Unexpected formation of 5-alkylidene derivatives of hydantoin from the Michael addition of 4-phenylurazole to fumaric esters

Article abstract of DOI:10.1016/j.tet.2016.02.024

An unexpected reaction between 4-phenylurazole and fumaric esters which led to the formation of 5-alkylidene derivatives of hydantoin is described in this paper. The reaction takes place in the presence of tetrabutylammonium bromide (TBAB), and 1,4-diaza-

Full text of DOI:10.1016/j.tet.2016.02.024

Accepted Manuscript
Unexpected formation of 5-alkylidene derivatives of hydantoin from the Michael
addition of 4-phenylurazole to fumaric esters
Zahra Soltanzadeh, Gholamhassan Imanzadeh, Nader Noroozi-Pesyan, Ertan Şahin,
Hemayat Hooshmand
PII:
S0040-4020(16)30087-4
10.1016/j.tet.2016.02.024
TET 27494
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 9 November 2015
Revised Date: 31 January 2016
Accepted Date: 8 February 2016
Please cite this article as: Soltanzadeh Z, Imanzadeh G, Noroozi-Pesyan N, Şahin E, Hooshmand
H, Unexpected formation of 5-alkylidene derivatives of hydantoin from the Michael addition of 4-
phenylurazole to fumaric esters, Tetrahedron (2016), doi: 10.1016/j.tet.2016.02.024.
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ACCEPTED MANUSCRIPT
Unexpected formation of 5-alkylidene derivatives of hydantoin from the Michael addition
of 4-phenylurazole to fumaric esters
Zahra Soltanzadeh, Gholamhassan Imanzadeh, Nader Noroozi-Pesyan, Ertan Şahin, Hemayat Hooshmand

ACCEPTED MANUSCRIPT
Unexpected formation of 5-alkylidene derivatives of hydantoin from
the Michael addition of 4-phenylurazole to fumaric esters
Zahra Soltanzadeha, Gholamhassan Imanzadeha, , Nader Noroozi-Pesyanb, Ertan Şahinc,
Hemayat Hooshmanda
aDepartment of Chemistry, Faculty of Basic Science, University of Mohaghegh Ardabili 56199-11367, Ardabil, Iran
bDepartment of Chemistry, Faculty of Science, Urmia University 57159, Urmia, Iran
cDepartment of Chemistry, Faculty of Science, Atatürk University 25240, Erzurum, Turkey
Abstract: An unexpected reaction between 4-phenylurazole and fumaric esters which led to the formation of 5-alkylidene
derivatives of hydantoin is described in this paper. The reaction takes place in the presence of tetrabutylammonium bromide
(TBAB), and 1,4-diaza-bicyclo[2,2,2]octane (DABCO) at 70 oC under solvent-free conditions.
Keywords: Unexpected products, Hydantoin derivatives, Michael addition, 4-Phenylurazole, Fumaric ester
1. Introduction
The hydantoin (imidazolidine-2,4-dione) skeleton is a 5-membered heterocyclic ring system having two nitrogen
atoms at positions 1 and 3 of the ring. This skeleton is found in a large number of naturally occurring and synthetic
biologically active heterocyclic compounds.1 The chemistry and the properties of hydantoin and its derivatives have
been investigated for more than 140 years. The studies indicate that these compounds have a broad range of biological
activities including anticonvulsants,2,3 antiarithmics,4 antitumor,5 antidepressants,6 antiviral agents,7 treatment of
epileptic seizures,8,9 epidermolysis bullosa,10 inflammatory conditions,11 cardiac antiarrhythmic,12 and for the
treatment of many more diseases including HIV.13 Additionally, hydantoin and its derivatives are also precursors for
the synthesis of α-amino acids and pyruvic acid derivatives.14-17 In this regard, 5-arylidene and 5-alkylidene
derivatives of hydantoin are potentially useful starting materials for the preparation of these acids because a broad
range of synthetic methodologies can be used to modify the exocyclic double bond to produce structural diversity.18
For these reasons, among the 5-membered heterocyclic ring systems, hydantoin has a privileged position in medicinal
chemistry.
