One-pot synthesis and characterization of some new types of 5,5′-disubstituted bis(imidazolidine-2,4-diones)

Article abstract of DOI:10.1002/jhet.1034

The synthesis and structural elucidation of some novel 5,5′- disubstituted spiro and nonspiro-bis-hydantoins are reported. The Bucherer Burge's method has been modified for the preparation of some 5,5′-substituted bis(imidazolidine-2,4-dione) derivatives starting with diketones (1-5) and dialdehydes (6, 7). In some cases, diastereoisomeric mixtures of compounds were obtained. The resulting bis-hydantoins (8-11, 13, 14) have not to our knowledge been previously reported in the literature.

Full text of DOI:10.1002/jhet.1034

288
One‐Pot Synthesis and Characterization of Some New Types of
5,5′‐Disubstituted Bis(imidazolidine‐2,4‐diones)
Vol 50
*
Ziba Khodaee, Asieh Yahyazadeh, and Nosrat O. Mahmoodi
Department of Organic Chemistry, University of Guilan, P. O. Box 1914 Rasht, Iran
*
E-mail: mahmoodi@guilan.ac.ir
Dedicated to Professor John L Belletire on the occasion of his birthday
Received March 15, 2011
DOI 10.1002/jhet.1034
Published online 7 March 2013 in Wiley Online Library (wileyonlinelibrary.com).
O
O
NH
HN
one-pot
R
O
R
R
R
O
O
NH
HN
bis- hydantoin
dialdehyde or diketone
O
The synthesis and structural elucidation of some novel 5,5′‐disubstituted spiro and nonspiro‐bis‐
hydantoins are reported. The Bucherer Burge’s method has been modified for the preparation of some
5,5′‐substituted bis(imidazolidine‐2,4‐dione) derivatives starting with diketones (1–5) and dialdehydes
(6, 7). In some cases, diastereoisomeric mixtures of compounds were obtained. The resulting bis‐hydantoins
(8–11, 13, 14) have not to our knowledge been previously reported in the literature.
J. Heterocyclic Chem., 50, 288 (2013).
INTRODUCTION
[12, 13]. Structures of all synthesized compounds in this
study were elucidated by the use of TLC, melting point,
Drug discovery continues to be an important area of
investigation for synthetic chemist. The bis‐hydantoin
compounds, as potential bis‐drugs, are expected to be
capable of double therapeutic behavior. Some pharmaco-
logical and therapeutic properties of bis‐hydantoins have
been reported [1–9]. For example, recently there has
been a growing concern about how to reduce or elimi-
nate infections completely, especially those caused by
antibiotic‐resistant bacterial strains. Some N‐halomine
derivatives of bis‐hydantoins possessing excellent bioci-
dal activity against a wide range of microorganisms
including fungi, bacteria, viruses, and yeasts have been
designed [4]. Other application of bis‐hydantoin deriva-
tives include their use as flame retardants for a variety
of polymeric systems, as intermediates for further transfor-
mations [10, 11] and as precursors to diaminodicarboxylic
acid derivatives [15]. Some bis‐imidazolidineiminothiones
exhibit cytotoxic activity against various tumor cell lines
as well as antiviral, antimicrobial, and antifungal properties
[2]. Also the 1,3,10,13‐tetraza‐dispiro[4.2.4.2] tetradecane‐
2,4,10,12‐tetraone 12 (a bis‐hydantoin) has been found to
function as a bis‐intercalator in recognizing specific DNA
sequences [7].
1
IR, and H‐NMR. Bis‐hydantoins were also analyzed by
13C‐NMR and mass spectromertry.
RESULTS AND DISCUSSION
A numbers of new and older synthetic methods have
been reported for the preparation of mono‐hydantoins
[1, 12–14, 16–19]. One such general method is the
Bucherer–Bergs synthesis of 5,5‐disubstituted hydantoins
from either aldehydes or ketones through the action
of potassium cyanide and ammonium carbonate. Our
work the Bucherer–Bergs procedure was modified to per-
mit its use for the one‐pot synthesis of some novel 5,5′‐
disubstituted bis(imidazolidine‐2,4‐dione) derivatives, as
depicted Schemes 1 and 2.
