Synthesis of 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-oxo-1-aryl-4,5-dihydro-1H-pyrrole-3-carboxylates, a new triazafulvalene system

Article abstract of DOI:10.1016/j.tet.2010.04.025

(2E,3Z)-2-(1-Methyl-2,5-dioxoimidazolidin-4-ylidene)-3-[(arylamino- or heteroarylamino)methylene]succinate 5 obtained by [2+2] cycloaddition of (5Z)-5-[(dimethylamino)methylene]-3-methylimidazolidine-2,4-dione (1) and dimethyl acetylenedicarboxylate (2) followed by substitution of the dimethylamino group with aromatic or heteroaromatic amines, afforded by heating in ethanol in the presence of potassium hydroxide, potassium salts 6. Acidification of 6 with hydrochloric acid afforded mixtures of (E)- and (Z)-isomers of methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-oxo-1-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylates. On the other hand, alkylation of compounds 6 with methyl iodide or benzyl bromide produced the corresponding methyl (E)-4-(2-methoxy- or 2-benzyloxy-1-methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-oxo-1-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylates 9, derivatives of a new triazafulvalene system.

Full text of DOI:10.1016/j.tet.2010.04.025

Tetrahedron 66 (2010) 4346e4356
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-oxo-
1-aryl-4,5-dihydro-1H-pyrrole-3-carboxylates, a new triazafulvalene system
*
ꢀ
ꢀ ꢀ
Uros Ursic, Jurij Svete, Branko Stanovnik
ꢀ
ꢀ
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, 1000 Ljubljana, Slovenia
a r t i c l e i n f o
a b s t r a c t
Article history:
(2E,3Z)-2-(1-Methyl-2,5-dioxoimidazolidin-4-ylidene)-3-[(arylamino- or heteroarylamino)methylene]
Received 29 December 2009
Received in revised form 16 March 2010
Accepted 6 April 2010
succinate
5
obtained by [2þ2] cycloaddition of (5Z)-5-[(dimethylamino)methylene]-3-methyl-
imidazolidine-2,4-dione (1) and dimethyl acetylenedicarboxylate (2) followed by substitution of the
dimethylamino group with aromatic or heteroaromatic amines, afforded by heating in ethanol in the
presence of potassium hydroxide, potassium salts 6. Acidification of 6 with hydrochloric acid afforded
mixtures of (E)- and (Z)-isomers of methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-
oxo-1-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylates. On the other hand, alkylation of compounds 6
with methyl iodide or benzyl bromide produced the corresponding methyl (E)-4-(2-methoxy- or 2-
benzyloxy-1-methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-oxo-1-phenyl-4,5-dihydro-1H-pyrrole-3-carb-
oxylates 9, derivatives of a new triazafulvalene system.
Available online 10 April 2010
Dedicated to Professor Saverio Florio, Uni-
versity of Bari, on the occasion of his 70th
birthday
Keywords:
Ó 2010 Elsevier Ltd. All rights reserved.
[2þ2] Cycloaddition
Triazafulvalene
Acetylenedicarboxylate
(Hetero)aromatic amine
1. Introduction
atoms in the cross-conjugated systems are the smallest group.
There are a number of aza-analogs of sesquifulvalenes derived from
The 3-(dimethylamino)propenoates and related enaminones
have been demonstrated to be versatile building blocks in the
synthesis of many heterocyclic systems,1aed including the prep-
aration of natural products and their analogs, such as aplysi-
nopsins,2a,b meridianines,3a,b dipodazines,4aec and triprostatins.5
We have also reported an efficient method for preparation and
functionalization of highly substituted 1-amino-2,3-dihydro-1H-
pyrroles, 1-amino-1H-pyrroles, and fused pyrrolo[3,2-d]oxazole
system from 1,2-diazabuta-1,3-dienes and 3-(dimethylamino)
prop-2-enoates,6 and the regio- and stereoselective one-pot syn-
thesis of oxazolo fused pyridazines.7 Recently, we reported on
microwave assisted regiospecific [2þ2] cycloadditions of electron
poor acetylenes to 2-(acylamino)-3-(dimethylamino)prop-2-
enoates, which resulted in the formation of (1E,3E)-1-(acyla-
mino)-4-(dimethylamino)buta-1,3-dienes,8aec and some of their
transformations.9
azolyl-substituted 1,4-dihydropyridines by deprotonation of the
1-alkyl-4-azolylpyridinium salts using an anionic ion-exchange
resin, such as Amberlit IRA-401.10aec Some triazafulvalenes have
been prepared from the 2-(4-pyridyl)substituted intermediates11
and 4H-imidazole derivatives.12
2. Results and discussion
When 2(10E),3(400E)-2-[(dimethylamino)methylene]-3-(1-meth-
yl-2,5-dioxoimidazolidin-4-ylidene)succcinate (3), obtained from
(5Z)-5-[(dimethylamino)methylene]-3-methylimidazolidine-2,4-di-
one (1) anddimethyl acetylenedicarboxylate(Scheme 1)8c by heating
in acetonitrile under reflux for several hours, was heated in ethanol
Me
N
Me
N
O
O
O
O
i
As an extension of this research, we report here on the synthesis
of triazafulvalenes. The aza- and thiafulvalenes have received
considerable attention in synthetic chemistry and material
sciences. Among the azafulvalenes, those possessing three nitrogen
NH
NMe2
NH
COOMe
COOMe
61 %
NMe2
1
3
* Corresponding author. Tel.: þ386 1 2419 100; fax: þ386 1 2419 220; e-mail
Scheme 1. Reagents and conditions: (i) dimethyl acetylenedicarboxylate 2, acetoni-
trile, reflux.
address: branko.stanovnik@fkkt.uni-lj.si (B. Stanovnik).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.04.025

ꢀ ꢀ
U. Ursic et al. / Tetrahedron 66 (2010) 4346e4356
4347
Me
N
O
O
i
NH
NMe2
COOMe
COOMe
3
Me
N
Me
N
O
COOMe
O
O
O
NH
NH
HN Ar
+
COOMe
COOMe
5a-k m
COOMe
5'a-i k m
HN Ar
,
, -
Amine
4a
4b
4c
5, 5'
a
Ar
phenyl
5 and 5', yield (%)
5 : 5'
Time (h)
64
61
53
71
87
97
53
96
67
68
83
38
49
94 : 6
5
b
c
4-methylphenyl
2-methylphenyl
4-fluorophenyl
4-bromophenyl
2-iodophenyl
95 : 5
5
66 : 34
38 : 62
12 : 88
87 : 13
78 : 22
30 : 70
44 : 56
100 : 0
95 : 5
5
4d
4e
d
e
5
6.5
6.5
6.5
6.5
5
4f
f
4g
4h
4i
g
3-methoxyphenyl
3-nitrophenyl
h
i
4-hydroxyphenyl
4j
j
4-hydroxy-2-chlorophenyl
1-naphthyl
5
4k
4l
k
l
6.5
5.5
5.5
5-chloropyridin-2-yl
pyrazin-2-yl
0 : 100
8 : 92
4m
m
Scheme 2. Reagents and conditions: (i) ArNH2$HCl 4aed,g,i,j or ArNH2 4e,f,h,kem and 37% HCl, EtOH, reflux.
with aromatic or heteroaromatic amines 4aem as hydrochlorides or
in the presence of hydrochloric acid for 5e6.5 h mixtures of the
corresponding dimethyl (2E,3Z)-2/(1-methyl-2,5-dioxoimidazoli-
din-4-ylidene)-3-[(arylamino- or heteroarylamino)methylene]suc-
cinates 5aek,m and (2E,3E)-isomers 50aek, m were obtained in
49e97% yield (Scheme 2).
dNH¼10.09e11.73 ppm due to the hydrogen bond formation with
the ester carbonyl group in comparison to dNH¼8.26e9.66 ppm in
50-(E) isomers (Fig. 1).
Orientation around the C]C double bond was confirmed by
HMBC for compounds 5i, 50i, and 5j. Namely, in compounds 5i and
3
5j the heterocoupling constants J13C,H¼10.7 Hz and 10.4 Hz,
These compounds were heated in ethanol in the presence of
potassium hydroxide for 1 to 3.5 h. The precipitated products were
separated by filtration and washed with ethanol to give products
6aee,g,h,m in the form of potassium salts as dark red powders
(Scheme 3). By dissolving compounds 6aed,g,h,m in water, and 6k
in ethanol, and adding concentrated aqueous hydrochloric acid,
mixtures of (E)-methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imida-
zol-4(5H)-ylidene)-5-oxo-1-phenyl-4,5-dihydro-1H-pyrrole-3-car-
boxylates 7aed,g,h,k,m and (Z)-isomers 70aed,g,h,k,m were
formed as yellow crystals (Scheme 4). Alkylation of potassium salts
6e,g,k with methyl iodide (8a) or benzyl bromide (8b) in DMF at
room temperature for 20e90 min produced the corresponding
dark red methyl (E)-4-[2-(alkoxy)-1-methyl-5-oxo-1H-imidazol-4
(5H)-ylidene]-1-aryl-5-oxo-4,5-dihydro-1H-pyrrole-3-carboxylates
9aec (Scheme 5).
respectively, indicate the trans orientation of ester carbonyl group
and proton attached to the double bond, while in compound 50i the
3
coupling constant J13C,H¼4.3 Hz, indicates the cis orientation
between the ester carbonyl group and proton attached to the
double bond (Fig. 2).
On the basis of 1H NMR spectra one can conclude that com-
pounds 6aec,g,h,k,m exist exclusively in one form, i.e., as (E)-4-
[(1H)-pyrrol-3(2H)-ylidene]-1H-imidazol-2-olates, while after
acidification with hydrochloric acid isomerization around the C]C
double bond took place to form also the corresponding (Z)-isomers
(Scheme 6).
By alkylation of compound 6k three products can be formed in
principle: 9k, 90k, and 900k, since O-alkylation can take place either
to the hydroxy group attached to the pyrrole or the imidazole ring,
or N-alkylation on the imidazole ring nitrogen atom can take place
(Fig. 3, Table 1).
3. Structure determination
On the basis of chemical shifts for the methyl groups at
dOMe¼3.64 ppm for 9g and dOMe¼3.65 ppm for 9k, which are
characteristic for the methyl groups attached to oxygen, one can
conclude that O-alkylation took place. Namely, the N-methyl
groups in imidazolidine-2,4-diones with the exocyclic double bond
The structure of 5-(Z)- and 50-(E) isomers was determined on
the basis of differences in chemical shifts for NHeAr protons.
