A facile and efficient one-pot synthesis of polysubstituted benzenes in guanidinium ionic liquids

Article abstract of DOI:10.1039/b921390b

A facile and efficient synthesis of polysubstituted benzenes has been developed via sequential Michael addition, Knoevenagel condensation and nucleophilic cyclization reactions of readily available chalcones with active methylene compounds in guanidinium

Full text of DOI:10.1039/b921390b

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www.rsc.org/greenchem | Green Chemistry
A facile and efficient one-pot synthesis of polysubstituted benzenes in
guanidinium ionic liquids†
Xin Xin,a,b Yan Wang,a,b Wu Xu,b Yingjie Lin,*b Haifeng Duanb and Dewen Dong*a
Received 14th October 2009, Accepted 19th February 2010
First published as an Advance Article on the web 23rd March 2010
DOI: 10.1039/b921390b
A facile and efficient synthesis of polysubstituted benzenes has been developed via sequential
Michael addition, Knoevenagel condensation and nucleophilic cyclization reactions of readily
available chalcones with active methylene compounds in guanidinium ionic liquids.
has been synthesized and used in many organic reactions, such
Introduction
as the Henry reaction and aldol reactions.15 In our recent work,
Polysubstituted benzenes represent an important class of or-
we achieved Knoeveagel condensation and Michael addition
ganic compounds with numerous applications in organic syn-
reactions in GILs.16 For a Heck reaction, we found GILs
thetic chemistry, natural product chemistry, medicinal chem-
could act as a solvent, as a strong base to facilitate b-hydride
istry, and material chemistry as well.1 So far, there are many ap-
elimination, and as a ligand to stabilize activated Pd species.17
proaches available for the synthesis of polysubstituted benzenes,
either by the modification of the given arenes via electrophilic
In continuation with our research interests regarding the
development of the synthetic utility of GILs, we envisaged
or nucleophilic substitutions,2 coupling reactions catalyzed by
to explore Michael addition reactions of malononitrile and
transition metals,3 and metalation-functionalization reactions,4
chalcones in GILs. By this research, we developed a facile and
or by the construction of the aromatic skeleton from acyclic
efficient protocol for the synthesis of polysubstituted benzenes
precursors. For the latter, a series of benzannulation reac-
from chalcones and active methylene compounds in GILs under
tions including the [3+2+1] Do¨tz reaction of Fischer carbene
mild reaction conditions. Herein, we wish to report our primary
complexes,5 Danheiser alkyne–cyclobutenone [4+2] cyclization,6
experimental results and the mechanisms involved.
[4+2] cycloaddition of metalacyclopentadienes with alkynes,7
transition-metal-catalyzed [2+2+2] and [4+2] cycloaddition,8
Results and discussion
[3+3] cyclocondensation of bielectrophiles and binucleophiles,9
1,6-electrocyclization reaction,10 and [5+1] benzannulation of
a-alkenoyl ketene-S,S-acetals and nitroalkane11 have been de-
veloped. Some of these methodologies have been applied in
the synthesis of natural products and met with considerable
success, as the formation of regioisomeric mixtures can be
avoided in most cases.12 Each of these approaches represents an
important advance toward the objective of a general method for
the synthesis of polysubstituted benzenes; however, to match
the increasing scientific and practical demands, it is still of
continued interest and great importance to explore novel and
efficient synthetic approaches.
According to our previous work, a series of GILs were prepared
from guanidines and inorganic or organic acids with varied
chemical structures as shown in Table 1.16 With a series of GILs
in hand, we selected GIL-1 as the reaction medium to investigate
the Michael addition of malononitrile to chalcones. Thus, the
reaction of chalcone 1a with malononitrile 2a (1.5 equiv.) was
initially performed in GIL-1 at room temperature under stirring.
As indicated by TLC, several products were formed after the
starting material◦ 1a was consumed. When the reaction was
conducted at 60 C, a main product was obtained, which was
characterized as a substituted benzene 3a18 on the basis of its
spectral and analytical data (Scheme 1).
