δ 181.5 (C-5), 160.5
1
3
from boiling toluene in dark green crystals (112 mg, 0.33 mmol).
(
(
C-2), 151.4 (C-6a), 150.6 (C-9), 146.3 (C-7a), 138.7 (C-12a), 133.7
C-4a), 130.7 (C-11), 127.3 (C-4), 123.81 (C-11a), 123.78 (C-12b),
1
Yield: 76%. H NMR (CDCl , 400 MHz): δ 8.75 (d, J = 8.3 Hz, 1H,
3
H-1), 8.63 (d, J = 1.7 Hz, 1H, H-4), 7.91 (dd, J = 8.3, 1.7 Hz, 1H, H-
2), 7.64 (d, J = 9.2 Hz, 1H, H-11), 6.73 (dd, J = 9.2, 2.7 Hz, 1H, H-
10), 6.50 (d, J = 2.7 Hz, 1H, H-8), 6.43 (s, 1H, H-6), 3.51 (q, J = 7.1
1
4
18.2 (C-3), 109.7 (C-10), 108.1 (C-1), 104.0 (C-6), 95.9 (C-8),
+
4.4 (CH ), 12.4 (CH ). HRMS (ESI): calcd for C H N O [M +
2
3
20 19
2
3
+
H] , m/z 335.1390, found: m/z 335.1405.
-Diethylamino-3-hydroxy-5H-benzo[a]phenoxazin-5-one
1
3
1
Hz, 4H, CH ), 1.29 (t, J = 7.1 Hz, 6H, CH ). C{ H} NMR (CDCl ,
9
2
3
3
9
7
(
7b). In a similar way, 1,7-naphthalenediol (6b, 1.00 g, 6.24 mmol)
was mixed with 5-diethylamino-2-nitrosophenol hydrochloride (1,
.44 g, 6.24 mmol) to form 9-diethylamino-3-hydroxy-5H-benzo[a]-
phenoxazin-5-one (7b), which was purified by flash chromatography
0−20% EtOH in EtOAc) and crystallized from absolute EtOH in
101 MHz): δ 181.5 (C-5), 152.8 (C-6a), 151.8 (C-9), 147.3 (C-7a),
137.5 (C-12a), 135.1 (C-4a), 133.2 (C-2), 131.9 (C-11), 131.8 (C-
12b), 130.6 (C-4), 125.6 (C-11a), 124.7 (C-1), 118.5 (C-3), 113.0
1
(CN), 110.5 (C-10), 105.7 (C-6), 96.3 (C-8), 45.3 (CH ), 12.6
2
+
+
(
(CH ). HRMS (ESI): calcd for C H N O [M + H] , m/z
3
21 18
3
2
1
dark green crystals (1.44 g, 4.30 mmol). Yield: 69%. H NMR
344.1394, found: m/z 344.1407.
1
482
J. Org. Chem. 2021, 86, 1471−1488