Regio- and Stereoselective Synthesis of Benzo-δ-sultams by Palladium-Catalyzed Hydrocarbonation of Alkynes

Article abstract of DOI:10.1055/s-0035-1561288

An efficient method for the synthesis of benzo-δ-sultams [(4Z)-4-benzylidene-2-(arylmethyl)-3,4-dihydro-2H-1,2-benzothiazine 1,1-dioxides] via palladium(0)-catalyzed hydrocarbonation of alkynes is presented. This method allows regioselective access to a variety of substituted benzosultams in excellent yields under mild conditions. The stereochemistry of the exocyclic double bond of the benzosultam derivatives is confirmed by single-crystal X-ray diffraction.

Full text of DOI:10.1055/s-0035-1561288

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2016, 48, 710–722
paper
710
S. Debnath, S. Mondal
Paper
Synthesis
Regio- and Stereoselective Synthesis of Benzo-δ-sultams by
Palladium-Catalyzed Hydrocarbonation of Alkynes
Sudarshan Debnath
O
O
Shovan Mondal*
R2
S
R1
N
R1
N
O
Department of Chemistry, Visva-Bharati University,
Santiniketan 731235, India
shovan.mondal@visva-bharati.ac.in
shovanku@gmail.com
S
Pd(PPh3)4 (4 mol%)
HCOONa (1.5 equiv)
DMF–H2O (7:3), 100 °C, 1 h
O
Br
R2
85–95%
a new entry to 2H-1,2-benzothiazine-1,1-dioxides
17 examples of new benzosultams
Received: 02.10.2015
Accepted after revision: 20.11.2015
Published online: 04.01.2016
O
N
Ph
Ph
O2
S
O2
S
Me
O
N
DOI: 10.1055/s-0035-1561288; Art ID: ss-2015-z0579-op
H
N
N
Abstract An efficient method for the synthesis of benzo-δ-sultams
[(4Z)-4-benzylidene-2-(arylmethyl)-3,4-dihydro-2H-1,2-benzothiazine
1,1-dioxides] via palladium(0)-catalyzed hydrocarbonation of alkynes is
presented. This method allows regioselective access to a variety of sub-
stituted benzosultams in excellent yields under mild conditions. The
stereochemistry of the exocyclic double bond of the benzosultam de-
rivatives is confirmed by single-crystal X-ray diffraction.
Me
O
OH
O
OCO2Et
2
1
11β-HSD2 inhibitor
ampiroxicam (COX-2)
O2
S
N
O2
Cl
S
NH
Keywords benzosultams, hydrocarbonation, regioselectivity, DFT
study
N
N
N
O
H
H
H
OH
3
4
Compounds having a benzosultam core moiety are an
important class of heterocycles due to their wide and di-
verse bioactivity.1 They show antimicrobial, antiviral, anti-
cancer, antileukemic, anti-HIV, and other promising activi-
ties.2 For example, compound 1 (Figure 1) acts as an 11β-
hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme
inhibitor;3 11β-HSD1 is an endoplasmic reticulum-associat-
ed enzyme that acts as a NADPH dependent reductase,
which converts inactive cortisone into the active glucocor-
ticoid cortisol.4 Oxicams, such as ampiroxicam (2), are used
as nonsteroidal anti-inflammatory drugs.5 Compound 3 and
several other benzosultams exhibit potential anti-HIV ac-
tivity.1a,6,7 Moreover, benzothiazine dioxide derivatives have
strong inhibitory property against Calpain I.8,9
Due to the importance of benzothiazine dioxides among
benzosultams, extensive attempts have been made to de-
velop new and efficient routes for their synthesis. For ex-
ample, Thibaudeau and co-workers reported an acid-cata-
lyzed Friedel–Crafts cyclization process (Scheme 1, eq. 1)
for the synthesis of benzothiazine dioxide derivatives.10
Murakami and co-workers presented a synthetic route to
benzothiazine dioxide derivatives by the rhodium-cata-
CXCR2 antagonist
anti-HIV agent
O2
O2
S
S
Me
O
Me
N
N
H
H
N
N
N
S
OH
OH
O
N
5
6
piroxicam
meloxicam
Figure 1 Biologically active benzothiazine dioxide derivatives
lyzed rearrangement reaction of N-arylsulfonylazetidin-3-
ols (Scheme 1, eq. 2).11 Pal and co-workers accessed benzo-
thiazine dioxide derivatives by N–C coupling through
iodine-mediated cyclization (Scheme 1, eq. 3).12 In our pre-
vious work we reported a one-pot synthetic strategy for the
synthesis of a series of benzothiazine dioxide by Sonogashira
coupling–cyclization (Scheme 1, eq. 4).13 Beside these pub-
lications, there are few other reports on the synthesis of
benzosultams.14 Among the previously reported synthetic
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 710–722

711
S. Debnath, S. Mondal
Paper
Synthesis
strategies, most approaches lead to benzothiazine dioxide
derivatives with varying substitution at the 3-position, but
few reports are available in the literature for the synthesis
of benzothiazine dioxide derivatives with substitution at
the 4-position. In our continued efforts in sultam and sul-
tone chemistry,1a,13,15 our present endeavor examines the
regio- and stereoselective synthesis of benzothiazine diox-
ide derivatives with substitution at 4-position by palladi-
um-catalyzed hydrocarbonation of alkynes (Scheme 1, eq.
5). Herein we report our results.
amides 20a–d were synthesized from commercially avail-
able 2-bromobenzenesulfonyl chloride (18) by reaction
with various aliphatic amines 19.
For the synthesis of our target benzothiazine dioxide
derivatives, i.e. benzosultams, by the palladium-catalyzed
hydrocarbonation of alkynes, we initiated our investigation
with substrate 16aa, optimizing the conditions for the for-
mation of 17aa (Table 1). Among the palladium catalysts,
Pd(PPh3)4 gave the best result rather than Pd(PPh3)2Cl2,
Pd2(dba)3, or Pd/C. The solvent screening revealed that N,N-
dimethylformamide–water mixture was the most appro-
priate solvent. In the absence of water the reaction failed to
convert 16aa into any cyclized product; the detailed role of
water was investigated in our previous work which showed
that water mainly ionized the sodium formate molecule,
As depicted in Scheme 2, the required precursors 16aa–
de were prepared by propargylation of sulfonamides 20a–d
followed by selective intermolecular Sonogashira cou-
pling16 with different iodobenzenes 22a–e. The sulfon-
previous work:
O
O
HF/SbF5 (0.16 mol/L)
SbF5 (13.6 mol%)
–20 °C, 10 min, 67%
O
O
S
S
NH
NH
R
R
(1)
Friedel-Crafts cyclization
7
Me
HO
Ph
O
8
[Rh(OH)(cod)]2 (2 mol%)
rac-DM-BINAP (5 mol%)
K2CO3 (2 equiv), toluene
60 °C, 12 h, 96%
O
O
S
Me
N
S
N
(2)
Me
O
HO
Ph
1,5-rhodium shift
Me
10
9
I2 (2.5 equiv),
K2CO3 (3 equiv)
acetonitrile, r.t.
