Reactions of 2-unsubstituted 1H-imidazole 3-oxides with 2,2-bis(trifluoromethyl)ethene-1,1-dicarbonitrile: A stepwise 1,3-dipolar cycloaddition

Article abstract of DOI:10.1002/hlca.200690129

The reaction of 1,4,5-trisubstituted 1H-imidazole-3-oxides 1 with 2,2-bis(trifluoromethyl)ethene-1,1-dicarbonitrile (7, BTF) yielded the corresponding 1,3-dihydro-2H-imidazol-2-ones 10 and 2-(1,3-dihydro-2H-imidazol- 2-vlidene)malononitriles 11, respectiv

Full text of DOI:10.1002/hlca.200690129

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Helvetica Chimica Acta – Vol. 89 (2006)
Reactions of 2-Unsubstituted 1H-Imidazole 3-Oxides with 2,2-
Bis(trifluoromethyl)ethene-1,1-dicarbonitrile: A Stepwise 1,3-Dipolar
Cycloaddition
by Grzegorz Mloston´*a), Marcin Jasin´ski1)a), Anthony Lindenb), and Heinz Heimgartner*b)
a
´
) University of Łódz, Department of Organic and Applied Chemistry, Narutowicza 68,
´
PL-90-136 Łódz
b) Organisch-chemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich
(phone: +41446354282; fax: +41446356836; e-mail: heimgart@oci.unizh.ch)
The reaction of 1,4,5-trisubstituted 1H-imidazole-3-oxides 1 with 2,2-bis(trifluoromethyl)ethene-1,1-
dicarbonitrile (7, BTF) yielded the corresponding 1,3-dihydro-2H-imidazol-2-ones 10 and 2-(1,3-dihydro-
2H-imidazol-2-ylidene)malononitriles 11, respectively, depending on the solvent used. In one example, a
1:1 complex, 12, of the 1H-imidazole 3-oxide and hexafluoroacetone hydrate was isolated as a second
product. The formation of the products is explained by a stepwise 1,3-dipolar cycloaddition and subse-
quent fragmentation. The structures of 11d and 12 were established by X-ray crystallography.
1. Introduction. – Imidazole N-oxides are interesting compounds with respect to
their applications as building blocks in the synthesis of imidazole derivatives [1–3]
and for their diverse biological activities [4–6]. Convenient syntheses of 2-unsubsti-
tuted imidazole N-oxides are condensations of a-(hydroxyimino) ketones with in situ
generated formimides [7], of a-amino oximes with orthoformates [8], and of diimines
with formaldoxime [9]. Generally, imidazole N-oxides are not available by direct oxi-
dation of the parent compound. However, a recent paper describes the preparation of
1-methylimidazole N3-oxide by treatment of 1-methyl-1H-imidazole in THF with H2O2
at room temperature [10]. Starting with imidazole N-oxides, preparations of imidazole-
2-thiones [7], 2-cyanoimidazoles [11], as well as parent imidazoles via deoxygenation
with PCl3 [12] were reported. Furthermore, the isomerization to give imidazol-2-ones
can easily be achieved by treatment with Ac2O [11] or photochemically [13].
The structure of 2-unsubstituted imidazole N-oxides relates to aldonitrones, which
are well-known 1,3-dipoles. In fact, they react with dipolarophiles, such as dimethyl ace-
tylenedicarboxylate [2][12], isocyanates, and isothiocyanates [2], as well as with thioke-
tones and thioketenes [7] to give finally products, which result from subsequent conver-
sions of the initially formed [2+3] cycloadducts. Of special mechanistic interest is the
reaction of 1a with thioketene 2, in which the formation of two sets of products, i.e., 3a/4
and 5/6 is an indication for the stepwise reaction pathway [7] (Scheme 1). The reaction
of the dipole 1a with the heterocumulene 2 leads to the zwitterionic intermediate A, in
which the formation of the five-membered unstable cycloadduct (Route a) competes
1
´
)
Part of the planned Ph.D. thesis of M. J., University of Łódz.
© 2006 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta – Vol. 89 (2006)
1305
Scheme 1
with the cyclization to yield thiirane 4 (Route b). Cycloreversion of the cycloadduct
leads to 5 and 6. These results prompted us to test other dipolarophiles in reactions
with 1H-imidazole 3-oxides of type 1. The electron-deficient 2,2-bis(trifluoromethyl)-
ethene-1,1-dicarbonitrile (7; BTF) was selected for the present study.
Apart from the fact that 7 has been used extensively in Diels–Alder reactions [14]
and in [2+2] cycloadditions [15], to the best of our knowledge, no [2+3] cycloadditions
with this dipolarophile have been reported.
2. Results and Discussion. – According to the previously described procedure, five
known and three new 1H-imidazole 3-oxides of type 1 were prepared by heating mix-
tures of a-(hydroxyimino) ketones 8 and the corresponding hexahydro-1,3,5-triazines
9, the trimers of the corresponding formimines, in EtOH (Scheme 2).
Scheme 2
All prepared compounds 1b–1i were isolated as colorless crystals, which contained
variable amounts of H2O. Removal of H2O was neither possible by drying under
reduced pressure nor by azeotropic distillation with toluene, because of the thermal
instability of 1, which was converted into the corresponding 2H-imidazol-2-ones. The
1H-imidazole 3-oxide hydrates of type 1·H2O showed a characteristic singlet at ca.
7.8–8.2 ppm in the 1H-NMR spectra. When the spectra were recorded from a solution

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Helvetica Chimica Acta – Vol. 89 (2006)
in CD3
exchange)2).
