Synthesis of 2-iminoimidazolidin-4-one derivatives by cyclization of 2-aryl-1-(4,6-dimethylpyrimidin-2-yl)guanidines with ethyl bromoacetate, dimethyl acetylenedicarboxylate, and maleic anhydride

Article abstract of DOI:10.1007/s11172-007-0216-8

Derivatives of 2-iminoimidazolidin-4-one, (E)-methyl (2-imino-5- oxoimidazolidin-4-ylidene)acetate, and (2-imino-5-oxo-imidazolidin-4-yl)acetic acid were synthesized by the cyclization of 2-aryl-1-(4,6-dimethylpyrimidin-2- yl)guanidines with ethyl bromoacetate, dimethyl acetylenedicarboxylate, and maleic anhydride, respectively.

Full text of DOI:10.1007/s11172-007-0216-8

Russian Chemical Bulletin, International Edition, Vol. 56, No. 7, pp. 1423—1430, July, 2007
1423
Synthesis of 2ꢀiminoimidazolidinꢀ4ꢀone derivatives by cyclization
of 2ꢀarylꢀ1ꢀ(4,6ꢀdimethylpyrimidinꢀ2ꢀyl)guanidines with ethyl bromoacetate,
dimethyl acetylenedicarboxylate, and maleic anhydride
A. S. Shestakov, O. E. Sidorenko, and Kh. S. Shikhalievꢀ
Voronezh State University,
1 Universitetskaya pl., 394006 Voronezh, Russian Federation.
Fax: +7 (473 2) 55 6890. Eꢀmail: chocd261@chem.vsu.ru
Derivatives of 2ꢀiminoimidazolidinꢀ4ꢀone, (E)ꢀmethyl (2ꢀiminoꢀ5ꢀoxoimidazolidinꢀ4ꢀ
ylidene)acetate, and (2ꢀiminoꢀ5ꢀoxoꢀimidazolidinꢀ4ꢀyl)acetic acid were synthesized by the
cyclization of 2ꢀarylꢀ1ꢀ(4,6ꢀdimethylpyrimidinꢀ2ꢀyl)guanidines with ethyl bromoacetate, diꢀ
methyl acetylenedicarboxylate, and maleic anhydride, respectively.
Key words: 2ꢀarylꢀ1ꢀ(4,6ꢀdimethylpyrimidinꢀ2ꢀyl)guanidines, ethyl bromoacetate, dimethyl
acetylenedicarboxylate, maleic anhydride, imidazole, NOESY, dielectrophiles, cyclization.
Scheme 1
Guanidines serve as convenient building blocks for
the formation of heterocyclic moieties with two nitrogen
atoms. The heterocyclization proceeds with the involveꢀ
ment of the N—C—N fragment of guanidine. The conꢀ
densation of the latter with the bisꢀelectrophilic twoꢀcarꢀ
bon fragment affords the imidazole system.1 αꢀHaloꢀ or
αꢀhydroxycarbonyl compounds are most often used as
dielectrophiles. In the present study, we investigated the
heterocyclization of unsymmetrical guanidines with comꢀ
mercially available ethyl bromoacetate 1, dimethyl aceꢀ
tylenedicarboxylate (DMAD) 2, and maleic anhydride 3.
Guanidines 4 were synthesized from pentaneꢀ2,4ꢀdione,
dicyanodiamide, and anilines.2
It was found that the reaction of ethyl bromoacetate 1
with guanidines 4 regioselectively produces 1ꢀarylꢀ2ꢀ[(4,6ꢀ
dimethylpyrimidinꢀ2ꢀyl)imino]imidazolidinꢀ4ꢀones 5
(Scheme 1). Excess guanidine acts as an acceptor of hydroꢀ
bromic acid that is eliminated in the reaction.
Ester 1 is an unsymmetrical twoꢀcarbon electrophile,
which can form two regioisomeric imidazolones in
reactions with the unsymmetrical bisꢀnucleophilic
R—NH—C—NH—R´ fragment of guanidines 4. Taking
into account that guanidines 4 contain three 1,3ꢀbiꢀ
nucleophilic moieties sharing the carbon atom, the
number of possible regioisomeric cyclization products
equals six. Strictly speaking, the involvement of the pyriꢀ
midine nitrogen atom in the reaction cannot be ruled out
as well. This reaction was described for 2ꢀaminopyrimidine
and ethyl bromoacetate.3 However, in the case under conꢀ
sideration, this reaction is hardly probable taking into
account the presence of the nucleophilic guanidine fragꢀ
ment. All possible cyclization products do not differ in
5
a
b
c
d
e
f
R1
H
H
3ꢀMe
3ꢀMeO
H
R2
H
2ꢀMe
4ꢀMe
4ꢀMeO
4ꢀEtO
4ꢀEt
5
g
h
i
j
k
l
R1
H
H
H
H
R2
3ꢀF
4ꢀF
4ꢀPh
4ꢀBu
4ꢀCl
2ꢀMeO
3ꢀCl
H
H
contradicts none of these structures. The data considered
below suggest that the cyclization affords compound 5.
