50 J . Org. Chem., Vol. 61, No. 1, 1996
J ohnson et al.
chloroform extracts were dried over anhydrous magnesium
sulfate, and the chloroform was removed on a rotary evapora-
tor at aspirator pressure. The residue was an oil which slowly
crystallized. The crystals were purified by washing with cold
diethyl ether under suction filtration to give colorless crystals
(4.78 g, 0.0316 mol, 42%): mp 61-62 °C (lit.10 mp 61-62 °C);
1H NMR (90 MHz, CDCl3) δ 3.80 (s, 3H), 7.20-7.90 (m, 5H);
sh (3.80) nm. Anal. Calcd for C10H12NClO3: C, 52.30; H, 5.27;
N, 6.10; Cl, 15.44. Found: C, 52.19; H, 5.14; N, 6.22; Cl, 15.66.
(Z)-O-Met h yl-4-p h en ylb en zoh yd r oxim oyl Ch lor id e
(1Zd ). A suspension of methyl 4-phenylbenzohydroxamate
(6.00 g, 0.0264 mol) in carbon tetrachloride (100 mL) was
placed in a 250-mL three-neck round-bottomed flask fitted
with a condenser, a calcium chloride drying tube, and a solid
addition funnel (Kontes No. 299400). Phosphorus pentachlo-
ride (5.50 g, 0.0264 mol) was added through the solid addition
funnel with stirring. The mixture was stirred and heated at
65 °C for 24 h. The flask was allowed to cool to room
temperature, and then the contents were poured into cold
water (100 mL). The mixture was cooled to 0 °C and then
filtered under suction to collect part of the product that was
suspended. The carbon tetrachloride layer was washed suc-
cessively with a saturated sodium bicarbonate solution, water,
a 6 M sodium hydroxide solution, and water. The carbon
tetrachloride extract was dried over anhydrous magnesium
sulfate, and the carbon tetrachloride was evaporated on a
rotary evaporator at aspirator pressure. The solid residue was
recrystallized from methanol to yield colorless crystals (6.32
g, 0.0257 mol, 97%): mp 110-111 °C; 1H NMR (90 MHz,
CDCl3) δ 4.10 (s, 3H), 7.30-8.00 (m, 9H); 13C NMR (200
MHz, CDCl3) δ 63.2, 127.0, 127.1, 127.5, 127.9, 128.9, 131.4,
IR (Nujol) 3237, 1655, 1595, 1576 cm-1
.
Meth yl 4-Meth oxyben zoh yd r oxa m a te (2b). This com-
pound was prepared as described for the hydroxamate 2a .
Recrystallization from water gave colorless crystals (60%): mp
102-103 °C (lit.10 mp 102-103 °C); 1H NMR (90 MHz, CDCl3)
δ 3.75 (s, 6H), 6.81-7.74 (dd, J ) 6 Hz, 4H), 10.17 (s, 1H); IR
(Nujol) 3179, 1653, 1574 cm-1
.
Meth yl 4-Meth ylben zoh yd r oxa m a te (2c) This compound
was prepared as described for the hydroxamate 2a . Recrys-
tallization from ether/hexanes gave colorless crystals (73%):
mp 70-71 °C (lit.10 mp 70-71 °C); 1H NMR (90 MHz, CDCl3)
δ 2.40 (s, 3H), 3.80 (s, 3H), 7.10-7.74 (dd, J ) 8 Hz, 4H); IR
(Nujol) 3470, 3407, 1659 cm-1
.
Meth yl 2,6-Dim eth oxyben zoh yd r oxa m a te (2e). Meth-
oxylamine hydrochloride (6.26 g, 0.0750 mol) was placed in a
500-mL three-neck round-bottomed flask fitted with a con-
denser, a calcium chloride drying tube, and an addition funnel.
Triethylamine (15.18 g, 0.1500 mol) in chloroform (HPLC
grade, 10 mL) was added with stirring to the solid methoxy-
lamine hydrochloride. Additional chloroform (10 mL) was
added to rinse the addition funnel. The reaction mixture was
stirred at room temperature for 30 min. A solution of 2,6-
dimethoxybenzoyl chloride (19.37 g, 0.0917 mol) in chloroform
(125 mL) was then added dropwise with stirring. The solution
was stirred for 1 h at room temperature. The mixture was
then washed successively with water, a 10% sodium bicarbon-
ate solution, and a 15% sodium hydroxide solution. The
aqueous layer obtained from the sodium hydroxide extraction
was acidified with concentrated hydrochloric acid at 0 °C and
then extracted with chloroform (2 × 100 mL). The chloroform
extracts were dried over anhydrous magnesium sulfate, and
the chloroform was removed on a rotary evaporator at aspira-
tor pressure. The residue was recrystallized from chloroform/
hexanes to give colorless crystals (6.54 g, 0.0324 mol, 43%):
mp 134-135 °C (lit.11 mp 126-128 °C); 1H NMR (90 MHz,
CDCl3) δ 3.79 (s, 9H), 6.52 (d, J ) 6 Hz, 2H), 7.27 (t, J ) 6 Hz,
1H), 8.51 (s, 1H); 13C NMR (300 MHz, CDCl3) δ 55.8, 64.2,
103.8, 111.8, 131.5, 157.9, 164.0; IR (Nujol) 3192, 1655, 1597
cm-1. Anal. Calcd for C10H13NO4: C, 56.87; H, 6.20; N, 6.63.
Found: C, 56.85; H, 6.20; N, 6.60.
137.0, 140.0, 143.2; IR (Nujol) 1576 cm-1
. Anal. Calcd for
C14H12NOCl: C, 68.44; H, 4.92; N, 5.70; Cl, 14.43. Found: C,
68.52; H, 4.93; N, 5.74; Cl, 14.49.
(E)-O-Met h yl-4-p h en ylb en zoh yd r oxim oyl Ch lor id e
(1Ed ). (Z)-O-Methyl-4-phenylbenzohydroximoyl chloride (2.62
g, 0.0107 mol) was dissolved in benzene (80 mL) and placed
in seven 20-mL quartz tubes. The test tubes were irradiated10
at 254 nm for 6 h. Immediately after irradiation, the benzene
solution was extracted with a saturated solution of potassium
carbonate (3 × 70 mL). The benzene extract was dried over
anhydrous magnesium sulfate, and the benzene was removed
on a rotary evaporator at aspirator pressure. The 1H NMR
spectrum of the oil residue showed that it was a mixture of
the (Z)- and (E)-O-methyl-4-phenylbenzohydroximoyl chlorides
in a ratio of 59:41 respectively. The residue (1.90 g, 0.007 73
mol) was fractionated by column chromatography (190 g of
MN-Kieselgel 60, 70-130 mesh ASTM silica gel). Elution with
benzene/hexanes (1:4) afforded starting material first (0.75 g,
0.0031 mol, 39% based on 1.90 g of the mixture) and then (E)-
O-methyl-4-phenylbenzohydroximoyl chloride (0.56 g, 0.0023
mol, 29% based on 1.90 g of the mixture, 72% recovery based
on the amount of E isomer present in the mixture). Recrys-
tallization from methanol yielded colorless crystals of 1E d
1
Meth yl 4-P h en ylben zoh yd r oxa m a te (2d ). This com-
pound was prepared as described for the hydroxamate
2e. Recrystallization from methanol gave colorless crystals
(0.26 g, 0.0011 mol, 46%): mp 63-64 °C; H NMR (90 MHz,
CDCl3) δ 4.00 (s, 3H), 7.40-8.00 (m, 9H); 13C NMR (300
MHz, CDCl3) δ 63.4, 126.7, 127.1, 128.0, 128.9, 129.6, 129.8,
1
139.9, 143.5, 146.1; IR (Nujol) 1568 cm-1
. Anal. Calcd for
(84%): mp 179-180 °C; H NMR (90 MHz, DMSO-d6) δ 3.80
(s, 3H), 7.40-8.00 (m, 9H); 13C NMR (200 MHz, DMSO-d6) δ
C14H12NOCl: C, 68.44; H, 4.92; N, 5.70; Cl, 14.43. Found: C,
68.33; H, 4.93; N, 5.66; Cl, 14.34.
63.2, 126.6, 126.8, 127.7, 128.1, 129.0, 131.0, 139.0, 143.1,
163.1; IR (Nujol) 3188, 1653 cm-1
. Anal. Calcd for C14H13-
(Z)-O-Met h yl-4-m et h oxyb en zoh yd r oxim oyl Br om id e
(1Zf). The procedure used for this synthesis was that of
J ohnson et al.13 in their synthesis of (Z)-O-methyl-4-nitroben-
zohydroximoyl bromide. The hydroximoyl bromide 1Zf was
recrystallized from hexanes to give colorless crystals (67%):
mp 59-60 °C (lit.12 mp 58-59 °C); 1H NMR (90 MHz, CDCl3)
δ 3.80 (s, 3H), 4.10 (s, 3H), 6.80-7.70 (dd, J ) 8 Hz, 4H); IR
NO2: C, 73.99; H, 5.77; N, 6.16. Found: C, 74.05; H, 5.82; N,
6.18.
(Z)-O-Meth yl-2,6-d im eth oxyben zoh yd r oxim oyl Ch lo-
r id e (1Ze). Methyl 2,6-dimethoxybenzohydroxamate (5.00 g,
0.0237 mol) was placed in
a 250-mL three-neck round-
bottomed flask fitted with a condenser, a calcium chloride
drying tube, and a solid addition funnel. Phosphorus pen-
tachloride (5.19 g, 0.0249 mol) was added through the solid
addition funnel with stirring. The mixture was heated and
stirred for 6 h at 56-60 °C. The liquid product was allowed
to cool to room temperature and was then slowly added to cold
water (40 mL). The precipitate that formed was filtered under
suction, and two additional recrystallizations from methanol
gave the analytical sample (3.08 g, 0.0134 mol, 59%): mp 120-
121°C; 1H NMR (200 MHz, CDCl3) δ 3.80 (s, 6H), 4.10 (s, 3H),
6.56 (d, J ) 6 Hz, 2H), 7.32 (t, J ) 6 Hz, 1H); 13C NMR (200
MHz, CDCl3) δ 55.9, 62.7, 103.9, 112.0, 131.1, 132.1, 158.8;
IR (Nujol) 1594 cm-1; UV-vis (methanol) λmax 285 (3.47), 237
(Nujol) 1607 cm-1
.
Ack n ow led gm en t. We gratefully acknowledge the
financial support of this work by a grant from the
National Science Foundation (RUI Grant no. CHE-921-
1435). We also acknowledge the support for E.C.R. by
a Minority Biomedical Research Support Program grant
from the National Institutes of Health (NIH-MBRS
Grant No. GM08256).
J O950938O