New heterocycles of 2,3-diaryl-substituted maleic hydrazides

Article abstract of DOI:10.1002/jhet.631

2,3-Diaryl-substituted maleic anhydrides were prepared by a modified one-pot synthesis of Perkin condensation using mixed sodium salts of arylglyoxylic acid and arylacetic acid with acetic anhydride in 1,4-dioxane. The treatment of these anhydrides with ammonium bicarbonate, or methanolic hydrazine, offered the corresponding 2,3-diaryl-substituted maleimides and maleic hydrazides (4,5-diaryl-substituted 1,2-dihydropyridazine-3,6-dione), respectively. Evidence obtained from NMR, UV, and mass spectra suggest that 2,3-diaryl-substituted maleic hydrazides do not exhibit monolactim forms. Ring contraction of the diaryl-substituted maleic hydrazide by nitrosation led to the formation of the corresponding maleimide. Interconversion between the corresponding maleic hydrazide and maleimide was observed following equilibrium reaction. Our experiment proposes that the chemistry of 2,3-diaryl-substituted maleic hydrazides rarely involves the function of ethylene moiety and resembles that of succinic hydrazine. Copyright

Full text of DOI:10.1002/jhet.631

November 2011
New Heterocycles of 2,3-Diaryl-Substituted Maleic Hydrazides
Hsiencheng Shih[1],a* Renshuay J. Shih,b and Dennis A. Carsona
1243
aDepartment of Medicine, University of California, San Diego, La Jolla, California 92093
bPharmatek Laboratories, 7730 Carroll Road, Suite 200, San Diego, California 92121
*E-mail: hsiencheng@sbcglobal.net
Received March 30, 2010
DOI 10.1002/jhet.631
Published online 19 July 2011 in Wiley Online Library (wileyonlinelibrary.com).
2,3-Diaryl-substituted maleic anhydrides were prepared by a modified one-pot synthesis of Perkin con-
densation using mixed sodium salts of arylglyoxylic acid and arylacetic acid with acetic anhydride in 1,4-
dioxane. The treatment of these anhydrides with ammonium bicarbonate, or methanolic hydrazine, offered
the corresponding 2,3-diaryl-substituted maleimides and maleic hydrazides (4,5-diaryl-substituted 1,2-
dihydropyridazine-3,6-dione), respectively. Evidence obtained from NMR, UV, and mass spectra suggest
that 2,3-diaryl-substituted maleic hydrazides do not exhibit monolactim forms. Ring contraction of the
diaryl-substituted maleic hydrazide by nitrosation led to the formation of the corresponding maleimide.
Interconversion between the corresponding maleic hydrazide and maleimide was observed following equi-
librium reaction. Our experiment proposes that the chemistry of 2,3-diaryl-substituted maleic hydrazides
rarely involves the function of ethylene moiety and resembles that of succinic hydrazine.
J. Heterocyclic Chem., 48, 1243 (2011).
INTRODUCTION
form, 2,3-diphenyl maleic hydrazide (4, mp 350ꢀC) [8], none
have been previously characterized by NMR.
Maleic hydrazide (1,2-dihydropyridazine-3,6-dione, 1)
is a well-known plant growth regulator [2] due to its
ability to inhibit glycogen synthase [3]. The growth in-
hibiting activity of 1 has been demonstrated to be asso-
ciated with its free radical intermediate, formed readily
by oxidation [4]. Although analysis of 1 by NMR indi-
cates that it favors the aromatic form of 3,6-dihydroxy-
pyridazine 1b, studies by ESR spectroscopy suggest it
exists almost entirely in the monolactim form, 6-hydrox-
ypyridazin-3(2H)-one, 1c [4]. Due to the tautomeric iso-
forms, the relative acidity of the hydroxyl proton in ma-
leic hydrazine offers beneficial properties in the design
of bioactive compounds [5].
Our research involved an interest in synthesizing a se-
ries of 2,3-diaryl substituted maleic hydrazides for their
role as potential glycogen synthase kinase-3 inhibitors,
as they potentially hold therapeutic benefits for treat-
ments of Type II diabetes, neurodegenerative diseases
such as Alzheimer’s disease, and certain forms of cancer
[9–11]. The current results of our research introduces
novel information regarding the preparation and chemis-
try of 2,3-diaryl-substituted maleic hydrazides.
Currently, only a few compounds of 2,3-disubstituted ma-
leic hydrazides have been reported in literature and are sug-
gested to favor specific monolactim forms. Of those reported,
such as 2,3-dimethyl (2, mp 347–351ꢀC) [6], 2-methyl-3-
phenyl (3, mp 322–326ꢀC) [7] and the notable monolactim
RESULTS AND DISCUSSION
It is well-known that one of the options for preparing
maleimide is from the reaction of maleic anhydride with
C
V
2011 HeteroCorporation

1244
H. Shih, R. J. Shih, and D. A. Carson
Vol 48
Scheme 1. Synthesis of diaryl-substituted maleic anhydrides, imides,
and hydrazides.
an amine [12]. Originally, we were interested in synthe-
sizing a reference maleimide, 5 (SB216763) [10], for bi-
ological study from its corresponding anhydride, 2-(2,4-
dichlorophenyl)-3-(1-methyl-3-indolyl)maleic anhydride,
6. In 1992, Davis et al, reported the synthesis of a series
of diaryl-substituted maleic anhydrides and maleimides
[13]. However, in using their procedure, we were unable
to isolate 6 from a small scale reaction (400 mg) of
1-methyl-3-indolylglyoxylyl chloride with 2,4-dichloro-
phenylacetic acid, using Et3N as a base in dichlorome-
thane [13]. The use of stronger bases such as sodium
methoxide, potassium t-butoxide, and sodium hydride in
THF at 60–100ꢀC, did not increase the isolation of the
desired product, 6, in the same scale reaction.
of 2,3-diaryl-substituted maleic anhydrides, 8–25
(Scheme 1; Table 1). We observed that the presence of
electron withdrawing groups, such as NO2 or Cl, may
activate the a-hydrogen of arylacetic acid and then
enhance condensation to increase the yield of product.
The yields of resulting products were observed in the
order of para- > meta- > ortho-substitution moieties of
phenylacetic acid in small-scale synthesis.
