Unexpected C-C bond cleavage: A route to 3,6-diarylpyridazines and 6-arylpyridazin-3-ones from 1,3-dicarbonyl compounds and methyl ketones

Article abstract of DOI:10.1021/jo301751e

An unexpected C-C bond cleavage has been revealed in the absence of metal. This observation has been exploited to develop an efficient approach toward 3,6-diarylpyridazines and 6-arylpyridazin-3-ones from simple and commercially available 1,3-dicarbonyl compounds and methyl ketones.

Full text of DOI:10.1021/jo301751e

Note
pubs.acs.org/joc
Unexpected C−C Bond Cleavage: A Route to 3,6-Diarylpyridazines
and 6‑Arylpyridazin-3-ones from 1,3-Dicarbonyl Compounds and
Methyl Ketones
Qinghe Gao,† Yanping Zhu,† Mi Lian,† Meicai Liu,† Jingjing Yuan,† Guodong Yin,*,‡ and Anxin Wu*,†
†Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University,
Wuhan 430079, P. R. China
‡Hubei Key Laboratory of Pollutant Analysis & Reuse Technology, College of Chemistry and Environmental Engineering, Hubei
Normal University, Huangshi 435002, P. R. China
S
* Supporting Information
ABSTRACT: An unexpected C−C bond cleavage has been
revealed in the absence of metal. This observation has been
exploited to develop an efficient approach toward 3,6-
diarylpyridazines and 6-arylpyridazin-3-ones from simple and
commercially available 1,3-dicarbonyl compounds and methyl
ketones.
Scheme 1. Deacylation Process
C−C bond formation and cleavage (activation) have attracted
considerable attention due to not only fundamental scientific
interest but also their potential utility in organic synthesis.1
Numerous useful C−C bond formation procedures have been
developed, and because of its inertness,2 the cleavage of the C−
C single bond has emerged as a tremendous challenge. In
recent years, significant progress has been achieved involving
two basic strategies to facilitate C−C bond cleavage. One is to
use strained molecules3 bearing three- and four-membered
rings, forming more stable complexes to release ring strain. On
the other hand, C−C bond cleavage of unstrained molecules is
required to generate stable intermediates by chelation
assistance4 or other means.5
C−C bond cleavage is frequently found in carbonyl
compounds, such as Baeyer−Villiger,6 haloform,7 and Haller−
Bauer8 reactions. Until now, few examples of the deacylation of
carbonyl compounds have been reported.9 A novel CuI-
catalyzed deacylation process was closely studied by Ma9a
(Scheme 1a) and Xi9c (Scheme 1b). Another interesting CuI-
catalyzed deacylation in the arylation/C−C activation process
was discovered by Lei’s group9d (Scheme 1c). Those reports
mainly focused on the metal-catalyzed deacylation approaches.
Until now, much attention has been paid to metal-free
transformations10 in organic synthesis for significant potential
economic and environmental benefits. However, the develop-
ment of a metal-free process to achieve C−C bond cleavage still
represents a fascinating topic. In this paper, a metal-free C−C
bond cleavage of 1,4-enediones for accessing pyridazines and
pyridazin-3-ones is described (Scheme 1d).
on the synthesis of pyridazines and pyridazin-3-ones from 1,3-
dicarbonyl compounds and methyl ketones.
In our previous study, we proposed a focusing domino
strategy to synthesize various substituted 1,4-enediones.14 In
view of the synthesis of pyridazines involving the reaction of
1,4-dicarbonyl compound with hydrazine, we envisioned a
novel one-pot, two-step synthesis of pyridazines from simple
and commercially available 1,3-dicarbonyl compounds and
methyl ketones.
