Synthesis of some novel imidazolidine derivatives and their metal complexes with biological and antitumor activity

Article abstract of DOI:10.1002/hc.20244

Halogenated imidazo(pyrazine,[1,4]-diazocine and quinoxaline), 9,10-anthraquinone-[6,7-e], phenanthroline[5,6-e] {imidazo[4,5-b]-pyrazine}, and naphtho[1,8-ef]imidazo[4,5-b][1,4] diazipen were obtained through interaction of imidazolidineiminothiones with

Full text of DOI:10.1002/hc.20244

Heteroatom Chemistry
Volume 17, Number 7, 2006
Synthesis of Some Novel Imidazolidine
Derivatives and Their Metal Complexes with
Biological and Antitumor Activity
Shaya Y. Al-Raqa, Ahmed M. Sh. ElSharief, Saied M. E. Khalil, and
Abdulkhaliq M. Al-Amri
Chemistry Department, Faculty of Science, Taibah University, Madinah Munawwarah,
Saudi Arabia
Received 20 June 2005; revised 19 December 2005
and synthetic origins [27] such as histidine, purines,
ABSTRACT: Halogenated imidazo(pyrazine,[1,4]-
biotin, and hydrantoin; thus, in this investigation
different types of fused imidazoles such as imi-
diazocine and quinoxaline), 9,10-anthraquinone-
[6,7-e],
phenanthroline[5,6-e]
{imidazo[4,5-b]-
dazo(pyrazine, [1,4]diazocine, quinoxaline, and tri-
azine), naphtho[1,8-ef]imidazo[4,5-b][1,4] diazipen-
9-one, and pyrrolo[2,3-d] imidazoles have been
synthesized.
Thus cyanothioformamides I were prepared
[1,20] and reacted by cycloaddition with phenyl
and p-chlorophenyl isocyanate to produce 1-
pyrazine}, and naphtho[1,8-ef]imidazo[4,5-b][1,4]
diazipen were obtained through interaction of im-
idazolidineiminothiones with the corresponding
diamino compounds. Imidazo[4,5-e] triazine and
pyrrolo[2,3-d]imidazole were prepared when the
iminothiones were reacted with thiocarbohydrazide
and with ethylphenyl acetate, separately. Some of the
synthesized compounds exhibited better biological
(phenyl
and
4-chlorophenyl)-3-aryl-5-imino-4-
thioxoimidazolidine-2-one II (Scheme 1).
ꢀ
C
and antitumor activities. 2006 Wiley Periodicals, Inc.
The imidazolidines II contain adjacent imino
and thione function in the 4 and 5 positions, which
have been shown to be reactive in a number of sub-
sequent ring closure reactions.
Heteroatom Chem 17:634–647, 2006; Published online
in Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.20244
Thus, interaction of IIe,g with ethylenediamine
in boiling ethanol took place easily through elimina-
tion of H2S and NH3 to afford a product that was
expected to have structure III (Scheme 2).
INTRODUCTION
A variety of heterocyclic ring closure reactions with
cyanothioformamides [1–3] give rise to imidazole
[4], oxazole [5], and thiazole [6,7]. Our interest in
the chemistry of cyanothioformamides [8–16] led us
to use them in the synthesis of various fused hetero-
cyclic systems [17–26].
However, the infrared spectrum showed the pres-
ence of N H stretching at 3300 cm−1, and the
1H NMR spectrum of IVb revealed the absence of
aliphatic protons while IVa showed in the aliphatic
region the triplet and quartet of C2H5 O group only
which led to postulate the tautomeric structure IV
as 1,3-diaryl-4,7-dihydroimidazo[4,5-b] pyrazine-2-
one. Mass spectrum of IVb: at m/z, 360, (0.4%),
M + 1; 358, (3.4%), M − 1; 127 (100%) base peak, p-
Cl·C6H4·NH2, 129 (33%) (127:129; 3:1 due to chlorine
atoms).
Since imidazoles and their fused derivatives are
key in many bioactive compounds of both natural
Correspondence to: Shaya Y. Al-Raqa; e-mail: shaya97@
hotmail.com.
c
ꢀ
2006 Wiley Periodicals, Inc.
634

Synthesis of Some Novel Imidazolidine Derivatives and Their Metal Complexes 635
FIGURE 2 Structure of VII.
SCHEME 1
easily detected) to produce a product that was ex-
pected to have structure VIa (Fig. 1).
Unfortunately, IR spectra exhibited the absence
of νC N (which exclude structure VIa) and the pres-
ence of a broadband at 3300–3100 (νNH, NH2) and
1710 cm−1 (νCO). 1H NMR of this product exhibited
at δ = 2.1 (3H, s, CH3), 6.7–6.9 (9H, m, Ar H), 8.3 (3H,
hump, NH, NH2), and 8.9 (2H, s, CONH2), both NH,
NH2 and CONH2 were disappeared by D2O. Mass
spectrum revealed M+ at m/z = 369 (3%, M − H2O),
133 (8.5%, p-CH3·C6H4·CNO), 119 (4.9%, C6H5NCO),
and 127 (100%). These data with elemental analyses
demonstrated structure VIb for this product.
SCHEME 2
Similarly, 1,4-diaminobutane was reacted suc-
cessfully with the iminothiones IIg to give V as
1,3-di(4-chlorophenyl)-4,5,8,9-tetrahydro-1H-imid-
azo[4,5-b][1,4] diazocin-2-(3H)-one (Fig. 1).
IR spectrum of V revealed the presence of the
NH stretching at 3300 cm−1. The 1H NMR spectrum
showed broad singlet at 8.9 ppm assigned to NH
protons, which disappeared by D2O. Eight aromatic
protons appeared as quartet at 7.3 and 7.5 ppm.
Six protons (4 aliphatic, 2 × CH2 and 2 olifinic,
CH CH ) appeared as multiplet at 3.55–5.35 ppm.
Mass spectra of V showed at m/z, 352, (3.3%), M − Cl.
The authors also studied the reaction be-
tween imidazolidineiminothiones II and diamino-
maleinonitrile where various products could be iso-
lated. Thus, the reaction between equimolar amount
of IIa and diaminomaleinonitrile was proceeded
easily through elimination of H2S (which could be
5-Imino-1,3-di(4-chlorophenyl)imidazolidine-4-
thione IIg was reacted with diaminomaleinonitrile
to produce two products. One of them showed the
absence of νC N and exhibited elemental and spec-
tral data compatible with VIc. The other revealed
νC N (2225) and νNH (3330) cm−1 and was given
1
structure VII, which was demonstrated by IR, H
NMR, mass spectra, and elemental analyses.