2. Results and Discussion
In line with our interest in the aza-Michael addition of amides and imides to α,β-unsaturated esters,19-21 in a recent
project we reported that the addition of 4-phenylurazole to acrylic esters produced the corresponding N1,N2-bis-
Michael adducts in good yield.22 This pleasing result inspired us, herein, to examine this process for fumaric esters
instead of acrylic esters. Therefore, we tried the Michael addition reaction of urazole 1 (1 mmol) to n-butyl fumarate
2d (1 mmol) as a model reaction, in order to produce the corresponding bis-Michael adduct. However, when the
o
reaction was conducted in the presence of the base DABCO (1 mmol) and organic salt TBAB (0.5 mmol) at 70 C,
surprisingly, a solid product was obtained with spectral data and an elemental analysis inconsistent with the expected
structure of Michael adduct 4 (R = n-Bu). Indeed, the data were in good agreement with the structure of an
unprecedented product 3d (R = n-Bu) assembled via ring-opening of urazole, followed by the formation of a
hydantoin ring (Scheme 1).
Scheme 1. The reaction leading to the synthesis of 3.
Corresponding author. Tel.: +98-453-351-4701; fax: +98-453-351-4702; e-mail: Imanzad2000@yahoo.com;
g_imanzadeh@uma.ac.ir
1

ACCEPTED MANUSCRIPT
The mass spectrum of 3d showed a molecular ion peak at m/z= 288 which was consistent with the mass of a 1:1
condensation product of the urazole 1 and ester 2d releasing 1 equivalent of ammonia, n-butanol, carbon dioxide, and
abstracting one molecule of water. The 1H NMR spectrum of the product exhibited a triplet at δ 0.96 (3H)
corresponding to the methyl group coupled to equivalent hydrogens of methylene group and clearly indicating that
only one n-butyl group has participated in the structure of the product. There were also a sextet and a quintet in the
spectrum at δ 1.43 (2H) and 1.69 (2H) that were related to the resonances of the methylene protons of CH3-CH2- and
1
CH3CH2-CH2- groups, respectively. We observed another triplet at δ 4.24 (2H) in the H NMR spectrum of this
product that was assigned to the CH2 group attached to an oxygen and split by two equivalent hydrogens, O-CH2-
CH2-. Also, there were two singlets in the spectrum at δ 6.04 (1H) and 9.18 that were related to hydrogen resonances
of vinyl and amide groups respectively. The aromatic region of spectrum showed a multiplet at δ 7.39-7.52 (5H) that
was in agreement with the presence of a mono-substituted benzene ring in the structure of the product 3d. Further
support for the structures of compounds 3 was obtained from the 13C NMR spectra of products where three downfield
signals (152.4, 161.3, 166.9 for 3d) corresponded to the presence of three carbonyl groups in the molecules. These
features were consistent with the production of (Z)-butyl 2-(2,5-dioxo-1-phenylimidazolidin-4-ylidene)acetate (3d).
Mechanistically, it is conceivable that the reaction initially proceeds via a proton abstraction from urazole 1 by
DABCO to produce anion intermediate 5. Michael addition reaction of this ion to fumaric ester 2 formed Michael
adduct 6 that in the DABCO media this adduct can be converted to anion intermediate 7. This intermediate produces
compound 8 through urazole ring-opening (arrows on 7). Compound 8 undergoes hydrolysis by adventitious water
and is subsequently decarboxylated to compound 9. Loss of an ammonia molecule from 9 (we confirmed the releasing
of ammonia gas by keeping of wet pH paper over the reaction flask) gives compound 10 which can be tautomerized to
corresponding (Z)-alkyl 2-(2,5-dioxo-1-phenylimidazolidin-4-ylidene)acetate 3 (Scheme 2).
O
O
COOR
NH
N
NH
NH
N
N
ROOC
+
+
NR3
2
5
O
O
1
HNR3
O
COOR
COOR
O
COOR
NH
N
NH
N
Base
N
N
7
O
COOR
6
O
COOR
O
O
N
H2O
C
N
C
COOR
NH3
COOR
NH2
N
ROH
CO2
N
9
8
O
O
NH3
O
N
O
H
H
OR
C
N
C
O
C
N
COOR
N
H
3
O
10
O
NR3 = DABCO
Scheme 2. Proposed mechanism for the formation 3.
