Access to [2,1]benzothiazine s,s-dioxides from β-substituted o-nitrostyrenes and sulfur

Article abstract of DOI:10.1021/acs.joc.0c00918

[2,1]Benzothiazine S,S-dioxides 2 were synthesized by simply heating o-nitrostyrenes with elemental sulfur in 3- picoline with complete atom economy. This reaction was found to occur without any added catalyst and consist of a cascade of reduction of the

Full text of DOI:10.1021/acs.joc.0c00918

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Article
Access to [2,1]benzothiazine S,S-dioxides
from #-Substituted o-Nitrostyrenes and Sulfur
Thi Mo Nguyen, Hoang Anh Cao, Thi Thuong Thuong Cao,
Satoki Koyama, Dinh Hung Mac, and Thanh Binh Nguyen
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00918 • Publication Date (Web): 03 Sep 2020
Downloaded from pubs.acs.org on September 4, 2020
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Access to [2,1]benzothiazine S,S-dioxides from -Substituted o-
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Nitrostyrenes and Sulfur
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Thi Mo Nguyen,b Hoang Anh Cao,b Thi Thuong Thuong Cao,b Satoki Koyama,b,c Dinh Hung Mac, b,*
Thanh Binh Nguyen a,*
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a Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université
Paris-Saclay, 1 avenue de la Terrasse, 91198 Gif-sur-Yvette, France
b Faculty of Chemistry, VNU University of Science, Vietnam National University in Hanoi, 19 Le
Thanh Tong, Hanoi, Viet Nam
c Department of Chemistry, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama,
Higashihiroshima, Hiroshima 739-8526, Japan
Email: macdinhhung@hus.edu.vn
thanh-binh.nguyen@cnrs.fr
ABSTRACT: [2,1]Benzothiazine S,S-dioxides 2 were synthesized by simply heating o-nitrostyrenes
with elemental sulfur in 3-picoline with complete atom economy. This reaction was found to occur
without any added catalyst and consist of a cascade of reduction of the nitro group, sulfuration of a C-
H of the double bond, oxidation of a sulfur atom to its highest oxidation state by the migration of two
oxygen atoms from the nitro group and formation of new N-S bond. Furthermore, the method could also
be applied to o-nitrocinnamamides and cinnamate esters.
Introduction
Cyclic sulfonamides or sultams exist widely in bioactive molecules and pharmaceuticals, which
frequently serve as a key scaffold for discovery of new drugs owning to their sulfonamide
pharmacophore. As a subgroup of sultam, [2,1]benzothiazine S,S-dioxide scaffolds have potent
biological activities (Figure 1).1 Indeed, A was demonstrated to be an inhibitor of nuclear factor kappaB
(NF-B), which is a pivotal transcription factor that regulates the gene expression involved in
inflammation and immune responses.2 Moreover, both B and C were found to inhibit focal adhesion
kinase (FAK), which regulates cell survival and proliferation pathways. While the inhibitory activity of
C is strong and selective,3 the derivatives B can restore, in a concentration dependent manner, the
antibacterial activity of CPX against SA-K2378, a norA-overexpressing strain.4 While many RNA
viruses such as Dengue, Zika, and several encephalitis viruses have been “re-discovered” over the years,
non-nucleoside derivative D displayed inhibitory activity against dengue NS5 RNA-dependent RNA
polymerase (RdRp).
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O
Me
R
H2N
O
S
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N
N
O
S
O
N
N
O
H
Me
N
B, FAK inhibitors
A, NF-B inhibitor
R = H, CO2Me
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O
S
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F
N
H
O
F
[2,1]benzothiazine-S-dioxide
R'
N
N
R
Br
O
O
O
S
O
N
O
Me
O
S
N
O
C, FAK inhibitors
R = 4-EtC6H4, R' = H
R = 4-t-BuC6H4CH2NH, R' = Me
Me
D, inhibitors of Dengue NS5 RdRp
Figure 1. 2,1-Benzothiazine S,S-dioxide and its bioactive examples
Consequently, the construction of these heterocyclic scaffolds has drawn considerable interest (Figure
2).5
4
Known methods:
X
O
Ar
S
O
O
6
S
O
HN
C6-N
Y
C4-C5
-HX
NH
5
H
H
(2)
(1)
Ar
-HY
Y = H, CO2H
4
5
3
X = H, halo, NH2
Ar
O
S
6
N
H
O
C4-C5 & C6-N
-TMSOTf, -MeOH
C3-C4
-CH2=CH2
benzothiazine-S-dioxide
(3)
(4)
-low atom efficiency
-loss of leaving group
-expensive catalyst
-complex substrates
4
Ar
O
5
6
O
TMS
OTf
H
S
3
N
Ar
O
S
4
H
N
MeO
O
H
CH2 H2C
Our approach: Formation of S-N & C3-S bond
self adjustment of oxidation states
4
3
R
5
6
redox neutral
100% atom efficiency
+
Ar
S
H
O
+
N
O-
Figure 2. Synthetic approaches to 2,1-Benzothiazine S,S-dioxides
The first approach involves a C-N bond formation via C-H cyclizing functionalization of NH
sulfonamides (Pathway 1: formation of C6-N bond) with strong oxidizing agents, including high
oxidation state iodine reagents such as PhI(OAc)2/h,6 PhI(OAc)2–I2,7 PhI(OAc)2 or K2S2O8 with NaBr,8
and dibromohydantoin.9 In some cases, further halogenation of the benzothiazine-S,S-dioxide products
is among frequently encountered side reactions. Silver-catalyzed Minisci-type decarboxylative
cyclization was also developed for this purpose.10
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Alternatively, C4-C5 bond formation via C-H functionalization (Pathway 2: formation of C4-C5 bond)
was also developed with a strong focus on using Pd catalyst.11
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Recently, the benzyne chemistry was exploited via formation of C4-C5 and C6-N (Pathway 3).12 The ring
closing metathesis reaction was also applied to the synthesis of this benzothiazine scaffold (Pathway
4).13
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Although these strategies could provide the expected products with high degree of structural diversity,
they all suffer from at least one of the following drawbacks: (i) use of expensive transition metal
catalysts and reagents; (ii) involvement of starting materials that were prepared via multistep sequences
of reactions with low global yields; (iii) formation of mixtures of regioisomers; and (iv) formation of
only one bond (except for pathway 3).
More importantly, in term of atom efficiency, none of the above-mentioned reactions could deliver the
products with conservation of the number of atoms due to the presence of leaving groups as well as
activating groups in the starting materials.
To address these issues, we suggested the incorporation of elemental sulfur to o-nitrostyrene 1 as a result
of a cascade of oxidation of the sulfur atom, sulfuration of the C-H bond in the -position of 2, reduction
of the nitro group. It should be noted that both aromatic nitro group and olefinic C-H bond are readily
obtained. In view of huge opportunity of using nitro group as a direct nitrogen synthon for aza
heterocyclic synthesis without prior reduction, we have developed a series of redox-neutral cascade
reactions involving aromatic nitro group as a 6-electron oxidizing group.14
We have applied successfully this strategy to 2-nitrochacones to provide a wide range of sultams.15 As
a continuation of our effort in the sulfur-involved construction of complex heterocycles, herein, we
described the reaction with o-nitrostyrenes 2 -substituted by an aza heterocycle.
Results & Discussion
The model reaction was conducted with o-nitrostilbazole 1a in sulfur (5 equiv) in the presence of 3-
picoline as a basic additive (Table 1). Below 120 °C, 1a remained unchanged (entry 1). To improve the
reaction, several parameters were varied, including temperatures and base additives. Gratifyingly, at 135
°C, the desired product 2a was isolated in 84% yield. Further screening of other bases revealed that
while similar pyridine bases such as 4-picoline or pyridine could provide the expected product 2a despite
lower yields (entries 3,4), the reactions promoted by bases stronger than pyridine such as N-
methylmorpholine, N-methylpiperidine or DIPEA resulted in complex mixtures even at lower
temperatures (entries 5-7).
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Table 1. Optimization of the reaction conditions
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entrya base
temp (°C)
120
yield (%)b
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2
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5
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7
3-picoline
-
3-picoline
135
84
60
62
25d
-
4-picoline
135
pyridine
135c
120c
100
N-methylmorpholine
N-methylpiperidine
DIPEA
100
-
a
b
c
Reaction conditions: 1a (0.2 mmol), S (1 mmol, 32 mg), base (1 mmol, 5 equiv). Isolated yield.
Reaction performed in a sealed tube. c Conversion determined by 1H NMR of the crude mixture.
With the optimized reaction conditions in hand (Table 1, entry 2), the synthetic potential of this reaction
was evaluated (Scheme 1). Initially, substrates with various substituents on the nitrophenyl ring were
investigated. In addition to methoxy groups, the reaction tolerated various halogen substituents, which
could be useful for further functionalization of the products. Generally, the desired benzothiazine 2 were
obtained in acceptable to satisfactory yields (67−85%) with halogen and methoxy substituents on the
phenyl moiety (2b-2e). To evaluate further applications of the developed protocol, other regiomeric
pyridyl substrates (1f-1i) as well as their benzo analogs such as quinol-2-yl and quinol-4-yl (1j-1n) were
evaluated and gave satisfactory results.
It was worth mentioning that reactions of nitro substrates bearing other heterocyclic substituent such as
piperazinyl and benzothiazol-2-yl were also successful, furnishing the corresponding benzothiazines
(2o-2p) in reasonably good yields. The common sulfonamide structure of this family of compounds was
supported by X-ray diffraction analysis performed on single crystals of compounds 2b and 2i (CCDC
1953702 and 1953703 respectively).
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Scheme 1. Synthesis of benzothiazine S,S-dioxides 2b-p
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To further expand the scope and enrich the compound library, we attempted to synthesize benzothiazines
bearing an amide or an ester group, which have been demonstrated to possess remarkable biological
activity,4 from the corresponding o-nitrocinnamides (1q-1t) or o-nitrocinnamates (1u-1v) (Scheme 2).
Gratifyingly, a variety of o-nitrocinnamamides and esters were competent substrates to yield the
corresponding benzothiazines 2q-2v in satisfactory yields.
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Scheme 2. Synthesis of benzothiazine S,S-dioxides 2b-p
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O
O
O
N
N
O
N
H
SO2
SO2
O
SO2
N
N
N
H
H
H
2q, 56%
2r, 58%
2s, 53%
O
O
OMe
OtBu
N
H
SO2
SO2
SO2
N
N
N
H
H
H
2t, 48%
2u, 63%
2v, 67%
Our present method had however limitation. The reaction failed with 2-nitrostilbene as well as its
derivative bearing an electron withdrawing group (EWG) on the phenyl ring without the nitro group
such as 4’-cyano, 3’-nitro and 2’-carboxymethyl 2-nitrostilbenes. In these cases, the starting o-
nitrostilbenes were recovered practically unchanged with some trans-cis isomerization of the olefin
double bond.
It is clear that the reactivity of sulfur incorporation requires a strong EWG at the  position of o-
nitrostyrene skeleton.
Based on these observations as well as on our previous results,15 we propose a plausible reaction
mechanism that starts with a Michael addition of the pyridine base to the olefin double bond strongly
polarized by the -EWG to form zwitterion A where the anionic moiety is stabilized by the -EWG
(Scheme 3). This anion species then attacks sulfur to provide polysulfide B. Subsequent extrusion of a
smaller thiocycle B with simultaneous cyclization leads to 7-menbered intermediates C. Stepwise
transfer of both oxygen atoms from nitrogen to sulfur proceeds via ring opening - ring closing process
with concomitant elimination of pyridine base and furnishes the final benzothiazine S,S-dioxides 2.16
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Scheme 3. Plausible reaction pathway
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In conclusion, we demonstrated that [2,1]benzothiazine S,S-dioxides 2 could be synthesized by simply
heating o-nitrostyrenes 2 with elemental sulfur in 3-picoline with complete atom economy. This reaction
consists in a cascade of reduction of the nitro group, sulfuration of a C-H of the double bond, oxidation
of a sulfur atom to its highest oxidation state by migration of two oxygen atoms from the nitro group
and formation of new N-S bond. Furthermore, the method could be applied to o-nitrocinnamamides and
cinnamate esters. Considering the importance of organosulfur compounds, especially sulfonamide
function in medicinal chemistry, we believe that this result is of great value for synthetic chemists and
pharmacologists, opening new opportunities of finding of new biologically active molecules.
Experimental Section
General Information
Reagents were obtained from commercial supplier and used without further purification. Analytical thin
layer chromatography (TLC) was purchased from Merck KGaA (silica gel 60 F254). Visualization of
the chromatogram was performed by UV light (254 nm) or KMnO4 or vanilline stains. Flash column
chromatography was carried out using kieselgel 35-70 µm particle sized silica gel (230-400 mesh).
NMR Chemical shifts are reported in (δ) ppm relative to tetramethylsilane (TMS) with the residual
solvent as internal reference (CDCl3, δ 7.26 ppm for 1H and δ 77.0 ppm for 13C; (DMSO-d6, δ 2.50
ppm for 1H and δ 39.5 ppm for 13C). Data are reported as follows: chemical shift, multiplicity (s = singlet,
d = doublet, t = triplet, q = quartet, m = multiplet), coupling constants (Hz) and integration.
General procedure for the synthesis of starting material (10 mmol scale)
Procedure A
In a round bottom flash was added 2-nitrobenzaldehyde (1 equiv), 4-picoline (1 equiv), (or 2-picoline,
2-methylquinoline, 4-methylquinoline), anhydride acetic (15 mL) and a few drops of piperidine. The
mixture was then refluxed in an oil bath overnight. After completion of the reaction, the mixture was
neutralized with a saturated aqueous solution of Na2CO3 then extracted with CH2Cl2 (2x50 mL). The
combined organic phase was then dried over anhydrous Na2SO4, filtered and evaporated under vacuum.
The product was purified by recrystallization or by column chromatography (eluent hexane: ethyl
acetate 2:1).
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Procedure B
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In a round bottom flask was added 3-bromopyridine (1 equiv), 1-nitro-2-vinylbenzene (1.2 equiv),
dichlorobis(tri-o-tolylphosphine)palladium (5 mol %), triethylamine (3 equiv) and DMF (10 mL). The
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mixture was heated to 110 C in and oil bath overnight and cooled to room temperature. The reaction
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mixture was diluted with ethyl acetate (50 mL) and the organic phase was washed with water and a
solution of brine then dried over MgSO4. The organic layer was then filtered and concentrated under
vacuum. The crude product was purified by chromatography on silica gel (hexane/ethyl acetate: 3/1 to
1/1) to give the coupling product.
Procedure C: Synthesis of amide derivatives
In a round bottom flash was added 2-nitrocinnamic acid (1 equiv), EDCI•HCl (1 equiv) in 10 mL of
DMF. The mixture was stirred for 15 minute and HOBt (1.2 equiv), amine (1.2 equiv), and triethylamine
(2 equiv) was added to this mixture respectively. After 24h, the reaction was quenched by water and
extracted with ethyl acetate (2x50 mL). and the organic phase was washed with water, a solution of
brine and dried over MgSO4. The organic solvent was then filtered, evaporated under vacuum. The crude
product was purified by chromatography on silica gel (hexane/ethyl acetate: 2/1) to give desired amide.
Procedure D: Synthesis of ester derivatives
In a round bottom flash was added 2-nitrobenzaldehyde (1 equiv) and the corresponding ylide (1.05
equiv) dissolved in dichloromethane. The mixture was stirred for 3 h at room temperature. The reaction
was then quenched by water and the organic phase was washed with water, a solution of brine and dried
over MgSO4. The organic layer was then filtered and concentrated under vacuum. The crude product
was purified by chromatography on silica gel (hexane/ethyl acetate: 9/1) to give desired ester.
Known compounds: 1a,17 1f,17 1h,17 1j,18 1u,19 1y,19 1q,20 1s,20 1t.21
(E)-4-(5-Fluoro-2-nitrostyryl)pyridine (1b)
N
F
NO2
The product was purified by column chromatography (eluent hexane: ethyl acetate 2:1).
Pale yellow solid (1.09 g, 45%).
1H NMR (500 MHz, CDCl3) δ 8.65 (d, J = 5.1 Hz, 2H), 7.94 (d, J = 8.7 Hz, 1H), 7.89 (d, J = 2.1 Hz,
1H), 7.79 (d, J = 16.1 Hz, 1H), 7.62 (dd, J = 8.7, 2.1 Hz, 1H), 7.44 (d, J = 5.3 Hz, 2H), 6.99 (d, J = 16.1
Hz, 1H).
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13C{1H} NMR (125 MHz, CDCl3) δ 165.0 (d, J = 257.0 Hz), 150.6, 144.2, 143.4, 135.6 (d, J = 9.3 Hz),
132.3, 128.1 (d, J = 10.0 Hz), 127.9 (t, J = 2.0 Hz), 121.4, 116.2 (d, J = 23.6 Hz), 115.4 (d, J = 24.3 Hz).
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HRMS m/z calculated for [M+Na]+ C13H9FN2NaO2 267.0546. Found 267.0549.
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(E)-4-(5-Chloro-2-nitrostyryl)pyridine (1c)
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N
Cl
NO2
The product was purified by column chromatography (eluent hexane: ethyl acetate 2:1).
Pale yellow solid (1.23, 47%).
1H NMR (500 MHz, CDCl3) δ 8.66 – 8.49 (m, 2H), 8.01 (d, J = 8.5 Hz, 1H), 7.77 (d, J = 16.1 Hz, 1H),
7.72 (d, J = 2.2 Hz, 1H), 7.44 (dd, J = 8.8, 2.3 Hz, 1H), 7.43 – 7.35 (m, 2H), 6.98 (d, J = 16.0 Hz, 1H)
13C{1H} NMR (125 MHz, CDCl3) δ 150.5, 146.1, 143.2, 139.9, 134.0, 132.2, 128.9, 128.5, 127.4,
126.6, 121.3.
HRMS m/z calculated for [M+Na]+ C13H9ClN2NaO2 283.0250. Found 283.0255.
(E)-4-(5-Bromo-2-nitrostyryl)pyridine (1d)
N
Br
NO2
The product was purified by column chromatography (eluent hexane: ethyl acetate 2:1).
Pale yellow solid (1.65, 54%).
1H NMR (500 MHz, CDCl3) δ 8.63 (d, J = 5.2 Hz, 2H), 7.91 (d, J = 8.7 Hz, 1H), 7.88 (d, J = 2.1 Hz,
1H), 7.75 (d, J = 16.1 Hz, 1H), 7.59 (dd, J = 8.7, 2.1 Hz, 1H), 7.39 (d, J = 5.7 Hz, 2H), 6.97 (d, J = 16.1
Hz, 1H).
13C{1H} NMR (125 MHz, CDCl3) δ 150.5, 146.7, 143.5, 134.1, 132.3, 132.1, 131.6, 128.5, 127.5,
126.6, 121.4.
HRMS m/z calculated for [M+Na]+ C13H9BrN2NaO2 326.9745. Found 326.9748
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(E)-4-(4,5-Dimethoxy-2-nitrostyryl)pyridine (1e)
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N
MeO
MeO
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NO2
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The product was purified by column chromatography (eluent hexane: ethyl acetate 2:1).
Pale yellow solid (1.60, 56%).
1H NMR (500 MHz, CDCl3) δ 8.60 (d, J = 5.1 Hz, 2H), 7.93 (dd, J = 16.1, 1.8 Hz, 1H), 7.64 (d, J = 1.5
Hz, 1H), 7.40 (d, J = 0.2 Hz, 2H), 7.06 (s, 1H), 6.86 (d, J = 16.0 Hz, 1H), 4.04 (s, 3H), 3.97 (d, J = 1.1
Hz, 3H).
13C{1H} NMR (126 MHz, CDCl3) δ 153.2, 149.9, 149.9, 149.0, 144.1, 140.5, 129.7, 129.6, 129.4,
127.0, 121.1, 109.5, 107.9, 56.4, 56.4.
HRMS m/z calculated for [M+Na]+ C15H14N2NaO4 309.0851. Found 309.0855.
(E)-3-(4,5-Dimethoxy-2-nitrostyryl)pyridine (1g)
MeO
MeO
N
NO2
The product was purified by column chromatography (eluent hexane: ethyl acetate 2:1).
Pale yellow solid (1.52, 53%).
1H NMR (500 MHz, CDCl3) δ 8.76 (s, 1H), 8.56 (d, J = 4.8 Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.86 (d,
J = 16.0 Hz, 1H), 7.66 (s, 1H), 7.42 (dt, J = 12.9, 8.1, 4.7 Hz, 1H), 7.09 (s, 1H), 6.96 (d, J = 16.1 Hz,
1H), 4.06 (s, 3H), 3.99 (s, 3H).
13C{1H} NMR (125 MHz, CDCl3) δ 153.4, 149.4, 149.2, 148.9, 140.6, 133.1, 132.6, 128.7, 127.9,
127.3, 123.9, 109.6, 108.1, 56.7, 56.6.
HRMS m/z calculated for [M+Na]+ C15H14N2NaO4 309.0851. Found 309.0856.
(E)-2-(5-Fluoro-2-nitrostyryl)pyridine (1i)
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5
F
N
6
7
8
NO2
9
The product was purified by column chromatography (eluent hexane: ethyl acetate 2:1).
Pale yellow solid (1.56, 64%).
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1H NMR (500 MHz, CDCl3) δ 8.52 (dt, J = 4.0, 2.1 Hz, 1H), 8.03 – 7.77 (m, 2H), 7.60 (tdd, J = 7.6, 3.6,
1.8 Hz, 1H), 7.35 (ddd, J = 12.6, 7.3, 3.3 Hz, 3H), 7.15 – 7.07 (m, 1H), 7.02 (ddt, J = 16.1, 9.5, 2.7 Hz,
2H).
13C{1H} NMR (125 MHz, CDCl3) δ 164.7 (d, J = 256.3 Hz), 154.3, 149.9, 144.3, 136.7, 135.8 (d, J =
9.8 Hz), 134.2, 127.8 (d, J = 10.0 Hz), 126.9, 123.2, 122.5, 115.6 (d, J = 23.7 Hz), 115.0 (d, J = 24.4
Hz).
HRMS m/z calculated for [M+Na]+ C13H9FN2NaO2 267.0546. Found 267.0551.
(E)-4-(-4,5-Dimethoxy-2-nitrostyryl)quinoline (1k)
N
MeO
MeO
NO2
The product was purified by column chromatography (eluent hexane: ethyl acetate 2:1 to 1:1).
Pale yellow solid (1.58, 47%).
1H NMR (500 MHz, CDCl3) δ 8.93 (d, J = 4.3 Hz, 1H), 8.19 (t, J = 8.5 Hz, 2H), 7.96 (d, J = 15.8 Hz,
1H), 7.76 (ddd, J = 8.3, 6.8, 1.2 Hz, 1H), 7.68 (s, 1H), 7.65 – 7.61 (m, 2H), 7.60 (d, J = 15.7 Hz, 1H),
7.16 (s, 1H), 4.09 (s, 3H), 4.00 (s, 3H).
13C{1H} NMR (125 MHz, CDCl3) δ 153.4, 149.9, 149.2, 148.3, 142.6, 140.7, 131.9, 130.0, 129.7,
127.6, 126.9, 126.6, 126.3, 123.4, 117.9, 110.0, 108.1, 56.7, 56.6
HRMS m/z calculated for [M+Na]+ C19H16N2NaO4 359.1008. Found 359.1012.
(E)-4-(5-Fluoro-2-nitrostyryl)quinoline (1l)
N
F
NO2
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The product was purified by column chromatography (eluent hexane: ethyl acetate 2:1 to 1:1).
Pale yellow solid (1.71, 58%).
7
8
9
1H NMR (500 MHz, CDCl3) δ 8.96 (d, J = 4.6 Hz, 1H), 8.25 (d, J = 8.8 Hz, 1H), 8.21 (d, J = 8.5 Hz,
1H), 8.18 (dd, J = 9.1, 5.1 Hz, 1H), 7.89 (d, J = 15.7 Hz, 1H), 7.81 (t, J = 7.7 Hz, 1H), 7.74 (d, J = 16.0
Hz, 1H), 7.71 – 7.64 (m, 2H), 7.54 (dd, J = 9.0, 2.8 Hz, 1H), 7.22 (ddd, J = 9.4, 7.1, 2.7 Hz, 1H).
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59
60
13C{1H} NMR (125 MHz, CDCl3) δ 165.1 (d, J = 257.1 Hz), 150.2, 148.6, 141.8, 136.0, 135.9, 130.3,
130.0, 129.8, 129.3, 128.2 (d, J = 10.0 Hz), 127.2, 126.2, 123.3, 118.2, 116.2 (d, J = 23.6 Hz), 115.7 (d,
J = 24.2 Hz).
19F NMR (471 MHz, CDCl3) δ -102.9.
HRMS m/z calculated for [M+Na]+ C17H11FN2NaO2 317.0702. Found 317.0707.
(E)-2-(2-Nitrostyryl)quinoline (1m)
N
NO2
The product was purified by column chromatography (eluent hexane: ethyl acetate 2:1).
Pale yellow solid (1.71, 62%).
1H NMR (500 MHz, CDCl3) δ 8.17 (d, J = 8.6 Hz, 1H), 8.10 (d, J = 16.3 Hz, 1H), 8.09 (d, J=8.0Hz,
1H), 8.02 (dd, J = 8.2, 1.3 Hz, 1H), 7.88 (dd, J = 8.0, 1.4 Hz, 1H), 7.81 (dd, J = 8.2, 1.4 Hz, 1H), 7.75
(d, J = 8.6 Hz, 1H), 7.73 – 7.70 (m, 1H), 7.68 – 7.62 (m, 1H), 7.53 (ddd, J = 8.1, 6.8, 1.2 Hz, 1H), 7.49
– 7.45 (m, 1H), 7.40 (d, J = 16.2 Hz, 1H).
13C{1H} NMR (125 MHz, CDCl3) δ 155.2, 148.2, 136.6, 134.3, 133.3, 132.3, 129.9, 129.4, 129.2,
128.8, 128.5, 127.6, 127.6, 126.7, 124.9, 118.9.
HRMS m/z calculated for [M+Na]+ C17H12N2NaO2 299.0796. Found 299.0798
(E)-2-(5-Chloro-2-nitrostyryl)quinoline (1n)
Cl
N
NO2
The product was purified by column chromatography (eluent hexane: ethyl acetate 2:1).
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Pale yellow solid (2.02, 65%).
5
6
7
8
1H NMR (500 MHz, DMSO-d6) δ 8.43 (d, J = 8.5 Hz, 1H), 8.20 (d, J = 2.3 Hz, 1H), 8.10 (d, J = 8.8 Hz,
1H), 8.07 (d, J = 16.0 Hz, 1H), 8.03 (dd, J = 8.5, 1.1 Hz, 1H), 7.99 (dd, J = 8.2, 1.4 Hz, 1H), 7.83 (d, J
= 8.5 Hz, 1H), 7.79 (ddd, J = 8.4, 6.9, 1.5 Hz, 1H),7.69 (dd, J = 8.8, 2.3 Hz, 1H)7.67 (d, J=16.0 Hz,
1H), 7.61 (ddd, J = 8.1, 6.8, 1.2 Hz, 1H).
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46
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49
50
51
52
53
54
55
56
57
58
59
60
13C{1H} NMR (125 MHz, DMSO-d6) δ 154.8, 148.0, 147.2, 138.9, 137.4, 134.9, 133.7, 130.6, 129.6,
129.4, 128.5, 128.4, 127.9, 127.6, 127.2, 127.1, 121.4.
HRMS m/z calculated for [M+Na]+ C17H11ClN2NaO2 333.0407. Found 333.0413
(E)-2-(2-Nitrostyryl)benzo[d]thiazole (1p)
N
S
NO2
The product was purified by column chromatography (eluent hexane: ethyl acetate 2:1).
Pale yellow solid (1.64, 58%).
1H NMR (500 MHz, DMSO-d6) δ 8.13 (dd, J = 8.0, 1.2 Hz, 1H), 8.09 (ddd, J = 8.1, 4.9, 1.3 Hz, 2H),
8.04 (d, J = 8.8 Hz, 1H), 7.96 (d, J = 16.0 Hz, 1H), 7.81 (t, J = 7.6 Hz, 1H), 7.67 (d, J = 16.1 Hz, 1H),
7.67 – 7.63 (m, 1H), 7.55 (tt, J = 8.3, 7.2, 2.2, 1.3 Hz, 1H), 7.47 (tt, J = 8.3, 7.2, 2.2, 1.2 Hz, 1H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 165.5, 153.4, 148.1, 134.3, 133.8, 131.8, 130.2, 130.1, 128.8,
126.7, 125.9, 125.8, 124.8, 122.9, 122.4.
HRMS m/z calculated for [M+Na]+ C15H10N2NaO2S 305.0361. Found 309.0853
(E)-1-Morpholino-3-(2-nitrophenyl)prop-2-en-1-one (1r)
O
N
O
NO2
The product was purified by column chromatography (eluent hexane: ethyl acetate 2:1).
Pale yellow solid (1.13, 43%).
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1H NMR (500 MHz, CDCl3) δ 8.03 (dd, J = 8.1, 1.2 Hz, 1H), 7.93 (d, J = 15.5 Hz, 1H), 7.63 (t, J = 15.8
Hz, 1H), 7.60 (d, J = 9.8 Hz, 1H), 7.51 (dt, J = 13.4, 8.5, 7.0, 1.8, 0.1 Hz, 1H), 6.68 (d, J = 15.4 Hz,
1H), 3.76 – 3.68 (m, 8H).
8
9
13C{1H} NMR (125 MHz, CDCl3) δ 165.0, 148.4, 137.9, 133.6, 131.8, 129.9, 129.4, 125.0, 122.6, 66.9.
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56
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58
59
60
HRMS m/z calculated for [M+Na]+ C13H14N2NaO4 285.0851. Found 285.0851.
General procedure
A mixture of 2-nitrostilbazole 1 (0.2 mmol) and sulfur (32 mg, 1 mmol) in 3-picoline (93 mg) was
heated and stirred in a 7-mL tube at 135 ºC under an argon atmosphere for 16 h (See Schemes 1, 2).
After removal of volatiles (0.1 mmHg, 100 ºC), the residue was purified by column chromatography on
silica gel (eluent hexane: ethyl acetate 2:1 to 1:1) to afford the product 2.
1-mmol scale synthesis of 2o
A mixture of (E)-2-(2-nitrostyryl)pyrazine 1o (227 mg, 1 mmol) and sulfur (160 mg, 5 mmol) in 3-
picoline (0.5 mL) was heated and stirred at 135 ºC in a 7-mL tube under an argon atmosphere for 16 h.
After removal of volatiles (0.1 mmHg, 100 ºC), methanol (2 mL) was added to the residue and the
resulting mixture was stirred at rt for 10 min to obtain a beige slurry (sonication could be applied). The
product was filtered, washed with methanol (2 mL x 3) and dried (0.1 mmHg, 100 ºC) to afford the
product 2 (199 mg, 73%).
3-(Pyridin-4-yl)-1H-benzo[c][1,2]thiazine 2,2-dioxide (2a)
N
SO2
N
H
Pale yellow solid. Yield 43 mg, 84%.
1H NMR (500 MHz, DMSO-d6) δ 8.83 – 8.63 (m, 2H), 8.01 (s, 1H), 7.77 – 7.70 (m, 2H), 7.69 (d, J =
1.5 Hz, 1H), 7.51 (td, J = 7.7, 1.5 Hz, 1H), 7.23 (td, J = 7.6, 1.1 Hz, 1H), 7.15 (d, J = 8.2 Hz, 1H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 150.6, 138.8, 138.6, 134.2, 133.1, 132.2, 131.0, 123.4, 121.9,
120.2, 117.9.
HRMS m/z calculated for [M+Na]+ C13H10N2NaO2S 281.0361. Found 281.0366.
6-Fluoro-3-(pyridin-4-yl)-1H-benzo[c][1,2]thiazine 2,2-dioxide (2b)
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F
6
7
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SO2
N
H
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46
47
48
49
50
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53
54
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56
57
58
59
60
Pale yellow solid. Yield 46 mg, 78%.
1H NMR (500 MHz, DMSO-d6) δ 8.72 (d, J = 5.1 Hz, 2H), 7.96 (s, 1H), 7.73 – 7.64 (m, 2H), 7.56 (dd,
J = 9.1, 3.0 Hz, 1H), 7.40 (td, J = 8.7, 3.0 Hz, 1H), 7.18 (dd, J = 8.9, 4.8 Hz, 1H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 157.9 (d, J = 239.2 Hz), 150.6, 138.5, 135.3, 134.4, 133.2,
122.0,121.4 (d, J = 9.1 Hz),120.2 (d, J = 8.2 Hz), 119.5 (d, J = 23.9 Hz), 116.1 (d, J = 23.6 Hz).
19F NMR (471 MHz, DMSO-d6) δ -120.0.
HRMS m/z calculated for [M+Na]+ C13H9FN2NaO2S 299.0266. Found 299.0269.
6-Chloro-3-(pyridin-4-yl)-1H-benzo[c][1,2]thiazine 2,2-dioxide (2c)
N
Cl
SO2
N
H
Pale yellow solid. Yield 49 mg, 75%.
1H NMR (500 MHz, DMSO-d6) δ 8.64 (d, J = 5.1 Hz, 2H), 7.87 (d, J = 2.2 Hz, 1H), 7.69 (s, 1H), 7.63
(d, J = 5.5 Hz, 2H), 7.44 (dd, J = 8.7, 2.5 Hz, 1H), 7.05 (dd, J = 8.8, 1.9 Hz, 1H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 150.4, 138.9, 138.3, 133.6, 133.0, 131.7, 129.8, 126.5, 122.1,
121.3, 120.1.
HRMS m/z calculated for [M+Na]+ C13H9ClN2NaO2S 314.9971. Found 314.9977.
6-Bromo-3-(pyridin-4-yl)-1H-benzo[c][1,2]thiazine 2,2-dioxide (2d)
N
Br
SO2
N
H
Pale yellow solid. Yield 57 mg, 72%.
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1H NMR (500 MHz, DMSO-d6) δ 8.79 (d, J = 5.2 Hz, 2H), 8.01 (s, 1H), 7.97 (d, J = 2.3 Hz, 1H), 7.78
(d, J = 5.2 Hz, 2H), 7.70 (dd, J = 8.7, 2.3 Hz, 1H), 7.13 (d, J = 8.6 Hz, 1H).
6
7
8
9
13C{1H} NMR (125 MHz, DMSO-d6) δ 149.9, 148.1, 142.5, 132.3, 131.4, 131.2, 128.1, 123.2, 122.2,
120.2, 106.3.
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53
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59
60
HRMS m/z calculated for [M+Na]+ C13H9BrN2NaO2S 358.9466. Found 358.9472.
6,7-Dimethoxy-3-(pyridin-4-yl)-1H-benzo[c][1,2]thiazine 2,2-dioxide (2e)
N
MeO
SO2
MeO
N
H
Pale yellow solid. Yield 53 mg, 82%.
1H NMR (500 MHz, DMSO-d6) δ 8.67 (d, J = 6.3 Hz, 1H), 7.90 (s, 1H), 7.66 (d, J = 6.3 Hz, 1H), 7.26
(s, 1H), 6.67 (s, 1H), 3.84 (s, 3H), 3.78 (s, 3H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 152.7, 150.5, 145.5, 139.2, 134.0, 129.8, 121.5, 113.1, 112.6,
101.3, 56.3, 56.3.
HRMS m/z calculated for [M+Na]+ C15H14N2NaO4S 341.0572. Found 341.0572.
3-(Pyridin-3-yl)-1H-benzo[c][1,2]thiazine 2,2-dioxide (2f)
N
SO2
N
H
Pale yellow solid. Yield 43 mg, 67%.
1H NMR (500 MHz, DMSO-d6) δ 8.88 (d, J = 2.4 Hz, 1H), 8.67 (dd, J = 4.9, 1.6 Hz, 1H), 8.09 (dt, J =
8.0, 2.0 Hz, 1H), 7.84 (s, 1H), 7.66 (dd, J = 7.8, 1.5 Hz, 1H), 7.55 (dd, J = 8.0, 4.8 Hz, 1H), 7.48 (td, J
= 7.8, 1.5 Hz, 1H), 7.22 (td, J = 7.6, 1.1 Hz, 1H), 7.15 (d, J = 8.0 Hz, 1H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 150.4, 148.6, 138.3, 135.7, 132.9, 132.9, 131.7, 130.7, 127.6,
124.2, 123.4, 120.5, 117.9.
HRMS m/z calculated for [M+Na]+ C13H10N2NaO2S 281.0361. Found 281.0366.
6,7-Dimethoxy-3-(pyridin-3-yl)-1H-benzo[c][1,2]thiazine 2,2-dioxide (2g)
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MeO
MeO
N
SO2
N
H
8
9
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13
14
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46
47
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50
51
52
53
54
55
56
57
58
59
60
Pale yellow solid. Yield 53 mg, 70%.
1H NMR (500 MHz, DMSO-d6) δ 8.84 (d, J = 2.4 Hz, 1H), 8.64 (dd, J = 4.7, 1.6 Hz, 1H), 8.05 (dt, J =
8.0, 2.0 Hz, 1H), 7.72 (s, 1H), 7.54 (dd, J = 8.0, 4.8 Hz, 1H), 7.25 (s, 1H), 6.69 (s, 1H), 3.85 (s, 3H),
3.79 (s, 3H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 152.2, 149.9, 148.3, 145.4, 135.2, 133.4, 132.7, 129.8, 127.9,
124.1, 113.4, 112.4, 101.4, 56.4, 56.2.
HRMS m/z calculated for [M+Na]+ C15H14N2NaO4S 341.0572. Found 341.0579
3-(Pyridin-2-yl)-1H-benzo[c][1,2]thiazine 2,2-dioxide (2h)
N
SO2
N
H
Pale yellow solid. Yield 43 mg, 82%.
1H NMR (500 MHz, DMSO-d6) δ 8.70 (d, J = 4.9 Hz, 1H), 8.15 (s, 1H), 7.94 (td, J = 7.8, 1.8 Hz, 1H),
7.89 (d, J = 7.9 Hz, 1H), 7.74 (d, J = 7.7 Hz, 1H), 7.55 – 7.38 (m, 2H), 7.19 (t, J = 7.5 Hz, 1H), 7.13 (d,
J = 8.1 Hz, 1H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 150.4, 149.1, 138.9, 137.9, 134.8, 133.3, 131.9, 131.0, 124.3,
123.2, 122.6, 120.2, 117.8.
HRMS m/z calculated for [M+Na]+ C13H10N2NaO2S 281.0361. Found 281.0366.
6-Fluoro-3-(pyridin-2-yl)-1H-benzo[c][1,2]thiazine 2,2-dioxide (2i)
F
N
SO2
N
H
Pale yellow solid. Yield 46 mg, 80%.
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1H NMR (500 MHz, DMSO-d6) δ 8.64 (d, J = 4.7 Hz, 1H), 8.08 (s, 1H), 7.88 (t, J = 7.8 Hz, 1H), 7.81
(d, J = 7.9 Hz, 1H), 7.60 (dd, J = 9.1, 2.9 Hz, 1H), 7.40 (dd, J = 7.5, 4.8 Hz, 1H), 7.30 (td, J = 8.7, 2.9
Hz, 1H), 7.09 (dd, J = 9.0, 4.7 Hz, 1H).
8
9
13C{1H} NMR (125 MHz, DMSO-d6) δ 158.0 (d, J = 239.0 Hz), 150.5, 148.7, 137.9, 136.2, 135.1,
132.4, 124.6, 122.8, 121.6 (d, J = 9.2 Hz), 119.9 (d, J = 8.3 Hz), 119.2 (d, J = 23.9 Hz), 116.3 (d, J =
23.4 Hz).
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59
60
19F NMR (471 MHz, DMSO-d6) δ -120.0.
HRMS m/z calculated for [M+Na]+ C13H9FN2NaO2S 299.0266. Found 299.0266.
3-(Quinolin-4-yl)-1H-benzo[c][1,2]thiazine 2,2-dioxide (2j)
N
SO2
N
H
Pale yellow solid. Yield 52 mg, 85%.
1H NMR (500 MHz, DMSO-d6) δ 9.02 (d, J = 4.4 Hz, 1H), 8.15 (dd, J = 8.4, 1.1 Hz, 1H), 8.10 (dd, J =
8.5, 1.3 Hz, 1H), 7.86 (ddd, J = 8.4, 6.8, 1.4 Hz, 1H), 7.74 (s, 1H), 7.72 – 7.63 (m, 3H), 7.53 (td, J =
7.8, 1.5 Hz, 1H), 7.29 – 7.14 (m, 2H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 150.4, 148.6, 138.6, 137.1, 136.9, 132.0, 131.9, 130.7, 130.5,
130.0, 128.1, 127.0, 126.0, 123.6, 123.4, 120.1, 118.1.
HRMS m/z calculated for [M+Na]+ C17H12N2NaO2S 331.0517. Found 331.0525
6,7-Dimethoxy-3-(quinolin-4-yl)-1H-benzo[c][1,2]thiazine 2,2-dioxide (2k)
N
O
SO2
O
N
H
Pale yellow solid. Yield 62 mg, 83%.
1H NMR (500 MHz, DMSO-d6) δ 9.00 (d, J = 4.4 Hz, 1H), 8.13 (dd, J = 8.5, 1.2 Hz, 1H), 8.11 (d, J =
7.1 Hz, 1H), 7.85 (ddd, J = 8.4, 6.8, 1.5 Hz, 1H), 7.69 (ddd, J = 8.3, 6.8, 1.3 Hz, 1H), 7.62 (d, J = 4.3
Hz, 1H), 7.59 (s, 1H), 7.25 (s, 1H), 6.74 (s, 1H), 3.86 (s, 3H), 3.76 (s, 3H).
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13C{1H} NMR (125 MHz, DMSO-d6) δ 152.4, 150.4, 148.7, 145.5, 137.6, 135.9, 133.6, 130.4, 130.0,
128.9, 127.9, 127.1, 126.0, 123.4, 112.9, 112.5, 101.6, 56.4, 56.3.
6
7
8
HRMS m/z calculated for [M+Na]+ C19H16N2NaO4S 391.0728. Found 391.0735
9
6-Fluoro-3-(quinolin-4-yl)-1H-benzo[c][1,2]thiazine 2,2-dioxide (2l)
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11
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59
60
N
F
SO2
N
H
Pale yellow solid. Yield 55 mg, 80%.
1H NMR (500 MHz, DMSO-d6) δ 9.02 (d, J = 4.3 Hz, 1H), 8.15 (d, J = 8.4 Hz, 1H), 8.09 (d, J = 8.4 Hz,
1H), 7.86 (t, J = 7.6 Hz, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.65 (d, J = 4.4 Hz, 1H), 7.55 (dd, J = 9.0, 3.0
Hz, 1H), 7.47 – 7.35 (m, 1H), 7.24 (dd, J = 9.0, 4.7 Hz, 1H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 157.9 (d, J = 239.1 Hz), 150.4, 148.6, 137.0, 135.4, 135.0,
133.3, 130.6, 130.0, 128.1, 126.8, 125.9, 123.5, 121.2 (d, J = 8.9 Hz), 120.4 (d, J = 8.3 Hz), 119.2 (d, J
= 23.8 Hz), 115.9 (d, J = 23.4 Hz).
HRMS m/z calculated for [M+Na]+ C17H11FN2NaO2S 349.0423. Found 349.0423
19F NMR (471 MHz, DMSO-d6) δ -120.0
3-(Quinolin-2-yl)-1H-benzo[c][1,2]thiazine 2,2-dioxide (2m)
N
SO2
N
H
Pale yellow solid. Yield 52 mg, 83%.
1H NMR (500 MHz, DMSO-d6) δ 8.44 (d, J = 8.6 Hz, 1H), 8.21 (s, 1H), 8.00 (dd, J = 8.4, 1.1 Hz, 1H),
7.97 – 7.95 (m, 1H), 7.93 (d, J = 8.6 Hz, 1H), 7.75 (ddd, J = 8.4, 6.9, 1.5 Hz, 1H), 7.72 (dd, J = 7.8, 1.3
Hz, 1H), 7.58 (ddd, J = 8.1, 6.9, 1.2 Hz, 1H), 7.43 (ddd, J = 8.1, 7.3, 1.5 Hz, 1H), 7.15 (td, J = 7.5, 1.1
Hz, 1H), 7.09 (d, J = 8.4 Hz, 1H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 149.7, 147.9, 139.0, 137.7, 135.3, 134.7, 132.2, 131.2, 130.9,
129.5, 128.4, 127.8, 127.6, 123.3, 120.4, 120.3, 117.8.
HRMS m/z calculated for [M+Na]+ C17H12N2NaO2S 331.0517. Found 331.0525
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6-Chloro-3-(quinolin-2-yl)-1H-benzo[c][1,2]thiazine 2,2-dioxide (2n)
5
6
7
8
9
Cl
N
SO2
N
H
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53
54
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58
59
60
Pale yellow solid. Yield 57 mg, 80%.
1H NMR (500 MHz, DMSO-d6) δ 8.54 (d, J = 8.6 Hz, 1H), 8.28 (s, 1H), 8.08 (d, J = 8.5 Hz, 1H), 8.04
(s, 0H), 7.99 (d, J = 8.6 Hz, 1H), 7.95 (d, J = 2.4 Hz, 1H), 7.85 (t, J = 7.7 Hz, 1H), 7.68 (t, J = 7.5 Hz,
1H), 7.56 (dd, J = 8.7, 2.5 Hz, 1H), 7.19 (d, J = 8.7 Hz, 1H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 149.4, 147.8, 137.9, 137.7, 136.4, 133.5, 131.8, 131.0, 130.1,
129.5, 128.5, 128.0, 127.7, 127.1, 121.6, 120.4, 119.7.
HRMS m/z calculated for [M+Na]+ C17H11ClN2NaO2S 365.0127. Found 365.0127
3-(Pyrazin-2-yl)-1H-benzo[c][1,2]thiazine 2,2-dioxide (2o)
N
N
SO2
N
H
Trituration of the crude reaction mixture afford the product as a pale brown solid. Yield 44 mg, 75% in
0.2-mmol scale; 199 mg, 73% in 1-mmol scale.
1H NMR (300 MHz, DMSO-d6) δ 9.30 (d, J = 1.4 Hz, 1H), 8.95 (d, J = 5.4 Hz, 2H), 8.48 (s, 2H), 7.96
(dd, J = 5.4, 1.5 Hz, 2H), 7.82 (dd, J = 7.9, 1.5 Hz, 2H), 7.55 (ddd, J = 8.2, 7.4, 1.5 Hz, 2H), 7.23 (td, J
= 7.6, 1.1 Hz, 2H), 7.17 (dd, J = 8.1, 1.0 Hz, 2H).
13C NMR (75 MHz, DMSO-d6) δ 159.2, 160.0, 155.9, 139.5, 136.6, 133.1, 132.3, 131.8, 123.4, 119.7,
118.9, 117.9.
HRMS m/z calculated for [M+Na]+ C12H9N3NaO2S 282.0313. Found 282.0327.
3-(Benzothiazol-2-yl)-1H-benzo[c][1,2]thiazine 2,2-dioxide (2p)
N
S
SO2
N
H
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Pale yellow solid. Yield 53 mg, 72%.
5
6
7
8
1H NMR (500 MHz, DMSO-d6) δ 8.36 (s, 1H), 8.13 (d, J = 7.9 Hz, 1H), 8.03 (d, J = 8.1 Hz, 1H), 7.80
(dd, J = 7.9, 1.4 Hz, 1H), 7.60 – 7.41 (m, 3H), 7.18 (t, J = 7.6 Hz, 1H), 7.11 (d, J = 8.1 Hz, 1H).
9
13C{1H} NMR (125 MHz, DMSO-d6) δ 157.7, 153.0, 139.0, 135.6, 135.3, 133.1, 131.7, 129.5, 127.5,
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126.6, 123.7, 123.4, 122.9, 120.0, 118.1.
HRMS m/z calculated for [M+Na]+ C15H10N2NaO2S2 337.0081. Found 337.0088
(2,2-Dioxido-1H-benzo[c][1,2]thiazin-3-yl)(piperidin-1-yl)methanone (2q)
O
N
SO2
N
H
Pale yellow solid. Yield 49 mg, 56%.
1H NMR (500 MHz, DMSO-d6) δ 7.52 (dd, J = 7.8, 1.4 Hz, 1H), 7.48 (s, 1H), 7.38 (td, J = 7.8, 1.5 Hz,
1H), 7.09 (t, J = 7.5 Hz, 1H), 7.03 (d, J = 8.1 Hz, 1H), 3.46 (br, 4H), 1.55-1.53 (m, 2H), 1.49 – 1.35 (m,
4H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 133.4, 131.9, 131.8, 130.6, 123.1, 119.6, 118.3, 24.3, 20.6.
HRMS m/z calculated for [M+Na]+ C14H16N2NaO3S 315.0779. Found 315.0784
(2,2-Dioxido-1H-benzo[c][1,2]thiazin-3-yl)(morpholino)methanone (2r)
O
N
SO2
O
N
H
Pale yellow solid. Yield 49 mg, 58%.
1H NMR (500 MHz, DMSO-d6) δ 7.56 (s, 1H), 7.53 (dd, J = 7.8, 1.4 Hz, 1H), 7.41 (td, J = 7.8, 1.5 Hz,
1H), 7.12 (t, J = 7.5 Hz, 1H), 7.05 (d, J = 8.0 Hz, 1H), 3.52 (br, 8H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 160.1, 138.7, 134.5, 132.2, 131.0, 130.8, 123.4, 119.6, 118.2,
66.7.
HRMS m/z calculated for [M+Na]+ C13H14N2NaO4S 317.0572. Found 317.0578
N-Benzyl-1H-benzo[c][1,2]thiazine-3-carboxamide 2,2-dioxide (2s)
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O
N
5
6
7
8
H
SO2
N
H
9
Pale yellow solid. Yield 53 mg, 53%.
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1H NMR (500 MHz, DMSO-d6) δ 8.72 (t, J = 6.0 Hz, 1H), 8.04 (s, 1H), 7.74 (dd, J = 7.9, 1.5 Hz, 1H),
7.53 (td, J = 7.8, 1.5 Hz, 1H), 7.42 – 7.32 (m, 4H), 7.27 (td, J = 6.0, 2.7 Hz, 1H), 7.21 (t, J = 7.5 Hz,
1H), 7.14 (d, J = 8.1 Hz, 1H), 4.47 (d, J = 6.0 Hz, 2H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 159.9, 139.5, 139.3, 137.7, 133.0, 131.5, 130.2, 128.9, 127.8,
127.5, 123.3, 119.2, 117.9, 43.2.
HRMS m/z calculated for [M+Na]+ C16H14N2NaO3S 337.0623. Found 337.0627
N-Phenyl-1H-benzo[c][1,2]thiazine-3-carboxamide 2,2-dioxide (2t)
O
N
H
SO2
N
H
Pale yellow solid. Yield 50 mg, 48%.
1H NMR (500 MHz, DMSO-d6) δ 10.39 (s, 1H), 8.08 (s, 1H), 7.72 (dd, J = 7.8, 1.4 Hz, 1H), 7.68 (d, J
= 8.0 Hz, 2H), 7.57 – 7.47 (m, 1H), 7.37 (t, J = 7.9 Hz, 2H), 7.20 (t, J = 7.5 Hz, 1H), 7.13 (dd, J = 8.1,
5.4 Hz, 2H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 159.1, 140.3, 138.8, 137.4, 133.0, 131.4, 130.7, 129.3, 124.7,
123.0, 120.4, 119.1, 118.2.
HRMS m/z calculated for [M+Na]+ C15H12N2NaO3S 323.0466. Found 323.0468
Methyl 1H-benzo[c][1,2]thiazine-3-carboxylate 2,2-dioxide (2u)
O
O
SO2
N
H
Pale yellow solid. Yield 40 mg, 63%.
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1H NMR (500 MHz, DMSO-d6) δ 7.86 (s, 1H), 7.31 (d, J = 7.8 Hz, 1H), 7.22 – 7.02 (m, 1H), 6.69 (d, J
= 8.4 Hz, 1H), 6.58 (t, J = 7.4 Hz, 1H), 3.75 (s, 3H).
6
7
8
9
13C{1H} NMR (125 MHz, DMSO-d6) δ 164.5, 141.3, 132.1, 131.1, 121.0, 116.7, 52.1.
HRMS m/z calculated for [M+Na]+ C10H9NNaO4S 262.0150. Found 262.0153.
tert-Butyl 1H-benzo[c][1,2]thiazine-3-carboxylate 2,2-dioxide (2v)
10
11
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60
O
O
SO2
N
H
Pale yellow solid. Yield 47 mg, 67%.
1H NMR (500 MHz, DMSO-d6) δ 7.65 (s, 1H), 7.19 (dd, J = 8.0, 1.6 Hz, 1H), 7.09 (ddd, J = 8.4, 6.8,
1.7 Hz, 1H), 6.61 (d, J = 8.4 Hz, 1H), 6.51 – 6.36 (m, 1H), 1.48 (s, 9H).
13C{1H} NMR (125 MHz, DMSO-d6) δ 163.6, 151.7, 140.6, 131.8, 131.1, 121.9, 120.5, 116.9, 115.3,
80.7, 40.8, 28.89.
HRMS m/z calculated for [M+Na]+ C13H15NNaO4S 304.0619. Found 304.0622.
ASSOCIATED CONTENT
Supporting information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.xxxxxxx.
Copies of 1H and 13C NMR spectra data for all new compounds. X-ray crystallographic data for 2b and
2i (CCDC 1953702 and 1953703 respectively).
This material is available free of charge via the Internet at http://pubs.acs.org.
ACKNOWLEDGMENTS
We thank Arch Nguyen Xuan Thang for his valuable assistance in the preparation of the cover.
REFERENCES
(1) (a) Ukrainets, I. V; Petrushova, L. A.; Dzyubenko, S. P.; Sim, G.; Grinevich, L. A. The Effective
Synthesis of N-(Arylalkyl)-1-R-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides as
Promising Analgesics of a New Chemical Class. Sci. Pharm. 2015, 83, 549. (b) Azotla-Cruz, L.;
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Page 24 of 26
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2
3
4
5
6
7
8
9
Lijanova, I. V.; Ukrainets, I. V.; Likhanova, N. V.; Olivares-Xometl, O.; Bereznyakova, N. L. New
Synthesis, Structure and Analgesic Properties of Methyl 1-R-4-Methyl-2,2-Dioxo-1H-2λ6,1-
Benzothiazine-3-Carboxylates. Sci. Pharm. 2017, 85, 2. (c) Ukrainets, I. V.; Hamza, G. M.; Burian, A.
A.; Shishkina, S. V.; Voloshchuk, N. I.; Malchenko, O. V. Sci. Pharm. 2018, 86, 9. (d) Ukrainets, I. V.;
Hamza, G. M.; Burian, A. A.; Voloshchuk, N. I.; Malchenko, O. V.; Shishkina, S. V.; Grinevich, L. A.;
Grynenko, V. V.; Sim, G. Molecular Conformations and Biological Activity of N-Hetaryl(aryl)alkyl-4-
methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides. Sci. Pharm. 2018, 86, 50.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(2) (a) Xie, Y.; Gong, G.; Liu, Y.; Deng, S.; Rinderspacher, A.; Branden, L.; Landry, D. W. Convenient
preparation of N-8-quinolinyl benzenesultams as novel NF-κB inhibitors. Tetrahedron Lett. 2008, 49,
2320. (b) Xie, Y.; Deng, S.; Thomas, C. J.; Liu, Y.; Zhang, Y.; Rinderspacher, A.; Huang, W.; Gong,
G.; Wyler, M.; Cayanis, E.; Aulner, N.; Toebben, U.; Chung, C.; Pampou, S.; Southall, N.; Vidovic, D.;
Schuerer, S.; Branden, L.; Davis, R. E.; Staudt, L. M.; Inglese, J.; Austin, C. P.; Landry, D. W.; Smith,
D. H.; Auld, D. S. Identification of N-(quinolin-8-yl)benzenesulfonamides as agents capable of down-
regulating NF-κB activity within two separate high-throughput screens of NF-κB activation. Bioorg.
Med. Chem. Lett. 2008, 18, 329.
(3) (a) Tomita, N.; Hayashi, Y.; Suzuki, S.; Oomori, Y.; Aramaki, Y.; Matsushita, Y.; Iwatani, M.;
Iwata, H.; Okabe, A.; Awazu, Y.; Ison , O.; Skene , R. J.; Hosfield, D. J.; Miki, H.; Kawamoto, T.; Hori,
A.; Baba, A. Structure-based discovery of cellular-active allosteric inhibitors of FAK. Bioorg. Med.
Chem. Lett. 2013, 23, 1779. (b) Iwatani, M.; Iwata, H.; Okabe, A.; Skene, R. J.; Tomita, N.; Hayashi,
Y.; Aramaki, Yoshio; Hosfield, D. J.; Akira Hori, A.; Baba, A.; Miki, H. Discovery and characterization
of novel allosteric FAK inhibitors. Eur. J. Med. Chem. 2013, 61, 49.
(4) Pieroni, M.; Sabatini, S.; Massari, S.; Kaatz, G.W.; Cecchetti, V.; Tabarrini, O. Searching for
innovative quinolone-like scaffolds: synthesis and biological evaluation of 2,1-benzothiazine 2,2-
dioxide derivatives. MedChemComm 2012, 3, 1092.
(5) (a) I. Ukrainets, V.; Petrushova, L. A.; Dzyubenko, S. P. 2,1-Benzothiazine 2,2-Dioxides. 1.
Synthesis, Structure, and Analgesic Activity of 1-R-4-Hydroxy-2,2-Dioxo-1H-2λ6,1-Benzothiazine-3-
Carboxylic Acid Esters. Chem. Heterocycl. Compds 2013, 49, 1378. (b) Manfroni, G.; Meschini, F.;
Costantino, F.; Tabarrini, O.; Cecchettia, V. N-Benzoyl-N-methylsulfonyl anthranilates: unexpected
cyclization reaction to 4-alkoxy-2,1-benzothiazines. Arkivoc 2011, 165. (c) Jeon, M.; Kim, M.; Kwon,
J.; Gong, Y.; Lee, D. A solid-phase synthetic method for 3,4-dihydro-1H-2,1-benzothiazin-4-one 2,2-
dioxide derivatives. Tetrahedron 2008, 64, 9060.
(6) (a) Togo, H.; Harada, Y.; Yokoyama, M. Preparation of 3,4-Dihydro-2,1-benzothiazine 2,2-Dioxide
Skeleton from N-Methyl 2-(Aryl)ethanesulfonamides with (Diacetoxyiodo)arenes. J. Org. Chem.
24
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The Journal of Organic Chemistry
1
2
3
4
5
6
7
2000, 65, 926. (b) Martinez, C.; Bosnidou, A. E.; Allmendinger, S.; Muniz, K. Towards Uniform Iodine
Catalysis: Intramolecular C−H Amination of Arenes under Visible Light. Chem. Eur. J. 2016, 22, 9929.
8
9
(7) Li, Y.; Ding, Q.; Qiu, G.; Wu, J. Synthesis of benzosultams via an intramolecular sp2 C–H bond
amination reaction of o-arylbenzenesulfonamides under metal-free conditions. Org. Biomol. Chem.
2014, 12, 149.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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29
30
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35
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40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(8) Li, L.; Li, Y.; Zhao, Z.; Luo, H.; Ma, Y. Facial Syntheses of Bromobenzothiazines via Catalyst-Free
Tandem C–H Amination/Bromination in Water. Org. Lett. 2019, 21, 5995.
(9) Ma, Y.; Gao, Y.; Jing, Y.; Kang, J.; Zhang, J.; Chen, X. Syntheses of Bromo-N-heterocycles through
Dibromohydantoin-Promoted Tandem C–H Amination/Bromination. J. Org. Chem. 2020, 85, 2918.
(10) Chen, J.; Wang, Q.; Li, X.; Zhao, Y. Silver-catalyzed intramolecular oxidative decarboxylative C-
H
arylation reactions for synthesis of biaryl sultams. Arkivoc 2019, DOI:
10.24820/ark.5550190.p010.846
(11) X= H: (a) Huang, R. Y.; Franke, P. T.; Nicolaus, N.; Lautens, M. Domino C–H functionalization
reactions of gem-dibromoolefins: synthesis of N-fused benzo[c]carbazoles. Tetrahedron 2013, 69, 4395.
(b) Laha, J. K.; Jethava, K. P.; Dayal, N. Palladium-Catalyzed Intramolecular Oxidative Coupling
Involving Double C(sp2)–H Bonds for the Synthesis of Annulated Biaryl Sultams. J. Org. Chem. 2014,
79, 8010. (c) You, C.; Yao, F.; Yan,T.; Cai, M. A highly efficient heterogeneous copper-catalyzed
Chan–Lam coupling reaction of sulfonyl azides with arylboronic acids leading to N-arylsulfonamides.
RSC Adv. 2016, 6, 43605. X = halogen (d) Guerra, W. D.; Rossi, R. A.; Pierini, A. B.; Barolo, S. M.
Synthesis of Dibenzosultams by “Transition-Metal-Free” Photoinduced Intramolecular Arylation of N-
Aryl-2-halobenzenesulfonamides. J. Org. Chem. 2016, 81, 4965. (e) Recio, J.; Filace, F.; Gala, E.;
Pérez-Redondo, A.; Álvarez-Buill, J.; Burgos, C. Studies on the preparation of aminobipyridines and
bipyridine sultams via an intramolecular free radical pathway. RSC Adv. 2020, 10, 10447. X = NH2: (f)
Singh Virk, T.; Ilawe, N. V.; Zhang, G.; Yu, C. P.; Wong, B. M.; Chan, J. M. W. Sultam-Based
Hetero[5]helicene: Synthesis, Structure, and Crystallization-Induced Emission Enhancement. ACS
Omega 2016, 1, 1336.
(12) Feng, S.; Li, S.; Li, J.; Wei, J. Palladium-catalyzed annulation of N-alkoxy benzsulfonamides with
arynes by C–H functionalization: access to dibenzosultams. Org. Chem. Front. 2019, 6, 517.
(13) Minville, J.; Poulin, J.; Dufresne, C.; Sturino, C. F. A general synthesis of quinolinones and
benzothiazine 1,1-dioxides via ring closing metathesis. Tetrahedron Lett. 2008, 49, 3677.
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The Journal of Organic Chemistry
Page 26 of 26
1
2
3
4
5
6
7
8
9
(14) (a) Nguyen, T. B.; Ermolenko, L.; Almourabit, A. Iron Sulfide Catalyzed Redox/Condensation
Cascade Reaction between 2-Amino/Hydroxy Nitrobenzenes and Activated Methyl Groups: A
Straightforward Atom Economical Approach to 2-Hetaryl-benzimidazoles and -benzoxazoles. J. Am.
Chem. Soc. 2013, 135, 118. (b) Nguyen, T. B.; Retailleau, P.; Almourabit, A. A Simple and
Straightforward Approach to Quinoxalines by Iron/Sulfur-Catalyzed Redox Condensation of o-
Nitroanilines and Phenethylamines. Org. Lett. 2013, 15, 5238. (c) Nguyen, T. B.; Ermolenko, L.;
Corbin, M.; Almourabit, A. Fe/S-catalyzed decarboxylative redox condensation of arylacetic acids with
nitroarenes. Org. Chem. Front. 2014, 1, 1157.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(15) Nguyen, T. B.; Retailleau, P. Redox-Neutral Access to Sultams from 2-Nitrochalcones and Sulfur
with Complete Atom Economy. Org. Lett. 2017, 19, 3879.
(16) Doepp, D.; Krueger, C.; Lauterfeld, P.; Raabe, E. Ungewöhnliche Photoisomerisierung eines
cyclischen Sulfonamids. Angew. Chem. 1987, 99, 142.
(17) Sayaka, N.; Kaori, E. U.; Shinya, F.; Makoto, M.; Yuichi, H.; Minoru, Y. Structural development
of tetrachlorophthalimides as liver X receptor β (LXRβ)-selective agonists with improved aqueous
solubility. Bioorg. Med. Chem. Lett. 2018, 28, 796.
(18) Tipson, R. S.; Walton, A. F. Studies in the Quinoline Series. IX. The
Mononitrophenyllepidylcarbinols and Related Compounds. J. Am. Chem. Soc. 1948, 70, 892.
(19) El-Batta, A.; Jiang, C.; Zhao, W.; Anness, R. L.; Cooksy, A.; Bergdahl, M. Wittig Reactions in
Water Media Employing Stabilized Ylides with Aldehydes. Synthesis of α,β-Unsaturated Esters from
Mixing Aldehydes, α-Bromoesters, and Ph3P in Aqueous NaHCO3. J. Org. Chem. 2007, 72, 5244.
(20) Lee, S. J.; Seo, H. A; Cheon, C. H. Synthesis of 2‐Aryl‐Substituted Indole‐3‐acetic Acid Derivatives
via Intramolecular Imino‐Stetter Reaction of Aldimines with Cyanide. Adv. Synth. Cat. 2016, 358, 1566.
(21) Vishnoi, S.; Agrawal, V.; Virendra, K. K. Synthesis and Structure−Activity Relationships of
Substituted Cinnamic Acids and Amide Analogues: A New Class of Herbicides. J. Agric. Food
Chem. 2009, 57, 3261.
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