Diketones 1−5 and dialdehydes 6, 7 (Fig. 1) upon
reaction with (NH4)2CO3 and KCN in a mixture of 50%
(v/v) EtOH/H2O solvent, led to the formation of several
new bis(imidazolidine‐2,4‐diones) (Fig. 2 and Table 1).
As we reported in our previous work [13], α‐diketones
when subjected to similar reaction conditions fragmented
to mono‐hydantoins. Therefore, to overcome this challenge
to prepare bis‐analogues, we replaced α‐diketones with
several different diketones containing alkyl, o‐alkyl,
indole‐alkyl and aryl linkages. The IR, 1H‐NMR, and
13C‐NMR spectral data of the products confirmed the
structures of the proposed bis‐hydantoins. Spectral data
for bis-hydantoin products showed typical symmetry
Since a wide range of bis‐heterocyclic compounds
have been reported to exhibit superior antibacterial
activities when compared to their mono‐heterocyclic
counterparts [2], in this study we decided to prepare some
novel bis‐hydantoins via one‐pot experimental pro-
tocol, developed from that used in our previous works
© 2013 HeteroCorporation

March 2013
One‐Pot Synthesis and Characterization of Some New Types of 5,5′‐Disubstituted Bis
289
(imidazolidine-2,4-diones)
Scheme 1. Synthesis of bis‐hydantoins.
O
H
NH
N
HN
O
O
O
O
NH
R
KCN, (NH4)2CO3, EtOH
R
R
O
R
HN
H2O, 50-70°C, 2-72hr, reflux
NH
,
HN
O
O
O
N
H
O
1-7
12
8-11,13,14
1
dissolved in deuterated DMSO as NMR solvent. IR data were
obtained with a Shimadzu 470 spectrometer. Melting points of
crystalline compounds were measured with an electrothermal
melting point apparatus and have not been corrected. Mass
spectra were obtained using a GC‐MS Agilent Technologies QP‐
5973N MSD instrument. Purification of crystalline compounds
was performed by recrystallization and in some cases by
of structure in most cases. For example, the H‐NMR
spectrum of 13 was consistent with a perfecty symmetrical
structure (e.g. the spectrum contained four signals
corresponding to 10 protons). However, in the remaining
cases additional peaks in the spectra may be due to a subtle
conformational phenomenon. For example, the spectrum
of compound 12 exhibited the presence of a conformer.
The NMR spectra of the bis‐hydantoins 8–11, with two
asymmetric carbon atoms in their structures, showed a
mixture of the dl and meso isomers (approximate ratio
85:15).
preparative thin‐layer chromatography with silica gel 60 GF254
.
All chemicals were purchased from Aldrich Chemical Company,
Merck or Fluka.
Typical reaction procedures and spectroscopic data for bis‐
hidantoins and their precursor are described below.
Typical experimental procedure for synthesis of diketones
1, 2. 1‐(4‐hydroxyphenyl)ethanone (4‐hydroxyacetophenone)
(5.12 g, 37.6 mmol) was dissolved in ethanol (50 mL) and KOH
(3.2 g, 80 mmol) was added. The mixture was equipped with
a reflux condenser and refluxed at 50−60°C for 15 min. Then
1,4‐dibromobutane (2.12 mL, 18 mmol) or 1,6‐dibromohexane
(2.73 mL, 18 mmol) was added to the reaction mixture
(for preparing 1 and 2, respectively) and the mixture refluxed
for 18 h. The reaction was cooled to room temperature and
resulting precipitate was filtered and recrystallized from ethanol.