1
the elemental composition, and the H NMR spectrum
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1372—1378, July, 2007.
1066ꢀ5285/07/5607ꢀ1423 © 2007 Springer Science+Business Media, Inc.

1424
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 7, July, 2007
Shestakov et al.
crossꢀpeaks between the proton of the free imino group
and the ortho protons of the phenyl group are absent in
the NOESY spectrum. Hence, the reaction of ethyl
bromoacetate 1 with guanidines 4 produces compounds
of general formula 5. These compounds can undergo ketoꢀ
enol tautomerism. The fact that the 1H NMR spectrum in
DMSOꢀd6 shows a singlet at δ 4.44 is indicative of
the almost complete shift of the equilibrium toward the
ketone form.
Dimethyl acetylenedicarboxylate was used as another
cyclizing agent. Guanidines 4 actively react with this comꢀ
pound in chloroform at room temperature, and these reꢀ
actions are also regioselective.
Preliminarily, we performed quantum chemical calꢀ
culations for the geometric parameters and the elecꢀ
tronic structures of guanidines 4 with the use of the
GAUSSIANꢀ03 program package.4 The calculations were
carried out by the density functional theory using the
B3LYP functional. The full geometry optimization of the
molecule was performed with the 3ꢀ21G* basis set. The
electronic structures were calculated using the 6ꢀ31G*
basis set. The choice of the basis set and the calculation
method was substantiated by the fact that a further inꢀ
crease in the accuracy of calculations did not lead to
substantial changes in the energies of the highest occuꢀ
pied molecular orbital (HOMO) and the lowest unoccuꢀ
pied molecular orbital (LUMO).
Ester 2 contains four electrophilic centers (two carboꢀ
nyl and two acetylenic carbon atoms). The reaction of
DMAD with guanidines would be expected to yield both
sixꢀmembered pyrimidinꢀ4ꢀones and fiveꢀmembered
imidazolinꢀ4ꢀones. In this case, the number of possible
regioisomers is 12. Taking into account the E,Z isomerism
in the case of the exocyclic position of the double bond in
imidazolinꢀ4ꢀones, it can easily be seen that the number
of possible isomers increases to 18. Therefore, in the case
under consideration, the formation of heterocycles correꢀ
sponding to structure 6 (Scheme 2) was not apparent.
Both the fiveꢀ and sixꢀmembered reaction products of
DMAD with 1,3ꢀbinucleophiles were described in the
literature. Xꢀray diffraction data show that triphenylꢀ
guanidine forms fiveꢀmembered imidazolidinone,6
whereas 2ꢀaminobenzothiazole gives sixꢀmembered pyriꢀ
midinone.7 The reactions of 2ꢀaminobenzothiazoles with
derivatives of hexꢀ3ꢀyneꢀ2,5ꢀdione, which is a ketone anaꢀ
log of DMAD, also produce pyrimidinone.8 Depending
on the number of substituents and the reaction condiꢀ
tions, the reactions of aminoguanidine derivatives with
DMAD give both imidazolidinones and pyrimidinones.9
In the 1H NMR spectra of the fiveꢀmembered cyclization
products, the signal for the βꢀenamine proton is shifted
upfield (δ ~5.9) compared to the analogous signal in
the spectra of the sixꢀmembered compounds (δ ~6.6).
Based on this fact, it was concluded that DMAD reacts
with unsubstituted guanidine to give the fiveꢀmembered
heterocycle.6 The position of the signal for this proton
(δ 5.54—5.71) in the spectra of the reaction products sugꢀ
gests that the reactions afford one of 12 possible imidꢀ
azolidinones. The ultimate choice was made based on the
NOESY data. The spectra were measured for comꢀ
pound 6c. It appeared that the βꢀenamine proton (δ 5.74)
and the protons of the —OCH3 group (δ 3.15) give crossꢀ
peaks with the ortho protons of the phenyl group (δ 7.79
and 7.81). This is possible only for two of 18 probable
cyclization products, viz., 6c and 6´c. Based on the aboveꢀ
considered evidence in favor of structure 5 assigned to the
cyclization product of guanidines 4 and ester 1, it can be
concluded that the reactions of compounds 4 and 2 proꢀ
duce compounds 6, whose structures are presented in
The calculations demonstrated that the region, where
the wave function of the HOMO differs from zero, is
located on the nitrogen atoms N(2) and N(3). Therefore,
these atoms should be involved in the ring formation in
orbitalꢀcontrolled reactions.
The structures of the heterocycles were confirmed by
the NOESY experiment. The spectrum of compound 5c
shows intense correlation peaks at δ 4.44/7.47 and
4.44/7.63, which correspond to the interactions between
the methylene protons of iminoimidazolidinone 5 and
the ortho protons of the phenyl group. These interactions
are possible only for two regioisomers, viz., 5c and 5´c.