16 h, 62–87%
O
O
O
O
S
R1
S
I
R1
R2
N
N
(3)
H
R3
R3
iodine-mediated
cyclization
R2
R2
11
12
O
O
Pd(PPh3)2Cl2, CuI, Et3N
DMF, 70 °C, sealed tube
7 h, 90–98%
S
R1
+
O
O
N
S
R1
H
N
(4)
Br
R2
one-pot Sonogashira
coupling–cyclization
14
13
15
present work:
Pd(PPh3)4 (4 mol%)
HCOONa(1.5 equiv)
DMF–H2O (7:3), 100 °C
1 h, 85–95%
O
O
N
R1
O
S
S
R1
N
R2
O
(5)
Pd-catalyzed
hydrocarbonation
of alkynes
Br
16
H
R2
17
Scheme 1 Various approaches towards the synthesis of benzothiazine dioxide
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 710–722

712
S. Debnath, S. Mondal
Paper
Synthesis
Table 1 Optimization of the Synthesis of Benzosultam 17aa by Palladi-
O
O
S
um-Catalyzed Hydrocarbonation of Alkynes
Cl
O
O
O
O
O
O
O
O
Br
S
Me
S
Me
S
R1
18
S
N
(a)
(b)
N
NHR1
N
+
Br
R1NH2
Br
Br
19
21a–d
20a–d
20a, R1 = Me, 99%
20b, R1 = Et, 99%
20c, R1 = Bn, 97%
20d, R1 = CH2Py, 95%
17aa
16aa
21a, 98%
21b, 98%
21c, 95%
21d, 95%
Entry Catalysta
Solvent
Time Temp
(°C)
Yield
(%)
I
1
2
Pd(PPh3)2Cl2 (5 mol%)b DMF–H2O (7:3)
2 h
2 h
2 h
2 h
4 h
2 h
1 h
1 h
100
100
100
100
120
100
100
100
trace
R2
Pd/C (5 mol%)b
DMF–H2O (7:3)
DMF–H2O (7:3)
DMF–H2O (7:3)
DMF–H2O (7:3)
DMF–H2O (7:3)
DMF–H2O (7:3)
DMF–H2O (7:3)
DMF–H2O (7:3)
DMF
–
c
R1
N
O
3
Pd2(dba)3 (5 mol%)
Pd2(dba)3 (10 mol%)
Pd2(dba)3 (10 mol%)
Pd(PPh3)4 (4 mol%)
Pd(PPh3)4 (4 mol%)
Pd(PPh3)4 (3 mol%)
Pd(PPh3)4 (4 mol%)
Pd(PPh3)4 (4 mol%)
10
15
S
(c)
R2
O
4
d
Br
16aa–de
5
–
6
88
92
84
70
16aa, R1 = Me, R2 = H, 98%
16ab, R1 = Me, R2 = Me, 98%
16bd, R1 = Et, R2 = OEt, 95%
16be, R1 = Et, R2 = OBn, 97%
16ca, R1 = Bn, R2 = H, 96%
16cb, R1 = Bn, R2 = Me, 95%
16cc, R1 = Bn, R2 = OMe, 97%
16cd, R1 = Bn, R2 = OEt, 95%
16ce, R1 = Bn, R2 = OBn, 96%
16da, R1 = CH2Py, R2 = H, 90%
7
8
16ac, R1 = Me, R2 = OMe, 95%
16ad, R1 = Me, R2 = OEt, 96%
16ae, R1 = Me, R2 = OBn, 95%
16ba, R1 = Et, R2 = H, 97%
16bb, R1 = Et, R2 = Me, 98%
16bc, R1 = Et, R2 = OMe, 96%
9
30 min 120
1 h 100
c
10
–
a In all cases HCOONa (1.5 equiv) were used.
b Ph3P (15 mol%) was used as additive.
c No product.
16de, R1 = CH2Py, R2 = OBn, 85%
d Complex mixture.
Scheme 2 Synthesis of benzosultam precursors 16aa–de. Reagents
and conditions: (a) EtOH, reflux, 2 h; (b) propargyl bromide (2 equiv),
MEK, K2CO3, NaI, reflux, 4 h; (c) Pd(PPh3)2Cl2 (5 mol%), CuI (12 mol%),
Et3N, THF, r.t., 8 h.
passed through a 7-endo-dig process then compound 17aa′
would be formed, and if the cyclization went through a 6-
exo-dig mode then (Z)-17aa or (E)-17aa would be formed
(Scheme 3).
thereby acting as hydride ion source.15d The catalyst loading
was also optimized and the reaction of 16aa to 17aa pro-
ceeded smoothly with 4 mol% Pd(PPh3)4 catalyst and was
complete within one hour at 100 °C. At low catalyst loading,
16aa was not fully converted into 17aa in one hour. Increas-
ing the time or temperature lead to decomposition of the
product and a lower yield of compound 17aa was obtained.
Treatment of compound 16aa (100 mg, 0.27 mmol) with
Pd(PPh3)4 (4 mol%) and sodium formate (28 mg, 0.41 mmol)
in N,N-dimethylformamide–water (7:3, 3 mL) under the op-
timized conditions afforded compound 17aa (72 mg, 92%)
as the only identified product.
Finally, the structure was confirmed by X-ray data and it
showed that the structure of the product obtained from
16aa was (Z)-17aa17 [Figure 2 (a)].
The sole product obtained after treatment of compound
16aa under the optimized conditions showed one extra ar-
omatic proton in its 1H NMR and in the 13C NMR there was
no peak found for acetylenic carbon atoms. This result con-
firmed that the product obtained from 16aa was cyclized
and the HRMS value of the synthesized compound was
308.0716, which also matched well with the theoretical val-
ue of cyclized product 308.0716 for [M + Na]+. The remain-
ing question concerns the regioselectivity: is the product
formed (Z)-17aa, (E)-17aa or 17aa′? If the cyclization
Figure 2 ORTEP diagram of benzosultams (a) 17aa (b) 17ab (the ther-
mal ellipsoid are drawn at the 50% probability level)
To identify the reasons for the selectivity observed in
this cyclization, the energies of both the transition states
(7-endo-dig and 6-exo-dig) were calculated by DFT. Opti-
mized geometry coordinates are given in the Supporting In-
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S. Debnath, S. Mondal
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Synthesis
O
O
Me
S
N
7-endo-dig
17aa'
O
O
S
Me
N
O
O
O
O
Br
S
Me
S
Me
N
N
6-exo-dig
or
16aa
(Z)-17aa
(E)-17aa
Scheme 3 Different cyclization modes
formation. For the 6-exo-dig cyclization mode, the reaction
passed through a lower activation energy barrier (6.38
kcal/mol) than that of the 7-endo-dig mode (Figure 3).
carbon and palladium of the C–Pd bond interact with acety-
lenic carbon atoms from the same side, this leads to (Z)-
17aa; from the opposite side, which is geometrically unfa-
vorable, this would lead to (E)-17aa. Therefore, the forma-
tion of product (E)-17aa by this route is not possible, al-
though it is energetically stable (Figure 4).
After standardization of the synthesis of benzothiazine
dioxide 17aa, we prepared 17 examples of benzothiazine
dioxide derivatives (17aa–de; Figure 5) to explore the scope
of the reaction.
The single-crystal X-ray diffraction analysis for benzo-
sultams 17ab18 was also obtained to further confirm the
structure [Figure 2 (b)].
In summary, an efficient route is achieved for the syn-
thesis of benzothiazine dioxide derivatives, i.e. benzosul-
tams, based on the palladium-catalyzed hydrocarbonation
of alkynes. This synthetic method is an efficient and con-
vergent route for the preparation of benzo-δ-sultams and it
should become widely acceptable to the synthetic organic
community due to its mildness, high efficiency, and regio-
selectivity. The possible reasons for the regioselectivity of
the palladium-catalyzed hydrocarbonation of alkynes and
stereoselectivity of the exocyclic double bond in the syn-
thesized compounds are explained by density functional
theory calculations. The structure of benzothiazine dioxide
derivatives were also confirmed by single-crystal X-ray dif-
fraction data.