Different solvents as well as solvent-free conditions were tested for the model reaction. The reaction failed in
DMF, DMSO, dichloromethane, chloroform, methanol, ethanol, acetone, ethyl acetate and water. The reaction is
successful only in the presence of organic salt TBAB, and made no significant progress without this salt under
solvent-free conditions.
In another study, we investigated the effect of organic and inorganic bases on the model reaction. All of tested
bases had catalytic effect on the reaction (Table 1). However, under the same experimental conditions, DABCO
showed excellent catalytic activity, which gave product 3d in a yield of 73% (Table 1, entry 9). In the presence of
NaOH, KOH and none alkaline media this product was produced in a trace yield (Table 1, entries 1,6,7).
Table 1. The reaction of urazole 1 with n-butyl
fumarate in the presence of different bases and
TBAB under solvent-free conditions
Entry
Basea
Time (min)
Yield (%)b
2

ACCEPTED MANUSCRIPT
1
2
3
4
5
6
7
8
9
None
Na2CO3
K2CO3
NEt3
360
360
360
360
360
360
360
360
100
Trace
30
40
15
Pyridine
NaOH
KOH
20
Trace
Trace
5
Sr2CO3
DABCO
73
aWith 4-phenylurazole(1.0 mmol), base (1.0 mmol), TBAB (0.5
mmol) and n-butyl fumarate (1.2 mmol) at 70°C.
bIsolated yield.
With the best reaction conditions in hand (DABCO 1.0 mmol, TBAB 0.5 mmol, 4-phenylurazole 1.0 mmol and n-
butyl fumarate 1.2 mmol at 70 °C), we next considered the scope of the reaction by employing different fumaric esters
2 with 4-phenyl urazole 1 (Table 2). From the Table 2, it is clear that, generally, the reactions in which alkoxy
fumarate had been employed, produced the corresponding hydantoin products 3 in moderate to good yields within
100-180 minutes (Table 2, entries 1-9,11,12). However, when benzyloxy fumarates were employed as Michael
acceptors, the TLC test not showed any progress to the reaction even after a long time (Table 2, entries 13-15). These
results can be attributed to the increased steric hindrance of the Michael acceptors. The existence of hindered -OR
groups on fumaric esters make them a weak Michael acceptors and hence addition is much more difficult to occur.
Under our conditions, the addition of Michael donor 1 to n-butyl fumarate (bearing small-OR groups) afforded the
desired product 3 in 73% yield within 100 min (Table 2, entry 4), while this addition to cyclohexyl fumarate (bearing
large -OR groups) provided a relatively low yield of 65% (Table 2, entry 12) than butyl fumarate within 180 min.
There was an exception that when decyl fumarate was used as a Michael acceptor, only the corresponding mono-
Michael adduct was obtained (Table 2, entry 10).
Table 2. The addition of urazole 1 to α,β-unsaturated esters 2 under
solvent-free conditions
Entry
1
R
CH3CH2
Product
3a
3b
3c
3d
3e
3f
Time (min)
100
Yield (%)a
60
65
85
73
80
70
70
75
65
85
80
65
-
2
CH3CH2CH2
CH3CHCH3
100
3
100
4
CH3(CH2)3
100
5
CH3CHCH2CH3
CH3CHCH2CH2CH3
(CH3)2CHCH2CH2
CH3(CH2)3CH(CH2CH3)CH2
CH3(CH2)7
150
6
150
7
3g
3h
3i
150
8
180
9
150
10
11
12
13
14
15
CH3(CH2)9
6j
150
CH3OCH2CH2
(CH2)5CH
3k
3l
150
180
PhCH2
-
1000
1000
1000
PhCHCH3
-
-
Cl-PhCH2
-
-
aIsolated yields.
