Cu(OTf)2/Et3N-promoted cyclocondensation of activated α-methylene alkenes and nitroolefins: a novel one-pot synthesis of polysubstituted benzenes

Article abstract of DOI:10.1016/j.tetlet.2008.11.081

A simple and efficient one-pot synthesis of polyfunctionalized benzenes has been developed via cyclocondensation of activated α-methylene alkenes such as vinyl malononitriles and ethyl vinyl cyanoacetates with nitroolefins using Cu(OTf)₂/Et

Full text of DOI:10.1016/j.tetlet.2008.11.081

Tetrahedron Letters 50 (2009) 636–639
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Cu(OTf)2/Et3N-promoted cyclocondensation of activated a-methylene
alkenes and nitroolefins: a novel one-pot synthesis of polysubstituted benzenes
*
Weike Su , Kai Ding, Zhiwei Chen
Key Laboratory of Pharmaceutical Engineering of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and efficient one-pot synthesis of polyfunctionalized benzenes has been developed via cyclo-
Received 26 August 2008
Revised 20 November 2008
Accepted 21 November 2008
Available online 27 November 2008
condensation of activated
tates with nitroolefins using Cu(OTf)2/Et3N as a novel catalytic system.
Ó 2008 Elsevier Ltd. All rights reserved.
a-methylene alkenes such as vinyl malononitriles and ethyl vinyl cyanoace-
Keywords:
Copper triflate
Activated alkenes
Nitroolefins
One-pot
Polysubstituted benzenes
As useful compounds in organic chemistry and natural product
chemistry, polysubstituted benzenes also play important roles in
medicinal chemistry for the fact that they have common structural
features in various bioactive molecules and are frequently em-
ployed as precursors for the synthesis of many bioactive heterocy-
clic compounds.1 Consequently, enormous number of procedures
have been developed for the construction of polysubstituted ben-
zenes. Aromatic substitutions, including Friedel–Crafts acylations
and alkylations,2 nucleophilic substitutions,3 and coupling reac-
tions4 based on the given aromatics are interpreted as traditional
approaches. On the other hand, the approach to construct aromatic
backbone from catenulate precursors has received growing inter-
est not only due to the short sequence and regioselectivity, but also
due to the advancement from the viewpoint of atom economy5 and
environmental concern. Herein, [3+2+1]Dotz reaction,6 [4+2]benz-
annulation,7 [3+3]cyclocondensation8, and Vilsmeier reagent
assisted arylation9 have been discovered and developed in recent
years.
In general, it is difficult to introduce amino, nitrile, and/or ester
group to the given aromatics. Some methods were developed to
synthesize these functionalized benzenes from acyclic compounds
as follows: (i) base-promoted cyclocondensation of arylethylidene-
and arylidenemalono- nitriles and the elimination of nitrile group
in succession, which provides polysubstituted 2-amino isophthalo-
nitriles,10 (ii) one-pot two-step tandem reaction of vinylmalono-
nitriles and nitroolefins promoted by two different kinds of bases
Table 1
Reaction of 2-(1phenylethylidene)malononitrile (1a) and (E)-(2-nitrovinyl)benzene
(3a) under different conditionsa
NH2
NC
CN
NC
NO2
NO2
Catalyst
Solvent
+
3a
1a
4a
Entry
Solvent
Catalyst
Loading (mol %)
Yieldsb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH2Cl2
CHCl3
Cu(OTf)2
5
0
79
82
82
64
56
81
Cu(OTf)2/Et3N
Cu(OTf)2/Et3N
Cu(OTf)2/Et3N
Zn(OTf)2/Et3N
Mg(OTf)2/Et3N
Sc(OTf)2/Et3N
CuCl2/ Et3N
Et3N
5/10
5/5
10/5
5/5
5/5
5/5
5/5
5
39 (52c)
35 (36d)
29
Piperidine
10
KOH
EtONa
100
100
5/5
5/5
5/5
5/5
5/5
5/5
0
Trace
0
62
71
79
Cu(OTf)2/Et3N
Cu(OTf)2/Et3N
Cu(OTf)2/Et3N
Cu(OTf)2/Et3N
Cu(OTf)2/Et3N
Cu(OTf)2/Et3N
DMF
EtOH
Dioxane
Toluene
55
40
a
The reaction was carried out at 80 °C reflux for 5 h.