Pyridazines and pyridazin-3-ones are versatile building blocks
in natural product syntheses11 and useful intermediates to
construct other heterocycles.12 Although several general
approaches to pyridazines and pyridazin-3-ones are known,13
to the best of our knowledge, no examples have been reported
Received: August 18, 2012
Published: October 12, 2012
© 2012 American Chemical Society
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Note
With the above idea in mind, we investigated the reaction of
2-benzoyl-1,4-diphenylbut-2-ene-1,4-dione (1a) and hydrazine
hydrate (NH2NH2·H2O) in t-BuOH at reflux. Unexpectedly,
the condensation product (3,6-diphenylpyridazin-4-yl)-
(phenyl)methanone (2a) was not the final product; instead,
3,6-diphenylpyridazine (3a) was obtained in 40% isolated yield
after cleavage of the benzoyl group of 2a (Table 1, entry 2).
crude product was treated with NH2NH2·H2O (15.0 mmol) in
t-BuOH at reflux for another 0.5 h. The desired pyridazine 3a
was isolated in 76% yield after the workup (Scheme 2).
a
Scheme 2. Scope of Methyl Ketones
a
Table 1. Optimization of the Reaction Conditions
b
entry
solvent
temp (°C) molar ratio (1: NH2NH2·H2O) yield (%)
1
2
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
MeOH
EtOH
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
80
1:1
<5
40
50
67
88
94
85
92
73
75
83
86
88
72
55
60
0
1:3
3
1:5
4
1:8
5
1:10
1:15
1:15
1:15
1:15
1:15
1:15
1:15
1:15
1:15
1:15
1:15
1:15
1:15
1:15
1:20
1:30
1:15
7
8
a
9
Isolated yields.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
n-PrOH
i-PrOH
n-BuOH
DMSO
DMF
The efficient formation of 3a prompted us to further study
the reaction scope. To our delight, different methyl ketones
with 5a, irrespective of their electronic or steric properties,
proceeded smoothly to afford their corresponding products in
moderate to good yields (60−82%; Scheme 2). For example,
substituted methyl ketones bearing electron-neutral (4-Me),
electron-rich (4-OMe, 2,4-OMe2, 3,4-OCH2O, 3,4-OCH2-
CH2O), electron-deficient (3,4-Cl2), and sterically hindered
(β-naphthyl) methyl ketones all performed efficiently to afford
the expected pyridazines in good yields (71−82%; 3a−f, h, i). It
should be noted that an electron-donating substituent attached
to the benzene ring caused a considerable increase in yield.
Gratifyingly, the sensitive hydroxy group (OH) in 4g was
compatible with these conditions to give the expected product
3g in 60% yield. Furthermore, heteroaryl ketones were also
discovered to be able to efficiently furnish the desired products
in moderate yields (68−75%; 3j−l).
Next, the scope of this reaction was extended to various 1,3-
dicarbonyl compounds (Scheme 3). When symmetrical 1,3-
diketones such as acetylacetone (5b) and 1,3-bis(4-
methoxyphenyl)propane-1,3-dione (5c) were employed, the
desired pyridazines 3m and 3c were isolated in 81% and 72%
yields, respectively. Interestingly, when unsymmetrical 1,3-
diketone (5d) was used in this system, the reaction exhibited
excellent selectivity and gave 3a in 89% yield, while 1-(4-
methoxyphenyl)-3-phenylpropane-1,3-dione (5e) resulted in
two products 3a and 3c in 78% overall yield with the molar
ratio of 1:1. Surprisingly, when ethyl benzoylacetate (5f) was
used, the C−C bond cleavage was also observed, and the
reaction proceeded smoothly to furnish 6-phenylpyridazin-3-
one (6a) in 75% yield under the standard conditions. Varied β-
keto esters were effective for this transformation. Both electron-
donating (OMe) and electron-withdrawing (NO2) groups
attached to the phenyl rings of 4a could afford their
corresponding products 6b and 6c in 72% and 67% yields.
Much to our satisfaction, naphthyl and heteroaryl methyl
80
MeCN
CHCl3
THF
reflux
reflux
reflux
reflux
reflux
25
H2O
Toluene
t-BuOH
t-BuOH
t-BuOH
t-BuOH
65
76
76
76
80
25
25
60
a
Reaction conditions: 1a (0.2 mmol), solvent (1 mL). The reaction
b
was performed for 0.5 h. Isolated yields.
Furthermore, 3a was further identified by X-ray diffraction
(Supporting Information, Figure S3). This result indicated that
we accidentally discovered a fascinating C−C bond cleavage
without any metal, which meanwhile led to an efficient
approach toward 3,6-diarylpyridazines under mild condition.
