Facile Synthesis of Benzo[ d ]azol-2(3 H)-ones Using 2-Phenoxycarbonyl-4,5-dichloropyridazin-3(2 H)-one as Green CO Source

Article abstract of DOI:10.1055/s-0034-1378783

Developing eco-friendly, stable, and easy-to-handle acyl sources is of great importance in synthetic and green chemistry. This study describes the synthesis of benzo[d]azol-2(3H)-ones such as benzo[d]thiazol-2(3H)-ones, benzo[d]oxazol-2(3H)-ones, and benzo[d]imidazol-2(3H)-ones using 2-phenoxycarbonyl-4,5-dichloropyridazin-3(2H)-one in one pot. The reaction reported is carried out under neutral or acidic conditions in the presence of zinc or sodium bicarbonate to give the corresponding heterocycles in good to excellent yields. The reaction uses a solid stable carbonyl source that is a recyclable functional-group carrier, pyridazin-3(2H)-one.

Full text of DOI:10.1055/s-0034-1378783

SYNLETT
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©
Georg Thieme Verlag Stuttgart · New York
2015, 26, 1985–1990
1985
letter
Synlett
K. E. Ryu et al.
Letter
Facile Synthesis of Benzo[d]azol-2(3H)-ones Using 2-Phenoxycar-
bonyl-4,5-dichloropyridazin-3(2H)-one as Green CO Source
Ki Eun Ryua
O
O
Bo Ram Kima
Gi Hyeon Sunga
Hyo Jae Yoon*b
C
Cl
PhO
N
N
ZH
Z
Cl
R
R
C O
Yong-Jin Yoon*a
– pyridazinone (reuse)
PhOH
N
H
NH2
–
a
Department of Chemistry & Research Institute of Natural Science,
Z = S, O, NH
R = H, X, NO2, Me, CF3, OMe
Gyeongsang National University, Jinju, 660-701, South Korea
yjyoon@gnu.ac.kr
b
Department of Chemistry, Korea University, Seoul, 136-701,
South Korea
hyoon@korea.ac.kr
Received: 01.05.2015
Accepted after revision: 12.06.2015
Published online: 23.07.2015
triphosgene,7 alkyl chloroformate,8 urea,9 carbonyl sul-
10
11
12
fide, carbon monoxide, carbon dioxide, and 1,1′-car-
13
DOI: 10.1055/s-0034-1378783; Art ID: st-2015-u0333-l
bonyldimidazole. These methods often require an expen-
sive catalyst, gaseous acyl source, moisture-sensitive and/or
toxic reagents, complicated reaction steps, long reaction
time, and/or high reaction temperature. Herein we demon-
strate a facile and efficient method for the synthesis of ben-
zo[d]azol-2(3H)-ones using an efficient CO source, 2-aryl-
oxy (or alkoxy)carbonyl-4,5-dichloropyridazin-3(2H)-ones
Abstract Developing eco-friendly, stable, and easy-to-handle acyl
sources is of great importance in synthetic and green chemistry. This
study describes the synthesis of benzo[d]azol-2(3H)-ones such as ben-
zo[d]thiazol-2(3H)-ones, benzo[d]oxazol-2(3H)-ones, and benzo[d]im-
idazol-2(3H)-ones using 2-phenoxycarbonyl-4,5-dichloropyridazin-
3(2H)-one in one pot. The reaction reported is carried out under neutral
or acidic conditions in the presence of zinc or sodium bicarbonate to
give the corresponding heterocycles in good to excellent yields. The re-
action uses a solid stable carbonyl source that is a recyclable functional-
group carrier, pyridazin-3(2H)-one.
(Scheme 1). The method reported here allowed us to pre-
pare benzo[d]thiazol-2(3H)-ones, benzo[d]oxazol-2(3H)-
ones, and benzo[d]imidazol-2(3H)-ones via aryloxy (or
alkoxy)carbonylation of the amino group and then intramo-
lecular cyclization in a one-pot synthesis and in moderate
to excellent yields.