In 1941, Koelsch and Wawzonek [12] investigated
various routes for anhydride formations and reported an
improved method of synthesizing diphenylmaleic anhy-
dride, 7. Their procedure involved a Perkin condensation
of the sodium or potassium salt of benzoylformic acid
with substituted phenylacetic acid in acetic anhydride.
In 1990, Fields et al. [14] prepared several hundred
grams of a series of diaryl-substituted maleic anhydrides
in high yields by following Koelsch and Wawzonek’s
procedure with some modification. Using this modifica-
tion, we were also able to obtain a 40% yield of 7,
while using a smaller scale reaction (250 mg of ben-
zoylformic acid). Our analysis of the Perkin condensa-
tion, which refluxes the sodium or potassium salt of one
acid with another acid in acetic anhydride, found that
the mixed salts of both acids can be formed during the
reaction. Accordingly, we developed a new modified
one-pot synthesis by refluxing a mixture of benzoylfor-
mic acid (250 mg), phenylacetic acid (1.0 molar equiv),
and NaH (2.5 molar equiv) in 1,4-dioxane for 30 min,
followed by addition of an excess acetic anhydride (6
molar equiv) with continuous reflux overnight. As a
result, our process granted a 69% yield of the desired
product, 7, without a need to prepare the sodium or po-
tassium salt of arylglyoxylic or arylacetic acid in
advance. It is important to note that 1-methyl-3-indolyl-
glyoxylic acid and 2,4-dichlorophenylacetic acid are
bulky compounds and will cause steric hindrance during
the subsequent condensation reaction. With this limita-
tion, however, we were able to obtain 6 in a yield of
11% using a small scale reaction (400 mg) by following
this same procedure. This convenient modified one-pot
procedure provided a yield up to 86% for a series
Subsequently,
the
reference
maleimides,
5
(SB216763) [10] and 26–28 (Scheme 1; Table 1), were
prepared from the reaction of the corresponding maleic
anhydrides with methanolic ammonium bicarbonate (6
equiv), or anhydrous ammonia in a steel bomb at
100ꢀC. The NMR spectra of 5, and 26–28 appeared
very similar to those of the corresponding maleic anhy-
drides, 6–9, except for the appearance of an imide pro-
ton peak around d11.2 (Fig. 1). In 1970, Berry and Bur-
awoy [8] reported the synthesis of 6-hydroxy-4,5-diphe-
nylpyridazine-3(2H)-one, 4, mp 350ꢀC, a monolactim
form of 2,3-diphenylmaleic hydrazide. They obtained
this compound by heating 7 and hydrazine hydrochlor-
ide in dilute hydrochloride (5 mL) and water (60 mL),
in a Carius tube at 185ꢀC for 12 h. Unfortunately, their
results did not include evidence of an NMR spectrum
for characterization of the product. In our experiment,
the treatment of 7 with anhydrous hydrazine (3 molar
equiv) and methanol in a steel bomb at 100ꢀC offered a
product with a much lower melting point, 216–217ꢀC.
In accordance with similar NMR chemical shift patterns
to 7, except for a single peak near d4.9 due to the pro-
tons of hydrazide (Fig. 1), we assigned the product as
2,3-diphenylmaleic hydrazide, 29. This simple method
permitted us to synthesize a series of diaryl-substituted
maleic hydrazides, 30–48, with good yields (Scheme 1;
Table 1). The NMR spectra of 30–48 were also in
excellent similarity with those of the corresponding ma-
leic anhydrides with the exception of protons pertaining
to hydrazides (Fig. 1).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2011
New Heterocycles of 2,3-Diaryl-Substituted Maleic Hydrazides
1245
Table 1
Synthesis of diaryl-substituted maleic anhydrides,
imides, and hydrazides.
.
Hetero
Product Atom (X)
Ar1
Ar2
Yield%
5
6
7
NH
O
O
2,4-Cl2C6H3 l-CH3-3-indolyl
2,4-Cl2C6H3 l-CH3-3-indolyl
75a
11
67
40
42
86
23
15
14
18
52
40
28
35
43
36
36
69
36
42
13
95a
42b
68a
80
75
72
95
64
32
64
95
54
48
71
89
59
58
95
72
94
54
44
95
C6H5
C6H5
C6H5
3,4-(HC3O)2C6H3
C4H3S
8
9
O
O
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C6H5
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
O
O
C6H5
2-ClC6H4
Figure 1. NMR spectra of the corresponding diaryl-substituted maleic
anhydride, imide, and hydrazide.
O
2-CH3OC6H4
2-CH3C6H4
2-NO2C6H4
3-ClC6H4
3-CH3OC6H4
3-CH3C6H4
3-NO2C6H4
3-ClC6H4
O
O
the pattern of [Ar1ACBCAAr2]þl was found in the
mass spectra of the corresponding maleic anhydrides,
imides, and hydrazides (Fig. 3). The identical
[Ar1ACBCAAr2]þl pattern seen in the ions are the
result of cleavages between the diaryl-substituted ethyl-
ene moiety and the rest of the heterocycle with loss of
O
O
O
O
O
O
O
4-CH3OC6H4
4-CH3C6H4
4-NO2C6H4
2,4-Cl2C6H3
3,4-(CH3O)2C6H3
l-CH3-3-indolyl
C6H5
O
O
O
O
NH
NH
NH
C6H5
C6H3S
C6H5
3,4-(CH3O)2C6H3
C4H3S
C6H5
NHNH
NHNH
NHNH
NHNH
NHNH
NHNH
NHNH
NHNH
NHNH
NHNH
NHNH
NHNH
NHNH
NHNH
NHNH
NHNH
NHNH
NHNH
NHNH
NHNH
2,4-Cl2C6H3 l-CH3-3-indolyl
C6H5
3,4-(CH3O)2C6H3
C4H3S
C6H5
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
C4H3S
2-ClC6H4
2-CH3OC6H4
2-CH3C6H4
2-NO2C6H4
3-ClC6H4
3-CH3OC6H4
3-CH3C6H4
3-NO2C6H4
3-ClC6H4
4-CH3OC6H4
4-CH3C6H4
4-NO2C6H4
2,4-Cl2C6H3
3,4-(CH3O)2C6H3
l-CH3-3-indolyl
a Method B-1.
b Method B-2.