This deacylation process prompted us to investigate the
reaction parameters. As shown in Table 1, the effect of solvents,
temperature, and molar ratios was examined to optimize the
reaction conditions, and we were pleased to find that 1,4-
enedione (1a) could react with 15 equiv of hydrazine hydrate in
t-BuOH at reflux for 0.5 h to afford the deacylated product 3a
in 94% yield (Table 1, entry 7). Motivated by our discovery, we
considered the possibility for the preparation 3a via a one-pot,
two-step reaction from acetophenone (4a) and 1,3-diphenyl-
propane-1,3-dione (5a) (Scheme 1d). Nevertheless, only trace
amounts of 3a were formed. Subsequently, the feasibility of this
strategy was verified by reaction of 1.0 mmol of 4a and 1.0
mmol of 5a in the presence of 1.1 mmol of CuO and 1.1 mmol
of iodine in 5 mL of DMSO at 70 °C for 12 h until complete
disappearance of the starting materials. After being extracted
with EtOAc and washed with aqueous solution of Na2S2O3, the
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Note
hydrazone A or B through a condensation reaction.
Subsequently, intramolecular cyclization led to the formation
of 2a. Then excess amount of hydrazine hydrate as a
nucleophilic agent could attack the carbonyl group of
intermediate 2a to produce intermediate C,8 which underwent
a deacylation process to furnish the desired product. In
addition, 6-arylpyridazin-3-ones were formed via a similar
process (Supporting Information, Figure S2).
Scheme 3. Scope of Methyl Ketones and 1,3-Dicarbonyl
Compounds
a
In summary, we have revealed an efficient C−C cleavage
process to construct 3,6-diarylpyridazines and 6-arylpyridazin-
3-ones without any metal. The reaction gave the desired
products from simple and commercially available 1,3-dicarbonyl
compounds and methyl ketones under mild conditions. This
deacylation has a broad substrate scope and high functional
group tolerance.
EXPERIMENTAL SECTION
■
General Information. All substrates and reagents were
commercially available and used without further purification. TLC
analysis was performed using precoated glass plates. Flash column
chromatography was performed on silica gel (200−300 mesh). IR
spectra were recorded as KBr pellets with absorption in cm−1. H
1
spectra were recorded in CDCl3 or DMSO-d6 on 400/600 MHz NMR
spectrometers and resonances (δ) are given in parts per million
relative to tetramethylsilane. 13C spectra were recorded in CDCl3 or
DMSO-d6 on 100/150 MHz NMR spectrometers and resonances (δ)
are given in ppm. HRMS were obtained on an apex-Ultra MS
equipped with APCI. MS was recorded using EI (70 eV). Melting
points were determined using an electrothermal capillary melting point
apparatus and not corrected.
a
b
Isolated yields. Reaction conditions: 2,2-dihydroxy-1-phenyletha-
none 4a′ (1.0 mmol) with 5b or 5d (1.0 mmol) was stirred at reflux in
CH3CN (5 mL) for 12 h. After evaporation, the crude product and
NH2NH2·H2O (15.0 mmol) were stirred in t-BuOH at reflux for
another 0.5−1 h.
General Procedure for the Synthesis of 3 and 6 (3a as an
Example). A mixture of acetophenone 4a (1.0 mmol), 1,3-
diphenylpropane-1,3-dione 5a (1.0 mmol), iodine (1.1 mmol), and
CuO (1.1 mmol) in DMSO (5 mL) was stirred at 70 °C for 12 h until
nearly completed conversion of the substrates by TLC analysis and
then extracted with EtOAc two times (2 × 30 mL). The extract was
washed with 10% Na2S2O3 solution (w/w). After drying over Na2SO4
and evaporation, hydrazine hydrate (15.0 mmol) was added and the
mixture were stirred at reflux in t-BuOH (5 mL) for 0.5−1 h. After the
reaction complete (as monitored by TLC), the solvent was removed
under reduce pressure, 50 mL of water was added to the residue, and
then the mixture was extracted with EtOAc three times (3 × 50 mL).
The extract was dried over anhydrous Na2SO4 and concentrated in
vacuo. The crude product was purified by column chromatography on
silica gel (eluent: petroleum ether/EtOAc) to afford the product 3a.
