Unexpected course of the reaction of 2-unsubstituted 1H-Imidazole 3-oxides with ethyl acrylate

Article abstract of DOI:10.1002/hlca.201100519

The attempted ethenylation at C(2) of 2-unsubstituted 1H-imidazole N-oxides with ethyl acrylate (= prop-2-enoate) in the presence of Pd(OAc)₂ does not occur. In contrast to the other aromatic N-oxides, the [2 + 3] cycloaddition of imidazole N-oxides predominates, and 3-hydroxyacrylates, isomeric with the cycloadducts, are key products for the subsequent reaction. The final products were identified as dehydrated 2 + 1 adducts of 1H-imidazole N-oxide and ethyl acrylate. The role of the catalyst is limited to the dehydration of the intermediate 3-hydroxypropanoates to give 1H-imidazol-2-yl-substituted acrylates.

Full text of DOI:10.1002/hlca.201100519

Helvetica Chimica Acta – Vol. 95 (2012)
577
Unexpected Course of the Reaction of 2-Unsubstituted 1H-Imidazole 3-
Oxides with Ethyl Acrylate
by Grzegorz Mloston´*a), Katarzyna Urbaniaka), Alicja Wojciechowskaa)1), Anthony Lindenb), and
Heinz Heimgartner*b)
a
´
´
´
´
) University of Łodz, Department of Organic and Applied Chemistry, Tamka 12, PL-91-403 Łodz
(phone: þ 48426355761; fax: þ 48426655162; e-mail: gmloston@uni.lodz.pl)
b) Organisch-chemisches Institut der Universitꢀt Zꢁrich, Winterthurerstrasse 190, CH-8057 Zꢁrich
(phone: þ 41446354282; fax: þ 41446356812; e-mail: heimgart@oci.uzh.ch)
The attempted ethenylation at C(2) of 2-unsubstituted 1H-imidazole N-oxides with ethyl acrylate
(¼ prop-2-enoate) in the presence of Pd(OAc)2 does not occur. In contrast to the other aromatic N-
oxides, the [2 þ 3] cycloaddition of imidazole N-oxides predominates, and 3-hydroxyacrylates, isomeric
with the cycloadducts, are key products for the subsequent reaction. The final products were identified as
dehydrated 2 þ 1 adducts of 1H-imidazole N-oxide and ethyl acrylate. The role of the catalyst is limited
to the dehydration of the intermediate 3-hydroxypropanoates to give 1H-imidazol-2-yl-substituted acrylates.
1. Introduction. – In recent years, several reports on the synthesis and applications
of 2-unsubstituted imidazole 3-oxides 1 were published. In contrast to six-membered
aromatic heterocyclic N-oxides, they cannot be prepared by direct oxidation of the
parent system, but the condensation of a-hydroxyimino ketones with methylidene
amines offers a convenient access to this group of reactive 1H-imidazole derivatives
[1][2]. One of the most characteristic features of their structure is the ꢂnitrone-likeꢃ
pattern, which enables diverse 1,3-dipolar cycloadditions with electron-deficient
acetylenes and ethenes, as well as isocyanates and thiocarbonyl compounds [2][3].
The initially formed [2 þ 3] cycloadducts have never been isolated, and secondary
processes occur leading to the products depicted in Scheme 1.
On the other hand, 1 can easily be arylated at C(2) in the presence of Pd(OAc)2
with preservation of the N-oxide function [4]. The conversion of N-oxides 1 to the
corresponding imidazoles occurs smoothly upon treatment with Raney-Ni at room
temperature [5].
The metal-catalyzed formation of new C,C bonds in aromatic and heteroaromatic
rings is a challenging task in modern organic synthesis, and the state of the art in the
field of imidazole derivatives has recently been reviewed [6]. A frequently studied
reaction is the ethenylation with acrylates leading to 3-arylprop-2-enoates. Despite the
potential importance of ethenylations of aromatic N-oxides, there are, to the best of our
knowledge, only two reports on Pd-catalyzed reactions of this type (Scheme 2). In one
case, pyridine 1-oxides 2 were converted regioselectively into 3-(pyridin-2-yl)prop-2-
enoates 3 with a preserved N-oxide group in high yields [7]. The second reaction
1
´
´
Master thesis of A. W., University of Łodz, 2011.
