Synthesis of [1,4]benzodioxino[2,3-c and 2,3-d]pyridazinones

Article abstract of DOI:10.1002/jhet.5570390412

Reaction of chloropyridazin-3-one 1, 5 and 10 with catechol in the presence of potassium carbonate gave the corresponding [1,4]benzodioxino[2,3-c and/or 2,3-d]pyridazinones 2, 7, 8 and 11.

Full text of DOI:10.1002/jhet.5570390412

Jul-Aug 2002
Synthesis of [1,4]Benzodioxino[2,3-c and 2,3-d]pyridazinones
685
Hyun-A Chung, Jeum-Jong Kim, Su-Dong Cho,
Sang-Gyeong Lee* and Yong-Jin Yoon*
Department of Chemistry and Research Institute of Natural Sciences
College of Natural Sciences, Gyeongsang National University
Chinju 660-701, Korea
Sung-Kyu Kim
Department of Science Education, Chinju National University of Education
Chinju 660-756, Korea
Received November 7, 2001
Reaction of chloropyridazin-3-one 1, 5 and 10 with catechol in the presence of potassium carbonate gave
the corresponding [1,4]benzodioxino[2,3-c and/or 2,3-d]pyridazinones 2, 7, 8 and 11.
J. Heterocyclic Chem., 39, 685 (2002).
In connection with our research program for the synthe-
(1 equivalent) in the presence of excess potassium carbon-
ate (2.5 equivalents) to afford only 2 in 90% yield (Method
B). Cyclization of 3, in the presence of potassium carbon-
ate (1 equivalent) in acetonitrile, also afforded compound
2 in 93% yield (Method C). According to our observation
by monitoring tlc, compound 3 was formed in the first step
and then cyclized to 2 in the second step. The structures of
2 and 3 were established by ir, nmr and elemental analysis.
In the infrared spectrum of 2, the absorption band of one
amide carbonyl was observed; whereas, the infrared spec-
trum of 3 showed the absorption bands of one amide car-
bonyl and one OH group. The proton magnetic resonance
sis of novel aryl heteroaryl cyclic ether containing
diazines, we needed to synthesize some [1,4]benzodiox-
inopyridazinone derivatives. However, there appear to be
only few related references [1-3]. Ames et al. [1] synthe-
sized 3-chloro[1,4]benzodioxino[2,3-c]pyridazine and
1-chloro[1,4]benzodioxino[2,3-d]pyridazine from cate-
chol and 3, 4, 5 (or 3, 4, 6)-trichloropyridazine in the pres-
ence of potassium carbonate or sodium hydride. Chupp
et al. [2] also synthesised similar derivatives by the ther-
mal fusion without a base. And Lee et al. [3] synthesized
the corresponding [1,4]benzodioxino[2,3-c]pyridazine by
Diels-Alder reaction between 2-vinyl-1,4-benzodioxin and
dibenzyl diazodicarboxylate. However, to the best of our
knowledge, the synthesis of [1,4]benzodioxinopyridazi-
none has not been reported. Therefore, we attempted to
synthesize the corresponding [1,4]benzodioxino[2,3-c, or
2,3-d]pyridazinones from 4,5-dichloro-, 4,5,6-trichloro-
and 4,5-dichloro-6-nitropyridazin-3-ones under basic con-
dition according to Ames's method [1].
spectra of 2 and 3 showed proton signals for CH (δ 3.76
3
for 2; δ 3.77 for 3) as singlet, phenyl (δ 6.90 for 2; δ 7.08
for 3) as multiplet and C6-H for pyridazin-3-one (δ 7.52
for 2; δ 7.37 for 3) as singlet, and also showed the proton
13
signal of OH for 3 at δ 9.60 as singlet. The C nmr spectra
for 2 and 3 also showed signals for the carbons of methyl,
carbonyl and phenyl groups involving the other carbons of
pyridazinone.
Reaction of 1 (1 equivalent) with catechol (1 equivalent)
and one equivalent of potassium carbonate in acetonitrile
at reflux temperature gave 2 (43%), 3 (16%) (Method A).