1H NMR of (VII) (δ, ppm): at δ = 7.1–7.3 (8H,
q, Ar H), 8.7, 9.1 (3H, 2H; hump, s; NH, NH2 and
CONH2; disappeared by D2O) and mass spectrum of
(VII) exhibited at m/z 442 (2.5%, M + 1).
The mechanism of formation of VIb,c could be
rationaled on bases that H2S and NH3, which evolved
during the reaction, could be added to the cyano
groups. In compound VII, the thione group was re-
acted only with one amino group (Fig. 2).
Also, 1,2-diamino-4,5-dibromobenzene, 3,4-
diaminotoluene, and 3,4-diaminobenzoic acid were
FIGURE 1 Structure of V and VI.
Heteroatom Chemistry DOI 10.1002/hc

636 Al-Raqa et al.
These products Xa–c are sulphur-free and the IR
spectra revealed the absence of NH stretching. The
1H NMR of Xa showed the expected singlet peak at
2.3 ppm assigned to the methyl protons. The spec-
trum of the aromatic protons appeared as a com-
plex pattern between 6.7 and 7.1 ppm. Mass spec-
trum of Xb showed a molecular ion peak at m/z
421, 1.2% (M − p-Cl·C6H4 ) with a base peak at m/z
238, 100%, 1,2-diaminoanthraquinone; 153, 3.47%
p-Cl·C6H4·NCO, and 149, 0.3% p-CH3O·C6H4·NCO.
Similarly,
5,6-diamino-1,10-phenanthroline
reacted successfully with the imidazolidineiminoth-
ione IIf through elimination of H2S and NH3 to
produce 6-(4-chlorophenyl)-8-phenyl-6H,8H-{[1,10]
phenanthrolino}[5,6-e]imidazo[4,5-b]pyrazine-7-one
XI (Fig. 5).
The IR measurements of this product showed the
absence of NH stretching. Mass spectra of XI exhib-
ited M+ at m/z 474(2.47%), 153, 100% (base peak);
p-Cl·C6H4·NCO); 155, 32.9% (3:1) due to the chlorine
atom.
A new type of fused imidazoles was achieved by
interaction of various imidazolidineiminothiones II
with 1,8-diaminonaphthalene, which proceeded eas-
ily through evolution of H2S and elimination of NH3
followed by precipitation of solid.
FIGURE 3 Structure of VIII and IX.
reacted successfully with the iminothiones IId,f,
and g, respectively, through elimination of H2S
and ammonia to yield 2-oxo-1,3-diaryl-1,3-dihydro-
2H-imidazo[4,5-b]quinoxalines VIIIa–c, respec-
tively (Fig. 3).
Mass spectrum of VIIIa exhibited M+ at m/z
1
560 (100% base peak), H NMR spectrum of VIIIb
showed the expected singlet assigned to the methyl
protons, and the 12 aromatic protons appeared as
multiplet at 6.5–6.9 ppm. Besides VIIIa, a by-product
could be isolated which structure was assigned to
IX as diimidazo [4,5-b: 4ꢁ,5ꢁ-e]pyrazine derivative
(Fig. 3). The product IX could be produced through
desulfurization of the iminothione under the reac-
tion conditions to give the corresponding iminocar-
bene, which then dimerized to produce IX. 1H NMR,
at δ = 3.85 (6H, s, 2 × OCH3), δ = 6.9–7.3 (16H, 2q,
Ar H), and mass spectrum, showed M+ at m/z 624
(1.3%). Formation of IX is in complete agreement
with the previous findings obtained by Khattak et al.
[6] and recently by El-Sharief et al. [14].
All of these experiments were found to yield
two products, one of them which was precipitated
during refluxing was analyzed for structure XII
as 8,10-diaryl-8H,10H-naphtho[1,8-ef]imidazo[4,5-
b][1,4]diazepin-9-one XIIa–d (Fig. 5). IR (no νNH
& NH2; νC O at 1690, νC N at 1620 cm−1). Mass
spectrum: XIIa, at m/z 402 (100%, M+, base peak);
XIIb, m/z = 436 (100%, M+, base peak).
Fragmentation pattern for mass spectrum of
XIIc is illustrated in Chart 1; XIId, m/z = 422 (100%,
M+, base peak). It is obvious that most of these prod-
ucts exhibited a molecular ion peak as base peak
through some light on their higher stability. Also,
most of the chlorinated compounds showed the per-
cent (3:1) and gave fragments up to M + 5.
In a similar fashion, 1,2-diaminoanthraquinone
was reacted with (IIa, d, and e) to produce 7,9-diaryl-
7H,9H,{[9,10]anthraquinone}[6,7-e]imidazo[4,5-b]
pyrazine-8-one X (Fig. 4). H2S could be easily
detected throughout the reaction period.
The other product was obtained when the reac-
tion mixture was concentrated, which showed ana-
lytical and spectral data compatible with the inter-
mediate XIII (Fig. 6).
IR measurements of XIII exhibited NH stretch-
ing underneath the NH2 stretching at 3360 and
1
3280 cm−1. H NMR of XIIId showed the aromatic
protons peak at 6.9–7.3 ppm, whereas the variable
NH and NH2 protons appeared as hump and overlap
with the aromatic protons at 7.0–7.3 ppm, which dis-
appeared by D2O. Mass spectra of XIIIb: 453 (1.1%
M+).
All the above-mentioned fused imidazoles were
obtained through interaction of the corresponding
FIGURE 4 Structure of X, XI, and XII.
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of Some Novel Imidazolidine Derivatives and Their Metal Complexes 637
FIGURE 5 Structure XI and XII.
CHART 1 Fragmentation pattern of compound (XIIc).
FIGURE 6 Structure of XIII and XIV.
Heteroatom Chemistry DOI 10.1002/hc

638 Al-Raqa et al.
1
and νC N at 1630 cm−1). The H NMR spectrum of
o-diamino compounds with the iminothione system
where the thione group was first reacted and then the
imino group to liberate H2S and NH3, respectively.
Another type of fused imidazoles could also
be synthesized through interaction of the imidazo-
lidinothione with active methylene compounds such
as ethyl phenylacetate. The thiocarbonyl group was
first reacted with the active methylene group (evolu-
tion of H2S) and then cyclization took place through
the imino group.
the product showed the expected singlet assigned to
the two methyl protons. The eight aromatic protons
occurred as quartet at 7.1–7.3 ppm. A broad singlet
at 8.7 ppm was assigned to the inner NH proton
disappeared by D2O. Mass spectrum of XVa: at m/z
416 (5.4%, M + 1).