Figure 3 Optimized structure of transition states for 6-exo-dig and 7-
endo-dig mode of cyclizations; hydrogen atoms are omitted for clarity
Therefore, the theoretical results of the two possible
pathways are well matched with the experimental results,
i.e. compound 17aa was obtained solely from sulfonamide
16aa. DFT calculations showed that the energy of (E)-17aa
is lower than that of (Z)-17aa by 10.28 kcal/mol. A possible
explanation for this may be that two distinct paths can exist
for the 6-exo-dig cyclization: one leading to the (Z)-car-
bopalladation product and another, more energy demand-
ing, leading to the (E)-carbopalladation product. When the
geometrically
unfavored
interaction
R
N
O
S
O
The reactions sensitive to air or moisture were carried out under a N2
atmosphere using dry solvents, unless otherwise noted. Column
chromatography was performed on silica gel (60–120 mesh); petro-
leum ether = PE. Reaction progress was monitored by TLC. TLC plates
were visualized with UV light (256 nm) and in an iodine chamber. IR
spectra were recorded using KBr discs. Melting points were recorded
in open capillaries and are uncorrected.
E-product
R
Pd
Z-product
geometrically
favored interaction
Figure 4 Geometrically favored and unfavored interactions in the 6-
exo-dig mode of cyclization
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 710–722

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S. Debnath, S. Mondal
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Synthesis
O
O
O
O
O
O
O
O
O
O
S
Me
S
Me
S
Me
S
Me
S
Me
N
N
N
N
N
(92%)
(90%)
(94%)
17ac
(91%)
(88%)
O
OMe
OEt
OBn
17aa
17ab
17ad
17ae
O
O
O
O
O
O
N
O
O
O
S
Et
S
Et
S
Et
S
Et
S
Et
N
N
N
N
(90%)
(93%)
(89%)
(92%)
O
(87%)
O
OMe
OEt
OBn
17ba
17bb
17bc
17bd
17be
O
O
O
S
O
O
S
O
O
O
N
S
Bn
Bn
Bn
S
Bn
S
Bn
N
N
N
N
(95%)
(91%)
(88%)
(93%)
(90%)
OMe
OEt
OBn
17ca
17cb
17cc
17cd
17ce
N
N
O
O
O
O
S
S
N
N
(87%)
(85%)
OBn
17da
17de
Figure 5 Summarized results of benzosultams
HRMS were recorded on a QTOF instrument. All 1H and 13C NMR spec-
tra were recorded in 400 and 100 MHz spectrometer, respectively, rel-
ative to internal CHCl3 (1H, δ = 7.26) and CDCl3 (13C NMR, δ = 77.16).
2-Bromo-N-ethylbenzenesulfonamide (20b)
Prepared following the typical procedure for 20a using 18 (500 mg,
1.96 mmol), EtOH (20 mL), and EtNH2 (0.7 mL, 7.83 mmol). The prod-
uct was purified by column chromatography (10% EtOAc–PE) to yield
20b (512 mg, 99%) as a white solid; mp 90–92 °C; Rf = 0.25 (10%
EtOAc–PE).
1H NMR (400 MHz, CDCl3): δ = 8.12 (dd, J = 8.0, 2.0 Hz, 1 H), 7.72 (dd,
J = 8.0, 1.6 Hz, 1 H), 7.48–7.38 (m, 2 H), 5.15 (br s, 1 H), 2.99–2.92 (m,
2 H), 1.08 (t, J = 7.2 Hz, 3 H).
2-Bromo-N-methylbenzenesulfonamide (20a); Typical Procedure
To a solution of commercially available 2-bromobenzenesulfonyl
chloride (18, 500 mg, 1.96 mmol) in EtOH (20 mL), MeNH2 (0.7 mL,
7.83 mmol) was added and the mixture was refluxed for 2 h. The re-
sidual solvent was evaporated under reduced pressure and the crude
product obtained was purified by column chromatography (10%
EtOAc–PE) to afford 20a12 (484 mg, 99%) as a white solid; mp 99–
101 °C; Rf = 0.20 (10% EtOAc–PE).
13C NMR (100 MHz, CDCl3): δ = 138.9, 135.1, 133.8, 131.7, 127.9,
119.7, 38.5, 15.0.
Anal. Calcd for C8H10BrNO2S: C, 36.38; H, 3.82; N, 5.30. Found: C,
36.69; H, 3.96; N, 5.03.
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S. Debnath, S. Mondal
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Synthesis
N-Benzyl-2-bromobenzenesulfonamide (20c)
1H NMR (400 MHz, CDCl3): δ = 8.12 (dd, J = 7.7, 1.7 Hz, 1 H), 7.72 (dt,
J = 7.8, 1.3 Hz, 1 H), 7.43 (td, J = 7.5, 1.4 Hz, 1 H), 7.37 (td, J = 7.6, 1.9
Hz, 1 H), 4.20 (d, J = 2.5 Hz, 2 H), 3.44 (q, J = 7.2 Hz, 2 H), 2.20 (t, J = 2.4
Hz, 1 H), 1.14 (t, J = 7.1 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 139.1, 135.7, 133.7, 132.2, 127.6,
120.6, 77.6, 73.3, 41.7, 35.8, 13.1.
Prepared following the typical procedure for 20a using 18 (500 mg,
1.96 mmol), EtOH (20 mL), and BnNH2 (315 mg, 2.93 mmol). The
product was purified by column chromatography (5% EtOAc–PE) to
yield 20c (619 mg, 97%) as a white solid; mp 94–96 °C; Rf = 0.30 (10%
EtOAc–PE).
1H NMR (400 MHz, CDCl3): δ = 8.12 (dd, J = 7.8, 1.9 Hz, 1 H), 7.69 (dd,
J = 7.8, 1.2 Hz, 1 H), 7.45 (td, J = 7.5, 1.3 Hz, 1 H), 7.39 (td, J = 7.7, 1.8
Hz, 1 H), 7.27–7.17 (m, 5 H), 5.42 (t, J = 5.6 Hz, 1 H), 4.10 (d, J = 6.2 Hz,
2 H).
13C NMR (100 MHz, CDCl3): δ = 139.0, 135.8, 135.1, 133.8, 131.8,
128.8, 128.1, 128.1, 128.0, 119.8, 47.7.
Anal. Calcd for C11H12BrNO2S: C, 43.72; H, 4.00; N, 4.64. Found: C,
44.07; H, 3.88; N, 4.41.
N-Benzyl-2-bromo-N-(prop-2-ynyl)benzenesulfonamide (21c)
Prepared following the typical procedure for 21a using 20c (400 mg,
1.23 mmol), MEK (10 mL), NaI (5 mg), and propargyl bromide (0.22
mL, 2.45 mmol). The product was purified by column chromatogra-
phy (5% EtOAc–PE) to yield 21c (424 mg, 95%) as a colorless gummy
liquid; Rf = 0.35 (10% EtOAc–PE).
Anal. Calcd for C13H12BrNO2S: C, 47.86; H, 3.71; N, 4.29. Found: C,
48.13; H, 3.50; N, 4.43.
2-Bromo-N-(pyridin-2-ylmethyl)benzenesulfonamide (20d)
IR (KBr): 3282, 2343, 1151, 1050 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.17 (dd, J = 7.7, 1.9 Hz, 1 H), 7.77 (dd,
J = 7.6, 1.4 Hz, 1 H), 7.48–7.39 (m, 2 H), 7.34–7.26 (m, 5 H), 4.59 (s, 2
H), 3.99 (d, J = 2.4 Hz, 2 H), 2.19 (t, J = 2.5 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 139.1, 135.8, 135.0, 133.9, 132.4,
128.9, 128.8, 128.2, 127.7, 120.8, 77.0, 73.8, 50.7, 35.7.