Yield of isolated product.
In the presence of 40 mol % of CuCl2 and 5 mol % of Et3N .
In the presence of 10 mol % of Et3N.
b
c
* Corresponding author. Tel./fax: +86 571 88320752.
E-mail address: suweike@zjut.edu.cn (W. Su).
d
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.11.081

W. Su et al. / Tetrahedron Letters 50 (2009) 636–639
637
Table 2
Table 3
Cu(OTf)2/Et3N promoted synthesis of 2-amino-3-nitro benzonitriles in refluxing
Cu(OTf)2/ Et3N promoted synthesis of ethyl 2-amino-3-nitro-benzoates in CH3CN at
CH3CN13
reflux14
NH2
NH2
NC
R1
CN
R2
EtOOC
R1
CN
R2
NC
R1
NO2
R3
5mol%Cu(OTf)2/Et3N
CH3CN, reflux, 5h
EtOOC
R1
NO2
R3
5mol%Cu(OTf)2/Et3N
CH3CN, reflux, 8h
NO2
NO2
R3
+
+
R3
R2
4
R2
1
2
3
3
5
Entry
R1
Ph
R2
R3
Product
Yielda (%)
Entry
1
R1
R2
R3
Product
Yielda (%)
66b
1
2
3
4
5
6
H
H
H
H
H
H
Ph
Ph
Ph
Ph
Ph
Ph
4a
4b
4c
4d
4e
4f
82
85
86
79
84
76
Ph
H
Ph
5a
4-MeC6H4
4-MeOC6H4
4-FC6H4
4-ClC6H4
3-ClC6H4
2
3
Ph
5b
66
64
5c
7
8
H
Ph
Ph
4g
4h
85
80
S
O
5
Ph
5d
5e
62
9
Ph
Ph
4i
4j
79
78
6
3-ClC6H4
Me
59b
a
Yield of isolated product based on 2
Geometrical isomers of 2 were used.
b
10
11
12
H
Ph
Ph
4k
4l
81
70
is indispensable. Then, the model reaction was investigated with a
variety of conditions. The results are summarized in Table 1.
As shown in Table 1, Cu(OTf)2 and Et3N, each of 0.05 equiv, gave
the best yield. The reaction gave low yield when 0.05 or 0.1 equiv
of Et3N alone was used (Table 1, entry 9). Furthermore, any sole or-
ganic or inorganic base gave a low yield or even no reaction
(Table 1, entries 10–12). CuCl2/Et3N system also gave lower yield
in 39% (52% with increased amount of the catalyst) (Table 1, entry
8). Other metal triflate/Et3N catalyst systems, such as Zn(OTf)2/
Et3N, Sc(OTf)3/Et3N, and Mg(OTf)2/Et3N, were studied, and only
Sc(OTf)3/Et3N showed good activity (Table 1, entries 5–7). We also
examined different solvents such as CH2Cl2, CHCl3, DMF, EtOH,
dioxane, and toluene. Among them, CH3CN was the best one.
With these preliminary results in hand, we paid our attention to
a wide scope of vinyl malononitriles 1. Subsequent studies were
carried out under the optimized conditions: with 5 mol % of
Cu(OTf)2 and 5 mol % of Et3N in CH3CN at reflux for 5 h. Satisfacto-
rily, most vinyl malononitriles reacted with nitroolefins completely
and afforded the corresponding products 4a–q in moderate to good
yields, as shown in Table 2.
First, a series of substituted phenylethylidene malononitriles
(Table 1, entries 1–6) were used to react with 3a. Both electron-
donating and electron-withdrawing substituents on phenyl were
tolerated. When phenyl was replaced with furanyl, the correspond-
ing product was obtained in high yields (Table 2, entry 7, 85%
yield). Furthermore, some vinyl malononitriles with aliphatic R1
and R2 were also subjected to the reactions with 3a, which simi-
larly gave the corresponding products in satisfactory yields (Table
2, entries 8–11). Furthermore, we successfully constructed a cyclo-
propyl benzene framework which was difficult to prepare via tra-
ditional approaches. Subsequently, when R2 = Me (Table 2,
entries 12 and 13), a considerable decrease in yields took place. In-
deed, no reaction of 2-(2-phenyl-1-p-tolylethylidene)malononitrile
with 3a was observed under the same conditions (Table 2, entry
14). This observation might be a result of steric hindrance. Finally,
a wide range of nitroolefins with different R3 were reacted with 1a.