3

ACCEPTED MANUSCRIPT
3. Summary
In summary, we have described an unexpected novel and interesting reaction between 4-phenylurazole and fumaric
esters in which different 5-alkylidene derivatives of hydantoin are formed. The products were produced under classic
reaction conditions in the presence of tetrabutylammonium bromide (TBAB) as an available organic salt. It was found
that 1,4-diaza-bicyclo[2,2,2]octane (DABCO) is the most suitable base for this reaction. The crystal structure of one
of the products showed both intra- and inter-molecular H-bonds. This later H-bond caused to dimeric form of this
molecule including eight-membered ring with centrosymmetric Ci form.
4. Experimental
4.1. General
α,β-Unsaturated esters were synthesized according to literature procedures.23 4-Phenylurazole was purchased from
Merck and used without further purification. Esters were transferred via syringe. Organic solvents were removed
under reduced pressure by rotary evaporator. Reactions were monitored by thin-layer chromatography (TLC) carried
out on silica gel plates (SILG/UV 254, Merk) using UV light as the visualizing agent. Chromatography was
performed on Merk 60 silica gel (230–240 mesh) with n-hexane and ethyl acetate mixtures (80:20) as eluent. FT-IR
spectra were recorded on a Perkin-Elmer RX-1 instrument. Mass spectra were recorded on a Shimadzu GC-MS-QP
1
1000PX. Elemental analysis for C, H, and N were performed using a Heraeus CHN-O-Rapid analyzer. H NMR and
13C NMR spectra were recorded mostly on a Bruker 400 MHz instrument. The melting points were determined in
open capillaries with a Stuart Melting Point Apparatus and are uncorrected. Chemical shifts were recorded in ppm
1
downfield from tetramethylsilane. J values were given in Hz. Abbreviations used in H NMR are s (singlet), d
(doublet), t (triplet), q (quartet) and m (multiplet).
4.2. General procedure for the Michael addition of 4-phenylurazole to fumaric esters
A well ground mixture of 4-phenylurazole (1.0 mmol), DABCO (1.0 mmol), and TBAB (0.5 mmol) was placed in
a flask. Fumaric ester (1.2 mmol) was added to this mixture and the flask was heated in the oil bath. When the oil bath
temperature reached 70 ˚C, a brown solution was formed. After keeping the reaction flask at this temperature for
stipulated time (Table 2), the reaction was completed as monitored by TLC. The flask was allowed to cool down to
room temperature and chloroform (30 mL) was added. The solution was stirred to dissolve all the solids. TBAB was
recovered by the addition of water (15 mL) to this solution, then collected and dried under vacuum. The chloroform
layer was washed with water (3×15 mL). After dried with sodium sulfate and removal of the organic solvent, the
residue was purified on short silica-gel column with n-hexane / ethyl acetate (9:1) as the eluent.
4.2.1. (Z)-ethyl 2-(2,5-dioxo-1-phenylimidazolidin-4-ylidene)acetate (3a). White crystal, mp 186-187 ˚C (191 ˚C)24; Rf
1
(20% ethyl acetate/hexane) 0.30; H NMR (400 MHz, CDCl3): δ ppm 1.34 (t, 3H, J = 7.1 Hz), 4.29 (q, 2H, J = 7.1
Hz), 6.02 (s, 1H), 7.39-7.51 (m, 5H), 9.18 (s, 1H); 13C NMR (100 MHz, CDCl3): 13.1, 60.4, 96.0, 124.8, 127.6, 128.2,
129.5, 137.7, 151.3, 160.3, 165.7; IR (KBr, cm-1): 3297, 2933, 1782, 1733, 1698, 1413, 1262, 772, 691; Anal. Calcd.
for C13H12N2O4: C, 60.00; H, 4.65; N, 10.76. Found: C, 60.56; H, 4.16; N, 10.23.
4.2.2. (Z)-propyl 2-(2,5-dioxo-1-phenylimidazolidin-4-ylidene)acetate (3b). White solid, mp 187-188 ˚C; Rf (20%
ethyl acetate/hexane) 0.50; 1H NMR (500 MHz, CDCl3): δ ppm 1.02 (t, 3H, J = 7.4 Hz), 1.77 (sextet, 2H, J = 7.3 Hz),
4.23 (t, 2H, J = 6.7 Hz), 6.07 (s, 1H), 7.43-7.55 (m, 5H), 9.20 (s, 1H); 13C NMR (125 MHz, CDCl3): 10.3, 21.9, 67.1,
97.1, 125.9, 128.7, 129.3, 130.6, 138.7, 152.3, 161.3, 166.9; IR (KBr, cm-1): 3299, 2965, 1788, 1734, 1681, 1411,
1274, 774, 691; Ms m/z (%): 274 (M+) (97), 270 (23), 251 (38), 232 (90), 224 (29), 214 (100), 188 (78), 119 (83), 68
(83); Anal. Calcd. for C14H14N2O4: C, 61.31; H, 5.14; N, 10.21. Found: C, 61.23; H, 5.09; N, 10.13.