But, compound 1 (1 equivalent) was reacted with catechol
In order to establish the position of the phenoxy group for
3, compound 3 was dechlorinated with Pd/C/H in methanol
2
to yield 4 in 81% yield. The position of the phenoxy group
for 4 was established by the coupling constant between the

686
H.-A Chung, J.-J. Kim, S.-D. Cho, S.-G. Lee and Y.-J. Yoon
Vol. 39
C4-H and C6-H. According to Katz, et al. [4] and Kweon, et
al. [5], the coupling constant between the C4-H and C6-H
for 5-substituted-pyridazin-3-ones is smaller than that
In the infrared spectrum of 13, we detected the absorp-
tion band of NH . The pmr spectrum of 13 also showed
2
the proton signals of NH at δ 5.85 involving methyl and
2
between C5-H and C6-H for the 4-substituted isomer (J
=
phenyl groups. It is easy to establish the position of the
phenoxy group for 14 by comparing the chemical shift val-
ues of C4-H with that of other 5-substituted derivatives
4,6
about 2Hz, J = about 5Hz). The coupling constant
5,6
between the C4-H and the C6-H for 4 was 2.8 Hz.
Treatment of 5 (1 equivalent) with catechol (1 equivalent)
in the presence of potassium carbonate (0.5 equivalent) in
acetonitrile gave 6 (50%), 7 (14%) and 8 (10%), whereas
reaction of 5 (1 equivalent) with catechol (1 equivalent) in
the presence of excess potassium carbonate (2.5 equiva-
lents) in acetonitrile afforded 7 (54%) and 8 (38%). In order
to confirm the structures of 6 and 2, dechlorination of com-
pound 6 or 7 with Pd/C/H in methanol yielded 4 (91%) or 2
2
(95%) (Method E or H). Compound 8 was also dechlori-
nated with Pd/C/H in methanol to give 9 in 88% yield
2
(method I). According to our observation during this reac-
tion by monitoring tlc, compound 6 was also formed in the
first step and then cyclized to 7 or 8 in the second step. The
infrared spectrum of 6 showed the absorption bands of OH
and amide carbonyl. The structures of 6 - 9 were established
by ir, nmr, elemental analyses and further reactions.
Reaction of 10 (1 equivalent) with catechol (1 equiva-
lent) in the presence of potassium carbonate (0.5 equiva-
lents) in acetonitrile afforded 8 (29%), 11 (28%) and 12
(19%) (Method K), whereas compound 10 (1 equivalent)
was reacted with catechol (1 equivalent) in the presence of
excess potassium carbonate (2.2 equivalents) to give 8
(29%) and 11 (22%) (Method J). In order to establish the
structure, compound 11 was reduced with NH Cl/Fe/
4
CH Cl /H O to give 13 in 90% yield. In order to establish
2
2
2
the structure, dechlorination of 12 with Pd/C/H in
2
methanol gave 6-amino-5-(2-hydroxyphenoxy)-2-
-
methylpyridazin-3-one (14). The structures of 8 and 11 14
were established by ir, nmr and elemental analyses.

Jul-Aug 2002
Synthesis of [1,4]Benzodioxino[2,3-c and 2,3-d]pyridazinones
687
13
terium oxide exchangeable); C nmr (dimethyl sulfoxide-d ): δ
such as 4. The chemical shift value of C4-H is smaller than
that of C6-H for 5-substituted derivatives. According to
our observation by monitoring tlc, the reaction of 10 with
catechol in the presence of potassium carbonate occurred
in two steps; 12 was formed in the first step and then
cyclized to 8 or 11 in the second step.
6
40.5, 116.8, 117.8, 120.1, 121.8, 127.4, 128.5, 140.5, 148.8,
154.3, 158.8 ppm.
Anal. Calcd. for C H N O Cl: C, 52.29; H, 3.59: N, 11.09.
11
9 2 3
Found: C, 52.37; H, 3.52: N, 11.07.
Method B.
Finally, the carbon at the 5-position on the pyridazine
ring is the most reactive site for phenoxide in 4,5-dichloro-
, 4,5,6-trichloro- and 4,5-dichloro-6-nitro-2-alkylpyri-
dazin-3-ones. And multichloropyridazin-3-ones are useful
materials for the synthesis of [1,4]benzodioxino[2,3-c or
2,3-d]pyridazinones.