)
ꢄ 2012 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Helvetica Chimica Acta – Vol. 95 (2012)
Scheme 1
reported is the transformation of quinoline N-oxides 4 to the prop-2-enoates 5. In these
reactions, a spontaneous deoxygenation of the N-oxide occurred [8].
Scheme 2
In a recent report, the synthesis of 2-hydroxy-3-(isoquinolin-1-yl)propanoates 6,
via the in situ generated isoquinoline N-oxide and acrylates (¼ prop-2-enoates) in the
presence of LiOH as a base, was described [9] (Scheme 3). It is worth mentioning that
this reaction proceeds without transition metal catalysis.
Scheme 3

Helvetica Chimica Acta – Vol. 95 (2012)
579
Thermal [2 þ 3] cycloadditions of acrylates with aromatic N-oxides, which, in
general, are recognized as poor 1,3-dipoles, are almost unknown. Huisgen et al. have
shown that phenanthridine N-oxide and ethyl acrylate react in DMF solution at 758 to
give products of type 6 [10]. The formation of the latter has been rationalized by a [2þ 3]
cycloaddition, followed by a spontaneous ring opening of the intermediate isoxazo-
lidine. In addition, the reaction of quinoline N-oxide with 2-methylacrylonitrile to
produce an analogous product identified as 2-hydroxy-2-methyl-3-(quinolin-2-yl)pro-
panenitrile has been reported [11].
Prompted by the results described in [7] and [8], we decided to study the reaction of
ethyl acrylate with 2-unsubstituted 1H-imidazole 3-oxides 1 both in the presence and in
the absence of a catalytic amount of Pd(AcO)2.
Results and Discussion. – In a preliminary experiment, equimolar amounts of ethyl
acrylate and 1-methyl-4,5-diphenyl-1H-imidazole 3-oxide (1a) were dissolved in
CHCl3. No reaction took place at room temperature nor when the solution was
heated to reflux. Therefore, the starting 1a and a fivefold excess of acrylate were
dissolved in N-methylpyrrolidone (NMP; 1-methylpyrrolidin-2-one), and the solution
was heated in an oil bath (1108). After ca. 1 h, the reaction was stopped, and
chromatographic workup led to an oily product. The spectroscopic data provided the
structure of the 3-hydroxypropanoate 7a (Scheme 4). Analogous products 7b – 7d were
obtained with 1-ethyl-, 1-propyl-, and 1-allyl-4,5-diphenyl-1H-imidazole 3-oxides,
respectively, in 26 – 33% yield. Attempted reactions with the corresponding 4,5-
dimethyl- or 4-methyl-5-phenyl-1H-imidazole 3-oxides led to complex mixtures of
products.
Scheme 4
The formation of the b-hydroxy esters 7 can be explained by an initial [2 þ 3]
cycloaddition to give 8 and subsequent opening of the isoxazolidine ring via cleavage of
the NꢀO bond, and aromatization of the imidazole unit.
To achieve the ethenylation product of 1a, a similar experiment with ethyl acrylate
was carried out in the presence of 5 mol% of Pd(OAc)2. After ca. 1 h, an analogous
result was obtained as in the absence of the catalyst. When the reaction time was
extended to 2.5 h, no 7a was present in the mixture. Chromatographic workup afforded
a crystalline material, which showed signals of two MeN and only one EtO group in the
1H-NMR spectrum. These data suggested that the new product contains two imidazole
and one propanoate moieties. The HR-MS exhibited the [M þ 1]þ peak at m/z
583.2700, which corresponds to a structure formed from two molecules 1a and one

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Helvetica Chimica Acta – Vol. 95 (2012)
molecule of ethyl acrylate after elimination of H2O. Finally, an X-ray crystal-structure
determination unambiguously disclosed the molecular structure of product 9a, which
formally corresponds to a Michael adduct of 1-methyl-4,5-diphenyl-1H-imidazol-2-one
(10a) with 2-(1H-imidazol-2-yl)acrylate 11a (Scheme 5 and Fig.). Most likely, the latter
compound is formed in situ by dehydration of 7a. The imidazol-2-one 10a can be
Scheme 5
Figure. ORTEP Plot [13] of the molecular structure of 9a (with 50% probability ellipsoids; arbitrary
atom numbering)

Helvetica Chimica Acta – Vol. 95 (2012)
581
formed in situ via thermal isomerization of 1a [12]. The analogous reaction course
leading to products 9 was established starting with 1b – 1d.