Also, IIg was reacted with ethyl cyanoacetate
through elimination of H2S to give XVb. The IR spec-
trum showed the presence of NH stretching at 3300
and CN stretching at 2217 cm−1. The 1H NMR spec-
trum of XVb showed the expected triplet peak as-
signed to the methyl protons, whereas the methylene
protons appeared as quartet at 4.1 ppm. The eight
aromatic protons occurred as quartet at 7.3 ppm. A
broad singlet at 8.9 ppm was assigned to the inner
NH proton disappeared by D2O.
Thus, interaction of ethyl phenylacetate with im-
idazolidineiminothiones IIg gave a product with el-
emental and spectral data compatible with struc-
ture XIV as 1,3-bis(4-chlorophenyl)-6-phenylpyrrolo
[2,3-d] imidazole-2,5-(1H, 3H) dione. The IR spec-
trum of XIV revealed the absence of NH stretching.
1
The H NMR spectrum of the product displayed a
multiplet peak at 7.2–7.4 ppm assigned to the aro-
matic protons. Fragmentation pattern for mass spec-
trum of XIV is illustrated in Chart 2.
Acetyl acetone was selected as another type of
active methylene to react with the iminothiones IIg,
where H2S could be easily detected throughout the
reaction period to give 3-[1,3-bis-(4-chlorphenyl)-5-
imino-2-oxo-imidazolidine-4-ylidene]-pentane-2,4-
dione XVa (Fig. 7). IR (νNH at 3270, νC O at 1700
It is obvious that the thione group in the imine
thione system could condense with active methylene
in presence of basic catalyst as sodium ethoxide.
Also, cyclization could be achieved with ethyl
phenylacetate, and the nonisolation of the cyclic
structure with ethyl cyanoacetate may be due to the
fact that the authors could not isolate all the prod-
ucts formed in this reaction, but the most isolatable
one.
CHART 2 Fragmentation pattern of compound (XIV).
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of Some Novel Imidazolidine Derivatives and Their Metal Complexes 639
FIGURE 7 Structure of XV and XVI.
Another type of fused imidazole was obtained
from interaction of imidazolidineiminothiones (IIg
and i) with thiocarbohydrazide through elimina-
tion of both H2S and NH3 to produce 1,3-diaryl-2H-
imidazo[4,5-e]triazine-2-one XVIa and b (Fig. 7).
IR measurements of the products showed the NH2
stretching at 3430 and 3350 cm−1 and NH stretching
at 3200 cm−1. The 1H NMR spectrum of XVIa showed
the expected eight aromatic protons as quartet at
7.0–7.3 ppm. A broad singlet occurred at 8.1 ppm
assigned to the NH and NH2 protons, which was dis-
appeared by D2O. Mass spectra of XVIb: at m/z = 432
(2.1%, M+), 153 (100%, base peak p-Cl·C6H4·NCO).
The authors synthesized some metal complexes
from the reaction between imidazolidineiminoth-
iones II with metal salts. Thus the reaction of the lig-
ands [L1(IId), L2(IIe), and L3(IIg)] with copper(II)
and cobalt(II) ions produced a series of mononuclear
metal complexes with formulae [(L)MCl2]·nH2O
(Table 1).
and Cu(II) cations while the absorption band of the
ν(C O) is not changed.
The magnetic moments of Co(II) complexes,
XVIIa and XVIIc (Table 1), were 4.40 and 4.80
BM, respectively, because of the spin-free value of
three unpaired electron, indicating that the Co(II)
is high-spin six-coordinate. Also, magnetic moment
of Cu(II) complex was 1.82 BM due to the spin one
electron.
The mass spectral data of the complexes (Table 1)
provide good evidence for their molecular formulas.
Complexes XVIIa–c (Fig. 8) show that the highest
mass peak with m/z, 844, 855, and 859, respectively,
agrees with formula weights of the complexes. The
complex XVIId shows the highest mass peak with
m/z, 814, due to formula weight M − 51.5.
On the basis of IR, mass spectral data, and
magnetic moments, the suggested structure of the
mononuclear complexes XVII is shown below.
Reactions of imidazolidineiminothiones II with
amines and hydrazines (one mole and excess) were
studied [15]. In this investigation, another type of
(amine, hydrazine, and sulpha) derivatives were
selected. Thus α,α-diamino-p-xylene was reacted
with IIg hopping to obtain a bis-imidazol of type
XVIII (Fig. 9), but instead, equimolar amounts were
reacted, followed by oxidation of the terminal amino
The IR spectra (Table 1) of the complexes ex-
hibit a broadband around 3450 cm−1 assigned for
ν(OH) of water molecules associated with the com-
plexes. Also, IR spectra showed that the absorption
of the NH, C N, and C S groups in the complexes
are shifted to lower frequencies, which indicate that
these groups participate in coordinating with Co(II)
TABLE 1 IR, Mass Spectral Data, and Magnetic Moments of XVII
IR Spectral Band (cm−1
νNH νCO νC N νC S
)
Mass Spectral Data
(m/z) Found (Calc.)
Complex
Magnetic Moment (BM)
XVIIa [(L1)2CoCl2]3.5H2O
XVIIb [(L1)2CuCl2]1.5H2O
XVIIc [(L2)2CoCl2]0.5H2O
XVIId [(L3)2CuCl2]
3310, 1730, 1520, 1390, 1100
(3350) (1730) (1590) (1450, 1170)
3360, 1730, 1520, 1380, 1190
(3400) (1730) (1590) (1430, 1150)
3400, 1730, 1500, 1410, 1180
(3450) (1730) (1570) (1460, 1200)
3260, 1750, 1500, 1420, 1110
(3370) (1725) (1585) (1440, 1170)
4.40
1.82
4.80
–
884 (884)
855 (852.5)
859 (857.7)
814(M − 18) (832)
Heteroatom Chemistry DOI 10.1002/hc

640 Al-Raqa et al.
FIGURE 8 Structure XVII.
group to produce 1,3-bis-(4-chlorophenyl)-4-imino-
5-(4-nitrosomethyl-benzylimino)imidazolidine-2-
one XIX (Fig. 9).