As mentioned in the Introduction, the transformation of N-oxides of type 1 into the
ACHTREUNG
parent imidazoles was typically carried out by treatment with PCl3 [1][3][12]. In our
laboratory, N-oxides 1 were deoxygenated by using freshly prepared Raney-Ni [16]
in EtOH at room temperature, and the corresponding imidazoles were obtained in
almost quantitative yield (e.g., 1b ! 3b (R1 =R2 =Me), 1d ! 3d (R1 =Ph, R2 =Bn)).
The first experiments with BTF (7) were carried out in CH2Cl2 with the N-oxides 1
as hydrates. The conversions were completed within ca. 15 min at room temperature.
The major product obtained in these reactions was the corresponding 1,3-dihydro-
2H-imidazol-2-one 10 (Scheme 3). In addition, small amounts of (1,3-dihydro-2H-imi-
dazol-2-ylidene)malononitriles 11 were detected. Carrying out the same reaction in
MeOH solution, compounds 11 were formed as the main products. Fractional crystal-
lization of the mixtures gave 11 as colorless or pale-yellow crystals. Unexpectedly, in the
experiment with 1d, in addition to 11d, the complex of the starting material with hexa-
fluoroacetone hydrate, depicted as structure 12 in Scheme 3, was isolated by concentra-
tion of the mother liquor and recrystallization of the residue from CH2Cl2.
Scheme 3
1,3-Dihydro-2H-imidazol-2-ones of type 10 are well documented compounds, and
the identification of 10b–10i was possible on the basis of their spectroscopic and ana-
lytical data as well as by comparison with original samples. The malononitrile deriva-
tives 11 are less well known. Their IR spectra (KBr) show two intense absorption
bands of the CN groups located at ca. 2195 and 2155 cmꢀ1. In the 13C-NMR spectra
((D6)DMSO or CDCl3), the C-atoms of the exocyclic formal C=C bond absorb at
148–146 ppm (C(2)) and 26–23 ppm (=C(CN)2), which is characteristic of this type
of ‘push-pull’ system [17][18]. These chemical shifts indicate a highly zwitterionic char-
acter of these compounds in solution, resulting in a low rotational barrier about the
exocyclic C=(CN)2 bond [17]. In accordance with this interpretation is the fact that
only one CN signal appears in the 13C-NMR spectrum. In the case of 12, the IR spec-
2
)
Very fast H/D exchange was observed in basic aqueous solution, whereas it was slow in the presence
of DCl [8].

Helvetica Chimica Acta – Vol. 89 (2006)
1307
trum showed the presence of a series of strong and broad absorption bands between
3400 and 2374 cmꢀ1, which were attributed to the associated OꢀH bonds. Another
1
strong absorption at 1213 cmꢀ1 revealed the presence of the CF3 group. In the H-
NMR spectrum recorded from a solution in CD3
C(2) of the imidazole ring occurred at 8.48 ppm and was downfield-shifted compared
with the corresponding signal in 1d.
A
Finally, the molecular structures of 11d and 12 were established by single-crystal X-
ray diffraction analysis (Figs. 1 and 2).
The asymmetric unit in the structure of 11d contains one molecule of the heterocy-
cle plus one highly disordered MeOH molecule. The disorder of the MeOH molecule
could not be modelled adequately. Therefore, the contribution of the solvent molecules
to the intensity data was removed by using the SQEEZE [20] routine of the PLATON
program [21]. The NH group of 11d forms an intermolecular H-bond with the N-atom
of one of the CN groups of a neighboring molecule. In turn, the acceptor molecule
donates the same type of H-bond back to the original molecule, therefore, forming cen-
trosymmetric dimers where the H-bonds form a closed loop with a graph set motif [22]
of R22(12). The five-membered heterocycle is almost planar, and the adjacent atoms
C(13), C(16), and C(22) deviate only slightly from this plane. The intraannular C,N-
Fig. 1. ORTEP Plot [19] of the molecular structure of 11d (arbitrary numbering of the atoms; 50%
probability ellipsoids)

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Helvetica Chimica Acta – Vol. 89 (2006)
Fig. 2. a) ORTEP Plot [19] of the molecular structure of 12 (arbitrary numbering of the atoms; 50%
probability ellipsoids) and b) packing diagram

Helvetica Chimica Acta – Vol. 89 (2006)
1309
bonds (N1),C(2) and N(3),C(2)) are short (1.349(2) and 1.346(2) Å, resp.); the bond
lengths are close to those of C=N bonds (ca. 1.30 Å). Similarly, the C,C-bonds to the
CꢁN groups, i.e., C(13),C(14) and C(13),C(15), show significant double-bond character
(1.406(2) and 1.408(2) Å, resp.). On the other hand, the formal C(2),C(13) double-bond
is rather long (1.426(2) Å). These data support a zwitterionic structure with the positive
charge delocalized between N(1),C(2), and N(3), and the negative one between
CN(14), C(13), and CN(15). Surprisingly, the plane of the malonodinitrile moiety is
twisted only slightly out of the heterocyclic plane (dihedral angle N(1)ꢀC(2)ꢀ
C(13)ꢀC(14)=ꢀ15.78).
There is one molecule of the zwitterionic oxide and one molecule of hexafluoropro-
pane-2,2-diol (hexafluoroacetone hydrate) in the asymmetric unit of structure 12. The
OH groups form intermolecular H-bonds with the oxide O-atom of two different zwit-
terions, so that each zwitterion accepts a H-bond at the same atom from two different
ketone hydrates. These interactions together link two zwitterions and two ketone
hydrates to give centrosymmmetric tetramers where the H-bonds form a closed loop
with a graph set motif of R24(12).