The UV absorption characteristics of diaryl-substi-
tuted maleic hydrazides are comparable to their corre-
sponding maleic anhydrides and imides (Fig. 2) suggest-
ing that they have similar chromophores.
Under further electron impact study, the strong char-
acteristic peak of a molecular ion with the same mass in
Figure 2. UV spectra of the corresponding diaryl-substituted maleic
anhydride, imide, and hydrazide.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1246
H. Shih, R. J. Shih, and D. A. Carson
Vol 48
Figure 3. Mass spectra of the corresponding diaryl-substituted maleic anhydride, imide, and hydrazide.
C2O3þl,C2O2NHþl, and C2O2N2H2þl, in the afore-
mentioned corresponding structures, respectively (Fig.
4). The data obtained from NMR, UV, and mass spectra
for the corresponding maleic anhydrides, imides, and
hydrazides, do not reveal information of hydroxyl group
and suggest that the 2,3-diaryl-substituted maleic hydra-
zides do not demonstrate the monolactim form.
the mono-nitroso hydrazine is formed initially by elec-
trophilic attack of nitrosonium cation, which is then fol-
lowed by the ring contraction and concomitant forma-
tion of the corresponding maleimides (Scheme 3).
Under hydrogenolysis using 10% palladium on car-
bon, these maleic hydrazide moieties remained intact,
but the nitro group present on the phenyl ring were
reduced to an amino group (d4.77, 2H, NH; 5.74, 2H,
NH2). The steric interference of the diaryl substituents
may play an important role in preventing the approach
of hydrogen on the ethylene moiety. Treatment of these
diaryl-substituted maleic hydrazides with methyl iodide
in the presence of NaH offered mono or dialkyl maleic
hydrazides as detected by mass spectra. These results
indicate that the NAN bond of these compounds do not
exhibit tautomerism as seen in pyridazine-3,6-diol, 1b,
or its monolatim form, 1c, and are vulnerable to electro-
philes, such as alkylating agents. Additionally, the
In addition to the previous information obtained from
NMR, UV, and mass spectra, the melting point of 4 was
significantly different from that of 29. The variation in
melting points may theoretically allow separation of
both products if produced in the same reaction. Conse-
quently, 4 and 29 should not be classified as tautomeric
isomers, contrasting 1, 1b, and 1c. Furthermore, it is
possible that a product of diphenyldiazoquinone, 49,
could be generated via further oxidation [15] of 29 dur-
ing the reaction conditions used to generate 4 [8], which
would be followed by hydration to form a di-monolac-
tim bishydrazide [16], 50 (Scheme 2). The elemental
analysis of this hypothesized compound, 50 (C, 73.0; H,
4.2; N, 10.6), closely follows the reported characteristic
of 4 (C, 72.6; H, 4.6; N, 10.7) [8]. As a result, we
deduce that 4 is not a monolactim form of 29, but a
bishydrazide, 50.
In studying the chemical functions of diaryl-substi-
tuted maleic hydrazides, compounds 29–32 were treated
with 1.2 equiv. of NaNO2 with 30% HOAc in CH2Cl2
at room temperature, but did not result in the production
of nitroso products. Instead, the chemical shift patterns
of the products were in excellent agreement with
those of the corresponding maleimides, 5, and 26–28.
The proposed mechanism for this reaction suggests that
Figure 4. The pattern of molecular ions in the mass spectra of the cor-
responding maleic imides, anhydrides, and hydrazides.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2011
New Heterocycles of 2,3-Diaryl-Substituted Maleic Hydrazides
1247
Scheme 2. Proposed formation of hypothesized bishydrazide 50.
2,3-Diaryl-substituted maleimides (3,4-diaryl-1H-pyrrole-
2,5-dione). A mixture of 2,3-diarylmaleic anhydride (200–400
mg, 1 molar equiv) and anhydrous ammonium bicarbonate (6
molar equiv), or saturated anhydrous NH3 in methanol (40
mL), was heated overnight in a stainless steel bomb at 100ꢀC.
After cooling, the reaction mixture was evaporated, dissolved
in EtOAc (50 mL) and washed with water. The organic phase
was dried over anhydrous magnesium sulfate and evaporated.
The residue was chromatographed on silica gel with a mixture
of 1% acetone in dichloromethane to give the desired product.
NaNO2 (1.2 equiv.) was added slowly to a mixture of 2,3-
diaryl-substituted maleic hydrazine (20–100 mg) in 10 mL of
30% HOAc in CH2Cl2 with stirring at RT for 30 min to 1 h.
The reaction mixture was evaporated. The residue in ethyl ace-
tate (50 mL) was washed twice with water and dried over an-
hydrous MgSO4 and then evaporated. The residue was chroma-
tographed on silica gel with a mixture of 1% acetone in
dichloromethane to give the product.
2,3-Diaryl-substituted maleic hydrazides (4,5-Diaryl-1,2-
dihydropyridazine-3,6-dione). A mixture of 2,3-diarylmaleic
anhydride (200–400 mg, 1 molar equiv) and anhydrous hydra-
zine (3 molar equiv) in methanol (50 mL) was heated in a
stainless steel bomb at 100ꢀC overnight. After cooling, the
resulting crystals were collected. The remaining solution was
evaporated. The residue was chromatographed on silica gel
with a mixture of 2% acetone in dichloromethane to give
another crop of product.
corresponding maleic hydrazides and maleimides are
interconvertable in an equilibrium condition during the
treatment of maleic hydrazide with methanolic ammo-
nium bicarbonate, or vice versa in the treatment of mal-
eimide with methanolic hydrazine at 60–100ꢀC (Scheme
1). The intermediate was identified by mass spectros-
copy as 2,3-diaryl-4-hydrazino-4-oxobut-2-enamide.
These 2,3-diaryl-substituted maleic hydrazides have
lower melting points than 4 and their solubility in
dichloromethane make them highly nonpolar. The feasi-
bility of ring-opening reactions induced by nucleophilic
or electrophilic reagents should not involve the ethylene
moiety function. We believe that the configurations seen
in these heterocyclic compounds result from the steric
repulsion and influence of strain between the two diaryl
substituents, which force out planarity of the aromatic
sextet.
In summary, the chemistry of 2,3-diaryl-substituted
maleic hydrazides resembles that of succinic hydrazine.
