β-Nitroacrylates as Starting Materials of Thiophene-2-Carboxylates Under Continuous Flow Conditions

Article abstract of DOI:10.1002/adsc.201801660

We report herein a general and efficient continuous flow-based protocol for synthesizing thiophene-2-carboxylates starting from ketal-functionalized β-nitroacrylates. The protocol involves (i) a promoter-free conjugate addition of thioacetic acid to β-nitroacrylates, (ii) a base-induced elimination of nitrous acid, and (iii) a final acid-promoted domino cyclization-aromatization process to afford the title targets. Thanks to the means of the flow chemistry and the use of solid supported systems, the three steps were combined in a whole flow chemical process, by which the products were isolated in good to excellent overall yields (38–88%). (Figure presented.).

Full text of DOI:10.1002/adsc.201801660

Title: β-Nitroacrylates as Starting Materials of Thiophene-2-
carboxylates Under Continuous Flow Conditions
Authors: Alessandro Palmieri, Elena Chiurchiù, Serena Gabrielli,
Roberto Ballini, and Yeersen Patehebieke
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801660
Link to VoR: http://dx.doi.org/10.1002/adsc.201801660

10.1002/adsc.201801660
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
β-Nitroacrylates as Starting Materials of Thiophene-2-
carboxylates Under Continuous Flow Conditions
Elena Chiurchiù,a Yeersen Patehebieke,a Serena Gabrielli,a Roberto Ballini,a and
Alessandro Palmieria,*
a
Green Chemistry Group, Chemistry Division, School of Science and Technology, University of Camerino, Via S.
Agostino n. 1, 62032 Camerino (MC), Italy
Fax: (+39)-0737-402297; phone: (+39)-0737-402262; e-mail: alessandro.palmieri@unicam.it
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. We report herein
a general and efficient Thanks to the means of the flow chemistry and the use of
continuous flow-based protocol for synthesizing thiophene- solid supported systems, the three steps were combined in a
2-carboxylates starting from ketal-functionalized β- whole flow chemical process, by which the products were
nitroacrilates. The protocol involves (i) a promoter-free isolated in good to excellent overall yields (38-88%).
conjugate addition of thioacetic acid to β-nitroacrilates, (ii) a
base-induced elimination of nitrous acid, and (iii) a final
acid-promoted domino cyclization-aromatization process to
afford the title targets.
Keywords: β-Nitroacrilates; Thiophenes; Flow chemistry;
Heterocycles; Solid supported systems
Following these studies, we were attracted by an
important scaffold such as thiophene-2-carboxylates
Introduction
4
(Scheme 2), molecular structures widely
β-Nitroacrilates are a versatile class of electron-
poor alkenes bonding an ester and a nitro group on α-
and β- position, respectively (Figure 1).
investigated for their own biological activities,[4] used
as key intermediates of biologically active targets,[5]
and explored for the preparation of liquid crystals.[6]
Thus, as development of our research, we have now
found a new profitable flow synthesis of 4 starting
from β-nitroacrylates type 1. Our protocol is based on
three different steps: (i) reaction of 1 with AcSH to
afford the Michael adduct 2, (ii) elimination of
nitrous acid to provide 3, and (iii) simultaneous
cleavage of the dioxolane ring and thioactetate ester
to furnish, via an intramolecular cyclization, the 2,5-
disubstituted thiophenes 4. By the means of the flow
Figure 1. Generic structure of β-nitroacrylates.
The simultaneous presence of both functionalities
makes these compounds useful reactive electrophilic
species and valuable building blocks of a variety of
highly functionalized materials.[1] In this context, we
recently discovered that ketal-functionalized β-
nitroacrylates type 1 are key precursors of important
heterocyclic systems, such as functionalized indoles[2]
and pyrroles[3] (Scheme 1).
chemistry
and
solid
supported
reagents
peculiarities,[7] these transformations were joined in a
single flow process to continuously produce the target
thiophenes avoiding any intermediates isolation and
purification, thus minimizing material and energy
consumptions with evident advantages from the
sustainable point of view (Scheme 2).
Moreover, this protocol offers the opportunity to
overcome several important drawbacks present in
published methodologies, such as low yields, limited
substrates scope, harsh reaction conditions, and the
use of expensive catalysts.[8]
Scheme 1. Use of ketal-functionalized β-nitroacrilates type
1 as precursors of cyclic systems.
1
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10.1002/adsc.201801660
Advanced Synthesis & Catalysis
Scheme 2. Experimental setup for the flow chemical process.
