2
-Substituted Benzoxazoles from R-Oxo-oximes
cis-1,2-Na p h th a len ed ion e 1-(O-m eth yloxim e) (21): yel-
167.6. Anal. Calcd for C13H10BrNO: C, 56.55; H, 3.65; N, 5.07.
Found: C, 56.39; H, 3.54; N, 4.73.
1
low oil; yield 8%; H NMR (CDCl
3
) δ 4.31 (s, 3H), 6.35 (d, J )
1
3
1
(
1
0.0 Hz, 1H), 7.33-7.44 (m, 4 H), 8.06-8.11 (m, 1H); C NMR
CDCl ) δ 65.8, 124.5, 128.3, 128.9, 129.6, 129.7, 129.9, 131.6,
43.0, 143.6, 179.0; HRMS (EI) calcd for C11 NO 187.0633,
7-Br om o-2-p h en yln a p h th o[1,2-d ][1,3]oxa zole (20c): 1.5
h, 54-60 °C; reddish needles after chromatography on silica
gel using hexanes/methylene chloride as eluant (100/1-5/1,
3
H
9
2
found 187.0640.
tr a n s-1,2-Na p h th a len ed ion e 1-(O-m eth yloxim e) (22):
v/v) and recrystallization from ethanol/methylene chloride (1/
1
1); yield 41%; mp 175-176 °C; H NMR (CDCl
3
) δ 7.51-7.57
1
oil; yield 7%; H NMR (CDCl
Hz, 1H), 7.35-7.47 (m, 4H), 8.67-8.70 (m, 1H); C NMR
CDCl ) δ 65.2, 126.9, 127.6, 129.8, 130.2, 130.9, 131.2, 131.9,
44.6, 145.2, 184.5; HRMS (EI) calcd for C11 NO 187.0633,
found 187.0633.
-Meth yln a p h th o[1,2-d ][1,3]oxa zole (18b): 17 h, 25 °C;
3
) δ 4.36 (s, 3H), 6.41 (d, J ) 9.9
(m, 3H), 7.66-7.75 (m, 3H), 8.11 (d, J ) 1.8 Hz, 1H), 8.26-
1
3
13
8.34 (m, 2H), 8.44 (d, J ) 8.9 Hz, 1H); C NMR (CDCl ) δ
3
(
1
3
112.0, 119.3, 124.0, 124.9, 125.0, 127.2, 127.4, 128.9, 130.2,
130.6, 131.3, 132.3, 137.7, 148.1, 162.7; HRMS (FAB) calcd
H
9
2
for C17H11BrNO 324.0018, found 324.0024.
2
Syn t h esis of 9,10-P h en a n t h r en ed ion e 9-(O-b en zyl-
oxim e) (13, tw o isom er s). A mixture of phenanthraquinone
12 (0.92 g, 4.4 mmol), O-benzylhydroxylamine hydrochloride
(0.80 g, 4.4 mmol), pyridine (0.93 mL), and EtOH (25 mL) was
stirred at 73-75 °C for 1 h. EtOH and pyridine were removed
under reduced pressure at 60-70 °C. About 15 mL of water
was added into the residue, the mixture was extracted with
ether (3 × 60 mL), and the combined extracts were dried over
colorless oil after chromatography on silica gel using hexanes/
1
methylene chloride as eluant (100/1-7/1, v/v); yield 40%; H
NMR (CDCl ) δ 2.72 (s, 3H), 7.47-7.53 (m, 1H), 7.59-7.65 (m,
3
2
(
1
H), 7.72 (d, J ) 8.9 Hz, 1H), 7.92 (d, J ) 8.1 Hz, 1H), 8.44
13
br d, J ) 8.4 Hz, 1H); C NMR (CDCl
25.0, 125.2, 126.2, 126.8, 128.4, 130.9, 136.5, 148.0, 162.8.
Anal. Calcd for C12 NO: C, 78.67; H, 4.96; N, 7.65. Found:
C, 78.40; H, 5.09; N, 7.89.
-Vin yln a p h th o[1,2-d ][1,3]oxa zole (18c): 1.5 h, 54-60
C; colorless oil after chromatography on silica gel using
hexanes/ethyl acetate as eluant (100/1-6/1, v/v); yield 32%;
3
) δ 14.6, 110.6, 121.8,
H
9
4
anhydrous MgSO . Evaporation of the solvent under reduced
2
pressure and purification by column chromatography on silica
gel using hexane/AcOEt (12/1-6/1, v/v) as eluent gave two
isomers of 9,10-phenanthrenedione 9-(O-benzyloxime) 13.