On the other hand, ionic liquids have attracted extensive
interest due to their non-volatility, non-flammability, excellent
chemical and thermal stability, high polarity and reusability.13,14
Over the past few years, a variety of catalytic reactions have
been successfully conducted with ionic liquids as solvents or
catalysts. Many interesting results have been obtained, which
have demonstrated the advantages of using ionic liquids as
alternatives for organic solvents. As a new generation of diverse
ionic liquids, a wide range of guanidinium ionic liquids (GILs)
Scheme 1 Reaction of chalcone 1a and malononitrile 2a.
The reaction conditions, including reaction media, i.e. GILs,
reaction temperature and the feed ratio of malononitrile 2a and
chalcone 1a, were then investigated. A series of reactions of
1a with 2a were conducted in GIL-1, which revealed that the
optimal results could be obtained when the reaction of 1a with
2.0 equivalents of 2a was carried out at room temperature for
aChangchun Institute of Applied Chemistry, Chinese Academy of
Sciences, Changchun, 130022, China
bDepartment of Chemistry, Jilin University, Changchun, 130012, China.
E-mail: dwdong@ciac.jl.cn
† Electronic supplementary information (ESI) available: Copies of NMR
spectra for the new compounds. See DOI: 10.1039/b921390b
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Table 1 Reactions of chalcone 1a with malononitrile 2a in different GILs
Entry
1
GIL
Anion
Cation
Viscosity/mPa sa
163
pHb
T/◦C
Time/h
4.0
Yield (%)c
89
GIL-1
12.38
60
2
3
4
GIL-2
GIL-3
GIL-4
345
308
142
12.23
11.20
6.20
60
60
60
10.0
10.0
10.0
35
19
55
5
6
7
GIL-5
GIL-6
GIL-7
149
263
206
5.08
1.46
8.13
60
60
95
10.0
10.0
10.0
0d
0e
43f
a For entries 1–6, measured at 60 ◦C; for entry 7, measured at 95 ◦C. b Measured with 0.1 M aqueous solution of GIL. c Isolated yield for 3a. d Only
the Michael adduct was formed. e No reaction. f Melting point 86 ◦C.
1.5 h, then 60 ◦C for 2.5 h, whereby the yield of 3a reached 89%
(Table 1, entry 1). The reactions of 1a with 2a in varied GILs
were examined. It was observed that the reactions of 1a with
2a proceeded slowly in GIL-2–4, with low to moderate yields
of 3a even after prolonged reaction time (Table 1, entries 2–4);
whereas in GIL-5, only the corresponding Michael adduct was
formed (Table 1, entry 5), and in GIL-6 no reaction occurred
(Table 1, entry 6). Since GIL-7 is solid at 60 ◦C, the reaction of
1a with 2a in GIL-7 was performed at a higher temperature at
which GIL-7 could act as the reaction medium. In this case, 3a
could be obtained but with low yield (Table 1, entry 7).
The above results suggested that the chemical structures of
GILs, including both the anion and cation parts, played a crucial
role in the cyclization reaction.19 Indeed, a significant hurdle in
the widespread application of ionic liquids is the effect that they
have on reaction outcomes. When a reaction is carried out in
an ionic liquid, differences in the rates and selectivities of the
process are often observed when compared to the corresponding
reaction in a molecular solvent or a different ionic liquid.20
At this stage there are limited reports detailing the origins
of such changes, which is in marked contrast to the extensive
understanding of the effect on reaction outcome upon changing
from one molecular solvent to another.21 In the present work,
from the data listed in Table 1, it seems that the GILs with
low viscosity and strong basicity would facilitate the cyclization
reaction of 1a with 2a.