Since imidazoles have various activities as
mentioned above [27], and sulfonamides have
been reported to exhibit antimicrobial, antifun-
gal [28], insulin releasing, carbonic anhydrase
inhibitory [29], anti-inflammatory [30], and an-
titumor properties [31], the authors decided to
couple both in one nucleus hopping to obtain
products with better activities. Thus, interaction
of II with sulphadiazine, sulphathiazole, and
sulphacetamide-furnished products that revealed el-
emental and spectral data compatible with structure
XXI as 4-(1,3-diaryl-5-imino-2-oxoimidazolidin-
1
The H NMR spectrum of the product was very
informative and proved the structure of the isolated
XIX. Thus the evidence of the assignment was based
on the appearance of the singlet peak at 3.7 ppm cor-
responding to the two methylene protons α to the ni-
troso group. There was also another singlet occurred
at 3.5 ppm assigned to the other two methylene pro-
tons adjacent to the imino group. The NH proton
appeared as a hump at 8.9 and disappeared by D2O
and at δ = 6.9–7.1 (12H, m, Ar H). Mass spectrum
of XIX revealed at m/z = 483 (2.4%, M + H2O); 466
(100%, base peak, M + 1).
4-ylideneamino)-benzenesulfonamide
(Fig. 10).
derivatives
1H NMR spectrum of XXIc showed all the ex-
pected signals. Thirteen aromatic protons occur as
multiplet between 6.9 and 7.2 ppm. Two singlets at
2.3 and 2.5 ppm, each integrating for three protons,
were assigned to the methyl attached to phenyl group
and methyl in the acetyl group, respectively. Two
broad singlets at 8.5 and 9.1 ppm were assigned to
Benzenesulfonyl hydrazide was also allowed to
react with the iminothiones IIg, where H2S could
be easily detected through the reaction time. The
isolated product was analyzed for structure XX
(Fig. 9) as 4-(phenylsulfonyl)hydrazono-1,3-bis(4-
chlorophenyl)-5-iminoimidazolidin-2-one.
FIGURE 9 Structure of XVIII, XIX, and XX.
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of Some Novel Imidazolidine Derivatives and Their Metal Complexes 641
FIGURE 10 Structure of XXI.
FIGURE 11 Structure of XXII and XXIII.
the NH and SO2NH protons, which were disappeared
by D2O.
Most of the synthesized compounds were found
to possess various antimicrobial activities toward all
the organisms used. Imidazopyrazine VIc was found
to possess the highest antimicrobial activity against
S. aureus, E. coli, and S. typhi. Imidazopyrazine IVa,
1,3-bis(4-chlorophenyl)imidazolidine-2-one deriva-
tives XVa and XX, also XXIa, which have sulphadi-
azine moiety and copper complex XVIIb, were found
to possess antimicrobial activities against most of the
microorganisms used.
Imidazolidine iminothiones IIh,j were subjected
to imine hydrolysis by dil HCl/EtOH to produce
4-thioxoimidazolidine-2,5-diones XXIIa,b (Fig. 11).
The IR spectra showed the disappearance of NH
stretching.
Interaction of these 4-thioxoimidazolidinones
XXIIa,b with copper turnings in p-xylene furnished
copper sulfide with sulfur-free products which their
elemental and spectral data were compatible with
structure XXIII as bis-imidazolidine-2,5-diones.
The IR spectrum showed the presence of
C O and C C stretching at 1710 and 1600 cm−1,
respectively.
Antifungal Activities
The selected compounds were also tested for their
antifungal activity using Aspergillus flavus and As-
pergillus niger. Some of the synthesized compounds
were found to possess antifungal activities toward
the microorganisms used, and the results are sum-
marized in Table 3.
The copper complexes (XVIIb and d) exhibited
higher activities. Imidazolidine containing sulphadi-
azine XXIa or sulphathiazole XXIb moieties and im-
idazopyrazine with two chlorine atoms (VIc) showed
better activity. Compounds IVa, VIIIa, XIIId, and
XVa were also found to possess antifungal activities
against the microorganisms used.
BIOLOGICAL ACTIVITY
Biological activity of the synthesized compounds
were done in Fermentation Biotechnology and Ap-
plied Microbiology (Ferm-Ban) Center, Al-Azhar
University, Cairo, Egypt.
Antimicrobial Activity
Compounds IVa, V, VIc, VIIIa, XIIa, XIIId, XIV,
XVa, XVIIb, XVIId, XX, XXIa, and XXIIb were
tested for their antimicrobial activity by the dif-
fusion agar technique using the gram-positive bac-
teria Bacillus subtilis and Staphylococcus aureus
and the gram-negative bacteria Escherichia coli and
Salmonella typhi. The results are summarized in
Table 2.
ANTITUMOR ACTIVITY OF SOME OF THE
SYNTHESIZED COMPOUNDS
Antitumor activity was estimated at Cairo University,
National Cancer Institute, Cancer Biology Depart-
ment, Pharmacology Unit. The results are summa-
rized in Table 4.
Heteroatom Chemistry DOI 10.1002/hc

642 Al-Raqa et al.
TABLE 2 Antimicrobial Screen of the Newly Synthesized Compounds
Test Organisms
Gram-positive
Gram-negative
Escherichia coli Salmonella typhi
Bacillus subtillus
Staphylococcus aureus
Samples 1% 2.5%
5%
1%
2.5%
5%
1% 2.5%
5%
1%
2.5%
5%
IVa
V
VIc
+
−
+
−
++
−
++
−
+++
−
+++
−
++
−
++
−
+++
−
+
−
++
−
+++
−
++
−
++
−
++
−
+++ +++
+++
−
++
−
++
−
+++
−
+++ +++
++++
−
VIIIa
XIIa
XIIId
XIV
XVa
XVIIb
XVIId
XX
−
−
−
+
+
+
−
+
+
−
−
−
−
−
−
+
+
+
−
+
+
+
−
−
−
−
−
−
−
−
−
−
−
+
+
+
+
−
+
+
+
+
+
+
+
+
+
+
+
+
+
+
++
+
++
++
−
+++
++
−
++
++
−
++
++
+
+
++
++
−
++
++
+
++
+
++
++
+
+
−
−
+
+
+
++
++
+
++
+
++
++
+
+
++
+
++
+
+
++
++
++
XXIa
XXIb
+
++
−
++
+
+
+
+
+
+
+
St. = Reference standard; chloramphenicol was used as standard antibacterial agent. The test was done using the diffusion agar technique.
Well diameter. 1 cm. . . (100 ꢀL of each concentration was tested). Inhibition values = 0.1–0.5 cm beyond control = +; Inhibition values = 0.6–1
cm beyond control = ++. Inhibition values = 1.1–1.5 cm beyond control = +++; 0 = not detected.