They react readily with oxidants, alkylating agents, other
electrophiles, and nucleophiles. Currently, we are inves-
tigating further into the chemical and biological activ-
ities of diaryl-substituted maleic hydrazides.
3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyr-
role-2,5-dione (SB216763) (5) [10,17]. Mp 195–197ꢀC; MS
m/z, 370 (Mþ); 1H NMR (DMSO-d6) d 3.89 (s, 3H, CH3),
6.32 (d, 1H, C4H), 6.78 (t, 1H, C6H), 7.12 (t, 1H, C5H),
7.35–7.50 (m, 3H, C7H, C05H, & C06H), 7.71 (s, 1H, C03H),
8.09 (s, 1H, C2H), 11.17 (s, 1H, NH).
EXPERIMENTAL
Melting points were taken on a Mel-Temp apparatus and are
1
uncorrected. H NMR spectra were obtained from Varian 500-
MHz. Mass spectra were recorded by a Hewlett-Packard 5890
GCMS instrument operated at 70 eV ionizing energy at the
Mass Spectrometry Facility, University of California, River-
side, CA. A DB-5 capillary column was used for the sample
introduction. All chemicals including 2-thiopheneglyoxylic
acid (95%) were purchased from Aldrich Chemical Company
and used without further purification.
Scheme 3. The proposed mechanism for the conversion of diaryl-sub-
stituted maleic hydrazide to imide.
General procedures. 2,3-Diaryl-substituted maleic anhy-
drides (3,4-diarylfuran-2,5-dione). To a mixture of arylglyox-
ylic acid (200–400 mg,1 molar equiv) and arylacetic acid (1
molar equiv) in dry 1,4-dioxane (60 mL), NaH (2.5 molar
equiv) was added and stirred at 100ꢀC for 30 min. Acetic
anhydride (5 molar equiv) was introduced dropwise to the
resulting suspension with stirring overnight. After cooling, the
reaction mixture was evaporated in vacuo. The residue was
dissolved in ethyl acetate (50 mL) and washed twice with
water. The organic phase was dried and evaporated. The resi-
due was chromatographed on silica gel with a mixture of 30%
hexane in dichloromethane to give desired product, or added
small amount of methanol (20 mL) to yield solidified product.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1248
H. Shih, R. J. Shih, and D. A. Carson
Vol 48
3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)furan-2,5-
3-(3-Nitrophenyl)-4-(2-thienyl)furan-2,5-dione (18). Mp
141-143 ꢀC; 1H NMR (DMSO-d6) d 7.22 (t, 1H, C4H), 7.77
(d, 1H, C5H), 7.89 (t, 1H, C50H), 7.94–7.99 (m, 2H, C3H,
C06H), 8.41 (s, 1H, C02H), 8.42 (d, 1H, C04H); Anal. Calcd.
for C14H7NO5S: C, 55.81; H, 2.34; N, 4.65. Found: C, 55.86;
H, 2.35; N, 4.57.
dione (6) [17] Mp 163–165ꢀC; 1H NMR (DMSO-d6) d 6.33
(d, 1H, C4H), 6.83 (t, 1H, C6H), 7.19 (t, 1H, C5H), 7.48 (d,
1H, C7H), 7.50–7.56 (m, 2H, C05H, C06H), 7.80 (s, 1H,
C03H), 8.29 (s, 1H, C2H).
3,4-Diphenylfuran-2,5-dione (7) [18] Mp 148–150ꢀC; MS
m/z, 250 (Mþ); 1H NMR (DMSO-d6) d 7.40–7.50 (m, 10 H,
phenyl protons).
3-(4-Chlorophenyl)-4-(2-thienyl)furan-2,5-dione (19). Mp
1
124–126ꢀC; MS m/z, 290 (Mþ); H NMR (DMSO-d6) d 7.20
3-(3,4-Dimethoxyphenyl)-4-phenylfuran-2,5-dione (8) [14]. Mp
1
(t, 1H, C4H), 7.55 (d, 2H, C02H, C06H), 7.64 (d, 2H, C03H,
C05H), 7.75 (d, 1H, C5H), 7.93 (d, 1H, C3H); Anal. Calcd. for
C14H7ClO3S: C, 57.84; H, 2.43. Found: C, 57.52; H, 2.51.
3-(4-Methoxyphenyl)-4-(2-thienyl)furan-2,5-dione (20). Mp
111–113ꢀC; MS m/z, 310 (Mþ); H NMR (DMSO-d6) d 3.46
(s, 3H, OCH3), 3.78 (s, 3H, OCH3), 6.92 (s, 1H, C02H), 7.04
(d, 1H, C05H), 7.18 (d, 1H, C06H), 7.42-7.50 (m, 5H, phenyl
protons).
1
124–126ꢀC; MS m/z, 286 (Mþ); H NMR (DMSO-d6) d 3.83
3,4-Di-2-thienylfuran-2,5-dione (9) [14] Mp 110-113ꢀC;
(s, 3H, CH3O), 7.10 (d, 2H, C03H, C05H), 7.19 (t, 1H, C4H),
7.50 (d, 2H, C02H, C06H), 7.76 (d,1H, C5H), 7.89 (d, 1H,
C3H); Anal. Calcd. for C15H10O4S.0.2H2O: C, 62.14; H, 3.62.
Found: C, 61.84; H, 3.52.
1
MS m/z, 262 (Mþ); H NMR (DMSO-d6) d 7.27 (t, 2H, C4H),
7.82 (d, 2H, C5H), 7.98 (d, 2H, C3H).
3-Phenyl-4-(2-thienyl)fuþran-2,5-dione (10) [14]. Mp 145-
147 ꢀC; MS m/z, 256 (M ); 1H NMR (DMSO-d6) d 7.19 (t,
1H, C4-H), 7.50–7.60 (m, 5H, phenyl protons), 7.73 (d, 1H,
C5H), 7.91 (d, 1H, C3H).
3-(4-Methylphenyl)-4-(2-thienyl)furan-2,5-dione (21). Mp
1
139–140ꢀC; MS m/z, 270 (Mþ); H NMR (DMSO-d6) d 2.39
(s, 3H, CH3), 7.19 (t, 1H, C4H), 7.36 (d, 2H, C30H, C05H),
7.42 (d, 2H, C02H, C06H), 7.45 (d, C5H), 7.90 (d, 1H, C3H);
Anal. Calcd. for C15H10O3S.0.1 H2O: C, 66.21; H, 3.78.