(3,6-Diphenylpyridazin-4-yl)(phenyl)methanone (2a):16 1H NMR
(600 MHz, CDCl3) δ (ppm) 8.20 (d, J = 7.2 Hz, 2H), 7.92 (s, 1H),
7.72−7.66 (m, 4H), 7.58−7.51 (m, 4H), 7.39−7.34 (m, 2H), 7.32 (br,
3H); 13C NMR (150 MHz, CDCl3) δ (ppm) 195.1, 157.5, 156.2,
137.1, 135.8, 135.4, 135.2, 134.3, 130.5, 129.8, 129.7, 129.2(4),
129.1(7), 128.8, 128.6, 127.1, 122.6; m/z 337.12 (M + 1, 17.528),
336.09 (M, 72.55).
ketones also proceeded efficiently to give the pyridazin-3-one
6d and 6e in 70% and 61% yields. For further investigation, in
the case of electron-deficient ethyl 4-nitrobenzoylacetate (5g),
the reaction delivered 6a with a satisfactory yield (74%). When
electron-donating group was attached to the phenyl ring of the
β-keto ester ethyl 4-methoxybenzoylacetate (5h), the yield
slightly dropped (65%; 6a). Significantly, the heterocycle
substrate ethyl 3-(furan-2-yl)-3-oxopropanoate (5i) was
employed and 6a was also obtained in 68% yield.
To gain some insights into the mechanism of this reaction
process, the reaction of 1a with hydrazine hydrate was
performed under the standard conditions. Benzohydrazide
(7), phenyl(3-phenyl-1H-pyrazol-5-yl)methanone (8a), and 5-
phenyl-1H-pyrazole15 (9) were detected by GC−MS (Support-
ing Information, Figure S1). In addition, 7 was also isolated and
characterized by 1H and 13C NMR. Furthermore, 2a was
synthesized according to the known method,16 which reacted
with hydrazine hydrate under the standard reaction conditions
to afford 3a in 92% yield (Scheme 4). This control experiment
indicated that the reaction between 1a and hydrazine hydrate
might undergo the intermediate 2a.
3,6-Diphenylpyridazine (3a):17 white solid; 176.3 mg (yield 76%);
mp 226−228 °C; IR (KBr) 3054, 1449, 1408, 868, 758, 744, 694
cm−1; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.16 (d, J = 6.4 Hz, 4H),
7.94 (s, 2H), 7.60−7.44 (m, 6H); 13C NMR (100 MHz, CDCl3) δ
(ppm) 157.6, 136.1, 130.0, 129.0, 126.9, 124.2; HRMS (APCI) m/z
[M + H]+ calcd for C16H13N2 233.1073, found 233.1074.
On the basis of the results described above and previous
reports,8,13 a possible mechanism of the present reaction was
described using 1a and hydrazine hydrate as an example
(Scheme 5). Initially, 1a reacted with hydrazine hydrate to give
3-Phenyl-6-(p-tolyl)pyridazine (3b):18 white solid; 194.3 mg (yield
79%); mp 187−189 °C; IR (KBr) 3054, 1608, 1511, 1428, 1410, 1260,
1248, 1175, 1035, 829, 791, 750, 693, 583 cm−1; 1H NMR (400 MHz,
CDCl3) δ (ppm) 8.15 (d, J = 7.6 Hz, 2H), 8.06 (d, J = 8.0 Hz, 2H),
7.89 (s, 2H), 7.57−7.47 (m, 3H), 7.34 (d, J = 8.0 Hz, 2H), 2.44 (s,
3H); 13C NMR (150 MHz, CDCl3) δ (ppm) 157.5, 157.3, 140.2,
136.1, 133.2, 129.9, 129.8, 129.0, 126.8(4), 126.7(5), 124.1, 123.9,
21.36; HRMS (APCI) m/z [M + H]+ calcd for C17H15N2 247.1230,
found 247.1231.
Scheme 4. Control Experiment
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Note
Scheme 5. Possible Mechanism
3-(4-Methoxyphenyl)-6-phenylpyridazine (3c):18 white solid;
214.8 mg (yield 82%); mp 197−199 °C; IR (KBr) 3057, 3031,
128.4, 126.6, 124.6, 123.7, 116.0, 104.8; HRMS (APCI) m/z [M + H]+
calcd for C16H13N2O 249.1022, found 249.1023.