To obtain additional support for the proposed reaction mechanism, three control
experiments were carried out. First, the isolated hydroxy ester 7b was dehydrated in
NMP solution at 1108 in the absence, as well as in the presence, of catalytic amounts of
Pd(OAc)2. After 1 h, the progress of the reaction in both cases was examined by
1H-NMR spectroscopy. Whereas the reaction performed in the presence of Pd(OAc)2
was complete, yielding 11b exclusively, the reaction without Pd(OAc)2 gave 11b only in
traces, and more than 90% of 7b were still present in the mixture. Second, a mixture of
the isolated 11b and imidazol-2-one 10b (R ¼ Et) were heated in NMP in the presence
1
of catalytic amounts of Pd(OAc)2. After 2 h, the H-NMR spectrum of the mixture
indicated the presence of unchanged substrates, and no 9b could be detected. In the
third experiment, equimolar amounts of 11b and 1a (R ¼ Me) were heated in NMP
solution at 1108 in the absence of Pd(OAc)2. After 1 h, the mixture was analyzed by
1H-NMR spectroscopy. However, also in this case, no traces of the expected ꢂmixed
productꢃ of type 9 were found in the mixture.
These results show that the formation of products 9 does not result from the
reaction of 11 either with isolated imidazol-2-ones 10 or with N-oxides 1. Therefore,
formulation of a convincing mechanism of a cascade reaction leading to the Michael
adducts of type 9 is not possible at the moment.
3. Conclusions. – The present study showed that 2-unsubstituted 1H-imidazole 3-
oxides, in contrast to quinoline and pyridine N-oxides, do not undergo the ethenylation
reaction with ethyl acrylate in the presence of Pd(OAc)2. The results indicate that,
under the applied conditions, the preferred reaction is the [2 þ 3] cycloaddition, which
occurs regioselectively, leading to 3-hydroxypropanoate, which is a product of the
spontaneous ring opening of the five-membered cycloadduct. It is worth mentioning
that the structures of the isolated hydroxy esters 7 do not correspond to those of the
products of analogous reactions with isoquinoline and quinoline N-oxides, respectively
[9 – 11]. The catalyst used in the reaction accelerates the dehydration of the hydroxy
ester, formed after ring opening of the initial isoxazolidine derivative.
The authors thank PD Dr. L. Bigler (University of Zurich) for recording HR-MS and Mrs.
´
´
Małgorzata Celeda (University of Łodz) for her skillful help in the preparation of starting 1H-imidazole
3-oxides.
Experimental Part
1. General. M.p.: MEL-TEMP. II (Aldrich); uncorrected. IR Spectra: NEXUS FT-IR instrument; in
KBr or as film; absorptions in cmꢀ1. 1H- and 13C-NMR spectra: BRUKER AVANCE III instrument (1H at
600 and 13C at 150 MHz) using solvent signal as reference; in CDCl3; chemical shifts (d) in ppm; coupling
constants J in Hz. The majority of the 13C signals were assigned with the aid of DEPT spectra. ESI-HR-
MS: Finnigan MAT-95 spectrometer.
2. Starting Materials. The used reagents and solvents such as ethyl acrylate, Pd(OAc)2, N-
methylpyrrolidone (NMP; 1-methylpyrrolidin-2-one), petroleum ether (PE), Et2O, diisopropyl ether
(iPr2O), pentane, and AcOEt are commercially available. 1H-Imidazole 3-oxides 1 were prepared
according to known protocols [2].
3. Reactions of 2-Unsubstituted 1H-Imidazole 3-Oxides with Ethyl Acrylate. A mixture of the
corresponding oxide 1 (1 mmol), ethyl acrylate (5 mmol), Pd(OAc)2 (5 mol%), and NMP (1 ml; used as

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Helvetica Chimica Acta – Vol. 95 (2012)
a solvent) was heated under Ar in an oil bath at 1108 for 40 – 45 min. After evaporation of the solvent
and excess ethyl acrylate by vacuum distillation (bulb-to-bulb), the residues were separated on prep.