Key words carbonylation, green chemistry, heterocycles, medicinal
chemistry, ring closure
2
-Aryloxy (or alkoxy)carbonyl-4,5-dichloropyridazin-
Benzo[d]azol-2(3H)-ones have been extensively studied
3(2H)-one derivatives are easily prepared from commercial
available 4,5-dichoropyridazin-3(2H)-one. Yoon et al.
in the past few decades as a central functional group for de-
1,2
veloping a variety of drugs and pesticides. Figure 1 shows
some examples of drugs and pesticides, the core structure
of which is based on benzo[d]azol-2(3H)-one moi-
demonstrated the utility of these heterocycles as synthetic
auxiliaries.1
4,15
2-Aryloxy (or alkoxy)carbonyl-4,5-dichloro-
pyridazin-3(2H)-ones involve an amide bond [–NC(=O)] and
an ester bond [–C(=O)OR, Scheme 1]. These bonds have dif-
1
f,m,s,u,3–6
ety.
Benzo[d]azol-2(3H)-one derivatives are commonly pre-
ferent reactivity for some nucleophiles (–NH , –OH, and –
2
pared by the reaction of 2-mercaptoanilines, 2-hydoxyani-
lines, and 1,2-diaminobenzenes with C=O sources such as
SH). In particular, the amide bond is highly chemoselective
against the amino group.15 2-Aryloxy (or alkoxy)carbonyl-
Cl
Cl
ZH
intramolecular
ZH
R1
cyclization
Z
acylation
R1
O
R1
N
O
O
N
NH
2
–
pyridazinone
– R OH
N
H
NH2
R2
R2
O
O
O
benzo[d]azol-2(3H)-one
Z = S, O, NH
R2 = akyl, aryl
1
R = H, X, NO2,
Me, CF3, OMe
Scheme 1 Newly designed method for synthesis of benzo[d]azol-2(3H)-ones using 2-aryloxy (or alkoxy)carbonyl-4,5-dichloropyridazin-3(2H)-ones
©
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K. E. Ryu et al.
Letter
S
O
N
S
N
O
O
N
Cl
O
N
H
Cl
O
N
Paraflex
Tiaramide
oral drug for the
treatment of asthma)
(treat muscle spasms/pain)
(
N
3
-[2-(azepan-1-yl)ethyl]-6-
propylbenzo[d]thiazol-2(3H)-one
alpha1-receptor)
OH
(
N
O
N
O
O
O
Ph
OH
N
N
H
NH
N
O
N
N-[2-(3-hydroxypyrrolidin-1-yl)-1-phenylethyl]-N-methyl-2-(2-oxo-
,3-dihydrobenzo[d]oxazol-5-yl)acetamide
2
N-[(1-butylpiperidin-4-yl)methyl]-2-oxo-3-propyl-2,3-dihydro-1H-
benzo[d]imidazole-1-carboxamide
(OP2 agonist)
(5-HT4 receptor agonists)
Cl
O
N
O
O
S
H
O
HN
N
S
S
O
O
P
O
O
HO
O
Phosalone
insecticide and acaricide)
Sibenadet
(beta-adrenergic agonist)
(
Figure 1 Some biological activities of benzo[d]azol-2(3H)-ones (bold structures)
Table 1 Base Screening for One-Pot Synthesis of Benzo[d]oxazol-
2
4
,5-dichloropyridazin-3(2H)-ones are an attractive acyl
(3H)-one (3a)a
source: they are i) based on 4,5-dichloropyridazin-3(2H)-
one that is a good leaving group, ii) usually a stable solid
and thus easy to handle, and iii) a reusable functional-
i) 2a, toluene,
reflux
ii) base, reflux
O
O
OH
O
Cl
Cl
14,15
group carrier (RFGC) heterocycle.