However, the formation of compound 5´c assumes that
the most easily accessible N(3) atom is not involved in
cyclization despite the fact that this atom, unlike the N(1)
and N(2) atoms, is involved in the reactions with such
electrophiles as isocyanates, acid chlorides, and sulfoꢀ
chlorides.2 The formation of a product analogous to 5c
was detected in the reaction of mixed anhydride of acetic
and chloroacetic acids with symmetrical diarylguanidines.5
Structure 5´c contradicts the aboveꢀconsidered calculaꢀ
tions of the electron distribution on HOMO. In addition,

2ꢀIminoimidazolidinꢀ4ꢀones from guanidines
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 7, July, 2007
1425
Scheme 2
6
a
b
c
d
R1
H
H
H
H
R2
H
4ꢀMe
3ꢀCF3
4ꢀCl
6
e
f
R1
3ꢀCl
H
R2
4ꢀCl
3ꢀMe
3ꢀEtO
g
H
Scheme 2. The presence of the aboveꢀmentioned correlaꢀ
tion peaks at δ 5.74/7.79 and 3.15/7.79 is evidence that
compounds 6 exist as Z isomers. Actually, the analysis of
the interatomic distances, which were estimated by the
quantum chemical calculations for compound 6c, shows
that the distances between these protons in the E isomer
are longer than 6 Å, which does not allow the observation
of the nuclear Overhauser effect.
(Scheme 3). As in the aboveꢀconsidered case, the number
of possible regioisomers is 12. In the reactions of disubstiꢀ
tuted guanidines with strong electrophiles, including anꢀ
hydrides, the attack occurs on the N(3) atom of guaniꢀ
dine.2 Hence, four regioisomers, in which this nitrogen
atom remains unsubstituted, can be excluded from conꢀ
sideration. Based on the analysis of the NOESY spectrum
for compound 7e, six other possible structures can be
rejected. Hence, two structures, 7e and 7´e, should be
considered. For these structures, the correlation peaks
between the methine proton of the heterocycle and the
ortho protons of the phenyl group can be observed. These
crossꢀpeaks are actually present in the spectrum at
δ 5.19/7.84 and 5.19/7.79.
The absence of crossꢀpeaks between the phenyl
ortho protons and either the protons of the carboxy group,
the presence of which would be evidence in favor of strucꢀ
ture 7´e, or the methylene protons, which would be eviꢀ
dence for structure 7e, does not allow us to decide beꢀ
tween these structures based only on the NOESY specꢀ
trum. However, the data published in the literature show
that structure 7e is more favorable. It is known that the
cyclization products with N,Sꢀbinucleophiles are often
We performed the analogous cyclization by heatꢀ
ing maleic anhydride 3 with guanidines 4 in dioxane

1426
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 7, July, 2007
Shestakov et al.
Scheme 3
7
a
b
c
d
R1
H
H
H
3ꢀMe
R2
4ꢀMeO
3ꢀCl
3ꢀMe
4ꢀMe
7
e
f
R1
H
2ꢀMeO
2ꢀCl
R2
3ꢀCF3
5ꢀMeO
4ꢀCl
g
analogous to those formed by N,Nꢀbinucleophiles.6 For
example, the reactions of maleic anhydride with thiocarbꢀ
amides10,11 and thioamides12 produce fiveꢀmembered
thiazolines. The Xꢀray diffraction study showed that the
reactions of amidines with arylmaleinimides afford fiveꢀ
membered oxoimidazole rather than oxopyrimidine deꢀ
rivatives.13
idinꢀ4ꢀone (5b), (E)ꢀ1ꢀ(3,4ꢀdimethylphenyl)ꢀ2ꢀ[(4,6ꢀdimethylꢀ
pyrimidinꢀ2ꢀyl)imino]imidazolidinꢀ4ꢀone (5c), (E)ꢀ1ꢀ(3,4ꢀdiꢀ
methoxyphenyl)imidazolidinꢀ2ꢀ[(4,6ꢀdimethylpyrimidinꢀ2ꢀ
yl)imino]ꢀ4ꢀone (5d), (E)ꢀ2ꢀ[(4,6ꢀdimethylpyrimidinꢀ2ꢀyl)imiꢀ
no]ꢀ1ꢀ(4ꢀethoxyphenyl)imidazolidinꢀ4ꢀone (5e), (E)ꢀ2ꢀ[(4,6ꢀdiꢀ
methylpyrimidinꢀ2ꢀyl)imino]ꢀ1ꢀ(4ꢀethylphenyl)imidazolidinꢀ4ꢀ
one (5f), (E)ꢀ2ꢀ[(4,6ꢀdimethylpyrimidinꢀ2ꢀyl)imino]ꢀ1ꢀ(3ꢀ
fluorophenyl)imidazolidinꢀ4ꢀone (5g), (E)ꢀ2ꢀ[(4,6ꢀdimethylꢀ
pyrimidinꢀ2ꢀyl)imino]ꢀ1ꢀ(4ꢀfluorophenyl)imidazolidinꢀ4ꢀ
one (5h), (E)ꢀ1ꢀ(biphenylꢀ4ꢀyl)ꢀ2ꢀ[(4,6ꢀdimethylpyrimidinꢀ2ꢀ
yl)imino]imidazolidinꢀ4ꢀone (5i), (E)ꢀ1ꢀ(4ꢀbutylphenyl)ꢀ2ꢀ
[(4,6ꢀdimethylpyrimidinꢀ2ꢀyl)imino]imidazolidinꢀ4ꢀone (5j),
(E)ꢀ1ꢀ(3,4ꢀdichlorophenyl)ꢀ2ꢀ[(4,6ꢀdimethylpyrimidinꢀ2ꢀ
yl)imino]imidazolidinꢀ4ꢀone (5k), and (E)ꢀ2ꢀ[(4,6ꢀdimethylꢀ
pyrimidinꢀ2ꢀyl)imino]ꢀ1ꢀ(2ꢀmethoxyphenyl)imidazolidinꢀ4ꢀone
(5l) were prepared. The yields, melting points, elemental analyꢀ
Experimental
1
The H NMR spectra were recorded on a Bruker ACꢀ300
instrument (300 MHz) at 20 °C in DMSOꢀd6 with Me4Si as the
internal standard. The 2D 1H NMR spectra were measured on a
Bruker DRXꢀ500 instrument (500 MHz) at 20 °C in DMSOꢀd6.