Prepared following the typical procedure for 20a using 18 (200 mg,
0.78 mmol), EtOH (10 mL), and pyridin-2-ylmethanamine (127 mg,
1.17 mmol). The product was purified by column chromatography
(30% EtOAc–PE) to yield 20d (233 mg, 95%) as a white solid; mp 110–
112 °C; Rf = 0.30 (30% EtOAc–PE).
1H NMR (400 MHz, CDCl3): δ = 8.48–8.44 (m, 1 H), 8.13–8.10 (m, 1 H),
7.66–7.62 (m, 1 H), 7.59–7.54 (m, 1 H), 7.44–7.39 (m, 1 H), 7.36–7.32
(m, 1 H), 7.16–7.12 (m, 2 H), 6.45–6.43 (m, 1 H), 4.23 (d, J = 5.4 Hz, 2
H).
Anal. Calcd for C16H14BrNO2S: C, 52.76; H, 3.87; N, 3.85. Found: C,
52.94; H, 4.04; N, 3.69.
2-Bromo-N-(prop-2-ynyl)-N-(pyridin-2-ylmethyl)benzenesulfon-
amide (21d)
13C NMR (100 MHz, CDCl3): δ = 154.7, 149.3, 138.8, 136.8, 135.2,
133.7, 131.7, 127.7, 122.8, 121.9, 120.2, 48.0.
Prepared following the typical procedure for 21a using 20d (200 mg,
0.61 mmol), MEK (10 mL), NaI (5 mg), and propargyl bromide (0.11
mL, 1.22 mmol). The product was purified by column chromatogra-
phy (20% EtOAc–PE) to yield 21d (212 mg, 95%) as a reddish gummy
liquid; Rf = 0.35 (30% EtOAc–PE).
Anal. Calcd for C12H11BrN2O2S: C, 44.05; H, 3.39; N, 8.56. Found: C,
44.34; H, 3.21; N, 8.45.
2-Bromo-N-methyl-N-(prop-2-ynyl)benzenesulfonamide (21a);
Typical Procedure
IR (KBr): 3282, 2346, 1153, 1054 cm–1
.
To a solution of 20a (400 mg, 1.60 mmol) in MEK (10 mL), K2CO3 (1.10
g, 7.99 mmol) and a catalytic amount of NaI (5 mg) were added. Then
propargyl bromide (0.28 mL, 3.20 mmol) was added and the mixture
was refluxed for 4 h. The residual solvent was evaporated under re-
duced pressure and the crude product obtained was purified by col-
umn chromatography (10% EtOAc–PE) to afford 21a (452 mg, 98%) as
a colorless gummy liquid; Rf = 0.25 (10% EtOAc–PE).
1H NMR (400 MHz, CDCl3): δ = 8.54–8.52 (m, 1 H), 8.17 (dd, J = 7.8, 1.8
Hz, 1 H), 7.74 (dd, J = 7.8, 1.4 Hz, 1 H), 7.66 (td, J = 7.6, 1.7 Hz, 1 H),
7.47–7.37 (m, 3 H), 7.21–7.17 (m, 1 H), 4.80 (s, 2 H), 4.16 (d, J = 2.4 Hz,
2 H), 2.13 (t, J = 2.5 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 156.2, 149.6, 139.1, 137.1, 135.8,
133.9, 132.4, 127.7, 122.8, 122.5, 120.8, 76.9, 73.8, 52.8, 37.0.
Anal. Calcd for C15H13BrN2O2S: C, 49.33; H, 3.59; N, 7.67. Found: C,
49.57; H, 3.70; N, 7.54.
IR (KBr): 3279, 2343, 1153, 1011 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.11 (dd, J = 7.8, 1.8 Hz, 1 H), 7.74 (dd,
J = 7.7, 1.2 Hz, 1 H), 7.45 (td, J = 7.5, 1.4 Hz, 1 H), 7.38 (td, J = 7.8, 1.9
Hz, 1 H), 4.14 (d, J = 2.4 Hz, 2 H), 2.94 (s, 3 H), 2.23 (t, J = 2.4 Hz, 1 H).
2-Bromo-N-methyl-N-(3-phenylprop-2-ynyl)benzenesulfon-
amide (16aa); Typical Procedure
13C NMR (100 MHz, CDCl3): δ = 138.2, 135.8, 133.8, 132.4, 127.6,
N2 gas was bubbled through a solution of 21a (100 mg, 0.35 mmol)
and Et3N (1 mL) in anhyd THF (3 mL) for 10 min. Then catalyst
Pd(PPh3)2Cl2 (12 mg, 5 mol%) and co-catalyst CuI (8 mg, 12 mol%)
were added to the mixture and it was stirred for a further 10 min. Io-
dobenzene (78 mg, 0.38 mmol) was then added and the mixture was
stirred for 8 h at r.t. under N2. Most of the solvent and Et3N were re-
moved under reduced pressure and the residue was subjected to
chromatography (silica gel, 10% EtOAc–PE) to afford 16aa (124 mg,
98%) as a colorless gummy liquid; Rf = 0.30 (10% EtOAc–PE).
120.7, 77.3, 73.7, 39.6, 34.4.
Anal. Calcd for C10H10BrNO2S: C, 41.68; H, 3.50; N, 4.86. Found: C,
41.39; H, 3.69; N, 4.98.
2-Bromo-N-ethyl-N-(prop-2-ynyl)benzenesulfonamide (21b)
Prepared following the typical procedure for 21a using 20b (400 mg,
1.51 mmol), MEK (10 mL), NaI (5 mg), and propargyl bromide (0.27
mL, 3.03 mmol). The product was purified by column chromatogra-
phy (10% EtOAc–PE) to yield 21b (448 mg, 98%) as a colorless gummy
liquid; Rf = 0.30 (10% EtOAc–PE).
IR (KBr): 2350, 2235, 1165, 1014 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.14 (dd, J = 7.9, 1.8 Hz, 1 H), 7.73 (dd,
J = 7.7, 1.1 Hz, 1 H), 7.44 (td, J = 7.6, 1.1 Hz, 1 H), 7.36 (td, J = 7.6, 1.7
Hz, 1 H), 7.31–7.27 (m, 5 H), 4.36 (s, 2 H), 3.03 (s, 3 H).
IR (KBr): 3280, 2338, 1161, 1027 cm–1
.
13C NMR (100 MHz, CDCl3): δ = 138.5, 135.9, 133.7, 132.5, 131.8,
128.7, 128.4, 127.6, 122.4, 120.7, 85.6, 82.4, 40.5, 34.7.
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S. Debnath, S. Mondal
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HRMS (ESI+): m/z [M
+
Na]+ calcd for C16H14BrNNaO2S:
N-{3-[4-(Benzyloxy)phenyl]prop-2-ynyl}-2-bromo-N-methylben-
385.9821/387.9801; found: 385.9824/387.9803.
zenesulfonamide (16ae)
Prepared following the typical procedure for 16aa using 21a (100 mg,
0.35 mmol), Et3N (1 mL), anhyd THF (3 mL), Pd(PPh3)2Cl2 (12 mg, 5
mol%), co-catalyst CuI (8 mg, 12 mol%), and 1-(benzyloxy)-4-iodo-
benzene (118 mg, 0.38 mmol). The product was purified by column
chromatography (10% EtOAc–PE) to yield 16ae (155 mg, 95%) as a red-
dish gummy liquid; Rf = 0.35 (10% EtOAc–PE).