Namely, the NH protons of 5-(Z) isomers appear at

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U. Ursic et al. / Tetrahedron 66 (2010) 4346e4356
4348
Me
N
Me
N
O
O
Ar
Me
i
N
N
O
O
O
O
i
O-K+
N
NH
NH
HN
+
MeOOC
MeOOC
MeOOC
MeOOC
COOMe
Ar
6a-d,g,h,k,m
HN
Ar
5a-e g h k m
5'a-e g h k m
, , , ,
, , , ,
O
O
N
O
Ar
N
Me
OH
Ar
OH
Me
N
N
N
+
O
O
N
Ar
Me
N
N
COOMe
MeOOC O
7'a-d g h k m
7a-d g h k m
, , , ,
, , , ,
N
O-K+
COOMe
6a-e,g,h,k,m
Ar
7 and 7', yield (%)
7 : 7'
phenyl
92
95
92
94
93
88
99
85
84 : 16
87 : 13
82 : 18
85 : 15
87 : 13
87 : 13
87 : 13
86 : 14
a
Comp. Ar
Yield (%)
Time (h)
4-methylphenyl
2-methylphenyl
4-fluorophenyl
3-methoxyphenyl
3-nitrophenyl
1-naphthyl
b
c
phenyl
85
53
57
94
79
94
85
79
87
3.5
2
6a
6b
6c
4-methylphenyl
2-methylphenyl
4-fluorophenyl
4-bromophenyl
3-methoxyphenyl
3-nitrophenyl
1-naphthyl
2
d
g
2
6d
6e
1
h
k
m
1
6g
6h
6k
6m
1
pyrazin-2-yl
1
Scheme 4. Reagents and conditions: (i) 37% HCl, H2O (6aed,g,h,m) or EtOH (6k), rt.
pyrazin-2-yl
1
recorded on an AutoSpecQ and Qtof-premier spectrometers, IR
spectra on a PerkineElmer Spectrum BX FTIR spectrophotometer.
Microanalyses were performed on a PerkineElmer CHN Analyser
2400 II. Column chromatography was performed on silica gel
(Fluka, silica gel 60, 0.04e0.06 mm).
Scheme 3. Reagents and conditions: (i) KOH (w0.19 M), EtOH, reflux.
at position-5 appear in a very narrow range of
d
¼3.00e3.25 ppm
regardless of (Z)- or (E)-orientation.13 Proton at 2-position, H2, was
determined by the HMBC spectrum with the 13C of the ester
carbonyl group attached to C3 (Fig. 4). The N-methyl group attached
to imidazole ring appears at dNMe¼3.17 ppm. The protons of these
Amines 4aem, methyl iodide (8a), benzyl bromide (8b), and
KOH (85%) are commercially available (SigmaeAldrich).
5.2. Dimethyl (2E,3E)-2-[(dimethylamino)methylene]-3-
(1-methyl-2,5-dioxoimidazolidin-4-ylidene)succinate (3)
0
0
methyl groups are coupled in HMBC spectrum to C2 and C5 atoms.
0
The coupling of methoxy protons with C2 confirms that methoxy
0
group is attached to C2 atom (Fig. 5). The methylation therefore
Dimethyl (2E,3E)-2-[(dimethylamino)methylene]-3-(1-methyl-
2,5-dioxoimidazolidin-4-ylidene)succinate (3) was prepared
according to a modified literature procedure.8c A mixture of di-
methyl acetylenedicarboxylate (2) (7.5 mL, 60 mmol) and (Z)-5-
[(dimethylamino)methylene]-3-methylimidazolidin-2,4-dione (1)
(5.07 g, 30 mmol) in acetonitrile (100 mL) was heated to reflux for
3 h. Volatile components were evaporated in vacuo and the residue
was crystallized from a mixture toluene (25 mL) and n-heptane
(2 mL). Yield: 5.71 g (61%) of yellow plates; mp 165e167 ꢀC, lit.
took place on the hydroxy group attached to the imidazole ring to
give compound 9k.
4. Conclusion
The synthesis of a new triazafulvalene system was developed
starting from (dimethylamino)methyleneimidazolidine-2,4-dione
1, which was transformed into the corresponding succinate 3 by
[2þ2] cycloaddition to dimethyl acetylenedicarboxylate. Treatment
of 3 with aromatic or heteroaromatic amines produced [(aryl-
amino- or heteroarylamino)methylene]succinates 5. These were
cyclized in the presence of potassium hydroxide into potassium
salts of triazafulvalne system 6. Alkylaton of 6 gave O-alkylated
derivatives 9.
165e167 ꢀC.8c 1H NMR (CDCl3):
d 2.99 (6H, br s, NMe2); 3.07 (3H, s,
NMe); 3.66 (3H, s, COOMe); 3.86 (3H, s, COOMe); 6.94 (1H, br s, NH);
7.65 (1H, s, 10-H).
5.3. General procedure for the synthesis of (2E,3Z)-dimethyl
2-(1-methyl-2,5-dioxoimidazolidin-4-ylidene)-3-[(arylamino)
methylene]succinates 5aef,m and (2E,3E)-dimethyl 2-
(1-methyl-2,5-dioxoimidazolidin-4-ylidene)-3-[(arylamino)
methylene]succinates 5aei,kem
5. Experimental
5.1. General
Amine hydrochlorides 4aed,g,i,j (1.2e2.2 mmol) or amines 4e,f,
h,kem (0.36e2.2 mmol) and 37% HCl (1e5 drops) were added to
a solution of dimethyl (2E,3E)-2-[(dimethylamino)methylene]-3-
(1-methyl-2,5-dioxoimidazolidin-4-ylidene)succinate (3) (0.33e
2 mmol) in ethanol (1.5e6 mL). The reaction mixture was heated to
Melting points were determined on a Kofler micro hot stage.
NMR spectra were obtained on a Bruker Avance DPX 300 at
300 MHz for 1H, and 75.5 MHz for 13C, using DMSO-d6 and CDCl3 as
solvents and TMS as the internal standard. Mass spectra were

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U. Ursic et al. / Tetrahedron 66 (2010) 4346e4356
4349
O
O
O
O
Ar
Me
Ar
Me
i
N
N
N
N
R
N
N
O-K+
O
COOMe
COOMe
9e,g,k
6e,g,k
Alkylhalide Compound
Ar
R
X
I
Yield (%)
Time (min)
3-methoxyphenyl
1-naphthyl
methyl
methyl
benzyl
92
91
41
40
20
90
8a
8a
8b
9g
9k
9e
I
4-bromophenyl
Br
Scheme 5. Reagents and conditions: (i) RX (8a,b), DMF, rt.
reflux. The precipitated products were filtered under reduced
pressure.
0.229 g (64%) of yellow needles; mp 207e210 ꢀC. Ratio of isomers:
5a/50a¼94:6. 1H NMR (CDCl3): (2E,3Z)-isomer:
d 3.00 (3H, s, NMe);
3.80 (3H, s, COOMe); 3.88 (3H, s, COOMe); 7.00e7.07 (2H, m, 2H of
Ph); 7.08e7.15 (1H, m, 1H of Ph); 7.31e7.38 (2H, m, 2H of Ph); 7.56
(1H, br s, NH); 7.69 (1H, d, J¼13.2 Hz, CHNH); 10.55 (1H, br d,
5.3.1. (2E,3Z)-Dimethyl 2-(1-methyl-2,5-dioxoimidazolidin-4-ylidene)-
3-[(phenylamino)methylene]succinate (5a) and (2E,3E)-dimethyl 2-(1-
methyl-2,5-dioxoimidazolidin-4-ylidene)-3-[(phenylamino)methylene]
succinate (50a). Prepared from 3 (0.311 g, 1 mmol) and aniline hy-
drochloride (4a) (0.156 g, 1.2 mmol) in ethanol (4 mL), 5 h. Yield:
J¼13.5 Hz, CHNH); (2E,3E)-isomer:
d 3.05 (3H, s, NMe); 3.78 (3H, s,
COOMe); 3.89 (3H, s, COOMe); 8.22 (1H, d, J¼14.2 Hz, CHNH); 8.49
(1H, br d, J¼13.9 Hz, CHNH). (Found: C, 56.94; H, 4.84; N, 11.82.
C17H17N3O6 requires: C, 56.82; H, 4.77; N, 11.69.) nmax (KBr) 3280,
3185, 3113, 2950, 1777, 1724, 1683, 1638, 1627, 1601, 1588, 1458,
1439, 1395, 1312, 1196, 1163, 752 cmꢁ1
.
5.3.2. (2E,3Z)-Dimethyl 2-(1-methyl-2,5-dioxoimidazolidin-4-ylidene)-
3-[(p-tolylamino)methylene]succinate (5b) and (2E,3E)-dimethyl 2-(1-
methyl-2,5-dioxoimidazolidin-4-ylidene)-3-[(p-tolylamino)methylene]
succinate (50b). Prepared from 3 (0.623 g, 2 mmol) and 4-methyl-
aniline hydrochloride (4b) (0.316 g, 2.2 mmol) in ethanol (6 mL),
5 h. Yield: 0.452 g (61%) of yellow needles; mp 189e193 ꢀC. Ratio of
isomers: 5b/50b¼95:5. 1H NMR (CDCl3): (2E,3Z)-isomer:
d 2.32 (3H,
s, PheMe); 2.95 (3H, s, NMe); 3.78 (3H, s, COOMe); 3.87 (3H, s,
COOMe); 6.89e6.95 (2H, m, 2H of Ph); 7.10e7.16 (2H, m, 2H of Ph);
7.65 (1H, d, J¼13.3 Hz, CHNH); 7.86 (1H, br s, NH); 10.53 (1H, br d,
J¼13.3 Hz, CHNH); (2E,3E)-isomer:
d 2.29 (3H, s, Ph-Me); 3.02 (3H, s,
Comp.
5a
5b
5c
(ppm), NHAr
10.55
Comp.
5'a
5'b
5'c
(ppm), NHAr
8.49
NMe); 3.77 (3H, s, COOMe); 3.88 (3H, s, COOMe); 7.50 (1H, br s, NH);
8.18 (1H, d, J¼14.2 Hz, CHNH); 8.37 (1H, br d, J¼14.5 Hz, CHNH).
(Found: C, 57.98; H, 5.17; N, 11.16. C18H19N3O6 requires: C, 57.90; H,
5.13; N, 11.25.) nmax (KBr) 3189, 3149, 2949, 1776, 1724, 1686, 1674,
10.53
10.56
10.32
10.09
10.65
10.30
10.44
10.30
10.73
11.34
8.37
8.26
8.87
1641, 1627, 1584, 1436, 1394, 1340, 1311, 1194, 1159, 783 cmꢁ1
.