The purity of the compounds and the course of the reactions
were monitored by TLC on Merck UVꢀ254 plates (chloroꢀ
form—methanol, 20 : 1, as the eluent).
2ꢀIminoimidazolidinꢀ4ꢀones 5 (general procedure). Ester 1
(1.2 mL, 11 mmol) was added dropwise to a solution of guaniꢀ
dine 4 (20 mmol) in dioxane (40 mL), and the reaction mixture
was heated at 90 °C for 5 h. The precipitate of guanidine
hydrobromide that formed upon cooling of the reaction mixture
was filtered off, and the filtrate was concentrated. The residue
was twice recrystallized from isopropyl alcohol. (E)ꢀ2ꢀ[(4,6ꢀDiꢀ
methylpyrimidinꢀ2ꢀyl)imino]ꢀ1ꢀphenylimidazolidinꢀ4ꢀone (5a),
(E)ꢀ2ꢀ[(4,6ꢀdimethylpyrimidinꢀ2ꢀyl)imino]ꢀ1ꢀoꢀtolylimidazolꢀ
1
sis data, and H NMR spectroscopic data for compounds 5a—l
are given in Table 1.
(E)ꢀMethyl (2ꢀiminoꢀ5ꢀoxoimidazolidinꢀ4ꢀylidene)acetates 6
(general procedure). Dimethyl acetylenedicarboxylate (1.35 mL,
11 mmol) was added dropwise to a solution of guanidine 4
(10 mmol) in chloroform (20 mL), during which the reaction
mixture warmed up and rapidly turned darkꢀred. After 1 h,
the solution was concentrated to a minimum volume and
passed through an alumina column. The eluate was concenꢀ
trated, and the residue was recrystallized from isopropyl alcoꢀ
hol. (E)ꢀMethyl 2ꢀ{(E)ꢀ2ꢀ[(4,6ꢀdimethylpyrimidinꢀ2ꢀyl)imino]ꢀ
5ꢀoxoꢀ3ꢀphenylimidazolidinꢀ4ꢀylidene}acetate (6a), (E)ꢀmethyl

2ꢀIminoimidazolidinꢀ4ꢀones from guanidines
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 7, July, 2007
1427
Table 1. Characteristics of 2ꢀiminoimidazolidinꢀ4ꢀones 5a—l
Comꢀ
pound
Yield M.p.
Found
Calculated
Molecular
formula
1H NMR, δ (J/Hz)
(%)
N
(%)
/°С
C
H
5a
5b
48
176
64.17 5.41 24.79 C15H15N5O
64.06 5.34 24.91
2.39 (s, 6 Н, 2 Me); 4.50 (s, 2 Н, СН2); 6.72 (s, 1 Н, Н(5),
pyrimidine); 7.19 (t, 1 Н, Н arom., J = 7.5); 7.40 (t, 2 Н,
H arom., J = 7.3); 7.90 (d, 2 Н, H arom., J = 7.5);
9.80 (br.s, 1 Н, NH)
2.21 (s, 3 Н, Me); 2.35 (s, 6 Н, 2 Me); 4.45 (s, 2 Н, СН2);
6.70 (s, 1 Н, Н(5), pyrimidine); 7.12 (d, 1 Н, H arom.,
J = 8.9); 7.28 (t, 1 Н, H arom., J = 8.9); 7.46 (d, 1 Н,
H arom., J = 8.9); 7.73 (t, 1 Н, H arom., J = 7.2);
9.21 (br.s, 1 Н, NH)
41
151
65.16 5.68 23.86 C16H17N5O
65.08 5.76 23.73
5c
5d
5e
5f
42
62
46
52
64
153
198
156
166
201
65.89 6.04 22.69 C17H19N5O
66.02 6.15 22.65
2.20, 2.23 (both s, 3 H each, 2 Me); 2.34 (s, 6 Н, 2 Me);
4.44 (s, 2 Н, СН2); 6.78 (s, 1 Н, Н(5), pyrimidine);
7.14 (d, 1 Н, H arom., J = 8.5); 7.47 (s, 1 Н, H arom.);
7.63 (d, 1 Н, H arom., J = 8.0); 11.44 (br.s, 1 Н, NH)