Reaction mechanisms for the formation of the imidazole derivatives 10 and 11 are
proposed in Scheme 4. The key intermediate is the zwitterion B, which is formed by a
nucleophilic addition of 1 onto 7. In CH2Cl2, B reacts with the H2O of the hydrate to
give C, which undergoes a subsequent fragmentation to yield 10. As the second prod-
uct, we postulate the adduct 13 of H2O and 7, which, however, could not be detected
after workup. The conversion of B to 11 in MeOH solution occurs via a 1,5-dipolar elec-
trocyclization, which yields the ‘cycloadduct’ D. Subsequent cleavage of the NꢀO
bond, followed by a retro-ene reaction finally leads to 11 and hexafluoroacetone,
which is immediately captured by H2O. The different reaction course in CH2Cl2 and
in MeOH is remarkable. A likely interpretation is the higher nucleophilicity of H2O
in an aprotic solvent like CH2Cl2 compared with MeOH, which reduces the nucleophi-
licity by solvation.
As shown in Scheme 4, H2O plays an important role in the formation of products in
the reaction of 1 and 7. For this reason, the reaction was repeated with anhydrous N-
oxides 1, which were prepared by drying the corresponding hydrates with activated
molecular sieves in CHCl3. Under these conditions, the (1,3-dihydro-2H-imidazol-2-yli-
dene)malononitriles 11 were formed in high yield (Scheme 4). Neither 1,3-dihydro-2H-
imidazol-2-ones 10 nor complexes of type 12 were present in the reaction mixtures.
In conclusion, the present study shows that 1H-imidazole 3-oxides 1 easily react
with BTF (7). Although the formation of products 11 can be explained by a formal

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Helvetica Chimica Acta – Vol. 89 (2006)
Scheme 4
[2+3] cycloaddition to give D the formation of 1,3-dihydro-2H-imidazol-2-ones 10 (in
the reaction involving H2O) clearly indicate a stepwise reaction mechanism. The com-
mon intermediate in the formation of all products is the zwitterion B, which is the prod-
uct of the regioselective attack of the ‘nitrone-like’ dipolar species 1 on 7. This reaction
can be regarded as the initial step of a Michael addition, thus leading to the activation of
C(2) of the imidazolium ring. In the light of these results, the combination 1/7 fulfils the
fundamental requirement for a stepwise course of a [2+3] cycloaddition, i.e., an elec-
tron-rich 1,3-dipole approaches an electron deficient dipolarophile [23][24].
The formation of 11 under anhydrous conditions can be of preparative importance
as derivatives of (1,3-dihydro-2H-imidazol-2-ylidene)malononitriles are known as
pharmacologically active compounds [25].
We thank the analytical sections of our institutes for spectra and analyses and F. Hoffmannn-La
Roche AG, Basel, for financial support. G. M. and M. J. acknowledge the financial support by the Polish
State Committee for Scientific Research (KBN-Grant No. PBZ-KBN-126/T09/12).
Experimental Part
1. General. M.p.: Melt-Temp. II apparatus (Aldrich); in capillaries; uncorrected. IR Spectra (KBr):
NEXUS FT-IR spectrophotometer; in KBr. 1H- and 13C-NMR spectra: Tesla BS567A (80 and 20 MHz,
resp.) or Bruker AC 300 instrument (300 and 75.5 MHz, resp.); in CDCl3, TMS as an internal standard.

Helvetica Chimica Acta – Vol. 89 (2006)
1311
The multiplicity of the 13C-NMR signals was deduced from the DEPT spectra. MS (EI or CI): Finnigan
MAT-90 or Finnigan SSQ-700 instruments. Elemental analyses were performed in the Analytical Labo-
ratory of the University of Zürich or in the Laboratory of the Polish Academy of Sciences (CBMiMM) in
´
Łódz.
2. Starting Materials. a-(Hydroxyimino) ketones 8 were obtained according to known protocols:
R1 =Me [26], R1 =Ph [27]. 1,3,5-Trisubstituted hexahydro-1,3,5-trizines 9 were prepared according to
known methods: R2 =Me [28], R2 =Bn [29], R2 =cHex (cyclohexyl) [30], R2 =cPr (cyclopropyl) [31],
and R2 =allyl [32].
3. Preparation of 1H-Imidazole 3-Oxides (1): Syntheses and properties of the N-oxides 1b–1f have
already been described [7][11][33]. Compounds 1g–1i, which have not been described so far, were pre-
pared by heating 1.2 mmol of the corresponding 1,3,5-hexahydrotriazine 9 with 1.0 mmol of 3-(hydroxy-
imino)-3-phenylpropan-2-one (8, R1 =Me) and a-benzil monoxime (8, R1 =Ph), respectively, in boiling
EtOH. After removal of the solvent in vacuo, the resulting mixture was treated with Et2O, cooled, then
N
the product was filtered, washed with cold acetone, and recrystallized. In the case of 1-allyl-4,5-diphenyl-
1H-imidazole 3-oxide (1i), the mixture also contained the isomeric 1,3-dihydro-2H-imidazol-2-one, which
was formed as a side product, and the separation of both compounds was achieved by column chroma-
tography (SiO2; AcOEt).