Further work including the chemical transformation,
complexation and biological activity of novel compounds
is under way in our laboratory.
A mixture of 1 (0.5 g, 2.79 mmoles), catechol (0.3 g, 2.79
mmoles), potassium carbonate (1 g, 6.98 mmoles) and acetoni-
trile (40 mL) was refluxed for 6.5 hours. After cooling to room
temperature, the reaction mixture was filtered and washed with
methylenechloride (10 mL x 5). The combined filtrate was evap-
orated under reduced pressure. The residue was triturated in
water (100 mL). The mixture was filtered, and the residue was
then washed with diethyl ether (20 mL) and dried in air to
afforded 2 in 90% (0.54 g) yield.
Cyclization of 3 to 2.
Method C.
EXPERIMENTAL
A mixture of 3 (0.5 g, 1.98 mmoles), potassium carbonate
(0.27 g, 1.98 mmoles) and acetonitrile (20 mL) was refluxed for
24 hours. After cooling to room temperature, the reaction mixture
was filtered and washed with chloroform (10 mL). The combined
filtrate was evaporated under reduced pressure. The resulting
residue was applied to the top of an open-bed silica gel column (5
x 2.5 cm). The column was eluted with chloroform. Fractions
containing 2 were combined and evaporated under reduced pres-
sure to afford 2 in 93% (0.4 g) yield. This product was identical
with 2 that were prepared by the Method A.
Melting points were determined with a Thomas-Hoover capil-
lary apparatus and are uncorrected. Magnetic resonance spectra
were obtained on a Brüker FTNMR-DRX 500 spectrometer with
chemical shift values reported in δ units (part per million) relative
to an internal standard (tetramethylsilane). Infrared spectral data
were obtained on a Hitachi 270-50 spectrophotometer. Elemental
analyses were performed with a Perkin Elmer 240C. Open-bed
chromatography was carried out on silica gel 60 (70-230 mesh,
Merck) using gravity flow. The column was packed as slurries
with the elution solvent. Compounds 1 [6], 5 [6] and 10 [7] were
prepared according to the reported methods.
2-Methyl-5-(2-hydroxyphenoxy)pyridazin-3-one (4).
Method D.
Reaction of 4,5-Dichloropyridazin-3-one (1) with Catechol.
Method A.
A mixture of Pd/C (0.3 g), 3 (0.5 g, 1.98 mmoles) and
methanol (20 mL) was stirred for 16 hours under a hydrogen
atmosphere (using a toy balloon) at room temperature. After
removal of the catalyst by filtration using Celite 545, the residue
was washed with methanol (10 mL). The solution was evapo-
rated under reduced pressure. The resulting residue was applied
to the top of an open-bed silica gel column (3 x 8 cm). The col-
umn was eluted with chloroform. Fractions containing the prod-
uct were combined and evaporated under reduced pressure. The
residue was triturated in diethyl ether. The mixture was filtered
and dried in air to give 4 in 81% (0.35 g) yield. mp 191-192°; ir
(potassium bromide): 3400-3000, 2970, 2750, 1645, 1595, 1520,
A mixture of 1 (10 g, 56 mmoles), catechol (6.2 g, 56 mmoles),
potassium carbonate (7.7 g, 56 mmoles) and acetonitrile (150 mL)
was refluxed for 23 hours. After cooling to room temperature, the
reaction mixture was filtered and washed with chloroform (10 mL
x 5) and then methanol (10 mL). The combined filtrate was evap-
orated under reduced pressure. The residue was applied to the top
of an open-bed silica gel column (3 x 20 cm). The column was
eluted with chloroform. Fractions containing 2 (R = 0.4, chloro-
f
form/diethyl ether = 9.5:0.5, v/v) were combined and evaporated
under reduced pressure. The resulting residue was recrystallized
from diethyl ether to give 2 in 43% (5.6 g) yield. mp 201-202°; ir
(potassium bromide): 3100, 3050, 2970, 2905, 1680, 1650, 1610,
-1
1470, 1405, 1350, 1290, 1240, 1195, 1030, 850, 780, 740 cm ;
1
H nmr (dimethyl sulfoxide-d ): δ 3.60 (s, 3H), 5.62 (d, 1H, J =
6
-1
1
2.8), 7.10 (m, 4H), 7.95 (d, 1H, J = 2.8), 9.92 ppm (s, OH, deu-
1500, 1395, 1320, 1290, 1145, 970, 760 cm ; H nmr (deuteri-
13
13
terium oxide exchangeable); C (dimethyl sulfoxide-d ): δ 38.8,
ochloroform): δ 3.76 (s, 3H), 6.90 (m, 4H), 7.52 ppm (s, 1H);
C
6
104.9, 117.6, 119.9, 122.3, 127.5, 131.4, 139.2 148.7, 159.1,
160.7 ppm.