2-Bromo-N-methyl-N-(3-p-tolylprop-2-ynyl)benzenesulfonamide
(16ab)
Prepared following the typical procedure for 16aa using 21a (100 mg,
0.35 mmol), Et3N (1 mL), anhyd THF (3 mL), Pd(PPh3)2Cl2 (12 mg, 5
mol%), co-catalyst CuI (8 mg, 12 mol%), and 1-iodo-4-methylbenzene
(83 mg, 0.38 mmol). The product was purified by column chromatog-
raphy (10% EtOAc–PE) to yield 16ab (128 mg, 98%) as a reddish gum-
my liquid; Rf = 0.30 (10% EtOAc–PE).
IR (KBr): 2343, 2229, 1163, 1015 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.14 (dd, J = 7.9, 1.7 Hz, 1 H), 7.72 (dd,
J = 7.9, 1.2 Hz, 1 H), 7.45–7.33 (m, 7 H), 7.24 (dt, J = 8.8, 1.8 Hz, 2 H),
6.88 (dt, J = 8.8, 1.9 Hz, 2 H), 5.05 (s, 2 H), 4.35 (s, 2 H), 3.03 (s, 3 H).
IR (KBr): 2344, 2230, 1160, 1012 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.14 (dd, J = 7.9, 1.8 Hz, 1 H), 7.72 (dd,
J = 7.8, 1.1 Hz, 1 H), 7.43 (td, J = 7.5, 1.1 Hz, 1 H), 7.35 (td, J = 7.8, 1.8
Hz, 1 H), 7.19 (d, J = 8.1 Hz, 2 H), 7.08 (d, J = 8.0 Hz, 2 H), 4.35 (s, 2 H),
3.03 (s, 3 H), 2.33 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.0, 138.4, 136.6, 135.8, 133.7,
133.3, 132.4, 128.7, 128.2, 127.6, 127.5, 120.7, 114.9, 114.7, 85.4, 81.0,
70.1, 40.5, 34.7.
Anal. Calcd for C23H20BrNO3S: C, 58.73; H, 4.29; N, 2.98. Found: C,
58.96; H, 4.48; N, 2.80.
13C NMR (100 MHz, CDCl3): δ = 138.8, 138.5, 135.9, 133.7, 132.5,
131.7, 129.1, 127.6, 120.8, 85.7, 81.7, 40.5, 34.7, 21.6.
Anal. Calcd for C17H16BrNO2S: C, 53.98; H, 4.26; N, 3.70. Found: C,
54.29; H, 4.43; N, 3.42.
2-Bromo-N-ethyl-N-(3-phenylprop-2-ynyl)benzenesulfonamide
(16ba)
Prepared following the typical procedure for 16aa using 21b (100 mg,
0.33 mmol), Et3N (1 mL), anhyd THF (3 mL), Pd(PPh3)2Cl2 (12 mg, 5
mol%), co-catalyst CuI (7 mg, 12 mol%), and iodobenzene (74 mg, 0.36
mmol). The product was purified by column chromatography (10%
EtOAc–PE) to yield 16ba (121 mg, 97%) as a colorless gummy liquid;
Rf = 0.35 (10% EtOAc–PE).
2-Bromo-N-[3-(4-methoxyphenyl)prop-2-ynyl]-N-methylben-
zenesulfonamide (16ac)
Prepared following the typical procedure for 16aa using 21a (100 mg,
0.35 mmol), Et3N (1 mL), anhyd THF (3 mL), Pd(PPh3)2Cl2 (12 mg, 5
mol%), co-catalyst CuI (8 mg, 12 mol%), and 1-iodo-4-methoxyben-
zene (89 mg, 0.38 mmol). The product was purified by column chro-
matography (10% EtOAc–PE) to yield 16ac (130 mg, 95%) as a reddish
gummy liquid; Rf = 0.30 (10% EtOAc–PE).
IR (KBr): 2232, 1161, 1024 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.16 (dd, J = 7.8, 1.6 Hz, 1 H), 7.71 (dd,
J = 7.9, 1.3 Hz, 1 H), 7.43 (td, J = 7.5, 1.1 Hz, 1 H), 7.37–7.26 (m, 6 H),
4.42 (s, 2 H), 3.54 (q, J = 7.2 Hz, 2 H), 1.22 (t, J = 7.1 Hz, 3 H).
IR (KBr): 2343, 2229, 1163, 1017 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.14 (dd, J = 7.8, 1.7 Hz, 1 H), 7.72 (dd,
J = 7.8, 1.4 Hz, 1 H), 7.43 (td, J = 7.6, 1.3 Hz, 1 H), 7.36 (td, J = 7.7, 1.8
Hz, 1 H), 7.25–7.22 (m, 2 H), 6.80 (dt, J = 8.9, 2.2 Hz, 2 H), 4.34 (s, 2 H),
3.80 (s, 3 H), 3.03 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 139.4, 135.8, 133.6, 132.3, 131.8,
128.6, 128.4, 127.6, 122.5, 120.7, 85.1, 82.8, 42.1, 36.7, 13.4.
Anal. Calcd for C17H16BrNO2S: C, 53.98; H, 4.26; N, 3.70. Found: C,
54.24; H, 4.07; N, 3.65.
13C NMR (100 MHz, CDCl3): δ = 159.9, 138.6, 135.9, 133.7, 133.3,
132.5, 127.6, 120.8, 114.5, 114.0, 85.5, 81.0, 55.4, 40.6, 34.7.
2-Bromo-N-ethyl-N-(3-p-tolylprop-2-ynyl)benzenesulfonamide
Anal. Calcd for C17H16BrNO3S: C, 51.79; H, 4.09; N, 3.55. Found: C,
51.60; H, 4.21; N, 3.82.
(16bb)
Prepared following the typical procedure for 16aa using 21b (100 mg,
0.33 mmol), Et3N (1 mL), anhyd THF (3 mL), Pd(PPh3)2Cl2 (12 mg, 5
mol%), co-catalyst CuI (7 mg, 12 mol%), and 1-iodo-4-methylbenzene
(79 mg, 0.36 mmol). The product was purified by column chromatog-
raphy (10% EtOAc–PE) to yield 16bb (127 mg, 98%) as a colorless gum-
my liquid; Rf = 0.35 (10% EtOAc–PE).
2-Bromo-N-[3-(4-ethoxyphenyl)prop-2-ynyl]-N-methylbenzene-
sulfonamide (16ad)
Prepared following the typical procedure for 16aa using 21a (100 mg,
0.35 mmol), Et3N (1 mL), anhyd THF (3 mL), Pd(PPh3)2Cl2 (12 mg, 5
mol%), co-catalyst CuI (8 mg, 12 mol%), and 1-ethoxy-4-iodobenzene
(95 mg, 0.38 mmol). The product was purified by column chromatog-
raphy (10% EtOAc–PE) to yield 16ad (136 mg, 96%) as a reddish gum-
my liquid; Rf = 0.30 (10% EtOAc–PE).
IR (KBr): 2227, 1165, 1026 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.16 (dd, J = 7.9, 1.8 Hz, 1 H), 7.71 (dd,
J = 7.8, 1.2 Hz, 1 H), 7.42 (td, J = 7.6, 1.4 Hz, 1 H), 7.34 (td, J = 7.5, 1.9
Hz, 1 H), 7.20–7.17 (m, 2 H), 7.09–7.07 (m, 2 H), 4.41 (s, 2 H), 3.54 (q,
J = 7.1 Hz, 2 H), 2.33 (s, 3 H), 1.22 (t, J = 7.3 Hz, 3 H).
IR (KBr): 2344, 2226, 1167, 1021 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.14 (dd, J = 7.8, 1.7 Hz, 1 H), 7.72 (dd,
J = 7.8, 1.2 Hz, 1 H), 7.43 (td, J = 7.6, 1.2 Hz, 1 H), 7.35 (td, J = 7.8, 1.8
Hz, 1 H), 7.22 (dt, J = 8.8, 2.0 Hz, 2 H), 6.79 (dt, J = 8.8, 2.0 Hz, 2 H),
4.34 (s, 2 H), 4.02 (q, J = 7.0 Hz, 2 H), 3.02 (s, 3 H), 1.40 (t, J = 7.0 Hz, 3
H).