1-Cyclopropyl-5-methyl-4-phenyl-1H-imidazole 3-Oxide (1g): 3 h; yield: 199 mg (93%). Colorless
needles. M.p. 172–1748 (acetone). IR: 3063s, 3020m, 2961s (br.), 1619m (br.), 1594m, 1497m, 1445m,
1422s, 1386vs, 1374vs, 1317m, 1258m, 1219s, 1150m, 1064w, 1036m, 894m, 843m, 825s, 769m, 755s, 697s
1
(br.). H-NMR: 7.27 (s, HꢀC(2)); 6.78–6.76, 6.60–6.47 (2m, 5 arom. H); 2.36–2.31 (m, 1 H of cPr);
1.50 (s, Me); 0.29–0.15 (m, 4 H of cPr). 13C-NMR: 129.9, 127.0, 124.4 (3s, arom. Cq, C(4), C(5)); 129.4,
128.2, 128.1 (3d, 5 arom. CH); 125.6 (d, C(2)); 27.0 (d, CH of cPr); 9.7 (q, Me); 6.4 (t, 2 CH2 of cPr).
EI-MS: 214 (100, M+C), 198 (62), 197 (67), 130 (30). Anal. calc. for C13
A
N2
O. = H O (216.52): C
1
8
2
72.12, H 6.63, N 12.94; found: C 72.09, H 6.57, N 12.93.
5-Methyl-4-phenyl-1-(prop-2-enyl)-1H-imidazole 3-Oxide (1h): 2 h; yield: 191 mg (89%). Colorless
crystals. M.p. 164–1678 (CH2Cl2/Et2O). IR: 3093w, 3063s, 3031m, 2980s, 2940vs, 1640m, 1626m, 1497m,
AHCTREUNG
1456m, 1428s, 1384vs, 1361m, 1348m, 1317m, 1268s, 1220s, 1142w, 932s, 852m, 836m, 762s, 719s, 699s.
1H-NMR: 7.91 (s, HꢀC(2)); 7.68–7.31 (m, 5 arom. H); 5.97–5.84 (m, ꢀCH=); 5.35–5.12 (m, =CH2);
4.48–4.46 (m, CH2N); 2.23 (s, Me). 13C-NMR: 131.3 (d, ꢀCH=); 130.5, 127.4, 122.5 (3s, arom. Cq,
C(4), C(5)); 129.7, 128.4, 128.2 (3d, 5 arom. CH); 124.9 (d, C(2)); 119.1 (t, =CH2); 48.0 (t, CH2); 9.3
(q, Me). CI-MS: 215 (100, [M+1]+), 199 (39). Anal. calc. for C13H14N2O (214.27): C 72.87, H 6.59, N
13.07; found: C 72.68, H 6.57, N 13.09.
4,5-Diphenyl-1-(prop-2-enyl)-1H-imidazole 3-Oxide (1i): 5 h; yield: 201 mg (73%). Colorless solid.
M.p. 176–1808 (CH2Cl2/Et2O). IR: 3065s, 3024m, 2991s, 2975s, 2935m, 1621m (br.), 1603m, 1585m,
G
1585m, 1507m, 1483s, 1458m, 1445s, 1423m, 1328s, 1344s, 1320m, 1306m, 1269m, 1208m, 1183m,
1
1077m, 1051m, 1024m, 993m, 955m, 944m, 930m, 814m, 769vs, 715vs, 704vs, 698vs. H-NMR: 8.07 (s,
HꢀC(2)); 7.58–7.24 (m, 10 arom. H); 5.93–5.80 (m, ꢀCH=); 5.33–5.15 (m, =CH2); 4.42–4.40 (m,
CH2N). 13C-NMR: 131.7 (d, ꢀCH=); 130.7, 129.6, 129.1, 128.1 (4d, 10 arom. CH); 130.8, 127.4, 127.1,
127.0 (4s, 2 arom. Cq, C(4), C(5)); 125.8 (d, C(2)); 119.6 (t, =CH2); 48.3 (t, CH2). CI-MS: 277 (63,
[M+1]+), 261 (100). Anal. calc. for C18H16N2O (276.34): C 78.24, H 5.84, N 10.14; found: C 78.10, H
5.85, N 10.11.
3. Deoxygenation of 1H-Imidazole 3-Oxides 1 with Raney-Ni. General Procedure. To a magnetically
stirred soln. of 1b (188 mg, 1.0 mmol) in EtOH (2 ml), a suspension of freshly prepared Raney-Ni [16] in
EtOH was added portionwise in intervals of ca. 10 min, until the conversion of the starting material was
complete (TLC). Then, the mixture was filtered in order to remove the black Ni precipitate, and the fil-
trate was evaporated to dryness. Imidazole 3b was obtained as pure material (1H-NMR). Analogous
treatment of 1d with Raney-Ni at r.t. yielded pure 3d.
1,5-Dimethyl-4-phenyl-1H-imidazole (3b): Yield: 165 mg (96%). Colorless oil [34]. IR (neat):
3150–2850m (br.), 1717m, 1663m, 1604s, 1580m, 1563w, 1508s, 1495s, 1472m, 1444s, 1423m, 1379s,
1
1320w, 1303w, 1239s, 1165m, 1138m, 1071m, 1012m, 939m, 772s, 739m, 703s, 632s. H-NMR: 7.73–7.10
(m, HꢀC(2), 5 arom. H); 3.57 (s, MeN); 2.38 (s, Me).

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Helvetica Chimica Acta – Vol. 89 (2006)
1-Benzyl-4,5-diphenyl-1H-imidazole (3d): Yield: 300 mg (97%). Colorless solid. M.p. 112–1158
([35]: 113–1158). IR: 3150–2950m (br.), 1602s, 1506s, 1497s, 1477m, 1455s, 1443s, 1433m, 1359s, 1254s,
1
1193m, 1068m, 1027m, 955s, 915m, 828m, 794s, 774s, 760vs, 724vs, 698vs, 668m, 654s. H-NMR: 7.81 (s,
HꢀC(2)); 7.67–6.75 (m, 15 arom. H); 4.98 (s, PhCH2).