nmr (dimethyl sulfoxide-d ): δ 40.1, 116.8, 117.7, 125.5, 125.9,
129.5, 135.2, 140.0, 140.5, 141.2, 155.4 ppm.
6
Anal. Calcd. for C H N O : C, 60.55; H, 4.62: N, 12.84.
Anal. Calcd. for C H N O : C, 61.11; H, 3.73: N, 12.96.
11 10
2 3
11
8 2 3
Found: C, 60.67; H, 4.70: N, 12.89.
Found: C, 61.34; H, 3.61: N, 13.07.
Fractions containing 3 (R = 0.1, chloroform/diethyl ether =
f
Method E.
9.5:0.5, v/v) were combined and evaporated under reduced pres-
sure. The resulting residue was recrystallized from
chloroform/diethyl ether to give 3 in 16% (2.3 g) yield. mp 206-
207°; ir (potassium bromide): 3400-3000, 1638, 1515, 1460,
A mixture of Pd/C (0.2 g), 6 (0.15 g, 0.52 mmoles) and
methanol (15 mL) was allowed to stirr for 22 hours under a
hydrogen atmosphere (using a toy balloon) at room temperature.
After removal of the catalyst by filtration using Celite 545, the
residue was washed with methanol (10 mL). The solution was
-1
1
1390, 1290, 1240, 750 cm ; H nmr (deuteriochloroform): δ
3.77 (s, 3H), 7.08 (m, 4H), 7.37 (s, 1H), 9.60 ppm (s, OH, deu-

688
H.-A Chung, J.-J. Kim, S.-D. Cho, S.-G. Lee and Y.-J. Yoon
Vol. 39
evaporated under reduced pressure. The resulting residue was
applied to the top of an open-bed silica gel column (3 x 8 cm).
The column was eluted with chloroform. Fractions containing the
product were combined and evaporated under reduced pressure.
The residue was triturated in diethyl ether. The mixture was fil-
tered and dried in air to give 4 in 91% (0.1 g) yield. This product
was identical with 4 that were prepared by the Method D.
n-hexane/ethyl acetate (5:1, v/v). Fractions containing 8 (R = 0.
f
4, n-hexane/ethyl acetate = 1:1, v/v) were combined and evapo-
rated under reduced pressure. The resulting residue was recrystal-
lized from diethyl ether to give 8 in 38% (0.45 g) yield.
Fractions containing 7 (R = 0.35, n-hexane/ethyl acetate = 1:1,
f
v/v) were combined and evaporated under reduced pressure. The
resulting residue was recrystallized from diethyl ether to give 7 in
54% (0.63 g) yield.
Reaction of 4,5,6-Trichloro-2-methylpyridazin-3-one (5) with
Catechol.
Dechlorination of a Mixture of 7 or 8.
Method F.
Method H.
A mixture of Pd/C (0.2 g), 7 (0.3 g, 1.20 mmoles) and
methanol (20 mL) was stirred for 3 hours under a hydrogen
atmosphere (using a toy balloon) at room temperature. After
removal of the catalyst by filtration using Celite 545, the residue
was washed with methanol (10 mL). The solution was evapo-
rated under reduced pressure to give 2 in 95% (0.25 g) yield. This
product was identical with 2 that were prepared by the Method A.
A mixture of 5 (0.7 g, 3.28 mmoles), catechol (0.36 g, 3.28
mmoles), potassium carbonate (0.23 g, 1.64 mmoles) and acetoni-
trile (15 mL) was stirred for 40 minutes at room temperature. The
mixture was filtered and washed with methylene chloride (10 mL x
3). The combined filtrate was evaporated under reduced pressure.