2.34 (s, 6 Н, 2 Me); 3.75, 3.81 (both s, 3 H each, 2 ОMe);
4.18 (s, 2 Н, СH2); 6.71 (s, 1 Н, Н(5), pyrimidine); 6.78
(d, 1 Н, Н arom., J = 7.4); 7.12 (d, 1 Н, H arom., J = 8.4);
7.62 (s, 1 Н, Н arom.); 11.20 (br.s, 1 Н, NH)
1.35 (t, 3 Н, СН2Me, J = 7.2); 2.36 (s, 6 Н, 2 Me);
4.31 (s, 2 Н, СН2); 4.45 (q, 2 Н, CН2Me, J = 7.2); 6.63
(s, 1 Н, Н(5), pyrimidine); 7.08 (d, 2 Н, H arom., J = 7.3);
7.54 (d, 2 Н, H arom., J = 8.6); 10.80 (br.s, 1 H, NH)
1.12 (t, 3 Н, СН2Me, J = 7.4); 2.32 (s, 6 Н, 2 Me); 2.64
(q, 2 Н, CН2Me, J = 7.4); 4.42 (s, 2 Н, СН2); 6.75 (s,
1 Н, Н(5), pyrimidine); 7.12 (d, 2 Н, H arom., J = 7.3);
7.62 (d, 2 Н, H arom., J = 8.6); 11.10 (br.s, 1 H, NH)
2.32 (s, 6 Н, 2 Me); 4.35 (s, 2 Н, СН2); 6.84 (s, 1 Н, Н(5),
pyrimidine); 7.05 (s, 1 Н, H arom.); 7.12 (d, 1 Н, H arom.,
J = 8.2); 7.26 (t, 1 Н, H arom., J = 8.2); 7.41 (d, 1 Н,
H arom., J = 8.3); 10.40 (br.s, 1 Н, NH)
59.64 5.50 20.41 C17H19N5O3
59.82 5.57 20.53
62.70 5.85 21.61 C17H19N5O2
62.77 5.85 21.54
66.08 6.19 22.51 C17H19N5O
66.02 6.15 22.65
5g
60.12 4.75 23.59 C15H14FN5O
60.20 4.68 23.41
5h
5i
61
58
221
212
59.91 4.56 23.36 C15H14FN5O
60.20 4.68 23.41
2.31 (s, 6 Н, 2 Me); 4.32 (s, 2 Н, СН2); 6.88 (s, 1 Н, Н(5),
pyrimidine); 7.25 (d, 2 Н, H arom., J = 7.6); 7.41 (d, 2 Н,
H arom., J = 8.5); 10.40 (br.s, 1 Н, NH)
2.30 (s, 6 Н, 2 Me); 4.36 (s, 2 Н, СН2); 6.82 (s, 1 Н, Н(5),
pyrimidine); 6.94 (d, 2 Н, H arom., J = 8.6); 7.21 (t, 1 Н,
H arom., J = 7.3); 6.33 (t, 2 Н, H arom., J = 7.4); 6.52
(d, 2 Н, H arom., J = 7.9); 7.75 (d, 2 Н, H arom., J = 8.5);
10.60 (br.s, 1 Н, NH)
70.83 5.30 19.70 C21H19N5O
70.59 5.32 19.61
5j
52
113
67.81 6.74 20.56 C19H23N5O
67.66 6.82 20.77
0.95 (t, 3 Н, СН2Me, J = 7.0); 1.39 (m, 2 Н, СН2CН2Me);
1.60 (m, 2 Н, СН2CН2СН2); 2.38 (s, 6 Н, 2 Me); 2.61 (t,
2 Н, ArCН2СН2, J = 7.5); 4.48 (s, 2 Н, СН2); 6.71 (s, 1 Н,
Н(5), pyrimidine); 7.19 (d, 2 Н, H arom., J = 7.6); 7.74 (d,
2 Н, H arom., J = 8.5); 11.60 (br.s, 1 Н, NH)
5k
5l
50
58
242
175
51.29 3.68 19.87 C15H13Cl2N5O 2.31 (s, 6 Н, 2 Me); 4.35 (s, 2 Н, СН2); 6.68 (s, 1 Н, Н(5),
51.43 3.71 20.00
pyrimidine); 7.42 (d, 1 Н, H arom., J = 8.5); 7.53 (s, 1 Н,
H arom.); 7.56 (d, 1 Н, H arom., J = 8.5);
9.85 (br.s, 1 Н, NH)
65.18 5.64 23.73 C16H17N5O
65.08 5.76 23.73
2.35 (s, 6 Н, 2 Me); 3.89 (s, 3 Н, ОMe); 4.27 (s, 2 Н, СН2);
6.61 (s, 1 Н, Н(5), pyrimidine); 7.00 (t, 1 Н, H arom.,
J = 8.5); 7.10 (d, 1 Н, H arom., J = 8.5); 7.32 (t, 1 Н,
H arom., J = 8.0); 7.44 (d, 1 Н, Н arom., J = 8.5);
11.60 (br.s, 1 Н, NH)

1428
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Shestakov et al.