Table 1. Optimization studies concerning the Michael
addition of AcSH to 2a.
Results and Discussion
1a
(M)
AcSH
(M)
Flow rate
(mL/h/pump) of 2a
Yield (%)[1]
Entry
With the purpose to find the best flow process
conditions, we started to investigate the first step,
then, based on the obtained results, we applied the
optimized parameters to set in series the second and
the third steps. In this context, we firstly studied the
Michael addition between thioacetic acid and the β-
nitroacrylate 1a (reference substrate).
a
b
c
d
e
f
g
h
i
0.4
0.2
0.1
0.05
0.1
0.1
0.1
0.1
0.1
0.1
0.44
0.22
0.11
0.055
0.11
0.11
0.11
0.15
0.2
0.5
0.5
0.5
0.5
1
1.5
2
1.5
1.5
1.5
49
53
58
57
56
59
53
62
69
63
A series of preliminarily batch studies highlighted
the formation of several by-products due to the
instability of 1a and 2a under protracted acidic
conditions. In fact, even testing a large variety of
reaction conditions, the best trial (0.2M in MeCN, 1.1
eq. AcSH, 1h) provided 2a only in poor yield (17%).
In order to minimize the contact between 1a and
2a with an excess of AcSH, and to minimize the by-
products formation, we implemented the flow
equipment shown in the Scheme 3. It consists of two
different reservoirs, respectively containing a solution
of 1a (Reservoir A) and a solution of AcSH
(Reservoir B), a T-mixing piece (T) and a PTFE coil
reactor (R1). Repeating the reaction under flow
conditions, 2a was isolated in 49% of yield (Table 1,
entry a) that, after a screening in terms of
stoichiometry, concentration and residence time, was
improved up to 69% of yield (Table 1, entry i).
k
[1]
0.25
Yield of pure isolated product, reaction performed in
MeCN.
Nevertheless, the adduct 2a partially decomposes
under column chromatography conditions. With the
aim to prevent this problem and maximize the yield,
we considered the possibility to execute the nitrous
acid elimination step in series. Hence, we connected
the coil reactor R1 to the reactor R2 packed with a
solid supported base (Scheme 4).
Scheme 4. Consecutive flow chemical Michael addition
and nitrous acid elimination processes.
By this equipment, we screened different bases and
solvents, obtaining the best yields conducing the
reactions in acetonitrile (97%) or toluene (91%) and
using 2 equivalents of carbonate on polymer support
(Table 2, entries g and i).
Scheme 3. Flow chemical Michael addition process.
2
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10.1002/adsc.201801660
Advanced Synthesis & Catalysis
Table 2. Optimization studies about the Michael addition
and nitrous acid elimination processes.
Table 3. Optimization studies about the third step:
conversion of 3a into 4a third steps.
Yield (%)[1]
Entry Supported base (eq.) Solvent
of 3a
a
b
c
d
e
f
g
h
i
PS-TBD (1)
PS-BEMP (1)
PS-F (1)
PS-DMAP (1)
PS-Carbonate (1)
PS-Carbonate (1.5)
PS-Carbonate (2)
PS-Carbonate (2)
PS-Carbonate (2)
PS-Carbonate (2)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
EtOAc
Toluene
41
52
33
28
62
78
97
75
91
Amb. 15
(g/mmol) (°C)
Temp.
Yield (%)[1]
of 4a
Entry
Solvent
a
b
c
d
e
f
1
1
1
1
2
3
3
3
80
MeCN
MeCN
MeCN
Toluene
Toluene
Toluene
26
35
30
58
77
93
100
110
100
100
100
100
100
j
2-MeTHF 61
[1] Yield of pure isolated product.
g
h
2-MeTHF 51
EtOAc 68
[1] Yield of pure isolated product.
Successively, we faced off the optimization of the
third step studying the conversion of 3a into the
target 4a. In this context, based on our experience on
dioxolane ring cleavage,[3,4,9] we selected Amberlyst
15 as supported acidic species and we ran exploratory
tests to set the appropriate reaction parameters such
as temperature, solvents and Amberlyst 15 amount.
After a series of trials, the best yield (93%) was
obtained in toluene, at 100°C and using 3g/mmol of
Amberlyst 15 (Table 3, entry f). The comparison of
the results (Table 2 and Table 3) identifies toluene as
the best solvent for the entire process.
Finally, in the interest of running the entire process
in the one continuous flow, we set in all steps
together testing the direct conversion of 1a into 4a.
As reported in the Scheme 5 the compound 4a was
isolated in excellent overall yield (84%).
Then, we verified the generality of our approach
submitting a wide range of ketal-functionalized β-
nitroacrylates type 1 to the optimized reaction
conditions. In all cases, thiophene-2-carboxylates 4a-
k were isolated in good to excellent overall yields
(38-88%) (Figure 2).
Scheme 5. Test of the entire process under flow continuous conditions: conversion of 1a into 4a.
Figure 2. Synthesis of thiophene-2-carboxylates 4a-k.
3
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10.1002/adsc.201801660
Advanced Synthesis & Catalysis
General Flow Procedure for the Synthesis of Compounds 4a-k.
According to the flow equipment reported in the Scheme 5
and in the supporting information (Figure S1), 10mL of a
0.1M solution of the β-nitroacrylate 1 in toluene (Reservoir
A) and 10 mL of a 0.2M thioacetic acid solution in toluene
(Reservoir B) were simultaneously pumped (Syringe
pumps model NE-300) with a flow rate of 1.5 mL/h/pump
into the T-connector before passing through a 2 mL coil
reactor (R1), then in a packed bed reactor (R2) containing 2
equivalents of PS-Carbonate (0.571 g, residence time ~11
min), and finally, in a further packed bed reactor (R3) filled
with Amberlyst 15 (3 g, residence time ~60 min) and
heated at 100°C. The entire process is pressurized by a
back pressure regulator set at 2 atm and the outflow was
collected into a round bottom flask. Terminate the reaction,
the solution was concentrated at reduced pressure and the
crude product purified by flash column chromatography
(Further chromatography techniques, such as the
centrifugal partition chromatography, can potentially be
associated to the flow process for directly purifying
products).[10]
Conclusion
In conclusion, we developed a new fruitfully and
general protocol for synthesizing thiophene-2-
carboxylates under flow chemical conditions. Indeed,
our method allows to prepare the title compounds in
good to excellent overall yields, with the possibility
to introduce a variety of aliphatic and aromatic
substituents at the 5-position, and different esters at
the 1-position. Moreover, by the means of the flow
chemistry combined with the use of solid supported
reagents, it was possible to avoid the isolation of any
intermediates, therefore minimizing the material and
energy consumptions with evident benefits from a
sustainable point of view. Finally, this procedure
represents a further evidence of the strategic utility of
ketal-functionalized β-nitroacrylates as key and
versatile precursors of heterocyclic systems.
Ethyl 5-methylthiophene-2-carboxylate 4a. Pale yellow
oil. IR (cm-1, neat): 749, 815, 1089, 1256, 1464, 1540,
1
1708. H-NMR (CDCl3, 400MHz) δ: 1.35 (t, 3H, J = 7.3
Hz), 2.51 (s, 3H), 4.31 (q, 2H, J = 7.3 Hz), 6.73-6.76 (m,
1H), 7.59 (d, 1H, J = 3.8 Hz). 13C-NMR (CDCl3, 100MHz)
δ: 14.6, 16.0, 61.1, 126.5, 131.6, 133.9, 148.0, 162.5. GC-
MS (70 eV): m/z: 170 ([M+], 29), 142 (19), 125 (100), 97
(16), 53 (15). Anal. Calcd. for C8H10O2S (170.23): C,
56.45; H, 5.92; S, 18.83. Found: C, 56.41; H, 5.89; S,
18.87.
Abbreviations
The following abbreviations are used in this
manuscript:
PS-Carbonate: Carbonate on polymer support
(Sigma-Aldrich code: 21850, loading:
3.5 mmol/g)
Ethyl thiophene-2-carboxylate 4b. Pale yellow oil. IR
1
(cm-1, neat): 718, 750, 1091, 1258, 1420, 1526, 1703. H-
NMR (CDCl3, 400MHz) δ: 1.37 (t, 3H, J = 6.8 Hz), 4.35
(q, 2H, J = 6.8 Hz), 7.08-7.11 (m, 1H), 7.53-7.55 (m, 1H),
7.79-7.81 (m, 1H). 13C-NMR (CDCl3, 100MHz) δ: 14.6,
61.4, 127.9, 132.4, 133.5, 134.3, 162.5. GC-MS (70 eV):
m/z: 156 ([M+], 19), 128 (25), 111 (100), 83 (7), 57 (5), 39
(15). Anal. Calcd. for C7H8O2S (156.20): C, 53.83; H,
5.16; S, 20.53. Found: C, 53.88; H, 5.19; S, 20.56.
PS-DMAP:
4-(Dimethylamino)pyridine,
polymer-bound (Sigma-Aldrich code:
39410, loading: 3 mmol/g)
PS-BEMP:
2-tert-Butylimino-2-diethylamino-
1,3-dimethylperhydro-1,3,2-
diazaphosphorine,
(Sigma-Aldrich
polymer-bound
code: 20026,
Ethyl 5-ethylthiophene-2-carboxylate 4c. Pale yellow oil.
IR (cm-1, neat): 749, 1088, 1246, 1278, 1454, 1464, 1705.
1H-NMR (CDCl3, 400MHz) δ: 1.31 (t, 3H, J = 7.3 Hz)
1.35 (t, 3H, J = 6.8 Hz), 2.86 (q, 2H, J = 7.3 Hz), 4.31 (q,
2H, J = 7.3 Hz), 6.76-6.79 (m, 1H), 7.61 (d, 1H, J = 3.8
Hz). 13C-NMR (CDCl3, 100MHz) δ: 14.6, 15.9, 24.1, 61.1,
124.7, 131.2, 133.7, 155.6, 162.6. GC-MS (70 eV): m/z:
184 ([M+], 47), 169 (37), 156 (12), 141 (48), 139 (100),
111 (12), 97 (10), 77 (9). Anal. Calcd. for C9H12O2S
(184.25): C, 58.67; H, 6.56; S, 17.40. Found: C, 58.63; H,
6.52; S, 17.36.
loading: 2.2 mmol/g)
PS-TBD:
PS-F:
1,5,7-Triazabicyclo[4.4.0]dec-5-ene
bound to polystyrene (Sigma-Aldrich
code: 01961, loading: 3.0 mmol/g)
Fluoride on polymer support (Sigma-
Aldrich code: 47060, loading: 3.0
mmol/g)
Ethyl 5-(4-chlorophenyl)thiophene-2-carboxylate 4d.
White solid, mp: 75-77. IR (cm-1, neat): 749, 812, 1091,
Experimental Section
1
1290, 1448, 1682. H-NMR (CDCl3, 400MHz) δ: 1.39 (t,
3H, J = 6.8 Hz), 4.36 (q, 2H, J = 6.8 Hz), 7.25 (d, 1H, J =
3.8 Hz), 7.37 (d, 2H, J = 8.5 Hz), 7.55 (d, 2H, J = 8.5 Hz),
7.74 (d, 1H, J = 3.8 Hz). 13C-NMR (CDCl3, 100MHz) δ:
14.6, 61.5, 124.1, 127.6, 129.5, 132.2, 133.2, 134.5, 134.8,
149.8, 162.4. GC-MS (70 eV): m/z: 266 ([M+], 81), 237
(48), 220 (100), 193 (22), 149 (51), 114 (10), 79 (8). Anal.
Calcd. for C13H11ClO2S (266.74): C, 58.54; H, 4.16; S,
12.02. Found: C, 58.58; H, 4.12; S, 11.99.
General Remarks
1HNMR analyses were recorded at 400 MHz on a
VarianMercury Plus 400. 13CNMR analyses were recorded
at 100 MHz. IR spectra were recorded with a PerkinElmer
FTIR spectrometer Spectrum Two UATR. Microanalyses
were performed with a CHNS-O analyzer Model EA 1108
from Fisons Instruments. GS-MS analyses were obtained
on a Hewlett-Packard GC/MS 6890N that works with the
EI technique (70 eV). PS-Carbonate, PS-DMAP, PS-
BEMP, PS-TBD and PS-F were purchased from Sigma–
Aldrich and used directly without any manipulation.
Amberlyst 15 was purchased from Sigma–Aldrich and
purified by soaking in methanol for 24 hours, then washing
with fresh methanol and THF and dried under vacuum.
Ethyl 5-([1,1'-biphenyl]-4-yl)thiophene-2-carboxylate
4e. White solid, mp: 136-138°C. IR (cm-1, neat): 650, 727,
904, 1098, 1268, 1702. 1H-NMR (CDCl3, 400MHz) δ: 1.40
(t, 3H, J = 7.3 Hz), 4.38 (q, 2H, J = 7.3 Hz), 7.33 (d, 1H, J
= 3.8 Hz), 7.35- 7.40 (m, 1H), 7.43-7.49 (m, 2H), 7.60-
7.66 (m, 4H), 7.70-7.74 (m, 2H), 7.78 (d, 1H, J = 3.8 Hz).
13C-NMR (CDCl3, 100MHz) δ: 14.6, 61.4, 123.8, 126.8,
127.2, 127.9, 128.0, 129.1, 132.6, 132.7, 134.5, 140.4,
141.8, 150.9, 162.5. GC-MS (70 eV): m/z: 308 ([M+], 100),
280 (46), 263 (47), 236 (17), 191 (48), 131 (13), 95 (12).
4
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10.1002/adsc.201801660
Advanced Synthesis & Catalysis
Anal. Calcd. for C19H16O2S (308.39): C, 74.00; H, 5.23; S,
10.40. Found: C, 74.04; H, 5.20; S, 10.37.
The authors thank the University of Camerino for the financial
support.
Methyl 5-phenethylthiophene-2-carboxylate 4f. White
solid, mp: 50-52°C. IR (cm-1, neat): 740, 824, 1091, 1254,
References
1
1461, 1703, 3009, 3033. H-NMR (CDCl3, 400MHz) δ:
2.97-3.03 (m, 2H), 3.12-3.18 (m, 2H), 3.86 (s, 3H), 6.75 (d,
1H, J = 3.8 Hz), 7.15-7.33 (m, 5H), 7.62 (d, 1H, J = 3.8
Hz). 13C-NMR (CDCl3, 100MHz) δ: 32.5, 37.8, 52.2, 125.8,
126.6, 128.6, 128.7, 131.1, 133.9, 140.6, 152.7, 163.0. GC-
MS (70 eV): m/z: 246 ([M+], 31), 155 (100), 126 (10), 91
(47), 65 (48). Anal. Calcd. for C14H14O2S (246.32): C,
68.27; H, 5.73; S, 13.02. Found: C, 68.32; H, 5.77; S,
12.98.
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Benzyl 5-methylthiophene-2-carboxylate 4g. Pale yellow
oil. IR (cm-1, neat): 744, 814, 1035, 1076, 1268, 1371,
[3] A. Palmieri, S. Gabrielli, M. Parlapiano, R. Ballini,
1
1451, 1691. H-NMR (CDCl3, 400MHz) δ: 2.52 (s, 3H),
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5.32 (s, 2H), 6.76 (d, 1H, J = 3.8 Hz), 7.30-7.46 (m, 5H),
7.65 (d, 1H, J = 3.8 Hz). 13C-NMR (CDCl3, 100MHz) δ:
16.0, 66.7, 126.6, 128.3, 128.4, 128.8, 131.1, 134.4, 136.2,
148.5, 162.3. GC-MS (70 eV): m/z: 232 ([M+], 45), 187
(11), 125 (100), 91 (48). Anal. Calcd. for C13H12O2S
(232.30): C, 67.22; H, 5.21; S, 13.80. Found: C, 67.17; H,
5.18; S, 13.76.
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Eur. J. Med. Chem. 2014, 83, 317-337.
Butyl thiophene-2-carboxylate 4h. Pale yellow oil. IR
1
(cm-1, neat): 750, 1092, 1257, 1419, 1526, 1705. H-NMR
[6] a) R. Cai, Samulski, E. T. Liq. Cryst. 1991, 9, 617-634;
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917.
(CDCl3, 400MHz) δ: 0.97 (t, 3H, J = 7.3 Hz), 1.40-1.41 (m,
2H), 1.65-1.77 (m, 2H), 4.30 (t, 2H, J = 6.8 Hz), 7.08-7.11
(m, 1H), 7.53-7.55 (m, 1H), 7.78-7.80 (m, 1H). 13C-NMR
(CDCl3, 100MHz) δ: 14.0, 19.4, 31.0, 65.2, 127.9, 132.4,
133.5, 134.3, 162.6. GC-MS (70 eV): m/z: 184 ([M+], 9),
128 (60), 111 (100), 83 (8), 56 (8), 39 (19). Anal. Calcd.
for C9H12O2S (184.25): C, 58.67; H, 6.56; S, 17.40. Found:
C, 58.62; H, 6.60; S, 17.37.
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Butyl 5-ethylthiophene-2-carboxylate 4i. Pale yellow oil.
IR (cm-1, neat): 750, 1089, 1253, 1278, 1449, 1526, 1705.
1H-NMR (CDCl3, 400MHz) δ: 0.96 (t, 3H, J = 7.3 Hz),
1.32 (t, 3H, J = 7.3 Hz), 1.39-1.50 (m, 2H), 1.67-1.75 (m,
2H), 2.86 (q, 2H, J = 7.3 Hz), 4.26 (t, 2H, J = 6.8 Hz),
6.77-6.79 (m, 1H), 7.63 (d, 1H , J = 3.8 Hz). 13C-NMR
(CDCl3, 100MHz) δ: 14.0, 15.9, 19.4, 24.1, 31.0, 65.0,
124.7, 131.2, 133.7, 155.6, 162.7. GC-MS (70 eV): m/z:
212 ([M+], 20), 156 (78), 141 (100), 139 (90), 124 (7), 111
(14). Anal. Calcd. for C11H16O2S (212.31): C, 62.23; H,
7.60; S, 15.10. Found: C, 62.27; H, 7.57; S, 15.13.
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Pradeepa Kumara, N. Ramesh, M. P. Sadashiva, H.
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Wünsch, J. Senger, P. Schultheisz, S. Schwarzbich, K.
Schmidtkunz, C. Michael, M. Klaß, S. Goskowitz, P.
Borchert, L. Praetorius, W. Sippl, M. Jung, N. Sewald,
ChemMedChem 2017, 12, 2044-2053; h) Y. Ge, P.
Diao, C. Xu, N. Zhang, C. Guo, Chin. Chem. Lett. 2018,
29, 903-906.
Propyl 5-heptylthiophene-2-carboxylate 4j. Pale yellow
oil. IR (cm-1, neat): 733, 748, 1086, 1258, 1281, 1461,
1
1708. H-NMR (CDCl3, 400MHz) δ: 0.88 (t, 3H, J = 7.3
Hz), 1.00 (t, 3H, J = 7.3 Hz), 1.21-1.41 (m, 8H), 1.62-1.81
(m, 4H), 2.82 (t, 2H, J = 7.7 Hz), 4.22 (t, 2H, J = 6.8 Hz),
6.77 (d, 1H, J = 3.8 Hz), 7.62 (d, 1H, J = 3.8 Hz). 13C-
NMR (CDCl3, 100MHz) δ: 10.7, 14.3, 22.4, 22.9, 29.2,
30.7, 31.7, 32.0, 66.7, 125.3, 131.2, 133.7, 154.2, 162.7.
GC-MS (70 eV): m/z: 268 ([M+], 45), 209 (64), 183 (96),
141 (100), 97 (51), 43 (25). Anal. Calcd. for C15H24O2S
(268.41): C, 67.12; H, 9.01; S, 11.94. Found: C, 67.17; H,
9.05; S, 11.91.
Propyl 5-(p-tolyl)thiophene-2-carboxylate 4k. White
solid, mp: 54-56°C. IR (cm-1, neat): 747, 806, 1086, 1234,
1263, 1344, 1447, 1539, 1701. 1H-NMR (CDCl3, 400MHz)
δ: 1.03 (t, 3H, J = 7.3 Hz), 1.72-1.85 (m, 2H), 2.38 (s, 3H),
4.26 (t, 2H, J = 6.8 Hz) 7.21 (d, 2H, 8.1 Hz), 7.25 (d, 1H, J
= 3.8 Hz), 7.53 (d, 2H, J = 8.1 Hz), 7.74 (d, 1H, J = 3.8
Hz). 13C-NMR (CDCl3, 100MHz) δ: 10.7, 21.5, 22.4, 66.9,
123.3, 126.3, 130.0, 131.0, 132.2, 134.4, 139.1, 151.6,
162.6. GC-MS (70 eV): m/z: 260 ([M+], 71), 218 (100),
201 (67), 173 (18), 129 (40). Anal. Calcd. for C15H16O2S
(260.35): C, 69.20; H, 6.19; S, 12.31. Found: C, 69.25; H,
6.22; S, 12.34.
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3407-3413
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Acknowledgements
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10.1002/adsc.201801660
Advanced Synthesis & Catalysis
S. N. Chen, G. F. Pauli, J. Nat. Prod. 2015, 78, 1765-
1796.
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10.1002/adsc.201801660
Advanced Synthesis & Catalysis
FULL PAPER
β-Nitroacrylates as Starting Materials of
Thiophene-2-carboxylates Under Continuous Flow
Conditions
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Elena Chiurchiù, Yeersen Patehebieke, Serena
Gabrielli, Roberto Ballini, and Alessandro
Palmieri*
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