Similar yields were obtained irrespective of R3 alternating from
substituted phenyl to heterocycles (Table 2, entries 14–17).
Ph
Me
13
14
4-ClC6H4
4-MeC6H4
Me
Ph
Ph
Ph
4m
/
67
0
14
15
Ph
Ph
H
H
4n
4o
83
82
O
S
16
17
Ph
Ph
H
H
4-MeOC6H4
3-NO2C6H4
4p
4q
83
81
a
Yield of isolated product.
for each step, which obtains a series of substituted 2-amino-3-nitro
benzonitriles.11 Unfortunately, these methods often suffer from
certain drawbacks such as long-playing procedures, hazardous
by-products and use of stoichiometric or even excess amount of
base. Therefore, how to synthesize polysubstituted benzenes effi-
ciently and catalytically is an important question to be answered
in organic synthesis.
Our group has reported metal triflates as excellent catalysts that
are widely used in organic synthesis.12 As part of our ongoing
interest in green chemistry and metal triflates-catalyzed organic
reactions, in this Letter, we will introduce a novel and efficient
one-pot synthesis of polyfunctionalized benzenes via the reactions
of activated
a-methylene alkenes and nitroolefins promoted by
catalytic amount of copper triflate and triethylamine. The products,
a series of 2-amino-3-nitro-benzonitriles and ethyl 2-amino-3-ni-
tro-benzoates, are obtained in good yields.
In our initial research, 5 mol % of Cu(OTf)2 was tested to pro-
mote the reaction of 2-(1-phenylethylidene)malononitrile (1a)
and (E)-(2-nitrovinyl) benzene (3a). Acetonitrile was selected as
solvent due to the solubility of the two starting materials. Disap-
pointedly, no product was observed after refluxing for 10 h. How-
ever, the reaction was kept at reflux for 5 h after Et3N was added,
and compound 4a was obtained in good yield. It i seems that a base

638
W. Su et al. / Tetrahedron Letters 50 (2009) 636–639
NC
CN
NC
CN
NO2
5mol%Cu(OTf)2/Et3N
S
+
NO2
CH
3CN, rt, 6h
S
H3CO
H3CO
6c
1c
Scheme 1. Reaction to obtain the intermediate 6c.
Miller, K. D.; Sledge, G. W.; Zheng, Q.-H. Bioorg. Med. Chem. Lett. 2006, 16, 4102;
(d) Nakamura, H.; Sasaki, Y.; Uno, M.; Yoshikawa, T.; Asano, T.; Ban, H. S.;
Fukazawa, H.; Shibuya, M.; Uehara, Y. Bioorg. Med. Chem. Lett. 2006, 16, 5127;
(e) Kaiah, T.; Lingaiah, B. P. V.; Narsaiah, B.; Shireesha, B.; Kumar, B. A.; Gururaj,
S.; Pathasarathy, T.; Sridhar, B. Bioorg. Med. Chem. Lett. 2007, 17, 3445; (f)
Romagnoli, R.; Baraldi, P. G.; Carrion, M. D.; Cara, G. L.; Preti, D.; Fruttarolo, F.;
Parani, M. G.; Tabrizi, M. A.; Tolomeo, M.; Grimando, S.; Cristina, A. D.;
Balazarini, J.; Hadfield, J. A.; Brancale, A.; Hamel, E. J. Med. Chem. 2007, 50,
2273; (g) Zhong, W.; Liu, H.; Kaller, M. R.; Henley, C.; Magal, E.; Nguyen, . T.;
Osslund, T. D.; Powers, D.; Rzasa, R. M.; Wang, H.-L.; Wang, W.; Xiong, X.;
Zhang, J.; Norman, M. H. Bioorg. Med. Chem. Lett. 2007, 17, 5384.
Cu(OTf)2
N
N
H
N
X
X
X
NO2
O2N
R1
R1
R1
R3
R3
R2
R2
R2
Et3N
NH
1
2
6
or
3
NH2
NH2
R2
X
NO2
R3
2. (a) Olah, G. In Friedel–Crafts and Related Reactions; Wiley Inter-science: New
York, 1963; vols. I–IV; (b) Pearson, D. E.; Buehler, C. A. Synthesis 1972, 533.
3. Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102,
1359.
4. Saito, S.; Yamamoto, Y. Chem. Rev. 2000, 100, 2901.
5. (a) Trost, B. M. Science 1991, 254, 1471; (b) Trost, B. M. Angew. Chem., Int. Ed.
Engl. 1995, 34, 259.
6. (a) Wang, H.; Huang, J.; Wulff, W. D.; Rheingold, A. L. J. Am. Chem. Soc. 2003,
125, 8980; (b) Vorogushin, A. V.; Wulff, W. D.; Hansen, H.-J. J. Am. Chem. Soc.
2002, 124, 6512.
X
NO2
H
X
NO2
R3
[O]
Air
R1
R1
R3
R1
R2
R2
X = CN or CO2Et
Scheme 2. Plausible reaction mechanism of 1 or 2 with nitroolefins.
4
5
or
7. (a) Asao, N.; Nogami, T.; Lee, S.; Yamamoto, Y. J. Am. Chem. Soc. 2003, 125,
10921; (b) Asao, N.; Takahashi, K.; Lee, S.; Kasahara, T.; Yamamoto, Y. J. Am.
Chem. Soc. 2002, 124, 12650; (c) Asao, N.; Aikawa, H.; Yamamoto, Y. J. Am. Chem.
Soc. 2004, 126, 7458.
To extend the scope of this reaction, other activated
a-methy-
lene alkenes, such as Knoveangal products 2 of ketones with ethyl
cyanoacetate, were made to react with nitroolefins 3 using the
present protocol. The formation of 5 from 2 required longer time
(8 h). In general, probably due to the comparatively weaker elec-
tron-withdrawing ability of COOEt than CN, these reactions gave
significantly lower yields than that of vinyl malononitriles with
nitroolefins. The products, a series of ethyl 2-amino-3-nitro benzo-
ates derivatives 5, were obtained in moderate yields. The results
are summarized in Table 3.
In addition, reaction of 2-(1-(4-methoxyphenyl)ethylidene)
malononitrile (1c) with (E)-2-(2-nitrovinyl)thiophene was carried
out at room temperature and was catalyzed by 5 mol % Cu(OTf)2
and 5 mol % Et3N for 6 h (Scheme 1). The detection of the Mi-
chael intermediate 6c indicates the ionic path of the whole
cyclocondensation.15
8. Langer, P.; Bose, G. Angew. Chem., Int. Ed. 2003, 42, 4033.
9. (a) Somogyi, L.; Debrecen, H. J. Hetero. Chem. 2007, 44, 1235; (b) Katritzky, A. R.;
Marson, C. M. J. Org. Chem. 1987, 52, 2726; (c) Katrizky, A. R.; Marson, C. M.;
Palenik, G.; Koziol, A. E.; Luce, H.; Karelson, M.; Chen, B. C.; Brey, W. Tetrahedron
1988, 44, 3209.
10. (a) Milart, P.; Wilamowski, J.; Sepiol, J.-J. Tetrahedron 1998, 54, 15643; (b)
Gewald, K.; Schill, W. J. Prakt. Chem. 1971, 313, 678; (c) Wang, X. S.; Zhang, M.
M.; Li, Q.; Yao, C. S.; Tu, S. J. Tetrahedron 2007, 63, 5265.
11. Xue, D.; Li, J.; Zhang, Z.-T.; Deng, J.-G. J. Org. Chem. 2007, 72, 5443.
12. (a) Su, W.; Li, J.; Zheng, Z.; Shen, Y. Tetrahedron Lett. 2005, 46, 6037; (b) Su, W.;
Jin, C. Org. Lett. 2007, 9, 993; (c) Su, W.; Hong, Z.; Shan, W.; Zhang, X. Eur. J. Org.
Chem. 2006, 2723; (d) Chen, J.; Wu, H.; Zheng, Z.; Jin, C.; Zhang, X.; Su, W.
Tetrahedron Lett. 2006, 47, 5383; (e) Yu, C.; Dai, X.; Su, W. Synlett 2007, 646; (f)
Su, W.; Chen, J.; Wu, H.; Jin, C. J. Org. Chem. 2007, 72, 4524.
13. General procedure for the synthesis of 2-amino-3-nitro-benzonitriles. To a mixture
of vinyl malononitrile (1 mmol) and nitroolefin (1 mmol) in CH3CN (3 mL),
Cu(OTf)2 (0.05 mmol, 18 mg) and triethylamine (0.05 mmol, 5 mg) were added.