4.2.3. (Z)-isopropyl 2-(2,5-dioxo-1-phenylimidazolidin-4-ylidene)acetate (3c). White crystal, mp 158-159 ˚C; Rf (20%
ethyl acetate/hexane) 0.40; 1H NMR (400 MHz, CDCl3): δ ppm 1.31 (d, 6H, J = 6.3 Hz), 5.15 (septet, 1H, J = 6.3 Hz),
5.99 (s, 1H), 7.38-7.51 (m, 5H), 9.26 (s, 1H); 13C NMR (100 MHz, CDCl3): 20.6, 68.1, 96.5, 124.8, 127.5, 128.2,
129.5, 137.4, 151.3, 160.3, 165.2; IR (KBr, cm-1): 3298, 2982, 1788, 1737, 1691, 1415, 1273, 771, 694; Anal. Calcd.
for C14H14N2O4: C, 61.31; H, 5.14; N, 10.21. Found: C, 61.89; H, 5.54; N, 10.16.
4.2.4. (Z)-butyl 2-(2,5-dioxo-1-phenylimidazolidin-4-ylidene)acetate (3d). White solid, mp 153-155 ˚C; Rf (20% ethyl
acetate/hexane) 0.52; 1H NMR (400 MHz, CDCl3): δ ppm 0.96 (t, 3H, J = 7.3 Hz), 1.43 (sextet, 2H, J = 7.3 Hz), 1.69
(quintet, 2H, J = 6.6 Hz), 4.24 (t, 3H, J = 6.6 Hz), 6.04 (s, 1H),7.39-7.52 (m, 5H), 9.18 (s, 1H);13C NMR (100 MHz,
CDCl3): 13.7, 19.1, 30.8, 65.3, 97.1, 125.9, 128.7, 129.3, 130.6, 138.7, 152.4, 161.3, 166.9; IR (KBr, cm-1): 3303,
2967, 1789, 1735, 1683, 1408, 1178, 773, 692; Ms m/z (%): 288 (M+) (51), 232 (27), 214 (62), 188 (23), 142 (100),
119 (91),100 (53), 91 (41), 68 (94), 57 (100); Anal. Calcd. for C15H16N2O4: C, 62.49; H, 5.59; N, 9.72. Found: C,
62.21; H, 5.46; N, 9.41.
4.2.5. (Z)-sec-butyl 2-(2,5-dioxo-1-phenylimidazolidin-4-ylidene)acetate (3e). White crystal, mp 134-135 ˚C; Rf (20%
ethyl acetate/hexane) 0.40; 1H NMR (400 MHz, CDCl3): δ ppm 0.86 (t, 3H, J = 7.6 Hz), 1.21 (d, 3H, J = 6 Hz), 1.52-
1.62 (m, 2H), 4.92 (sextet, 1H, J = 6 Hz), 5.95 (s, 1H), 7.33-7.44 (m, 5H), 9.13 (s, 1H); 13C NMR (100 MHz, CDCl3):
9.6, 19.4, 28.7, 73.6, 97.5, 125.8, 128.6, 129.2, 130.6, 138.6, 152.3, 161.4, 166.5; IR (KBr, cm-1): 3287, 2973, 1785,
4

ACCEPTED MANUSCRIPT
1733, 1697, 1412, 1266, 772, 696; Anal. Calcd. for C15H16N2O4: C, 62.49; H, 5.59; N, 9.72. Found: C, 62.66; H, 5.10;
N, 10.18.