1
1449, 1419, 1398, 822, 785, 747, 690 cm−1; H NMR (400 MHz,
3-(3,4-Dichlorophenyl)-6-phenylpyridazine (3h): white solid;
213.7 mg (yield 71%); mp 179−181 °C; IR (KBr) 3040, 2925,
1471, 1449, 1416, 1375, 1030, 832, 793, 756, 699 cm−1; 1H NMR (400
MHz, CDCl3) δ (ppm) 8.27 (s, 1H), 8.14 (d, J = 6.8 Hz, 2H), 8.01−
7.81 (m, 3H), 7.63−7.44 (m, 4H); 13C NMR (150 MHz, CDCl3) δ
(ppm) 158.1, 155.4, 135.9, 135.6, 134.4, 133.4, 131.0, 130.3, 129.1,
128.7, 127.0, 125.9, 124.3, 123.9; HRMS (APCI) m/z [M + H]+ calcd
for C16H11Cl2N2 301.0294, found 301.0295.
CDCl3) δ (ppm) 8.20−8.10 (m, 4H), 7.90−7.87 (m, 2H), 7.58−7.47
(m, 3H), 7.06 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H); 13C NMR (150 MHz,
CDCl3) δ (ppm) 161.3, 158.7, 157.1, 157.0, 136.2, 129.9, 129.0, 128.3,
126.8, 124.1, 123.5, 114.4, 55.4; HRMS (APCI) m/z [M + H]+ calcd
for C17H15N2O 263.1179; found: 263.1180.
3-(2,4-Dimethoxyphenyl)-6-phenylpyridazine (3d): white solid;
224.8 mg (yield 77%); mp 157−160 °C; IR (KBr) 3044, 2960, 2934,
2839, 1612, 1408, 1305, 1282, 1212, 1161, 1139, 831, 756, 697 cm−1;
1H NMR (600 MHz, CDCl3) δ (ppm) 8.17−8.10 (m, 4H), 7.82 (d, J
= 9.0 Hz, 1H), 7.55−7.51 (m, 2H), 7.50−7.46 (m, 1H), 6.69 (d, J =
9.0 Hz, 1H), 6.59 (s, 1H), 3.89 (s, 3H), 3.88 (s, 3H); 13C NMR (150
MHz, CDCl3) δ (ppm) 162.3, 158.6, 156.8, 156.5, 136.5, 132.0, 129.7,
128.9, 128.2, 126.8, 122.9, 118.5, 105.3, 99.0, 55.5(4), 55.4(9); HRMS
(APCI) m/z [M + H]+ calcd for C18H17N2O2 293.1285, found
293.1285.
3-(Naphthalen-2-yl)-6-phenylpyridazine (3i):19 white solid; 220
mg (yield 78%); mp 196−198 °C; IR (KBr) 3054, 1439, 1408, 1132,
1121, 862, 855, 827, 793, 742, 692 cm−1; 1H NMR (400 MHz,
CDCl3) δ (ppm) 8.62 (s, 1H), 8.38−8.26 (m, 1H), 8.22−8.12 (m,
2H), 8.05−7.90 (m, 5H), 7.54 (br, 5H); 13C NMR (100 MHz,
CDCl3) δ (ppm) 157.6, 136.1, 134.1, 133.4, 130.1, 129.1, 128.8, 127.8,
127.1, 126.9, 126.7, 126.6, 124.3, 124.2, 124.1; HRMS (APCI) m/z [M
+ H]+ calcd for C20H15N2 283.1230, found 283.1231.
3-(Furan-2-yl)-6-phenylpyridazine (3j):20 white solid; 151 mg
(yield 68%); mp 198−200 °C; IR (KBr) 3059, 1604, 1488, 1448,
1425, 1162, 1080, 1004, 865, 789, 827, 784, 737, 694 cm−1; 1H NMR
(400 MHz, CDCl3) δ (ppm) 8.13 (d, J = 6.8 Hz, 2H), 7.89 (s, 2H),
7.62 (s, 1H), 7.57−7.46 (m, 3H), 7.41 (d, J = 3.2 Hz, 1H), 6.62 (s,
1H); 13C NMR (100 MHz, CDCl3) δ (ppm) 157.1, 150.9, 150.7,
144.4, 136.1, 130.0, 129.0, 126.8, 123.9, 122.1, 112.6, 110.3; HRMS
(APCI) m/z [M + H]+ calcd for C14H11N2O 223.0866, found
223.0867.