The reaction mixture was stirred at reflux for 5 h. After the completion of the
reaction, EtOAc (15 mL) was added to dilute the reaction solution. Then, the
mixture was washed with water and brine. The combined organic phases were
dried and concentrated in vacuo, and the residue was purified by column
chromatography (hexane/AcOEt = 8:1) to afford compounds 4.
Based on the experimental results, a plausible mechanism was
proposed in Scheme 2, involving the Michael addition of activated
14. General procedure for the synthesis of ethyl 2-amino-3-nitro-benzoates. To a
mixture of 2 (1 mmol) and nitroolefin (1 mmol) in CH3CN (3 mL), Cu(OTf)2
(0.05 mmol, 18 mg) and triethylamine (0.05 mmol, 5 mg) were added. The
reaction mixture was stirred at reflux for 8 h. After the completion of the
reaction, EtOAc (15 mL) was added to dilute the reaction solution. Then, the
mixture was washed with water and brine. The combined organic phases were
dried and concentrated in vacuo, and the residue was purified by column
chromatography (hexane/AcOEt = 8:1) to afford compounds 5.
15. Procedure for the synthesis of 6c. To a mixture of 1c (1 mmol) and (E)-2-(2-
nitrovinyl)thiophene (1 mmol) in CH3CN (3 mL), Cu(OTf)2 (0.05 mmol, 18 mg)
and triethylanmine (0.05 mmol, 5 mg) were added. The reaction mixture was
stirred at room temperature for 6 h. After the completion of the reaction, EtOAc
(15 mL) was added to dilute the reaction solution. Then, the mixture was
washed with water and brine. The combined organic phases were dried and
concentrated in vacuo, and the residue was purified by column
a
-methylene alkenes and nitroolefins, the cyclation catalyzed by
Cu(OTf)2 and Et3N, and the oxidation in atmosphere.
In summary, we have developed a simple, convenient and effi-
cient synthetic protocol for polysubstituted benzenes using
Cu(OTf)2/Et3N as a novel catalytic system in CH3CN. The simplicity,
efficiency, easy work-up, short reaction time, and the need for cat-
alytic amount of base make it a preferred procedure for the prep-
aration of polysubstituted benzenes.
Acknowledgments
We thank the National Key Technology R&D Program
2007BAI34B00 and National Natural Science Foundation of China
[20676123] for financial support.
chromatography (hexane/AcOEt = 10:1) to afford the 6c as
crystalline powder.
a yellow
Spectral data for selected products:
3-Amino-2-nitro-1-phenyl-9,10-dihydrophenanthrene-4-carbonitrile (4h): Yellow
crystals, mp 201–202 °C (201.2–203.4 °C11), yield: 80%. 1H NMR (500 MHz,
CDCl3): d 8.24 (t, J = 2.0 Hz, 1H), 7.40–7.47 (m, 5H), 7.28 (dd, J1 = 6.5 Hz,
J2 = 8.5 Hz, 1H), 7.20–7.22 (m, 2H), 5.66 (s, 2H), 2.63–2.65 (m, 2H), 2.38–2.40
(m, 2H). 13C NMR (125 Hz, CDCl3): d 143.3, 142.5, 140.4, 139.8, 135.7, 131.1,
130.5, 128.8, 128.6, 128.0, 127.9, 127.4, 127.1, 117.2, 95.4, 29.1, 26.0. IR (KBr)
References and notes
1. Recent selected examples: (a) Warshakoon, N. C.; Sheville, J.; Bhatt, R. T.; Ji, W.;
Mendez-Andino, J. L.; Meyers, K. M.; Kim, N.; Wos, J. A.; Mitchell, C.; Paris, J. L.;
Pinney, B. B.; Reizes, O.; Hu, X. E. Bioorg. Med. Chem. Lett. 2006, 16, 5207; (b)
Frazier, K.; Jazan, E.; McBride, C. M.; Pecchi, S.; Renhowe, P. A.; Shafer, C. M.;
Taylor, C.; Bussiere, D.; He, M. M.; Jansen, J. M.; Lapointe, M.; Ma, S.; Vora, J.;
Wiesmann, J. Bioorg. Med. Chem. Lett. 2006, 16, 2247; (c) Wang, J. Q.; Gao, M.;
m
max: 3466, 3382, 2214, 1620, 1512, 920, 706 cmÀ1. MS (EI): m/z (%) = 341 (54,
M+), 305 (100).