4.2.6. (Z)-pentan-2-yl 2-(2,5-dioxo-1-phenylimidazolidin-4-ylidene)acetate (3f). White solid, mp 112-113 ˚C; Rf (20%
1
ethyl acetate/hexane) 0.55; H NMR (400 MHz, CDCl3): δ ppm 0.93 (t, 3H, J = 7.3 Hz), 1.28 (d, 3H, J = 6.3 Hz),
1.30-1.40 (m, 2H), 1.49-1.55 (m, 1H), 1.61-1.66 (m, 1H), 5.06 (sextet, 1H, J = 6.2 Hz), 6.01 (s, 1H), 7.38-7.50 (m,
5H), 9.22 (s, 1H); 13C NMR (100 MHz, CDCl3): 12.8, 17.5, 18.9, 36.9, 71.2, 96.5, 124.8, 127.6, 128.2, 129.5, 137.5,
151.3, 160.3, 165.4; IR (KBr, cm-1): 3317, 2960, 1783, 1733, 1697, 1414, 1271, 772, 696; Anal. Calcd. for
C16H18N2O4: C, 63.56; H, 6.00; N, 9.27. Found: C, 63.42; H, 5.19; N, 9.69.
4.2.7. (Z)-isopentyl 2-(2,5-dioxo-1-phenylimidazolidin-4-ylidene)acetate (3g). White solid, mp 125-126 ˚C; Rf (20%
ethyl acetate/hexane) 0.55; 1H NMR (400 MHz, CDCl3): δ ppm 0.88-0.92 (m, 1H), 0.93-0.96 (m, 6H), 1.59 (q, 2H, J =
6.8 Hz), 4.26 (t, 2H, J = 6.8 Hz), 6.02 (s, 1H), 7.38-7.51 (m, 5H), 9.26 (s, 1H); 13C NMR (100 MHz, CDCl3): 21.3,
23.9, 36.1, 63.0, 95.9, 124.8, 127.7, 128.2, 129.5, 137.6, 151.3, 160.3, 165.8; IR (KBr, cm-1): 3266, 2958, 1785, 1736,
1699, 1416, 1263, 771, 695; Anal. Calcd. for C16H18N2O4: C, 63.56; H, 6.00; N, 9.27. Found: C, 63.27; H, 5.82; N,
9.75.
4.2.8. (Z)-2-ethylhexyl 2-(2,5-dioxo-1-phenylimidazolidin-4-ylidene)acetate (3h). White solid, mp 89-90 ˚C; Rf (20%
1
ethyl acetate/hexane) 0.54; H NMR (400 MHz, CDCl3): δ ppm 0.89-0.93 (m, 6H), 1.30-1.43 (m, 8H), 1.61 (septet,
1H, J = 6 Hz), 4.15 (dd, 2H, J1 = 5.7 Hz, J2 = 2.5 Hz), 6.04 (s, 1H), 7.39-7.51 (m, 5H), 9.26 (s, 1H); 13C NMR (100
MHz, CDCl3): 9.9, 13.0, 21.9, 22.6, 27.8, 29.2, 37.6, 66.7, 96.0,124.8, 127.6, 128.2, 129.5, 137.6, 151.3, 160.3, 165.9;
IR (KBr, cm-1): 3272, 2961, 1785, 1736, 1678, 1417, 1264, 773, 697; Anal. Calcd. for C19H24N2O4: C, 66.26; H, 7.02;
N, 8.13. Found: C, 65.87; H, 6.79; N, 7.91.
4.2.9. (Z)-octyl 2-(2,5-dioxo-1-phenylimidazolidin-4-ylidene)acetate (3i). White solid, mp 119-120 ˚C; Rf (20% ethyl
1
acetate/hexane) 0.58; H NMR (400 MHz, CDCl3): δ ppm 0.89 (t, 3H, J = 7 Hz), 1.28-1.39 (m, 10H), 1.69 (quintet,
2H, J = 6.7 Hz), 4.22 (t, 2H, J = 6.7 Hz), 6.03 (s, 1H), 7.39-7.51 (m, 5H), 9.20 (s, 1H); 13C NMR (100 MHz, CDCl3):
13.0, 21.6, 24.8, 27.5, 28.1, 30.7, 64.5, 96.0, 124.8, 127.6, 128.2, 129.5, 137.7, 151.3, 160.3, 165.8; IR (KBr, cm-1):
3277, 2925, 1784, 1735, 1698, 1412, 1265, 772, 695; Anal. Calcd. for C19H24N2O4: C, 66.26; H, 7.02; N, 8.13. Found:
C, 66.89; H, 6.12; N, 7.63.