Found: C, 66.18; H, 3.47.
3-(2-Chlorophenyl)-4-(2-thiþenyl)furan-2,5-dione (11). Mp
1
ꢀ
118-119 C; MS m/z, 290 (M ); H NMR (DMSO-d6) d 7.23
(t, 1H, C4H), 7.52-7.58 (m, 2H, C04H, C06H), 7.63 (t, 1H,
C05H), 7.70-7.74 (m, 2H, C30H, C5H), 7.98 (d, 1H, C3H);
Anal. Calcd. for C14H7ClO3S: C, 57.84; H, 2.43; S, 11.03.
Found: C, 58.23; H, 2.82; S, 10.84.
3-(4-Nitrophenyl)-4-(2-thienyl)furan-2,5-dione (22). Mp
143–144ꢀC; MS m/z, 301 (Mþ); 1H NMR (DMSO-d6) d 7.22
(t, 1H, C4H), 7.73 (d, 1H, C5H), 7.81 (d, 2H, C02H, C06H),
7.97 (d, 1H, C3H), 8.41 (d, 2H, C03H, C05H); Anal. Calcd. for
C14H7NO5S: C, 55.81; H, 2.34; N, 4.65. Found: C, 55.80; H,
2.16; N, 4.64.
3-(2-Methoxyphenyl)-4-(2-thienyl)furan-2,5-dione (12). Mp
1
125–126ꢀC; MS m/z, 286 (Mþ); H NMR (DMSO-d6) d 3.70
(s, 3H, CH3O), 7.13 (t, 1H, C4H), 7.15-7.23 (m, 2H, C03H,
C05H), 7.37 (d, C06H), 7.56 (t, 1H, C04H), 7.71 (d, 1H, C5H),
7.93 (d, 1H, C3H); Anal. Calcd. for C15H10O4S: C, 62.93; H,
3.52. Found: C, 62.56; H, 3.85.
3-(2,4-Dichlorophenyl)-4-(2-þthienyl)furan-2,5-dione (23). Mp
1
140–141ꢀC; MS m/z, 324 (M ); H NMR (DMSO-d6) d 7.25
(t, 1H, C4H), 7.57 (d, 1H, C05H), 7.69 (d, 1H, C06H), 7.76 (d,
1H, C5H, 7.94 (d, 1H, C3H), 8.01 (s, 1H, C03H); Anal. Calcd.
for C14H6Cl2O3S: C, 51.71; H. 1.86. Found: C, 51.55; H, 2.08.
3-(3,4-Dimethoxyphenyl)-4-(2-thienyl)furan-2,5-dione (24). Mp
3-(2-Methylphenyl)-4-(2-thienyl)furan-2,5-dione (13). Mp
1
109–110ꢀC; MS m/z, 270 (Mþ); H NMR (DMSO-d6) d 2.14
(s, 3H, CH3), 7.19 (t, 1H, C4H), 7.31-7.48 (m, 4H, C03H,
C04H, C05H, C06H), 7.62 (d, 1H, C5H), 7.92 (d, 1H, C3H);
Anal. Calcd. for C15H10O3S: C, 66.65; H, 3.73. Found: C,
66.41; H, 4.14.
1
184–185ꢀC; MS m/z, 316 (Mþ); H NMR (DMSO-d6) d 3.69
(s, 3H, OCH3), 3.83 (s, 3H, OCH3), 7.11 ( s,1H, C02H), 7.14
(bs, 2H, C05H, C06H), 7.2 (t,1H, C4H), 7.81 (d,1H, C5H), 7.89
(d,1H, C3H); Anal. Calcd. for C16H12O5S: C, 60.75; H, 3.82.
Found: C, 60.40; H, 3.54.
3-(2-Nitrophenyl)-4-(2-thienyl)furan-2,5-dione (14). Mp
144–145ꢀC; MS m/z, 301 (Mþ), 1H NMR (DMSO-d6) d 7.22
(t, 1H, C4H), 7.72 (d, 1H, C5H), 7.75 (d, 1H, C06H), 7.92 (t,
1H, C04H), 7.98 (d, 1H, C3H), 8.01 (t, 1H, C05H), 8.42 (d, 1H,
C03H); Anal. Calcd. for C14H7NO5S: C, 55.81; H, 2.34; N,
4.65. Found: C, 55.44; H, 2.10; N, 4.60.
3-(3-Chlorophenyl)-4-(2-thienyl)furan-2,5-dione (15). Mp
90–91ꢀC; MS m/z, 290 (Mþ); 1H NMR (DMSO-d6) d 7.21 (t,
1H, C4H), 7.49 (d, 1H, C04H), 7.58–7.77 (m, 3H, C02H, C05H,
C06H), 7.76 (d, C5H), 7.95 (d, 1H, C3H); Anal. Calcd. for
C14H7ClO3S: C, 57.84; H, 2.43. Found: C, 57.98; H, 2.34.
3-(3-Methoxyphenyl)-4-(2-thienyl)furan-2,5-dione (16). Mp
99–100ꢀC; MS m/z, 286 (Mþ); 1H NMR (DMSO-d6) d 3.76
(s, 3H, CH3O), 7.07–7.09 (m, 2H, C02H, C04H), 7.11-7.14 (m,
1H, C06H), 7.20 (t, 1H, C4H), 7.48 (t, 1H, C05H), 7.76 (d, 1H,
C5H), 7.92 (d, 1H, C3H); Anal. Calcd. for C15H10O4S.0.1Hex-
ane: C, 62.77; H, 3.97. Found: C, 62.94; H, 4.05.
3-(1-Methyl-1H-indol-3-yl)-4-(2-thienyl)furan-2,5-dione (25)
[13]. Mp 122–124ꢀC; 1H NMR (DMSO-d6) d 3.94 (s, 3H,
CH3), 6.75 (d, 1H, C04H), 6.70 (t, 1H, C06H), 7.11 (t, 1H,
C4H), 7.24 (t, 1H, C05H), 7.31 (d, 1H, C5H), 7.59 (d, 1H,
C07H), 7.85 (d, 1H, C3H), 8.08 (s,1H, C02H).