Having established the optimal conditions for the cyclization,
we intended to determine its scope and limitations with respect
to the chalcones with varied substituents. Thus, a range of
reactions of chalcones 1b–i with malononitrile 2a were carried
out in GIL-1 under the optimized conditions as described in
Table 1, entry 1. The reactions of 1b–h with 2a proceeded
smoothly to afford the corresponding substituted benzenes 3b–
h22 in good yields (Table 2, entries 2–8). In the case of chalcone
1i with very a strong electron-withdrawing group, i.e. NO2, the
reaction proceeded slowly to give the corresponding benzene 3i
with poor yield (Table 2, entry 9). Nevertheless, the efficiency
of the cyclization proved to be suitable for most chalcones 1
bearing electron-donating (Table 2, entries 1–3, 5) and electron-
withdrawing aryl groups (Table 2, entries 4, 6–8).
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Table 2 Synthesis of polysubstituted benzenes 3a,30
Substrate
Entry
1
R1
R2
Time/hb
3
Yield (%)c
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
1a
1a
1a
1a
H
H
H
H
H
4-CH3
2-CH3O
4-Cl
3,4-(OCH2O)
H
4-CH3O
4-Cl
4-NO2
H
4.0
4.0
4.0
3.5
4.5
4.0
4.0
3.5
5.0
4.0
4.0
4.0
4.0
3a
3b
3c
3d
3e
3f
3g
3h
3i
3a
3a
3a
3a
89
76
85
81
84
79
83
86
32
85
82
73
69
H
4-Cl
4-Cl
4-Cl
H
H
H
Scheme 2 Plausible mechanism of the cyclization reaction of chalcones
1 and malonitrile 2a.
9
10d
11e
12f
13g
H
H
H
deprotonation of B and subsequent intramolecular cycloaddi-
tion take place to generate intermediate D, which undergoes an
elimination of hydrogen cyanide and aromatization to give a
substituted m-triphenyl 3.
H
H
a Reagents and conditions: 1 (2.0 mmol), 2a (4.0 mmol), GIL-1 (5.0 mL),
r.t. 1.5 h, then 60 ◦C 2.0–3.5 h. b Total reaction time. c Isolated yield.
d Reuse of GIL-1 from entry 1. e Reuse of GIL-1 from entry 10. f Reuse
of GIL-1 from entry 11. g Reuse of GIL-1 from entry 12.
The cyclocondensation of chalcone 1 with malononitrile 2a
involves a two-component, three-molecule reaction process.
With the aim of expanding the scope of this protocol, we
performed the reaction of chalcone 1a with ethyl-2-cyanoacetate
2b and then malononitrile 2a under the identical reaction
conditions. Unfortunately, the reaction produced a complex
mixture. When 1a and nitroethane 2c (1.0 equiv.) were subjected
to GIL-1 at room temperature for 3.0 h, followed by the addition
of 2a (1.0 equiv.) at 60 ◦C, the reaction proceeded smoothly to
furnish a product, which was characterized as a substituted m-
triphenyl 4a (Table 3, entry 1).
Clearly, GIL-1 plays dual roles as a solvent and a catalyst in
the cyclization reactions of 1 and 2a to polysubstituted benzenes
of type 3. In the present work, it was found that the organic
compounds could be easily extracted from the reaction mixture
by diethyl ether, which prompted us to investigate the reusability
of GIL-1. Thus, the reactions of 1a and 2a were carried out
with the used GIL-1 following the similar fashion as described
above (Table 2, entries 10–13). It was observed that GIL-1 could
attain good catalytic activity even when it was used for the fifth
time. The results demonstrated that GIL-1 could be reused, at
least for several times, after removal of the organic products by
extraction with diethyl ether.
Table 3 Synthesis of polysubstituted benzenes 4a,31
Actually, m-triphenyls23 are useful intermediates and act as
building blocks for cyclophanes24 to create a large molec-
ular cavity25 and host–guest complexes.26 In addition, some
m-triphenyls have been reported showing important optical
properties.27 So far, there are many approaches available for the
synthesis of m-terphenyls;18,22,28 however, most of these methods
suffer from several drawbacks, such as multi-step reactions, long
reaction time, lower product yields, harsh refluxing conditions,
or excess of volatile organic solvents. We herein provided an
alternative one-pot synthesis of polysubstituted m-triphenyls of
type 3 under mild reaction conditions.