3-(Benzo[d][1,3]dioxol-5-yl)-6-phenylpyridazine (3e): white solid;
220.8 mg (yield 80%); mp 174−177 °C; IR (KBr) 3054, 2904, 1506,
1489, 1450, 1267, 1237, 1046, 934, 818, 789,749, 692 cm−1; 1H NMR
(400 MHz, CDCl3) δ (ppm) 8.12 (d, J = 6.8 Hz, 2H), 7.88−7.77 (m,
2H), 7.75−7.71 (m, 1H), 7.62−7.57 (m, 1H), 7.56−7.45 (m, 3H),
6.94 (d, J = 8.0 Hz, 1H), 6.04 (s, 2H); 13C NMR (100 MHz, CDCl3) δ
(ppm) 157.2, 157.0, 149.4, 148.5, 136.1, 130.3, 129.9, 129.0, 126.8,
124.1, 123.6, 121.1, 108.6, 107.2, 101.5; HRMS (APCI) m/z [M + H]+
calcd for C17H13N2O2 277.0972, found 277.0973.
3-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-6-phenylpyridazine (3f):
white solid; 226.2 mg (yield 78%); mp 170−174 °C; IR (KBr)
3059, 2925, 1586, 1507, 1451, 1412, 1319, 1285, 1257, 1132, 1065,
861, 791, 749, 693 cm−1; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.13
(d, J = 6.8 Hz, 2H), 7.90−7.78 (m, 2H), 7.72 (s, 1H), 7.65 (d, J = 8.4
Hz, 1H), 7.57−7.44 (m, 3H), 7.00 (d, J = 8.0 Hz, 1H), 4.31 (s, 4H);
13C NMR (100 MHz, CDCl3) δ (ppm) 157.1, 156.9, 145.5, 144.0,
136.2, 129.8, 129.5, 128.9, 126.8, 124.1, 123.5, 120.2, 117.8, 115.9,
64.5, 64.3; HRMS (APCI) m/z [M + H]+ calcd for C18H15N2O2
291.1128, found 291.1129.
3-Phenyl-6-(thiophene-2-yl)pyridazine (3k):21 white solid; 178.5
mg (yield 75%); mp 160−162 °C; IR (KBr) 3065, 1546, 1450, 1433,
1406,1300, 851, 835, 787, 748, 697 cm−1; 1H NMR (400 MHz,
CDCl3) δ (ppm) 8.10 (d, J = 7.6 Hz, 2H), 7.85−7.76 (m, 2H), 7.69−
7.63 (m, 1H), 7.55−7.44 (m, 4H), 7.17−7.11 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ (ppm) 157.2, 153.4, 140.5, 135.8, 129.9, 129.1,
128.9, 128.0, 126.6, 126.1, 123.9, 122.6; HRMS (APCI) m/z [M + H]+
calcd for C14H11N2S 239.0637, found 239.0638.
3-(Benzofuran-2-yl)-6-phenylpyridazine (3l): white solid; 201.3 mg
(yield 74%); mp 215−217 °C; IR (KBr) 3042, 1603, 1580, 1446,
1421, 1260, 1029, 1008, 827, 790, 751, 738, 693 cm−1; 1H NMR (400
MHz, CDCl3) δ (ppm) 8.15 (d, J = 7.2 Hz, 2H), 8.07 (d, J = 9.2 Hz,
1H), 7.94 (d, J = 8.8 Hz, 1H), 7.77 (s, 1H), 7.71 (d, J = 7.6 Hz, 1H),
7.61−7.43 (m, 4H), 7.41−7.34 (m, 1H), 7.33−7.27 (m, 1H); 13C
NMR (150 MHz, CDCl3) δ (ppm) 157.6, 155.5, 152.3, 150.9, 135.8,
130.1, 129.0, 128.5, 126.8, 125.7, 123.8, 123.5, 122.9, 122.1, 111.5,
4-(6-Phenylpyridazin-3-yl)phenol (3g): white solid; 148.8 mg
(yield 60%); mp 227−229 °C; IR (KBr) 3055, 1609, 1598, 1511,
1
1443, 1408, 1253, 835, 791, 750, 694 cm−1; H NMR (400 MHz,
DMSO-d6) δ (ppm) 10.0 (s, 1H), 8.26−8.16(m, 4H), 8.09 (d, J = 8.4
Hz, 2H), 7.61−7.51 (m, 3H), 6.95 (d, J = 8.4 Hz, 2H); 13C NMR (100
MHz, DMSO-d6) δ (ppm) 159.5, 157.0, 156.3, 136.1, 129.9, 129.1,
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Note
106.2; HRMS (APCI) m/z [M + H]+ calcd for C18H13N2O 273.1022,
found 273.1023.