TLC plates (SiO2; hexane or PE/AcOEt 1:1) to give products 7 as pale yellow oils. Analogous results
were obtained when the reactions were carried out without the addition of catalytic amounts of
Pd(OAc)2.
When the reactions were carried out for 2 – 2.5 h, no 3-hydroxypropanoates 7 were detected in the
crude mixtures. Separation by prep. TLC gave solid materials identified as products 9, which
subsequently were purified by crystallization from mixtures of PE or pentane with small amounts of
Et2O or iPr2O.
Ethyl 3-Hydroxy-2-(1-methyl-4,5-diphenyl-1H-imidazol-2-yl)propanoate (7a). Yield: 98 mg (28%).
Pale-yellow oil. IR (film): 3355 (OH), 3062, 2981, 2959, 2934, 2248, 1733 (C¼O), 1603, 1507, 1465, 1443,
1301, 1243, 1185, 1072, 1055, 1044, 910, 732, 700, 648. 1H-NMR (CDCl3): 1.34 (t, J ¼ 7.1, MeCH2O); 3.35 (s,
MeN); 3.92 (t, J ¼ 4.0, HOCH2CH); 4.25 – 4.35 (m, MeCH2O); 4.46 (d, J ¼ 4.0, HOCH2CH); 5.16 (br. s,
OH); 7.14 – 7.52 (m, 10 arom. H). 13C-NMR (CDCl3): 14.2 (MeCH2O); 31.0 (MeN); 45.9 (HOCH2CH);
61.7, 63.5 (2 CH2O); 126.4, 126.6, 128.1, 128.8, 129.1, 130.9 (10 arom. CH); 129.4, 130.8, 134.2, 136.3 (2
arom. C, C(4), C(5)); 143.9 (C(2)); 169.8 (C¼O). HR-ESI-MS: 351.1730 ([M þ H]þ, C21H23N2O3þ ; calc.
351.1703).
Ethyl 2-(1-Ethyl-4,5-diphenyl-1H-imidazol-2-yl)-3-hydroxypropanoate (7b). Yield: 120 mg (33%).
Pale-yellow oil. IR (film): 3355 (OH), 3057, 2982, 2937, 2875, 2305, 1736 (C¼O), 1603, 1507, 1473, 1446,
1327, 1266, 1181, 1072, 1045, 1029, 955, 738, 774, 700. 1H-NMR (CDCl3): 1.14 (t, J ¼ 7.2, MeCH2N); 1.34 (t,
J ¼ 7.0, MeCH2O); 3.77 – 3.84 (m, MeCH2N); 3.92 (t, J ¼ 4.0, HOCH2CH); 4.21 – 4.34 (m, MeCH2O);
4.42 (d, J ¼ 4.0, HOCH2CH); 5.22 (br. s, OH); 7.14 – 7.52 (m, 10 arom. H). 13C-NMR (CDCl3): 14.2
(MeCH2O); 15.9 (MeCH2N); 38.7 (MeCH2N); 45.8 (HOCH2CH); 61.7, 62.9 (2 CH2); 126.3, 126.5, 128.0,
128.9, 129.1, 131.1 (10 arom. CH); 128.6, 131.2, 134.2, 136.6 (2 arom. C, C(4), C(5)); 143.2 (C(2)); 170.1
(C¼O). HR-ESI-MS: 365.1870 ([M þ H]þ, C22H25N2O3þ ; calc. 365.1860).
Ethyl 2-(4,5-Diphenyl-1-propyl-1H-imidazol-2-yl)-3-hydroxypropanoate (7c). Yield: 110 mg (29%).
Pale-yellow oil. IR (film): 3351 (OH), 3060, 2970, 2935, 2876, 1736 (C¼O), 1603, 1507, 1470, 1445, 1369,
1239, 1179, 1073, 1046, 1028, 968, 775, 699. 1H-NMR (CDCl3): 0.78 (t, J ¼ 7.4, MeCH2CH2N); 1.34 (t, J ¼
7.1, MeCH2O); 1.47 – 1.54 (m, MeCH2CH2N); 3.68 – 3.71 (m, CH2N); 3.93 (t, J ¼ 4.2, HOCH2CH); 4.27 –
4.32 (m, MeCH2); 4.43 (d, J ¼ 4.2, HOCH2CH); 5.18 (br. s, OH); 7.13 – 7.51 (m, 10 arom. CH). 13C-NMR
(CDCl3): 11.0 (MeCH2CH2N); 14.2 (MeCH2); 23.8 (MeCH2CH2N); 45.5 (CH2N); 45.9 (HOCH2CH);
61.5, 62.9 (2 CH2); 126.3, 126.5, 128.0, 128.8, 129.1, 131.1 (10 arom. CH); 128.0, 131.2, 134.2, 136.5 (2 arom.