The residue was applied to the top of an open-bed silica gel column
(2.5 x 12 cm). The column was eluted with methylene chloride.
Fractions containing 6 (R = 0.2, methylene chloride) were com-
f
Method I.
bined and the solvent was evaporated off under reduced pressure.
The resulting residue was recrystallized from diethyl ether to give
6 in 50% (0.3 g) yield. mp 154-155°; ir (potassium bromide):
3400-3000, 2960, 2875, 1658, 1590, 1505, 1300, 1275, 1170,
A mixture of Pd/C (0.2 g), 8 (0.2 g, 0.80 mmoles) and
methanol (20 mL) was stirred for 2.6 hours under a hydrogen
atmosphere (using a toy balloon) at room temperature. After
removal of the catalyst by filtration using Celite 545, the residue
was washed with methanol (10 mL). The solution was evapo-
rated under reduced pressure to give 9 in 88% (0.15 g) yield. mp
212-213°; ir (potassium bromide): 3150, 3050, 2950, 1680, 1640,
-1
1
1010, 990, 770 cm ; H nmr (dimethyl sulfoxide-d ): δ 3.60 (s,
6
3H), 6.83 (m, 4H), 9.63 ppm (s, OH, deuterium oxide exchange-
13
able);
C nmr (dimethyl sulfoxide-d ): δ 39.0, 116.6, 117.7,
6
118.9, 123.9, 124.5, 135.2, 143.2, 146.7, 149.5, 154.3 ppm.
Anal. Calcd. for C H N O Cl : C, 46.02; H, 2.81: N, 9.76.
-1
1
1510, 1480, 1295, 780, 760 cm ; H nmr (deuteriochloroform +
11
8
2
3
2
dimethyl sulfoxide-d ): δ 3.50 (s, 3H), 6.30 (s, 1H), 6.95 ppm (m,
Found: C, 46.10; H, 2.91: N, 9.81.
6
13
4H); C nmr (deuteriochloroform + dimethyl sulfoxide-d ): δ
Fractions containing 7 or 8 were also combined and the solvent
evaporated off under reduced pressure. The resulting residue was
recrystallized from diethyl ether to give 7 (14%) or 8 (10 %)
yield, respectively. Compound 7: mp 225-226°; ir (potassium
bromide): 3100, 3050, 1690, 1640, 1600, 1500, 1390, 1310,
6
38.8, 109.9, 116.7, 117.0. 124.8, 125.3, 138.5, 139.6, 141.0,
146.3, 161.1 ppm.
Anal. Calcd. for C H N O : C, 61.11; H, 3.73: N, 12.96.
11
8 2 3
Found: C, 61.22; H, 3.81: N, 13.01.
-1
1
1265, 1245, 1145, 1060, 990, 920, 770 cm ; H nmr (deuteri-
Reaction of 4,5,-Dichloro-6-nitropyridazin-3-one (10) with
Catechol.
13
ochloroform): δ 3.74 (s, 3H), 6.95 ppm (m, 4H); C nmr (deu-
teriochloroform): δ 40.7, 117.5, 118.0, 126.3, 126.7, 130.2,
136.6, 137.9, 140.6, 141.1, 155.0 ppm.
Method J.
Anal. Calcd. for C H N O Cl: C, 52.71; H, 2.82: N, 11.18.
11
7 2 3
A mixture of 10 (1.0 g, 4.46 mmoles), catechol (0.5 g, 4.46
mmoles), potassium carbonate (1.36 g, 9.81 mmoles) and ace-
tonitrile (40 mL) was stirred for 21 hours at room temperature.
After filtering the mixture, the filtrate was evaporated under
reduced pressure. The residue was applied to the top of an open-
bed silica gel column (2.5 x 15 cm). The column was eluted with
methylene chloride/n-hexane (1:1, v/v). Fractions containing 11
Found: C, 52.81; H, 2.96: N, 2.88. These found values do not
match calculated. If these are in error please replace with actual
values at the galley proof stage. Please be advised that editorial
policy requires a value within ± 0.4 of calculated for carbon and
hydrogen.