4. Synthesis of 1,3-Dihydro-2H-imidazol-2-ones (10). General Procedure. To a magnetically stirred
soln. of 1.0 mmol 1H-imidazole 3-oxide 1 (hydrates with variable amounts of H2O) in ca. 10 ml of
CH2Cl2, a soln. of 2,2-bis(trifluoromethyl)ethene-1,1-dicarbonitrile (7, BTF) (235 mg, 1.1 mmol) in
CH2Cl2 (4 ml) was added dropwise at r.t., and stirring was continued for 20 min. Then, the solvent was
evaporated and the semi-solid residue was triturated with Et2O to give a colorless, crystalline material,
G
which was identified as 10, contaminated with traces of the corresponding 11. Purification of the main
product was achieved by crystallization from MeOH or from a mixture of hexane and CH2Cl2.
1,3-Dihydro-1,5-dimethyl-4-phenyl-2H-imidazol-2-one (10b). Yield: 118 mg (63%). Colorless crys-
tals. M.p. (decomp.) 246–2498 (MeOH; [11]: 246–2518). IR: 3200–2800m (br., NH), 1675vs (C=O),
1599m, 1503m, 1468m, 1434m, 1396m, 1384m, 845m, 766m, 745m, 700m, 666m. 1H-NMR (CD3
7.48–7.15 (m, 5 arom. H); 3.22 (s, MeN); 2.21 (s, Me).
A
1,3-Dihydro-1-methyl-4,5-diphenyl-2H-imidazol-2-one (10c). Yield: 182 mg (73%). Colorless crys-
tals. M.p. (dec.) 284–2878 (MeOH; [11]: 286–2908). IR: 3200–2640m (br. NH); 1679vs (C=O); 1604s,
1
1507s, 1455s, 1432m, 1390s, 1024m, 955m, 866m, 834m, 768s, 746m, 723m, 698s, 668m. H-NMR: 9.53
(br. s, NH); 7.55–7.25 (m, 5 arom. H); 7.16 (br. s, 5 arom. H); 3.14 (s, Me).
1-Benzyl-1,3-dihydro-4,5-diphenyl-2H-imidazol-2-one (10d). Yield: 257 mg (79%). Colorless crys-
tals. M.p. (dec.) 221–2268 (MeOH; [31]: 176–1788). IR: 3200–2800s (br., NH), 1686vs (C=O), 1604m,
1
1508m, 1497m, 1445s, 1400s, 1345m, 1075w, 935w, 769s, 746m, 720m, 696s, 667m. H-NMR (CD3
7.36–6.87 (m, 10 arom. H); 7.17 (br. s, 5 arom. H); 4.78 (s, CH2N).
A
1-Cyclohexyl-1,3-dihydro-4,5-diphenyl-2H-imidazol-2-one (10f). Yield: 229 mg (72%). Colorless
crystals. M.p. (dec.) 287–2908 (EtOH; [11]: 286–2908). IR: 3200–2800s (br., NH), 1674vs (C=O),
1603m, 1507m, 1444m (br.), 1375s, 1351m, 800m, 763s, 752m, 702s, 692s, 666m. 1H-NMR (CD3
OD):
G
7.58–7.24 (m, 5 arom. H); 7.12 (br. s, 5 arom. H); 3.65–3.43 (m, 1 H of cHex); 2.55–0.80 (m, 10 H of
cHex).
1-Cyclopropyl-1,3-dihydro-5-methyl-4-phenyl-2H-imidazol-2-one (10g). Yield: 154 mg (72%). Col-
orless crystals. M.p. (dec.) 198–2008 (CH2Cl2/hexane). IR: 3150–2750m (br., NH), 1679vs (C=O),
1642m, 1602m, 1504m, 1456m, 1414m, 1374m, 1032m, 835m, 763s, 747s, 698m. 1H-NMR: 9.62 (br. s,
NH); 7.43–7.22 (m, 5 arom. H); 2.74–2.67 (m, 1 H of cPr); 2.32 (s, Me); 1.04–1.01 (m, 4 H of cPr).
13C-NMR: 154.8 (s, C=O); 130.5, 117.7, 117.2 (3s, arom. Cq, C(4), C(5)); 128.8, 126.7, 126.1 (3d, 5
arom. CH); 22.9 (d, CH of cPr); 10.3 (q, Me); 6.7 (t, 2 CH2 of cPr). CI-MS: 216 (14), 215 (100,
[M+1]+), 214 (5, M+C). Anal. calc. for C13H14N2O (214.27): C 72.87, H 6.59, N 13.07; found: C 71.75,
H 6.09, N 12.72.
1,3-Dihydro-5-methyl-4-phenyl-1-(prop-2-enyl)-2H-imidazol-2-one (10h). Yield: 141 mg (66%). Col-
orless crystals. M.p. (dec.) 183–1848 (MeOH). IR: 3200–2650m (br., NH), 1694vs (C=O), 1640s, 1599m,
1503m, 1458m, 1430m, 1408s, 1386m, 1345m, 937m, 923m, 843m, 764s, 741s, 701m, 669m. 1H-NMR: 10.68
(br. s, NH); 7.44–7.20 (m, 5 arom. H); 5.98–5.85 (m, ꢀCH=); 5.20–5.09 (m, =CH2); 4.35–4.32 (m, CH2);
2.22 (s, Me). 13C-NMR: 154.1 (s, C=O); 133.4 (d, ꢀCH=); 128.7, 126.5, 126.0 (3d, 5 arom. CH); 130.4,
117.8, 115.8 (3s, arom. Cq, C(4), C(5)); 116.2 (t, =CH2); 42.8 (t, CH2); 9.7 (q, Me). CI-MS: 215 (100,
[M+1]+), 214 (5, M+C), 188.2 (8). Anal. calc. for C13H14N2O (214.27): C 72.87, H 6.59, N 13.07; found:
C 72.87, H 6.53, N 12.98.