Table 2. Characteristics of (E)ꢀmethyl (2ꢀiminoꢀ5ꢀoxoimidazolidinꢀ4ꢀylidene)acetates 6a—g
Comꢀ
pound
Yield M.p.
Found
Calculated
Molecular
formula
1H NMR, δ (J/Hz)
(%)
N
(%)
/°С
C
H
6a
6b
6c
6d
6e
6f
29
198
61.73 4.76 20.15 C18H17N5O3
61.54 4.84 19.94
2.35 (s, 6 Н, 2 Me); 3.15 (s, 3 Н, ОMe); 5.71 (s, 1 Н,
—СН=); 6.80 (s, 1 Н, Н(5), pyrimidine); 7.16 (d, 2 Н,
Н arom., J = 8.0); 7.36 (t, 2 Н, H arom., J = 7.5); 7.42
(t, 1 Н, H arom., J = 7.6); 11.80 (br.s, 1 Н, NH)
2.12 (s, 3 Н, Me); 2.33 (s, 6 Н, 2 Me); 3.22 (s, 3 Н, ОMe);
5.62 (s, 1 Н, —СН=); 6.74 (s, 1 Н, Н(5), pyrimidine);
7.21, 7.53 (both d, 2 H each, Н arom., J = 8.2);
11.60 (br.s, 1 Н, NH)
2.32 (s, 6 Н, 2 Me); 3.15 (s, 3 Н, ОMe); 5.74 (s, 1 Н,
—СН=); 6.70 (s, 1 Н, Н(5), pyrimidine); 7.71 (d, 1 Н,
J = 8.0); 7.74 (t, 1 Н, H arom., J = 7.9); 7.79 (d, 1 Н,
J = 8.0); 7.81 (s, 1 Н, Н arom.); 11.50 (br.s, 1 Н, NH)
2.34 (s, 6 Н, 2 Me); 3.14 (s, 3 Н, ОMe); 5.71 (s, 1 Н,
—СН=); 6.89 (s, 1 Н, Н(5), pyrimidine); 7.30,
7.60 (both d, 2 H each, Н arom., J = 8.2);
38
41
42
43
65
193
195
202
177
159
62.28 5.16 19.25 C19H19N5O3
62.47 5.21 19.18
54.54 3.80 16.70 C19H16F3N5O3
54.42 3.82 16.71
56.10 4.12 18.08 C18H16ClN5O3
56.02 4.15 18.15
11.80 (br.s, 1 Н, NH)
51.48 3.62 16.61 C18H15Cl2N5O3 2.32 (s, 6 Н, 2 Me); 3.18 (s, 3 Н, ОMe); 5.58 (s, 1 Н,
51.43 3.57 16.67
—СН=); 6.72 (s, 1 Н, Н(5), pyrimidine); 7.19, 7.54
(both d, 1 H each, Н arom., J = 8.1); 8.10
(s, 1 Н, Н arom.); 11.50 (br.s, 1 Н, NH)
2.36 (s, 6 Н, 2 Me); 2.52 (s, 3 Н, Me); 3.17 (s, 3 Н, ОMe);
5.70 (s, 1 Н, —СН=); 6.82 (s, 1 Н, Н(5), pyrimidine);
7.95 (d, 1 Н, Н arom., J = 7.8); 7.32 (d, 1 Н, H arom.,
J = 8.1); 7.61 (t, 1 Н, Н arom., J = 7.7); 7.81 (s, 1 Н,
Н arom.); 11.70 (br.s, 1 Н, NH)
62.36 5.32 19.06 С19H19N5O3
62.47 5.21 19.18
6g
44
160
60.84 5.46 17.61 C20H21N5O4
60.76 5.32 17.72
1.33 (t, 3 Н, ОСН2Me, J = 7.2); 2.34 (s, 6 Н, 2 Me);
3.16 (s, 3 Н, ОMe); 3.90 (q, 2 Н, ОCН2Me, J = 7.2);
5.70 (s, 1 Н, —СН=); 6.83 (s, 1 Н, Н(5), pyrimidine);
7.10, 7.50 (both d, 2 H each, Н arom., J = 8.2);
11.50 (br.s, 1 Н, NH)
Table 3. Characteristics of (2ꢀiminoꢀ5ꢀoxoimidazolidinꢀ4ꢀyl)acetic acids 7a—g
Comꢀ
pound
Yield M.p.