TABLE 3 Antifungal Screen of the Newly Synthesized Compounds
Test Organisms
Aspergillus flavus
2.5%
Aspergillus niger
2.5%
Samples
1%
5%
1%
5%
IVa
V
VIc
−
−
+
−
−
−
−
−
+
+
−
+
−
−
−
+
−
−
−
−
−
−
−
−
−
+
+
−
+
+
+
−
+
−
−
−
−
+
+
+
+
+
+
+
−
+
++
++
−
+
VIIIa
XIIa
XIIId
XIV
XVa
XVIIb
XVIId
XX
+
−
−
−
−
+
−
−
−
−
−
−
+
+
++
++
+
+
++
−
+
+
XXIa
XXIb
+
++
+
+
−
++
St. = Reference standard; grisofluvine was used as a standard antifungal agent. The test was done using the diffusion agar technique. Well
diameter. 1 cm. . . (100 μL of each concentration was tested). Inhibition values = 0.1–0.5 cm beyond control = +; Inhibition values = 0.6–1 cm
beyond control = ++. Inhibition values = 1.1–1.5 cm beyond control = +++; 0 = not detected.
Screening Test
Antitumor activity: (In Vitro Study). Reagent
The compounds tested were IVb, VIb, VIc, XIIIa,
XIIId, XVb, XVIId, XXIa, and XXIb.
1. RPMI 1640 medium (Sigma)
Procedure
2. Ehrlich Ascites Carcinoma cells (EAC) suspen-
sion (2.5 × 105/mL)
1. EAC cells were obtained by needle aspiration of
ascetic fluid from the preinoculated mice under
aseptic conditions [32].
3. Trypan blue dye: A stock solution was prepared
by dissolving 1 g of the dye in (100-mL) distilled wa-
ter. The working solution was then prepared by dilut-
ing 1 mL of the stock solution with g mL of distilled
water. The stain was then used for staining the dead
EAC cells.
2. The cells were tested for viability and contamina-
tion by staining certain cell volume of this fluid by
an equal volume of the working solution of trypan
blue dye [33].
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of Some Novel Imidazolidine Derivatives and Their Metal Complexes 643
TABLE 4 Antitumor Activity of Some of the Synthesized Compounds Using (EAC)
% Inhibition of Cell Viability (μg/mL)
Sample No.
100
50
25
IVb
VIb
VIc
60
100
95
40
90
90
10
80
80
XIIIa
XIIId
XVb
XVIId
XXIa
XXIb
50
90
100
100
50
40
80
90
100
20
20
80
70
100
10
100
80
70
3. The ascetic fluid was diluted to 1:10 with saline to
University, Cairo, Egypt. Found: C, H, N for all com-
pounds were within 0.4 from the theoretical value.
contain 2.5 × 106 cells on a hemocytometer.
4. In a set of sterile test tubes, 0.1 mL of tumor
cells suspension, 0.8 mL of RPMI 1640 media, and
0.1 mL of each tested compound (corresponding
to 0.1, 1.0, 10, 102, 103, 104, 105, and 106 μg) were
mixed. The test tubes were incubated at 37 for 2 h.
Trypan blue [33] exclusion test was carried out to
calculate the percentage of nonviable cells. Com-
pounds producing more than 70% nonviable cells
are considered active [34].
Cyanothioformamides (Ia–f)
Compounds (Ia–e) were previously prepared [1,20],
and the p-bromo derivative (If) was similarly pre-
pared. p-Bromophenylcyanothioformamide If; yel-
low crystals, m.p. 126◦C from (chloroform/n-hexane)
(55% yield), IR: νNH (3200), νCN (2217); H NMR:
6.7 (4H, q, p-substituted), 8.3 (1H, hump, NH, dis-
1
appeared by D2O).
No. of nonviable
% of nonviable cells =
× 100
No. of cells
Imidazolidineimnothiones (IIa–j)
The results of antitumor activity for the synthe-
sized compounds indicated that compounds VIb,
VIc, XIIId, XVb, XVIId, and XXIb showed a signif-
icant activity toward Ehrlich ascites carcinoma tu-
mor cells (in vitro). The compound that exhibited
the highest activity (XVIId) is the one of copper
complexes with the ligand (imidazolidine iminoth-
ione) having two chlorine atoms. Imidazopyrazine
with alkyl group (VIb) also showed higher activity.
Compounds having chlorine atom (VIc), (XIIId and
XVb), or methyl and thiazolyl groups (XXIb) were
found to have more powerful activity than the other
compounds.
Compounds (IIa–g) were previously prepared [16],
and IIh–j were similarly obtained: 1-Phenyl-3-
(4-bromophenyl)-5-imino-4-thioxoimidazolidine-2-
one (IIh). Pale yellow crystals. m.p. 167◦C from
ethanol (45%), IR: absence of νC N and the pres-
ence of νNH (3250), νCO (1700), and νCS·N <
(1490.1150); 1H-NMR, 6.8–7.0 (9H, m, Ar H), 8.4
(1H, s, NH, disappeared by D2O).
1-(4-Chlorophenyl)-3-(4-bromophenyl)-5-imino-4-
thioxoimidazolidine-2-one (IIi). Pale yellow crystals,
m.p. 196◦C from ethanol (45%), 1H NMR: 6.9–
7.1(8H, q, Ar H), 8.5 (1H, s, NH, disappeared by
D2O).
1-(4-Chlorophenyl)-3-(3-chlorophenyl)-5-imino-4-
thioxoimidazolidine-2-one (IIj). Pale yellow crystals,
m.p. 141◦C from ethanol (40%); IR: no νCN and
νNH (3300), νCO (1710); MS, M+ at m/z 349(100%;
base peak).
EXPERIMENTAL
All melting points are uncorrected and determined
on digital Gallen Kamp MFB-595 instrument. IR
spectra (KBr) (cm−1) were measured on a Shimadzu
440 spectrometer. 1H NMR spectra (delta, ppm) were
obtained in dimethyl sulfoxide on a Varian Gemini
200 (200 MHz) spectrometer, using TMS as an inter-
nal standard; chemical shifts are reported as δ units.
Mass spectra (m/z, %) were obtained on GC MS-QP
100 Ex mass spectrometer at 70 eV. Elemental anal-
yses were carried out at Micro Analytical Unit, Cairo
General Procedure for the Reactions Between
Imidazolidineiminothiones (II) and the
Diamino Compounds
A mixture of II (0.005 mole) and the requisite di-
amine (0.006 mole) in ethanol (25 mL) was refluxed
Heteroatom Chemistry DOI 10.1002/hc

644 Al-Raqa et al.
for 5 h (till H2S ceased), and the reaction mixture
was then cooled and decomposed on to cold dil HCl.