ACKNOWLEDGMENTS
■
3-Methyl-6-phenylpyridazine (3m):22 white solid; 137.7 mg (yield
81%); mp 101−104 °C; IR (KBr) 3061, 1587, 1450, 1416, 1113, 1012,
This work was supported by the National Natural Science
Foundation of China (Grant Nos. 21032001, 21102042) and
PCSIRT (No. IRT0953). We also thank Dr. Chuanqi Zhou,
Hebei University, for analytical support.
1
851, 772, 741, 751, 692, 565 cm−1; H NMR (400 MHz, CDCl3) δ
(ppm) 8.05 (d, J = 6.8 Hz, 2H), 7.74 (d, J = 8.8 Hz, 1H), 7.53−7.46
(m, 3H), 7.37 (d, J = 8.4 Hz, 1H), 2.74 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ (ppm) 158.4, 157.1, 136.3, 129.6, 128.9, 127.2, 126.8, 123.9,
22.0; HRMS (APCI) m/z [M + H]+ calcd for C11H11N2 171.0917,
found 171.0918.
REFERENCES
■
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Science 2006, 313, 662.
6-Phenylpyridazin-3(2H)-one (6a):13b yellow solid; 112.4−129.7
mg (yield 65−75%); mp 199−201 °C; IR (KBr) 2925, 2854, 1650,
1593, 1574, 1007, 856, 775, 736, 687, 587 cm−1; 1H NMR (400 MHz,
CDCl3) δ (ppm) 12.46 (s, 1H), 7.87−7.75 (m, 3H), 7.45−7.48 (m,
3H), 7.11 (d, J = 9.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ (ppm)
162.1, 145.7, 134.4, 132.1, 131.7, 130.1, 129.6, 128.9, 125.9; MS (EI)
m/z 173.19 (M + 1, 12.00), 172.13 (M, 100.00), 171.11 (M − 1,
16.20), 144.11 (25.18), 116.08 (21.76), 115.08 (99.60).
6-(4-Methoxyphenyl)pyridazin-3(2H)-one (6b):13b yellow solid;
145.4 mg (yield 72%); mp 185−188 °C; IR (KBr) 2931, 2839, 1650,
1
1594, 1573, 1512, 1251, 1008, 828, 558, 506 cm−1; H NMR (400
MHz, CDCl3) δ (ppm) 12.31 (s, 1H), 7.80−7.69 (m, 3H), 7.07 (d, J =
8.8 Hz, 1H), 6.98 (d, J = 8.4 Hz, 2H), 3.86 (s, 3H); 13C NMR (100
MHz, CDCl3) δ (ppm) 161.8, 160.7, 145.4, 131.5, 130.1, 127.3, 127.0,
114.3, 55.4; MS (EI) m/z 203.14 (M + 1, 12.75), 202.15 (M, 100.00),
201.15 (M − 1, 4.43), 145.11 (66.11), 131.08 (12.13), 115.07 (11.24),
103.08 (11.59), 102.06 (20.63).
6-(4-Nitrophenyl)pyridazin-3(2H)-one (6c):23 yellow solid; 145.4
mg (yield 67%); mp 247−249 °C; IR (KBr) 3317, 3222, 1633, 1518,
1
1342, 857, 756, 697 cm−1; H NMR (600 MHz, DMSO-d6) δ (ppm)
(6) Ten Brink, G.-J.; Arends, I. W. C. E.; Sheldon, R. A. Chem. Rev.
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(b) Mehta, G.; Venkateswaran, R. V. Tetrahedron 2000, 56, 1399.
(c) Ishihara, K.; Yano, T. Org. Lett. 2004, 6, 1983.