To gain insight into the mechanism of the cyclization, a
separate experiment was conducted. The reaction of 1b with
malononitrile 2a (1.0 equiv.) was performed in GIL-1 at room
temperature, and the Michael adduct (A-b, see ESI†) was
obtained in high yield. On the basis of the experimental
results combined together with reports from the literature,18,22
a mechanism for this cyclization is proposed, as depicted in
Scheme 2. Initially, Michael addition of malononitrile 2a to
the chalcone 1 leads to the formation of adduct A,16b which
undergoes a Knoevenagel condensation with another molecule
of 2a to afford intermediate B. In the presence of basic GIL-1,
Substrate
Entry
1
R1
R2
Time b/h
4
Yield c(%)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
1a
1a
1a
1a
H
H
H
H
H
4-CH3
2-CH3O
4-Cl
3,4-(OCH2O)
H
4-CH3O
4-Cl
4-NO2
H
6.5
6.0
7.0
5.5
7.0
6.0
7.5
6.5
8.0
6.5
6.5
6.5
6.5
4a
4b
4c
4d
4e
4f
4g
4h
4i
4a
4a
4a
4a
82
77
72
80
79
69
82
83
0d
79
73
70
66
H
4-Cl
4-Cl
4-Cl
H
H
H
9
10e
11f
12g
13h
H
H
H
H
H
a Reagents and conditions: (i) 1 (2.0 mmol), 2c (2.0 mmol), GIL-1
(5.0 mL), r.t. 2.5–3.5 h; (ii) 2a (2.0 mmol), 60 ◦C, 3.0–4.0 h. b Total
reaction time. c Isolated yield. d Complex mixture was formed. e Reuse
of GIL-1 from entry 1. f Reuse of GIL-1 from entry 10. g Reuse of GIL-1
from entry 11. h Reuse of GIL-1 from entry 12.
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Encouraged by this result, a range of reactions among
chalcones 1, nitroethane 2c and malononitrile 2a were carried
out in GIL-1 under the conditions as described in Table 3,
entry 1. The reactions of chalcones 1b–h with nitroethane
2c and malononitrile 2a proceeded smoothly to afford the
corresponding substituted benzenes 4b–h in moderate to good
yields (Table 3, entries 2–8). In the case of 1i, however,
substituted benzene 4i was not obtained (Table 3, entry 9).
The reusability of GIL-1 was also studied, and the results
revealed that GIL-1 could maintain good catalytic activity
for five runs (Table 3, entries 10–13). The efficiency of the
cyclization has been demonstrated for chalcones 1a–1h bearing
electro-neutral, electron-rich, or electron-deficientaryl groups. It
should be mentioned that when chalcone 1a, nitromethane 2d or
nitropropane 2e, and malononitrile 2a were subjected to GIL-
1 under the identical conditions, only a complex mixture was
obtained. Nevertheless, we provided a novel one-pot synthesis
of polysubstituted benzenes of type 4.
Recently, Xue et al. and Su et al. achieved the synthesis
of polysubstituted m-triphenyls by one-pot reaction of vinyl
malononitriles with nitroolefins, in which an oxidation reaction
was involved as described in Scheme 3.29 In contrast with their
work, we obtained the polysubstituted benzene 4 without the
nitro substituent group, which indicated that a different mech-
anism might be involved in the cyclization process. Moreover,
we performed the reaction of 1b with nitroethane 2c (1.0 equiv.)