C, C(4), C(5)); 143.5 (C(2)); 170.1 (C¼O). HR-ESI-MS: 379.2013 ([M þ H]þ, C23H27N2O3þ ; calc.
379.2016).
Ethyl 2-(4,5-diphenyl-1-(prop-2-en-1-yl)-1H-imidazol-2-yl)-3-hydroxypropanoate (7d). Yield:
100 mg (27%). Pale-yellow oil. IR (film): 3366 (OH), 3058, 2982, 2936, 2868, 1736 (C¼O), 1603, 1508,
1462, 1444, 1370, 1328, 1266, 1181, 1100, 1044, 1030, 924, 775, 738, 701. 1H-NMR (CDCl3): 1.34 (t, J ¼ 7.1,
MeCH2O); 3.86 (t, J ¼ 4.1, HOCH2CH); 4.24 – 4.31 (m, MeCH2O); 4.34 – 4.37 (m, HOCH2CH); 4.38 –
4.42 (m, CH2N); 4.92 (dd, J ¼ 17.0, 0.7, CH2¼CH); 5.20 (dd, J ¼ 10.0, 0.7, CH2¼CH); 5.77 – 5.85 (m,
CH2¼CH); 7.14 – 7.50 (m, 10 arom. CH). 13C-NMR (CDCl3): 14.2 (MeCH2); 45.7 (HOCH2CH); 45.9
(CH2N); 61.7, 62.8 (2 CH2); 117.1 (CH¼CH2); 126.4, 126.6, 128.1, 128.9, 129.0, 131.0, 132.9 (10 arom. CH,
CH¼CH2); 128.0, 131.2, 134.2, 136.5 (2 arom. C, C(4), C(5)); 143.5 (C(2)); 170.0 (C¼O). HR-ESI-MS:
377.1860 ([M þ H]þ, C23H25N2Oþ3 ; calc. 377.1864).
Ethyl 3-(2,3-Dihydro-3-methyl-2-oxo-4,5-diphenyl-1H-imidazol-1-yl)-2-(1-methyl-4,5-diphenyl-1H-
imidazol-2-yl)propanoate (9a). Yield: 60 mg (21%). Pale-yellow crystals. M.p. 193 – 1958 (PE/iPr2O).
IR (KBr): 3057, 2978, 2954, 1736 (C¼O), 1684 (C¼O), 1602, 1505, 1452, 1395, 1368, 1297, 1208, 1156,
1072, 1025, 918, 852, 777, 700, 615, 505. 1H-NMR (CDCl3): 1.23 (t, J ¼ 7.1, MeCH2O); 3.22 (s, MeN); 3.35
(s, MeN); 4.09 – 4.14 (m, 1 H of MeCH2O); 4.17 – 4.23 (m, 1 H of MeCH2O); 4.42 (dd, J ¼ 14.0, 8.2, 1 H of
CH2N); 4.58 (dd, J ¼ 14.0, 7.0, 1 H of CH2N); 4.90 (t, J ¼ 7.5, CH2CH); 7.07 – 7.22 (m, 20 arom. CH).
13C-NMR (CDCl3): 14.1 (MeCH2); 28.8, 31.1 (2 MeN); 42.1 (CH2CH); 42.6 (CH2N); 61.4 (MeCH2);
126.0, 126.8, 127.9, 128.0, 128.4, 128.5, 129.0, 130.1, 130.6, 130.9 (20 arom. CH); 121.5, 121.6, 128.6, 129.0,
129.5, 131.3, 134.7, 137.0, 142.5 (4 arom. C, 2 C(4), 2 C(5), C(2)); 153.9, 169.6 (2 C¼O). HR-ESI-MS:
583.2700 ([M þ H]þ, C37H35N4Oþ3 ; calc. 583.2703).