1,1′‐((Butane‐1,4‐diylbis(oxy))bis(4,1‐phenylene))
CONCLUSION
By modification of the Bucherer–Bergs reaction, sev-
eral novel bis‐hydantoins were successfully designed
and synthesized in one‐pot fashion. Diastereoisomeric
mixtures of products were obtained in some cases. The
bis‐hydantoins (8–11, 13, 14) prepared have not been
previously described.
diethanone (1). White powder crystals. m.p. (recrystallized
from ethanol) 140°C. yield 50%, 2.96 g. 1H NMR (500
MHz, DMSO‐d6): δ = 1.90 (p, 2 H, 2 × CHaHb), 2.49 (s, 3
H, 2 × CH3), 2.50 (DMSO), 3.31 (H2O), 4.13 (t, 2 H, 2 ×
CHaHbO), 7.03 (d, J = 8.81 Hz, 2 H, 4 × CH, Ar), 7.91 (d,
J = 8.81 Hz, 2 H, 4 × CH, Ar) ppm. IR (KBr,): vmax = 1250
EXPERIMENTAL
General remarks. High‐resolution 1H‐NMR (500 MHz)
and 13C‐NMR (125 MHz) spectra were obtained with a Bruker
500 DRX‐Avance NMR spectrometer. Compounds were
Scheme 2. Schematic reaction mechanism.
CN
O
HO
CN
R
H2N
R
R
NH3
2 KCN
R
2 O
C
O
R
R
O
OH
NC
NC
NH2
O
-
O
O
O
HN
NH
O
HN
HN
C
N
C
R
O
R
NH
H2O
R
R
R
R
N
C
O
HN
NH
C
O
-
O
NH
NH
HN
O
O
O
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

290
Z. Khodaee, A. Yahyazadeh, and N. O. Mahmoodi
Vol 50
O
O
Table 1
Reaction time and yields of produced bis‐hydantoins.
O
O
O
O
Bis‐hydantoin
1
2
O
O
Entry
product
Time (h)
Yield (%)
M.P. (°C)
1
2
3
4
5
6
7
8
9
24
72
48
72
3
40
35
77
41
63
86
20
200dec.
220dec.
180dec.
136
>290dec.
295dec.
120
O
O
10
11
12
13
14
O
O
4
3
24
72
H
H
O
O
O
H
H
O
H
N
N
H
O
through the dropping funnel at an even rate during 15 min and then
the mixture refluxed under 50–65°C for 2 h. The solution was
poured slowly, with constant stirring, into a mixture of cracked
ice. The residual liquid was filtered using a Buchner funnel and
the solid washed with cool diethylether (20 mL) and
recrystallized from ethanol. Toluene (6 mL) instead of benzene
was used for the synthesis of 4.
O
5
6
7
Figure 1. Structure of diketones (1–5) and dialdehydes (6,7).
(C―O), 1600 (C═C), 1675 (C═O), 2850–2950 (Ali H), 3050
(Ar H) cm−1
1,6‐Diphenylhexane‐1,6‐dione (3). White powder crystals.
1
.
m.p. (recrystallized from ethanol) 106°C. yield 50%, 0.66 g. H
1,1′‐((Hexane‐1,6‐diylbis(oxy))bis(4,1‐phenylene))diethanone
(2). White powder crystals. m.p. (recrystallized from ethanol)
141°C. yield 99%, 6.36 g. 1H NMR (500 MHz, DMSO‐d6):
δ = 1.47 (P, J = 6.94 Hz, 2 H, 2 × CHaHb), 1.74 (p, J = 6.38, 6.35
Hz, 2 H, 2 × CHaHb), 2.49 (DMSO), 2.50 (s, 3 H, 2 × CH3), 3.32
(H2O), 4.05 (t, J = 6.46 Hz, 2 H, 2 × CHaHbO), 7.00 (d, J = 8.85
Hz, 2 H, 4 × CH, Ar), 7.90 (d, J = 8.84 Hz, 2 H, 4 × CH, Ar)
ppm. IR (KBr): vmax = 1250 (C―O), 1600 (C═C), 1667 (C═O),
2850–2930 (Ali H), 3050 (Ar H) cm−1.
NMR (500 MHz, DMSO‐d6): δ = 1.68 (P, J = 3.53, 2.87, 3.82
Hz, 2 H, 2 × CHaHb), 2.49 (DMSO), 3.07 (t, J = 6.5 Hz, 2 H,
2 × CHaHbCO), 3.32 (H2O), 7.51 (t, J = 7.75 Hz, 2 H, 4 × CH,
Ar), 7.62 (t, J = 7.39 Hz, 1 H, 2 × CH, Ar), 7.97 (dd, J = 8.15,
1.2 Hz, 2 H, 4 × CH, Ar) ppm. IR (KBr): vmax = 1590 (C═C),
1680 (C═O), 2860‐2930 (Ali H), 3050 (Ar H) cm‐1.