5.3.3. (2E,3Z)-Dimethyl 2-(1-methyl-2,5-dioxoimidazolidin-4-ylidene)-
3-[(o-tolylamino)methylene]succinate (5c) and (2E,3E)-dimethyl 2-(1-
methyl-2,5-dioxoimidazolidin-4-ylidene)-3-[(o-tolylamino)methylene]
succinate (50c). Prepared from 3 (0.623 g, 2 mmol) and 2-methyl-
aniline hydrochloride (4c) (0.316 g, 2.2 mmol) in ethanol (6 mL),
5 h. Yield: 0.393 g (53%) of yellow needles; mp 214e218 ꢀC. Ratio of
5d
5e
5'd
5'e
8.90
a
5f
5'f
8.83
9.18
8.72
/
5g
5h
5i
5'g
5'h
5'i
isomers: 5c/50c¼66:34. 1H NMR (DMSO-d6): (2E,3Z)-isomer:
d 2.30
(3H, s, Ph-Me); 2.91 (3H, s, NMe); 3.65 (3H, s, COOMe); 3.68 (3H, s,
COOMe); 7.01 (1H, dt, J¼7.4, 1.1 Hz, 1H of Ph); 7.17e7.29 (2H, m, 2H
of Ph); 7.40 (1H, d, J¼7.7 Hz, 1H of Ph); 7.96 (1H, d, J¼12.9 Hz,
CHNH); 10.56 (1H, br d, J¼13.0 Hz, CHNH); 10.70 (1H, br s, NH);
5j
5'j
(2E,3E)-isomer: d 2.28 (3H, s, PheMe); 2.90 (3H, s, NMe); 3.59 (3H, s,
COOMe); 3.68 (3H, s, COOMe); 7.06e7.12 (1H, m, 1H of Ph); 7.70 (1H,
d, J¼14.0 Hz, CHNH); 8.26 (1H, br d, J¼13.8 Hz, CHNH); 10.11 (1H, br
s, NH). (Found: C, 57.73; H, 4.95; N, 11.21. C18H19N3O6 requires: C,
57.90; H, 5.13; N, 11.25.) nmax (KBr) 3191, 3142, 1779, 1723, 1684,
9.05
9.47
9.66
5k
5l
5'k
5'l
/
a
5m
5'm
1636, 1625, 1598, 1437, 1337, 1314, 1198, 1159, 754 cmꢁ1
.
a Overlapped by other protons .
5.3.4. (2Z,3E)-Dimethyl 2-[(4-fluorophenylamino)methylene]-3-(1-
methyl-2,5-dioxoimidazolidin-4-ylidene)succinate (5d) and (2E,3E)-
Figure 1. Structure determination of isomers 5 and 50 with 1H NMR spectroscopy.

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U. Ursic et al. / Tetrahedron 66 (2010) 4346e4356
4350
Me
N
Me
N
Me
N
O
O
O
O
O
O
NH
H
NH
HN
NH
H
MeOOC
MeOOC
MeOOC
OH
C
C
MeOO
MeOO
C
MeOO
NH
H
NH
Cl
3
J
3
3
J
C,H = 4.3 Hz
J
C,H = 10.7 Hz
C,H = 10.4 Hz
HO
HO
5i
5'i
5j
Figure 2. Determination of the configuration around the C]C double bond by HMBC.
H
H
H
Table 1
Chemical shifts
O
O
O
O
Ar
Ar
Me
O
Ar
Me
O
N
N
N
N
N
N
Comp.
d
(ppm), OMe
d (ppm), OCH2Ph
H
H
N
N
CDCl3
DMSO-d6
CDCl3
:B
COOMe
COOMe
9g
9k
9e
3.64
3.65
d
3.48
3.49
d
d
d
5.65
B:
O
N
O
N
O
Ar
O
(2E,3E)-isomer:
d 2.89 (3H, s, NMe); 3.56 (3H, s, COOMe); 3.70 (3H,
H
s, COOMe); 7.02e7.10 (2H, m, 2H of Ph); 7.40e7.46 (2H, m, 2H of Ph);
7.90 (1H, d, J¼13.4 Hz, CHNH); 8.90 (1H, br d, J¼13.4 Hz, CHNH);
10.61 (1H, br s, NH). (Found: C, 46.82; H, 3.71; N, 9.54. C17H16BrN3O6
requires: C, 46.59; H, 3.68; N, 9.59.) nmax (KBr) 3335, 2950, 1781,
1734,1693,1681,1630,1591,1581,1487,1453,1431,1321,1243,1209,
N
N
Me
Me
MeOOC
O
MeOOC
O
Scheme 6. Isomerization around the C]C double bond.
1148, 824, 620 cmꢁ1
.
dimethyl 2-[(4-fluorophenylamino)methylene]-3-(1-methyl-2,5-di-
oxoimidazolidin-4-ylidene)succinate (50d). Prepared from 3(0.623 g,
2 mmol) and 4-fluoroaniline hydrochloride (4d) (0.325 g,
2.2 mmol) in ethanol (6 mL), 5 h. Yield: 0.537 g (71%) of yellow
needles; mp 207e214 ꢀC. Ratio of isomers: 5d/50d¼38:62. 1H NMR
5.3.6. (2Z,3E)-Dimethyl 2-[(2-iodophenylamino)methylene]-3-(1-
methyl-2,5-dioxoimidazolidin-4-ylidene)succinate (5f) and (2E,3E)-
dimethyl 2-[(2-iodophenylamino)methylene]-3-(1-methyl-2,5-di-
oxoimidazolidin-4-ylidene)succinate (50f). Prepared from 3 (0.623 g,
2 mmol), 2-iodoaniline (4f) (0.482 g, 2.2 mmol), and 37% HCl (5
drops) in ethanol (6 mL), 6.5 h. Yield: 0.943 g (97%) of yellow nee-
dles; mp 216e221 ꢀC. Ratio of isomers: 5f/50f¼87:13. EIMS:
(DMSO-d6): (2Z,3E)-isomer:
d 2.90 (3H, s, NMe); 3.66 (3H, s,
COOMe); 3.67 (3H, s, COOMe); 7.33e7.40 (4H, m, 4H of Ph); 7.79 (1H,
d, J¼13.4 Hz, CHNH); 10.32 (1H, br d, J¼13.3 Hz, CHNH); 10.68 (1H,
br s, NH); (2E,3E)-isomer: d 2.91 (3H, s, NMe); 3.59 (3H, s, COOMe);
m/z¼485 (Mþ). 1H NMR (DMSO-d6): (2Z,3E)-isomer:
d 2.92 (3H, s,
3.67 (3H, s, COOMe); 7.15e7.27 (4H, m, 4H of Ph); 7.84 (1H, d,
J¼14.1 Hz, CHNH); 8.87 (1H, br d, J¼14.1 Hz, CHNH); 10.07 (1H, br s,
NH). (Found: C, 54.00; H, 4.26; N, 11.16. C17H16FN3O6 requires: C,
54.11; H, 4.27; N, 11.14.) nmax (KBr) 3192, 3149, 2951, 1777, 1722,
1683, 1642, 1627, 1601, 1517, 1436, 1396, 1335, 1308, 1207, 1192, 1158,
NMe); 3.67 (3H, s, COOMe); 3.69 (3H, s, COOMe); 6.82e6.89 (1H, m,
1H of Ph); 7.33e7.49 (2H, m, 2H of Ph); 7.87 (1H, dd, J¼7.9,1.3 Hz,1H
of Ph); 7.95 (1H, d, J¼12.7 Hz, CHNH); 10.65 (1H, br d, J¼12.8 Hz,
CHNH); 10.74 (1H, br s, NH); (2E,3E)-isomer:
d 2.90 (3H, s, NMe);
829 cmꢁ1
.
3.62 (3H, s, COOMe); 3.73 (3H, s, COOMe); 6.76e6.82 (1H, m, 1H of
Ph); 7.85 (1H, d, J¼12.4 Hz, CHNH); 10.46 (1H, br s, NH). (Found: C,
42.35; H, 3.33; N, 8.62. C17H16IN3O6 requires: C, 42.08; H, 3.32; N,
8.62.) EI-HRMS: m/z¼485.0096 (Mþ); C17H16IN3O6 requires:
m/z¼485.0084 (Mþ). nmax (KBr) 3188, 3149, 2947, 1777, 1723, 1686,
1678, 1641, 1613, 1436, 1359, 1334, 1307, 1292, 1193, 1158, 762,
5.3.5. (2Z,3E)-Dimethyl 2-[(4-bromophenylamino)methylene]-3-(1-
methyl-2,5-dioxoimidazolidin-4-ylidene)succinate (5e) and (2E,3E)-
dimethyl 2-[(4-bromophenylamino)methylene]-3-(1-methyl-2,5-di-
oxoimidazolidin-4-ylidene)succinate (50e). Prepared from 3 (0.623 g,
2 mmol), 4-bromoaniline (4e) (0.378 g, 2.2 mmol), and 37% HCl
(5 drops) in ethanol (6 mL), 6.5 h. Yield: 0.760 g (87%) of orange and
yellow needles; mp 195e198 ꢀC and 230e233 ꢀC. Ratio of isomers:
615 cmꢁ1
.
5.3.7. (2Z,3E)-Dimethyl 2-[(3-methoxyphenylamino)methylene]-3-(1-
methyl-2,5-dioxoimidazolidin-4-ylidene)succinate (5g) and (2E,3E)-di-
methyl 2-[(3-methoxyphenylamino)methylene]-3-(1-methyl-2,5-diox-
oimidazolidin-4-ylidene)succinate (50g). Prepared from 3 (0.623 g,
2 mmol) and 3-methoxyaniline hydrochloride (4g) (0.351 g,
5e/50e¼12:88. 1H NMR (DMSO-d6): (2Z,3E)-isomer:
d 2.91 (3H, s,
NMe); 3.59 (3H, s, COOMe); 3.67 (3H, s, COOMe); 7.16e7.24 (2H, m,
2H of Ph); 7.46e7.53 (2H, m, 2H of Ph); 7.72 (1H, d, J¼13.0 Hz,
CHNH); 10.09 (1H, br d, J¼13.1 Hz, CHNH); 10.12 (1H, br s, NH);
O
5
O
5'
MeO
O
5'
O
5
O
5'
1' Me
N
1' Me
N
1' Me
N
5
1N
1N
1N
2'
2'
2'
4
4'
4
4'
4 4'
2
2
2
N3'
N3'
N3'
3 COOMe
3 COOMe
MeOOC Me
OMe
O
3
O
9k
9'k
9''k
Figure 3. Possible products of alkylation of potassium 1H-imidazol-2-olate 6k.

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U. Ursic et al. / Tetrahedron 66 (2010) 4346e4356
4351
Figure 4. Aromatic part of 2D HMBC spectrum of compound 9b.
2.2 mmol) in ethanol (6 mL), 6.5 h. The product did not precipitate
from ethanol, so water was added (3 mL) and cooled to ꢁ18 ꢀC,
which resulted in the precipitation of the product. Yield: 0.410 g
(53%) of yellow needles; mp 188e203 ꢀC. Ratio of isomers: 5g/
d, J¼14.0 Hz, CHNH); 8.83 (1H, br d, J¼14.1 Hz, CHNH); 10.08 (1H, s,
NH). (Found: C, 55.64; H, 5.02; N, 10.74. C18H19N3O7 requires: C,
55.53; H, 4.92; N, 10.79.) nmax (KBr) 3191, 3149, 2951, 1780, 1726,
1683, 1644, 1623,1607, 1584, 1495, 1455, 1436, 1279, 1191, 1152, 1043,
50g¼78:22. 1H NMR (DMSO-d6): (2Z,3E)-isomer:
d
2.91 (3H, s, NMe);
775 cmꢁ1
.