3,4-Diphenyl-1H-pyrrole-2,5-dione (26) [19]. Mp 214–
1
216ꢀC; H NMR (DMSO-d6,) d 7.36 (m, phenyl), 11.21 (NH).
3-(3,4-Dimethoxyphenyl-4-phenyl-)-þ1H-pyrrole-2,5-dione
(27). Mp 207–208ꢀC; MS m/z, 309 (M ); 1H NMR (DMSO-
d6) d 3.46 (s, 3H, OCH3), 3.75 (s, 3H, OCH3), 6.87 (s, 1H,
C02H), 6.95 (d, 1H, C05H), 7.07 (d, 1H, C06H), 7.32–7.42 (m,
5H, phenyl protons), 11.4 (s, 1H, NH), Anal. Calcd. for
C18H15NO4: C, 69.89; H, 4.89; N4.53. Found: C, 70.09; H,
5.13; N, 4.31.
3,4-Di-2-thienyl-1H-pyrrole-2,5-dione (28). Mp 200–202ꢀC;
1
3-(3-Methylphenyl)-4-(2-thþienyl)furan-2,5-dione (17). Mp
MS m/z, 261 (Mþ); H NMR (DMSO-d6) d 7.19 (t, 2H, C4H),
1
105–106ꢀC; MS m/z, 270 (M ); H NMR (DMSO-d6) d 2.35
7.71 (d, 2H, C5H), 7.87 (d, 2H, C3H), 11.35 (s, 1H, NH);
Anal. Calcd. for C12H7NO2S2.0.1H2O: C, 54.80; H, 2.76; N,
5.33. Found: C, 54.78; H, 3.09; N, 5.34.
(s, 3H, CH3), 7.19 (t, 1H, C4H), 7.30 (d, 1H, C04H), 7.32 (s,
1H, C02H), 7.37 (d, 1H, C06H), 7.44 (t, 1H, C05H), 7.75 (d,
1H, C5H), 7.90 (d, 1H, C3H); Anal. Calcd. for C15H10O3S: C,
66.65; H, 3.73. Found: C, 66.60; H, 3.97.
4,5-Diphenyl-1,2-dihydropyridazine-3,6-dione (29). Mp
1
216–217ꢀC; MS m/z, 264 (Mþ); H NMR (DMSO-d6) d 4.87
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2011
New Heterocycles of 2,3-Diaryl-Substituted Maleic Hydrazides
1249
(s, 2H, NH), 7.26–7.43 (m, 10H, phenyl protons); Anal. Calcd.
for C16H12N2O2: C, 72.72; H, 4.58; N, 10.67. Found: C,
72.37; H, 4.98; N, 10.67.
(m, 3H, C02H, C04H, C05H), 7.66 (d, 1H, C5H), 7.82 (d, 1H,
C3H); Anal. Calcd. C14H9ClN2O2S: C, 55.26; H, 2.98; N,
9.21. Found: C, 55.49; H, 3.37; N, 9.34.
4-(2,4-Dichlorophenyl)-5-(1-methyl-1H-indol-3-yl)-1,2-dihy-
dropyridazine-3,6-dione (30). Mp 256–258ꢀC; MS m/z, 385
4-(3-Methoxyphenyl)-5-(2-thienyl)-1,2-dihydropyridazine-3,6-
dione (39). Mp 142–144ꢀC; MS m/z, 300 (Mþ); 1H NMR
(DMSO-d6) d 3.74 (s, 3H CH3O), 4.85 (s, 2H, NH), 6.99 (s,
1H, C02H), 7.0 (d, 1H, C04H), 7.06 (d, 1H, C06H), 7.11 (t, 1H,
C4H), 7.42 (t, 1H, C05H), 7.65 (d, 1H, C5H), 7.79 (d, 1H,
C3H); Anal. Calcd. for C15H12N2O3S: C, 59.99; H, 4.03; N,
9.33. Found: C, 60.04; H, 4.15; N, 9.46.
4-(3-Methylphenyl)-5-(2-thienyl)-1,2-dihydropyridazine-3,6-
dione (40). Mp 176–177ꢀC; MS m/z, 284 (Mþ); 1H NMR
(DMSO-d6) d 2.33 (s, 3H, CH3), d 4.86 (s, 2H, NH), 7.11 (d,
1H, C4H), 7.20–7.25 (m, 3H, C02H, C04H, C05H), 7.30 (d, 1H,
C06H), 7.64 (d, 1H, C5H), 7.77 (d, 1H, C3H); Anal. Calcd. for
C15H12N2O2S: C, 63.36; H, 4.25; N, 9.85. Found: C, 63.11, H,
4.54; N, 9.99.
4-(3-Nitrophenyl)-5-(2-thienyl)-1,2-dihydropyridazine-3,6-
dione (41). Mp 176–178ꢀC; MS m/z, 315 (Mþ); 1H NMR
(DMSO-d6) d 4.90 (s, 2H, NH), 7.15 (d, 1H, C4H), 7.67 (d,
1H, C5H), 7.80–7.84 (m, 2H, C3H, C05H), 7.93 (d, 1H, C06H),
8.32–8.38 (m, 2H, C02H, C04H); Anal. Calcd. for
C14H9N3O4S: C, 53.33; H, 2.88; N, 13.33. Found: C, 53.37; H,
2.79; N, 13.07.
1
(Mþ); H NMR (DMSO-d6) d 3.89 (s, 3H, CH3), 4.89 (s, 2H,
NH), 6.33 (d, 1H, C4H), 6.77 (t, 1H, C6H).7.13 (t, 1H, C5H),
7.37 (d, 1H, C7H), 7.39-7.49 (m, 2H, C05H, C06H), 7.72 (s,
1H, C03H), 8.13 (s, 1H, C2H); Anal. Calcd. for
C19H13N3Cl2O2: C, 59.09; H, 3.39; N, 10.88. Found: C, 58.83;
H, 3.46; N, 10.53.