1. Ethylenediamine and IIe gave a solid, which
recrystallized from ethanol to give IVa m.p. 235◦C
(3H, s, OCH3), 6.9 (10H, m, Ar H), MS: 560 (100,
M+, base peak, C22H13O2ClBr2), 559 (26.4, M − 1),
561 (33.1, M + 1), 562 (52.3, M + 2), 563 (15.9,
M + 3), 564 (2.8, M + 4). Concentration of the alco-
hol mother liquid of experiment (4-i) furnished IX,
1
(25%), IR: νNH (3300), νCO (1680); H NMR: 1.1
1
(3H, t, CH3), 4.1(2H, q, CH2), 7.2–7.4 (10H, m, Ar H),
8.1 (2H, s, 2NH, disappeared by D2O). Ethylenedi-
amine and IIg furnished a product that recrystallized
from ethanol: water (1:1) to give IVb, m.p. 295◦C
(15%), IR: νNH (3320), νCO (1690): 1H NMR: 7.3–7.5
(10H, q, 2 p-substituted + CH = CH underneath the
quartet), MS: 359 (0.4) M + 1, (C17H12N4OCl2), 358
(3.4) M−1, 127 (100; base peak) p-Cl·C6H4·NH2, 129
(33), (127:129 – 3:1 due to chlorine atoms).
m.p. 270◦C from ethanol (15%). H NMR, 3.85 (6H,
s, 2 × OCH3), 6.9–7.3 (16H, 2q, Ar H), MS (%): 624
(1.3, M+, C32H22N6O4Cl2), 625 (0.9, M + 1), 626 (2.3,
M + 2), 627 (1.8, M + 3), and 457 (100, base peak).
ii. 3,4-Diaminotoluene and IIf gave a product
that recrystallized from ethanol to give VIIIb, m.p.
1
215◦C (30%). H NMR: 2.1 (3H, s, CH3), 6.5 – 6.9
(12H, m, Ar H); MS: M+, 386 (7.0), (C22H15N4OCl)
and 153 (100. base peak, p-ClC6H4·NCO).
2. 1,4-Diaminobutane and IIg gave a solid that
crystallized from ethanol:water (1:1) to give V, m.p.
iii. 3,4-Diaminobenzoic acid and IIg yield a solid
that recrystallized from ethanol to give VIIIc, m.p.
225◦C, (25%). IR: no νNH, NH2, νOH (COOH) broad-
band (3100–2500), νCO (1690, 1650) and νC N
(1630) 1H NMR: 9.3 (1H, s, OH, disappeared by D2O),
6.7–6.9 (11 H, m, Ar H).
1
280◦C (17%), IR: NH (3300), CO (1700); H NMR:
3.55–5.35 (6H, m, 2 × CH2 + CH CH ), 7.3–7.5
(8H, q, Ar H), 8.9 (2H, broad singlet, 2NH, disap-
peared by D2O), MS: 351 (3.3) M Cl, (C19H16N4OCl2)
353 (0.9), 354 (1.3), 153 (6.5) p-Cl·C6H4·NCO, 127
(100, base peak) p-Cl·C6H4·NH2, 129 (30) (127:129 –
3:1 due to chlorine atoms).
5. 1,2-Diaminoanthraquinone and IIa precipi-
tated a solid during reflux, which collected and re-
crystallized from ethanol to give Xa, m.p. 220◦C
(45%). IR, absence of νNH, NH2 and the presence of
νCO (1720, 1680), νC N (1630); 1H NMR, 2.3 (3H, s,
CH3), 6.7–7.1 (15H, m, Ar H).
3. Diaminomaleinonitrile and IIa gave a solid
that recrystallized from ether/n-hexane to give VIb,
m.p. 280◦C decomp. (20%), IR showed the absence
of νC N and the presence of νNH2 and NH (3300–
1,2-Diaminoanthraquinone and IId precipitated
a product during reflex, which was filtered off
and recrystallized from ethanol to give Xb m.p.
250◦C (55%). 1H NMR: 3.9 (3H, s, OCH3), 6.7–
7.2 (14H, m, Ar H), MS: (C30H17N4O4Cl) at m/z
421 (1.2, M − p-Cl·C6H4), 238 (100, base peak, 1.2-
diaminoanthraqunone), 153 (3.5, p-Cl·C6H4·NCO)
and 149 (0.3, p-CH3O·C6H4·NCO).
1
3100), νCO (1710), H NMR: 2.1 (3H, s, CH3), 6.7–
6.9 (9H, m, Ar H), 8.3 (3H, hump, NH & NH2),
8.9 (2H, s, CO N H2), both NH, NH2, and CONH2
were disappeared by D2O. MS: 369 (3) M − H2O,
(C20H17N7O2) 370 (0.3), 368 (8.7), 367 (1.3), 133 (8.5)
p-CH3·C6H4·NCO, 119 (4.9) C6H5NCO and 127 (100)
p-Cl·C6H4·NH2. Diaminomaleinonitrile and IIg pre-
cipitated a product during reflux, which filtered off
and recrystallized from ethanol to give VIc, m.p.
280◦C decomp. (25%). IR: (no νC N) and 3350–3150
1,2-Diaminoanthraquinone and IIe furnished a
product that recrystallized from ethanol to give Xc,
m.p. 260◦C (60%). IR: νCO (1730, 1685), νC N
1
1
(νNH, νNH2) 1710 (νCO); H NMR: 6.9–7.1 (8H, q,
(1630); H NMR: 1.2 (3H, t, CH3), 4.1 (2H, q, CH2),
Ar H), 8.7 (3H, hump. NH, NH2), 9.3 (2H, s, CO
NH2), both NH, NH2, and CONH2 disappeared by
D2O·MS: (C19H13N7O2Cl2), 396 (24.1) M − HCONH2,
396 (77.6), 153 (72.1) p-Cl·C6H4·NCO, 127 (50) p-
Cl·C6H4·NH2 and 64 (100). Concentration of the al-
cohol mother liquid furnished a product that recrys-
tallized from ether/n-hexane to give VII, m.p. 140◦C
(20%). IR: νC N (2225), νNH (3330), 1H NMR, 7.1–
7.3 (8H, q, Ar H), 8.7, 9.1 (3H, 2H, 2s, NH, NH2
and CONH2, disappeared by D2O), MS: 442 (2.5,
M + 1), (C19H13N7O2Cl2), 443 (4.7, M + 2), 444 (6.1,
M + 3), 153 (18.7, p-Cl·C6H4·NCO) and 127 (100%,
p-Cl·C6H4·NH2).
and 6.6–7.2 (14H, m, Ar H).