Helvetica Chimica Acta – Vol. 95 (2012)
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Crystals of 9a suitable for the X-ray crystal-structure determination were grown from CH2Cl2/iPr2O.
Ethyl 3-(2,3-Dihydro-3-ethyl-2-oxo-4,5-diphenyl-1H-imidazol-1-yl)-2-(1-ethyl-4,5-diphenyl-1H-imi-
dazol-2-yl)propanoate (9b). Yield: 70 mg (23%). Pale-yellow crystals. M.p. 165 – 1688 (PE/Et2O). IR
(KBr): 3063, 2979, 2934, 1744 (C¼O), 1674 (C¼O), 1602, 1506, 1446, 1407, 1352, 1302, 1229, 1201, 1061,
1027, 958, 862, 772, 700, 609, 542. 1H-NMR (CDCl3): 1.06 – 1.14 (m, 2 MeCH2N); 1.23 (t, J ¼ 7.1,
MeCH2O); 3.66 – 3.72 (m, 1 H of MeCH2N); 3.72 – 3.77 (m, 1 H of MeCH2N); 3.79 – 3.85 (m, 1 H of
MeCH2N); 3.89 – 3.95 (m, 1 H of MeCH2N); 4.06 – 4.12 (m, 1 H of MeCH2O); 4.19 – 4.24 (m, 1 H of
MeCH2O); 4.40 (dd, J ¼ 14.0, 7.0, 1 H of CH2N); 4.63 (dd, J ¼ 14.0, 8.0, 1 H of CH2N); 4.94 (t, J ¼ 7.4,
CH2CH); 7.08 – 7.49 (m, 20 arom. CH). 13C-NMR (CDCl3): 14.0, 14.7 (2 MeCH2N); 16.2 (MeCH2); 36.6,
38.6 (2 MeCH2N); 41.5 (CH2CH); 43.3 (CH2N); 61.3 (MeCH2); 125.9, 126.7, 127.8, 127.9, 127.9, 128.3,
128.4, 128.5, 129.0, 130.3, 130.5, 130.9 (20 arom. CH); 120.9, 121.8, 128.4, 128.5, 129.3, 131.7, 134.7, 137.3,
142.0 (4 arom. C, 2 C(4), 2 C(5), C(2)); 153.4, 169.6 (2 C¼O). HR-ESI-MS: 611.3020 ([M þ H]þ,
C39H39N4Oþ3 ; calc. 611.3016).
Ethyl 3-(2,3-Dihydro-2-oxo-4,5-diphenyl-3-propyl-1H-imidazol-1-yl)-2-(4,5-diphenyl-1-propyl-1H-
imidazol-2-yl)propanoate (9c). Yield: 50 mg (16%). Pale-yellow crystals. M.p. 136 – 1388 (PE/Et2O).
IR (KBr): 3057, 2965, 2934, 2875, 1740 (C¼O), 1683 (C¼O), 1603, 1505, 1448, 1403, 1367, 1296, 1227,
1196, 1155, 1073, 1027, 918, 868, 775, 699, 645, 616, 509. 1H-NMR (CDCl3): 0.65, 0.67 (2t, J ¼ 7.4, 2
MeCH2CH2N); 1.23 (t, J ¼ 7.1, MeCH2O); 3.58 – 3.84 (m, 2 MeCH2CH2); 4.07 – 4.13 (m, 1 H of
MeCH2O); 4.17 – 4.23 (m, 1 H of MeCH2O); 4.43 (dd, J ¼ 14.0, 8.0, 1 H of CH2N); 4.65 (dd, J ¼ 14.0, 6.7,
1 H of CH2N); 4.90 (t, J ¼ 7.4, CH2CH); 7.07 – 7.49 (m, 20 arom. CH). 13C-NMR (CDCl3): 11.0 (2
MeCH2CH2N); 14.0 (MeCH2); 22.5, 24.0 (2 MeCH2CH2N); 41.6 (CH2CH); 43.2, 43.3 (2 MeCH2CH2N);
45.3 (CH2N); 61.3 (MeCH2); 125.9, 126.8, 127.7, 127.8, 127.9, 128.3, 128.4, 128.5, 128.9, 130.3, 130.6, 131.0
(20 arom. CH); 121.2, 121.8, 128.7, 129.4, 131.8, 134.7, 137.2, 142.4 (4 arom. C, 2 C(4), 2 C(5), C(2)); 153.6,
169.6 (2 C¼O). HR-ESI-MS: 639.3333 ([M þ H]þ, C41H43N4O3þ ; calc. 639.3329).