O
PhO
N
N
–
–
pyridazinone
PhOH
N
H
Initially, the synthesis of benzo[d]oxazol-2(3H)-one
from 2-aminophenol (1a) using 2-phenoxycarbonyl-4,5-di-
NH2
1a
Entry
3a
2a
13
chloropyridazin-3(2H)-one (2a) in refluxing toluene was
investigated. In the absence of base the reaction gave the
expected product 3a in 15% yield (Table 1, entry 1). To im-
prove the yield of the product, we tried to optimize the re-
action conditions by treating with a base (Table 1): the one-
pot reaction that comprises acylation by 2a and intramolec-
ular cyclization was explored with eight different bases. We
found that sodium bicarbonate showed the best result (92%
yield; Table 1, entry 2).
Base
–
Time (h, step i + ii)
Yield of 3a (%)b
1
2
3
4
5
6
7
8
4 (4 + 0)
15
92
76
42c
86
NaHCO
Na CO
3
2.5 (1.5 + 1)
4 (3 + 1)
2
3
NaOH
KHCO
4 (3 + 1)
3
3 (1 + 2)
K2CO3
pyridine
Et
DMAP
5 (1 + 4)
43c
We examined solvent effect with seven different sol-
34c
4.5 (2 + 2.5)
4.5 (2 + 2.5)
4 (1.5 + 2.5)
17
vents for the synthesis of 3a from 1a with 2a (Table 2).
Among seven solvents, toluene showed the best result (92%
yield; Table 2, entry 2). Based on these two sets of prelimi-
nary experiments, we were able to determine the opti-
mized reaction conditions for the one-pot synthesis of ben-
zo[d]oxazol-2(3H)-one: 1a (1 equiv), 2a (1.2 equiv), NaHCO3
N
44c
82
3
9
a
2
-Aminophenol (1a, 1 equiv) and phenoxycarbonyl-4,5-dichloropyridazin-
(3H)-one (2a, 1.2 equiv) in toluene (5 mL) with base (1 equiv).
Isolated yields.
Amide intermediate remained.
2
b
c
(1 equiv) in refluxing toluene.
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Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1985–1990

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K. E. Ryu et al.
Letter
Table 2 Solvent Screening for One-Pot Synthesis of Benzo[d]oxazol-
(3H)-one (3a)a
We also examined the ability of 2a for the synthesis of
2
benzo[d]imidazol-2(3H)-ones from 1,2-phenylenediamine.
We studied the solvent effect for the reaction of 4a with 2a
(Table 4). Among seven solvents, toluene showed the best
result without any additives (90% yield; Table 4, entry 2).
Thus we selected the following as the optimized condi-
tions: 4a (1 equiv), 2a (1.2 equiv) in refluxing toluene.
For synthesizing benzo[d]thiazol-2(3H)-one (11a), we
performed the reaction of 2a with 2-mercaptoaniline (6a)
in refluxing toluene. The reaction did not give the desired
product 11a; compounds 7–10 (and other unknown by-
products) were formed (Scheme 2). According to the obser-
vation by TLC, compounds 7 and/or 8 first formed, which
were then further acylated to yield 9 and 10. Compound 10
was the final major product of the reaction.
i) 2a, solvent, reflux
ii) NaHCO3, reflux
OH
O
O
–
–
pyridazinone
PhOH
N
H
NH2
1a
3a
Entry
Solvent
Time (h, step i + ii)
Yield of 3a (%)b
1
2
3
4
5
6
n-hexane
4 (2 + 2)
18c
92
toluene
2.5 (1.5 + 1)
3 (1 + 2)
CHCl
3
29c
75
EtOAc
THF
3 (1 + 2)
3 (1 + 2)
65
CH
2
Cl
2
6 (1.5 + 4.5)
3 (1 + 2)
tracec
80
Table 4 Solvent Screening for One-Pot Synthesis of Benzo[d]imidazol-
7
MeCN
2
(3H)-one (5a)a,17
a
2-Aminophenol 1a (1 equiv) and 2a (1.2 equiv) in solvent (5 mL) with
NaHCO
3
(1 equiv).
b
H
N
Isolated yields for one-pot synthesis.
Amide intermediate remained.