Found
Calculated
Molecular
formula
1H NMR, δ (J/Hz)
(%)
N
(%)
/°С
C
H
7a
44
224
58.46 5.23 19.06 C18H19N5O4
58.54 5.15 18.97
2.45 (s, 6 Н, 2 Me); 2.87 (dd, 1 Н, СН2, J = 4.4, J = 17.9);
3.13 (dd, 1 Н, СН2, J = 5.6, J = 17.9); 3.79 (s, 1 Н, ОMe);
4.64 (t, 1 Н, СH, J = 6.8); 6.92 (s, 1 Н, Н(5),
pyrimidine); 6.98 (d, 2 Н, H arom., J = 7.2); 7.24
(d, 2 Н, H arom., J = 7.7); 12.15 (br.s, 1 H, СООН);
12.33 (s, 1 Н, NH)
7b
36
305
54.44 4.29 18.63 C17H16ClN5O3 2.39 (s, 6 Н, 2 Me); 2.69 (dd, 1 Н, СН2, J = 4.8, J = 18.3);
54.60 4.28 18.74
2.94 (dd, 1 Н, СН2, J = 5.8, J = 18.3); 4.93 (t, 1 Н, СH,
J = 6.6); 6.97 (s, 1 Н, Н(5), pyrimidine); 7.37 (d, 1 Н,
H arom., J = 7.4); 7.53 (t, 1 Н, H arom., J = 8.4); 7.72
(d, 1 Н, H arom., J = 7.6); 8.12 (s, 1 Н, H arom.);
12.2 (br.s, 1 H, СООН); 12.41 (s, 1 Н, NH)
(to be continued)

2ꢀIminoimidazolidinꢀ4ꢀones from guanidines
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 7, July, 2007
1429
Table 3 (continued)
Comꢀ
pound
Yield M.p.
Found
Calculated
Molecular
formula
1H NMR, δ (J/Hz)
(%)
N
(%)
/°С
C
H
7c
7d
29
302
61.25 5.30 19.80 C18H19N5O3
61.19 5.38 19.83
2.28 (s, 3 Н, Me); 2.45 (s, 6 Н, 2 Me); 2.82 (dd, 1 Н, СН2,
J = 4.5, J = 18.1); 3.08 (dd, 1 Н, СН2, J = 5.7,
J = 18.1); 4.69 (t, 1 Н, СH, J = 6.8); 6.85 (s, 1 Н, Н(5),
pyrimidine); 7.10 (d, 1 Н, H arom., J = 7.5); 7.22 (d, 1 Н,
H arom., J = 7.8); 7.38 (t, 1 Н, Н arom., J = 7.5);
7.52 (s, 1 Н, H arom.); 12.23 (br.s, 1 H,
СООН); 12.46 (s, 1 Н, NH)
29
235
62.23 3.78 18.98 C19H21N5O3
62.12 5.72 19.07
2.26 (s, 3 Н, 2 Me); 2.31 (s, 3 Н, Me); 2.49 (s, 6 Н, Me);
2.89 (dd, 1 Н, СН2, J = 4.3, J = 18.3); 3.16 (dd, 1 Н,
СН2, J = 5.2, J = 18.3); 4.61 (t, 1 Н, СH, J = 7.1);
6.99 (s, 1 Н, Н(5), pyrimidine);
7.12 (d, 1 Н, H arom., J = 8.1); 7.41
(d, 1 Н, H arom., J = 8.3); 7.50 (s, 1 Н, H arom.);
12.12 (br.s, 1 H, СООН); 12.34 (s, 1 Н, NH)
7e
7f
32
42
25
273
241
257
52.96 3.88 17.10 C18H16F3N5O3 2.32 (s, 6 Н, 2 Me); 2.69 (dd, 1 Н, СН2, J = 4.8, J = 18.0);
53.07 3.93 17.20
2.84 (dd, 1 Н, СН2, J = 5.8, J = 18.0); 5.19 (t, 1 Н, СH,
J = 6.6); 6.89 (s, 1 Н, Н(5), pyrimidine); 7.59 (d, 1 Н,
H arom., J = 7.3); 7.68 (t, 1 Н, H arom., J = 8.6); 7.84
(d, 1 Н, H arom., J = 7.4); 7.79 (s, 1 Н, H arom.)
11.00—13.00 (br.s, 2 H, NH, СООН)
57.16 5.35 17.50 С19H21N5O5
57.14 5.26 17.54
2.48 (s, 6 Н, 2 Me); 2.78 (dd, 1 Н, СН2, J = 4.6, J = 18.2);
3.04 (dd, 1 Н, СН2, J = 5.9, J = 18.2); 3.74, 3.82
(both s, 3 H each, ОMe); 4.62 (t, 1 Н, СH, J = 7.0); 6.67 (s,
1 Н, Н(5), pyrimidine); 6.86, 6.97
(both d, 1 H each, H arom., J = 7.7); 7.06 (s, 1 Н, H arom.);
12.41 (br.s, 1 H, СООН); 12.69 (s, 1 Н, NH)
50.36 3.61 17.08 C17H15Cl2N5O3 2.41 (s, 6 Н, 2 Me); 2.93 (dd, 1 Н, СН2, J = 4.5, J = 18.2);