4-(3,4-Dimethoxyphenyl)-5-phenyl-1,2-dihydropyridazine-3,6-
dione (31). Mp 171–173ꢀC; MS m/z, 324 (Mþ); 1H NMR
(DMSO-d6) d 3.46 (s, 3H, OCH3), 3.76 (s, 3H, OCH3), 4.84
(s, 2H, NH), 6.86 (s, 1H, C02H), 6.98 (d, 1H, C05H), 7.10 (d,
1H, C06H), 7.3-7.5 (m, 5H, phenyl protons); Anal. Calcd. for
C18H16N2O2.0.25 H2O: C, 65.73; H, 5.06; N, 8.52. Found: C,
65.85; H, 5.18; N, 8.64.
4,5-Di-2-thienyl-1,2-dihydrþopyridazine-3,6-dione (32). Mp
1
194–196ꢀC; MS m/z, 276 (M ); H NMR (DMSO-d6) d 4.85
(s, 2H, NH), 7.21 (t, 2H, 2C4H), 7.73 (d, 2H, 2C5H), 7.88 (d,
2H, 2C3H); Anal. Calcd. for C12H8N2O2S2: C, 52.16; H, 2.92;
N, 10.14; S, 23.2. Found: C, 51.96; H, 3.30; N, 10.23; S,
22.82.
4-Phenyl-5-(2-thienyl)-1,2-dihydropyridazine-3,6-dione (33). Mp
1
4-(4-Chlorophenyl)-5-(2-thienyl)-1,2-dihydropyridazine-3,6-
dione (42). Mp 158–159ꢀC; MS m/z, 304 (Mþ); 1H NMR
(DMSO-d6) d 4.86 (s, 2H, NH), 7.16 (t, 1H, C4H), 7.49 (d,
2H, C02H, C06H), 7.59 (d, 2H, C03H, C05H), 7.66 (d, 1H,
194–196ꢀC; MS m/z, 270 (Mþ); H NMR (DMSO-d6) d 4.85
(s, 2H, NH), 7.11 (t, 1H, C4AH), 7.43–7.46 (m, 2H, C03H,
C05H), 7.48–7.53 (m, 3H, C02H, C04H, C06H), 7.63 (d, 1H,
C5H), 7.79 (d, 1H, C3H); Anal. Calcd. for C14H10N2O2S.0.2
H2O: C, 61.39; H, 3.83; N, 10.23. Found: C, 61.49; H, 4.15;
N, 10.48.
C5H),
7.81
(d,
1H,
C3H);
Anal.
Calcd.
for
C14H9N2ClO2S.0.2H2O: C, 54.53; H, 3.07; N, 9.08. Found: C,
54.43; H, 3.02; N, 9.00.
4-(2-Chlorophenyl)-5-(2-thienyl)-1,2-dihydropyridazine-3,6-
dione (34). Mp 194–195ꢀC; MS m/z, 304 (Mþ); 1H NMR
(DMSO-d6) d 4.93 (s, 2H, NH), 7.14 (t, 1H, C4H), 7.45-7.52
(m, 2H, C04H, C06H), 7.54–7.61 (m, C03H, C05H), 7.67 (d, 1H,
C5H), 7.83 (d, 1H, C3H), Anal. Calcd. for C14H9ClN2O2S: C,
55.26; H, 2.98; N, 9.21. Found: C, 55.13; H, 3.29; N, 9.30.
4-(2-Methoxyphenyl)-5-(2-thienyl)-1,2-dihydropyridazine-3,6-
dione (35). Mp 139–140ꢀC; MS m/z, 300 (Mþ); 1H NMR
(DMSO-d6) d 3.66 (s, 3H, CH3O), 4.86 (s, 2H, NH), 7.08 (t,
1H, C05H), 7.11 (t, 1H, C4H), 7.17 (d, 1H, C03H), 7.25 (d, 1H,
C06H), 7.50 (t, C04H), 7.60 (d, C5H), 7.77 (d, 1H, C3H); Anal.
Calcd. for C15H12N2O3S: C, 59.98; H, 4.07; N, 9.33. Found:
C, 59.62; H, 4.27; N, 9.38.
4-(4-Methoxyphenyl)-5-(2-thienyl)-1,2-dihydropyridazine-3,6-
dione (43). Mp 153–156ꢀC; MS m/z, 300 (Mþ); 1H NMR
(DMSO-d6) d 3.83 (s, 3H, CH3O), 4.83 (s, 2H, NH), 7.06 (d,
2H, C03H, C05H), 7.12 (t, 1H, C4H), 7.42 (d, 2H, C02H,
C06H), 7.66 (d, 1H, C5H), 7.77 (d, 1H, C3H); Anal. Calcd. for
C15H12N2O3S: C, 59.98; H, 4.04; N, 9.33. Found: C, 59.76; H,
4.30; N, 9.36.
4-(4-Methylphenyl)-5-(2-thienyl)-1,2-dihydropyridazine-3,6-
dione (44). Mp 173–175ꢀC; MS m/z, 284 (Mþ); 1H NMR
(DMSO-d6) d 2.37 (s, 3H, CH3), 7.10 (t, 1H, C4H), 7.30–7.50
(q, 4H, C02H, C03H, C05H, C006H), 7.64 (d, 1H, C5H), 7.77 (d,
1H, C3H); Anal. Calcd. for C15H12N2O2S: C, 63.36; H, 4.25;
N, 9.85. Found: C, 63.63; H, 4.60; N, 9.71.
4-(2-Methylphenyl)-5-(2-thienyl)-1,2-dihydropyridazine-3,6-
dione (36). Mp 187–188; MS m/z, 284 (Mþ); 1H NMR
(DMSO-d6) d 2.14 (s, 3H, CH3), 4.85 (s, 2H, NH), 7.11 (t,
1H, C4H), 7.23 (d, 1H, C03H), 7.33 (t, 1H, C04H), 7.38 (d, 1H,
C06H), 7.41 (t, 1H, C05H), 7.51 (d, 1H, C5H), 7.77 (d,1H,
C3H); Anal. Calcd. for C15H12N2O2S: C, 63.36; H, 4.25; N,
9.85. Found: C, 63.40; H, 4.24; N, 9.91.
4-(2-Nitrophenyl)-5-(2-thienyl)-1,2-dihydropyridazine-3,6-
dione (37). Mp 195–196ꢀC; MS m/z, 315 (Mþ); 1H NMR
(DMSO-d6) d 4.97 (s, 2H, NH), 7.14 (t, 1H, C4H), 7.62 (d,
1H, C5H), 7.70(d, 1H, C06H), 7.82–7.86 (m, 2H, C04H, C3H),
7.93 (t, 1H, C05H), 8.35 (d, 1H, C03H); Anal. Calcd. for
C14H9N3O4S: C, 53.33; H, 2.87; N, 13.33. Found: C, 53.20; H,
3.01; N, 13.50.