NH2
NH2
c
2a, solvent, reflux
O
–
–
pyridazinone
PhOH
N
H
The substrate scope was examined with seven 2-amino-
phenol derivatives under the optimized conditions (Table
). Reactions of compounds 1 with 2a gave 3a–g in 64–97%
4a
5a
3
Yield of 5a (%)b
Entry
Solvent
Time (h)
yields. The reaction times for 2-aminophenols having elec-
1
2
3
4
5
6
7
n-hexane
toluene
EtOAc
AcOH
15
11
15
15
15
15
11
–c
tron-withdrawing groups, such as Cl and NO , were longer
2
90
than that for 1a, and their yields were lower than that for
1a. On the other hand, the results of 2-aminophenols hav-
3c
ing electron-donating groups such as Me and OMe, and 1a
were similar. All synthesized compounds were confirmed
by FT-IR and NMR spectroscopy and HRMS.
–c
THF
–c
CH
2
Cl
2
trace
72
Table 3 Synthesis of Benzo[d]oxazol-2(3H)-ones 3a
n-BuOH
a
b
c
1
,2-Phenylenediamine 4a (1 equiv) and 2a (1.2 equiv) in solvent (5 mL).
Isolated yields.
i) 2a, toluene, reflux
ii) NaHCO3, reflux
OH
O
Amide intermediate remained.
R1
R1
O
–
–
pyridazinone
PhOH
N
NH2
Table 5 Synthesis of Benzo[d]imidazol-2(3H)-ones 5a
H
1
3
H
N
NH2
R1
Yield of 3 (%)b
Entry
Time (h, step i + ii)
2
a, toluene
R1
R1
O
reflux
1
2
3
4
5
6
H
2.5 (1.5 + 1)
5 (4 + 1)
3a 92
3b 64c
3c 97
3d 88
3e 95
3f 89
N
H
NH2
3-Cl
4
5
3-Me
4-Cl
1.5 (1 + 0.5)
6 (4 + 2)
Entry
R1
Time (h)
Yield of 5 (%)b
4-Me
1.5 (1 + 0.5)
3.5 (2.5 + 1)
2.5 (1 + 1.5)
1
2
3
4
H
11
29
29
18
10
5a 90
5b 70c
5c 89
5d 86
5e 94
4-O
2
N
4-F
7
4-MeO
3g 92
4-Cl
a
4-O N
Compounds 1 (1 equiv) and 2a (1.2 equiv) in toluene (5 mL) with NaHCO
3
2
(
1 equiv).
b
c
5
4-Me
Isolated yields for one-pot synthesis.
Starting material (1b) remained.
a
Compounds 4 (1 equiv) and 2a (1.2 equiv) in toluene (10 mL).
Isolated yields.
b
c
Unknown byproduct was formed.
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K. E. Ryu et al.
Letter
acetic acid. Compounds 6a–c were reacted with 2a in the
presence of zinc to give 11a (80%), 11b (82%), and 11c
H2N
SH
S
S
(58%), respectively (Table 6, entries 2, 4, and 6).
We evaluated the reactivity of pyridazinone 2 with dif-
+
+
NHCO2Ph
NH2
ferent substituents under the one-pot reaction conditions
described above (see Table S4 in the Supporting Informa-
tion). Although the reaction of compound 7 with 2-(4-ni-
trophenoxy)carbonyl derivative 2e did not give the desired
product, the reaction of 7 with other pyridazinones 2b–d,
and 2f–h afforded the product 11a in 46–82% yields. Thus
we selected 2-phenoxycarbonyl-4,5-dichloropyridazin-
7
8
H2N
PhO CHN
2
S
S
S
S
SH
2a
NHCO2Ph
2
NHCO Ph
toluene,
reflux
NH2
9
10
3
(2H)-one (2a) as CO source.