3-Amino-5-(furan-2-yl)-4-nitrobiphenyl-2-carbonitrile (4n): Yellow crystals,
mp 164–165 °C, yield: 83%. 1H NMR (500 MHz, CDCl3): d 7.50–7.58 (m, 5H),

W. Su et al. / Tetrahedron Letters 50 (2009) 636–639
7.26 (s, 1H), 7.05 (s, 1H), 6.76 (d, J = 3.2 Hz, 1H), 6.53 (dd, J1 = 2.0 Hz, Ethyl 5-amino-6-nitro-7-phenyl-2,3-dihydro-1H-indene-4-carboxylate
639
(5d):
J1 = 3.2 Hz, 1H), 6.58 (s, 2H). 13C NMR (125 Hz, CDCl3): d 117.0, 110.7, 107.3,
106.7, 99.5, 92.3, 92.1, 90.9, 80.5, 78.2, 74.8, 74.1. MS (EI): m/z (%) = 302 (23,
M+), 232 (100). HRMS calcd for C17H11N3O3 (M+): 305.0800; found: 305.0801.
Ethyl 2-amino-3-nitro-4-(thiophen-2-yl)-5,6,7,8-tetrahydronaphthalene-1-carboxylate
(5c): Yellow crystals, mp 173–174 °C, yield: 64%. 1H NMR (400 MHz, CDCl3): d
7.41 (dd, J1 = 0.8 Hz, J2 = 5.2 Hz, 1H), 7.05 (dd, J1 = 3.6 Hz, J2 = 5.2 Hz, 1H), 6.88
(dd, J1 = 1.2 Hz, J2 = 3.2 Hz, 1H), 5.03 (d, J = 2.4 Hz, 2H), 4.44 (q, J = 6.8 Hz, 2H),
2.85 (t, J = 6.4 Hz, 2H), 2.45 (t, J = 6.4 Hz, 2H), 1.65–1.74 (m, 4H), 1.41 (t, J = 6.8 Hz,
3H). 13C NMR (100 MHz, CDCl3): d 167.8, 141.2, 137.0, 135.3, 130.8, 128.0, 127.8,
127.0, 126.9, 119.7, 64.6, 29.1, 27.7, 22.3, 22.2, 14.2. MS (EI): m/z (%) = 347 (12,
M++1), 346 (42, M+), 282 (100). HRMS calcd for C17H18N2O4S (M+): 346.0987;
found: 346.0988.
Yellow crystals, mp 94–95 °C, yield: 62%. 1H NMR (400 MHz, CDCl3): d 7.34–
7.42 (m, 3H), 7.20–7.23 (m, 2H), 6.93 (s, 2H), 4.41 (q, J = 7.2 Hz, 2H), 3.27 (t,
J = 7.6 Hz, 2H), 2.57 (t, J = 7.6 Hz, 2H), 1.92–1.99 (m, 2H), 1.42 (t, J = 7.2 Hz, 3H).
13C NMR (100 MHz, CDCl3): d 168.0, 152.3, 143.6, 137.6, 137.6, 137.0, 132.3,
128.5, 128.0, 127.5, 110.9, 61.1, 36.8, 31.6, 24.6, 14.3. MS (EI): m/z (%) = 327 (12,
M++1), 326 (100). HRMS calcd for C18H18N2O4 (M+): 326.1267; found: 326.1269.
2-(1-(4-Methoxyphenyl)-4-nitro-3-(thiophen-2-yl)butylidene)malononitrile (6c):
Yellow crystalline powder; mp 84–85 °C; yield: 92%. 1H NMR (400 MHz,
CDCl3): d = 7.62 (dd, J1 = 2.4 Hz, J2 = 6.4 Hz, 2H), 7.54 (d, J = 8.8 Hz, 1H), 6.98–
7.04 (m, 3H), 6.89 (s, 1H), 5.68 (s, 1H), 3.87–3.90 (m, 4H), 2.62 (s, 3H). MS (EI): m/z
(%) = 353 (10, M+), 197 (100). HRMS (EI) calcd for C18H15N3O3S ([M]+) 353.3950;
found: 353.3947.