°
1
H NMR (CDCl
17.7, 1.0 Hz, 1H), 6.86 (dd, J ) 17.7, 11.1 Hz, 1H), 7.51-
.57 (m, 1H), 7.63-7.69 (m, 1H), 7.76 (d, J ) 9.0 Hz, 1H), 7.80
d, J ) 9.0 Hz, 1H), 7.96 (d, J ) 8.4 Hz, 1H), 8.49 (br d, J )
3
) δ 5.85 (dd, J ) 11.1, 1.0 Hz, 1H), 6.49 (dd, J
Isomer 1: yellow solid (0.28 g, 0.89 mmol, 20%), mp 77-78
1
)
7
(
8
1
°C; H NMR (300 MHz, DMSO-d
6
) δ 5.47 (s, 2H), 7.35-7.62
(m, 8H), 7.76-7.82 (m, 1H), 7.96-8.06 (m, 2H), 8.24-8.32 (m,
2H); 13C NMR (75 Hz, DMSO-d
) δ 79.6, 123.5, 124.1, 125.5,
128.1, 129.0, 128.5, 128.6, 128.6, 128.8, 130.1, 131.0, 131.3,
131.7, 134.4, 136.1, 136.9, 146.7, 182.3. Anal. Calcd for C21
NO : C, 80.48; H, 4.82; N, 4.47. Found: C, 80.12; H, 4.89; N,
4.45. Isomer 2: yellow solid (0.7 g, 2.23 mmol, 51%), mp 73-
6
1
3
.1 Hz, 1H); C NMR (CDCl
25.4, 126.4, 127.1, 128.6, 131.1, 137.1, 147.6, 161.4; HRMS
NO 195.0684, found 195.0682.
-(4-Nitr op h en yl)n a p h th o[1,2-d ][1,3]oxa zole (18d ): 1.5
3
) δ 110.7, 122.0, 123.8, 124.1,
15
H -
(
EI) calcd for C13
2
H
9
2
1
h, 54-60 °C; yellow prisms after chromatography on silica gel
6
75 °C; H NMR (300 MHz, DMSO-d ) δ 5.51 (s, 2H), 7.35-
using hexanes/ethyl acetate as eluant (100/1-10/1, v/v); yield
7.63 (m, 8H), 7.81 (t, J ) 7.8 Hz, 1H), 8.01 (d, J ) 7.8 Hz,
1
13
2
1
4%; mp 215-217 °C; H NMR (CDCl
3
) δ 7.60 (t, J ) 7.9 Hz,
1H), 8.27-8.31 (m, 2H), 8.56 (d, J ) 8.1 Hz, 1H); C NMR
H), 7.72 (t, J ) 7.3 Hz, 1H), 7.76 (d, J ) 8.8 Hz, 1H), 7.88 (d,
3
(75 Hz, CDCl ) δ 79.6, 123.4, 124.1, 125.6, 128.2, 128.4, 128.5,
J ) 8.8 Hz, 1H), 8.00 (d, J ) 8.1 Hz, 1H), 8.39 (d, J ) 8.8 Hz,
H), 8,49 (d, J ) 8.8 Hz, 2H), 8.59 (d, J ) 8.1 Hz, 1H); 13
NMR (CDCl ) δ 110.8, 122.2, 124.2, 125.9, 126.6, 127.5, 127.9,
28.7, 131.3, 133.0, 137.7, 148.6, 149.0, 159.8; HRMS (EI) calcd
for C17 290.0691, found 290.0693.
128.6 (2C), 128.8, 130.6, 131.0, 131.3, 131.7, 134.7, 136.1,
136.7, 147.0, 184.4. Anal. Calcd for C21 : C, 80.48; H,
2
C
H15NO
2
3
4.82; N, 4.47. Found: C, 80.36; H, 4.85; N, 4.31.