1,3-Dihydro-4,5-diphenyl-1-(prop-2-enyl)-2H-imidazol-2-one (10i): Yield: 226 mg (82%). Colorless
crystals. M.p. (dec.) 218–2218 (MeOH). IR: 3200–2800m (br., NH), 1682vs (C=O), 1647m, 1571m,
1507w, 1444w, 1430w, 1394m, 1370w, 1358w, 1143w, 939w, 921w, 768m (br.), 705m, 694m, 667m. 1H-
NMR ((D6)DMSO): 10.84 (br. s, NH); 7.51–7.20 (m, 10 arom. H); 5.79–5.66 (m, ꢀCH=); 5.07–4.82
(m, =CH2); 4.10–4.05 (m, CH2N). 13C-NMR: 152.8 (s, C=O); 133.8 (d, ꢀCH=); 130.5, 128.8, 128.7,
128.2, 126.4, 125.3 (6d, 10 arom. CH); 129.5, 120.3, 117.2 (3s, 2 arom. Cq, C(4), C(5)); 115.7 (t, =CH2);
42.3 (t, CH2). CI-MS: 277 (100, [M+1]+), 276 (18), 235 (5). Anal. calc. for C18H16N2O (276.34): C
78.24, H 5.84, N 10.14; found: C 77.89, H 5.76, N 10.15.

Helvetica Chimica Acta – Vol. 89 (2006)
1313
5. Synthesis of 2-(1,3-Dihydro-2H-imidazol-2-ylidene)propanedinitrile (11). General Procedure. To a
stirred soln. of 1.0 mmol 1H-imidazole 3-oxide 1 (anh. form, obtained by drying over freshly activated
molecular sieves (4 Å)) in ca. 10 ml of dry CHCl3, a soln. of 7 (235 mg, 1.1 mmol) in CHCl3 (3 ml) was
added dropwise at r.t., and stirring was continued for 20 min. The solvent was evaporated i.v., and the
residue was triturated with ca. 3 ml of Et2O. The colorless solid was filtered and purified by recrystalli-
G
zation from MeOH.
2-(1,3-Dihydro-1,5-dimethyl-4-phenyl-2H-imidazol-2-ylidene)propanedinitrile (11b). Yield: 111 mg
(47%). Pale violet crystals. M.p. (dec.) 219–2238 (MeOH). IR: 3250–2800s (br., NH), 2198vs (CN),
1
2157vs (CN), 1640m, 1589vs (C=C(CN)2), 1503m, 1488s, 1442m, 1421m, 1218w, 1141w, 767s, 697s. H-
NMR ((D6)DMSO): 7.48 (br. s, 5 arom. H); 3.57 (s, MeN); 2.24 (s, Me). 13C-NMR ((D6)DMSO): 146.1
(s, C=C(CN)2); 128.6, 128.2, 127.9 (3d, 5 arom. CH); 124.7 124.1 (2s, arom. Cq, C(4), C(5)); 120.3 (s,
C=C(CN)2); 31.5 (q, MeN); 22.4 (s, C=C(CN)2); 9.0 (q, Me). EI-MS: 236 (100, M+C), 221 (27), 196
(69), 130 (23), 77 (24).
2-(1-Benzyl-1,3-dihydro-4,5-diphenyl-2H-imidazol-2-ylidene)propanedinitrile (11d). Yield: 182 mg
(49%). Pale yellow crystals. M.p. (dec.) 198–2038 (MeOH). IR: 3200–2800m (br., NH), 2198vs (CN),
2164vs (CN), 1640m, 1597m, 1580vs (C=C(CN)2), 1506w, 1497w, 1470m, 1452m, 1431m, 1344w (br.),
1
1227w, 769m, 731m, 698s. H-NMR: 11.28 (br. s, NH); 7.47–6.96 (m, 10 arom. H); 7.25 (br. s, 5 arom.
H); 5.23 (s, CH2). 13C-NMR: 148.4 (s, C=C(CN)2); 135.1 (s, arom. Cq); 131.0, 130.0, 129.2, 128.7, 128.6,
127.9, 127.1, 126.4 (8d, 15 arom. CH); 127.7, 126.7, 126.6, 126.5 (4s, 2 arom. Cq, C(4), C(5)); 119.5 (s,
C=C(CN)2); 47.6 (t, CH2); 26.7 (s, C=C(CN)2). CI-MS: 376 (29), 375 (100, [M+1]+), 285 (9).
Suitable crystals for the X-ray crystal-structure determination of 11d were obtained from MeOH by
slow evaporation of the solvent.
2-(1-Cyclohexyl-1,3-dihydro-5-methyl-4-phenyl-2H-imidazol-2-ylidene)propanedinitrile
(11e).
Yield: 133 mg (44%). Colorless needles. M.p. (dec.) 255–2568 (MeOH). IR: 3200–2850s (br., NH),
2196vs (CN), 2156vs (CN), 1645m, 1599m, 1570vs (C=C(CN)2), 1496w, 1457m, 1439m, 1340w, 1273w,
1237w, 818w, 769m, 701m. 1H-NMR ((D6)DMSO): 7.47 (br. s, 5 arom. H); 4.49–4.35 (m, 1 H of
cHex); 2.36 (s, Me); 2.06–1.85, 1.70–1.62, 1.41–1.19 (3m, 10 H of cHex). 13C-NMR ((D6)DMSO):
146.0 (s, C=C(CN)2); 128.5, 128.4 (2d, 5 arom. CH); 127.6, 126.8, 123.3 (3s, arom. Cq, C(4), C(5));
120.9 (s, C=C(CN)2); 57.7 (d, CH of cHex); 30.7, 25.7, 21.2 (3t, 5 CH2 of cHex); 24.3 (s, C=C(CN)2);
11.4 (q, Me). EI-MS: 304 (11, M+C), 222 (100), 197 (10), 77 (18), 55 (33).
