Substrate-controlled and site-selective [3+2] cycloadditions of N-heterocyclic carbene derived ambident dipoles

Article abstract of DOI:10.1002/chem.200601482

2-Aryl thiocarbamoyl benzimidazolium and imidazolinium inner salts derived from benzimidazole and imidazoline carbenes are unique ambident C-C-S and C-C-N 1,3-dipolar systems, which undergo highly efficient and site-selective cycloaddition reactions with

Full text of DOI:10.1002/chem.200601482

DOI: 10.1002/chem.200601482
Substrate-Controlled and Site-Selective [3+2] Cycloadditions of N-
Heterocyclic Carbene Derived Ambident Dipoles
Ying Cheng,* Mei-Fang Liu, De-Cai Fang,* and Xue-Mei Lei[a]
Abstract: 2-Aryl thiocarbamoyl benzi-
midazolium and imidazolinium inner
salts derived from benzimidazole and
imidazoline carbenes are unique ambi-
dent C-C-S and C-C-N 1,3-dipolar sys-
tems, which undergo highly efficient
and site-selective cycloaddition reac-
tions with dimethyl acetylenedicarbox-
ylate or dibenzoylacetylene to furnish
spiro(imidazole-2,3’-thiophene) deriva-
tives in excellent yields. When treated
with ethyl propiolate, methyl acrylate
or acrylonitrile, spiro(imidazole-2,3’-
pyrrole) derivatives were formed in
good yields. Theoretical studies re-
vealed an asynchronous concerted
mechanism for both the C-C-S and C-
C-N 1,3-dipolar cycloaddition reac-
tions. The site selectivity in the [3+
2] cycloaddition reaction of ambident
1,3-dipoles was predictably regulated
by both the electronic and steric effects
of dipolarophiles.
Keywords: 1,3-dipoles · carbenes ·
cycloaddition · heterocycles · site
selectivity
Introduction
of a’-hydroxy enones and nitrones. Another strategy to con-
trol regio- and stereoselectivity is the application of a well-
defined nanosized environment. For example, Ye and co-
workers recently reported a successful regioselective 1,3-di-
polar cycloaddition reaction of azides with alkynes using
molecularly imprinted polymers as regioselective nanoreac-
tors.[3a] Most of the 1,3-dipolar systems reported to date are
either of the propargyl–allenyl type, including diazoalkanes,
azides, dinitrogen oxide, nitrile ylides, nitrile imines and ni-
trile oxides, or allyl type, such
as azomethine ylides, azome-
thine imines, nitrones, carbonyl
ylides, carbonyl imines and car-
bonyl oxides (Scheme 1). All of
these dipolar compounds share
two common structural fea-
tures: first, they are all heteroa-
1,3-Dipolar cycloaddition reactions constitute one of the
most powerful protocols in organic synthesis.[1] Most 1,3-di-
polar cycloaddition reactions proceed through a concerted
mechanism,[1a] although two-stage reactions through zwitter-
ionic intermediates have also been reported.[2] The interac-
tion between unsymmetrical reagents in a 1,3-dipolar cyclo-
addition reaction can give two isomeric adducts depending
on the relative position of the substituent in the cycloadduct.
The development of 1,3-dipolar cycloaddition reactions has
in recent years entered into a new stage in terms of control-
ling regio-[2c,3] and stereoselectivity.[4] An important method
for the regulation of regio- and stereoselectivity in 1,3-dipo-
lar cycloadditions is to change the electronic and steric ef-
fects of the reactants with Lewis acid catalysts. This ap-
proach has been exemplified by the excellent work of
Palomo et al.,[5] in which the perfect combination of both
tom-centred dipoles; second,
Scheme 1. General structures
regio- and stereoselectivity was achieved in the Cu
mediated (OTf=triflate) 1,3-dipolar cycloaddition reaction
A
they each contain only one di- of 1,3-dipoles.
polar component. The carbon-
centred 1,3-dipoles, and com-
pounds that can act as two or more different 1,3-dipoles,
have scarcely been explored.
[a] Prof. Dr. Y. Cheng, M.-F. Liu, Prof. Dr. D.-C. Fang, X.-M. Lei
Chemistry Department
Beijing Normal University
Beijing 100875 (China)
Fax : (+86)10-5880-2075
E-mail: ycheng2@bnu.edu.cn
dcfang@bnu.edu.cn
Imidazoline and benzimidazole carbenes, or their dimers,
were reported to react with isothiocyanates to form [1+1]
adducts, namely, 2-aryl thiocarbamoyl imidazolinium[6] and
benzimidazolium inner salts,[7] or [1+2] adducts (i.e., di-
thiohydantoins),[6b,8] under different reaction conditions. The
2-aryl thiocarbamoyl imidazolinium and benzimidazolium
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
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FULL PAPER
inner salts can have two different 1,3-dipolar resonance can-
onical forms: C-C-S 1,3-dipole A and C-C-N 1,3-dipole B
(Scheme 2). Winberg and Coffman[6a] and Regitz et al.[6b]
were prepared from the reactions of benzimidazole carbenes
2 or imidazoline carbenes 6 with aryl isocyanates at 0–208C.
Carbenes 2 and 6 were generated in situ by the deprotona-
tion of the corresponding benzimidazolium salts 1 or imida-
zolinium salts 5 with sodium hydride. All the N,N’-dialkyl
benzimidazolium salts 4 or imidazolinium salts 7 were ob-
tained as sole products in 65–89% yield. In the case of the
N,N’-diaryl imidazoline carbene 6g, N,N’-diaryl imidazolini-
um salt 7gd (28%) was obtained along with dithiohydantoin
8gd (33%; Scheme 2). The latter product 8gd was most
likely derived from the cycloaddition reaction of 7gd with
another equivalent of isothiocyanate. The different out-
comes between N,N’-dialkyl imidazoline carbenes and N,N’-
diaryl imidazoline carbenes were most probably due to the
different stabilities of the imidazolinium inner salts 7. These
carbene-derived 1,3-dipoles are stabilised by delocalisation
of the positive charge of the cation centre on the adjacent
nitrogen atoms and the negative charge on the sulfur atom
and aryl amino substituent. Because of this electronic effect,
an alkyl-substituted amino group is a stronger electron
donor than a phenyl-substituted amino group; therefore, the
N,N’-dialkyl imidazolinium salt should be more stable than
the N,N’-diaryl substituted analogue.
Scheme 2. Preparation of 2-aryl thiocarbamoyl benzimidazolium and imi-
dazolinium inner salts.
Reaction of 2-aryl thiocarbamoyl benzimidazolium salts 4
and imidazolinium salts 7 with DMAD or dibenzoylacety-
lene: We initially examined the reaction of 4 and 7 with the
highly electron-deficient agent DMAD as the dipolarophile.
When treated with one equivalent of DMAD in 1,2-di-
chloroethane at ambient temperature, the zwitterion 4 was
very rapidly transformed into the red–purple spiro(benzimi-
dazoline-2,3’-dihydrothiophenes) 9 in 85–95% yield, and a
small amount (4%) of dark green spiro(benzimidazoline-
2,3’-dihydropyrrole) 10 was also obtained (Scheme 3). Nei-
ther the substituent effect on the dipoles (Table 1, entries 5–
9) nor the reaction conditions (Table 1, entries 1–5) altered
the reaction pathway. 2-Phenylthiocarbamoyl imidazolinium
salts 7 acted in a similar manner to their benzimidazolium
analogues 4 on reaction with DMAD. Under identical con-
ditions, the zwitterionic adducts 7 derived from imidazoline
carbenes were found to behave predominantly as the C-C-S
rather than the C-C-N 1,3-dipolar systems, thus forming spi-
ro(imidazoline-2,3’-dihydrothiophene) cycloproducts 11 in
excellent yields, although a tiny amount of by-product spi-
ro(imidazoline-2,3’-dihydropyrrole) 12 was isolated.
claimed, respectively, that N,N’-diethyl-2-thiocarbamoyl imi-
dazolinium and N,N’-diphenyl-2-thiocarbamoyl imidazolini-
um salts behaved as the C-C-N 1,3-dipoles in all cycloaddi-
tion reactions with dimethyl acetylenedicarboxylate
(DMAD), dibenzoylacetylene and other electron-deficient
alkenes to give spiro(tetrahydroimidazole-2,3’-pyrrole) de-
rivatives. Recently, we found for the first time that the 2-
aryl thiocarbamoyl benzimidazolium and imidazolinium
inner salts actually behaved as the novel ambident C-C-S or
C-C-N 1,3-dipolar components.[9] These salts underwent
highly site-selective 1,3-dipolar cycloaddition reactions with
DMAD or ethyl propiolate to furnish imidazole–spiro(thio-
phene) or imidazole–spiro(pyrrole) derivatives, respectively,
A
in good-to-excellent yields. It was the reactivity of these new
1,3-dipolar systems and the site-selectivity of their [3+2] cy-
cloadditions with different dipolarophiles that intrigued us.
The control or regulation of the site selectivity should be of
great importance. To explore the reactivity and selectivity,
or the applications, of the C-C-S and C-C-N 1,3-dipolar
components and obtain deep insight into the reaction mech-
anism, we systematically investigated the 1,3-dipolar cyclo-
addition reactions of 2-aryl thiocarbamoyl benzimidazolium
and imidazolinium inner salts with different electron-defi-
cient acetylene and olefin derivatives by means of experi-
mental and theoretical approaches.
Following the reaction with DMAD, the interaction be-
tween zwitterions 4 or 7 and dibenzoylacetylene was ex-
plored. Under identical conditions as those for the reaction
with DMAD, both 4 and 7 reacted with dibenzoylacetylene
quickly and efficiently to afford C-C-S cycloaddition product
spiro(benzimidazoline-2,3’-dihydrothiophene) 13 or spiro(i-
midazoline-2,3’-dihydrothiophene) derivatives 14 in 86–94%
Results and Discussion
yield. It is worth noting that the imidazole–spiro(pyrrole)-
type products were not detected (see Scheme 3 and
Table 2).