in GIL-1 at room temperature, and obtained Michael adducts
(isomers F-b, F-b¢, see ESI†). According to our experimental
results, a mechanism for the cyclization reaction of chalcone
1 with nitroethane 2c and malononitrile 2a is proposed, as
depicted in Scheme 4. Similar to the cyclization reaction of
chalcone 1 and malonitrile 2a (see Scheme 2), the reaction
commences from the Michael addition of nitroethane 2c to
chalcone 1. Subsequently, Knoeveangel condensation of the
adduct F with malononitrile 2a occurs to give intermediate
G, which undergoes an intramolecular cycloaddition to afford
intermediate I. In the presence of basic GIL-1, elimination
of nitrous acid (HNO2), rather than oxidation by air, and an
aromatization of J furnishes the polysubstituted m-triphenyl of
type 4. Most possibly, in the case of nitromethane 2d, both
elimination of HNO2 and an oxidation take place, and hence
lead to the formation of a complex mixture.
Conclusions
In summary, a facile and efficient one-pot synthesis of poly-
substituted m-triphenyl of type 3 and 4 has been developed
via sequential Michael addition, Knoevenagel condensation and
nucleophilic cyclization reactions of readily available chalcones
1 with active methylene compounds malononitrile 2a, and
nitroethane 2c/malononitrile 2a, respectively, in guanidinium
ionic liquid, GIL-1. Valuable features of this protocol including
simple procedure, mild conditions, good yields, and reusable
solvent, i.e. GILs, make it an efficient and promising synthetic
strategy to build benzene skeletons.
Acknowledgements
Financial support of this research by the National Natural
Science Foundation of China (20572013 and 20872136) is greatly
acknowledged.
Notes and references
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30 Typical procedure for the Synthesis of polysubstituted benzenes 3 (3c as
an example): To a solution of chalcone 1c (2.0 mmol) in GIL-1 (5 mL)
was added malononitrile 2a (4.0 mmol) in one portion, and stirred
at room temperature for 1.5 h. After the substrate 1c was consumed
(monitored by TLC), the resulting mixture was heated to 60 ◦C,
stirred for 2.5 h, then cooled to room temperature and extracted
with diethyl ether (3 ¥ 20 mL). The combined organic phases were
concentrated in vacuo, and purified by flash chromatography (silica
gel, petroleum ether: ethyl acetate = 15 : 1, v : v) to give 3c as a white
solid (85%).Selected data for 3c: White solid; mp 168-169 ◦C; 1H
NMR (400 MHz, CDCl3) d = 3.87 (s, 3H), 5.29 (s, 2H), 6.86 (s,
1H), 7.03-7.08 (m, 2H), 7.28 (m, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.46-
7.49 (m, 3H), 7.58-7.60 (m, 2H); 13C NMR (100 MHz, DMSO) d =
55.4, 93.5, 96.3, 111.7, 115.7, 116.0, 119.3, 120.6, 126.4, 128.5, 128.6,
129.3, 130.2, 130.9, 137.4, 147.6, 149.5, 153.3, 156.0; Anal. Calcd for
C21H15N3O: C, 77.52; H, 4.65; N, 12.91; Found: C, 77.38; H, 4.61; N,
12.83.
3i: Yellow solid; mp 239-241 ◦C; H NMR (400 MHz, CDCl3) d =
1
5.45 (s, 2H), 6.90 (s, 1H), 7.52-7.55 (m, 3H), 7.57 (d, J = 8.0 Hz,
2H), 7.76 (d, J = 8.8 Hz, 2H), 8.37 (d, J = 8.8 Hz, 2H); 13C NMR
(100 MHz, DMSO) d = 93.9, 95.1, 115.6, 115.7, 118.4, 123.6, 127.9,
128.5, 128.7, 129.5, 130.2, 137.2, 143.7, 147.5, 150.1, 154.0; Anal.
Calcd for C20H12N4O2: C, 70.58; H, 3.55; N, 16.46; Found: C, 70.79;
H, 3.60; N, 16.53.