1,6‐Di‐p‐tolylhexane‐1,6‐dione (4). White powder crystals.
m.p. (recrystallized from ethanol) 132°C. yield 60%, 0.88 g.
1H‐NMR (500 MHz, DMSO‐d6): δ = 1.66 (P, J = 2.79, 2.60,
3.73 Hz, 2 H, 2 × CHaHb), 2.36 (s, 3 H, 2 ×CH3), 2.49
(DMSO), 3.02 (t, 2 H, 2 × CHaHbCO), 3.31 (H2O), 7.31 (d,
J = 7.95 Hz, 2 H, 4 × CH, Ar), 7.86 (d, J = 8.07 Hz, 2 H,
4 × CH, Ar) ppm. IR (KBr): vmax = 1600 (C═C), 1670
(C═O), 2850–2930 (Ali H), 3050 (Ar H) cm–1.
Typical experimental procedure for synthesis of diketones
3, 4. A mixture of anhydrous Aluminum chloride (1.67 g,
12.5 mmol) and benzene (used in excess as reactant and
solvent, 6 mL) was placed in a three‐necked flask equipped with
a stirrer, a reflux condenser, and a dropping funnel. With rapid
stirring, adipoyl chloride (0.73 mL, 5 mmol) was added
Experimental procedure for synthesis of dialdehyde 7.
This compound was prepared in our laboratory according to the
literature procedure [20].
Typical experimental procedure for synthesis of bis‐
hydantoins 8–14. CAUTION: HCN may be liberated; wear
gloves and work in hood. Dialdehyde or diketone (1–7)
(8 mmol) was dissolved in 50 mL of a 1:1 (v/v) mixture of
ethanol and water in a 100‐mL round‐bottom flask equipped
with a stirrer and reflux condenser, and potassium cyanide (2.16
g, 33 mmol) and ammonium carbonate (6.38 g, 66 mmol) were
added . The mixture was allowed to reflux at 50–70°C with
constant stirring for 2−72 h. The solution was allowed to cool
to room temperature, acidified to pH = 2 by drop‐wise addition
of concentrated HCl with constant stirring and the resulting
precipitate after isolation by filtration was recrystallized from
ethanol. All products were solids.
O
NH
O
NH
HN
O
HN
O
O
O
O
O
O
NH
O
O
NH
O
HN
8
HN
9
O
O
HN
HN
NH
NH
O
O
O
HN
O
O
HN
O
NH
NH
10
11
5,5′‐((butane‐1,4‐diylbis(oxy))bis(4,1‐phenylene))bis(5‐
methylimidazolidine‐2,4‐dione) (8). White powder crystals.
m.p. (recrystallized from ethanol) 200°Cdec.. yield 40%, 1.5 g. H
NMR (500 MHz, DMSO‐d6): δ = 1.60 (s, 3 H, 2 ×CH3), 1.87
(p, J = 3.18, 3.01 Hz, 2 H, 2 × CHaHb), 2.49 (DMSO), 3.31
(H2O), 4.03 (t, J = 5.89 Hz, 1 H, 2 × CHaO), 4.12 (t, J = 5.8,
3.7 Hz, 1 H, 2 × CHbO), 6.94 (d, J = 8.87 Hz, 1 H, 2 × CH, Ar),
7.03 (d, J = 6.89 Hz, 1 H, 2 × CH, Ar), 7.35 (d, J = 8.83 Hz, 1 H,
O
H
O
O
NH
O
NH
HN
NH
NH
H
H
O
1
O
HN
H
N
H
N
O
N
H
H
H
O
H
O
O
O
N
N
HN
HN
O
NH
14
12
13
Figure 2. Structure of synthesized bis‐hydantoin derivatives.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2013
One‐Pot Synthesis and Characterization of Some New Types of 5,5′‐Disubstituted Bis
291
(imidazolidine-2,4-diones)
2 × CH, Ar), 7.91 (d, J = 8.83 Hz, 1 H, 2 × CH, Ar), 8.50 (w s, N1H
meso), 8.52 (s, 0.5 H, 2 × N1H dl), 10.67 (br s, 2 × N3H) ppm. 13
(4 × CH, Ar), 128.87 (4 × CH, Ar), 129.82 (2 × CH, Ar), 130.09
C
(2 × C, Ar), 135.11 (2 × C═O, urea), 157.38 (2 × C═O) ppm. IR
(KBr): vmax = 1600 (C═C), 1700(asym C═O), 1715 (sym C═O),
2850‐2950 (Ali H), 3050 (Ar H), 3150 (w N3H), 3250 (N1H)
cm−1. Exact mass: (M+): calcd. for C24H26N4O4, 434.1954; found
434.1957.