The structures of all the products were fully characterised
by spectroscopic studies and microanalysis. This characteri-
A
Preparation of 2-aryl thiocarbamoyl benzimidazolium and
imidazolinium inner salts: Herein, 2-aryl thiocarbamoyl ben-
zimidazolium inner salts 4 or imidazolinium inner salts 7
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4283

Y. Cheng, D.-C. Fang et al.
Table 2. The 1,3-dipolar cycloaddition reactions between 4 or 7 and di-
benzoylacetylene.[a]
Entry
Starting material
R2
Product Yield
[%]
Compd R1
Ar
1
2
3
4
5
6
7
8
9
4ba
4ca
4cb
4cc
4cd
4da
4 fa
4ga
7da
7ea
7gd
nBu
nBu
Bz
Bz
Bz
Bz
nBu
Bz
Bz
Ph
Ph
13ba
13ca
89
92
92
90
91
91
88
87
93
86
94
Bz
Bz
Bz
Bz
Et
Et
nBu
Bz
p-MeOC6H4 13cb
p-ClC6H4 13cc
p-NO2C6H4 13cd
Ph
Ph
Ph
Ph
13da
13 fa
13ga
14da
14ea
Bz
10
11
p-MeOBz p-MeOBz Ph
Ph Ph
p-NO2C6H4 14gd
[a] Reaction conditions: 1,2-dichloroethane, RT, 0.5 h.
200–210 ppm. These spectroscopic characteristics are very
useful for the differentiation of the imidazole–spiro(thio-
phene) and imidazole–spiro
studies.
A
The aforementioned results clearly indicated that the
zwitterions 4 and 7 act predominantly as the powerful C-C-S
dipolar component towards DMAD and dibenzoylacetylene.
It should be noted that these
Scheme 3. Reaction of 1,3-dipoles 4 and 7 with DMAD or dibenzoylace-
tylene.
results are in sharp contrast to
Table 1. The 1,3-dipolar cycloaddition reactions between 4 or 7 and DMAD.
those previously reported.[6a,b]
Entry
Starting material
Reaction
conditions
Product
Yield
[%]
Clearly, the structures of 11aa
and 14gd were wrongly as-
signed in these earlier reports.
Compd
R1
R2
Ar
Ph
1
2
4ba
nBu
nBu
nBu
nBu
nBu
Bz
nBu
DCE, 50–608C, 0.5 h
CH3CN, 50–608C, 0.5 h
THF, 50–608C, 0.5 h
acetone, 50–608C, 0.5 h
DCE, RT, 0.5 h
9ba
10ba
9ba
10ba
9ba
10ba
9ba
10ba
9ba
10ba
9ca
10ca
9cb
10cb
9cc
90
5
4ba
4ba
4ba
4ba
4ca
4cb
4cc
4 cd
7aa
7da
nBu
nBu
nBu
nBu
Bz
Ph
78
[a]
–
Reaction of 2-aryl thiocarbamo-
yl benzimidazolium salts 4 and
imidazolinium salts 7 with ethyl
propiolate, methyl acrylate or
acrylonitrile: A quite different
reaction pathway was encoun-
tered when ethyl propiolate was
used as the dipolarophile in re-
action with 4 and 7. Under
identical conditions as those for
the reaction of DMAD and di-
benzoylacetylene with 4 and 7,
the reaction of 4 with ethyl pro-
piolate proceeded very slowly.
Only at elevated temperatures
and with excess amounts of
ethyl propiolate did the reac-
tions go to completion. At
reflux in 1,2-dichloroethane or
3
Ph
64
8
85
6
90
4
4
Ph
5
Ph
6
Ph
DCE, RT, 0.5 h
95
[a]
–
7
Bz
Bz
p-MeOC6H4
p-ClC6H4
p-NO2C6H4
Ph
DCE, RT, 0.5 h
88
[a]
–
8
Bz
Bz
DCE, RT, 0.5 h
87
[a]
10cc
9 cd
–
9
Bz
Bz
DCE, RT, 0.5 h
85
[a]
10 cd
11aa
12aa
11da
12da
–
10
11
Et
Et
DCE, RT, 0.5 h
95
[a]
–
Bz
Bz
Ph
DCE, RT, 0.5 h
92
3
[a] A tiny amount of minor product was observed. DCE=1,2-dicholorethane.
sation indicated that 9–14 were the [1+1] adducts of the
two starting materials. To identify the isomers beyond
doubt, the structures of 9ca and 10ba were determined un-
ambiguously by single-crystal X-ray diffraction studies.[10] It
is worth noting that in the 13C NMR spectra the diagnostic
C=N signals for the dihydrothiophene products 9, 11, 13 and
14 were at d=165–175 ppm and the C=S signals for the di-
hydropyrroles 10 and 12 were in the downfield range d=
THF, all the zwitterions 4 and 7, except 2-para-nitro-
phenylthiocarbamoyl benzimidazolium 4 cd, reacted with
five equivalents of ethyl propiolate to furnish 15 and 17 as
the major products, respectively, in 73–82% yield within
0.5–1.5 h, along with 16 and 18 in 5–15% yield (see
Scheme 4 and Table 3). Most surprisingly, however, the
major products 15 and 17 were imidazole–spiro
A
products. This outcome clearly indicated that 4 and 7 be-
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Regioselectivity of 1,3-Dipolar Cycloaddition Reactions
FULL PAPER
vious on reaction with electron-deficient alkenes, such as
methyl acrylate and acrylonitrile. The reaction of benzimida-
zolium salts 4 with methyl acrylate or acrylonitrile was total-
ly inefficient under all the reaction conditions employed. On
the contrary, however, in CHCl3 or THF at reflux and in the
presence of a large excess of the dipolarophile, imidazolini-
um 7 acted as the C-C-N 1,3-dipolar component in the
smooth addition to methyl acrylate or acrylonitrile, thus pro-
ducing tetrahydropyrrole derivatives 19[10] or 20, respective-
ly, in good yields (see Scheme 5 and Table 4). Apparently,
Scheme 5. The cycloaddition reactions between 7 and methyl acrylate or
Scheme 4. Reaction of dipoles 4 and 7 with ethyl propiolate.
acrylonitrile.
the zwitterions
4 were less
Table 3. The 1,3-dipolar cycloaddition reactions between 4 or 7 and ethyl propiolate.
active than 7, as an aromatic
benzimidazoline cation should
be more stable than an aliphatic
tetrahydroimidazole cation. It
was interesting to note that an
organic base can promote the
reaction process. Thus, im-
proved chemical yields were
achieved in the presence of trie-
thylamine (See Table 4, en-
tries 3 and 4). Zwitterion 7 was
not very stable at an elevated
Entry
Starting material
R2
Reaction
conditions
Product
Yield
[%]
Compd
R1
Bz
Ar
1
2
3
4
5
4cb
Bz
Bz
Bz
Bz
p-MeOC6H4
DCE, reflux for 20 min
DCE, reflux for 1.5 h
DCE, reflux for 7 h
THF, reflux for 1.5 h
THF, reflux for 1.5 h
15cb
16cb
15cc
16cc
15cd
16cd
17da
18da
17ea
18ea
81
10
81
5
48
–
73
15
71
15
4cc
4 cd
7da
7ea
Bz
Bz
Bz
p-ClC6H4
p-NO2C6H4
Ph
p-MeOBz
p-MeOBz
Ph
haved mainly as C-C-N 1,3-di-
polar components in the addi-
tion to ethyl propiolate. The re-
action of 4 cd with ethyl propio-
late took a longer time (7 h)
and gave a lower yield (48%)
of product 15 cd. It is not diffi-
cult to understand why 4 cd
gave a lower yield of the C-C-N
cycloaddition product as its C-
Table 4. The 1,3-dipolar cycloaddition reactions between 7 and methyl acrylate or acrylonitrile.
Entry
Starting materials
Reaction
Product
Yield
[%]
7
R
Ar
conditions
1
2
3
4
5
6
7
8
7da
7ea
7ec
7ec
7 fc
7da
7ea
7ec
Bz
Ph
Ph
p-ClC6H4
p-ClC6H4
p-ClC6H4
Ph
methyl acrylate
methyl acrylate
methyl acrylate
methyl acrylate
methyl acrylate
acrylonitrile[a]
acrylonitrile
CHCl3, Et3N 608C, 7 h
CHCl3, Et3N 608C, 8 h
CHCl3, Et3N refluxing, 10 h
CHCl3, refluxing, 15 h
CHCl3, Et3N refluxing, 22 h
THF, Et3N, refluxing, 12h
THF, Et3N, reflux, 9 h
19da
19ea
19ec
19ec
19 fc
20da
20ea
20ec
84
88
71
38
88
83
88
86
p-MeOBz
p-MeOBz
p-MeOBz
p-ClBz
Bz
p-MeOBz
p-MeOBz
Ph
p-ClC6H4
acrylonitrile
THF, Et3N, reflux, 14 h
C-N dipolar component has the [a] Acrylonitrile is a carcinogenic compound.
weakest nucleophilicity among
the 1,3-dipoles employed.
The ambident reactivity of the benzimidazolium and imi-
dazolinium species and their completely opposite site-selec-
tive cycloaddition reactions were intriguing. To examine the
generality of the site selectivity in the 1,3-dipolar cycloaddi-
tion reactions of the ambident 1,3-dipolar components,
other dipolarophiles were tested.
temperature and underwent intramolecular cyclisation to
form spiro(tetrahydroimidazole-2,3’-indoline-2-thione).
Zwitterion 7 was stabilised in the presence of an organic
base probably because of the interaction of a base with the
cation centre, and therefore its tendency to intramolecular
cyclisation with the phenyl moiety was alleviated.
Although both the benzimidazolium and imidazolinium
dipolar systems showed almost identical reactivities towards
the electron-deficient alkynes, different reactivities were ob-
It should be pointed out that other a,b-unsaturated
alkyne and alkenes, including methyl 2-butynoate, methyl
crotonate, diethyl fumarate, diethyl maleate and fumaroni-
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4285

Y. Cheng, D.-C. Fang et al.
trile, were not good 1,3-dipolarophiles towards benzimidazo-
lium and imidazolinium inner salts. No reaction was ob-
served under various conditions.
uct. Therefore, the reaction proceeded most likely through a
concerted but asynchronous mechanism. The activation bar-
riers, activation enthalpies, activation entropies and activa-
tion free energies, which were obtained by using the
B3LYP/6–31G* method, are summarised in Table 5.