9.95 (s, 1H), 8.55 (d, J = 8.4 Hz, 1H), 8.44 (d, J = 9.0 Hz, 2H), 7.85−
7.78 (m, 1H), 7.55 (s, 2H); 13C NMR (100 MHz, DMSO-d6) δ (ppm)
164.8, 156.7, 155.2, 148.6, 141.3, 135.9, 134.1, 128.8, 128.6, 128.3,
124.3; MS (EI) m/z 217.14(M, 4.23), 184.15 (69.36), 176.39 (6.65),
166.13 (7.49), 165.23 (5.23), 159.21 (100.00).
6-(Naphthalen-2-yl)pyridazin-3(2H)-one (6d):24 yellow solid;
155.4 mg (yield 70%); mp 241−246 °C; IR (KBr) 2925, 2854,
(9) (a) Chen, Y.; Wang, Y. J.; Sun, Z. M.; Ma, D. W. Org. Lett. 2008,
10, 625. (b) Malakar, C. C.; Schmidt, D.; Conrad, J.; Beifuss, U. Org.
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Cui, L. Y.; Guo, S. H.; Wang, J. J.; Zhang, X. Y. Eur. J. Org. Chem.
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A Z.; Yang, S. R. J. Org. Chem. 2010, 75, 6700. (b) Bajracharya, G. B.;
Daugulis, O. Org. Lett. 2008, 10, 4625. (c) Yan, Y. Z.; Xu, K.; Fang, Y.;
Wang, Z. Y. J. Org. Chem. 2011, 76, 6849. (d) Liu, W.; Cao, H.; Zhang,
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1
1717, 1655, 1585, 1013, 827, 737, 480 cm−1; H NMR (600 MHz,
DMSO-d6) δ (ppm) 13.29 (s, 1H), 8.46 (s, 1H), 8.24 (d, J = 10.2 Hz,
1H), 8.07−7.99 (m, 3H), 7.98−7.94 (m, 1H), 7.61−7.55 (m, 2H),
7.06 (d, J = 9.6 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ (ppm)
160.4, 143.7, 133.1, 132.9, 132.0, 131.6, 130.3, 128.6, 128.5, 127.6,
127.0, 126.8, 125.2, 123.0; MS (EI) m/z 223.18 (M + 1, 15.60),
222.16 (M, 100.00), 221.17 (M-1, 11.08), 194.15 (16.42), 166.13
(16.03), 165.11 (78.65), 164.10 (17.79), 163.11 (15.52), 152.11
(10.84), 139.12 (10.31), 115.13 (12.94).
6-(Thiophene-2-yl)pyridazin-3(2H)-one (6e):25 yellow solid; 108.6
mg (yield 61%); mp 153−157 °C; IR (KBr) 3371, 3081, 3068, 2928,
1
2850, 1678, 1657, 1587, 1009, 832, 729, 594 cm−1; H NMR (600
MHz, DMSO-d6) δ (ppm) 13.11 (s, 1H), 8.06 (d, J = 9.6 Hz, 1H),
7.71−7.69 (m, 1H), 7.65 (d, J = 4.8 Hz, 1H), 7.18−7.15 (m, 1H), 7.02
(d, J = 9.6 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ (ppm) 160.0,
140.6, 139.1, 130.7, 130.2, 128.2(4), 128.1(8), 126.5; MS (EI) m/z
179.09 (M + 1, 11.28), 178.10 (M, 100.00), 122.06 (18.83), 121.04
(86.89).
ASSOCIATED CONTENT
■
S
* Supporting Information
(13) (a) Mason, J. W.; Aldous, D. L. In The Chemistry of Heterocyclic
Compounds; Weissberger, A., Taylor, E. C., Eds.; Wiley-Interscience:
New York, 1973; Vol. 28, p 24. (b) Coates, W. J.; Mckillop, A.
Synthesis 1992, 334.
1
Evidence in support of the hypothetic mechanism and H and
13C NMR spectra of compounds 3a−m and 6a−e. This
material is available free of charge via the Internet at http://
pubs.acs.org.
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Heterocycles 1991, 32, 1387.
(17) Nakayama, J.; Konishi, T.; Ishii, A.; Hoshino, M. Bull. Chem. Soc.
Jpn. 1989, 62, 2608.
AUTHOR INFORMATION
Corresponding Author
*E-mail: gdyin@hbnu.edu.cn; chwuax@mail.ccnu.edu.cn.
Notes
■
The authors declare no competing financial interest.
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The Journal of Organic Chemistry
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