13C NMR (100 MHz, CDCl3): δ = 139.4, 138.8, 135.8, 133.6, 132.3,
131.7, 129.1, 127.6, 120.7, 119.4, 85.3, 82.1, 42.0, 36.7, 21.6, 13.4.
HRMS (ESI+): m/z [M
+
Na]+ calcd for C18H18BrNNaO2S:
414.0134/416.0114; found: 414.0138/416.0116.
13C NMR (100 MHz, CDCl3): δ = 159.3, 138.6, 135.9, 133.7, 133.3,
132.4, 127.6, 120.8, 114.5, 114.3, 85.6, 80.9, 63.7, 40.6, 34.7, 14.9.
2-Bromo-N-ethyl-N-[3-(4-methoxyphenyl)prop-2-ynyl]benzene-
sulfonamide (16bc)
Anal. Calcd for C18H18BrNO3S: C, 52.95; H, 4.44; N, 3.43. Found: C,
52.72; H, 4.28; N, 3.72.
Prepared following the typical procedure for 16aa using 21b (100 mg,
0.33 mmol), Et3N (1 mL), anhyd THF (3 mL), Pd(PPh3)2Cl2 (12 mg, 5
mol%), co-catalyst CuI (7 mg, 12 mol%), and 1-iodo-4-methoxyben-
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S. Debnath, S. Mondal
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zene (85 mg, 0.36 mmol). The product was purified by column chro-
matography (10% EtOAc–PE) to yield 16bc (130 mg, 96%) as a reddish
gummy liquid; Rf = 0.35 (10% EtOAc–PE).
mmol). The product was purified by column chromatography (5%
EtOAc–PE) to yield 16ca (116 mg, 96%) as a reddish gummy liquid;
Rf = 0.40 (10% EtOAc–PE).
IR (KBr): 2345, 2227, 1161, 1027 cm–1
.
IR (KBr): 2344, 2230, 1150, 1051 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.15 (dd, J = 7.9, 1.8 Hz, 1 H), 7.71 (dd,
J = 7.9, 1.1 Hz, 1 H), 7.42 (td, J = 8.0, 1.0 Hz, 1 H), 7.34 (td, J = 7.8, 1.9
Hz, 1 H), 7.23 (dt, J = 8.9, 2.1 Hz, 2 H), 6.80 (dt, J = 8.9, 2.0 Hz, 2 H),
4.40 (s, 2 H), 3.80 (s, 3 H), 3.53 (q, J = 7.1 Hz, 2 H), 1.1 (t, J = 7.1 Hz, 3
H).
1H NMR (400 MHz, CDCl3): δ = 8.20 (dd, J = 7.8, 1.6 Hz, 1 H), 7.74 (dd,
J = 7.9, 1.2 Hz, 1 H), 7.44 (td, J = 7.6, 1.1 Hz, 1 H), 7.39–7.25 (m, 11 H),
4.69 (s, 2 H), 4.20 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 139.3, 135.8, 135.4, 133.8, 132.5,
131.8, 128.9, 128.9, 128.7, 128.4, 128.2, 127.7, 122.4, 120.9, 85.6, 82.3,
51.2, 36.6.
13C NMR (100 MHz, CDCl3): δ = 159.9, 139.4, 135.8, 133.5, 133.3,
132.3, 127.6, 120.7, 114.6, 114.0, 85.0, 81.4, 55.4, 42.0, 36.7, 13.4.
Anal. Calcd for C22H18BrNO2S: C, 60.01; H, 4.12; N, 3.18. Found: C,
60.29; H, 4.25; N, 2.99.
Anal. Calcd for C18H18BrNO3S: C, 52.95; H, 4.44; N, 3.43. Found: C,
52.77; H, 4.30; N, 3.64.
N-Benzyl-2-bromo-N-(3-p-tolylprop-2-ynyl)benzenesulfonamide
2-Bromo-N-[3-(4-ethoxyphenyl)prop-2-ynyl]-N-ethylbenzenesul-
(16cb)
fonamide (16bd)
Prepared following the typical procedure for 16aa using 21c (100 mg,
0.27 mmol), Et3N (1 mL), anhyd THF (3 mL), Pd(PPh3)2Cl2 (10 mg, 5
mol%), co-catalyst CuI (6 mg, 12 mol%), and 1-iodo-4-methylbenzene
(66 mg, 0.30 mmol). The product was purified by column chromatog-
raphy (5% EtOAc–PE) to yield 16cb (118 mg, 95%) as a reddish gummy
liquid; Rf = 0.40 (10% EtOAc–PE).
Prepared following the typical procedure for 16aa using 21b (100 mg,
0.33 mmol), Et3N (1 mL), anhyd THF (3 mL), Pd(PPh3)2Cl2 (12 mg, 5
mol%), co-catalyst CuI (7 mg, 12 mol%), and 1-ethoxy-4-iodobenzene
(90 mg, 0.36 mmol). The product was purified by column chromatog-
raphy (10% EtOAc–PE) to yield 16bd (133 mg, 95%) as a reddish gum-
my liquid; Rf = 0.35 (10% EtOAc–PE).
IR (KBr): 2339, 2227, 1150, 1050 cm–1
.
IR (KBr): 2343, 2225, 1161, 1029 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.20 (dd, J = 7.9, 1.7 Hz, 1 H), 7.74 (dd,
J = 7.7, 1.1 Hz, 1 H), 7.44 (td, J = 7.6, 1.0 Hz, 1 H), 7.38–7.28 (m, 6 H),
7.17 (d, J = 8.0 Hz, 2 H), 7.09 (d, J = 8.0 Hz, 2 H), 4.69 (s, 2 H), 4.19 (s, 2
H), 2.35 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 139.4, 138.9, 135.8, 135.5, 133.7,
132.5, 131.7, 129.1, 128.9, 128.9, 128.2, 127.7, 120.9, 119.3, 85.8, 81.5,
51.2, 36.7, 21.6.
1H NMR (400 MHz, CDCl3): δ = 8.15 (dd, J = 7.9, 1.8 Hz, 1 H), 7.71 (dd,
J = 7.8, 1.3 Hz, 1 H), 7.42 (td, J = 7.6, 1.4 Hz, 1 H), 7.34 (td, J = 7.6, 1.6
Hz, 1 H), 7.21 (dt, J = 8.7, 2.0 Hz, 2 H), 6.78 (dt, J = 8.8, 2.0 Hz, 2 H),
4.39 (s, 2 H), 4.01 (q, J = 7.0 Hz, 2 H), 3.53 (q, J = 7.1 Hz, 2 H), 1.40 (t, J =
7.0 Hz, 3 H), 1.21 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.3, 139.4, 135.7, 133.5, 133.3,
132.2, 127.6, 120.7, 114.5, 114.3, 85.1, 81.3, 63.7, 42.0, 36.7, 14.9,
13.4.
Anal. Calcd for C23H20BrNO2S: C, 60.80; H, 4.44; N, 3.08. Found: C,
61.02; H, 4.28; N, 3.32.
Anal. Calcd for C19H20BrNO3S: C, 54.03; H, 4.77; N, 3.32. Found: C,
54.33; H, 4.54; N, 3.49.