Compound 8: mp 219-220°; ir (potassium bromide): 3100,
-1
2970, 1680, 1659, 1630, 1510, 1445, 1300, 1070, 920, 770 cm ;
(R = 0. 4, methylene chloride) were combined and the solvent
f
1
H nmr (deuteriochloroform): δ 3.70 (s, 3H), 7.10 ppm (m, 4H) ;
C nmr (deuteriochloroform): δ 35.1, 112.1, 112.3, 112.7, 120.2,
121.0, 133.5, 134.5, 135.5, 137.4, 153.0 ppm.
evaporated off under reduced pressure. The resulting residue was
recrystallized from n-hexane to give 11 in 22% (0.25 g) yield. mp
261-262°; ir (potassium bromide): 3125, 3050, 2905, 1695, 1640,
1605, 1560, 1535, 1505, 1390, 1360, 1290, 1250, 1160, 1070,
13
Anal. Calcd. for C H N O Cl: C, 52.71; H, 2.82: N, 11.18.
11
7 2 3
-1
1
Found: C, 52.78; H, 2.90: N, 11.23.
1010, 875, 810 cm ; H nmr (dimethyl sulfoxide-d ): δ 3.71 (s,
6
13
3H), 7.10 ppm (m, 4H); C nmr (dimethyl sulfoxide-d ): δ 40.3,
6
Method G.
117.1, 117.2, 126.3, 126.6, 134.8, 136.3, 138.7, 139.3, 139.9,
154.1 ppm.
A mixture of 5 (1.0 g, 4.68 mmoles), catechol (0.52 g, 4.68
mmoles), potassium carbonate (1.62 g, 11.71 mmoles) and ace-
tonitrile (50 mL) was stirred for 40 minutes at room temperature.
The reaction mixture was then filtered and washed with chloro-
form (30 mL). The combined filtrate was evaporated under
reduced pressure. The residue was applied to the top of an open-
bed silica gel column (2.5 x 30 cm). The column was eluted with
Anal. Calcd. for C H N O : C, 50.58; H, 2.70; N, 16.09.
11
7 3 5
Found: C, 50.61; H, 2.81: N, 16.12.
Fractions containing 8 (R = 0.35, methylene chloride) were
f
combined and evaporated under reduced pressure. The resulting
residue was recrystallized from diethyl ether to give 8 in 29%
(0.32 g).

Jul-Aug 2002
Method K.
Synthesis of [1,4]Benzodioxino[2,3-c and 2,3-d]pyridazinones
689
Anal. Calcd. for C H N O : C, 57.14; H, 3.92; N, 18.17.
11
9 3 3
Found: C, 57.23; H, 4.02: N, 18.24.
A mixture of 10 (1.0 g, 4.46 mmoles), catechol (0.5 g, 4.46
mmoles), potassium carbonate (0.3 g, 2.23 mmoles) and acetoni-
trile (40 mL) was stirred for 3.6 hours at room temperature. After
filtering the mixture, the filtrate was evaporated under reduced
pressure. The residue was applied to the top of an open-bed silica
gel column (2.5 x 15 cm). The column was eluted with methylene
4-Amino-2-methyl-5-(2-hydroxyphenoxy)pyridazin-1-one (14).
A mixture of Pd/C (0.2 g), 12 (0.3 g, 1.01 mmoles) and
methanol (20 mL) was stirred for 14 hours under a hydrogen
atmosphere (using a toy balloon) at room temperature. After
removal of the catalyst by filtration using Celite 545, the
residue was washed with methanol (10 mL). The solution was
evaporated under reduced pressure. The residue was applied
to the top of an open-bed silica gel column (2.5 x 8 cm). The
column was eluted with ethyl acetate. Fractions containing the
product were combined and evaporated under reduced pres-
sure to give 14 in 43% (0.1 g) yield. mp 213-214°; ir (potas-
sium bromide) 3450, 3350, 3230, 3060, 2950, 1660, 1630,
chloride/n-hexane (1:1, v/v). Fractions containing 11 (R = 0. 4,
f
methylene chloride) were combined and evaporated under
reduced pressure. The resulting residue was recrystallized from
n-hexane to give 11 in 28% (0.32 g) yield.
Fractions containing 8 (R = 0.35, methylene chloride) were
f
combined and evaporated under reduced pressure. The resulting
residue was recrystallized from diethyl ether to give 8 in 29%
(0.32 g) yield.
-1
1
1580, 1500, 1465, 1330, 1265, 1205, 760 cm
; H nmr
Fractions containing 12 (R = 0.22, methylene chloride) were
f
(dimethyl sulfoxide-d ): δ 3.47 (s, 3Η), 5.53 (s, NH , deu-
6
2
combined and evaporated under reduced pressure. The resulting
residue was recrystallized from ethyl acetate/n-hexane (1:2, v/v )
to give 12 in 19 % (0.25 g) yield. mp 131-133°; ir (potassium bro-
mide): 3550, 3500-3100 (broad doublet), 3050, 1650, 1580,
terium oxide exchangeable), 5.81 (s, 1H), 7.01 (m, 4Η), 9.80
ppm (s, OH, deuterium oxide exchangeable); C nmr
13
(dimethyl sulfoxide-d ): δ 38.3, 101.8, 117.6, 119.9, 122.4,
6
126.9, 140.0, 148.3, 148.8, 153.3, 154.0 ppm.
-1
1490, 1465, 1350, 1270, 1230, 1170, 1090, 1050, 760, 750 cm ;
Anal. Calcd for C H N O : C, 56.65; H, 4.75; N, 18.02.
1
11 11 3 3
H nmr (dimethyl sulfoxide-d ): δ 3.67 (s, 3H), 6.94 (m, 4H),
6
Found: C, 56.70; H, 4.82: N, 18.14.
13
9.74 ppm (s, OH, deuterium oxide exchangeable); C nmr
(dimethyl sulfoxide-d ): δ 38.9, 115.6, 116.6, 117.8, 119.2, 124.8,
143.0, 145.0, 146.7, 150.0, 154.7 ppm.
6
Acknowledgments.
This work was supported by the Brain Korea 21 project.
Anal. Calcd. for C H N O Cl: C, 44.39; H, 2.71: N, 14.12.
11
8 3 5
Found: C, 44.42; H, 2.83: N, 14.23.
REFERENCES AND NOTES
4-Amino-2-methyl[1,4]benzodioxino[2,3-d]pyridazin-1-one
(13).
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534 (1975).
[2] J. P. Chupp, C. R. Jones and M. L. Dahl, J. Heterocyclic
Chem., 30, 789 (1993).
[3] T. V. Lee, A. J. Leigh and C. B. Chapleo, Tetrahedron, 46,
921 (1990).
[4] D. Z. Katz, D. S. Wise and L. B. Towsend, J. Heterocyclic
Chem, 20, 369 (1983).
[5] D. H. Kweon, Y. J. Kang, H. A Chung and Y. J. Yoon, J.
Heterocyclic Chem., 35, 819 (1998).
[6] S. D. Cho, W. Y. Choi and Y. J. Yoon, J. Heterocyclic
Chem., 35, 1579 (1996).
A mixture of 11 (0.3 g, 1.15 mmoles), iron powder (0.5 g),
ammonium chloride (1.2 g), water (20 mL) and methylene chlo-
ride (20 mL) was refluxed for 2 hours. After cooling at room tem-
perature, the mixture was applied to the top of an open-bed silica
gel column (2.5 x 10 cm). The column was eluted with methylene
chloride. Fractions containing the product were combined and
evaporated under reduced pressure to give 13 in 90% (0.24 g)
yield. mp 260-261°; ir (potassium bromide) 3500, 3290, 3200,
2940, 2920, 1690, 1620, 1550, 1510, 1270, 1190, 1125, 980, 760
-1
1
cm ; H nmr (dimethyl sulfoxide-d ): δ 3.42 (s, 3H), 5.85 (s,
6
13
2H, deuterium oxide exchangeable), 7.09 ppm (m, 4H) ; C nmr
(dimethyl sulfoxide-d ): δ 39.0, 117.7, 118.0, 126.5, 126.8,
132.8, 134.7, 141.0, 141.6, 142.1, 153.3 ppm.
[7] D. H. Kweon, S. D. Cho, S. K. Kim, J. W. Chung and Y. J.
Yoon, J. Heterocyclic Chem., 33, 1915 (1996).
6