6. 5,6-Diamino-1.10-phenanthroline and IIf pre-
cipitated a product, which was collected and re-
crystallized from ethanol to give XI, m.p. 245◦C
1
(35%). H NMR revealed the aromatic protons as
multiplet at δ = 7.1–7.4 ppm. MS: 474 (2.47, M+,
C27H15N6OCl), 475 (1.19, M + 1), 476 (1.25, M + 2),
477 (0.71, M + 3), 478 (0.61, M + 4), 153 (100%, base
peak, p-Cl·C6H4·NCO), and 119 (18.41, C6H5·NCO).
7. 1,8-Diaminonaphthoquinone and IIa precip-
itated a product during reflux, which was collected
and recrystallized from dioxane to give XIIa m.p.
>300◦C, (25%) IR: showed no νNH or NH2 and νCO
(1690), νC N (1620), 1H NMR: 2.5 (3H, s, CH3), 6.7–
7.2 (15H, m, Ar H). MS: 402 (100, M+, base peak,
C26H18N4O), 403 (31.9, M + 1), 404 (4.32, M + 2), 405
(0.6, M + 3). Similarly, XIIb, m.p. > 300◦C from
4. i. 1,2-Diamino-4,5-dibrombenzene and IId fur-
nished a solid that recrystallized from ethanol to
give VIIIa, m.p. 225◦C (35%). IR: (no νNH, NH2,
1
or CS), νCO(1690) and νC N(1630); H NMR: 4.1
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of Some Novel Imidazolidine Derivatives and Their Metal Complexes 645
Cl·C6H4·NCO), 153 (8%, p-Cl·C6H4·NCO), and 127
dioxane (30%), 1H NMR: 2.6 (3H, s, CH3), 6.9–
7.3 (14H, m, Ar H); MS: 436 (100, M+, base peak,
C26H17N4OCl), 437 (33.95, M + 1), 438 (39.8, M + 2),
439 (10, M + 3), 440 (1.6, M + 4). XIIc, m.p. > 300◦C
(100%, base peak, p-Cl·C6H4·NH2).
Imidazo[4,5- e]triazine-2-one (XVIa,b)
1
from dioxane, (33%), H NMR: 1.2 (3H, t, CH3), 4.1
1. A mixture of thiocarbohydrazide (0.005 mole)
and IIg (0.005 mole) in absolute ethanol (25 mL)
was refluxed for 5 h (H2S must be ceased). The
product that precipitated was filtered off, washed
with ethanol, and recrystallized from ethanol to give
XVIa, m.p. 250◦C (45%). IR: NH2(3430, 3350), NH
(3200), CO (1690), and C N (1630); MS: 388 (5.4,
M + 1, C16H11N7OCl2), 389 (19.1, M + 2), 390 (16.2,
M + 3), 391 (13.6, M + 4), 392 (10.8, M + 5), and 153
(100, base peak, p-Cl·C6H4·NCO).
(2H, q, CH2), 6.9–7.3 (14H, m, Ar H). MS: 466(9.4,
M+, C27H19N4O2Cl), 127 (100). XIId, m.p. > 300◦C
from dioxane, (25%), MS: 422 (100, M+, base peak,
C25H15N4OCl), 423 (29.9, M + 1), 424 (38.0, M + 2),
425 (10.4, M + 3), 426 (1.3, M + 4), and 427 (0.4,
M + 5).
Concentration of the alcohol mother liquid of
these experiments then treated with cold dil HCl
(if necessary) furnished, XIIIa, m.p. >300◦C from
ethanol (20%), IR: νNH and NH2 (broadband 3360–
3280), νCO (1680) and νC N (1620); MS: 455(0.93,
M + HCl, C26H21N5O·HCl), 418(1.7, M − 1), and 334
(100, base peak). XIIIb, m.p. > 300◦C from ethanol
2. In a similar fashion, thiocarbohydrazide and
1
IIi gave XVIb, m.p. 195◦C from ethanol (40%), H
NMR: 7.1–7.3 (8H, m, Ar H) and 8.3 (3H, hump, NH
and NH2, disappeared by D2O).
1
(25%), H NMR: 2.3(3H, s, CH3), 7.0–7.2 (14H, m,
Ar H), 8.3–8.4 (3H, broad singlet, NH and NH2, dis-
appeared by D2O), MS: 453 (1.1, M+, C26H20N5OCl),
452 (2.85, M − 1), 454 (0.74, M + 1), 455(0.39,
M + 2), 127 (100, base peak). XIIIc, m.p. >300◦C
Preparation of Metal Complexes XVII
Ethanolic solutions of metal chloride and the ligand
were mixed in a molar ratio 2:1 (L:M) and refluxed
for 2–3 h. The resulting precipitates were filtered,
washed with ethanol and then with ether, and finally
air-dried. The complexes are stable in solid state, and
soluble in acetone, ethanol, and dimethylformamide.
1,3-Bis(4-chlorophenyl)-4-imino-5-(4-nitrosome-
thyl benzylimino)imidazolidine-2-one XIX. A mixture
of α,α-diamino p-xylene (0.005 mole) and IIg (0.01
mole) was dissolved in absolute ethanol (25 mL) and
refluxed for 5 h (H2S must be ceased). The product
that precipitated was filtered off and recrystallized
from ethanol to give XIX, m.p. 265◦C (35%). IR:
NH (3250), CO (1690), and C N (1630), MS (%):
483 (2.4, M + H2O), 466 (100, base peak, M + 1,
C23H17N5O2Cl2), 467 (29.19, M + 2), 468 (98.69,
M + 3), 469 (27.41, M + 4), 470 (3.75, M + 5), and
153 (3.72, p-Cl·C6H4·NCO).
1
from ethanol (20%), H NMR: 2.2 (3H, t, CH3), 4.2
(2H, q, CH2), 7.1–7.3 (14H, m, Ar H), 7.3–7.4 (3H,
brood s, NH and NH2, disappeared by D2O). MS:
483 (1.15, M+, C27H22N5O2Cl), 127 (100). XIIId, m.p.
>300◦C from ethanol (25%); MS: 457 (1.43, M + H2O,
C25H18N5OCl·H2O), 439 (0.29, M+) 438 (0.89, M − 1),
440 (0.32, M + 1), 166 (100).
Interaction of Imidazolidineiminothions ( IIg )
with Active Methylene Compounds
1. Pyrollo [2.3-d] imidazole derivative (XIV). To a
solution of IIg (0.005 mole) and ethylphenyl acetate
(0.005 mole) in absolute ethanol (30 mL), sodium
ethoxide (0.005 mole) was added and the mixture
was refluxed for 7 h. Decomposition of the reac-
tion mixture with cold dil HCl furnished a prod-
uct that crystallized from ethanol to give XIV, m.p.