Ethyl 3-[2,3-Dihydro-2-oxo-4,5-diphenyl-3-(prop-2-en-1-yl)-1H-imidazol-1-yl]-2-[4,5-diphenyl-1-
(prop-2-en-1-yl)-1H-imidazol-2-yl]propanoate (9d): Yield: 65 mg (21%). Pale-yellow crystals. M.p.
132 – 1348 (pentane/Et2O). IR (KBr): 3439, 3061, 3025, 2980, 2923, 1734 (C¼O), 1694 (C¼O), 1602, 1505,
1445, 1396, 1351, 1256, 1228, 1194, 1161, 1098, 1071, 1028, 944, 923, 866, 777, 702, 667, 650, 615, 543, 502.
1H-NMR (CDCl3): 1.20 (t, J ¼ 7.1, MeCH2O); 4.05 – 4.10 (m, 1 H of MeCH2O); 4.15 – 4.20 (m, 1 H of
MeCH2O); 4.20 – 4.30 (m, NCH2CH¼CH); 4.35 – 4.48 (m, NCH2CH¼CH); 4.43 (dd, J ¼ 14.0, 7.5, 1 H of
CH2N); 4.62 (dd, J ¼ 14.0, 7.0, 1 H of CH2N); 4.81 – 4.85 (m, CH2¼CH); 4.97 (dd, J ¼ 10.0, 0.7, 1 H of
CH2¼CH); 5.06 (dd, J ¼ 10.0, 0.7, 1 H of CH2¼CH); 5.09 (t, J ¼ 7.0, CH2CH); 5.73 – 5.83 (m, 2 CH2¼CH);
7.08 – 7.45 (m, 20 arom. CH). 13C-NMR (CDCl3): 14.0 (MeCH2); 41.8 (CH2CH); 43.1, 43.9, 45.8 (3
CH2N); 61.3 (CH2O); 116.6, 116.8 (2 CH2¼CH); 126.0, 126.8, 127.9, 128.01, 128.02, 128.3, 128.4, 128.7,
128.8, 130.4, 130.6, 131.1, 133.3, 133.4 (2 CH2¼CH, 20 arom. CH); 121.3, 121.8, 128.1, 128.5, 129.0, 129.04,
129.1, 131.3 (4 arom. C, 2 C(4), 2 C(5), C(2)); 153.4, 169.5 (2 C¼O). HR-ESI-MS: 635.3011 ([M þ H]þ,
C41H39N4Oþ3 ; calc. 635.3016).
4. Dehydration of 3-Hydroxypropanoate 7b. Experiment A (in the presence of Pd(OAc)2). A soln. of
7b (1 mmol) in NMP (1 ml) was heated in an oil bath at 1108 for 1 h in the presence of a cat. amount (ca.
15 mg) of Pd(OAc)2. Then, the solvent was evaporated by vacuum distillation, and the crude mixture was
separated by prep. TLC (SiO2; PE/AcOEt 3 :2) to give ethyl 2-(1-ethyl-4,5-diphenylimidazol-2-yl)prop-2-
enoate (11b) as a semi-solid material. This quite unstable compound was used for further experiments
with no additional purification. Yield after chromatographic workup: 240 mg (68%). IR (KBr): 3058,
1
2963, 2932, 2872, 1734, 1602, 1506, 1261, 1096, 1024, 803, 773, 696. H-NMR (CDCl3): 1.06 (t, J ¼ 7.2,
MeCH2N); 1.36 (t, J ¼ 7.1, MeCH2O); 3.80 (q, J ¼ 7.2, MeCH2N); 4.34 (q, J ¼ 7.1, MeCH2O); 6.36, 6.79
(2d, J ¼ 1.4, ¼CH2); 7.14 – 7.49 (m, 10 arom. CH). 13C-NMR (CDCl3): 14.2, 19.9 (2 MeCH2); 39.6 (CH2N);
61.5 (CH2O); 126.2, 126.8, 128.0, 128.7 129.0, 131.0 (10 arom. CH); 133.9 (C¼CH2); 129.4, 131.3, 132.9,
134.5, 137.7, 142.9 (2 arom. C, C(2), C(4), C(5), C¼CH2); 165.3 (C¼O). ESI-MS (MeCN): 369 (20, [M þ
Na]þ), 347 (100, [M þ 1])þ. HR-EI-MS (70 eV): 346.1681 (Mþ, C22H22N2Oþ2 ; calc. 346.1687).