31 Typical procedure for the synthesis of polysubstituted benzenes 4 (4a as
an example): To a solution of chalcone 1a (2.0 mmol) in GIL-1 (5 mL)
was added nitroethane 2c (2.0 mmol) in one portion and stirred at
room temperature for 3.0 h. After the substrate 1a was consumed
(monitored by TLC), malononitrile 2a (2.0 mmol) was added. The
resulting mixture was heated to 60 ◦C, stirred for 3.5 h, then cooled to
room temperature and extracted with diethyl ether (3 ¥ 20 mL). The
combined organic phases were concentrated in vacuo, and purified
by flash chromatography (silica gel, petroleum ether : ethyl acetate =
15 : 1, v : v) to give 4a as a wh◦ite solid (82%).Selected data for 4:
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2008, 112, 10989–11004; (c) A. Zhu, T. Jiang, B. Han, J. Huang, J.
Zhang and X. Ma, New J. Chem., 2006, 30, 736–740.
20 H. M. Yau, S. J. Chan, S. R. D. George, J. M. Hook, A. K. Croft and
J. B. Harper, Molecules, 2009, 14, 2521–2534.
1
21 (a) E. D. Bates, R. D. Mayton, I. Ntaiand and J. H. Davis, Jr, J. Am.
Chem. Soc., 2002, 124, 926–927; (b) J. L. Anthony, E. J. Maginnand
and J. F. Brennecke, J. Phys. Chem. B, 2002, 106, 7315–7320; (c) C.
Cadena, J. L. Anthony, J. K. Shah, T. I. Morrow, J. F. Brennecke and
E. J. Maginn, J. Am. Chem. Soc., 2004, 126, 5300–5308; (d) A. M.
Scurto, S. N. V. K. Aki and J. F. Brennecke, J. Am. Chem. Soc., 2002,
124, 10276–10277; (e) W. Wu, B. Han, H. Gao, Z. Liu, T. Jiang and
J. Huang, Angew. Chem., Int. Ed., 2004, 43, 2415–2417; (f) J. Huang,
A. Riisager, P. Wasserscheidb and R. Fehrmann, Chem. Commun.,
2006, 4027–4029.
22 For compounds 3b, 3d and 3f–h, see: (a) L. Rong, H. Han, F. Yang,
H. Yao, H. Jiang and S. Tu, Synth. Commun., 2007, 37, 3767–3772.
For compounds 3b, 3d and 3f, also see: (b) K. U. Sadek, M. A. Selim
and R. A. Motaleb, Bull. Chem. Soc. Jpn., 1990, 63, 652–654 For
compound 3e, see: (c) F. M. El-Taweel, J. Prakt. Chem., 1990, 332,
762–766.
4a: white solid: mp 202-204 C; H NMR (300 MHz, CDCl3) d =
2.11 (s, 3H), 4.62 (s, 2H), 6.77 (s, 1H), 7.29-7.32 (m, 2H), 7.38-7.45 (m,
6H), 7.57 (d, J = 6.6 Hz, 2H); 13C NMR (75 MHz, CDCl3) d = 14.4,
94.1, 118.0, 118.5, 120.9, 127.6, 128.3, 128.31, 128.5, 128.6, 128.9,
138.8, 140.9, 142.5, 147.0, 149.3; IR (KBr, cm-1) 818, 1092, 1494,
1545, 1589, 1641, 2208, 3382; Anal. Calcd for C20H16N2: C 84.48; H
5.67; N 9.85; Found: C 84.55; H 5.78; N 9.81.
◦
1
4b: white solid: mp 185-187 C; H NMR (400 MHz, CDCl3) d =
2.11 (s, 3H), 2.41 (s, 3H), 4.59 (s, 2H), 6.76 (s, 1H), 7.19-7.23 (m, 4H),
7.39-7.46 (m, 3H), 7.55-7.57 (m, 2H). 13C NMR (75 MHz, CDCl3)
d = 14.4, 21.2, 93.9, 118.0, 118.6, 120.9, 128.3, 128.5, 128.6, 128.8,
128.9, 137.4, 137.9, 138.9, 142.5, 147.0, 149.3. IR (KBr, cm-1) 826,
966, 1018, 1269, 1548, 1637, 1676. Anal. Calcd for C21H18N2: C,
84.53; H, 6.08; N, 9.39; Foun◦d: C, 84.39; H, 6.13; N, 9.42.