Spirobis‐hydantoin (12). Cream powder crystals. m.p.
(recrystallized from ethanol) >290°Cdec.. yield 63%, 1.26 g.
1H NMR (500 MHz, DMSO‐d6): δ = 1.59 (d, J = 9.02 Hz, 2 H,
4 × CHa), 1.63–1.67 (m, CHa minor stereoisomer), 1.95 (d,
J = 9.34 Hz, 2 H, 4 × CHb), 2.05‐2.09 (m, CHb minor
stereoisomer), 2.49 (DMSO), 3.33 (H2O), 8.17 (w s, 2 × N1H
minor stereoisomer), 8.48 (s, 1 H, 2 × N1H), 10.56 (br s, 1 H,
2 × N3H) ppm. 13C NMR (125 MHz, DMSO‐d6): δ = 27.81
(4 × CH2), 40.36 (DMSO), 60.15 (2 × C5, ring), 155.23
NMR (125 MHz, DMSO‐d6): δ = 21.99 (2 × CH3), 24.24 (2 ×
CH2), 40.23 (DMSO), 65.52 (2 × CH2O), 75.30 (2 × C5, ring),
120.12 (4 × CH, Ar), 129.19 (4 × CH, Ar), 136.33 (2 × C, Ar),
155.74 (2 × C, Ar), 157.79 (2 × C═O, urea), 173.33 (2 × C═O)
ppm. IR (KBr): vmax = 1250 (C―O), 1600 (C═C), 1718 (asym
C═O), 1760 (sym C═O), 2850–2950 (Ali H), 3050 (Ar H), 3150
(w N3H), 3250 (N1H) cm‐1. Exact mass: (M+): calcd. for
C24H26N4O6, 466.1852; found 466.1856.
5,5′‐((Hexane‐1,6‐diylbis(oxy))bis(4,1‐phenylene))bis(5‐
methylimidazolidine‐2,4‐dione) (9). White powder crystals. m.p.
(recrystallized from ethanol) 220°Cdec.. yield 35%, 1.4 g. 1H
NMR (500 MHz, DMSO‐d6): δ = 1.46 (p, J = 3.97, 3.79 Hz,
2 H, 2 × CHaHb), 1.59 (s, 3 H, CH3), 1.64 (s, 3 H, CH3), 1.73
(p, J = 6.63, 7.19, 6.77 Hz, 2 H, 2 × CHaHb), 2.49 (DMSO), 3.34
(H2O), 3.95 (t, J = 6.49 Hz, 1 H, 2 × CHaO), 4.06 (t, J = 6.48 Hz,
1 H, 2 × CHbO), 6.92 (d, J = 8.81 Hz, 1 H, 2 × CH, Ar), 7.01
(d, J = 8.81 Hz, 1 H, 2 × CH, Ar), 7.28 (d, J = 5.38 Hz, 1 H,
2 × CH, Ar), 7.91 (d, J = 8.78 Hz, 1 H, 2 × CH, Ar), [8.48 (w s,
2 × N1H meso), 8.49 (s, 2 × N1H dl), 1 H], 8.90 (w s, 2 × N3H)
ppm. 13C NMR (125 MHz, DMSO‐d6): δ = 25.19 (2 × CH3),
25.81 (2 × CH2), 29.21 (2 × CH2), 40.31 (DMSO), 67.30
(2 × CH2O), 70.11 (2 × C5, ring), 115.33 (4 × CH, Ar), 124.41
(4 × CH, Ar), 134.09 (2 × C, Ar), 156.16 (2 × C, Ar), 159.49
(2 × C═O, urea), 179.81 (2 × C═O) ppm. IR (KBr): vmax = 1250
(C―O), 1600 (C═C), 1718(asym C═O), 1760 (sym C═O),
2850‐2930 (Ali H), 3040 (Ar H), 3150 (w N3H), 3250 (N1H) cm‐1.