Experiment B (in the absence of Pd(OAc)2). A soln. of 7b (1 mmol) in NMP (1 ml) was heated in an
oil bath at 1108 for 1 h. Then, the solvent was evaporated by vacuum distillation, and the crude, oily
1
mixture was analyzed by H-NMR spectroscopy. In this case, 7b was still the main component of the
crude mixture.

584
Helvetica Chimica Acta – Vol. 95 (2012)
5. X-Ray Crystal-Structure Determination of 9a (Table and Fig.)2). All measurements were
conducted on an Agilent Technologies SuperNova area-detector diffractometer [14], with MoKa
radiation (l ¼ 0.71073 ꢅ) from a micro-focus X-ray source, and an Oxford Instruments Cryojet XL
cooler. Data reduction was performed with CrysAlisPro [14]. The intensities were corrected for Lorentz
and polarization effects, and an empirical absorption correction using spherical harmonics [14] was
applied. The space group was uniquely determined by the systematic absences. Equivalent reflections
were merged. The data collection and refinement parameters are compiled in the Table. A view of the
molecule is shown in the Figure. The structure was solved by direct methods using SHELXS97 [15],
which revealed the positions of all non-H-atoms. The non-H-atoms were refined anisotropically. All of
the H-atoms were placed in geometrically calculated positions and refined by using a riding model where
Table. Crystallographic Data for Compound 9a
Crystallized from
CH2Cl2/iPrO2
Empirical formula
Formula weight [g molꢀ1
Crystal color, habit
C37H34N4O3
582.70
colorless, prism
]
Crystal dimensions [mm]
Temp. [K]
0.08 ꢁ 0.20 ꢁ 0.40
160(1)
Crystal system
monoclinic
Space group
P21/c
Z
4
Reflections for cell determination
2q Range for cell determination [8]
9701
4 – 59
Unit cell parameters
a [ꢅ]
b [ꢅ]
c [ꢅ]
b [8]
15.5476(6)
10.0461(3)
19.8750(7)
95.067(3)
3092.20(19)
1.252
0.0805
w
V [ꢅ3]
Dx [g cmꢀ3
]
m(MoKa) [mmꢀ1
Scan type
]
2q(max) [8]
59.1
Transmission factors (min; max)
Total reflections measured
Symmetry independent reflections
Reflections with I > 2s(I)
Reflections used in refinement
Parameters refined
0.731; 1.000
28418
7690
5820
7690
401
Final
R(F) [I > 2s(I) reflections]
wR(F2) (all data)
0.0447
0.1160
Weights
w ¼ [s2(F2o ) þ (0.0484P)2 þ 0.9470P]ꢀ1
where P ¼ (F2o þ 2Fc2 )/3
1.030
Goodness of fit
Secondary extinction coefficient
Final Dmax/s
0.0026(5)
0.001
0.30; ꢀ 0.20
D1 (max; min) [e ꢅꢀ3
]
2
)
CCDC-859644 contains the supplementary crystallographic data for this contribution. These data
can be obtained free of charge from the Cambridge Crystallographic Data Centre, via
www.ccdc.cam.ac.uk/data_request/cif.

Helvetica Chimica Acta – Vol. 95 (2012)
585
each H-atom was assigned a fixed isotropic displacement parameter with a value equal to 1.2 Ueq of its
parent C-atom (1.5 Ueq for the Me groups). The refinement of the structure was carried out on F2 by using
full-matrix least-squares procedures, which minimized the function Sw(F2o – Fc2 )2. A correction for
secondary extinction was applied. Neutral-atom scattering factors for non-H-atoms were taken from
[16a], and the scattering factors for H-atoms were taken from [17]. Anomalous dispersion effects were
included in Fc [18]; the values for f’ and f’’ were those of [16b]. The values of the mass attenuation
coefficients are those of [16c]. The SHELXL97 program [15] was used for all calculations.
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Received December 28, 2011