1
4c: white solid: mp 171-173 C; H NMR (400 MHz, CDCl3) d =
1.98 (s, 3H), 3.79 (s, 3H), 4.56 (s, 2H), 6.74 (s, 1H), 7.00-7.04 (m, 2H),
7.16 (d, J = 8.0 Hz, 1H), 7.36-7.43 (m, 4H), 7.58 (d, J = 8.0 Hz,
2H). 13C NMR (100 MHz, CDCl3) d = 14.3, 55.4, 94.3, 110.7, 118.1,
120.2, 120.6, 121.3, 128.2, 128.5, 128.6, 129.3, 129.7, 130.6, 138.9,
142.3, 143.7, 148.7, 156.3. Anal. Calcd for C21H18N2O: C, 80.23; H,
5.77; N, 8.91; Found: C, 80.11; H, 5.67; N, 8.82.
23 A. Saednya and H. Hart, Synthesis, 1996, 1455–1458.
24 (a) H. Hart and P. Rajakumar, Tetrahedron, 1995, 51, 1313–1336;
(b) R. S. Grewal, H. Hart and T. K. Vinod, J. Org. Chem., 1992, 57,
2721–2726.
25 P. Rajakumar and A. Kannan, Tetrahedron Lett., 1993, 34, 4407–
◦
1
4410.
4d: white solid: mp 190-191 C; H NMR (300 MHz, CDCl3) d =
2.09 (s, 3H), 4.62 (s, 2H), 6.72 (s, 1H), 7.23-7.25 (m, 2H), 7.40-7.45
(m, 5H), 7.54-7.57 (m, 2H). 13C NMR (75 MHz, CDCl3) d = 14.4,
94.4, 117.8, 118.4, 120.6, 128.4, 128.5, 128.6, 130.3, 133.7, 138.6,
139.3, 142.7, 145.7, 149.3. IR (KBr, cm-1) 695, 1037, 1233, 1250,
1438, 1501, 1641, 2208, 3388. Anal. Calcd for C20H15ClN2: C, 75.35;
H, 4.74; N, 8.79; Found: C, 7◦5.44; H, 4.65; N, 8.81.
26 G. Bringmann, R. Walter and R. Weirich, Angew. Chem., Int. Ed.
Engl., 1990, 29, 977–991.
27 S. Janusz and M. Piotr, Tetrahedron, 1985, 41, 5261–5265.
28 (a) P. Victory, J. I. Borrel, A. Vidal-Ferran, C. Seoane and J. L. Soto,
Tetrahedron Lett., 1991, 32, 5375–5378; (b) J. Griffiths, M. Lockwood
and B. Roozpeikar, J. Chem. Soc., Perkin Trans. 2, 1977, 1608–1610;
(c) S. Cui, X. Lin and Y. Wang, J. Org. Chem., 2005, 70, 2866–2869;
(d) B. Glettner, F. Liu, X. B. Zeng, M. Prehm, U. Baumeister, G.