2-(1-Cyclohexyl-1,3-dihydro-4,5-diphenyl-2H-imidazol-2-ylidene)propanedinitrile (11f). Yield: 193
mg (53%). Colorless crystals. M.p. (dec.) 278–2858 (MeOH). IR: 3250–2800s (br., NH), 2198vs (CN),
2161vs (CN), 1636m, 1596s, 1572vs (C=C(CN)2), 1504m, 1451s, 1435s, 1407m, 1336w, 1226w, 1224m,
1
1111w, 1074w, 1018w, 894w, 792m, 773s, 749m, 700vs. H-NMR: 7.55–7.07 (m, 10 arom. H); 4.43–4.33
(m, 1 H of cHex); 1.95–0.77 (m, 10 H of cHex). 13C-NMR: 148.8 (s, C=C(CN)2); 133.1, 131.3, 130.2,
129.8, 128.6 (5d, 10 arom. CH); 132.6, 130.0, 128.9, 127.0 (4s, 2 arom. Cq, C(4), C(5)); 122.5 (s, C=
C(CN)2); 61.3 (d, CH of cHex); 33.9, 27.2, 25.9 (3t, 5 CH2 of cHex); 24.8 (s, C=C(CN)2). CI-MS: 368
(28), 367 (100, [M+1]+), 342 (6), 319 (5). Anal. calc. for C24H22N4 (366.47): C 78.66, H 6.05, N 15.29;
found: C 78.37, H 6.02, N 15.25.
2-(1-Cyclopropyl-1,3-dihydro-5-methyl-4-phenyl-2H-imidazol-2-ylidene)propanedinitrile
(11g).
Yield: 120 mg (46%). Pale yellow crystals. M.p. (dec.) 241–2448 (MeOH). IR: 3250–2850s (br., NH),
2193vs (CN), 2155vs (CN), 1647m, 1603m, 1575vs (C=C(CN)2), 1503s, 1473m, 1447m, 1435m, 1416m,
1369m, 1330w (br.), 1229w, 1107w, 1038m, 1012w, 843m, 769s, 742m, 710m, 696s, 666m. 1H-NMR
((D6)DMSO): 7.49–7.44 (m, 5 arom. H); 3.18–3.12 (m, 1 H of cPr); 2.31 (s, Me); 1.22–1.09 (2m, 4 H
of cPr). 13C-NMR ((D6)DMSO): 148.3 (s, C=C(CN)2); 128.5, 128.1, 127.9 (3d, 5 arom. CH); 127.8,
125.1, 124.6 (3s, arom. Cq, C(4), C(5)); 120.3 (s, C=C(CN)2); 26.5 (s, C=C(CN)2); 24.1 (d, CH of cPr);
10.2 (q, Me); 10.1 (t, 2 CH2 of cPr). EI-MS: 262 (67, M+C), 222 (35), 221 (100), 130 (28), 103 (20), 77 (24).
2-(1,3-Dihydro-5-methyl-4-phenyl-1-(prop-2-enyl)-2H-imidazol-2-ylidene)propanedinitrile
(11h).
Yield: 160 mg (61%). Colorless crystals. M.p. (dec.) 200–2058 (MeOH). IR: 3250–2850s (br., NH),
2194vs (CN), 2153vs (CN), 1646s, 1579vs (C=C(CN)2), 1504s, 1475s, 1444m, 1433m, 1414m, 1320m,
1
1288w, 1272w, 1229w, 1154w (br.), 988m, 934m, 923w, 791m, 769s, 698s. H-NMR ((D6)DMSO): 12.75
(br. s, NH); 7.49–7.37 (m, 5 arom. H); 6.02–5.92 (m, ꢀCH=); 5.29–5.02 (m, =CH2); 4.73–4.72 (m,
CH2); 2.21 (s, Me). 13C-NMR ((D6)DMSO): 146.3 (s, C=C(CN)2); 132.0 (d, ꢀCH=); 128.5, 128.3,

1314
Helvetica Chimica Acta – Vol. 89 (2006)
128.1 (3d, 5 arom. CH); 127.7, 125.0, 123.7 (3s, arom. Cq, C(4), C(5)); 120.0 (s, C=C(CN)2); 117.1 (t, =
CH2); 45.8 (t, CH2); 23.2 (s, C=C(CN)2); 8.7 (q, Me). EI-MS: 262 (47, M+C), 222 (43), 221 (100), 130
(25), 77 (17).
6. Isolation of the Complex 12. To a soln. of the monohydrate of 1d (344 mg, 1.0 mmol) in MeOH (4
ml), a soln. of 7 (235 mg, 1.1 mmol) in MeOH (2 ml) was added dropwise, and the mixture was stirred
magnetically for 20 min at r.t. The solvent was evaporated i.v., and the oily residue was triturated with
ca. 3 ml of Et2O. The separated solid was dissolved in hot MeOH and left to cool. In the refrigerator, crys-
N
tals of 11d formed. They were filtered, and the mother liquor was evaporated i.v. to dryness. The colorless
residue was dissolved in CH2Cl2 to give, after cooling in the refrigerator overnight, anal. pure crystals of
the 1:1 complex of hexafluoroacetone hydrate and 1-benzyl-4,5-diphenyl-1H-imidazole 3-oxide (12).