4.2.10. Didecyl 2-(3,5-dioxo-4-phenyl-1,2,4-triazolidin-1-yl)succinate (6j). White solid, mp 102-103 ˚C; Rf (20%
1
ethyl acetate/hexane) 0.77; H NMR (400 MHz, CDCl3): δ ppm 0.80 (t, 6H, J = 6.8 Hz), 1.16-1.22 (m, 28H), 1.53-
1.56 (m, 4H), 2.92 (dd, 2H, J1=16 Hz, J2 = 7 Hz), 3.99-4.14 (m, 4H), 5.13 (dd, 1H, J1 = 7.6, J2 = 5.4 Hz), 7.28-7.45 (m,
5H), 8.32 (s, 1H); 13C NMR (100 MHz, CDCl3): 13.0, 21.6, 24.6, 24.7, 27.3, 28.1, 28.1, 28.2, 28.2, 28.2, 28.2, 28.3,
28.4, 30.8, 33.3, 54.7, 64.7, 65.6, 75.6, 76.0, 76.3, 124.4, 127.2, 128.0, 130.0, 152.7, 153.0, 167.2, 169.3; IR (KBr,
cm-1): 3175, 2921, 1787, 1742, 1690, 1449, 1274, 764, 699; Anal. Calcd. for C32H51N3O6: C, 66.99; H, 8.96; N, 7.32.
Found: C, 67.28; H, 8.31; N, 7.64.
4.2.11. (Z)-2-methoxyethyl 2-(2,5-dioxo-1-phenylimidazolidin-4-ylidene)acetate (3k). White crystal, mp 123-124 ˚C;
Rf (20% ethyl acetate/hexane) 0.11; 1H NMR (400 MHz, CDCl3): δ ppm 3.42 (s, 3H), 3.66 (t, 2H, J = 4.6 Hz), 4.39 (t,
2H, J = 4.7 Hz), 6.06 (s, 1H), 7.39-7.51 (m, 5H), 9.27 (s, 1H); 13C NMR (100 MHz, CDCl3): 58.0, 63.1, 69.0, 95.7,
124.8, 127.6, 128.2, 129.5, 137.9, 151.3, 160.2, 165.3; IR (KBr, cm-1): 3313, 2931, 1783, 1734, 1692, 1415, 1269,
768, 693; Anal. Calcd. for C14H14N2O5: C, 57.93; H, 4.86; N, 9.65. Found: C, 58.12; H, 4.35; N, 9.22.
4.2.12. (Z)-cyclohexyl 2-(2,5-dioxo-1-phenylimidazolidin-4-ylidene)acetate (3l). White solid, mp 226-227 ˚C; Rf (20%
1
ethyl acetate/hexane) 0.42; H NMR (400 MHz, CDCl3): δ ppm 1.25-1.58 (m, 6H), 1.74-1.90 (m, 4H), 4.90 (m, 1H),
6.02 (s, 1H), 7.33-7.62 (m, 5H), 9.20 (s, 1H); 13C NMR (100 MHz, CDCl3): 22.6, 24.2, 30.5, 72.9, 96.6, 124.8, 127.6,
128.2, 129.6, 137.4, 151.3, 160.4, 165.2; IR (KBr, cm-1): 3267, 2932, 1785, 1733, 1699, 1414, 1261, 771, 695; Anal.
Calcd. for C17H18N2O4: C, 64.96; H, 5.77; N, 8.91. Found: C, 65.27; H, 5.42; N, 9.26.