230◦C (25%), IR: no ν(NH, CS.N), νCO (1690), νC N
(1635) and νC C (1600); 1H NMR exhibited the aro-
matic protons at δ = 7.2–7.4 ppm. MS: 433(0.3, M+
C23H13N3O2Cl2), 434 (0.2, M + 1) 432 (0.7, M − 1),
153 (8, p-Cl·C6H4·NCO), and 127 (100).
4-(Phenylsulphonyl)hydrazono-1,3-bis(4-chloro-
phenyl)-5-iminoimidazolidine-2-one XX. A mixture
of benzenesulphonyl hydrazide (0.005 mole) and
IIg (0.005 mole) was reacted as above to give XX,
m.p. 240◦C from benzene (40%). IR: NH (3250), CO
1
(1695), and SO2 N (1450, 1170), H NMR: 6.1–7.4
2. Acetylacetone and IIg gave XVa, m.p. 81◦C,
(13H, m, Ar H), 8.5 and 8.9 (2H, 2 humps, 2 NH,
disappeared by D2O), MS (%): (C21H15N5O3SCl2);
334 (2.16, M − p-Cl·C6H4·NCO), 153 (42.76, p-
Cl·C6H4·NCO), 157 (7.52, C6H5SO2NH2), and 77
(100, base peak, C6H5 ).
Interaction of imidazolidineiminothiones II with
sulpha derivatives to give XXla–d. A solution of
IIa (0.005 mole) and sulphadiazine (0.005 mole)
in absolute ethanol (30 mL) was refluxed for 5 h.
1
from ethanol (30%), H NMR: 2.4 (3H, s, CH3-Ar),
2.7 (3H, s, CH3 CO), 7.1–7.3 (8H, m, Ar H), and 8.7
(1H, broad s, NH, disappeared by D2O); MS: 416 (3.2,
M + 1, C20H15N3O3Cl2), 417 (5.4, M + 2), 418 (42.7,
M + 3), 419 (29.3, M + 4), and 127 (100, base peak,
p-Cl·C6H4·NH2).
3. Ethylcyano acetate and IIg gave XVb, m.p.
130◦C from ethanol (25%), MS: 275 (36%, M − p-
Heteroatom Chemistry DOI 10.1002/hc

646 Al-Raqa et al.
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The product that precipitated was filtered off and
recrystallized from ethanol to give XXIa, m.p.
245◦C (55%). IR: NH (3300–3250), CO (1690),
C N (1630); 1H NMR: 2.2 (3H, s, CH3), 6.9–7.1
(16H, m, Ar H), 8.3 (1H, s, NH), and 9.1 (1H,
s, SO2NH), both NH were disappeared by D2O.
MS: (C26H21N7O3S); 263 (0.3, M-sulphadiazine); 265
(2.04), 250 (5.31, sulphadiazine), 251 (3.98), 149
(100), 133 (34.56, p-CH3·C6H4·NCO), and 119 (10.9;
C6H5NCO).
Sulphathiazole and IIa were similarly reacted to
1
produce XXIb, m.p. 220◦C, from ethanol (35%). H
NMR: 2.2 (3H, s, CH3), 6.8–7.1 (15H, m, Ar H), 8.3
(1H, s, NH), and 9.1 (1H, s, SO2 NH), the last two sig-
nals were disappeared by D2O. MS: (C25H20N6O3S2);
438 (0.23, M − C6H6); 263 (1.0, M-sulphathiazole),
255 (19.96, sulphathiazole), 191 (100), 133 (1.22,
p-CH3·C6H4·NCO), and 119 (3.63, C6H5·NCO). Also,
sulphacetamide and IIa gave XXIc; m.p. 110◦C, from
ethanol, (40%). MS: (C24H21N5SO4); 295 (100, base
peak), 296 (25.9), 297 (8.5), 298 (6.6), 133 (6.4), and
119 (6).
In a similar manner, sulphadiazine and IIg gave
XXId, m.p. 210◦C from ethanol, (35%). 1H NMR: 7.0–
7.3 (15H, m, Ar H), 8.4, 9.1 (2H, 2 broad signal. NH,
SO2 NH, disappeared by D2O); MS: 454 (0.2, M −
Cl·C6H4), 153 (16.7, p-Cl·C6H4·NCO), and 127 (100,
base peak, p-Cl·C6H4 – NH2).
4-Thioxoimidazlidine-2,5-diones XXIIa,b. A so-
lution of IIh (0.005 mole) in boiling ethanol (25 mL)
was treated with dil HCl (1:1) drop by drop. The ob-
tained product was collected, washed with water, and
recrystallized from ethanol to give XXIIa, m.p. 140◦C
(45%), IR spectrum revealed the absence of νNH.
Similarly IIj gave XXIIb, m.p. 108◦C, from ethanol
(40%); IR: no νNH.
Bis-imidazolidine-2,5-diones XXIIIa,b. To a so-
lution of XXIIa (0.005 mole) in p-xylene (20 mL),
copper turnings (0.5 gm; excess) were added. The re-
action mixture was refluxed for 3 h. Filteration of xy-
lene (to separate Cu S) gave a product which recrys-
tallized from dioxane to give XXIIIa; m.p. >300◦C
(30%). XXIIb similarly gave XXIIIb, m.p. >300◦C,
1
from dioxane (35%). H NMR of XXIIIb exhibited
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Afinidad 2004, 511, 240.
[25] El-Sharief, A. M. Sh.; Mahmoud, F. F.; Taha, N. M.
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[26] El-Sharief, A. M. Sh.; El-Gaby, M. S. A.; Atalla, A.
A.; El-Adasy, A. A. A. Heteroatom Chem 2005, 16(3),
218.
[27] Graziak, M. P.; Ding, H. Acta Chim Slov 2000, 47, 1.
[28] El-Gaby, M. S. A.; Micky, J. A.; Taha, N. M.; El-
Sharief, M. A. M. Sh.; Acta Chim Slov 2002, 49,
159.
the aromatic protons at δ = 7.0–7.3 ppm; MS of
XXIIIa: 656 (24.8; M+), 657 (8.4, M + 1), 658 (47.17,
M + 2), 659 (15.8, M + 3), 660 (30.0, M + 4), 197
(18.48, p-Br·C6H4·NCO), 181 (100, base peak, p-
Br·C6H4NC), and 119 (33.46, C6H5·NCO).
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