3.64 (3H, s, COOMe); 3.67 (3H, s, COOMe); 3.76 (3H, s, OMe); 6.65
(1H, dd, J¼8.2, 2.2 Hz, 40-H or 60-H); 6.87 (1H, dd, J¼8.0, 2.0 Hz, 40-H
or 60-H); 6.95 (1H, t, J¼2.2 Hz, 20-H); 7.24 (1H, t, J¼8.1 Hz, 50-H); 7.87
(1H, d, J¼13.3 Hz, CHNH); 10.30 (1H, d, J¼13.3 Hz, CHNH); 10.70 (1H,
5.3.8. (2E,3Z)-Dimethyl 2-(1-methyl-2,5-dioxoimidazolidin-4-yliden)-
3-[(3-nitrophenylamino)methylene]succinate (5h) and (2E,3E)-dimethyl
2-(1-methyl-2,5-dioxoimidazolidin-4-ylidene)-3-[(3-nitro-
phenylamino)methylene]succinate (50h). Prepared from 3 (0.623 g,
2 mmol), 3-nitroaniline (4h) (0.304 g, 2.2 mmol), and 37% HCl (5
drops) in ethanol (6 mL), 6.5 h. Yield: 0.778 g (96%) of yellow
s, NH); (2E,3E)-isomer: d 2.93 (3H, s, NMe); 3.60 (3H, s, COOMe); 3.67
(3H, s, COOMe); 3.75 (3H, s, OMe); 6.76 (1H, t, J¼2.2 Hz, 20-H);
6.77e6.82 (1H, m, 40-H or 60-H); 7.25 (1H, t, J¼8.1 Hz, 50-H); 7.89 (1H,
Figure 5. Carbonyl part of 2D HMBC spectrum of compound 9k.

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U. Ursic et al. / Tetrahedron 66 (2010) 4346e4356
4352
needles; mp 168e177 ꢀC. Ratio of isomers: 5h/50h¼30:70. 1H NMR
3149, 2947, 1779, 1723, 1685, 1674, 1636, 1611, 1594, 1437, 1329,
1307, 1267, 1190, 1156, 768 cmꢁ1
(DMSO-d6): (2E,3Z)-isomer:
d
2.92 (3H, s, NMe); 3.67 (3H, s,
.
COOMe); 3.68 (3H, s, COOMe); 7.77e7.82 (1H, m,1H of Ph); 7.96 (1H,
d, J¼13.0 Hz, CHNH); 8.28 (1H, t, J¼2.1 Hz, 20-H); 10.44 (1H, d,
5.3.12. (2E,3E)-Dimethyl2-[(5-chloropyridin-2-ylamino)methylene]-3-
J¼13.1 Hz, CHNH); 10.75 (1H, s, NH); (2E,3E)-isomer:
d
2.93 (3H, s,
(1-methyl-2,5-dioxoimidazolidin-4-ylidene)succinate (50l). Prepared
NMe); 3.63 (3H, s, COOMe); 3.68 (3H, s, COOMe); 7.58e7.70 (2H, m,
2H of Ph); 7.84e7.90 (1H, m, 1H of Ph); 7.94 (1H, d, J¼13.6 Hz,
CHNH); 8.05 (1H, t, J¼2.0 Hz, 20-H); 9.18 (1H, d, J¼13.6 Hz, CHNH);
10.15 (1H, s, NH). (Found: C, 50.57; H, 4.08; N, 13.78. C17H16N4O8
requires: C, 50.50; H, 3.99; N, 13.86.) nmax (KBr) 3301, 3225, 2957,
1781, 1764, 1731, 1701, 1636,m 1615, 1585, 1531, 1471, 1433, 1351,
from 3 (0.104 g, 0.33 mmol), 5-chloropyridine-2-amine (4l)
(0.047 g, 0.36 mmol), and 37% HCl (1 drop) in ethanol (1.5 mL),
5.5 h. Yield: 0.050 g (38%) of yellow needles; mp 220e223 ꢀC. 1H
NMR (DMSO-d6): d 2.89 (3H, s, NMe); 3.58 (3H, s, COOMe); 3.70 (3H,
s, COOMe); 6.63 (1H, d, J¼8.8 Hz, 30-H); 7.73 (1H, dd, J¼8.8, 2.7 Hz,
40-H); 8.28 (1H, d, J¼2.6 Hz, 60-H); 8.56 (1H, d, J¼12.6 Hz, CHNH);
9.47 (1H, br d, J¼12.6 Hz, CHNH); 10.68 (1H, s, NH). (Found: C,
48.53; H, 3.81; N, 14.11. C16H15ClN4O6 requires: C, 48.68; H, 3.83; N,
14.19.) nmax (KBr) 3328, 2957, 1777, 1734, 1705, 1698, 1676, 1653,
1277, 1255, 1130, 737 cmꢁ1
.
5.3.9. (2Z,3E)-Dimethyl 2-[(4-hydroxyphenylamino)methylene]-3-(1-
methyl-2,5-dioxoimidazolidin-4-ylidene)succinate (5i) and (2E,3E)-di-
methyl 2-[(4-hydroxyphenylamino)methylene]-3-(1-methyl-2,5-dioxo-
1632, 1593, 1482, 1473, 1432, 1365, 1236, 1152, 1135, 832 cmꢁ1
.
imidazolidin-4-ylidene)succinate (50i). Prepared from
3
(0.623 g,
5.3.13. (2E,3Z)-Dimethyl 2-(1-methyl-2,5-dioxoimidazolidin-4-ylidene)-
3-[(pyrazin-2-ylamino)methylene]succinate (5m) and (2E,3E)-dimethyl
2-(1-methyl-2,5-dioxoimidazolidin-4-ylidene)-3-[(pyrazin-2-ylamino)
methylene]succinate (50m). Prepared from 3 (0.467 g, 1.5 mmol),
pyrazine-2-amine (4m) (0.157 g, 1.65 mmol), and 37% HCl (5 drops)
in ethanol (3 mL), 5.5 h. Yield: 0.263 g (49%) of yellow needles; mp
211e214 ꢀC. Ratio of isomers: 5m/50m¼8:92. EIMS: m/z¼361 (Mþ).
2 mmol) and 4-hydroxyaniline hydrochloride (4i) (0.320 g,
2.2 mmol) in ethanol (6 mL), 5 h. Yield: 0.503 g (67%) of yellow
needles; mp 187e192 ꢀC. Ratio of isomers: 5i/50i¼44:56. 1H NMR
(DMSO-d6): (2Z,3E)-isomer:
d 2.91 (3H, s, NMe); 3.62 (3H, s,
COOMe); 3.67 (3H, s, COOMe); 6.70e6.76 (2H, m, 2H of Ph);
7.09e7.14 (2H, m, 2H of Ph); 7.70 (1H, d, J¼13.5 Hz, CHNH); 9.32
(1H, s, OH); 10.30 (1H, d, J¼13.5 Hz, CHNH); 10.63 (1H, s, NH);
1H NMR (DMSO-d6): (2E,3Z)-isomer:
COOMe); (2E,3E)-isomer:
d
2.93 (3H, s, NMe); 3.76 (3H, s,
(2E,3E)-isomer:
d
2.91 (3H, s, NMe); 3.58 (3H, s, COOMe); 3.67 (3H, s,
d 2.90 (3H, s, NMe); 3.60 (3H, s, COOMe);
COOMe); 6.70e6.76 (2H, m, 2H of Ph); 6.99e7.05 (2H, m, 2H of Ph);
7.79 (1H, d, J¼14.3 Hz, CHNH); 8.72 (1H, d, J¼14.4 Hz, CHNH); 9.26
3.72 (3H, s, COOMe); 8.14 (1H, d, J¼2.5 Hz, 1H of Ar); 8.24e8.28 (2H,
m, 2H of Ar); 8.53 (1H, d, J¼12.5 Hz, CHNH); 9.66 (1H, br d,
(1H, s, OH); 10.00 (1H, s, NH). 13C NMR (DMSO-d6):
d
24.1, 50.8, 50.9,
J¼12.5 Hz, CHNH); 10.74 (1H, s, NH). 13C NMR (CDCl3):
d 24.2, 51.1,
51.8, 52.0, 91.5, 93.0, 110.6, 115.8, 115.9, 118.4, 118.7, 127.5, 128.9,
132.0, 133.2, 142.7, 153.8, 154.0, 154.1, 154.2, 161.7, 161.9, 167.1, 167.4,
167.5,167.8. (Found: C, 54.11; H, 4.78; N,10.99. C17H17N3O7 requires:
C, 54.40; H, 4.57; N, 11.20.) nmax (KBr) 3191, 3137, 2952, 1775, 1706,
1683, 1637, 1617, 1520, 1457, 1438, 1355, 1335, 1313, 1212, 1194, 1162,
52.1, 100.2, 103.8, 134.5, 136.0, 137.1, 137.3, 141.8, 149.0, 153.9, 161.8,
166.0, 167.1. (Found: C, 49.41; H, 4.25; N, 18.98. C15H15N5O6
requires: C, 49.86; H, 4.18; N, 19.38.) EI-HRMS: m/z¼361.1033 (Mþ);
C15H15N5O6 requires: m/z¼361.1022 (Mþ). nmax (KBr) 3325, 2954,
1776, 1731, 1705, 1653, 1636, 1540, 1502, 1455, 1434, 1393, 1294,
828 cmꢁ1
.
1247, 1188, 1155, 1077, 836, 618 cmꢁ1
.
5.3.10. (2Z,3E)-Dimethyl 2-[(2-chloro-4-hydroxyphenylamino)meth-
ylene]-3-(1-methyl-2,5-dioxoimidazolidin-4-ylidene)succinate
(5j). Prepared from 3 (0.623 g, 2 mmol) and 4-hydroxy-2-chloro-
aniline hydrochloride (4j) (0.396 g, 2.2 mmol) in ethanol (6 mL), 5 h.
Yield: 0.554 g (68%) of yellow needles; mp 233e235 ꢀC. 1H NMR
5.4. General procedure for the synthesis of potassium (E)-4-[4-
(methoxycarbonyl)-2-oxo-1-aryl-1H-pyrrol-3(2H)-ylidene]-1-
methyl-5-oxo-4,5-dihydro-1H-imidazol-2-olates 6aee,g,h,k,m
Potassium hydroxide (0.028e0.099 g) was added to a solution of
a mixture of (2E,3Z)-dimethyl 2-(1-methyl-2,5-dioxoimidazolidin-
4-ylidene)-3-[(arylamino)methylene]succinate 5aee,g,h,k,m and
(2E,3E)-dimethyl 2-(1-methyl-2,5-dioxoimidazolidin-4-ylidene)-3-
[(arylamino)methylene]succinate 50aee,g,h,k,m (0.5e1.5 mmol) in
ethanol (2.5e8 mL). The reaction mixture was heated to reflux. The
precipitated product was filtered under reduced pressure.