Yield: 40 mg (8%). Colorless prisms. M.p. (dec.) 116–1178 (CH2Cl2). IR: 3450–2360s (br., H-bridged
Table. Crystallographic Data for Compounds 11d and 12
11d
12
Crystallized from
MeOH
MeOH
Empirical formula
Formula weight
C25H18N4 ·MeOH
406.49
C22H18N2O·C3
510.43
A
G
G
Crystal color, habit
Crystal dimensions [mm]
Temp. [K]
colorless, prism
0.10×0.27×0.27
160(1)
colorless, plate
0.05×0.20×0.37
160(1)
Crystal system
Space group
triclinic
P1
triclinic
P1
ꢀ
ꢀ
Z
2
2
Reflections for cell determination
5940
5206
2q Range for cell determination [8]
4–60
4–55
Unit cell parameters a [Å]
9.5540(5)
10.2090(4)
11.7472(6)
70.527(3)
79.331(2)
77.549(3)
1046.82(9)
1.289
10.5912(4)
10.8967(4)
11.6654(5)
87.757(3)
79.724(3)
62.052(2)
1168.67(8)
1.450
b [Å]
c [Å]
a [8]
b [8]
g [8]
V [Å3]
Dx [g cmꢀ3
]
m(MoKa) [mmꢀ1
Scan type
]
0.0809
f and w
60
0.127
f and w
55
2q(max) [8]
Total reflections measured
Symmetry independent reflections
Reflections with I>2s(I)
Reflections used in refinement
Parameters refined
25346
6094
3346
6092
26435
5333
3721
5331
268
334
Final R(F) [I>2s(I) reflections]
0.0661
0.1974
0.1065; 0
0.995
0.0446
0.1155
0.0520; 0.1644
1.057
wR(F2) (all data)
Weighting parameters [a; b]a)
Goodness-of-fit
Secondary extinction coefficient
Final Dmax/s
0.048(9)
0.001
0.37; ꢀ0.29
0.034(3)
0.001
0.20; ꢀ0.21
D1 (max; min) [e Åꢀ3
]
a) wꢀ1 =s 2(F2o)+(aP)2 +bP where P=(Fo2 +2F2c )/3.

Helvetica Chimica Acta – Vol. 89 (2006)
1315
OD): 8.48 (s, CH);
1
OH), 1277m, 1213vs (CF3), 1173s, 1148m, 1093s, 957m, 721s, 698s. H-NMR (CD3
ACHTREUNG
7.52–6.84 (m, 15 arom. H); 5.11 (s, CH2). 19F-NMR (CD3
A
(100, [MꢀC3H2F6O2 +1]+). Anal. calc. for C25H20F6N2O3 (510.43): C 58.83, H 3.95; found C 58.43, H 3.98.
7. X-Ray Crystal-Structure Determination of 11d and 12 (Table and Figs. 1–2)3). All measurements
were performed on a Nonius KappaCCD diffractometer [36] using graphite-monochromated MoKa radi-
ation (l 0.71073 Å) and an Oxford Cryosystems Cryostream 700 cooler. The data collection and refine-
ment parameters are given in the Table, and views of the molecules are shown in Figs. 1 and 2. Data
reduction was performed with HKL Denzo and Scalepack [37]. The intensities were corrected for Lor-
entz and polarization effects but not for absorption. Equivalent reflections were merged. The structures
were solved by direct methods using SIR92 [38], which revealed the positions of all non-H-atoms. The
asymmetric unit of 11d contains one molecule of the heterocycle and one highly disordered MeOH mol-
ecule. The disorder of the latter could not be modelled adequately, so the SQUEEZE routine [20] of the
program PLATON [21] was employed. This procedure, which allows the disordered solvent molecules to
be omitted entirely from the subsequent refinement model, gave better refinement results, and there
were no significant peaks of residual electron density to be found in the voids of the structure. The pro-
cedure leaves one cavity of 111 Å3 per unit cell. The electron count in the disordered region was calcu-
lated to be 26 e per cavity, although this can be an underbound. Allowing for two MeOH molecules per
cavity (one per asymmetric unit, which corresponds with the estimate from the original attempt to model
the solvent molecule) yields 36 e, and this estimate was used in the subsequent calculation of the empiri-
cal formula, formula weight, density, linear absorption coefficient, and F(000). The asymmetric unit of 12
contains two chemically distinct moieties. The non-H-atoms of 11d and 12 were refined anisotropically.
The HN-atom of 11d and the HO-atoms of 12 were paced in the positions indicated by difference electron
density maps, and their positions were allowed to refine together with individual isotropic displacement
parameters. All remaining H-atoms were placed in geometrically calculated positions and refined using a
riding model where each H-atom was assigned a fixed isotropic displacement parameter with a value
equal to 1.2 Ueq of its parent C-atom. The refinement of each structure was carried out on F2 using
full-matrix least-squares procedures, which minimized the function Sw(F2o ꢀFc2)2. Corrections for secon-
dary extinction were applied. In each case, two reflections, whose intensities were considered to be
extreme outliers, were omitted from the final refinement. Neutral atom scattering factors for non-H-
atoms were taken from [39a], and the scattering factors for H-atoms were taken from [40]. Anomalous
dispersion effects were included in Fc [41]; the values for f’ and f’’ were those of [39b]. The values of the
mass attenuation coefficients are those of [39c]. All calculations were performed using the SHELXL97
[42] program.
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Received March 21, 2006