In the reaction of 7aa with DMAD at 298 K, the relative
free energy in the C-C-S cycloaddition is 0.98 kcalmolꢀ1
more favourable than that of the C-C-N cycloaddition. On
the contrary, however, the activation free energy of the C-C-
N 1,3-dipolar reaction is about 2kcalmol ꢀ1 less than that of
the C-C-S pathway in the case of the reaction between 7aa
and methyl propiolate. The results of these calculations are
in good agreement with the experimental observations. In
Computational study of the mechanism, reactivity and site
selectivity of the reactions: The highly site-selective 1,3-di-
polar cycloaddition reactions of the 2-aryl thiocarbamoyl
benzimidazolium and imidazolinium inner salts are remarka-
ble. In particular, their clear-cut cycloaddition reaction path-
ways between the C-C-S and C-C-N 1,3-dipolar systems
when treated with different alkynes and alkenes are intrigu-
ing. Our experimental studies show that neither the substitu-
ent effect on dipoles 4 and 7 nor the reaction conditions can
change the reaction pathway. It is the structure of the dipo-
larophile that affects the reactivity of the dipole and
switches the site selectivity of the reaction. To shed light on
the different selectivity of the zwitterionic species towards
different dipolarophiles, density functional theory B3LYP/6–
31G* was employed to investigate the mechanisms of the re-
actions depicted in Scheme 6. The calculation indicated that
ꢀ
each of the transition states illustrated in Figure 1, the C S
ꢀ
ꢀ
or C N bond being formed was shorter than the C C bond
being formed, thus indicating that the nucleophilic attack of
the sulfur or nitrogen atom on the unsaturated carbon atom
initiated this cycloaddition reaction. As indicated in Table 5,
both the C-C-S and C-C-N reaction pathways of 7aa with
DMAD have lower activation barriers, enthalpies and free
energies because DMAD is the most electrophilic and
active 1,3-dipolarophile among those on which we per-
formed calculations. Although two transition states for the
C-C-S and C-C-N 1,3-dipolar cycloaddition reactions
(Table 5, entries 1 and 2) have almost the same activation
barriers and activation enthalpies, the contribution of entro-
py to the free energy caused a difference of about 1 kcal
molꢀ1 in the activation free energy. This entropy effect led
to the competition of two reaction processes, and the C-C-S
cycloaddition is, therefore, the predominant process. The
disfavoured C-C-N pathway in this case is most probably
due to a strong steric repulsion between the phenyl group
on the nitrogen atom and the carboxylate group in the C-C-
N reaction process. When the reaction was carried out in di-
chloroethane, single-point SCRF-B3LYP/6–31G* calcula-
tions showed that the difference in free energy increased to
1.6 kcalmolꢀ1, thus leading to the formation of the major
and minor products in a ratio of 93:7. In the reaction of 7aa
with methyl propiolate, calculations showed the C-C-N 1,3-
dipolar cycloaddition to be the favoured path way and the
calculated ratio of the C-C-N/C-C-S products is 97:3. It is in-
teresting to note that the reaction transition state of 7aa
with methyl acrylate has a much higher activation barrier,
enthalpy and free energy (Table 5, entry 6), which is in good
agreement with the experimental observation that 7 was a
much less reactive 1,3-dipole to methyl acrylate or acryloni-
trile.
Scheme 6. Computational reactions of 7aa with DMAD, methyl propio-
late, methyl 2-butynoate, methyl acrylate, dimethyl fumarate and methyl
crotonate.
the cycloaddition of 7aa with DMAD or methyl propiolate
can proceed through two different reaction pathways by
using both the C-C-S and C-C-N dipoles, respectively. Com-
pound 7aa only acted as a C-C-N 1,3-dipole to a,b-unsatu-
rated alkyne and alkenes, including methyl 2-butynoate,
methyl acrylate, dimethyl fumarate or methyl crotonate, as
the transition states for the C-C-S 1,3-dipolar reactions
could not be located; therefore, such reactions are probably
not favoured under the present conditions. Eight transition
states have been located for the reactions in Scheme 6
(Figure 1). In each transition state, the two bonds that are
forming have quite different lengths, but no intermediate
could be located between the reactants and the final prod-
The theoretical calculations indicate a steric effect that
plays a determinant role in the C-C-N cycloaddition process.
For example, the reactions of 7aa with methyl acrylate and
methyl 2-butynoate have similar activation barriers, enthal-
pies and free energies (Table 5, entries 5 and 6), but actually
the latter reaction did not take place under the conditions
employed as result of the unfavourable steric effect in the
C-C-N cycloaddition reaction. The dimethyl fumarate, an
alkene substituted by two electron-withdrawing groups,
should be a more reactive dipolarophile than methyl acry-
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Regioselectivity of 1,3-Dipolar Cycloaddition Reactions
FULL PAPER
Figure 1. Optimised (B3LYP/6–31G*) transition structures (TS; bond lengths in Š) for the reactions between 7aa and DMAD, methyl propiolate,
methyl 2-butynoate, methyl acrylate, dimethyl fumarate or methyl crotonate.
The reactivity of ambident
benzimidazolium and imidazoli-
Table 5. The calculated activation barriers, activation enthalpies, activation entropies and activation free ener-
gies of 1,3-dipolar cycloaddition reactions between 7aa and different alkynes and alkenes based on the
nium 1,3-dipoles and the site se-
lectivity of the [3+2] cycloaddi-
tion reactions are best interpret-
ed by both the electronic and
steric effects of the dipolaro-
philes. When dipoles 4 or 7
were treated with strong elec-
trophilic dipolarophiles, such as
DMAD and dibenzoylacetylene,
both the C-C-S and C-C-N cy-
cloaddition pathways appear fa-
vourable as a result of the low
activation free energies. Howev-
B3LYP/6–31G* method.
Entry Reaction
DE°[a] (298 K) DH° (298 K) DS° (298 K)
DG° (298 K)
[kcalmolꢀ1
]
[kcalmolꢀ1
]
[calmolꢀ1 Kꢀ1
]
[kcalmolꢀ1
]
ꢁ
1
2
3
4
5
6
7
8
7aa + MeCO2C CCO2Me ! 11
6.26.5
6.1
8.5
12.5
15.9
15.0
ꢀ49.0
ꢀ52.0
ꢀ45.0
ꢀ42.8
ꢀ53.1
ꢀ49.7
ꢀ51.4
ꢀ53.9
21.1
22.1
22.9
24.8
32.2
30.5
35.0
35.4
ꢁ
7aa + MeCO2C CCO2Me ! 12
6.6
9.4
ꢁ
7aa + HC CCO2Me ! 17
ꢁ
7aa + HC CCO2Me ! 18
12.1
16.4
15.7
19.9
19.6
ꢁ
7aa + MeC CCO2Me ! 21
7aa + H2C=CHCO2Me ! 19
7aa + MeO2CHC=CHCO2Me ! 22 19.1
7aa + MeHC=CHCO2Me ! 23
18.5
[a] The activation barrier without zero-point energy correction.
late. On the contrary, however, the reaction of 7aa with di-
methyl fumarate has much high activation barrier, enthalpy
and free energy than with methyl acrylate. The steric factors
clearly counterbalance the electronic preference in these re-
actions.
er, the huge steric hindrance in the C-C-N process drove the
reaction to follow the C-C-S pathway. On the other hand,
the C-C-N cycloaddition reaction should be a generally pre-
ferred process in the reactions with less active dipolaro-
philes. If the dipolarophiles, such as ethyl propiolate, methyl
Chem. Eur. J. 2007, 13, 4282 – 4292
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4287

Y. Cheng, D.-C. Fang et al.
508 [M+1]; elemental analysis calcd (%) for C28H33N3O4S: C 66.25, H
6.55, N 8.28; found: C 66.32, H 6.43, N 8.20.
acrylate and acrylonitrile, have less steric hindrance in their
approach to the C-C-N dipoles, the reaction will afford the
C-C-N cycloaddition product as the major or sole product.
Less reactive and sterically bulky dipolarophiles are not fav-
oured in a C-C-N cycloaddition process, and they inhibit the
1,3-dipolar cycloaddition.
Dimethyl
pyrrole)-2’-thione-4’,5’-dicarboxylate (10ba): 5% yield; m.p. 122–1238C,
IR (KBr): n˜ =1755, 1702, 1646, 1595, 1497 cmꢀ1 1H NMR (500 MHz,
CDCl3): d=7.47–7.55 (m, 3H), 7.28 (d, 3J
(H,H)=7.3 Hz, 2H), 6.61 (dd,
3J(H,H)=5.4 and 3.2Hz, 2H), 6.32 (dd, 3J
(H,H)=5.4 and 3.2Hz, 2H),
3.74 (s, 3H), 3.67 (s, 3H), 3.15 (qt, 3J(H,H)=7.3 Hz, 2H), 3.02 (qt, 3J-
(H,H)=7.2Hz, 2H), 1.60 (qt, 3J
(H,H)=7.4 Hz, 4H), 1.38 (m, 4H),
0.94 ppm (t, 3J(H,H)=7.3 Hz, 6H); 13C NMR (125 MHz, CDCl3): d=
1,3-dibutyl-1’-phenyl-2’,3’-dihydrospiro(benzimidazoline-2,3’-
;
AHCTREUNG
A
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
AHCTREUNG
Conclusion
208.5, 161.5, 160.9, 147.1, 140.0, 135.7, 129.8, 127.4, 117.8, 113.6, 103.1,
97.6, 53.5, 52.0, 44.8, 31.0, 20.5, 14.0 ppm; MS (MALDI-TOF): m/z (%):
506 [Mꢀ1]; elemental analysis calcd (%) for C28H33N3O4S: C 66.25, H
6.55, N 8.28; found: C 66.41, H 6.85, N 8.38.
We have demonstrated experimentally and theoretically that
the 2-aryl thiocarbamoyl benzimidazolium and imidazolini-
um inner salts derived from N-heterocyclic carbenes are a
unique type of ambident C-C-S and C-C-N 1,3-dipolar sys-
tems. These compounds acted predominately as C-C-S di-
poles in cycloaddition reactions with alkynes bearing two
electron-withdrawing groups to furnish spiro(imidazole-2,3’-
thiophene) compounds in excellent yields. When treated
with alkynes and alkenes substituted with one electron-with-
drawing group, they behaved as a C-C-N 1,3-dipolar compo-
nent to produce good yields of spiro(imidazole-2,3’-pyrrole)
derivatives as products. Both the C-C-S and C-C-N 1,3-dipo-
lar cycloaddition reactions proceeded through an asynchro-
nous concerted mechanism. This study has revealed the reg-
ularity of the reactivity of an ambident bis(1,3-dipolar)
system and the site selectivity in [3+2] cycloaddition reac-
tions. The site selectivity of the cycloaddition reactions was
predictably controlled by both the electronic and steric ef-
fects of the dipolarophiles. The applications of these ambi-
dent 1,3-dipolar systems in cycloaddition reactions provide
very simple synthetic approaches to complex cyclic systems,
which are not easily prepared by other synthetic methods.
Dimethyl 1,3-dibenzyl-2’-phenylimino-2’,3’-dihydrospiro(benzimidazoline-
2,3’-thiophene)-4’,5’-dicarboxylate (9ca): 95% yield; m.p. 123–1248C; IR
(KBr): n˜ =1739, 1734, 1640, 1495 cmꢀ1 1H NMR (500 MHz, C6D6): d=
;
7.63 (d, 3J
(m, 4H), 6.98 (t, 3J
6.66 (dd, 3J(H,H)=5.4 and 3.2Hz, 2H), 6.32 (dd, 3J
3.2Hz, 2H), 4.74 (d, 3J(H,H)=16.2Hz, 2H), 4.60 (d, 3J
(H,H)=16.2Hz,
A
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
2H), 3.42 (s, 3H), 3.30 ppm (s, 3H); 13C NMR (125 MHz, CDCl3): d=
165.4, 163.7, 161.6, 150.6, 139.5, 137.6, 134.8, 129.8, 129.1, 128.7, 128.1,
127.6, 127.3, 125.8, 119.3, 118.8, 113.5, 104.9, 53.4, 52.7, 49.1 ppm; MS
(ESI): m/z (%): 576 [M+1]; elemental analysis calcd (%) for
C34H29N3O4S: C 70.94, H 5.08, N 7.30; found: C 70.92, H 5.19, N 7.59.
Dimethyl
(benzimidazoline-2,3’-thiophene)-4’,5’-dicarboxylate (9cb): 88% yield;
m.p. 134–1358C; IR (KBr): n˜ =1735, 1719, 1635, 1597, 1503 cmꢀ1
1H NMR (500 MHz, CDCl3): d=7.51 (d, 3J
(H,H)=7.3 Hz, 4H), 7.33 (t,
3J(H,H)=7.6 Hz, 4H), 7.28 (t, 3J(H,H)=7.2Hz, 2H), 6.82(d, 3J
(H,H)=
8.8 Hz, 2H), 6.64 (d, 3J(H,H)=8.8 Hz, 2H), 6.52 (d, 3J
( H,H)=2.8 Hz,
2H), 6.11 (dd, 3J(H,H)=5.1, 3.1 Hz, 2H), 4.54 (d, 3J
(H,H)=16.0 Hz,
2H), 4.38 (d, 3J
(H,H)=16.0 Hz, 2H), 3.87 (s, 3H), 3.80 (s, 3H), 3.67 ppm
1,3-dibenzyl-2’-para-methoxyphenylimino-2’,3’-dihydrospiro-
AHCTREUNG
;
AHCTREUNG
A
N
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
(s, 3H); 13C NMR (125 MHz, CDCl3): d=163.8, 163.1, 161.7, 157.9, 143.3,
139.6, 137.6, 135.1, 129.7, 129.1, 128.1, 127.6, 127.2, 126.1, 121.4, 118.8,
114.3, 113.5, 104.8, 102.1, 55.4, 53.4, 52.7, 49.1 ppm; MS (ESI): m/z (%):
606 [M+1]; elemental analysis calcd (%) for C35H31N3O5S: C 69.40, H
5.16, N 6.94; found: C 69.41, H 5.18, N 6.85.
Dimethyl 1,3-Dibenzyl-2’-para-chlorophenylimino-2’,3’-dihydrospiro(ben-
zimidazoline-2,3’-thiophene)-4’,5’-dicarboxylate (9cc): 87% yield;
m.p. 119–1208C; IR (KBr): n˜ =1739, 1721, 1636, 1598, 1496 cmꢀ1
;
1H NMR (500 MHz, CDCl3): d=7.50 (d, 3J
ACHTREUNG
Experimental Section
3J
C
G
ACHTREUNG
ACHTREUNG
The melting points are uncorrected. Column chromatography was per-
formed on 200–300-mesh silica gel. The experimental procedure for prep-
aration of 2-aryl thiocarbamoyl benzimidazolium inner salts 4 and imida-
zolinium inner salts 7, full characterisation of 4 and 7 and the computa-
tional calculated data are given in the Supporting Information.
8.6 Hz, 2H), 6.15 (dd, 3J
ACHTREUNG
16.3 Hz, 2H), 4.37 (d, 3J
ppm; 13C NMR (125 MHz, CDCl3): d=166.7, 163.6, 161.4, 148.9, 139.3,
137.5, 134.2, 131.2, 129.9, 129.2, 129.1, 128.5, 128.1, 127.6, 127.3, 126.1,
120.7, 118.9, 113.5, 104.7, 102.0, 53.5, 52.8, 50.5, 49.0 ppm; MS (ESI): m/z
(%): 610 [M+1]; elemental analysis calcd (%) for C34H28ClN3O4S: C
66.93, H 4.63, N 6.89; found: C 66.91, H 4.87, N 6.93.
General procedure for the reaction of 4 and 7 with DMAD or dibenzoyl-
acetylene: A solution of DMAD or dibenzoylacetylene (1 mmol) in 1,2-
dichloroethane (10 mL) was added dropwise to a solution of benzimida-
zolium salt 4 (1 mmol) or imidazolinium salt 7 (1 mmol) in 1,2-dichloro-
ethane (20 mL) at ambient temperature (20–308C). The reaction mixture
was then stirred at room temperature for 0.5 h. After removal of the sol-
vent, the residue was purified by column chromatography on silica gel
with petroleum ether (30–608C)/ethyl acetate (5:1) as the eulant to
afford 9 and 10, 11 and 12, and 13 or 14, respectively.
Dimethyl 1,3-Dibenzyl-2’-para-nitrophenylimino-2’,3’-dihydrospiro(benzi-
midazoline-2,3’-thiophene)-4’,5’-dicarboxylate
m.p. 140–1418C; IR (KBr): n˜ =1745, 1703, 1648, 1601, 1587, 1519,
1497 cmꢀ1 1H NMR (500 MHz, CDCl3): d=8.09 (d, 3J
(H,H)=8.9 Hz,
2H), 7.50 (d, 3J(H,H)=6.8 Hz, 4H), 7.32–7.37 (m, 6H), 6.59 (dd, 3J-
(H,H)=5.4, 3.2Hz, 2H), 6.33 (d, 3J(H,H)=8.9 Hz, 2H), 6.23 (dd, 3J-
(H,H)=5.4, 3.2Hz, 2H), 4.65 (d, 3J(H,H)=16.3 Hz, 2H), 4.36 (d, 3J-
(H,H)=16.3 Hz, 2H), 3.90 (s, 3H), 3.69 ppm (s, 3H); 13C NMR
(9 cd):
85%
yield;
;
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
A
ACHTREUNG
Dimethyl 1,3-dibutyl-2’-phenylimino-2’,3’-dihydrospiro(benzimidazoline-
2,3’-thiophene)-4’,5’-dicarboxylate (9ba): 90% yield; m.p. 70–718C, IR
AHCTREUNG
(KBr): n˜ =1740, 1720, 1644, 1593, 1501 cmꢀ1
;
1H NMR (500 MHz, C6D6):
(H,H)=7.6 Hz, 2H), 7.02 (t,
(H,H)=5.2and 3.1 Hz, 2H), 6.51 (dd,
(H,H)=5.1 and 3.2Hz, 2H), 3.39–3.49 (m, 4H), 3.43 (s, 3H), 3.30 (s,
(125 MHz, CDCl3): d=169.5, 163.5, 161.0, 156.0, 145.2, 139.0, 137.5,
132.9, 130.3, 128.6, 127.7, 127.5, 125.1, 119.4, 119.1, 104.7, 102.2, 53.6,
53.0, 48.8 ppm; MS (ESI): m/z (%): 621 [M+1]; elemental analysis calcd
(%) for C34H28N4O6S: C 65.80, H 4.55, N 9.03; found: C 65.90, H 4.45, N
8.89.
3
d=7.21 (t, J
(H,H)=7.8 Hz, 2H), 7.14 (d, 3J
ACHTREUNG
3J
3J
(H,H)=7.3 Hz, 1H), 6.89 (dd, 3J
ACHTREUNG
ACHTREUNG
3H), 1.79–1.93 (m, 4H), 1.36–1.41 (m, 4H), 0.93 ppm (t, 3J
(H,H)=
7.3 Hz, 6H); 13C NMR (125 MHz, CDCl3): d=166.5, 163.8, 161.6, 150.9,
139.6, 132.4, 131.5, 129.3, 125.9, 119.3, 118.2, 112.8, 103.3, 53.4, 52.6, 45.1,
31.2, 20.6, 14.0 ppm; MS (MALDI-TOF): m/z (%): 506 [Mꢀ1]/507 [M+]/
Dimethyl 1,3-diethyl-2’-phenylimino-2’,3’-dihydrospiro(imidazolidine-2,3’-
thiophene)-4’,5’-dicarboxylate (11aa): 95% yield; m.p. 140–1418C; IR
1
(KBr): n˜ =1740, 1644, 1593 cmꢀ1; H NMR (500 MHz, CDCl3): d=7.38 (t,
4288
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 4282 – 4292

Regioselectivity of 1,3-Dipolar Cycloaddition Reactions
FULL PAPER
3J
7.4 Hz, 2H), 3.89 (s, 3H), 3.82 (s, 3H), 3.45–3.46 (m, 2H), 3.19–3.21 (m,
2H), 2.80–2.86 (m, 2H), 2.63–2.68 (m, 2H), 1.16 ppm (t, 3J
(H,H)=
A
G
G
1,3-Dibenzyl-2’-para-chlorophenylimino-2’,3’-dihydrospiro(benzimidazo-
line-2,3’-thiophene)-4’,5’-diylbisphenylmethanone (13cc): 90% yield;
m.p. 136–1378C; IR (KBr): n˜ =1650, 1641, 1597, 1580, 1497 cmꢀ1
;
7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3): d=167.3, 164.6, 161.0, 151.2,
138.7, 131.7, 129.3, 125.4, 119.7, 98.1, 53.1, 52.6, 47.9, 43.3, 14.2 ppm; MS
(EI): m/z: 241 (80), 300 (100), 404 [M+1, 45%]; elemental analysis calcd
(%) for C20H25N3O4S: C 59.53, H 6.25, N 10.41; found: C 59.54, H 6.55, N
10.37.
1H NMR (500 MHz, CDCl3): d=7.50 (d, 3J
3J(H,H)=7.5 Hz, 1H), 7.36 (d, 3J
(H,H)=7.0 Hz, 2H), 7.25–7.33 (m,
11H), 7.22 (t, 3J(H,H)=8.0 Hz, 2H), 7.05 (t, 3J
(H,H)=7.5 Hz, 2H), 6.62
(d, 3J(H,H)=8.5 Hz, 2H), 6.53 (brs, 2H), 6.13 (dd, 3J
(H,H)=5.0, 3.0 Hz,
2H), 4.77 (d, 3J(H,H)=16.0 Hz, 2H), 4.67 ppm (d, 3J
(H,H)=16.5 Hz,
A
A
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
2H); 13C NMR (125 MHz, CDCl3): d=190.5, 190.4, 166.8, 149.1, 143.5,
139.6, 138.1, 137.4, 135.9, 134.1, 133.0, 131.3, 129.3, 128.7, 128.5, 128.2,
127.4, 127.3, 121.0, 118.7, 104.4, 49.5 ppm; MS (ESI): m/z (%): 702
[M+1]; elemental analysis calcd (%) for C44H32ClN3O2S: C 75.25, H 4.59,
N 5.98; found: C 75.10, H 4.86, N 5.94.
Dimethyl
2,3’-thiophene)-4’,5’-dicarboxylate (11da): 92% yield; m.p. 177 8C
(decomp); IR (KBr): n˜ =1737, 1725, 1640 cmꢀ1 1H NMR (500 MHz,
CDCl3): d=7.46–7.49 (m, 6H), 7.35 (t, 3J
(H,H)=7.3 Hz, 4H), 7.26–7.29
(m, 3H), 7.14 (d, 3J(H,H)=7.5 Hz, 2H), 4.16 (d, 3J
(H,H)=12.7 Hz, 2H),
3.99 (s, 3H), 3.85 (s, 3H), 3.69 (d, 3J
(H,H)=12.7 Hz, 2H), 3.20–3.21 (m,
1,3-dibenzyl-2’-phenylimino-2’,3’-dihydrospiro(imidazolidine-
;
AHCTREUNG
A
ACHTREUNG
AHCTREUNG
1,3-Dibenzyl-2’-para-nitrophenylimino-2’,3’-dihydrospiro(benzimidazo-
line-2,3’-thiophene)-4’,5’-diylbisphenylmethanone (13 cd): 91% yield;
2H), 3.11–3.12ppm (m, 2H); 13C NMR (125 MHz, CDCl3): d=166.7,
164.6, 161.0, 151.0, 138.6, 137.6, 133.4, 129.5, 128.7, 128.2, 127.1, 125.8,
119.9, 97.8, 53.5, 53.2, 52.6, 48.3 ppm; MS (ESI): m/z (%): 528 [M+1]; el-
emental analysis calcd (%) for C30H29N3O4S: C 68.29, H 5.54, N 7.96;
found: C 68.00, H 5.90, N 7.86.
m.p. 138–1398C; IR (KBr): n˜ =1650, 1597, 1585, 1500 cmꢀ1
;
1H MNR
(H,H)=
(H,H)=7.7 Hz,
(500 MHz, CDCl3): d=8.16 (d, 3J
6.8 Hz, 4H), 7.48 (t, 3J(H,H)=7.6 Hz, 1H), 7.38 (d, 3J
2H), 7.34 (t, 3J
(H,H)=7.4 Hz, 1H), 7.29–7.31 (m, 8H), 7.24 (t, J
7.5 Hz, 2H), 7.08 (t, 3J(H,H)=7.5 Hz, 2H), 6.57 (d, 3J
(H,H)=8.3 Hz,
4H), 6.19 (d, 3J(H,H)=3.4 Hz, 2H), 4.82 (d, 3J
(H,H)=16.4 Hz, 2H),
4.66 ppm (d, 3J(H,H)=16.4 Hz, 2H); 13C NMR (125 MHz, CDCl3): d=
A
ACHTREUNG
A
ACHTREUNG
3
N
(H,H)=
Dimethyl 1,3-dibenzyl-1’-phenyl-2’,3’-dihydrospiro(imidazolidine-2,3’-pyr-
role)-2’-thione-4’,5’-dicarboxylate (12da): 3% yield; m.p. 147–1488C; IR
A
ACHTREUNG
A
ACHTREUNG
(KBr): n˜ =1751, 1724, 1639, 1495 cmꢀ1 1H NMR (500 MHz, C6D6): d=
;
AHCTREUNG
7.60 (d, 3J
(H,H)=7.3 Hz, 2H), 7.12–7.16 (m, 4H), 7.06–7.09 (m, 1H), 4.23 (d, 3J-
(H,H)=13.2Hz, 2H), 4.06 (d, 3J
(H,H)=13.2Hz, 2H), 3.64 (s, 3H), 3.53–
A
N
190.2(2C =O), 169.6, 156.2, 145.2, 142.5, 139.3, 137.9, 137.3, 135.8, 134.3,
133.2, 128.7, 128.6, 128.5, 128.3, 127.5, 127.4, 125.2, 119.7, 118.9, 104.5,
49.4 ppm; MS (ESI): m/z (%): 713 [M+1]; elemental analysis calcd (%)
for C44H32N4O4S: C 74.14, H 4.53, N 7.86; found: C 74.15, H 4.66, N 7.72.
ACHTREUNG
A
ACHTREUNG
3.55 (m, 2H), 3.25–3.27 (m, 2H), 3.25 ppm (s, 3H); 13C NMR (125 MHz,
C6D6): d=209.2, 161.8, 160.5, 147.0, 139.1, 136.7, 129.1, 129.0, 128.9,128.4,
127.2, 116.5, 95.1, 53.5, 52.2, 51.3, 47.9 ppm; MS (ESI): m/z (%): 528
[M+1]; elemental analysis calcd (%) for C30H29N3O4S: C 68.29, H 5.54, N
7.96; found: C 68.21, H 5.62, N 7.99.
1-Butyl-3-ethyl-2’-phenylimino-2’,3’-dihydrospiro(benzimidazoline-2,3’-
thiophene)-4’,5’-diylbisphenylmethanone (13da): 91% yield; m.p. 116–
1178C; IR (KBr): n˜ =1655, 1644, 1595, 1503 cmꢀ1
;
1H NMR (500 MHz,
(H,H)=
(H,H)=7.6 Hz, 2H), 6.57–6.59 (m, 2H), 6.30–6.34
(m, 2H), 3.51–3.57 (m, 1H), 3.42–3.49 (m, 2H), 3.36–3.40 (m, 1H), 1.81
(qt, 3J(H,H)=7.5 Hz, 2H), 1.46–1.51 (m, 2H), 1.39 (t, 3J
(H,H)=7.2Hz,
3H), 1.00 ppm (t, 3J(H,H)=7.4 Hz, 3H); 13C NMR (125 MHz, CDCl3):
CDCl3): d=7.38–7.49 (m, 8H), 7.21–7.27 (m, 3H), 7.18 (t, 3J
7.6 Hz, 2H), 7.04 (d, 3J
ACHTREUNG
1,3-Dibutyl-2’-phenylimino-2’,3’-dihydrospiro(benzimidazoline-2,3’-thio-
phene)-4’,5’-diylbisphenylmethanone (13ba): 89% yield; m.p. 117–1188C;
AHCTREUNG
IR (KBr): n˜ =1652, 1594, 1507 cmꢀ1
7.37–7.48 (m, 8H), 7.21–7.27 (m, 3H), 7.18 (t, J
;
1H NMR (500 MHz, CDCl3): d=
G
ACHTREUNG
3
A
AHCTREUNG
(d, 3J
3J
(H,H)=5.2, 3.2Hz, 2H), 3.43–3.49 (m, 2H), 3.31–3.37 (m, 2H), 1.79
(qt, 3J(H,H)=7.5 Hz, 4H), 1.42–1.51 (m, 4H), 0.99 ppm (t, 3J
(H,H)=
A
(H,H)=5.0, 3.1 Hz, 2H), 6.31 (dd,
d=191.1, 190.5, 166.7, 151.0, 141.9, 139.7, 139.0, 138.1, 136.1, 134.0, 133.8,
133.0, 129.4, 128.7, 128.6 (d), 128.3, 125.9, 119.5, 118.0 (d), 104.2, 103.1,
103.0, 45.5, 39.6, 31.0, 20.8, 14.1, 14.0 ppm; MS (ESI): m/z (%): 572
[M+1]; elemental analysis calcd (%) for C36H33N3O2S: C 75.63, H 5.82, N
7.35; found: C 75.50, H 6.14, N 7.46.
ACHTREUNG
C
ACHTREUNG
7.4 Hz, 6H); 13C NMR (125 MHz, CDCl3): d=191.1, 190.4, 166.7, 151.0,
142.2, 139.6, 138.1, 136.1, 134.0, 133.7, 133.0, 129.4, 128.7, 128.6, 128.2,
125.9, 119.5, 118.0, 104.4, 103.1, 45.5, 31.0, 20.8, 14.0 ppm; MS (ESI): m/z
(%): 600 [M+1], 638 [M+K]+; elemental analysis calcd (%) for
C38H37N3O2S: C 76.10, H 6.22, N 7.01; found: C 76.03, H 6.21, N 7.04.
1-Benzyl-3-ethyl-2’-phenylimino-2’,3’-dihydrospiro(benzimidazoline-2,3’-
thiophene)-4’,5’-diylbisphenylmethanone (13 fa): 88% yield; m.p. 132–
1
1338C; IR (KBr): n˜ =1655, 1595, 1502cm ꢀ1; H NMR (500 MHz, CDCl3):
1,3-Dibenzyl-2’-phenylimino-2’,3’-dihydrospiro(benzimidazoline-2,3’-thio-
phene)-4’,5’-diylbisphenylmethanone (13ca): 92% yield; m.p.135–136 8C;
d=7.46–7.50 (m, 3H), 7.36–7.41 (m, 7H), 7.20–7.27 (m, 6H), 7.12 (t, 3J-
A
N
ACHTREUNG
IR (KBr): n˜ =1648, 1596, 1501 cmꢀ1 1H NMR (500 MHz, CDCl3): d=
;
7.3 Hz, 1H), 6.48 (t, 3J
7.53 (d, 3J
(H,H)=6.8 Hz, 4H), 7.24–7.31 (m, 9H), 7.18–7.21 (m, 3H), 7.04 (t, 3J-
(H,H)=7.9 Hz, 2H), 6.78 (d, 3J(H,H)=7.5 Hz, 2H), 6.51 (dd, 3J
(H,H)=
5.2, 3.1 Hz, 2H), 6.11 (dd, 3J(H,H)=5.2, 3.2 Hz, 2H), 4.77 (d, 3J
(H,H)=
16.3 Hz, 2H), 4.71 ppm (d, 3J(H,H)=16.3 Hz, 2H); 13C NMR (75 MHz,
A
N
1H), 6.07 (d, J
ACHTREUNG
(d, 3J
1.44 ppm (t, 3J
A
N
ACHTREUNG
A
ACHTREUNG
190.8, 190.5, 166.2, 150.9, 142.7, 139.6, 139.3, 138.1, 137.5, 136.0, 134.0,
133.4, 132.9, 129.3, 128.7, 128.6, 128.5, 128.2, 127.3, 127.2, 125.9, 119.4,
118.7, 117.9, 104.5, 104.1, 103.0, 49.4, 39.8, 14.1 ppm; MS (ESI): m/z (%):
606 [M+1]; elemental analysis calcd (%) for C39H31N3O2S: C 77.33, H
5.16, N 6.94; found: C 77.35, H 5.40, N 6.84.
AHCTREUNG
CDCl3): d=190.7, 190.5, 165.7, 150.8, 144.1, 139.7, 138.2, 137.4, 135.9,
134.1, 132.9, 129.3, 128.7, 128.6 (d), 128.2, 127.4, 127.3, 125.9, 119.5, 118.7,
104.5, 104.1, 49.7 ppm; MS (ESI): m/z (%): 668 [M+1], 706 [M+K]+; ele-
mental analysis calcd (%) for C44H33N3O2S: C 79.14, H 4.98, N 6.29;
found: C 78.80, H 5.29, N 6.30.
1-Benzyl-3-butyl-2’-phenylimino-2’,3’-dihydrospiro(benzimidazoline-2,3’-
thiophene)-4’,5’-diylbisphenylmethanone (13ga): 87% yield; m.p. 129–
1,3-Dibenzyl-2’-para-methoxyphenylimino-2’,3’-dihydrospiro(benzimid-
1
1308C; IR (KBr): n˜ =1648, 1596, 1501 cmꢀ1; H NMR (500 MHz, CDCl3):
ACHTREUNG
d=7.48 (d, 3J
A
ACHTREUNG
;
7.40 (m, 7H), 7.19–7.28 (m, 6H), 7.11 (t, 3J
3J(H,H)=7.6 Hz, 2H), 6.61 (t, 3J
7.5 Hz, 1H), 6.36 (d, 3J
1H), 4.75 (d, 3J
ACHTREUNG
A
ACHTREUNG
G
N
ACHTREUNG
ACHTREUNG
A
ACHTREUNG
A
N
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
AHCTREUNG
A
ACHTREUNG
3H); 13C NMR (125 MHz, CDCl3): d=190.8, 190.6, 163.2, 157.9, 144.3,
143.5, 139.8, 138.3, 137.5, 136.0, 134.0, 132.8, 128.7, 128.60, 128.57, 128.49,
128.1, 127.4, 127.2, 121.6, 118.6, 114.3, 104.4, 104.3, 55.5, 49.7 ppm; MS
(ESI): m/z (%): 698 [M+1]; elemental analysis calcd (%) for
C45H35N3O3S: C 77.45, H 5.06, N 6.02; found: C 77.16, H 5.32, N 5.96.
AHCTREUNG
(125 MHz, CDCl3): d=190.9, 190.4, 166.3, 150.9, 143.1, 139.9, 139.5,
138.2, 137.5, 136.0, 134.0, 133.4, 133.0, 129.3, 128.7, 128.6, 128.5, 128.2,
127.3, 127.2, 125.9, 119.5, 118.8, 118.0, 104.5, 104.2, 103.2, 49.5, 45.7, 31.0,
20.8, 14.0 ppm; MS (ESI): m/z (%): 634 [M+1], 672[ M+K]+; elemental
Chem. Eur. J. 2007, 13, 4282 – 4292
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4289

Y. Cheng, D.-C. Fang et al.
analysis calcd (%) for C41H35N3O2S: C 77.70, H 5.57, N 6.63; found: C
77.64, H 5.83, N 6.75.
U
N
1,3-Dibenzyl-2’-phenylimino-2’,3’-dihydrospiro(imidazolidine-2,3’-thio-
phene)-4’,5’- diylbisphenylmethanone (14da): 93% yield; m.p. 139–
1408C; IR (KBr): n˜ =1653, 1595, 1578, 1485 cmꢀ1
,
1447; 1H NMR
(H,H)=
(H,H)=7.3 Hz,
(H,H)=6.5 Hz, 4H), 7.17–7.28 (m, 14H), 4.46 (d, 3J-
(H,H)=13.3 Hz, 2H), 4.08 (d, 3J
(H,H)=13.3 Hz, 2H), 3.22 (brs, 2H),
(500 MHz, CDCl3): d=7.62(d, 3J
7.1 Hz, 2H), 7.48 (d, 3J(H,H)=7.6 Hz, 2H), 7.39 (t, 3J
1H), 7.35 (d, 3J
G
ACHTREUNG
H
A
ACHTREUNG
A
N
3.14 ppm (brs, 2H); 13C NMR (125 MHz, CDCl3): d=192.1, 190.6, 167.8,
151.4, 142.6, 139.4, 138.6, 138.4, 136.2, 133.8, 133.0, 129.5, 129.0, 128.9,
128.5, 128.3, 128.2, 127.1, 125.7, 119.9, 99.9, 53.9, 48.6 ppm; MS (ESI):
m/z (%): 620 [M+1]; elemental analysis calcd (%) for C40H33N3O2S:
C 77.52, H 5.37, N 6.78; found: C 77.03, H 5.74, N 6.49.
CDCl3): d=7.47 (s, 1H), 7.43 (d, 3J
(H,H)=7.1 Hz, 4H), 7.26–7.31 (m, 6H), 7.18 (d, 3J
6.55 (brs, 2H), 6.16–6.18 (m, 2H), 4.29 (d, 3J
(H,H)=15.7 Hz, 2H), 4.20
(d, 3J(H,H)=15.7 Hz, 2H), 4.16 (q, 3J
(H,H)=7.1 Hz, 2H), 1.13 ppm (t,
3J(H,H)=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3): d=205.0, 161.3,
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
AHCTREUNG
144.8, 140.3, 137.3, 135.8, 134.3, 129.6, 128.4, 128.0, 127.4, 126.2, 118.5,
117.6, 104.9, 98.2, 60.5, 49.2, 14.0 ppm; MS (ESI): m/z (%): 566 [M+1];
elemental analysis calcd (%) for C33H28ClN3O2S: C 70.01, H 4.99, N 7.42;
found: 69.80, H 5.27, N 7.31.
1,3-Di(para-methoxy)benzyl-2’-phenylimino-2’,3’-dihydrospiro(imidazoli-
dine-2,3’-thiophene)-4’,5’- diylbisphenylmethanone (14ea): 86% yield;
m.p. 143–1448C; IR (KBr): n˜ =1698, 1634, 1596, 1544, 1499, 1469 cmꢀ1
;
3
1H NMR (500 MHz, CDCl3): d=7.63 (d, J
(H,H)=7.4 Hz, 2H), 7.47–7.52
(m, 5H), 7.41 (t, 3J
(H,H)=8.4 Hz, 4H), 4.39 (d, 3J
A
Ethyl 1,3-dibenzyl-2’-para-chlorophenylimino-2’,3’-dihydrospiro(benzimi-
dazoline-2,3’-thiophene)-4’-carboxylate (16cc): 5% yield; m.p. 153–
A
N
ACHTREUNG
13.0 Hz, 2H), 3.79 (s, 3H), 3.16 (brs, 2H), 3.08 (brs, 2H) ppm; 13C NMR
(75 MHz, CDCl3): d=192.0, 190.6, 167.8, 158.7, 151.4, 142.4, 139.5, 138.4,
136.2, 133.8, 133.0, 130.8, 129.6, 129.4, 129.3, 129.0, 128.9, 128.5, 128.3,
125.6, 119.9, 113.6, 99.8, 55.2, 53.2, 48.4 ppm; MS (ESI): m/z (%): 680
[M+1]; elemental analysis calcd (%) for C42H37N3O4S: C 74.20, H 5.49, N
6.18; found: C 74.14, H 5.93, N 6.14.
1548C; IR (KBr): n˜ =1685, 1642, 1597, 1584, 1508 cmꢀ1
;
1H NMR
3
(500 MHz, CDCl3): d=7.80 (s, 1H), 8.45 (d, J
A
7.33 (m, 6H), 7.23 (d, 3J
ACHTREUNG
A
ACHTREUNG
3
4.31 (d, J
(t, 3J
A
ACHTREUNG
AHCTREUNG
149.1, 140.0, 139.9, 138.0, 131.0, 129.2, 128.5, 127.6, 127.2, 124.5, 120.7,
118.4, 103.7, 97.4, 60.9, 48.7, 13.7 ppm; MS (ESI): m/z (%): 566 [M+1];
elemental analysis calcd (%) for C33H28ClN3O2S: C 70.01, H 4.99, N 7.42;
found: 69.91, H 5.21, N 7.39.
1,3-Diphenyl-2’-para-nitrophenylimino-2’,3’-dihydrospiro(imidazolidine-
2,3’-thiophene)-4’,5’- diylbisphenylmethanone (14gd): 94% yield;
m.p. 172–1738C; IR (KBr): n˜ =1657, 1596, 1586, 1519, 1496 cmꢀ1
;
1H NMR (500 MHz, CDCl3): d=8.22 (d, 3J
3J(H,H)=7.5 Hz, 4H), 7.34 (t, 3J(H,H)=7.4 Hz, 1H), 7.26 (t, 3J
7.3 Hz, 1H), 7.16 (d, 3J
(H,H)=8.0 Hz, 4H), 7.03–7.06 (m, 4H), 7.01 (d,
3J(H,H)=7.9 Hz, 2H), 6.98 (d, 3J(H,H)=8.1 Hz, 2H), 6.80 (d, 3J
(H,H)=
8.1 Hz, 2H), 6.74 (d, 3J
(H,H)=7.5 Hz, 2H), 4.16 (brs, 2H), 3.94 ppm
ACHTREUNG
A
N
A
Ethyl
line-2,3’-pyrrole)-2’-thione-4’-carboxylate (15 cd): 48% yield; m.p. 167–
1688C; IR (KBr): n˜ =1697, 1636, 1595, 1525, 1494 cmꢀ1 1H NMR
(500 MHz, CDCl3): d=8.32(d, 3J
(H,H)=8.9 Hz, 2H), 7.52 (s, 1H), 7.44
(d, 3J(H,H)=9.0 Hz, 2H), 7.38 (d, 3J
(H,H)=5.5 Hz, 4H), 7.26–7.30 (m,
6H), 6.59–6.60 (m, 2H), 6.21–6.23 (m, 2H), 4.28 (d, 3J
(H,H)=16.2Hz,
2H), 4.25 (d, 3J(H,H)=17.6 Hz, 2H), 4.17 (q, 3J
(H,H)=7.1 Hz, 2H), 1.13
(t, 3J(H,H)=7.1 Hz, 3H) ppm; 13C NMR (125 MHz, CDCl3): d=205.3,
1,3-dibenzyl-1’-para-nitrophenyl-2’,3’-dihydrospiro(benzimidazo-
ACHTREUNG
G
;
N
ACHTREUNG
(brs, 2H); 13C NMR (125 MHz, CDCl3): d=190.2, 190.1, 173.1, 156.7,
145.8, 145.2, 144.6, 139.2, 137.2, 136.1, 133.8, 132.6, 129.4, 128.54, 128.49,
128.2, 128.1, 125.4, 120.9, 119.4, 117.0, 96.4, 47.2 ppm; MS (ESI): m/z
(%): 637 [M+1]; elemental analysis calcd (%) for C38H28N4O4S: C 71.68,
H 4.43, N 8.80; found: C 71.60, H 4.58, N 8.68.
A
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
AHCTREUNG
161.1, 146.6, 143.5, 142.4, 140.1, 137.1, 128.4, 128.1, 127.5, 125.2, 124.8,
118.7, 118.2, 104.9, 98.3, 60.8, 49.2, 13.9 ppm; MS (ESI): m/z (%): 577
[M+1]; elemental analysis calcd (%) for C33H28N4O4S: C 68.73, H 4.89, N
9.72; found C 68.74, H 5.10, N 9.58.
General procedure for the reaction of 2-thiocarbamoyl benzimidazolium
4 or imidazolinium inner salts 7 with ethyl propiolate: Ethyl propiolate
(5 mmol) was mixed with benzimidazolium salts 4 (1 mmol) or imidazoli-
nium salts 7 (1 mmol) in 1,2-dichloroethane or THF (20 mL) at ambient
temperature. The reaction mixture was stirred at reflux for a period of
time. After removal of the solvent, the residue was purified by column
chromatography on silica gel with petroleum ether (30–608C)/ethyl ace-
tate (5:1) as the eulant. The green-crystalline products 15 and red by-
products 16 or orange-crystalline products 17 and colourless crystalline
by-products 18 were isolated.
Ethyl
1,3-dibenzyl-1’-phenyl-2’,3’-dihydrospiro(imidazolidine-2,3’-pyr-
role)-2’-thione-4’-carboxylate (17da): 73% yield; m.p. 134–1358C; IR
1
(KBr): n˜ =1692, 1628, 1589 cmꢀ1; H NMR (500 MHz, CDCl3): d=7.48 (s,
1H), 7.48 (t, 3J
ACHTREUNG
5H), 7.24 (d, 3J
G
ACHTREUNG
3
(d, J
A
ACHTREUNG
2H), 3.23–3.26 (m, 2H), 1.41 ppm (t, 3J
ACHTREUNG
(125 MHz, C6D6): d=209.7, 161.4, 145.4, 139.6, 138.1, 128.9, 128.8, 128.3,
128.0, 127.0, 125.3, 118.0, 95.2, 59.7, 53.4, 48.2, 14.4 ppm; MS (ESI): m/z
(%): 484 [M+1]; elemental analysis calcd (%) for C29H29N3O2S: C 72.02,
H 6.04, N 8.69; found: C 72.10, H 6.11, N 8.71.
Ethyl
azoline-2,3’-pyrrole)-2’-thione-4’-carboxylate
m.p. 169–1708C; IR (KBr): n˜ =1711, 1698, 1626, 1601, 1510, 1495 cmꢀ1
1H NMR (500 MHz, CDCl3): d=7.47 (s, 1H), 7.43 (d, 3J
(H,H)=6.3 Hz,
4H), 7.29–7.31 (m, 6H), 7.17 (d, 3J(H,H)=8.2Hz, 2H), 7.97 (d, 3J-
(H,H)=8.2Hz, 2H), 6.53 (brs, 2H), 6.14 (brs, 2H), 4.31 (d, 3J
(H,H)=
15.5 Hz, 2H), 4.14–4.20 (m, 4H), 3.85 (s, 3H), 1.13 ppm (t, 3J
(H,H)=
1,3-dibenzyl-1’-para-methoxyphenyl-2’,3’-dihydrospiro(benzimid-
ACHTREUNG
(15cb): 81% yield;
;
AHCTREUNG
R
Ethyl 1,3-dibenzyl-2’-phenylimino-2’,3’-dihydrospiro(imidazolidine-2,3’-
thiophene)-4’-carboxylate (18da): 15% yield; m.p. 102–1038C; IR (KBr):
A
ACHTREUNG
U
n˜ =3057, 1696, 1640, 1582cm ꢀ1 1H NMR (500 MHz, CDCl3): d=7.78 (s,
;
6.7 Hz, 3H); 13C NMR (125 MHz, CDCl3): d=204.8, 161.4, 159.4, 145.9,
140.5, 137.5, 130.3, 128.3, 127.9, 127.3, 126.3, 118.4, 117.1, 114.6, 104.9,
98.2, 60.4, 55.6, 49.3, 14.0 ppm; MS (ESI): m/z (%): 562[ M+1]; elemen-
tal analysis calcd (%) for C34H31N3O3S: C 72.70, H 5.56, N 7.48; found: C
72.60, H 5.71, N 7.39.
1H), 7.41–7.45 (m, 6H), 7.32(t, 3J
3H), 7.08 (d, 3J(H,H)=7.6 Hz, 2H), 4.37 (q, 3J
(d, 3J(H,H)=13.6 Hz, 2H), 3.80 (d, 3J
(H,H)=13.4 Hz, 2H), 3.29 (brs,
4H), 1.42ppm (t, 3J(H,H)=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3):
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
d=170.2, 161.7, 151.4, 140.7, 139.4, 129.3, 128.4, 128.2, 127.5, 126.9, 125.4,
119.8, 93.1, 60.4, 53.4, 48.9, 14.5 ppm; MS (ESI): m/z (%): 484 [M+1]; el-
emental analysis calcd (%) for C29H29N3O2S: C 72.02, H 6.04, N 8.69;
found: C 72.00, H 6.00, N 8.62.
Ethyl 1,3-dibenzyl-2’-para-methoxyphenylimino-2’,3’-dihydrospiro(benzi-
midazoline-2,3’-thiophene)-4’-carboxylate (16cb): 10% yield; m.p. 156–
1578C; IR (KBr): n˜ =1687, 1642, 1584, 1504 cmꢀ1 1H NMR (500 MHz,
;
CDCl3): d=7.81 (s, 1H), 8.46 (d, 3J
6H), 6.83 (d, 3J(H,H)=8.8 Hz, 2H), 6.64 (d, 3J
(dd, 3J(H,H)=5.1, 3.2Hz, 2H), 6.15 (dd, 3J
(H,H)=5.1, 3.2Hz, 2H), 4.37
(d, 3J(H,H)=16.2Hz, 2H), 4.31 (d, 3J(H,H)=16.2Hz, 2H), 4.12 (q, 3J-
G
Ethyl 1,3-di(para-methoxy)benzyl-1’-phenyl-2’,3’-dihydrospiro(imidazoli-
dine-2,3’-pyrrole)-2’-thione-4’-carboxylate (17ea): 71% yield; m.p. 116–
A
ACHTREUNG
A
N
1178C; IR (KBr): n˜ =1717, 1616, 1512cm ꢀ1 1H NMR (500 MHz, C6D6):
;
A
N
d=7.54 (d, 3J
(H,H)=8.4 Hz, 4H), 7.26 (s, 1H), 7.06–7.14 (m, 5H), 6.92
U
4290
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 4282 – 4292

Regioselectivity of 1,3-Dipolar Cycloaddition Reactions
FULL PAPER
(d, 3J
(H,H)=13.2Hz, 2H), 3.99 (d, 3J
3.42(s, 8H), 1.72 ppm (t,
3J(H,H)=7.1 Hz, 3H); 13C NMR (125 MHz,
C6D6): d=209.9, 161.5, 159.2, 145.3, 138.2, 131.5, 130.0, 128.9, 127.7,
125.4, 118.2, 113.8, 95.1, 59.7, 54.6, 52.9, 48.3, 14.5 ppm; MS (ESI): m/z
(%): 544 [M+1]; elemental analysis calcd (%) for C31H33N3O4S: C 68.48,
H 6.12, N 7.73; found: C 68.66, H 6.53, N 8.12.
A
G
yield; m.p. 98–998C; IR (KBr): n˜ =1739, 1490, 1436 cmꢀ1
;
1H NMR
3
N
U
(500 MHz, CDCl3): d=7.49–7.51 (m, 6H), 7.34 (d, J
C
N
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
2.94 (m, 1H) ppm; 13C NMR (125 MHz, CDCl3): d=197.8, 170.0, 138.7,
137.73, 136.66, 133.8, 133.0, 132.7, 130.2, 129.7, 129.4, 128.5, 128.4, 126.4,
96.4, 55.4, 53.4, 52.6, 52.0, 49.4, 48.7, 46.4 ppm; MS (ESI): m/z (%): 574
[M+1]; elemental analysis calcd (%) for C28H26Cl3N3O2S: C 58.49, H
4.56, N 7.31; found: C 58.74, H 4.33, N 7.25.
Ethyl 1,3-di(para-methoxy)benzyl-2’-phenylimino-2’,3’-dihydrospiro(imi-
dazolidine-2,3’-thiophene)-4’-carboxylate (18ea): 15% yield; m.p. 119–
1208C; IR (KBr): n˜ =1726, 1634, 1610, 1579 cmꢀ1 1H NMR (500 MHz,
;
CDCl3): d=7.76 (s, 1H), 7.44 (t, 3J
(H,H)=8.3 Hz, 4H), 7.24 (t, 3J(H,H)=7.3 Hz, 1H), 7.07 (d, 3J
7.5 Hz, 2H), 6.85 (d, 3J(H,H)=8.4 Hz, 4H), 4.35 (q, 3J
(H,H)=7.0 Hz,
2H), 3.86 (d, 3J(H,H)=13.3 Hz, 2H), 3.82 (s, 6H), 3.72 (d, 3J
(H,H)=
13.2Hz, 2H), 3.24 (brs, 4H), 1.41 ppm (t, (H,H)=7.1 Hz, 3H);
3J
ACHTREUNG
1,3-Dibenzyl-4’-cyano-1’-phenyl-2’,3’,4’,5’-tetrahydrospiro(imidazolidine-
2,3’-pyrrole)-2’-thione (20da): 83% yield; m.p.149–1508C; IR (KBr): n˜ =
A
G
ACHTREUNG
1
2250, 1597, 1496, 1454, 1434 cmꢀ1; H NMR (500 MHz, CDCl3)?d?=7.66
U
ACHTREUNG
(d, 3J
5H), 7.39 (t, J
9.5 Hz, 1H), 4.08–4.22 (m, 4H), 3.81 (t, J
(H,H)=11.9 Hz, 1H), 3.31–3.36 (m, 2H), 3.19–3.23 ppm (m, 2H);
A
ACHTREUNG
U
ACHTREUNG
3
ACHTREUNG
AHCTREUNG
3
3
13C NMR (125 MHz, CDCl3): d=170.2, 161.7, 158.7, 151.4, 140.4, 140.4,
131.5, 129.5, 129.3, 125.3, 119.8, 113.6, 92.9, 60.4, 55.3, 52.7, 48.8,
14.5 ppm; MS (ESI): m/z (%): 544 [M+1]; elemental analysis calcd (%)
for C31H33N3O4S: C 68.48, H 6.12, N 7.73; found: C 68.23, H 6.24, N 7.69.
A
AHCTREUNG
13C NMR (75 MHz, CDCl3): d=196.8, 139.8, 138.6, 137.5, 129.7, 129.1,
128.7, 128.6, 128.5, 127.9, 127.6, 127.4, 125.2, 116.9, 95.5, 55.4, 53.9, 52.6,
49.6, 49.4, 34.5 ppm; MS (ESI): m/z (%): 439 [M+1]; elemental analysis
calcd (%) for C27H26N4S: C 73.94, H 5.98, N 12.77; found: C 73.83, H
6.24, N 12.57.
General procedure for the reaction of 2-thiocarbamoyl benzimidazolium
4 or imidazolinium inner salts 7 with methyl acrylate or acrylonitrile:
Imidazolinium salt 7 (100 mg) was mixed with redistilled methyl acrylate
(2mL) or acrylonitrile (2mL) in solution with triethylamine (1 mL) and
CHCl3 (10 mL) at ambient temperature. The reaction mixture was
heated to reflux for a period of time. The pale yellow crystalline products
19 or 20 were isolated from the reaction by chromatography on silica gel
with petroleum ether (60–908C)/ethyl acetate (5:1) as the eluant.
1,3-Di(para-methoxy)benzyl-4’-cyano-1’-phenyl-2’,3’,4’,5’-tetrahydrospiro-
AHCTREUNG
;
A
ACHTREUNG
AHCTREUNG
A
N
ACHTREUNG
Methyl
2,3’-pyrrole)-2’-thione-4’-carboxylate (19da): 83% yield; m.p. 157–1588C;
IR (KBr): n˜ =1726, 1497, 1440 cmꢀ1 1H NMR (500 MHz, CDCl3): d=
7.59 (d, 3J
(H,H)=7.4 Hz, 2H), 7.52–7.53 (m, 4H), 7.37–7.41 (m, 5H),
7.33 (t, 3J(H,H)=7.6 Hz, 2H), 7.22–7.29 (m, 2H), 4.67 (dd, 3J
(H,H)=
11.7, 9.2Hz, 1H), 4.15 (s, 2H), 4.10 (d, 3J
(H,H)=11.9 Hz, 1H), 3.99 (dd,
3J(H,H)=11.7, 9.6 Hz, 1H), 3.79 (t, 3J(H,H)=9.3 Hz, 1H), 3.70 (d, 3J-
(H,H)=11.9 Hz, 1H), 3.29–3.31 (m, 1H), 3.14–3.19 (m, 2H), 2.97–
1,3-dibenzyl-1’-phenyl-2’,3’,4’,5’-tetrahydrospiro(imidazolidine-
N
ACHTREUNG
3
AHCTREUNG
;
AHCTREUNG
ACHTREUNG
(m, 2H) ppm; 13C NMR (125 MHz, CDCl3): d=196.8, 159.1, 159.0, 139.8,
130.5, 130.2, 129.7, 129.1, 128.7, 125.3, 117.0, 114.4, 114.0, 113.8, 95.2,
55.5, 55.33, 55.29, 53.2, 52.0, 49.5, 49.2, 34.5 ppm; MS (ESI): m/z (%): 499
[M+1]; elemental analysis calcd (%) for C29H30N4O2S: C 69.85, H 6.06, N
11.24; found: C 69.80, H 6.18, N 11.14.
U
ACHTREUNG
AHCTREUNG
G
ACHTREUNG
ACHTREUNG
2.99 ppm (m, 1H); 13C NMR (125 MHz, CDCl3): d=197.9, 170.2, 140.6,
139.5, 138.5, 129.5, 128.9, 128.4, 128.3, 128.20, 128.17, 127.1, 127.0, 125.3,
96.7, 55.7, 54.0, 52.7, 52.5, 49.5, 48.9, 46.6 ppm; MS (EI): 55 (100), 91
(95), 471 ([M+], 6%); elemental analysis calcd (%) for C28H29N3O2S: C
71.30, H 6.20, N 8.91; found: C 71.21, H 6.32, N 8.96.
1,3-Di(para-methoxy)benzyl-4’-cyano-1’-para-chlorophenyl-2’,3’,4’,5’-tet-
rahydrospiro(imidazolidine-2,3’-pyrrole)-2’-thione (20ec): 86% yield;
m.p. 129–1308C; IR (KBr): n˜ =2244, 1611, 1512, 1491 cmꢀ1
;
1H NMR
(H,H)=
(H,H)=8.4 Hz,
(H,H)=9.5 Hz, 1H), 4.12
(H,H)=9.9 Hz, 1H), 3.98–4.04 (m, 3H), 3.84 (s, 3H), 3.83 (s, 3H),
3.78 (t, 3J(H,H)=9.5 Hz, 1H), 3.66 (d, 3J
(H,H)=11.9 Hz, 1H), 3.26–3.32
(500 MHz, CDCl3): d=7.55 (d, 3J
8.7 Hz, 2H), 7.41 (d, 3J(H,H)=8.7 Hz, 2H), 7.35 (d, 3J
2H), 6.91 (d, 3J(H,H)=7.4 Hz, 4H), 4.20 (t, 3J
(t, 3J
(H,H)=8.4 Hz, 2H), 7.50 (d, 3J
ACHTREUNG
G
ACHTREUNG
Methyl 1,3-di(para-methoxy)benzyl-1’-phenyl-2’,3’,4’,5’-tetrahydrospiro-
U
ACHTREUNG
ACHTREUNG
AHCTREUNG
;
N
ACHTREUNG
(m, 2H), 3.16–3.18 ppm (m, 2H); 13C NMR (125 MHz, CDCl3): d=197.1,
159.1, 159.0, 138.1, 134.3, 130.4, 130.2, 129.9, 129.5, 129.1, 126.5, 116.9,
114.0, 113.8, 95.2, 55.33, 55.29, 55.2, 53.2, 52.0, 49.5, 49.2, 34.4 ppm; MS
(ESI): m/z (%): 533 [M+1]; elemental analysis calcd (%) for
C29H29ClN4O2S: C 65.34, H 5.48, N 10.51; found: C 65.57, H 5.31, N
10.75.
A
N
ACHTREUNG
ACHTREUNG
E
ACHTREUNG
11.7 Hz, 1H), 3.25–3.29 (m, 1H), 3.10–3.14 (m, 2H), 2.90–2.94 ppm (m,
1H); 13C NMR (125 MHz, CDCl3): d=198.0, 170.3, 158.74, 158.69, 140.6,
131.5, 130.6, 130.1, 129.5, 129.3, 128.2, 125.3, 113.7, 113.6, 96.4, 55.7, 55.3,
55.2, 53.3, 52.5, 52.0, 49.3, 48.8, 46.5 ppm; MS (ESI): m/z (%): 532
[M+1]; elemental analysis calcd (%) for C30H33N3O4S: C 67.77, H 6.26, N
7.90; found: C 67.39, H 5.98, N 7.66.
Computational methods: Density functional calculations were performed
with the Gaussian 03 program package (see the Supporting Information).
The geometric parameters of the possible transition states, reactants and
products were optimised with B3LYP/6–31G* method and verified with
the number of imaginary frequencies. To mimic real experimental condi-
tions, a single-point polarised continuum model (PCM)[11] and the solvent
1,2-dichloroethane (dielectric constant e=10.36, 298.15 K) were em-
ployed to investigate some of reactions, which is denoted as SCRF-
B3LYP/6–31G*.
Methyl 1,3-di(para-methoxy)benzyl-1’-para-chlorophenyl-2’,3’,4’,5’-tetra-
hydrospiro(imidazolidine-2,3’-pyrrole)-2’-thione-4’-carboxylate
71% yield; m.p. 123–1248C; IR (KBr): n˜ =1724, 1612, 1512, 1494,
1437 cmꢀ1 1H NMR (500 MHz, CDCl3): d=7.48 (brs, 6H), 7.29 (d, 3J-
(H,H)=7.5 Hz, 2H), 6.91 (d, 3J(H,H)=8.5 Hz, 2H), 6.86 (d, 3J
(H,H)=
8.5 Hz, 2H), 4.65 (dd, 3J
(H,H)=11.4, 9.3 Hz, 1H), 4.04 (s, 2H), 3.92–4.04
(m, 2H), 3.84 (s, 3H), 3.82 (s, 3H), 3.77 (t, 3J
(H,H)=9.3 Hz, 1H), 3.58
(d, 3J
(H,H)=11.6 Hz, 1H), 3.24–3.25 (m, 1H), 3.08–3.13 (m, 2H), 2.89–
(19ec):
;
G
ACHTREUNG
ACHTREUNG
AHCTREUNG
ACHTREUNG
2.92 ppm (m, 1H); 13C NMR (75 MHz, CDCl3): d=198.3, 170.1, 158.8,
158.7, 139.0, 133.7, 131.3, 130.4, 130.0, 139.6, 129.3, 126.5, 113.7, 113.6,
96.3, 55.5, 55.3, 55.2, 53.3, 52.5, 52.0, 49.3, 48.7, 46.3 ppm; MS (ESI): m/z
(%): 566 [M+1]; elemental analysis calcd (%) for C30H32ClN3O4S: C
63.65, H 5.70, N 7.42; found: C 63.60, H 6.15, N 7.16.
Acknowledgements
This study was supported by the National Natural Science Foundation of
China for Distinguished Young Scholars (No. 20525207), the National
Natural Science Foundation of China (No. 20672013), the Program for
Methyl 1,3-di(para-chloro)benzyl-1’-para-chlorophenyl-2’,3’,4’,5’-tetrahy-
drospiro(imidazolidine-2,3’-pyrrole)-2’-thione-4’-carboxylate (19 fc): 88%
Chem. Eur. J. 2007, 13, 4282 – 4292
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4291

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Received: October 18, 2006
Revised: December 9, 2006
Published online: February 26, 2007
4292
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Chem. Eur. J. 2007, 13, 4282 – 4292