(DMSO-d6):
d 2.91 (3H, s, NMe); 3.64 (3H, s, COOMe); 3.68
(3H, s, COOMe); 6.79 (1H, dd, J¼2.6, 8.9 Hz, 50-H); 6.92 (1H, d,
J¼2.7 Hz, 30-H); 7.43 (1H, d, J¼9.1 Hz, 60-H); 7.86 (1H, d,
J¼12.9 Hz, CHNH); 9.76 (1H, s, OH); 10.69 (1H, s, NH); 10.73
(1H, d, J¼13.0 Hz, CHNH). 13C NMR (DMSO-d6):
d 24.0, 51.2,
52.0, 93.2, 114.1, 115.5, 115.8, 117.0, 121.5, 128.4, 128.5, 147.3,
153.9, 154.0, 161.7, 167.5, 167.7. (Found: C, 49.68; H, 3.96; N,
10.25. C17H16ClN3O7 requires: C, 49.83; H, 3.94; N, 10.25.)
nmax (KBr) 3309, 3191, 3124, 2953, 1775, 1702, 1684, 1632,
5.4.1. Potassium (E)-4-[4-(methoxycarbonyl)-2-oxo-1-phenyl-1H-pyr-
rol-3(2H)-ylidene]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-2-olate
(6a). Prepared from a mixture of (2E,3Z)-dimethyl 2-(1-methyl-
2,5-dioxoimidazolidin-4-ylidene)-3-[(phenylamino)methylene]
succinate (5a) and (2E,3E)-dimethyl 2-(1-methyl-2,5-dioxoimida-
zolidin-4-ylidene)-3-[(phenylamino)methylene]succinate (50a)
(0.180 g, 0.5 mmol) and KOH (0.028 g, 0.42 mmol) in ethanol
(3 mL), 3.5 h. Yield: 0.155 g (85%) of fine dark red powder; mp
decomposition above 250 ꢀC. EIMS: m/z¼327 ((MꢁK)Hþ). 1H NMR
1608, 1513, 1440, 1337, 1297, 1206, 1162, 990, 842, 614 cmꢁ1
.
5.3.11. (2E,3Z)-Dimethyl 2-(1-methyl-2,5-dioxoimidazolidin-4-ylidene)-
3-[(naphthalen-1-ylamino)methylen]succinate (5k) and (2E,3E)-di-
methyl 2-(1-methyl-2,5-dioxoimidazolidin-4-ylidene)-3-[(naphthalen-
1-ylamino)methylen]succinate (50k). Prepared from
3
(0.623 g,
2 mmol), 1-naphthylamine (4k) (0.304 g, 2.2 mmol), and 37% HCl
(5 drops) in ethanol (6 mL), 6.5 h. Yield: 0.678 g (83%) of yellow
needles; mp 216e219 ꢀC. Ratio of isomers: 5k/50k¼95:5. 1H NMR
(DMSO-d6):
d 2.83 (3H, s, NMe); 3.58 (3H, s, COOMe); 7.17e7.23
(1H, m, 1H of Ph); 7.30 (1H, s, 50-H); 7.37e7.44 (2H, m, 2H of Ph);
7.58e7.63 (2H, m, 2H of Ph). (Found: C, 52.58; H, 3.46; N, 11.21.
C16H12KN3O5 requires: C, 52.59; H, 3.31; N, 11.50.) EI-HRMS:
m/z¼327.0862 ((MꢁK)Hþ); C16H13N3O5 requires: m/z¼327.0855
((MꢁK)Hþ). nmax (KBr) 2952, 1738, 1712, 1691, 1659, 1571, 1503,
(DMSO-d6): (2E,3Z)-isomer:
d 2.92 (3H, s, NMe); 3.70 (3H, s,
COOMe); 3.72 (3H, s, COOMe); 7.50e7.56 (2H, m, 2H of Ar); 7.62
(1H, ddd, J¼1.1, 6.9, 8.0 Hz, 1H of Ar); 7.67e7.74 (2H, m, 2H of Ar);
7.95 (1H, d, J¼8.3 Hz, 1H of Ar); 8.00 (1H, dd, J¼1.2, 8.2 Hz, 1H of
Ar); 8.11 (1H, d, J¼12.6 Hz, CHNH); 10.76 (1H, s, NH); 11.34 (1H, d,
1448, 1389, 1224, 1199, 1120, 1034, 767, 621 cmꢁ1
.
J¼12.7 Hz, CHNH); (2E,3E)-isomer:
d
9.05 (1H, d, J¼13.4 Hz,
CHNH); 10.30 (1H, s, NH). (Found: C, 61.41; H, 4.69; N, 10.28.
C21H19N3O6 requires: C, 61.61; H, 4.68; N, 10.26.) nmax (KBr) 3189,
5.4.2. Potassium (E)-4-[4-(methoxycarbonyl)-2-oxo-1-p-tolyl-1H-pyr-
rol-3(2H)-ylidene]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-2-olate

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(6b). Prepared from a mixture of (2E,3Z)-dimethyl 2-(1-methyl-
2,5-dioxoimidazolidin-4-ylidene)-3-[(p-tolylamino)methylene]
succinate (5b) and (2E,3E)-dimethyl 2-(1-methyl-2,5-dioxoimid-
azolidin-4-ylidene)-3-[(p-tolylamino)methylene]succinate (50b)
(0.187 g, 0.5 mmol) and KOH (0.028 g, 0.42 mmol) in ethanol
(3 mL), 2 h. Yield: 0.101 g (53%) of fine dark red powder; mp
dioxoimidazolidin-4-ylidene)succinate (5g) and (2E,3E)-dimethyl
2-[(3-methoxyphenylamino)methylene]-3-(1-methyl-2,5-dioxo-
imidazolidin-4-ylidene)succinate (50g) (0.506 g, 1.3 mmol) and
KOH (0.086 g, 1.3 mmol) in ethanol (6 mL), 1 h. Yield: 0.482 g (94%)
of fine dark red powder; mp 240e242 ꢀC with decomposition.
ESI-MS: m/z¼396.1 (MHþ). 1H NMR (DMSO-d6):
d 2.84 (3H, s,
280e282 ꢀC with decomposition. 1H NMR (DMSO-d6):
d
2.31 (3H, s,
NMe); 3.59 (3H, s, COOMe); 3.78 (3H, s, OMe); 6.77 (1H, ddd, J¼8.2,
2.6, 1.0 Hz, 400-H or 600-H); 7.18 (1H, ddd, J¼8.0, 2.0, 1.0 Hz, 400-H or
600-H); 7.25 (1H, t, J¼2.2 Hz, 200-H); 7.30 (1H, t, J¼8.1 Hz, 500-H); 7.32
PheMe); 2.83 (3H, s, NMe); 3.58 (3H, s, COOMe); 7.17e7.23 (2H, m,
2H of Ph); 7.25 (1H, s, 50-H); 7.44e7.50 (2H, m, 2H of Ph). 13C NMR
(DMSO-d6):
d
20.5, 24.3, 50.7, 98.7, 111.9, 122.0, 127.0, 129.2, 134.3,
(1H, s, 50-H). 13C NMR (DMSO-d6):
d 24.2, 50.7, 55.1, 98.6, 107.7,
135.2, 156.6, 164.2, 165.4, 166.8, 168.4. (Found: C, 53.61; H, 3.85; N,
10.88. C17H14KN3O5 requires: C, 53.82; H, 3.72; N, 11.08.) nmax (KBr)
2955, 1739, 1709,1691, 1656, 1571, 1516, 1447, 1389, 1220, 1207, 1115,
110.6, 112.2, 113.9, 126.6, 129.5, 138.6, 156.7, 159.5, 164.2, 165.3,
166.8, 168.3. EI-HRMS m/z¼396.0585 (MHþ); C17H15KN3O5
requires: m/z¼396.0598 (MHþ). nmax (KBr) 2965, 1739, 1710, 1690,
1655, 1605, 1573, 1560, 1495, 1448, 1389, 1260, 1211, 1121, 1031, 802,
1029, 610 cmꢁ1
.
632 cmꢁ1
.
5.4.3. Potassium (E)-4-[4-(methoxycarbonyl)-2-oxo-1-o-tolyl-1H-pyr-
rol-3(2H)-ylidene]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-2-olate
(6c). Prepared from a mixture of (2E,3Z)-dimethyl 2-(1-methyl-2,5-
dioxoimidazolidin-4-ylidene)-3-[(o-tolylamino)methylene]succi-
nate (5c) and (2E,3E)-dimethyl 2-(1-methyl-2,5-dioxoimidazolidin-
4-ylidene)-3-[(o-tolylamino)methylene]succinate (50c) (0.187 g,
0.5 mmol) and KOH (0.028 g, 0.42 mmol) in ethanol (2.5 mL), 2 h.
Yield: 0.108 g (57%) of fine dark red powder; mp 285e287 ꢀC with
5.4.7. Potassium (E)-4-[4-(methoxycarbonyl)-1-(3-nitrophenyl)-2-oxo-1H-
pyrrol-3(2H)-ylidene]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-2-olate
(6h). Prepared from a mixture of (2E,3Z)-dimethyl 2-(1-methyl-2,5-
dioxoimidazolidin-4-ylidene)-3-[(3-nitrophenylamino)methylene]
succinate (5h) and (2E,3E)-dimethyl 2-(1-methyl-2,5-dioxoimida-
zolidin-4-ylidene)-3-[(3-nitrophenylamino)methylene]succinate
(50h) (0.202 g, 0.5 mmol) and KOH (0.035 g, 0.5 mmol) in ethanol
(2.5 mL), 1 h. Yield: 0.175 g (85%) of fine dark red powder; mp
decomposition above 267 ꢀC. ESI-MS: m/z¼373.1 ((MꢁK)Hþ2 ), 411.0
decomposition. 1H NMR (DMSO-d6):
d 2.14 (3H, s, Ph-Me); 2.84 (3H,
s, NMe); 3.57 (3H, s, COOMe); 7.00 (1H, s, 50-H); 7.12e7.18 (1H, m,1H
of Ph); 7.22e7.34 (3H, m, 3H of Ph). (Found: C, 53.74; H, 3.83; N,
10.99. C17H14KN3O5 requires: C, 53.82; H, 3.73; N, 11.08.) nmax (KBr)
3150, 1742, 1717, 1695, 1648, 1569, 1543, 1496, 1440, 1389, 1224,
(MHþ). 1H NMR (DMSO-d6):
d 2.85 (3H, s, NMe); 3.61 (3H, s,
COOMe); 7.51 (1H, s, 50-H); 7.69 (1H, t, J¼8.2 Hz, 500-H); 8.02 (1H,
ddd, J¼8.3, 2.3, 0.9 Hz, 400-H or 600-H); 8.08 (1H, ddd, J¼8.2, 2.1,
0.9 Hz, 400-H or 600-H); 8.70 (1H, t, J¼2.2 Hz, 200-H). 13C NMR (DMSO-
1196, 1114, 1028, 750, 623 cmꢁ1
.
d6):
d 24.3, 50.8, 97.9, 113.3, 115.8, 119.2, 125.3, 127.2, 130.2, 138.4,
5.4.4. Potassium (E)-4-[1-(4-fluorophenyl)-4-(methoxycarbonyl)-2-
oxo-1H-pyrrol-3(2H)-ylidene]-1-methyl-5-oxo-4,5-dihydro-1H-imi-
dazol-2-olate (6d). Prepared from a mixture of (2Z,3E)-dimethyl
2-[(4-fluorophenylamino)methylene]-3-(1-methyl-2,5-dioxoimi-
dazolidin-4-ylidene)succinate (5d) and (2E,3E)-dimethyl 2-[(4-
fluorophenylamino)methylene]-3-(1-methyl-2,5-dioxoimidazoli-
din-4-ylidene)succinate (50d) (0.189 g, 0.5 mmol) and KOH (0.035 g,
0.5 mmol) in ethanol (2.5 mL), 2 h. Yield: 0.180 g (94%) of fine dark
red powder; mp 276e278 ꢀC with decomposition. 1H NMR (DMSO-
147.9, 156.9, 164.1, 165.2, 166.7, 168.0. EI-HRMS: m/z¼373.0777
((MꢁK)Hþ2 ); C16H13N4O7 requires: m/z¼373.0784 ((MꢁK)H2þ). nmax
(KBr) 2954, 1734, 1694, 1667, 1572, 1531, 1487, 1442, 1388, 1351,
1256, 1203, 1120, 1034, 735, 625 cmꢁ1
.