In order to further investigation of product structures, the crystal structure of 3a is shown in Fig. 1. For the crystal
structure determination, the single crystal of the compound 3a was used for data collection on a four-circle Rigaku R-
AXIS RAPID-S diffractometer (equipped with a two dimensional area IP detector). The graphite-monochromatised
Mo Kα radiation (λ = 0.71073 Å) and oscillation scans technique with ꢀω = 5° for one image were used for data
collection. The lattice parameters were determined by the least-squares methods on the basis of all reflections with
F2>2σ (F2). Integration of the intensities, correction for Lorentz and polarization effects and cell refinement was
performed using Crystal Clear (Rigaku/MSC Inc., 2005) software.25 The structures were solved by direct methods
using SHELXL201326 and refined by a full-matrix least-squares procedure using the program SHELXL2013.26 H-atoms
were positioned geometrically and refined using a riding model. The final difference Fourier maps showed no peaks
of chemical significance. Crystal packing diagram of 3a are in sheet form across the intra- and inter-molecular H-
bonds (Fig. 2). The crystallographic data and selected bond length, angles and torsion angles are summarized in
Tables 3 and 4, respectively. Crystallographic data were deposited in CSD under CCDC-1435008 registration number
and are available free of charge upon request to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44-1223-
336033, e-mail: deposit@ccdc.cam.ac.uk).
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Figure 1. ORTEP diagram of 3a.
(b)
(a)
(c)
(d)
Figure 2. Crystal packing diagram of 3a (a). View from the cell a axis (b), b axis (c) and c axis (d).
Compound 3a show two type H-bonds. This compound formed a dimer form via two intermolecular H-bonds
between N2–H2ꢁꢁꢁꢁꢁO1 atoms with d(NꢁꢁꢁꢁꢁO) distance of 3.059 Å and made an eight-membered ring with
centrosymmetric (Ci) form (Fig. 3). This compound also formed intramolecular H-bond N2–H2 and oxygen atom of
carbonyl group in esteric moiety (N2–H2ꢁꢁꢁꢁꢁO3) with d(NꢁꢁꢁꢁꢁO) distance of 2.817 Å. In other word, the H2 atom has a
bifurcated inter- and intra-molecular H-bonds with both O1 and O3 atoms.
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Figure 3. Inter- and intra-molecular H-bond distances in 3a. Formation of eight-membered ring with centrosymmetric Ci
form and assigned with dense dot ( ).
Table 3. Crystallographic data for compound 3a
Crystal data
C13H12N2O4
γ = 85.669 (4)°
V = 596.88 (10) Å3
Z = 2
Mr = 260.25
Triclinic, P1
a = 5.3027 (5) Å
F(000) = 272
b = 8.6900 (9) Å
Dx = 1.448 Mg m−3
Mo Kα radiation, λ = 0.71073 Å
µ = 0.11 mm−1
T = 0 K
c = 13.2153 (12) Å
α = 80.225 (4)°
β = 85.234 (4)°
Data collection
13152 measured reflections
2969 independent reflections
1579 reflections with I > 2σ(I)
Rint = 0.105
θmax = 28.4°, θmin = 3.1°
h = −7→7
k = −11→11
l = −17→17
Refinement
R[F2 > 2σ(F2)], wR(F2), S
Refinement on F2
Least-squares matrix: full
0.065, 0.155, 1.01
0 restraints
Hydrogen site location: inferred
from neighbouring sites
ꢀρmax = 0.20 e Å−3
ꢀρmin = −0.27 e Å−3
Table 4. The selected bond length (Å), angle (°) and
torsion angle (ϕ) for 3a
C9—C10
C11—C10
O2—C7
O1—C8
O3—C11
N2—C8
N1—C7
1.325 (3)
1.458 (3)
1.206 (3)
1.207 (3)
1.207 (3)
1.365 (3)
1.378 (3)
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N1—C8
1.408 (3)
124.1
C8—N2—H2
C9—N2—H2
124.1
O1—C8—N2
127.7 (2)
123.7 (2)
−67.0 (3)
178.6 (2)
1.2 (5)
O3—C11—C10
C7—N1—C6—C5
C7—C9—C10—C11
C10—C9—C7—O2
O1—C8—N2—H2
C7—C9—C10—H10
N2—H2ꢁꢁꢁꢁꢁO1—C8
0.64
−1.42
−14.05
Acknowledgment
Authors are grateful of University of Mohaghegh Ardabili for the financial support and the laboratories of Tehran
and Tabriz University for the product analysis.
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