Ungar and C. Tschierske, Angew. Chem., Int. Ed., 2008, 47, 6080–
6083; (e) J. M. Antelo Miguez, L. A. Adrio, A. S. Pedrares, J. M. Vila
and K. K. Hii, J. Org. Chem., 2007, 72, 7771–7774; (f) J. D. Bauer,
M. S. Foster, J. D. Hugdahl, K. L. Burns, S. W. May, S. H. Pollock,
H. G. Cutler and S. J. Cutler, Med. Chem. Res., 2007, 16, 119–129;
(g) L. Rong, H. Han, H. Jiang and S. Tu, Synth. Commun., 2008, 38,
3530–3542; (h) C. Yan, X. Song, Q. Wang, J. Sun, U. Siemeling and
C. Bruhnb, Chem. Commun., 2008, 1440–1442.
1
4e: white solid: mp 167-168 C; H NMR (300 MHz, CDCl3) d =
2.11 (s, 3H), 4.60 (s, 2H), 6.00 (s, 2H), 6.73-6.78 (m, 3H), 6.86 (d, J =
7.2 Hz, 1H), 7.39-7.46 (m, 3H), 7.55 (d, J = 6.6 Hz, 2H). 13C NMR
(75 MHz, CDCl3) d = 14.4, 94.0, 101.2, 108.2, 109.5, 118.0, 118.6,
120.9, 122.4, 128.3, 128.51, 128.55, 134.7, 138.8, 142.5, 146.6, 147.1,
147.5, 149.3. IR (KBr, cm-1) 695, 1037, 1233, 1250, 1438, 1501, 1641,
2208, 3388. Anal. Calcd for C21H16N2O2: C, 76.81; H, 4.91; N, 8.53;
Found: C, 77.13; H, 4.82; N, 8.72.
4f: white solid: mp 211-212 ◦C; 1H NMR (300 MHz, CDCl3)
d = 2.11 (s, 3H), 4.63 (s, 2H), 6.72 (s, 1H), 7.28-7.30 (d, J =
6.9 Hz, 2H), 7.38-7.43 (m, 5H), 7.46-7.52 (m, 2H). 13C NMR
(75 MHz, CDCl3) d = 14.4, 93.9, 117.8, 119.0, 120.7, 127.7, 128.3,
128.8, 128.9, 129.9, 134.5, 137.2, 140.7, 141.2, 147.1, 149.4. IR
29 (a) D. Xue, J. Li, Z. Zhang and J. Deng, J. Org. Chem., 2007, 72,
5443–5445; (b) W. Su, K. Ding and Z. Chen, Tetrahedron Lett., 2009,
50, 636–639.
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Green Chem., 2010, 12, 893–898 | 897
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(KBr, cm-1) 826, 966, 1018, 1269, 1548, 1637, 1676. Anal. Calcd for
C20H15ClN2: C, 75.35; H, 4.74; N, 8.79; Found: C, 75.17; H, 4.86; N,
8.73.
4g: white solid: mp 203-204 C; H NMR (400 MHz, CDCl3) d =
2.12 (s, 3H), 3.86 (s, 3H), 4.60 (s, 2H), 6.71 (s, 1H), 6.97 (d, J =
8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 7.50
(d, J = 8.0 Hz, 2H). 13C NMR (75 MHz, CDCl3) d = 14.4, 55.3,
113.7, 117.8, 119.0, 120.8, 128.7, 129.9, 130.1, 133.0, 134.4, 137.3,
141.1, 146.8, 149.4, 159.2. IR (KBr, cm-1) 826, 966, 1018, 1269, 1548,
1637, 1676. Anal. Calcd for C21H17ClN2O: C, 72.31; H, 4.91; N, 8.03;
Found: C, 72.52; H, 4.81; N, ◦8.17.
1
4h: white solid: mp 209-211 C; H NMR (300 MHz, CDCl3) d =
◦
1
2.08 (s, 3H), 4.64 (s, 2H), 6.67 (s, 1H), 7.22 (d, J = 8.1 Hz, 2H), 7.40-
7.43 (m, 4H), 7.48 (d, J = 8.1 Hz, 2H). 13C NMR (75 MHz, CDCl3)
d = 14.3, 94.1, 117.6, 118.8, 120.3, 128.5, 128.8, 129.8, 130.2, 133.8,
134.6, 137.0, 139.0, 141.4, 145.8, 149.4. IR (KBr, cm-1) 818, 1092,
1466, 1496, 1640, 2208, 3381. Anal. Calcd for C20H14Cl2N2: C, 68.00;
H, 3.99; N, 7.93; Found: C, 67.68; H, 4.12; N, 7.79.
898 | Green Chem., 2010, 12, 893–898
This journal is
The Royal Society of Chemistry 2010
©