5.4.8. Potassium (E)-4-[4-(methoxycarbonyl)-1-(naphthalen-1-yl)-2-
oxo-1H-pyrrol-3(2H)-ylidene]-1-methyl-5-oxo-4,5-dihydro-1H-imid-
azol-2-olate (6k). Prepared from a mixture of (2E,3Z)-dimethyl
2-(1-methyl-2,5-dioxoimidazolidin-4-ylidene)-3-[(naphthalen-
1-ylamino)methylene]succinate (5k) and (2E,3E)-dimethyl 2-
(1-methyl-2,5-dioxoimidazolidin-4-ylidene)-3-[(naphthalen-1-
ylamino)methylene]succinate (50k) (0.623 g, 1.5 mmol) and KOH
(0.099 g, 1.5 mmol) in ethanol (8 mL), 1 h. Yield: 0.490 g (79%) of
fine dark red powder; mp 288e290 ꢀC with decomposition.
d6):
d 2.83 (3H, s, NMe); 3.58 (3H, s, COOMe); 7.19e7.28 (2H, m, 2H
of Ph); 7.29 (1H, s, 50-H); 7.58e7.67 (2H, m, 2H of Ph). (Found: C,
49.94; H, 3.05; N, 10.71. C16H11FKN3O5 requires: C, 50.13; H, 2.89; N,
10.96.) nmax (KBr) 2953, 1737, 1713, 1698, 1656, 1571, 1513, 1449,
1392, 1225, 1200, 1118, 1029, 847, 609 cmꢁ1
.
ESI-MS: m/z¼416 (MHþ). 1H NMR (DMSO-d6):
d 2.86 (3H, s, NMe);
5.4.5. Potassium (E)-4-[1-(4-bromophenyl)-4-(methoxycarbonyl)-2-
oxo-1H-pyrrol-3(2H)-yliden]-1-methyl-5-oxo-4,5-dihydro-1H-imi-
dazol-2-olate (6e). Prepared from a mixture of (2Z,3E)-dimethyl
2-[(4-bromophenylamino)methylene]-3-(1-methyl-2,5-dioxoimi-
dazolidin-4-ylidene)succinate (5e) and (2E,3E)-dimethyl 2-[(4-
bromophenylamino)methylene]-3-(1-methyl-2,5-dioxoimidazoli-
din-4-ylidene)succinate (50e) (0.219 g, 0.5 mmol) and KOH (0.035 g,
0.5 mmol) in ethanol (2.5 mL), 1 h. Yield: 0.175 g (79%) of fine dark
red powder; mp decomposition above 255 ꢀC. 1H NMR (DMSO-d6):
3.60 (3H, s, COOMe); 7.13 (1H, s, 50-H); 7.44 (1H, dd, J¼7.3, 1.0 Hz,
1H of Ar); 7.63e7.51 (4H, m, 4H of Ar); 7.95e8.04 (2H, m, 2H of
Ar). 13C NMR (DMSO-d6):
d 24.2, 50.7, 98.1, 111.3, 123.2, 125.2,
125.5, 126.3, 126.6, 127.9, 128.1, 129.8, 133.8, 134.2, 156.4, 165.3,
165.4, 166.6, 168.2. EI-HRMS: m/z¼416.0636 (MHþ); C20H15KN3O5
requires: m/z¼416.0649 (MHþ). nmax (KBr) 3167, 1748, 1716, 1695,
1645, 1597, 1567, 1542, 1445, 1408, 1395, 1202, 1183, 1122, 1042,
774, 622 cmꢁ1
.
d
2.84 (3H, s, NMe); 3.59 (3H, s, COOMe); 7.33 (1H, s, 50-H);
7.55e7.60 (2H, m, 2H of Ph); 7.61e7.66 (2H, m, 2H of Ph). 13C NMR
(DMSO-d6): 24.3, 50.8, 98.3, 112.7, 117.2, 123.6, 125.9, 131.6, 136.9,
5.4.9. Potassium (E)-4-[4-(methoxycarbonyl)-2-oxo-1-(pyrazin-2-yl)-
1H-pyrrol-3(2H)-ylidene]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-
2-olate (6m). Prepared from a mixture of (2E,3Z)-dimethyl 2-(1-
methyl-2,5-dioxoimidazolidin-4-ylidene)-3-[(pyrazin-2-ylamino)
methylene]succinate (5m) and (2E,3E)-dimethyl 2-(1-methyl-2,5-
dioxoimidazolidin-4-ylidene)-3-[(pyrazin-2-ylamino)methylene]
succinate (50m) (0.307 g, 0.85 mmol) and KOH (0.056 g,
0.85 mmol) in ethanol (3.5 mL), 1 h. Yield: 0.271 g (87%) of fine
dark red powder; mp 279e281 ꢀC with decomposition. EIMS:
d
157.0, 164.1, 165.4, 166.9, 168.3. (Found: C, 43.10; H, 2.64; N, 9.14.
C16H11BrKN3O5 requires: C, 43.29; H, 2.50; N, 9.46.) nmax (KBr) 2953,
1740,1713,1693,1658,1570,1493,1444,1390,1254,1227,1199,1119,
1029, 835 cmꢁ1
.
5.4.6. Potassium (E)-4-[4-(methoxycarbonyl)-1-(3-methoxyphenyl)-
2-oxo-1H-pyrrol-3(2H)-ylidene]-1-methyl-5-oxo-4,5-dihydro-1H-
imidazol-2-olate (6g). Prepared from a mixture of (2Z,3E)-di-
methyl 2-[(3-methoxyphenylamino)methylene]-3-(1-methyl-2,5-
m/z¼330.1 ((MꢁK)Hþ2 ). 1H NMR (DMSO-d6):
d 2.85 (3H, s, NMe);
3.62 (3H, s, COOMe); 7.59 (1H, s, 50-H); 8.43 (1H, d, J¼2.6 Hz, 600-
H); 8.47 (1H, dd, J¼2.6, 1.5 Hz, 500-H); 9.63 (1H, d, J¼1.5 Hz, 300-H).

ꢀ ꢀ
U. Ursic et al. / Tetrahedron 66 (2010) 4346e4356
4354
13C NMR (DMSO-d6):
d
24.3, 51.0, 97.5, 115.0, 121.8, 136.5, 140.2,
(3 drops) in water (3 mL), 15 min. Yield: 0.105 g (92%) of yellow nee-
142.6, 146.3, 157.7, 163.8, 165.2, 166.8, 168.1. (Found: C, 41.24; H,
2.84; N, 16.87. C14H10KN5O5$½KOH requires: C, 42.53; H, 2.68; N,
17.71.) EI-HRMS: m/z¼330.0847 ((MꢁK)Hþ2 ); C14H12N5O5 requires:
m/z¼330.0838 ((MꢁK)H2þ). nmax (KBr) 2952, 1718, 1696, 1656,
1568, 1530, 1481, 1446, 1429, 1395, 1254, 1232, 1208, 1127, 1049,
dles; mp 164e171 ꢀC (tolueneen-heptane). Ratio of isomers: 82:18. 1H
NMR (DMSO-d6): major isomer:
NMe); 3.68 (3H, s, COOMe); 7.24e7.40 (4H, m, 4H of Ph); 7.78 (1H, s, 2-
H); 11.29 (1H, br s, OH); minor isomer: 2.14 (3H, s, PheMe); 2.96 (3H,
d 2.16 (3H, s, PheMe); 2.96 (3H, s,
d
s, NMe); 3.81 (3H, s, COOMe); 8.35 (1H, s, 2-H); 11.64 (1H, br s, OH).
(Found: C, 60.10; H, 4.41; N, 12.18. C17H15N3O5 requires: C, 59.82; H,
4.43; N, 12.31.) nmax (KBr) 3261, 2948, 1779, 1729, 1695, 1644, 1564,
729 cmꢁ1
.
5.5. General procedure for the synthesis of (E)-methyl 4-(2-
hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-oxo-
1-aryl-4,5-dihydro-1H-pyrrole-3-carboxylates 7aed,g,h,k,m
and (Z)-methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4
(5H)-ylidene)-5-oxo-1-aryl-4,5-dihydro-1H-pyrrole-3-
carboxylates 70aed,g,h,k,m
1460, 1390, 1345, 1293, 1240, 1205, 1155, 1128, 1011, 750, 621 cmꢁ1
.