6a
S
Table 6 Synthesis of Benzo[d]thiazol-2(3H)-ones 11a
X
O
N
H
i) 2a (1.2 equiv), AcOH,
r.t. or reflux
ii) Zn (5 equiv), reflux
SH
S
1
1a
O
Scheme 2 Reaction of 2-mercaptoaniline (6a) with 2a
R1
R1
N
H
NH2
6
11
To synthesize the desired product 11a,17 we needed to
determine the reaction conditions that predominantly yield
the intermediate 8. Since compound 10 was the major
product in the reaction above, we attempted to develop se-
quential reactions comprising i) acylation to form com-
pound 10 and ii) reductive intramolecular cyclization of 10
via compound 8 to form the final product 11a (Scheme 3).
From the solvent-screending study for the acylation of 7
Entry
R1
Total time (h) and temp and time for Yield of 11 (%)b
(
step i + step ii)
1
2
3
4
5
H
1.5 (r.t., 1.5 h)c
11a 4
H
2.5 (r.t., 1.5 h + reflux, 1 h)
2 (reflux, 3 h)c
11a 80
11b trace
11b 82
11c 49e
11c 58e
Cl
Cl
CF
CF
4 (reflux, 3 h + reflux, 1 h)
4.5 (reflux, 4.5 h)c
d
3
3
(Table S1 in the Supporting Information) we found that tol-
d
6
5.5 (reflux, 5 h + reflux, 0.5 h)
uene and acetonitrile gave the product 10 in ca. 90% yield;
other solvents such as acetic acid, chloroform, tetrahydro-
furan, and dichloromethane gave the product 10 in good
yields (80–87%). For the reductive cyclization step, the di-
sulfide bond in 10 was reduced with zinc in acetic acid;16
use of five equivalents of zinc showed the best result while
the zinc-free reaction did not proceed (Table S3 in the Sup-
porting Information). To demonstrate the formation of 11a
from 7 in the one-pot synthesis, we chose acetic acid as a
solvent for both acylation and reductive cyclization reac-
tions. Table 6 shows the results of the one-pot synthesis
with various 2-mercaptoaniline derivatives. The reaction
conditions were as following: starting material 7 (1 equiv),
a
Compounds 6 (1 equiv), 2a (1.2 equiv), and Zn (5 equiv) in AcOH (5 mL).
Isolated yields for one-pot synthesis.
This reaction was carried out in the absence of zinc.
b
c
d
e
6
c·HCl was used.
Unknown byproduct was formed.
This work demonstrates the ability of 2-phenoxycar-
bonyl-4,5-dichloropyridazin-3(2H)-one for the one-pot
synthesis of benzo[d]oxazol-2(3H)-ones (seven examples),
benzo[d]imidazol-2(3H)-ones (five examples), and ben-
zo[d]thiazol-2(3H)-ones (three examples) in good to excel-
lent yields. For the synthesis, 2-phenoxycarbonyl-4,5-di-
chloropyridazin-3(2H)-one was an efficient, atom-econom-
ic, and eco-friendly acyl source: i) it is a stable (air- and
moisture-insensitive) solid and thus easy to handle, ii) reus-
2a (1.2 equiv) at room temperature under acetic acid to
form 10, and then addition of zinc (5 equiv) in refluxing
PhO2CHN
SH
SH
S
S
Zn
2
a
S
2
O
AcOH
– PhOH
toluene, reflux
NHCO2Ph
N
H
NH2
NHCO2Ph
reductive
cyclization
6a
acylation
10
8
11a
Scheme 3 Synthesis of 11a from the reaction of 6a with 2a in the presence of zinc in acetic acid
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1985–1990

1
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K. E. Ryu et al.
Letter
able 4,5-dichloropyridazin-3(2H)-one is isolated easily
upon completion of reaction, and iii) it does not require any
additives for acylation reaction (it is a metal-free and cata-
lyst-free reaction).
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This research was supported by Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded by
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M. A.; Hameed, S.; Kressler, J. Asian J. Chem. 2013, 25, 509.
(
14) (a) Lee, H. G.; Kim, M. J.; Park, S. E.; Kim, J. J.; Kim, B. R.; Lee, S.