1
Syn th esis of P h en a n th r o[9,10-d ]oxa zol-2-yl-p h en yl-
m eth a n on e (25). A mixture of the starting oxime 9 (0.223 g,
1.00 mmol), 1-(2-oxo-2-phenyl-ethyl)-pyridinium bromide 24
(0.306 g, 1.1 mmol), and triethylamine (0.35 mL) was refluxed
in methanol for 1.5 h. The yellow precipitate was filtered and
washed with methanol and hexane to give the product (0.295
10 2 3
H N O
Gen er a l P r oced u r e for P r ep a r a tion of 7-Br om on a p h -
th o[1,2-d ][1,3]oxa zoles (20a -c). A mixture of the starting
oxime (3.97 mmol), anhydrous potassium carbonate (1.02 g,
7
.40 mmol), the electrophile (6.64 mmol, 15a , 15e, or 15f), and
1
9
dry DMF (30 mL) was stirred at 54-60 °C for 1.5 h under
nitrogen. The mixture was cooled to 20 °C, and water (70 mL)
was added slowly. The resultant solution was extracted with
ether (3 × 60 mL), and the combined extracts were dried over
g, 0.91 mmol): yield 91%; mp 188-189 °C (lit. 201-203 °C);
1
H NMR (CDCl
3
) δ 7.61 (t, J ) 7.1 Hz, 2H), 7.66-7.77 (m,
5H), 8.41-8.44 (m, 1H), 8.59-8.62 (m, 1H), 8.65-8.70 (m, 4H);
1
3
C NMR (CDCl
127.0, 127.6, 127.8, 128.2, 128.5, 129.4, 130.9, 131.1, 134.0,
2
135.0, 135.3, 146.2, 156.8, 179.3. Anal. Calcd for C22H13NO :
3
) δ 120.5, 122.2, 123.0, 123.5, 123.7, 125.9,
4
anhydrous MgSO . Evaporation of the solvent in vacuo and
purification of the residue by column chromatography on silica
gel gave the corresponding products.
C, 81.72; H, 4.05; N, 4.33. Found: C, 81.40; H, 4.01; N, 4.28.
7
-Br om on a p h th o[1,2-d ][1,3]oxa zole (20a ): 1.5 h, 54-60
C; colorless prisms after chromatography on silica gel using
hexanes/ethyl acetate as eluant (100/1-6/1, v/v); yield 54%;
Ack n ow led gm en t. We thank National Institute of
Advanced Industrial Science and Technology, J apan for
online Integrated Spectral Data Base System for Or-
ganic Compounds.
°
1
mp 111-112 °C; H NMR (CDCl
3
) δ 7.68-7.78 (m, 3H), 8.12
(
1
1
d, J ) 2.7 Hz, 1H), 8.23 (s, 1H), 8.37 (dd, J ) 8.6, 3.8 Hz,
1
3
H); C NMR (CDCl
3
) δ 112.1, 119.4, 123.7, 125.0, 125.5,
Su p p or tin g In for m a tion Ava ila ble: Crystallographic
data (excluding structure factors) for structures 4, 5, and 18a
have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication numbers CCDC
30.4, 130.5, 132.2, 135.5, 147.5, 151.8. Anal. Calcd for C11
BrNO: C, 53.25; H, 2.44; N, 5.65. Found: C, 53.11; H, 2.27;
N, 5.65.
6
H -
7
-Br om o-2-eth yln a p h th o[1,2-d ][1,3]oxa zole (20b): 1.5 h,
2
04291, 204292, and 210734. Copies of the data can be
5
4-60 °C; pale yellow prisms after chromatography on silica
obtained, free of charge, on application to CCDC, 12 Union
Rd., Cambridge CB2 1EZ, U.K (Fax 44(0) 1223-336033) or
e-mail deposit@ccdc.cam.ac.uk.
gel using hexanes/ethyl acetate as eluant (100/1-5/1, v/v); yield
1
3
3
4%; mp 59-61 °C; H NMR (CDCl
3
) δ 1.50 (t, J ) 7.6 Hz,
H), 3.06 (q, J ) 7.6 Hz, 2H), 7.61 (d, J ) 8.7 Hz, B part of AB
system, 1H), 7.64 (d, J ) 8.7 Hz, A part of AB system, 1H),
J O026771Y
7
(
.68 (dd, J ) 8.7, 1.8 Hz, 1H), 8.07 (d, J ) 1.8 Hz, 1H), 8.32
1
3
dt, J ) 8.7, 0.6 Hz, 1H); C NMR (CDCl
3
) δ 11.3, 22.3, 111.8,
(19) Awad, W. I.; Salih, Z. S.; Aiube, Z. H. J . Chem. Soc., Perkin
1
18.9, 123.7, 124.1, 124.7, 130.0, 130.4, 132.0, 136.6, 148.0,
Trans. 1 1977, 1280-1282.
J . Org. Chem, Vol. 68, No. 23, 2003 9099