5.5.4. (E)-Methyl 1-(4-fluorophenyl)-4-(2-hydroxy-1-methyl-5-oxo-
1H-imidazol-4(5H)-ylidene)-5-oxo-4,5-dihydro-1H-pyrrole-3-car-
boxylate (7d) and (Z)-methyl 1-(4-fluorophenyl)-4-(2-hydroxy-1-
methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-oxo-4,5-dihydro-1H-
pyrrole-3-carboxylate (70d). Prepared from potassium (E)-4-[1-
(4-fluorophenyl)-4-(methoxycarbonyl)-2-oxo-1H-pyrrol-3(2H)-
ylidene]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-2-olate (6d)
(0.127 g, 0.33 mmol) and 37% HCl (4 drops) in water (2.5 mL),
15 min. Yield: 0.108 g (94%) of yellow needles; mp 207e210 ꢀC
(toluene). Ratio of isomers: 85:15. 1H NMR (DMSO-d6): major
HCl of 37% (2e13 drops) was added to a suspension of potas-
sium (E)-4-[4-(methoxycarbonyl)-2-oxo-1-aryl-1H-pyrrol-3(2H)-
ylidene]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-2-olate 6a-d,
g,h,k,m (0.1e1 mmol) in water (1e8 mL) or in case of 6k
(0.5 mmol) in ethanol (2 mL). The suspension was stirred at room
temperature. The precipitated product was filtered under reduced
pressure and washed with water.
isomer:
m, 2H of Ph); 7.59e7.66 (2H, m, 2H of Ph) of yellow crystals; 8.02
(1H, s, 2-H); 11.39 (1H, br s, OH); minor isomer: 2.97 (3H, s,
d 2.96 (3H, s, NMe); 3.69 (3H, s, COOMe); 7.28e7.37 (2H,
d
5.5.1. (E)-Methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-
ylidene)-5-oxo-1-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylate (7a)
and (Z)-methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-
ylidene)-5-oxo-1-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylate
(70a). Prepared from potassium (E)-4-[4-(methoxycarbonyl)-2-
oxo-1-phenyl-1H-pyrrol-3(2H)-ylidene]-1-methyl-5-oxo-4,5-di-
hydro-1H-imidazol-2-olate (6a) (0.037 g, 0.1 mmol) and 37% HCl
(2 drops) in water (1 mL), 15 min. Yield: 0.030 g (92%) of yellow
needles; mp 194e200 ꢀC. Ratio of isomers: 84:16. 1H NMR (DMSO-
NMe); 3.83 (3H, s, COOMe); 8.50 (1H, s, 2-H); 11.56 (1H, br s, OH).
(Found: C, 55.79; H, 3.64; N, 12.02. C16H12FN3O5 requires: C,
55.66; H, 3.50; N, 12.17.) nmax (KBr) 3274, 1792, 1780, 1731, 1721,
1690, 1639, 1513, 1455, 1440, 1390, 1235, 1123, 1012, 848,
613 cmꢁ1
.
5.5.5. (E)-Methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-
ylidene)-1-(3-methoxyphenyl)-5-oxo-4,5-dihydro-1H-pyrrole-3-car-
boxylate (7g) and (Z)-methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imi-
dazol-4(5H)-ylidene)-1-(3-methoxyphenyl)-5-oxo-4,5-dihydro-1H-
pyrrole-3-carboxylate (70g). Prepared from potassium (E)-4-[4-
(methoxycarbonyl)-1-(3-methoxyphenyl)-2-oxo-1H-pyrrol-3(2H)-
ylidene]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-2-olate (6g) (0.395 g,
1 mmol) and 37% HCl (13 drops) in water (8 mL), 15 min. Yield:
0.333 g (93%) of yellow needles; mp 210e213 ꢀC (tolueneeDMF).
d6): major isomer:
d 2.96 (3H, s, NMe); 3.70 (3H, s, COOMe);
7.29e7.36 (1H, m, 1H of Ph); 7.44e7.52 (2H, m, 2H of Ph); 7.57e7.63
(2H, m, 2H of Ph); 8.04 (1H s, 2-H); 11.38 (1H, br s, OH); minor
isomer:
d 2.97 (3H, s, NMe); 3.84 (3H, s, COOMe); 8.51 (1H, s, 2-H);
11.63 (1H, br s, OH). (Found: C, 58.74; H, 3.91; N, 12.76. C16H13N3O5
requires: C, 58.72; H, 4.00; N, 12.84.) nmax (KBr) 3285, 3077, 2955,
1793, 1779, 1730, 1718, 1692, 1640, 1559, 1455, 1440, 1390, 1346,
Ratio of isomers: 87:13. 1H NMR (DMSO-d6): major isomer:
d 2.96
1231, 1147, 1124, 1013, 929, 750, 710, 620 cmꢁ1
.
(3H, s, NMe); 3.70 (3H, s, COOMe); 3.76 (3H, s, OMe); 6.86e6.92
(1H, m, 1H of Ph); 7.13e7.22 (2H, m, 2H of Ph); 7.33e7.43 (1H, m,
1H of Ph); 8.07 (1H, s, 2-H); 11.40 (1H, br s, OH); minor isomer:
5.5.2. (E)-Methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-
ylidene)-5-oxo-1-p-tolyl-4,5-dihydro-1H-pyrrole-3-carboxylate (7b)
and (Z)-methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-
ylidene)-5-oxo-1-p-tolyl-4,5-dihydro-1H-pyrrole-3-carboxylate
(70b). Prepared from potassium (E)-4-[4-(methoxycarbonyl)-2-
oxo-1-p-tolyl-1H-pyrrol-3(2H)-yliden]-1-methyl-5-oxo-4,5-dihy-
dro-1H-imidazol-2-olate (6b) (0.190 g, 0.5 mmol) and 37% HCl
(4 drops) in water (4 mL), 15 min. Yield: 0.162 g (95%) of yellow
needles; mp 176e182 ꢀC (toluene). Ratio of isomers: 87:13. 1H NMR
d
2.97 (3H, s, NMe); 3.81 (3H, s, COOMe); 3.84 (3H, s, OMe);
6.91e6.97 (1H, m, 1H of Ph); 8.51 (1H, s, 2-H); 11.62 (1H, br s, OH).
(Found: C, 57.31; H, 4.25; N, 11.83. C17H15N3O6 requires: C, 57.14;
H, 4.23; N, 11.76.) nmax (KBr) 3285, 3075, 2954, 1784, 1728, 1688,
1637, 1599, 1557, 1495, 1440, 1393, 1264, 1218, 1124, 1013, 753,
625 cmꢁ1
.
5.5.6. (E)-Methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-
ylidene)-1-(3-nitrophenyl)-5-oxo-4,5-dihydro-1H-pyrrole-3-carbox-
ylate (7h) and (Z)-methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imida-
zol-4(5H)-ylidene)-1-(3-nitrophenyl)-5-oxo-4,5-dihydro-1H-pyrrole-
3-carboxylate (70h). Prepared from potassium (E)-4-[4-(methoxy-
carbonyl)-1-(3-nitrophenyl)-2-oxo-1H-pyrrol-3(2H)-ylidene]-1-
methyl-5-oxo-4,5-dihydro-1H-imidazol-2-olate (6h) (0.328 g,
0.8 mmol) and 37% HCl (7 drops) in water (6 mL), 15 min. Yield:
0.263 g (88%) of orange needles; mp 245e254 ꢀC (tolueneeDMF).
(DMSO-d6): major isomer:
3.69 (3H, s, COOMe); 7.25e7.31 (2H, m, 2H of Ph); 7.44e7.49 (2H, m,
2H of Ph); 7.99 (1H, s, 2-H); 11.35 (1H, br s, OH); minor isomer: 2.34
d 2.33 (3H, s, PheMe); 2.96 (3H, s, NMe);
d
(3H, s, Ph-Me); 2.97 (3H, s, NMe); 3.83 (3H, s, COOMe); 7.40e7.45 (2H,
m, 2H of Ph); 8.46 (1H, s, 2-H); 11.62 (1H, br s, OH). (Found: C, 60.01;
H, 4.39; N, 12.24. C17H15N3O5 requires: C, 59.82; H, 4.43; N, 12.31.)
nmax (KBr) 3274, 3155, 2954, 1789, 1735, 1719, 1707, 1691, 1637, 1559,
1517, 1449, 1388, 1346, 1239, 1122, 821, 748, 606 cmꢁ1
.
Ratio of isomers: 87:13. 1H NMR (DMSO-d6): major isomer:
d 2.97
5.5.3. (E)-Methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-
ylidene)-5-oxo-1-o-tolyl-4,5-dihydro-1H-pyrrole-3-carboxylate (7c)
and (Z)-methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-
ylidene)-5-oxo-1-o-tolyl-4,5-dihydro-1H-pyrrole-3-carboxylate
(70c). Prepared from potassium (E)-4-[4-(methoxycarbonyl)-2-
oxo-1-o-tolyl-1H-pyrrol-3(2H)-ylidene]-1-methyl-5-oxo-4,5-dihy-
dro-1H-imidazol-2-olate (6c) (0.126 g, 0.33 mmol) and 37% HCl
(3H, s, NMe); 3.72 (3H, s, COOMe); 7.77 (1H, t, J¼8.2 Hz, 500-H); 8.08
(1H, ddd, J¼8.2, 2.1, 0.8 Hz, 400-H or 600-H); 8.15 (1H, ddd, J¼8.2, 2.2,
0.8 Hz, 400-H or 600-H); 8.24 (1H, s, 2-H); 8.64 (1H, t, J¼2.1 Hz, 200-
H); 11.54 (1H, br s, OH); minor isomer:
d 2.98 (3H, s, NMe); 3.86
(3H, s, COOMe); 7.78 (1H, t, J¼8.2 Hz, 500-H); 8.52 (1H, t, J¼2.0 Hz,
200-H); 8.69 (1H, s, 2-H). (Found: C, 51.69; H, 3.24; N, 15.01.
C16H12N4O7 requires: C, 51.62; H, 3.25; N, 15.05.) nmax (KBr) 3099,

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U. Ursic et al. / Tetrahedron 66 (2010) 4346e4356
4355
2956, 1788, 1740, 1684, 1628, 1561, 1533, 1443, 1386, 1351, 1316,
1240, 1197, 1109, 1042, 737, 619 cmꢁ1
4.61; N, 11.32.) ESI-HRMS: m/z¼372.1193 (MHþ); C18H18N3O6
requires: m/z¼372.1196 (MHþ). nmax (KBr) 2956, 1780, 1730, 1700,
1605, 1555, 1498, 1440, 1387, 1277, 1254, 1225, 1195, 1162, 1130,
.
5.5.7. (E)-Methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-
ylidene)-1-(naphthalen-1-yl)-5-oxo-4,5-dihydro-1H-pyrrole-3-car-
boxylate (7k) and (Z)-methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imi-
dazol-4(5H)-ylidene)-1-(naphthalen-1-yl)-5-oxo-4,5-dihydro-1H-
pyrrole-3-carboxylate (70k). Prepared from potassium (E)-4-[4-
(methoxycarbonyl)-1-(naphthalen-1-yl)-2-oxo-1H-pyrrol-3(2H)-
ylidene]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-2-olate (6k)
(0.208 g, 0.5 mmol) and 37% HCl (6 drops) in ethanol (2 mL),
10 min. Yield: 0.186 g (99%) of yellow needles; mp 192e194 ꢀC
(toluene). Ratio of isomers: 83:17. 1H NMR (DMSO-d6): major
1102, 1023, 751, 624 cmꢁ1
.
5.6.2. (E)-Methyl 4-(2-methoxy-1-methyl-5-oxo-1H-imidazol-4(5H)-
ylidene)-1-(napthalen-1-yl)-5-oxo-4,5-dihydro-1H-pyrrole-3-car-
boxylate (9k). Methyliodide (8a) (0.038 mL, 0.6 mmol) was added
to a solution of potassium (E)-4-[4-(methoxycarbonyl)-1-(naph-
thalen-1-yl)-2-oxo-1H-pyrrol-3(2H)-ylidene]-1-methyl-5-oxo-
4,5-dihydro-1H-imidazol-2-olate (6k) (0.208 g, 0.5 mmol) in DMF
(2 mL) while stirring. The reaction mixture was stirred at room
temperature for 20 min. Water (0.5 mL) was added to the reaction
mixture and then volatile components were evaporated in vacuo.