G.; Yoon, Y. J. Synlett 2009, 2809. (b) Sung, G. H.; Kim, B. R.; Ryu,
K. E.; Kim, J. J.; Yoon, Y. J. Bull. Korean Chem. Soc. 2014, 35, 2758.
15) Sung, G. H.; Kim, B. R.; Lee, S. G.; Kim, J. J.; Yoon, Y. J. Curr. Org.
Chem. 2012, 16, 852.
(i) Wang, W.; Zhang, G. P.; Song, B. A.; Wang, H.; Jin, L. H.; Hu, D.
(
(
(
T.; Yang, S. Chin. J. Org. Chem. 2007, 27, 279. (j) Bonuga, Y. R.;
Nath, A. R. Pharma Chem. 2012, 4, 2396. (k) Eroll, D. D.; Aytemir,
M. D.; Yulğ, N. Eur. J. Med. Chem. 1996, 31, 731. (l) Huang, Q.;
Qian, X.; Song, G.; Cao, S. Pest Manag. Sci. 2003, 59, 933.
16) Velikorodov, A. V.; Kuanchalieva, A. K.; Melent’eva, E. A.; Titova,
O. L. Russian J. Org. Chem. 2011, 47, 1353.
17) Synthesis of 3: General Procedure
(
m) Fishback, J. A.; Mesangeau, C.; Poupaert, J. H.; McCurdy, C.
R.; Matsumoto, R. R. Eur. J. Pharmacol. 2011, 653, 1.
n) Delhomel, J. F.; Yous, S.; Depreux, P.; Lesieur, D. J. Heterocycl.
A mixture of 2-phenoxycarbonyl-4,5-dichloropyridazin-3(2H)-
one (2a, 1.2 equiv), compounds (1, 1 equiv), and toluene (5 mL)
was stirred at reflux conditions until 1 was consumed (moni-
(
Chem. 2001, 38, 633. (o) Ucar, H.; Derpoorten, K. V.;
Cacciaguerra, S.; Spampinato, S.; Stables, J. P.; Depovere, P.; Isa,
M.; Masereel, B.; Delarge, J.; Poupaert, J. H. J. Med. Chem. 1998,
tored by TLC). After adding NaHCO (1 equiv), the mixture was
3
refluxed until the intermediate was consumed (monitored by
TLC). After cooling to r.t., the resulting precipitate was filtered
off and washed with THF. The solvent was evaporated under
reduced pressure. The resulting residue was transferred to an
open-bed silica gel column (3 × 10 cm). The column was eluted
with n-hexane–THF (3:1, v/v). Fractions containing compounds
41, 1943. (p) Terefenko, E. A.; Kern, J.; Fensome, A.; Wrobel, J.;
Zhu, Y.; Cohen, E.; Winneker, R.; Zhang, Z.; Zhang, P. Bioorg.
Med. Chem. Lett. 2005, 15, 3600. (q) Hammach, A.; Barbosa, A.;
Gaenzler, F. C.; Fadra, T.; Goldberg, D.; Hao, M. H.; Kroe, R. R.;
Liu, P.; Qian, K. C.; Ralph, M.; Sarko, C.; Soleymanzadeh, F.; Mos,
N. Bioorg. Med. Chem. Lett. 2006, 16, 6316. (r) Weinstock, J.;
Gaitanopoulos, D. E.; Stringer, O. D.; Franz, R. G.; Hieble, J. P.;
Kinter, L. B.; Mann, W. A.; Flaim, K. E.; Gessner, G. J. Med. Chem.
3
were combined and evaporated under reduced pressure to
give compounds 3.
Benzo[d]oxazol-2(3H)-one (3a)
16
Yield: 340 mg (92%); white solid; mp 140 °C (lit. 141–142 °C).
IR (KBr): 3215, 1772, 1733, 1480, 1398, 1307, 1253, 1147, 1009,
1987, 30, 1166. (s) Austin, R. P.; Barton, P.; Bonnert, R. V.;
Brown, R. C.; Cage, P. A.; Cheshire, D. R.; Davis, A. M.; Dougall, I.