7g
50.00 3.68 17.16
3.21 (dd, 1 Н, СН2, J = 5.9, J = 18.2); 4.76 (t, 1 Н, СH,
J = 6.9); 7.10 (s, 1 Н, Н(5), pyrimidine); 7.52 (d, 1 Н,
H arom., J = 7.8); 7.72 (s, 1 Н, H arom.); 8.59 (d, 1 Н,
H arom., J = 7.8); 12.17 (br.s, 1 H, СООН);
12.62 (s, 1 Н, NH)
2ꢀ{(E)ꢀ2ꢀ[(4,6ꢀdimethylpyrimidinꢀ2ꢀyl)imino]ꢀ5ꢀoxoꢀ3ꢀpꢀtolylꢀ
imidazolidinꢀ4ꢀylidene}acetate (6b), (E)ꢀmethyl 2ꢀ{(E)ꢀ2ꢀ[(4,6ꢀ
dimethylpyrimidinꢀ2ꢀyl)imino]ꢀ5ꢀoxoꢀ3ꢀ[3ꢀ(trifluoroꢀ
methyl)phenyl]imidazolidinꢀ4ꢀylidene}acetate (6c), (E)ꢀmethyl
{2ꢀ(E)ꢀ3ꢀ(4ꢀchlorophenyl)ꢀ2ꢀ[(4,6ꢀdimethylpyrimidinꢀ2ꢀ
yl)imino]ꢀ5ꢀoxoimidazolidinꢀ4ꢀylidene}acetate (6d), (E)ꢀmethyl
2ꢀ{(E)ꢀ3ꢀ(3,4ꢀdichlorophenyl)ꢀ2ꢀ[(4,6ꢀdimethylpyrimidinꢀ2ꢀ
yl)imino]ꢀ5ꢀoxoimidazolidinꢀ4ꢀylidene}acetate (6e), (E)ꢀmethyl
2ꢀ{(E)ꢀ2ꢀ[(4,6ꢀdimethylpyrimidinꢀ2ꢀyl)imino]ꢀ5ꢀoxoꢀ3ꢀ
mꢀtolylimidazolidinꢀ4ꢀylidene}acetate (6f), and (E)ꢀmethyl
2ꢀ{(E)ꢀ2ꢀ[(4,6ꢀdimethylpyrimidinꢀ2ꢀylimino]ꢀ3ꢀ(2ꢀethoxypheꢀ
nyl)ꢀ5ꢀoxoimidazolidinꢀ4ꢀylidene}acetate (6g) were prepared.
The yields, melting points, elemental analysis data, and 1H NMR
spectroscopic data for compounds 6a—g are given in Table 2.
(2ꢀIminoꢀ5ꢀoxoimidazolidinꢀ4ꢀyl)acetic acids 7 (general proꢀ
cedure). A solution of guanidine 4 (10 mmol) and anhydride 3
(10 mmol) in dry dioxane (15 mL) was kept at 70 °C for 3 h. The
precipitate that formed was filtered off and recrystallized from
dioxane. An additional amount (20—30%) of the somewhat less
pure product can be isolated from the filtrate by pouring the
latter into cold water followed by recrystallization of the preꢀ
cipitate that formed from dioxane. (E)ꢀ2ꢀ{2ꢀ[(4,6ꢀDimethylꢀ
pyrimidinꢀ2ꢀyl)imino]ꢀ3ꢀ(4ꢀmethoxyphenyl)ꢀ5ꢀoxoimidazolꢀ
idinꢀ4ꢀyl}acetic acid (7a), (E)ꢀ2ꢀ{3ꢀ(3ꢀchlorophenyl)ꢀ2ꢀ[(4,6ꢀ
dimethylpyrimidinꢀ2ꢀyl)imino]ꢀ5ꢀoxoimidazolidinꢀ4ꢀyl}acetic
acid (7b), (E)ꢀ2ꢀ{2ꢀ[(4,6ꢀdimethylpyrimidinꢀ2ꢀyl)imino]ꢀ5ꢀoxoꢀ
3ꢀmꢀtolylimidazolidinꢀ4ꢀyl}acetic acid (7c), (E)ꢀ3ꢀ(3,4ꢀdiꢀ
methylphenyl)ꢀ2ꢀ{2ꢀ[(4,6ꢀdimethylpyrimidinꢀ2ꢀyl)imino]ꢀ5ꢀ
oxoimidazolidinꢀ4ꢀyl}acetic acid (7d), (E)ꢀ2ꢀ{2ꢀ[(4,6ꢀdimethylꢀ
pyrimidinꢀ2ꢀyl}imino]ꢀ5ꢀoxoꢀ3ꢀ[3ꢀ(trifluoromethyl)pheꢀ
nyl]imidazolidinꢀ4ꢀyl}acetic acid (7e), (E)ꢀ2ꢀ{3ꢀ(2,5ꢀdimethꢀ
oxyphenyl)ꢀ2ꢀ[(4,6ꢀdimethylpyrimidinꢀ2ꢀyl)imino]ꢀ5ꢀoxoimidꢀ
azolidinꢀ4ꢀyl}acetic acid (7f), and (E)ꢀ2ꢀ{3ꢀ(2,4ꢀdichloroꢀ
phenyl)ꢀ2ꢀ[(4,6ꢀdimethylpyrimidinꢀ2ꢀyl)imino]ꢀ5ꢀoxoimidꢀ
azolidinꢀ4ꢀyl}acetic acid (7g) were prepared. The yields, meltꢀ
ing points, elemental analysis data, and 1H NMR spectroscopic
data for compounds 7a—g are given in Table 3.
References
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1430
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Received January 29, 2007;
in revised form April 11, 2007