Exact mass: (M+): calcd. for C26H30N4O6, 494.2165; found
494.2167.
(2 × C═O, urea), 176.22 (2 × C═O) ppm. IR (KBr): vmax
=
1575 (C═C), 1730 (asym C═O), 1770 (sym C═O), 2750–3050
(Ali H), 3170 (sh N3H), 3260 (N1H) cm–1. Exact mass: (M+):
calcd. for C10H12N4O4, 252.0859; found 252.0856.
5,5′‐(1,4‐Phenylene)bis(imidazolidine‐2,4‐dione) (13). Cream
powder crystals; m.p. (recrystallized from ethanol) 295°Cdec.
.
yield 86%, 1.88 g. 1H NMR (500 MHz, DMSO‐d6): δ = 2.49
(DMSO), 3.34 (H2O), 5.17 (s, 1 H, 2 × CH5CON), 7.35 (s,
2 H, 4 × CH, Ar), 8.40 (s, 1 H, 2 × N1H), 10.79 (s, 1 H,
2 × N3H); 13C NMR (125 MHz, DMSO‐d6): δ = 40.36
(DMSO), 61.80 (2 × C5, ring), 127.90 (4 × CH, Ar), 136.95
(2 × C, Ar), 158.35 (2 × C═O, urea), 174.93 (2 × C═O) ppm.
IR (KBr): vmax = 1515 (C═C), 1700 (asym C═O), 1780 (sym
C═O), 2755 (CH5CON), 3000 (Ar H), 3200 (N3H), 3300
(N1H) cm–1. Exact mass: (M+): calcd. for C12H10N4O4,
274.0702; found 274.0706.
5,5′‐(Butane‐1,4‐diyl)bis(5‐phenylimidazolidine‐2,4‐dione)
(10). White powder crystals. m.p. (recrystallized from ethanol) 180°
Cdec.. yield 77%, 2.50 g. 1H NMR (500 MHz, DMSO‐d6): δ = 1.19
(m, 2 H, CHaHb), 1.68 (m, 2 H, CHaHb), 1.84 (m, 1 H, CHa), 2.01
(m, 1 H, CHb), 2.49 (DMSO), 3.07 (m, 2 H, CHaHb), 3.33
(H2O),7.30 (t, J = 6.93 Hz, 1 H, 1 × CH, Ar), 7.37 (t, J = 7.38
Hz, 2 H, 2 × CH, Ar), 7.47‐7.53 (m, J = 8.22, 2.45, 8.36, 7.48
Hz, 4 H, 4 × CH, Ar), 7.62 (t, J = 7.07 Hz, 1 H, 1 × CH, Ar),
7.96 (t, J = 10.17 Hz, 2 H, 2 × CH, Ar), 8.60 (s, 1 H, 2 × N1H
dl), 8.64 (w s, 2 × N1H meso), 10.74 (s, 1 H, 2 × N3H) ppm.
13C NMR (125 MHz, DMSO‐d6): δ = 24.24 (2 × CH2), 38.63 (2
× CH2), 40.40 (DMSO), 68.30 (2 × C5, ring), 126.20 (1 × CH,
Ar), 128.61 (1 × CH, Ar), 128.75 (2 × CH, Ar), 129.28 (2 ×
CH, Ar), 129.55 (2 × CH, Ar), 133.89 (2 × CH, Ar), 137.59 (1
× C, Ar), 140.05 (1 × C, Ar), 157.39 (2 × C═O, urea), 177.04
(2 × C═O), 200.87(solvent) ppm. IR (KBr): vmax = 1590
(C═C), 1715(asym C═O), 1765 (sym C═O), 2850‐2920 (Ali
H), 3040 (Ar H), 3150 (sh N3H), 3235 (N1H) cm‐1. Exact mass:
(M+): calcd. for C22H22N4O4, 406.1641; found 406.1638.