Water (5 mL) was added to the residue and the product was
extracted with chloroform (2ꢂ5 mL). The organic phase was dried
with Na2SO4, which was then filtered off and chloroform was
evaporated in vacuo. Yield: 0.1þ78 g (91%) of red needles; mp
isomer:
m, 5H of Ar); 7.91 (1H, s, 2-H); 8.04e8.11 (2H, m, 2H of Ar); 11.35
(1H, br s, OH); minor isomer: 2.97 (3H, s, NMe); 3.82 (3H, s,
d 2.98 (3H, s, NMe); 3.71 (3H, s, COOMe); 7.55e7.67 (5H,
d
COOMe); 8.48 (1H, s, 2-H); 11.71 (1H, br s, OH). (Found: C, 63.87;
H, 4.09; N, 11.12. C20H15N3O5 requires: C, 63.66; H, 4.01; N,
11.14.) nmax (KBr) 3262, 1782, 1729, 1695, 1642, 1441, 1395, 1198,
174e177 ꢀC. EIMS: m/z¼391 (M ). 1H NMR (DMSO-d6):
d 3.02
1126, 1004, 783, 619 cmꢁ1
.
(3H, s, NMe); 3.48 (3H, s, OMe); 3.67 (3H, s, COOMe); 7.56e7.68
(5H, m, 5H of Ar); 8.01 (1H, s, 2-H); 8.03e8.09 (2H, m, 2H of Ar).
5.5.8. (E)-Methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-
ylidene)-5-oxo-1-(pyrazin-2-yl)-4,5-dihydro-1H-pyrrole-3-carboxyl-
ate (7m) and (Z)-methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4
(5H)-ylidene)-5-oxo-1-(pyrazin-2-yl)-4,5-dihydro-1H-pyrrole-3-
carboxylate (70m). Prepared from potassium (E)-4-[4-(methoxy-
carbonyl)-2-oxo-1-(pyrazin-2-yl)-1H-pyrrol-3(2H)-ylidene]-1-
methyl-5-oxo-4,5-dihydro-1H-imidazol-2-olate (6m) (0.245 g,
0.67 mmol) and 37% HCl (8 drops) in water (6 mL), 15 min. Yield:
0.186 g (85%) of yellow needles; mp 247e250 ꢀC (tolueneeDMF).
1H NMR (CDCl3):
d 3.17 (3H, s, NMe); 3.64 (3H, s, OMe); 3.82 (3H,
s, COOMe); 7.44 (1H, dd, J¼7.3, 1.1 Hz, 1H of Ar); 7.50e7.58 (3H,
m, 3H of Ar); 7.61 (1H, s, 2-H); 7.66e7.73 (1H, m, 1H of Ar);
7.89e7.95 (2H, m, 2H of Ar). 13C NMR (CDCl3):
d 25.7, 33.5, 52.0,
108.0, 110.5, 122.5, 125.2, 125.5, 126.9, 127.5, 128.7, 129.7, 129.8,
132.1, 134.6, 136.9, 141.9, 155.2, 161.7, 163.9, 164.9. (Found: C,
64.57; H, 4.38; N, 10.64. C21H17N3O5 requires: C, 64.45; H, 4.38;
N, 10.74.) EI-HRMS: m/z¼391.117700 (Mþ); C21H17N3O5 requires:
m/z¼391.116821 (Mþ). nmax (KBr) 3131, 2951, 1781, 1729, 1715,
1695, 1667, 1605, 1438, 1406, 1387, 1370, 1272, 1197, 1139, 1092,
Ratio of isomers: 86:14. 1H NMR (DMSO-d6): major isomer:
d 2.97
(3H, s, NMe); 3.73 (3H, s, COOMe); 8.16 (1H, s, 2-H); 8.54e8.61 (2H,
1017, 746, 623 cmꢁ1
.
m, 2H of Het); 9.39 (1H, d, J¼0.7 Hz, 300-H); 11.63 (1H, br s, OH);
minor isomer:
d
2.99 (3H, s, NMe); 3.88 (3H, s, COOMe); 8.66 (1H, s,
5.6.3. (E)-Methyl 4-[2-(benzyloxy)-1-methyl-5-oxo-1H-imidazol-4
(5H)-ylidene]-1-(4-bromophenyl)-5-oxo-4,5-dihydro-1H-pyrrole-
3-carboxylate (9e). Benzyl bromide (8b) (0.060 mL, 0.5 mmol) was
added to a solution of potassium (E)-4-[1-(4-bromophenyl)-4-
(methoxycarbonyl)-2-oxo-1H-pyrrol-3(2H)-yliden]-1-methyl-5-
oxo-4,5-dihydro-1H-imidazol-2-olate (6e) (0.222 g, 0.5 mmol) in
DMF (2 mL) while stirring. The reaction mixture was stirred at
room temperature for 1.5 h. Water (0.5 mL) was added to the
reaction mixture and then volatile components were evaporated in
vacuo. Water (5 mL) was added to the residue and the product was
extracted with chloroform (2ꢂ5 mL). The organic phase was dried
with Na2SO4, which was then filtered off and chloroform was
evaporated in vacuo and the residue was purified by column
chromatography on silica gel (ethyl acetateepetroleum ether¼1:3,
Rf¼0.3). Fractions containing the product were combined and
evaporated in vacuo. Yield: 0.102 g (41%) of red oil. EIMS: m/z¼495
2-H); 11.52 (1H, br s, OH). (Found: C, 51.33; H, 3.52; N, 21.28.
C14H11N5O5 requires: C, 51.07; H, 3.37; N, 21.27.) nmax (KBr) 3135,
2955, 1772, 1733, 1702, 1641, 1570, 1473, 1444, 1426, 1389, 1247,
1224, 1189, 1151, 1137, 1011, 761, 716 cmꢁ1
.
5.6. Alkylation of potassium (E)-4-[4-(methoxycarbonyl)-
2-oxo-1-aryl-1H-pyrrol-3(2H)-ylidene]-1-methyl-5-oxo-
4,5-dihydro-1H-imidazol-2-olate
5.6.1. (E)-Methyl 4-(2-methoxy-1-methyl-5-oxo-1H-imidazol-4(5H)-
ylidene)-1-(3-methoxyphenyl)-5-oxo-4,5-dihydro-1H-pyrrole-3-car-
boxylate (9g). Methyliodide (8a) (0.030 mL, 0.44 mmol) was added
to
a solution of potassium (E)-4-[4-(methoxycarbonyl)-1-(3-
methoxyphenyl)-2-oxo-1H-pyrrol-3(2H)-ylidene]-1-methyl-5-
oxo-4,5-dihydro-1H-imidazol-2-olate (6g) (0.158 g, 0.4 mmol) in
DMF (2 mL) while stirring. The reaction mixture was stirred at
room temperature for 40 min. Water (2 mL) was added to the
reaction mixture and then volatile components were evaporated in
vacuo. Water (5 mL) was added to the residue and the product was
extracted with chloroform (2ꢂ5 mL). The organic phase was dried
with Na2SO4, which was then filtered off and chloroform was
evaporated in vacuo. Yield: 0.137 g (92%) oþf red needles; mp
228e230 ꢀC (toluene). ESI-MS: mz¼372.1 (MH ). 1H NMR (CDCl3):
(Mþ). 1H NMR (CDCl3):
d 3.18 (3H, s, NMe); 3.75 (3H, s, COOMe);
5.65 (2H, s, CH2); 7.17e7.25 (2H, m, 2H of Ph); 7.26e7.33 (5H, m, 5H
of Ph); 7.55 (1H, s, 2-H); 7.55e7.60 (2H, m, 2H of Ph). 13C NMR
(CDCl3):
d 25.7, 48.0, 51.7, 109.0, 111.5, 120.3, 124.0, 127.6,
127.9, 128.6, 132.4, 134.6, 134.7, 134.8, 138.4, 154.8, 161.5,
163.3, 163.4. EI-HRMS: m/z¼495.0440 (Mþ); C23H18BrN3O5
requires: m/z¼495.0430 (Mþ). nmax (KBr) 3092, 2950, 1783, 1727,
1693, 1606, 1493, 1446, 1390, 1377, 1244, 1167, 1118, 1035, 1008, 923,
d
3.16 (3H, s, NMe); 3.65 (3H, s, OMe); 3.82 (3H, s, OMe); 3.84 (3H, s,
828, 752, 699 cmꢁ1
.
OMe); 6.84e6.89 (1H, m, 1H of Ph); 6.97e7.02 (2H, m, 2H of Ph);
7.31e7.39 (1H, m, 1H of Ph); 7.67 (1H, s, 2-H). 1H NMR (DMSO-d6):
Acknowledgements
d
2.99 (3H, s, NMe); 3.49 (3H, s, OMe); 3.66 (3H, s, COOMe); 3.80
(3H, s, OMe); 6.90 (1H, ddd, J¼1.0, 2.4, 8.3 Hz, 1H of Ph); 7.13e7.19
The financial support from Slovenian Research Agency through
grants P0-0502-0103, P1-0179 and J1-6689-0103-04 is gratefully
acknowledged. We thank the pharmaceutical companies Krka d.d.
(Novo mesto, Slovenia) and Lek d.d., a Sandoz Company (Ljubljana,
Slovenia) for the financial support.
(2H, m, 2H of Ph); 7.37 (1H, t, J¼8.4 Hz, 1H of Ph); 8.12 (1H, s, 2-H).
13C NMR (DMSO-d6):
d 25.2, 32.9, 51.1, 55.3,107.2, 108.3,110.2,112.3,
114.7, 129.8, 136.5, 136.7, 139.3, 155.0, 159.6, 161.4, 163.0, 163.3.
(Found: C, 58.46; H, 4.66; N, 11.12. C18H17N3O6 requires: C, 58.22; H,

ꢀ ꢀ
U. Ursic et al. / Tetrahedron 66 (2010) 4346e4356
4356
ꢀ
B.; Svete, J. Tetrahedron: Asymmetry 2007, 18, 464; (c) Wagger, J.; Groselj, U.;
Meden, A.; Svete, J.; Stanovnik, B. Tetrahedron 2008, 64, 2801.
5. Wagger, J.; Svete, J.; Stanovnik, B. Synthesis 2008, 1436.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2010.04.025.
ꢀ
6. Attanasi, O. A.; Favi, G.; Filippone, P.; Golobic, A.; Stanovnik, B.; Svete, J. J. Org.
Chem. 2005, 70, 4307.
ꢀ
7. Attanasi, O. A.; Favi, G.; Filippone, P.; Golobic, A.; Perulli, F. R.; Stanovnik, B.;
Svete, J. Synlett 2007, 2971.
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