4-(4-Nitrophenyl)-5-(2-thienyl)-1,2-dihydropyridazine-3,6-
dione (45). Mp 209–210ꢀC; MS m/z, 315 (Mþ); 1H NMR
(DMSO-d6,) d 4.90 (s, 2H, NH), 7.14 (t, 1H, C4H), 7.63 (d,
1H, C5H), 7.72 (d, 2H, C20H, C06H), 7.85 (d, 1H, C3H), 8.37
(d, 2H, C03H, C05H); Anal. Calcd. for C14H9N3O4S: C, 53.33;
H, 2.87; N, 13.33. Found: C, 52.98; H, 3.19; N, 13.42.
4-(2,4-Dichlorophenyl)-5-(2-thienyl)-1,2-dihydrþopyridazine-
1
3,6-dione (46). Mp 173–175ꢀC; MS m/z, 338 (M ); H NMR
(DMSO-d6) d 4.93 (s, 2H, NH), 7.17 (t, 1H, CA4H), 7.52 (d,
1H, C05H), 7.62 (d, 1H, C06H), 7.64 (d, 1H, C5H), 7.85 (d,
1H, 3H), 7.88 (s, 1H, C03H); Anal. Calcd. for C14H8N2Cl2O2S:
C, 49.57; H, 2.38; N, 8.26. Found: C, 49.56; H, 2.53; N, 8.17.
4-(3,4-Dimethoxyphenyl)-5-(2-thienyl)-1,2-dihydropyridazine-
1
3,6-dione (47). Mp 182–184ꢀC; MS m/z, 330 (Mþ); H NMR
4-(3-Chlorophenyl)-5-(2-thienyl)-1,2-dihydropyridazine-3,6-
dione (38). Mp 142–144ꢀC; MS m/z, 304 (Mþ); 1H NMR
(DMSO-d6) d 7.14 (t, 1H, C4H), 7.42 (d, 1H, C06H), 7.5–7.6
(DMSO-d6) d 3.67 (s, 3H, OCH3), 3.81 (s, 3H, OCH3), 4.83
(s, 2H, NH), 7.0–7.1 (m, 3H, C02H, C05H, C06H), 7.2 (t, 1H,
C4H), 7.81 (d, 1H, C5H), 7.89 (d, 1H, C3H); Anal. Calcd. for
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1250
H. Shih, R. J. Shih, and D. A. Carson
Vol 48
[6] Horning, R. H.; Amstutz, E. D. J Org Chem 1955, 20, 707.
[7] Bly, R. K.; Zoli, E. C.; Moore, J. A. J Org Chem 1964, 29,
C16H14N2O4S: C, 58.17; H, 4.27; N, 8.48. Found: C, 57.81; H,
4.22; N, 8.37.
2128.
4-(1-Methyl-1H-indol-3-yl)-5-(2-thienyl)-1,2-dihydropyrida-
zine-3,6-dione (48). Mp 210–212ꢀC; MS m/z, 323 (Mþ); 1H
NMR (DMSO-d6) d 4.83 (s, 2H, NH), 6.69 (d, 1H, C04H),
6.95 (t, 1H, C06H), 7.03 (t, 1H, C4H), 7.17–7.24 (m, 2H,
C07H, C5H), 7.55 (d, 1H, C05H), 7.71 (d, 1H, C3H), 7.93 (s,
1H, C20H); Anal. Calcd. for C17H13N3O2S: C, 63.54; H, 4.38;
N, 12.72; S, 9.65. Found: C, 63.14; H, 4.05; N, 12.99; S, 9.92.
[8] Berry, R. W. R.; Burawoy, R. A. J Chem Soc C 1970,
1316.
[9] Cross, D. A.; Culbert, A. A.; Chalmers, K. A.; Facci, L.;
Skaper, S. D. J Neurochem 2001, 77, 94.
[10] Meijer, L.; Flajolet, M.; Greengard, P. Trends Pharmacol
Sci 2004, 25, 241.
[11] Gurwitz, D.; Eldar-Finkelman, H. Drug Discov Today 2001,
6, 1072.
Acknowledgment. An abstract of this article was presented at
the 41st ACS Western Regional Meeting (October 9–13, 2007).
[12] Koelsch, C. F.; Wawzonek, S. J Org Chem 1941, 6, 684.
[13] Davis, P. D.; Hill, C. H.; Lawtom, G.; Nixon, J. S.; Wilkin-
son, S. E.; Hurst, S. A.; Keech, E.; Turner, S. J Med Chem 1992, 35,
177.
REFERENCES AND NOTES
[14] Fields, E. K.; Behrend, S. J.; Meyerson, S.; Winzenburg,
M. L.; Ortega, B. R.; Hall, K Jr. J Org Chem 1990, 55, 5165.
[15] Clement, R. A. J Org Chem 1960, 25, 1724.
[16] Kealy, T. J Am Chem Soc 1962, 84, 996.
[17] Coghan, M. P.; Fenwick, A. E.; Haigh, D.; Holder, J. C.;
Ife, R. J.; Reith, A. R.; Smith, D. G.; Ward, R.W. ( 2000) WO
200021927-A2 (cited reference for SB216763, but no data recorded).
[18] Heller, G. Annalen 1908, 358, 355.
[1]
Present address: Quadstar International Corporation, 1250
W. Monte, Mesa, AZ 85202.
[2] Audus, L. J. Plant Growth Substances, 2nd ed.; Hill: Lon-
don, 1959.
[3] Ozkan, A.; Yanikolu, A. J Appl Entomol 1999, 123, 211.
[4] Holton, D. M.; Hoyle, P. M.; Murphy, D. Tetrahedron Lett
1979, 30, 2821.
[5] Greenwood, J. R; Capper, H. R.; Allan, R. D.; Johnston, G.
A. R. J Chem 1988, 1, Article 21.
[19] Davis, P. D.; Bit, R. A. Tetrahedron Lett 1990, 31, 5201.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet