Efficient access to polysubstituted amidines, benzimidazoles and pyrimidines from amides

Article abstract of DOI:10.1016/j.tet.2009.12.034

Polysubstituted amidines, benzimidazoles and pyrimidines were synthesized via the electrophilic activation of amides with trifluoromethanesulfonic anhydride and 2-chloropyridine. The one-pot protocol is concise and efficient and the substrates are readily available.

Full text of DOI:10.1016/j.tet.2009.12.034

Tetrahedron 66 (2010) 1208–1214
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient access to polysubstituted amidines, benzimidazoles and pyrimidines
from amides
,
a,b,
*
Jing Wang a, Zhenxing He a, Xiaopeng Chen a, Wangze Song a, Ping Lu a , Yanguang Wang
*
a Department of Chemistry, Zhejiang University, Zheda Road 38#, Hangzhou, Zhejiang Province 310027, China
b State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Polysubstituted amidines, benzimidazoles and pyrimidines were synthesized via the electrophilic acti-
vation of amides with trifluoromethanesulfonic anhydride and 2-chloropyridine. The one-pot protocol is
concise and efficient and the substrates are readily available.
Received 17 October 2009
Received in revised form
7 December 2009
Accepted 11 December 2009
Available online 16 December 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Amides
Amidines
Benzimidazoles
Pyrimidines
Electrophilic activation
1. Introduction
diazoacetate through finely tuning the electrophilicity of the acti-
vated N-aryl amides using the combination of Tf2O, 2-ClPy and
Amidines are an important class of compounds for their bi-
ological properties1 and applications in heterocyclic synthesis.2
Consequently, their synthesis has received much attention.3 Con-
ventional methods for the preparation of polysubstituted amidines
include imidoylation of amines with imidoyl chlorides,4 imidate
fluoroborates,5 iminium triflates,6 iminium sulfonates,7 or
imidoylbenzotriazoles.3b
2,6-Cl2Py in a certain ratio.13 As the extension of these preliminary
results, we considered the amide itself function as a weak nucleo-
phile and tested the possibility of the self-dimerization of amides.
We herein report the details of this effort.
2. Results and discussion
As previous reported, amide is attractive starting material due to
their easily accessible. However, amide itself is seldom used in or-
ganic synthesis for its relative stable. The nitrogen atom of the
amide donates its lone pair electrons to C–N bond, both nucleo-
philicity of nitrogen and electrophilicity of carbonyl are hence de-
creased. There are several ways to activate the amide functional
group in the literature. Among those methods, combination of
trifluoromethanesulfonic anhydride (Tf2O) and pyridine or
2-chloropyridine (2-ClPy) is hitherto the most attractive and
feasible way. In the presence of a suitable nucleophile, a variety of
compounds such as piperidines,8 carboxylic acid derivatives,9
amines,10 pyrimidines,11 and pyridines12 were thus constructed via
this electrophilic activation of amide pathway. Recently, we also
developed a one-pot domino synthesis of indoles from amides and
Initially, we chose to focus our attention on the reaction of
N-phenylbenzamide (1a). As we expected, when the combination
of Tf2O and 2-ClPy was used as the activating reagent, the amidine
2a was readily obtained (Scheme 1).
In order to obtain the optimized reaction conditions, several
combinations of base additive were investigated (Table 1). When
pyridine and its analogous (Py, 2-ClPy, and 2,6-Cl2Py) were used as
base additive (Table 1, entries 8, 7, and 4, respectively), dimerized
product 2a was isolated in moderate to good yield. Other base
additives such as DMAP, triethylamine or DBU (Table 1, entries 9, 10
and 11, respectively) were found to be ineffective in this one-pot
approach. 2-ClPy functioned as base additive was thereby screened
for further investigation. By comparison, refluxing is necessary for
reaction completeness (Table 1, entries 4, 5 and 6), whereas half
hour is enough (Table 1, entries 2, 3 and 4). Dimerization may also
occur using Tf2O as the sole activating reagent but with relatively
lower yield (Table 1, entries 1 and 2). The mechanism presented in
Scheme 1 showed slightly difference between with or without the
* Corresponding authors. Tel./fax: þ86 571 87951512.
E-mail addresses: pinglu@zju.edu.cn (P. Lu), orgwyg@zju.edu.cn (Y. Wang).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.12.034

J. Wang et al. / Tetrahedron 66 (2010) 1208–1214
1209
Table 2
O
Synthesis of amidines 2a
Ph
Ph
N
H
R2
O
N
R1
2-ClPy (0.6 equiv)
Tf2O (0.6 equiv)
O
weaker electrophile
R1
R2
N
R2
N
H
R1
1a
DCM
C ~ reflux, 0.5 h
OTf
Ph
78°
1
2
Ph
N
Tf2O
1a
Entry
R1
R2
Product
Yieldb (%)
stronger electrophile
2-ClPy
Ph
N
Ph
1
2
3
4
5
6
7
8
Ph
Ph
Ph
2-ClC6H4
Ph
Ph
Ph
Ph
Ph
n-C5H11
2a
2b
2c
2d
2e
2f
85
85
84
80
79
83
90
89
OTf
Ph
O
N
Ph
1a
4-MeOC6H4
Ph
N
OTf
OTf
H
Ph
N
Ph
2a
2-Me-4-MeO-C6H3
4-MeC6H4
4-BrC6H4
2-MeC6H4
Ph
N
2-ClPy
Ph
2g
2h
Cl
the strongest electrophile
Scheme 1. Formation of amidine 2a.
Ph
2i
2j
84
82
O
S
9
4-MeC6H4
10
a
Table 1
Survey of reaction conditions for preparation of amidine 2a
All reactions were performed on 1 mmol of amide.
Isolated yield refers to amide.
b
Ph
N
O
Tf2O (0.6 equiv)
DCM
base additive
Ph
Ph
Ph
N
H
O
N
Ph
Ph
1a
Table 3
2a
Synthesis of 1-acyl-benzimidazoles 4a
O
R2
NH
Entry
Base additive (equiv)
Temperature (ꢀC)
Time (h)
Yielda (%)
R1
R1
N
2-ClPy (1.2 equiv)
Tf2O (1.2 equiv)
R1
R1
1
2
3
4
5
6
7
8
none
ꢁ78wreflux
ꢁ78wreflux
ꢁ78wreflux
ꢁ78wreflux
ꢁ78wrt.
8
8
3
50
88
86
85
75
20
78
80
R2
R2
2-ClPy (0.6)
2-ClPy (0.6)
2-ClPy (0.6)
2-ClPy (0.6)
2-ClPy (0.6)
2,6-Cl2Py (0.6)
Py (0.6)
DMAP (0.6)
TEA (0.6)
DBU (0.6)
N
DCM
-78°C ~ reflux 0.5 h
NH
R2
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
O
O
4
ꢁ78
3
ꢁ78wreflux
ꢁ78wreflux
ꢁ78wreflux
ꢁ78wreflux
ꢁ78wreflux
Entry
R1
R2
Product
Yieldb (%)
9
10
11
trace
trace
trace
1
2
3
4
5
6
7
H
H
Cl
Cl
Ph
4-ClC6H4
Ph
4-MeC6H4
Ph
4-ClC6H4
2-MeC6H4
4a
4b
4c
4d
4e
4f
62
58
60
66
55
51
58
a
Isolated yield refers to amide 1a.
CH3
CH3
H
participation of 2-ClPy. In comparison with phosphoric anhydride14
as activating reagent, our method is more general and efficient.
Using the optimized reaction condition, we explored the scope
of the reaction with a variety of the accessible amides (Table 2). In
all cases, amides 1 proceeded to furnish the corresponding
substituted amidines 2. Both the amides with an aromatic acyl
(Table 2, entries 1–7) and the amides with an aliphatic acyl (Table 2,
entry 8) gave good to excellent yields (79–90%). The amide with
heterocycles such as furan or thiophene (Table 2, entries 9 and 10,
respectively) could also undergo the reaction. Moreover, the in-
ductive effects of the N-aryl side of amide on the reaction were
insignificant (Table 2, entries 1, 3, 5 and 6).
When the amides 3a–3g, derived from symmetric 1,2-dia-
minobenzenes, were used as the substrates, N-acyl benzimidazoles
4 were constructed in moderate yields (Table 3). Unsymmetrically
substituted diamides 5 afforded a mixture of two isomers 6 and 7
(Table 4). The structure of 7c was unambiguously determined by
X-ray diffraction analysis.15
4g
a
All reactions were performed on 1 mmol of amide.
Isolated yield refers to amide.
b
Table 4
Synthesis of 1-acyl-benzimidazoles 6 and 7a
N
R2
R2
R2
NH
R1
R1
N
O
2-ClPy (1.2 equiv)
Tf2O (1.2 equiv)
O
6
DCM
-78°C ~ reflux 0.5 h
R1
NH
R2
N
N
R2
R2
O
5
O
7
Entry
R1
R2
Product
6aþ7a (4:3)b
Yieldc (%)
Since benzimidazoles are of wide applications as drugs with
biological and pharmaceutical impact,16 and as molecular pre-
cursors for the development of ligands,17 dyes18 and polymers,19
our reaction provides a novel synthetic method leading to this
important class of heterocyclic compounds.
1
2
Me
Cl
Ph
53
32
24
24
30
2-MeC6H4
6b
7b
6c
7c
3
NO2
Ph
Using optical diamide 8 as the substrate, derived from (1R,2R)-
a
All reactions were performed on 1 mmol of amide 5.
The ratio for 6a/7a was determined by 1H NMR spectra.
Isolated yield refers to amide.
b
c
cyclohexane-1,2-diamine, chrial dihydroimidazoles
obtained in excellent yields (Scheme 2).
9
were

1210
J. Wang et al. / Tetrahedron 66 (2010) 1208–1214
O
O
R1
2-ClPy(1.2 equiv)
Tf2O (1.2 equiv)
NH
N
N
R1
R1
DCM
-78°C~reflux 0.5h
NH
R1
O
9a: R1=Ph, 90% yield
8
9b: R1=2-MeC6H4, 85% yield
Scheme 2. Synthesis of dihydroimidazoles 9.
Furthermore, when the amine part of amide was changed to 1,8-
diaminonaphthlene, an intramolecular ring closure reaction also
occurred and pyrimidine derivatives 11 were generated (Scheme 3).
Similarly, when N,N0-diphenylphthalamide 12 was used as the
substrate, we obtained isoindol-1-one 13 (Scheme 4).
O
O
R
O
Figure 1. X-ray diffraction structure of 2a.
2-ClPy(1.2 equiv)
Tf2O (1.2 equiv)
R
NH HN
R
N
N
R
DCM
-78°C~reflux 0.5h
11a: R=Ph, 73% yield
10
11b: R=4-ClC6H4, 56% yield
Scheme 3. Synthesis of pyrimidines 11.
NHPh
Ph
N
2-ClPy(1.2 equiv)
Tf2O (1.2 equiv)
O
O
N
Ph
DCM
-78°C~reflux 0.5h
O
NHPh
12
13 65% yield
Scheme 4. Synthesis of isoindolone 13.
As an expansion of this synthetic method, we could conve-
niently remove the acyl group of amidines 2 using excess hydrazine
hydrate in DCM at room temperature (Table 5). The hydrazinolysis
gave the corresponding amidines 14 in excellent yields.
Structure of benzamidine 2a was determined by X-ray diffrac-
tion analysis (Fig. 1).20 The C]N double bond adopted a Z config-
uration. Rotation of both N(1)–(25) and N(1)–C(26) resulted in four
ultimate conformers I, II, III and IV (Fig. 2). Conformer I has the
lowest energy and its structure is eventually consistent with the
crystal structure which was shown in Figure 1. Energy differences
for II, III and IV in comparison with I, respectively, were calculated
to be 1.3, 2.3 and 0.7 kcal/mol higher. Inter-conversion among those
four ultimate conformers led to the complexity of 1H and 13C NMR
spectra at room temperature. This kind of complexity for N-
Figure 2. Four ultimate conformers calculated by B3LYP/6–31G (d) method. Grey, blue,
red, and white balls represent C, N, O and H, respectively.
acylamidines has also reported previously by Tebby.14 Simplified
NMR spectra could be expected either by raising the temperature in
the case of 2b (see Supplementary data) or by deacylation of ami-
dines 2a, 2e and 2j via hydrazinolysis as examples (Table 5). It is
also noteworthy that 4, 6, 7, 9, 11 and 13 present neat 1H and 13C
NMR spectra due to the rigidity of these heterocyclic structures.
Table 5
Synthesis of amidines 14a
3. Conclusion
R2
N
R1
R2
HN
N
.
NH2NH2 H2O
R1
In conclusion, we have developed a one-pot approach to poly-
substituted amidines, benzimidazoles and pyrimidines via the
electrophilic activation of amides with trifluoromethanesulfonic
anhydride and 2-chloropyridine. The present method is concise
and efficient, and the reaction substrates are readily available.
O
N
R1
DCM
R1
R2
2
14
Entry
R1
R2
Product
Yieldb (%)
1
2
Ph
4-MeC6H4
Ph
Ph
14a
14b
98
95
4. Experimental
4.1. General
3
4-MeC6H4
14c
95
S
Infrared spectra were obtained on a FTIR spectrometer. 1H NMR
spectra were recorded on 500 MHz or 400 MHz spectrometer. The
a
All reactions were performed on 1 mmol of amide.
Isolated yield refers to 2.
b

J. Wang et al. / Tetrahedron 66 (2010) 1208–1214
1211
chemical shifts were reported relative to internal standard TMS (0)
in CDCl3 or 2.5 in DMSO-d6. The following abbreviations were used
to describe peak patterns where appropriate: b¼broad, s¼singlet,
d¼doublet, t¼triplet, q¼quartet, m¼multiplet. Coupling constants
were reported in Hertz (Hz). 13C NMR were recorded on 125 MHz or
100 MHz spectrometer, referred to the internal solvent signals (77.0
for CDCl3 or 40.0 for DMSO-d6). MS and HRMS were obtained using
ESI ionization. Melting points were measured with micro melting
point apparatus.
2.33–2.12 (m, 6H); 13C NMR (DMSO-d6, 125 MHz)
d
172.5, 158.7,
158.1, 157.8, 155.8, 141.1, 137.6, 137.0, 136.2, 133.0, 132.7, 132.6, 132.1,
131.4, 130.7, 130.1, 130.0, 129.4, 129.2, 129.0, 128.9, 128.7, 128.7,
128.5, 127.9, 126.5, 119.8, 118.5, 117.7, 116.3, 115.8, 112.6, 112.2, 111.5,
111.0, 55.7, 55.6, 55.5, 55.4, 19.5, 18.7, 18.6, 17.7; IR (KBr) v 3060,
2949, 1677, 1618, 1579, 1501, 1280, 1250, 695 cmꢁ1; MS (ESI) m/z
465.1 ([MþH]þ); HRMS (ESI) calcd for C30H28N2O3 ([MþH]þ),
465.2173; found, 465.2196.
4.2.5. N,N0-Bis(4-methylphenyl)-N-benzoylbenzamidine (2e). Ethyl
4.2. General Procedure for the synthesis of amidines 2
acetate/Petroleum ether (1/6) was used as eluent. White solid; mp
127–128 ꢀC; 1H NMR (DMSO-d6, 500 MHz)
d
8.01–7.77 (m, 2H),
7.50–6.37 (m, 16H), 2.21–2.12 (m, 6H); 13C NMR (DMSO-d6,
125 MHz) 172.7, 170.4, 157.9, 154.2, 146.5, 146.1, 138.6, 138.3, 137.0,
To a mixture of amide 1 (1 mmol) and 2-ClPy (0.6 mmol) in
DCM (1.6 mL) was gradually added a solution of Tf2O (0.6 mmol) in
DCM (0.4 mL) via a syringe at ꢁ78 ꢀC. The reaction mixture was
kept at ꢁ78 ꢀC for 5 min and at ambient temperature for addi-
tional 5 min and then refluxed for 0.5 h. The reaction mixture was
diluted with DCM (25 mL). The organic layer was sequentially
washed with the saturated aqueous CuSO4 solution (10 mL), brine
(15 mLꢂ2), and water (10 mL). The organic layer was dried over
anhydrous Na2SO4 and filtered. The filtrate was concentrated un-
der vacuum and the residue was purified by silica gel column
chromatography by using a mixture of ethyl acetate and petro-
leum ether as the eluent.
d
136.6, 135.8, 135.6, 134.4, 133.7,132.4, 131.7, 131.4, 130.5, 130.3, 130.1,
129.8, 129.6, 129.2, 128.7, 128.5, 128.0, 125.9, 121.4, 120.6, 119.7, 21.0,
20.9, 20.8; IR (KBr) v 3058, 2919, 1671, 1623, 1510, 1286, 817,
695 cmꢁ1; MS (ESI) m/z 405.1 ([MþH]þ); HRMS (ESI) calcd for
C28H24N2O ([MþH]þ), 405.1961; found, 405.1966.
4.2.6. N,N0-Bis(4-bromophenyl)-N-benzoylbenzamidine (2f). Ethyl
acetate/Petroleum ether (1/6) was used as eluent. White solid; mp
169–170 ꢀC; 1H NMR (DMSO-d6, 500 MHz)
d
8.01–7.80 (m, 2H),
7.52–7.23 (m, 13H), 6.71–6.46 (m, 3H); 13C NMR (DMSO-d6,
125 MHz) 172.6,170.2,158.5, 148.1,140.5,140.2, 136.3, 135.2,133.5,
d
4.2.1. N,N0-Diphenyl-N-benzoylbenzamidine (2a). Ethyl acetate/
132.6, 132.3, 132.1, 132.0, 131.8, 130.8, 130.5, 129.4, 128.9, 128.7,
128.1, 122.9, 122.0, 120.3, 119.3, 117.2, 115.9; IR (KBr) v 3064, 1653,
1631, 1484, 1326, 1281, 831, 715, 694 cmꢁ1; MS (ESI) m/z 555.0
([MþNa]þ); HRMS (ESI) calcd for C26H18Br2N2O ([MþNa]þ),
554.9678; found, 554.9705.
Petroleum ether (1/6) was used as eluent. White solid; mp
174–175 ꢀC; 1H NMR (DMSO-d6, 500 MHz)
d
8.04–7.77 (m, 2H),
7.51–6.49 (m, 18H); 13C NMR (DMSO-d6, 125 MHz)
d
172.8, 170.5,
158.2, 154.8, 149.0, 148.6, 141.3, 140.9, 136.8, 135.6, 134.1, 132.3,
131.9, 131.6, 130.5, 130.4, 129.6, 129.3, 128.8, 128.7, 128.5, 128.3,
127.3, 126.5, 126.1, 124.7, 123.6, 120.6, 119.7; IR (KBr) v 3068, 3031,
1654, 1627, 1594, 1489, 1340, 1277, 765, 693 cmꢁ1; MS (ESI) m/z
399.4 ([MþNa]þ); HRMS (ESI) calcd for C26H20N2O ([MþNa]þ),
399.1468; found, 399.1484.
4.2.7. N,N0-Bis(2-methylphenyl)-N-benzoylbenzamidine (2g). Ethyl
acetate/Petroleum ether (1/6) was used as eluent for column
chromatography. White solid; mp 117–118 ꢀC; 1H NMR (DMSO-d6,
500 MHz)
9H), 7.06–7.05 (m, 2H), 6.77–6.76 (m, 2H), 6.00–5.98 (m, 1H), 2.38
(s, 3H), 2.14 (s, 3H); 13C NMR (DMSO-d6, 125 MHz)
172.4, 157.8,
d 7.79–7.78 (m, 2H), 7.41–7.38 (m, 3H), 7.31–7.15 (m,
4.2.2. N,N0-Diphenyl-N-(2-chlorobenzoyl)-2-chlorobenzamidine
d
(2b). Ethyl acetate/Petroleum ether (1/6) was used as eluent. White
147.7, 140.1, 139.7, 136.7, 136.1, 132.8, 132.3, 131.6, 131.5, 130.4,
130.3, 129.3, 129.0, 128.8, 128.7, 128.6, 128.2, 127.4, 126.5, 124.4,
123.6, 118.8, 117.6, 18.5, 18.3, 17.4; IR (KBr) v 3066, 2924, 1677, 1627,
1491, 1294, 1269, 757, 698 cmꢁ1; MS (ESI) m/z 405.1 ([MþH]þ);
HRMS (ESI) calcd for C28H24N2O ([MþH]þ), 405.1961; found,
405.1959.
solid; mp 151–152 ꢀC; 1H NMR (DMSO-d6, 500 MHz)
d 7.67–7.64
(m, 2H), 7.49 (d, J¼7.5 Hz, 2H), 7.35–7.22 (m, 9H), 7.05–7.02 (m, 2H),
6.85–6.82 (m, 1H), 6.49 (d, J¼7.5 Hz, 2H); 13C NMR (DMSO-d6,
125 MHz) d 168.6, 154.8, 147.7, 140.1, 136.6, 132.4, 132.1. 131.8, 131.6,
131.5, 131.4, 130.7, 130.4, 130.1, 129.7, 129.5, 129.2, 129.0, 128.8,
128.5, 127.8, 127.3, 127.2, 126.9, 124.7, 124.0, 120.8, 119.5; IR (KBr) v
3061, 1677, 1645, 1590, 1492, 1327, 1294, 772, 695 cmꢁ1; MS (ESI)
m/z 445.1 ([MþH]þ); HRMS (ESI) calcd for C26H18Cl2N2O ([MþH]þ),
445.0869; found, 445.0883.
4.2.8. N-Phenyl-N-(1-(phenylimino)hexyl)hexanamide (2h). Ethyl
acetate/Petroleum ether (1/6) was used as eluent. Yellow oil; 1H
NMR (DMSO-d6, 500 MHz)
d 7.48–6.90 (m, 8H), 6.72–6.70 (m, 2H),
2.58–2.33 (m, 3H), 1.94–1.46 (m, 4H), 1.29–1.23 (m, 5H), 1.06–0.97
4.2.3. N,N0-Bis(4-methoxyphenyl)-N-benzoylbenzamidine
(2c). Ethyl acetate/Triethylamine/Petroleum ether (1/1/6) was
used as eluent. Yellow solid; mp 154–155 ꢀC; 1H NMR (DMSO-d6,
(m, 4H), 0.86–0.83 (m, 3H), 0.76–0.71 (m, 3H); 13C NMR (DMSO-d6,
125 MHz)
d 174.6, 173.0, 162.1, 148.8, 140.7, 139.3, 129.8, 129.5,
129.1, 128.8, 128.1, 127.7, 124.2, 123.8, 119.8, 119.6, 36.8, 36.5, 34.1,
31.3, 31.1, 30.9, 30.3, 26.0, 25.7, 25.2, 24.7, 22.4, 22.3, 22.2, 21.8,
14.4, 14.3, 14.1, 14.0; IR (KBr) v 3062, 2956, 2860, 1687, 1655, 1594,
1492, 1289, 1249, 758, 697 cmꢁ1; MS (ESI) m/z 387.3 ([MþNa]þ);
HRMS (ESI) calcd for C24H32N2O ([MþNa]þ), 387.2407; found,
387.2425.
500 MHz)
d
8.04–7.78 (m, 2H), 7.51–7.12 (m, 9H), 6.91–6.42 (m,
172.8,
7H), 3.68–3.60 (m, 6H); 13C NMR (DMSO-d6, 125 MHz)
d
170.4, 158.2, 157.9, 157.6, 157.0, 155.8, 154.3, 140.5, 142.2, 141.7,
139.6, 137.1, 135.7, 134.4, 133.7, 133.5, 132.5, 131.5, 131.3, 130.5,
130.2, 129.4, 129.2, 128.7, 128.6, 128.2, 127.4, 123.1, 122.0, 121.2,
114.7, 114.6, 114.4, 55.7, 55.6, 55.5; IR (KBr) v 3061, 2953, 1651,
1624, 1578, 1508, 1345, 1249, 829, 697 cmꢁ1; MS (ESI) m/z 437.4
([MþH]þ); HRMS (ESI) calcd for C28H24N2O3 ([MþH]þ), 437.1860;
found, 437.1880.
4.2.9. N-(Furan-2-yl(phenylimino)methyl)-N-phenylfuran-2-carbox-
amide (2i). Ethyl acetate/Petroleum ether (1/4) was used as eluent.
White solid; mp 149–150 ꢀC; 1H NMR (DMSO-d6, 500 MHz)
d
7.93–
7.80 (m, 1H), 7.70 (s, 1H), 7.43–7.17 (m, 6H), 7.07–7.01 (m, 2H), 6.78–
6.37 (m, 6H); 13C NMR (DMSO-d6, 125 MHz)
160.8, 159.4, 150.1,
4.2.4. N,N0-Bis(2-methyl-4-methoxyphenyl)-N-benzoylbenzamidine
d
(2d). Ethyl acetate/Petroleum ether (1/4) was used as eluent. Yel-
149.2, 148.0, 147.6, 147.1, 147.0, 146.8, 146.0, 145.2, 144.6, 140.6,
139.9, 129.8, 129.5, 129.4, 129.2, 127.5, 127.3, 127.0, 126.3, 125.1,
124.3, 120.3, 119.5, 118.8, 118.6, 118.3, 116.5, 113.2, 112.7, 112.6; IR
(KBr) v 3137, 3123, 1673, 1645, 1592, 1461, 1323, 1304, 1179, 753,
low solid; mp 179–180 ꢀC; 1H NMR (DMSO-d6, 500 MHz)
d 7.78 (m,
2H), 7.40 (br s, 3H), 7.30–7.27 (m, 3H), 7.19 (br s, 2H), 6.78–6.55 (m,
4H), 6.32 (d, J¼6 Hz, 1H), 5.88–5.76 (m, 1H), 3.71–3.57 (m, 6H),

1212
J. Wang et al. / Tetrahedron 66 (2010) 1208–1214
693 cmꢁ1; MS (ESI) m/z 357.0 ([MþH]þ); HRMS (ESI) calcd for
C22H16N2O3 ([MþH]þ), 357.1234; found, 357.1238.
21.8, 21.4; IR (KBr) v 3033, 1711, 1605, 1438, 1314, 1271, 1228, 1178,
828 cmꢁ1; MS (ESI) m/z 394.9 ([MþH]þ); HRMS (ESI) calcd for
C22H16Cl2N2O ([MþH]þ), 395.0712; found, 395.0715.
4.2.10. N-(Thiophen-2-yl(p-tolylimino)methyl)-N-p-tolylthiophene-
2-carboxamide (2j). Ethyl acetate/Petroleum ether (1/3) was used
as eluent for column chromatography. Yellow solid; mp
4.3.5. N-Benzoyl-2-phenyl-5,6-dimethylbenzimidazole (4e). Ethyl
acetate/Petroleum ether (1/6) was used as eluent. White solid; mp
173–174 ꢀC; 1H NMR (DMSO-d6, 500 MHz)
d
7.82–6.55 (m, 14H),
125–126 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
7.65 (m, 2H), 7.62 (s, 1H),
7.55 (m, 2H), 7.47 (t, J¼7.6 Hz, 1H), 7.30 (t, J¼8 Hz, 3H), 7.24 (m, 3H),
2.39 (s, 3H), 2.33 (s, 3H); 13C NMR (CDCl3, 100 MHz)
169.2, 153.1,
2.28–2.23 (m, 6H); 13C NMR (DMSO-d6, 125 MHz)
d
165.3, 163.4,
152.1, 149.1, 146.6, 144.8, 141.4, 139.1, 138.9, 137.4, 137.0, 134.6,
134.3, 133.8, 133.5, 133.0, 132.7, 132.5, 132.2, 131.7, 130.3, 130.2,
130.1, 129.8, 128.8, 128.1, 127.9, 127.5, 127.2, 125.4, 120.4, 119.3, 21.2,
21.0; IR (KBr) v 3094, 3073, 3018, 2922, 1647, 1624, 1510, 1412,
1355, 1238, 1110, 854, 817, 754, 745, 716 cmꢁ1; MS (ESI) m/z 416.8
([MþH]þ); HRMS (ESI) calcd for C24H20N2OS2 ([MþH]þ), 417.1090;
found, 417.1086.
d
141.4, 134.0, 133.8, 133.4, 133.4, 133.3, 130.7, 130.4, 129.5, 129.1,
128.5, 128.2, 120.2, 113.4, 20.6, 20.3; IR (KBr) v 3061, 1697, 1598,
1448, 1325, 1281, 1226, 1176, 700 cmꢁ1; MS (ESI) m/z 327.0
([MþH]þ); HRMS (ESI) calcd for C22H18N2O ([MþH]þ), 327.1492;
found, 327.1489.
4.3.6. N-(4-Chlorobenzoyl)-2-(4-chlorophenyl)-5,6-dimethylbenz-
imidazole (4f). Ethyl acetate/Petroleum ether (1/6) was used as
eluent. White solid; mp 213–214 ꢀC; 1H NMR (CDCl3, 400 MHz)
4.3. Procedure for the synthesis of 4, 6, 7, 9, 11 and 13
A solution of Tf2O (1.2 mmol) in DCM (0.4 mL) was added into
a mixture of amide (1 mmol) and 2-ClPy (1.2 mmol) in DCM
(1.6 mL) via a syringe at ꢁ78 ꢀC. The reaction temperature was
firstly kept at ꢁ78 ꢀC for 5 min and raised to ambient temperature
for 5 min. After the mixture was refluxed for 0.5 h, the reaction
mixture was diluted with DCM (25 mL). Organic layer was then
sequentially washed with saturated aqueous CuSO4 solution
(10 mL), water (10 mL) and brine (15 mLꢂ2). Then dried over an-
hydrous Na2SO4, and evaporated under reduced pressure. The
crude product was purified by silica gel column chromatography.
d
7.64 (s, 1H), 7.61 (d, J¼3.6 Hz, 2H), 7.50 (d, J¼8.4 Hz, 2H), 7.35 (d,
J¼8.4 Hz, 2H), 7.27 (d, J¼8.0 Hz, 2H), 7.21 (s, 1H), 2.39 (s, 3H), 2.33
(s, 3H); 13C NMR (CDCl3, 100 MHz)
168.0, 151.8, 141.3, 140.8,
d
135.9, 134.5, 133.8, 133.2, 131.8, 131.4, 130.3, 129.2, 129.0, 128.7,
130.4, 113.2, 20.6, 20.3; IR (KBr) v 3090, 3060, 1698, 1588, 1460,
1322, 1278, 1225, 1174, 1090, 845 cmꢁ1; MS (ESI) m/z 395.1
([MþH]þ); HRMS (ESI) calcd for C22H16Cl2N2O ([MþH]þ),
395.0712; found, 395.0713.
4.3.7. N-(2-Methylbenzoyl)-2-(2-methylphenyl)benzimidazole
(4g). Ethyl acetate/Petroleum ether (1/3) was used as eluent. White
4.3.1. N-Benzoyl-2-phenylbenzimidazole (4a). Ethyl acetate/Petro-
solid; mp 113–114 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
7.85 (d, J¼8 Hz,
leum ether (1/4) was used as eluent. White solid; mp 150–151 ꢀC;
1H), 7.49 (d, J¼8 Hz, 1H), 7.42–7.39 (m, 1H), 7.34–7.31 (m, 1H), 7.27–
1H NMR (CDCl3, 400 MHz)
d
7.88 (d, J¼7.6 Hz, 1H), 7.70 (d, J¼8 Hz,
2H), 7.60 (m, 2H), 7.51 (t, J¼7.6 Hz, 1H), 7.46 (d, J¼8 Hz, 1H), 7.41–
7.26 (m, 7H); 13C NMR (CDCl3, 100 MHz)
169.1, 154.0, 142.9, 134.9,
7.22 (m, 2H), 7.19–7.02 (m, 6H), 2.36 (s, 3H), 2.34 (s, 3H); 13C NMR
(CDCl3, 100 MHz)
d 168.8, 153.4, 142.8, 138.2, 136.9, 133.7, 133.7,
d
131.9, 131.2, 131.0, 130.2, 129.7, 129.5, 129.0, 125.4, 125.2, 124.9,
124.6, 120.2, 113.7, 20.0, 19.7; IR (KBr) v 3056, 2956, 1704, 1537,
1452, 1329, 1308, 1220, 1146, 934, 891, 764, 750 cmꢁ1; MS (ESI) m/z
327.1 ([MþH]þ); HRMS (ESI) calcd for C22H18N2O ([MþH]þ),
327.1492; found, 327.1489.
134.0, 133.1, 130.5, 130.4, 129.8, 129.2, 128.7, 128.3, 124.6, 124.5,
120.2, 113.1; IR (KBr) v 3058, 1702, 1598, 1451, 1334, 1286, 1226,
751 cmꢁ1; MS (ESI) m/z 299.1 ([MþH]þ); HRMS (ESI) calcd for
C20H14N2O ([MþH]þ), 299.1179; found, 299.1190.
4.3.2. N-(4-Chlorobenzoyl)-2-(4-chlorophenyl)benzimidazole
4.3.8. N-Benzoyl-2-phenyl-6-methylbenzimidazole (6a) and N-Ben-
zoyl-2-phenyl-5-methylbenzimidazole (7a). Ethyl acetate/Petro-
leum ether (1/3) was used as eluent. White solid; mp 115–116 ꢀC;
(4b). Ethyl acetate/Petroleum ether (1/3) was used as eluent. White
solid; mp 185–186 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
7.87 (d, J¼7.6 Hz,
1H), 7.67 (d, J¼8 Hz, 2H), 7.55 (d, J¼8 Hz, 2H), 7.40 (m, 4H), 7.32 (m,
3H); 13C NMR (CDCl3, 100 MHz)
167.8, 152.7, 142.9, 141.1, 136.3,
1H NMR (CDCl3, 400 MHz) (6a:7a¼4:3, total 37H)
d
7.76–7.12 (m,
d
31H), 2.50 (s, 3H), 2.44 (s, 3H); 13C NMR (CDCl3, 100 MHz)
d 169.2,
134.7, 131.9, 131.2, 130.4, 129.3, 128.8, 128.7, 125.0, 124.8, 120.4,
113.0; IR (KBr) v 3089, 3056, 1705, 1587, 1449, 1328, 1288, 1224,
758 cmꢁ1; MS (ESI) m/z 367.2 ([MþH]þ); HRMS (ESI) calcd for
C20H12Cl2N2O ([MþH]þ), 367.0398; found, 367.0415.
169.1, 154.0, 153.4, 143.2, 141.0, 135.2, 134.9, 134.3, 133.8, 133.2,
133.2, 133.0, 130.6, 130.6, 130.5, 129.6, 129.6, 129.2, 129.1, 128.6,
128.6, 128.2, 126.0, 125.9, 120.0, 119.7, 113.0, 112.7, 21.8, 21.5; IR
(KBr) v 3059, 3030, 2924, 2864, 1709, 1598, 1478, 1450, 1327, 1308,
1288, 1225, 1178, 906, 768, 698 cmꢁ1; MS (ESI) m/z 313.1 ([MþH]þ);
HRMS (ESI) calcd for C21H16N2O ([MþH]þ), 313.1335; found,
313.1331.
4.3.3. N-Benzoyl-2-phenyl-5,6-dichlorobenzimidazole (4c). Ethyl
acetate/Petroleum ether (1/6) was used as eluent. White solid; mp
131–132 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
7.94 (s, 1H), 7.69 (s, 1H),
7.63 (m, 2H), 7.55 (m, 2H), 7.50 (m, 1H), 7.35–7.24 (m, 5H); 13C NMR
(CDCl3, 100 MHz) 168.5, 155.5, 142.1, 134.4, 134.0, 132.3, 130.5,
130.3, 129.6, 129.2, 128.8, 128.7, 128.6. 128.5, 121.3, 114.6; IR (KBr) v
4.3.9. N-(2-Methylbenzoyl)-2-(2-methylphenyl)-5-chloro-
benzimidazole (6b). Ethyl acetate/Petroleum ether (1/6) was used
as eluent. White solid; mp 109–110 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
3102, 3062, 1695, 1599, 1438, 1323, 1297, 1280, 1224, 718, 693 cmꢁ1
;
d
7.75 (d, J¼8.8 Hz, 1H), 7.64 (s, 1H), 7.38 (d, J¼8.8 Hz, 1H), 7.26–7.02
MS (ESI) m/z 389.0 ([MþNa]þ); HRMS (ESI) calcd for C20H12Cl2N2O
(m, 8H), 2.36 (s, 3H), 2.32 (s, 3H); 13C NMR (CDCl3,100 MHz)
d
168.7,
([MþNa]þ), 389.0219; found, 389.0230.
154.0, 141.4, 138.3, 136.9, 134.3, 133.3, 132.1, 131.3, 130.8, 130.5,
130.3, 129.8, 129.7, 128.9, 125.4, 125.3, 125.2, 121.0, 114.1, 20.0, 19.7;
IR (KBr) v 3087, 3021, 2959, 2927, 1705, 1600, 1484, 1457, 1308, 1257,
1217, 1150, 1079, 943, 903, 771, 735 cmꢁ1; MS (ESI) m/z 361.2
([MþH]þ); HRMS (ESI) calcd for C22H17ClN2O ([MþH]þ), 361.1102;
found, 361.1097.
4.3.4. N-(4-Methylbenzoyl)-2-(4-methylphenyl)-5,6-di-
chlorobenzimidazole (4d). Ethyl acetate/Petroleum ether (1/6) was
used as eluent. White solid; mp 184–185 ꢀC; 1H NMR (CDCl3,
400 MHz)
J¼8 Hz, 2H), 7.17 (d, J¼8 Hz, 2H), 7.10 (d, J¼7.6 Hz, 2H), 2.38 (s, 3H),
2.31 (s, 3H); 13C NMR (CDCl3, 100 MHz)
168.3, 155.8, 146.0, 142.3,
140.7,134.1,130.8,129.6,129.4,129.2,129.0, 128.2, 126.7,121.1,114.2,
d
7.92 (s, 1H), 7.59 (d, J¼8.4 Hz, 2H), 7.52 (s, 1H), 7.48 (d,
d
4.3.10. N-(2-Methylbenzoyl)-2-(2-methylphenyl)-6-chloro-
benzimidazole (7b). Ethyl acetate/Petroleum ether (1/6) was used

J. Wang et al. / Tetrahedron 66 (2010) 1208–1214
1213
as eluent. White solid; mp 115–116 ꢀC; 1H NMR (CDCl3, 400 MHz)
1582, 1450, 1328, 1244, 1180, 1145, 1090, 769 cmꢁ1; MS (ESI) m/z
349.2 ([MþH]þ); HRMS (ESI) calcd for C24H16N2O ([MþH]þ),
349.1335; found, 349.1340.
d
7.82 (d, J¼1.6 Hz, 1H), 7.47 (d, J¼8.8 Hz, 1H), 7.31 (dd, J1¼1.6 Hz,
J2¼8.8 Hz, 1H), 7.29–7.03 (m, 8H), 2.35 (s, 3H), 2.32 (s, 3H); 13C NMR
(CDCl3, 100 MHz)
d 168.6, 154.6, 143.6, 138.3, 136.9, 133.4, 132.3,
132.1,131.3,130.5,130.3,130.2,129.7,128.9,125.5,125.2,120.1,114.6,
20.0, 19.6; IR (KBr) v 3088, 3014, 2926, 1707, 1602, 1488, 1454, 1326,
1308, 1276, 1220, 1149, 906, 767, 739 cmꢁ1; MS (ESI) m/z 361.2
([MþH]þ); HRMS (ESI) calcd for C22H17ClN2O ([MþH]þ), 361.1102;
found, 361.1097.
4.3.16. N-(4-Chlorobenzoyl)-2-(4-chlorophenyl) pyrimidine (11b). Ethyl
acetate/Petroleum ether (1/4) was used as eluent. Yellow solid; mp
156–157 ꢀC; 1H NMR (CDCl3, 400 MHz)
d 7.53 (m, 3H), 7.48–7.40 (m,
5H), 7.30 (t, J¼8 Hz, 1H), 7.22 (m, 4H), 7.18 (m, 1H); 13C NMR (CDCl3,
100 MHz) d 170.7, 152.6, 140.1, 139.7, 136.5, 135.8, 135.5, 134.5, 133.8,
130.6, 129.3, 129.1, 128.9, 128.3, 127.5, 123.8, 122.2, 120.9, 119.4,
108.3; IR (KBr) v 3057, 1680,1625, 1579, 1489, 1323, 1255, 1088,
824 cmꢁ1; MS (ESI) m/z 417.0 ([MþH]þ); HRMS (ESI) calcd for
C24H14Cl2N2O ([MþH]þ), 417.0556; found, 417.0571.
4.3.11. N-Benzoyl-2-phenyl-6-nitrobenzimidazole (6c). Ethyl ace-
tate/Petroleum ether (1/3) was used as eluent. White solid; mp
137–138 ꢀC; 1H NMR (CDCl3, 400 MHz)
d 8.45 (s, 1H), 8.32 (d,
J¼8.8 Hz, 1H), 7.94 (d, J¼8.8 Hz, 1H), 7.68 (d, J¼8 Hz, 2H), 7.63
(d, J¼8 Hz, 2H), 7.55 (t, J¼7.6 Hz, 1H), 7.39–7.29 (m, 5H); 13C
4.3.17. 2-Phenyl-3-(phenylimino)isoindol-1-one (13). Ethyl acetate/
Triethylamine/Petroleum ether (1/1/6) was used as eluent for
column chromatography. Yellow solid; mp 150–151 ꢀC; 1H NMR
NMR (CDCl3, 100 MHz)
d 168.2, 158.2, 147.1, 144.7, 134.8, 134.4,
132.0, 130.8, 130.6, 139.4, 129.3, 129.0, 128.6, 120.3, 120.2, 109.8;
IR (KBr) v 3111, 2924, 2852, 1713, 1527, 1515, 1342, 1279, 1221,
902, 779, 734, 721 cmꢁ1; MS (ESI) m/z 344.4 ([MþH]þ); HRMS
(ESI) calcd for C20H13N3O3 ([MþH]þ), 344.1030; found,
344.1022.
(CDCl3, 400 MHz)
d
7.96 (d, J¼7.6 Hz, 1H), 7.59 (t, J¼7.2 Hz, 1H),
7.53 (m, 4H), 7.38 (m, 4H), 7.19 (t, J¼7.2 Hz, 1H), 6.97 (d, J¼7.2 Hz,
2H), 6.67 (d, J¼7.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz)
d 167.1,
151.2, 148.7, 133.3, 133.0, 132.2, 132.1, 129.4, 129.3, 128.9, 128.0,
127.9, 125.8, 124.1, 123.8, 119.6; IR (KBr) v 3059, 1741,1679, 1597,
1492, 1384, 1184, 1127, 707 cmꢁ1; MS (ESI) m/z 321.2 ([MþNa]þ);
HRMS (ESI) calcd for C20H14N2O ([MþNa]þ), 321.0998; found,
321.0999.
4.3.12. N-Benzoyl-2-phenyl-5-nitrobenzimidazole (7c). Ethyl ace-
tate/Petroleum ether (1/3) was used as eluent. White solid; mp
146–147 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
8.76 (d, J¼1.6 Hz, 1H), 8.24
(dd, J1¼2 Hz, J2¼8.8 Hz, 1H), 7.69 (d, J¼8 Hz, 2H), 7.63–7.54 (m, 4H),
7.39–7.29 (m, 5H); 13C NMR (CDCl3, 100 MHz)
168.4, 156.9, 145.1,
d
142.6, 138.9, 134.8, 132.1, 130.7, 130.6, 129.3, 129.2, 129.0, 128.6,
120.0, 116.5, 113.0; IR (KBr) v 3095, 3076, 2924, 2854, 1715, 1519,
1349, 1310, 1220, 1144, 928, 825, 742, 694 cmꢁ1; MS (ESI) m/z 344.3
([MþH]þ); HRMS (ESI) calcd for C20H13N3O3 ([MþH]þ), 344.1030;
found, 344.1022.
4.4. Procedure for the synthesis of 14
The mixture of amidine 2 (1 mmol) in DCM (10 mL) and excess
hydrazine hydrate was stirred over night and then diluted with
DCM (10 mL). The solution was washed with water (20 mL) and the
aqueous layer was extracted with DCM (10 mL). The combined
organic layer was washed with brine, dried over Na2SO4, concen-
trated under reduced pressure, and subjected to flash chromatog-
raphy using ethyl acetate/petroleum ether (1/4) as eluent.
4.3.13. (3aR,7aR)-1-Benzoyl-2-phenylhexahydrobenzimidazole
(9a). Ethyl acetate/Petroleum ether (1/2) was used as eluent.
20
White solid; [
a]
þ160.44 (c 1.0, DMF); mp 116–117 ꢀC; 1H NMR
D
(CDCl3, 500 MHz)
d 7.47–7.45 (m, 2H), 7.34–7.32 (m, 2H), 7.25–7.23
(m, 1H), 7.17–7.08 (m, 5H), 3.78–3.73 (m, 1H),3.52–3.46 (m, 1H),
2.60–2.57 (m, 1H), 2.47–2.44 (m, 1H), 1.95–1.86 (m, 2H), 1.62–1.39
(m, 4H); 13C NMR (CDCl3, 125 MHz)
d
169.4, 161.7, 135.4, 131.7,
4.4.1. N,N0-Diphenylbenzamidine (14a). White solid; mp 150–
131.2, 130.0, 129.1, 128.5, 128.0, 127.8, 126.9, 72.6, 70.4, 30.4, 29.2,
25.6, 24.4; IR (KBr) v 3072, 2966, 2935, 2860, 1650, 1596, 1448,
1396, 1332, 1298, 1076, 782, 729, 695, 661 cmꢁ1; MS (ESI) m/z
305.1 ([MþH]þ); HRMS (ESI) calcd for C20H20N2O ([MþH]þ),
305.1648; found, 305.1644.
151 ꢀC; 1H NMR (DMSO-d6, 500 MHz)
d 9.25 (s, 1H), 7.92 (d,
J¼7.5 Hz, 2H), 7.31 (s, 7H), 7.03 (d, J¼6.5 Hz, 2H), 6.99 (d, J¼6.0 Hz,
1H), 6.76 (d, J¼6.0 Hz, 1H), 6.60 (d, J¼6.5 Hz, 2H); 13C NMR (DMSO-
d6, 125 MHz)
d 155.2, 151.1, 141.9, 135.3, 129.4, 128.8, 128.5, 122.8,
122.4, 121.4, 120.0; IR (KBr) v 3301, 3055, 1626, 1588, 1536, 1486,
1441, 1333, 1223, 758, 699 cmꢁ1; MS (ESI) m/z 273.3 ([MþH]þ);
HRMS (ESI) calcd for C19H16N2 ([MþH]þ), 273.1386; found,
273.1374.
4.3.14. (3aR,7aR)-1-(2-Methylbenzoyl)-2-(2-methylphenyl)hexahy-
drobenzimidazole (9b). Ethyl acetate/Petroleum ether (1/3) was
20
used as eluent. White solid; [
a
]
þ121.46 (c 1.0, DMF). Mp 260–
D
261 ꢀC; 1H NMR (CDCl3, 500 MHz)
d
7.12–6.84 (m, 8H), 3.69–
4.4.2. N,N0-Bis(4-methyl)phenylbenzamidine (14b). White solid;
3.64 (m, 1H), 3.51–3.45 (m, 1H), 2.72–2.41 (m, 2H), 2.27–2.24
mp 134–135 ꢀC; 1H NMR (DMSO-d6, 500 MHz)
d 9.05 (s, 1H), 7.77
(m, 6H), 1.95–1.88 (m, 2H), 1.63–1.44 (m, 4H); 13C NMR (CDCl3,
(d, J¼7.5 Hz, 2H), 7.30 (d, J¼3.5 Hz, 3H), 7.27 (d, J¼4.5 Hz, 2H), 7.08
125 MHz)
d 170.0, 160.6, 136.1, 135.6, 135.4, 131.6, 130.4, 130.0,
(d, J¼7.5 Hz, 2H), 6.83 (d, J¼7.5 Hz, 2H), 6.46 (d, J¼7.5 Hz, 2H) 2.25
129.6, 129.1, 128.0, 124.9, 124.8, 72.1, 68.9, 30.4, 29.1, 25.5, 24.4,
19.4, 19.3; IR (KBr) v 3278, 3062, 3022, 2924, 2856, 1633, 1533,
1330, 1307, 743, 724, 688 cmꢁ1; MS (ESI) m/z 333.0 ([MþH]þ);
HRMS (ESI) calcd for C20H24N2O ([MþH]þ), 333.1961; found,
333.1954.
(s, 3H), 2.13 (s, 3H); 13C NMR (DMSO-d6, 125 MHz)
d 155.1, 148.6,
139.5, 135.5, 131.0, 129.7, 129.4, 129.3, 129.2, 128.5, 122.6, 120.0,
21.0, 20.8; IR (KBr) v 3367, 3022, 2922, 1625, 1592, 1526, 1505,
1335, 1218, 1101, 821, 701 cmꢁ1; MS (ESI) m/z 300.9 ([MþH]þ);
HRMS (ESI) calcd for C21H20N2 ([MþH]þ), 301.1699; found,
301.1695.
4.3.15. N-Benzoyl-2-phenylpyrimidine (11a). Ethyl acetate/Petro-
leum ether (1/4) was used as eluent. Yellow solid; mp 151–152 ꢀC;
4.4.3. N,N0-Bis(4-methylphenyl)thiophene-2-carboximidamide
1H NMR (CDCl3, 400 MHz)
d
7.58 (d, J¼7.6 Hz, 2H), 7.51 (d, J¼8 Hz,
1H), 7.42 (m, 5H), 7.35 (t, J¼7.2 Hz, 1H), 7.29 (t, J¼8 Hz, 1H), 7.22–
7.14 (m, 6H); 13C NMR (CDCl3, 100 MHz)
172.0, 154.0, 140.6, 137.4,
(14c). Yellow solid; mp 118–119 ꢀC; 1H NMR (DMSO-d6, 500 MHz)
d
9.04 (s, 1H), 7.66–6.54 (m, 11H), 2.21 (s, 6H); 13C NMR (DMSO-d6,
d
125 MHz) d 148.6, 148.1, 139.1, 134.8, 131.3, 130.4, 129.5, 129.3, 126.9,
135.9, 135.6, 134.6, 133.0, 130.0, 129.2, 128.5, 128.4, 128.2, 128.0,
127.5, 123.2, 121.8, 121.0, 118.9, 107.7; IR (KBr) v 3057, 1710,1626,
122.0, 120.4, 20.9; IR (KBr) v 3281, 3090, 3025, 2919, 2863, 1590,
1518, 1421, 1318, 1241, 1219, 852, 817, 712 cmꢁ1; MS (ESI) m/z 307.0

1214
J. Wang et al. / Tetrahedron 66 (2010) 1208–1214
([MþH]þ); HRMS (ESI) calcd for C19H18N2S ([MþH]þ), 307.1263;
4. (a) Tsatsas, G.; Delaby, R.; Quevauviller, A.; Damiens, R.; Blanpin, O. Ann. Pharm.
Fr. 1956, 4, 607; (b) Paul, H.; Weise, A.; Dettmer, R. Chem. Ber. 1965, 98, 1450;
(c) Tsatsas, G.; Delaby, R. Ann. Pharm. Fr. 1956, 4, 621.
found, 307.1254.
5. Weintraub, L.; Oles, S. R.; Kalish, N. J. Org. Chem. 1968, 33, 1679.
6. Charette, A. B.; Grenon, M. Tetrahedron Lett. 2000, 41, 1677.
7. Oxley, P.; Peak, D. A.; Short, W. F. J. Chem. Soc. 1948, 1618.
Acknowledgements
8. Charette, A. B.; Grenon, M.; Lemire, A.; Pourashraf, M.; Martel, J. J. Am. Chem.
Soc. 2001, 123, 11829.
9. Charette, A. B.; Grenon, M. Can. J. Chem. 2001, 79, 1694 and references therein.
10. Barbe, G.; Charette, A. B. J. Am. Chem. Soc. 2008, 130, 18.
We thank the National Natural Science Foundation of China (No.
20872128) for financial support of this research.
11. Movassaghi, M.; Hill, M. D. J. Am. Chem. Soc. 2006, 128, 14254.
12. (a) Movassaghi, M.; Hill, M. D.; Ahmad, O. K. J. Am. Chem. Soc. 2007, 129, 10096;
(b) Movassaghi, M.; Hill, M. D. J. Am. Chem. Soc. 2006, 128, 4592.
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Supplementary data
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2009.12.034.
15. CCDC 756618 contains the supplementary crystallographic data for compounds
7c. These data can be obtained free of charge via www.ccdc.cam.ac.uk/
data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting
The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2
1EZ, UK; fax: þ44 1223 336033.
References and notes
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20. CCDC 750493 contains the supplementary crystallographic data for compounds
2a. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_
request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ,
UK; fax: þ44 1223 336033.