G.; Ince, F. S.; Pairaudeau, G.; Young, A. J. Med. Chem. 2003, 46,
–1 1
9
7
=
44, 739, 718, 701, 574 cm . H NMR (300 MHz, DMSO-d ): δ =
6
13
.10–7.26 (m, 3 H), 9.87 (s, 1 H). C NMR (75 MHz, DMSO-d ): δ
110.17, 110.25, 122.76, 124.23, 129.42, 143.90, 156.23. HRMS
6
3210. (t) Ogino, U.; Ohtake, N.; Nagae, Y.; Matsuda, K.; Moriya,
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1985–1990

1
990
Synlett
K. E. Ryu et al.
Letter
+
(
m/z): [M] calcd for C H NO : 135.0320; found: 135.0319. See
Synthesis of 11 – General Procedure
7
5
2
the Supporting Information for experimental details and char-
acterization data for all compounds.
Synthesis of 5: General Procedure
A mixture of 2-phenoxycarbonyl-4,5-dichloropyridazin-3(2H)-
one (2a, 1.2 equiv), compounds 6 (1 equiv), and AcOH (5 mL)
was stirred at r.t. (for 11a) or at reflux conditions (for 11b,c)
until 6 was consumed (monitored by TLC). After adding zinc
powder (5 equiv), the mixture was refluxed for 0.5 h. After
cooling to r.t., the resulting precipitate was filtered off and
washed with CH Cl (for 11a) or THF (for 11b,c), the solvent was
A mixture of 2-phenoxycarbonyl-4,5-dichloropyridazin-3(2H)-
one (2a, 1.2 equiv), compounds 4 (1 equiv), and toluene (10 mL)
was stirred at reflux conditions until amide intermediate was
consumed (monitored by TLC). After cooling to r.t., the resulting
precipitate was filtered off and the solvent was evaporated
under reduced pressure. The residue was transferred to an
open-bed silica gel column (3 × 7 cm). The column was eluted
with n-hexane–THF (1:2, v/v). Fractions containing compounds
2
2
evaporated under reduced pressure. The resulting residue was
transferred to an open-bed silica gel column (3 × 10 cm). The
column was eluted with CH Cl –EtOAc (10:1, v/v). Fractions
2
2
containing compounds 11 were combined and evaporated
under reduced pressure to give compounds 11.
5
were combined and evaporated under reduced pressure to
give compounds 5.
Benzo[d]imidazol-2(3H)-one (5a)
Yield: 335 mg (90%); white solid; mp 320–322 °C (lit. 305–
Benzo[d]thiazol-2(3H)-one (11a)
Yield: 341 mg (93%); light yellow solid; mp 138–139 °C (lit.7a
139–141 °C). IR (KBr): 3307, 3154, 3108, 3054, 3946, 2881,
2823, 2740, 2674, 1680, 1592, 1463, 1413, 1214, 1222, 742,
9
308 °C). IR (KBr): 3178, 3114, 3027, 2910, 2807, 2726, 1743,
–1
1
–1 1
1483, 1361, 1270, 1197, 1027, 736, 703, 597 cm . H NMR (300
701, 642 cm . H NMR (300 MHz, DMSO-d ): δ = 7.10–7.15 (m,
6
1
3
13
MHz, DMSO-d ): δ = 6.91 (s, 4 H), 10.56 (s, 2 H). C NMR (75
2 H), 7.26–7.31 (m, 1 H), 7.55–7.58 (m, 1 H), 11.89 (s, 1 H).
C
6
MHz, DMSO-d ): δ = 108.42, 113.27, 120.49, 126.96, 129.63,
NMR (75 MHz, DMSO-d ): δ = 111.44, 122.56, 122.66, 123.23,
6
6
+
+
1
30.24, 155.28. HRMS: m/z [M] calcd for C H N O: 134.0480;
126.38, 136.27, 169.98. HRMS: m/z [M] calcd for C H NOS:
7
6
2
7
5
found: 134.0480.
151.0092; found: 151.0091.
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1985–1990