5,5′‐(1,1′‐(Butane‐1,4‐diyl)bis(1H‐indole‐3,1‐diyl))bis
(imidazolidine‐2,4‐dione) (14). Beige powder crystals. m.p.
(recrystallized from ethanol) 120°C. Yield 20%, 0.75 g. 1H NMR
(500 MHz, DMSO‐d6): δ = 1.82 (m, 2 H, 2 × CHaHb), 2.49
(DMSO), 3.31 (H2O), 4.31 (m, 2 H, 2 × CHaHbN), 5.37 (s, 1 H, 2
× CH5CON), 7.23–7.30 (m, J = 7.22, 7.48, 7.73, 7.93 Hz, 2 H, 4
× CH, Ar), 7.61 (d, J = 8.04 Hz, 1 H, 2 × CH, Ar), 7.80 (s, 1 H,
CH, olefin), 8.10 (d, J = 7.54 Hz, 1 H, 2 × CH, Ar), 8.29 (s, 1 H,
2 × N1H), 9.88 (s, 1 H, 2 × N3H) ppm. 13C NMR (125 MHz,
DMSO‐d6): δ = 26.36 (2 × CH2), 40.39 (DMSO), 53.20 (2 ×
CH2N), 61.90 (2 × C5H, ring), 107.88 (2 × CH, Ar), 111.78 (2 ×
C, pyrrolic), 115.11 (2 × CH, Ar), 118.23 (2 × CH, Ar), 120.08 (2
× CH, Ar), 124.52 (2 × C, Ar), 128.08 (2 × CH, pyrrolic), 136.82
(2 × C, Ar), 155.15 (2 × C═O, urea), 174.83 (2 × C═O) ppm. IR
(KBr): vmax = 1605 (C═C), 1715(asym C═O), 1770 (sym C═O),
2850‐2930 (Ali H), 3050 (Ar H), 3100 (Olepine H), 3200 (sh
N3H), 3300 (sh N1H) cm‐1. Exact mass: (M+): calcd. for
C26H24N6O4, 484.1859; found 484.1858.
5,5′‐(Butane‐1,4‐diyl)bis(5‐(p‐tolyl)imidazolidine‐2,4‐dione)
(11). Cream powder crystals. m.p. (recrystallized from ethanol)
136°C. yield 41%, 1.44 g. 1H NMR (500 MHz, DMSO‐d6):
δ = 1.85 (m, 1 H, CHa), 1.98 (m, 1 H, CHb), 2.17 (t, J = 7.19 Hz,
2 H, CHaHb), 2.23 (t, J = 7.21 Hz, 2 H, CHaHb), 2.27 (s, 3 H,
CH3), 2.36 (s, 3 H, CH3), 2.49 (DMSO), 2.98 (t, J = 7.21 Hz,
2 H, CHaHb), 3.32 (H2O), 7.18 (d, J = 7.98 Hz, 2 H, 2 × CH, Ar),
7.31 (d, J = 7.91 Hz, 2 H, 2 × CH, Ar), 7.36 (d, J = 8.09 Hz, 2 H,
2 × CH, Ar), 7.86 (d, J = 8.01 Hz, 2 H, 2 × CH, Ar), 8.54 (w s,
2 × N1H meso), 8.58 (s, 1 H, 2 × N1H dl), 10.70 (br s, 1 H,
2 × N3H) ppm. 13C NMR (125 MHz, DMSO‐d6): δ = 21.40
(CH3), 21.98 (CH3), 24.31 (CH2), 25.06 (CH2), 34.54 (CH2),
38.36 (CH2), 40.39 (DMSO), 68.15 (2 × C5, ring), 126.10
Acknowledgments. The partial support of this research by the
Research Committee of University of Guilan is gratefully
acknowledged. We also acknowledge the useful suggestions
made by Professor Douglas Fry of Ricerca Biosciences, USA.
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