N-Benzyl-2-bromo-N-[3-(4-methoxyphenyl)prop-2-ynyl]ben-
zenesulfonamide (16cc)
N-{3-[4-(Benzyloxy)phenyl]prop-2-ynyl}-2-bromo-N-ethylben-
zenesulfonamide (16be)
Prepared following the typical procedure for 16aa using 21c (100 mg,
0.27 mmol), Et3N (1 mL), anhyd THF (3 mL), Pd(PPh3)2Cl2 (10 mg, 5
mol%), co-catalyst CuI (6 mg, 12 mol%), and 1-iodo-4-methoxyben-
zene (71 mg, 0.30 mmol). The product was purified by column chro-
matography (5% EtOAc–PE) to yield 16cc (125 mg, 97%) as a colorless
gummy liquid; Rf = 0.40 (10% EtOAc–PE).
Prepared following the typical procedure for 16aa using 21b (100 mg,
0.33 mmol), Et3N (1 mL), anhyd THF (3 mL), Pd(PPh3)2Cl2 (12 mg, 5
mol%), co-catalyst CuI (7 mg, 12 mol%), and 1-(benzyloxy)-4-iodo-
benzene (113 mg, 0.36 mmol). The product was purified by column
chromatography (10% EtOAc–PE) to yield 16be (155 mg, 97%) as a
reddish gummy liquid; Rf = 0.40 (10% EtOAc–PE).
IR (KBr): 2341, 2225, 1153, 1041 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.20 (dd, J = 7.9, 1.8 Hz, 1 H), 7.74 (dd,
J = 7.7, 1.1 Hz, 1 H), 7.44 (td, J =7.6, 1.3 Hz, 1 H), 7.38–7.29 (m, 6 H),
7.21 (dt, J = 8.9, 2.0 Hz, 2 H), 6.81 (dt, J = 8.9, 2.0 Hz, 2 H), 4.68 (s, 2 H),
4.18 (s, 2 H), 3.81 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.9, 139.4, 135.8, 135.5, 133.7,
133.3, 132.5, 128.9, 128.8, 128.2, 127.7, 120.9, 114.5, 114.0, 85.6, 80.8,
55.4, 51.1, 36.7.
IR (KBr): 2344, 2225, 1160, 1019 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.16 (dd, J = 7.8, 1.7 Hz, 1 H), 7.71 (dd,
J = 7.9, 1.2 Hz, 1 H), 7.44–7.32 (m, 7 H), 7.23 (td, J = 8.8, 1.9 Hz, 2 H),
6.88 (td, J = 8.8, 2.0 Hz, 2 H), 5.05 (s, 2 H), 4.40 (s, 2 H), 3.52 (q, J = 7.1
Hz, 2 H), 1.21 (t, J = 7.1 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.1, 139.4, 136.6, 135.7, 133.5,
133.3, 132.3, 128.8, 128.3, 127.6, 120.7, 114.9, 114.8, 85.0, 81.5, 70.2,
42.0, 36.7, 13.4.
Anal. Calcd for C23H20BrNO3S: C, 58.73; H, 4.29; N, 2.98. Found: C,
58.47; H, 4.42; N, 3.15.
Anal. Calcd for C24H22BrNO3S: C, 59.51; H, 4.58; N, 2.89. Found: C,
59.26; H, 4.74; N, 2.76.
N-Benzyl-2-bromo-N-[3-(4-ethoxyphenyl)prop-2-ynyl]benzene-
sulfonamide (16cd)
N-Benzyl-2-bromo-N-(3-phenylprop-2-ynyl)benzenesulfonamide
(16ca)
Prepared following the typical procedure for 16aa using 21c (100 mg,
0.27 mmol), Et3N (1 mL), anhyd THF (3 mL), Pd(PPh3)2Cl2 (10 mg, 5
mol%), co-catalyst CuI (6 mg, 12 mol%), and 1-ethoxy-4-iodobenzene
Prepared following the typical procedure for 16aa using 21c (100 mg,
0.27 mmol), Et3N (1 mL), anhyd THF (3 mL), Pd(PPh3)2Cl2 (10 mg, 5
mol%), co-catalyst CuI (6 mg, 12 mol%), and iodobenzene (62 mg, 0.30
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S. Debnath, S. Mondal
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Synthesis
(75 mg, 0.30 mmol). The product was purified by column chromatog-
raphy (5% EtOAc–PE) to yield 16cd (126 mg, 95%) as a colorless gum-
my liquid; Rf = 0.40 (10% EtOAc–PE).
benzene (93 mg, 0.30 mmol). The product was purified by column
chromatography (20% EtOAc–PE) to yield 16de (127 mg, 85%) as a
reddish gummy liquid; Rf = 0.45 (30% EtOAc–PE).
IR (KBr): 2343, 2225, 1147, 1047 cm–1
.
IR (KBr): 2345, 2227, 1157, 1006 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.20 (dd, J = 7.8, 1.6 Hz, 1 H), 7.74 (dd,
J = 7.8, 1.1 Hz, 1 H), 7.44 (td, J = 7.6, 1.3 Hz, 1 H), 7.38–7.29 (m, 6 H),
7.20 (dt, J = 8.9, 2.0 Hz, 2 H), 6.80 (dt, J = 8.8, 2.1 Hz, 2 H), 4.69 (s, 2 H),
4.05 (s, 2 H), 4.02 (q, J = 7.0 Hz, 2 H), 1.42 (t, J = 7.0 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 8.55–8.53 (m, 1 H), 8.20 (dd, J = 7.9, 1.6
Hz, 1 H), 7.72–7.67 (m, 2 H), 7.51 (d, J = 7.9 Hz, 1 H), 7.45–7.31 (m, 7
H), 7.22–7.18 (m, 1 H), 7.15 (dt, J = 8.8, 1.9 Hz, 2 H), 6.85 (dt, J = 8.8,
1.9 Hz, 2 H), 5.05 (s, 2 H), 4.90 (s, 2 H), 4.33 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 159.3, 139.3, 135.7, 135.5, 133.7,
133.2, 132.4, 128.8, 128.8, 128.2, 127.7, 120.8, 114.5, 114.2, 85.7, 80.7,
63.7, 51.1, 36.7, 29.8, 14.9.
13C NMR (100 MHz, CDCl3): δ = 159.0, 156.7, 149.5, 139.3, 137.1,
135.7, 133.7, 133.3, 132.5, 128.8, 128.3, 127.7, 127.6, 122.8, 122.3,
120.8, 114.8, 114.7, 85.4, 80.8, 70.2, 53.3, 38.0.
HRMS (ESI+): m/z [M
506.0396/508.0376; found: 506.0400/508.0373.
+
Na]+ calcd for C24H22BrNNaO3S:
Anal. Calcd for C28H23BrN2O3S: C, 61.43; H, 4.23; N, 5.12. Found: C,
61.66; H, 4.36; N, 4.98.
N-Benzyl-N-{3-{4-(benzyloxy)phenyl]prop-2-ynyl}-2-bromoben-
(4Z)-4-Benzylidene-2-methyl-3,4-dihydro-2H-1,2-benzothiazine
zenesulfonamide (16ce)
1,1-Dioxide (17aa); Typical Procedure
Prepared following the typical procedure for 16aa using 21c (100 mg,
0.27 mmol), Et3N (1 mL), anhyd THF (3 mL), Pd(PPh3)2Cl2 (10 mg, 5
mol%), co-catalyst CuI (6 mg, 12 mol%), and 1-(benzyloxy)-4-iodo-
benzene (94 mg, 0.30 mmol). The product was purified by column
chromatography (5% EtOAc–PE) to yield 16ce (144 mg, 96%) as a red-
dish gummy liquid; Rf = 0.50 (10% EtOAc–PE).
To a mixture of 16aa (100 mg, 0.27 mmol) and sodium formate (28
mg, 0.41 mmol) in DMF–H2O (7:3, 3 mL), Pd(PPh3)4 (13 mg, 4 mol%)
was added and the mixture was heated at 100 °C for 1 h. The mixture
was cooled, H2O (10 mL) was added, and it was extracted with EtOAc
(3 × 10 mL). The combined EtOAc extracts were washed with H2O (4 ×
10 mL) and brine (10 mL), and dried (Na2SO4). The solvent was dis-
tilled off to furnish a viscous mass that was purified by column chro-
matography (silica gel, 10% EtOAc–PE) to give 17aa (72 mg, 92%) as a
white solid; mp 131–133 °C; Rf = 0.25 (10% EtOAc–PE).
IR (KBr): 2345, 2226, 1150, 1028 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.20 (dd, J = 7.9, 1.6 Hz, 1 H), 7.74 (dd,
J = 7.7, 1.1 Hz, 1 H), 7.46–7.29 (m, 12 H), 7.21 (td, J = 8.8, 1.9 Hz, 2 H),
6.89 (td, J = 8.7, 2.0 Hz, 2 H), 5.07 (s, 2 H), 4.68 (s, 2 H), 4.18 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 159.1, 139.3, 136.6, 135.7, 135.5,
133.7, 133.3, 132.5, 128.9, 128.8, 128.8, 128.3, 128.2, 127.7, 127.6,
120.8, 114.9, 114.8, 85.5, 80.9, 70.2, 51.1, 36.7.
IR (KBr): 1600, 1163, 1049 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.88–7.82 (m, 2 H), 7.57 (td, J = 7.6, 1.4
Hz, 1 H), 7.50–7.41 (m, 4 H), 7.37–7.33 (m, 1 H), 7.29–7.26 (m, 2 H),
4.67 (d, J = 1.3 Hz, 2 H), 2.70 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 135.5, 134.3, 133.3, 132.6, 131.9,
129.4, 129.1, 128.9, 128.4, 126.2, 125.6, 124.8, 52.0, 36.4.
HRMS (ESI+): m/z [M
+
Na]+ calcd for C29H24BrNNaO3S:
568.0552/570.0532; found: 568.0557, 570.0535.
HRMS (ESI+): m/z [M + Na]+ calcd for C16H15NNaO2S: 308.0716; found:
308.0716.
2-Bromo-N-(3-phenylprop-2-ynyl)-N-(pyridin-2-ylmethyl)ben-
zenesulfonamide (16da)
(4Z)-2-Methyl-4-(4-methylbenzylidene)-3,4-dihydro-2H-1,2-ben-
zothiazine 1,1-Dioxide (17ab)
Prepared following the typical procedure for 16aa using 21d (100 mg,
0.27 mmol), Et3N (1 mL), anhyd THF (3 mL), Pd(PPh3)2Cl2 (10 mg, 5
mol%), co-catalyst CuI (6 mg, 12 mol%), and iodobenzene (61 mg, 0.30
mmol). The product was purified by column chromatography (20%
EtOAc–PE) to yield 16da (109 mg, 90%) as a reddish gummy liquid;
Rf = 0.40 (30% EtOAc–PE).
Prepared following the typical procedure for 17aa using 16ab (100
mg, 0.26 mmol), sodium formate (27 mg, 0.39 mmol), and Pd(PPh3)4
(12 mg, 4 mol%) in DMF–H2O (7:3, 3 mL) at 100 °C for 1 h. The product
was purified by column chromatography (10% EtOAc–PE) to yield
17ab (71 mg, 90%) as a white solid; mp 132–134 °C; Rf = 0.25 (10%
EtOAc–PE).
IR (KBr): 2345, 2230, 1154, 1083 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.56–8.53 (m, 1 H), 8.21 (dd, J = 8.0, 1.6
Hz, 1 H), 7.72–7.66 (m, 2 H), 7.51 (d, J = 7.8 Hz, 1 H), 7.43 (td, J = 7.6,
1.2 Hz, 1 H), 7.34 (td, J = 7.7, 1.8 Hz, 1 H), 7.29–7.18 (m, 6 H), 4.90 (s, 2
H), 4.36 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 156.6, 149.5, 149.3, 137.1, 135.7,
133.8, 132.6, 131.8, 128.6, 128.3, 127.7, 122.8, 122.3, 122.3, 120.8,
85.5, 82.2, 53.3, 37.9.
IR (KBr): 1590, 1160, 1047 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.87–7.80 (m, 2 H), 7.58–7.53 (m, 1 H),
7.48–7.42 (m, 2 H), 7.26–7.15 (m, 4 H), 4.67 (s, 2 H), 2.69 (s, 3 H), 2.39
(s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 138.5, 134.5, 133.2, 132.7, 132.5,
131.9, 129.6, 129.4, 128.9, 125.6, 125.4, 124.8, 52.1, 36.4, 21.4.
Anal. Calcd for C21H17BrN2O2S: C, 57.15; H, 3.88; N, 6.35. Found: C,
57.35; H, 3.71; N, 6.24.
HRMS (ESI+): m/z [M + Na]+ calcd for C17H17NNaO2S: 322.0872; found:
322.0871.
N-{3-[4-(Benzyloxy)phenyl]prop-2-ynyl}-2-bromo-N-(pyridin-2-
(4Z)-4-(4-Methoxybenzylidene)-2-methyl-3,4-dihydro-2H-1,2-
ylmethyl)benzenesulfonamide (16de)
benzothiazine 1,1-Dioxide (17ac)
Prepared following the typical procedure for 16aa using 21d (100 mg,
0.27 mmol), Et3N (1 mL), anhyd THF (3 mL), Pd(PPh3)2Cl2 (10 mg, 5
mol%), co-catalyst CuI (6 mg, 12 mol%), and 1-(benzyloxy)-4-iodo-
Prepared following the typical procedure for 17aa using 16ac (100
mg, 0.25 mmol), sodium formate (26 mg, 0.38 mmol), and Pd(PPh3)4
(12 mg, 4 mol%) in DMF–H2O (7:3, 3 mL) at 100 °C for 1 h. The product
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 710–722

719
S. Debnath, S. Mondal
Paper
Synthesis
was purified by column chromatography (10% EtOAc–PE) to yield
17ac (75 mg, 94%) as a white solid; mp 143–145 °C; Rf = 0.25 (10%
EtOAc–PE).
1H NMR (400 MHz, CDCl3): δ = 7.86 (dd, J = 7.8, 1.1 Hz, 1 H), 7.80 (d, J =
8.0 Hz, 1 H), 7.55 (td, J = 7.8, 1.2 Hz, 1 H), 7.48–7.40 (m, 4 H), 7.38–
7.34 (m, 1 H), 7.29 (d, J = 7.3 Hz, 2 H), 4.69 (d, J = 1.2 Hz, 2 H), 3.06 (q,
J = 7.2 Hz, 2 H), 0.97 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 135.6, 134.6, 134.6, 132.5, 131.5,
129.3, 128.9, 128.9, 128.4, 126.7, 125.2, 124.9, 48.1, 43.2, 13.4.
IR (KBr): 1595, 1170, 1041 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.85 (dd, J = 7.8, 1.2 Hz, 1 H), 7.80 (d, J =
7.9 Hz, 1 H), 7.55 (td, J = 7.7, 1.4 Hz, 1 H), 7.47–7.42 (m, 1 H), 7.39 (s, 1
H), 7.25–7.20 (m, 2 H), 6.97–6.93 (m, 2 H), 4.68 (d, J = 1.1 Hz, 2 H),
3.85 (s, 3 H), 2.69 (s, 3 H).
HRMS (ESI+): m/z [M + Na]+ calcd for C17H17NNaO2S: 322.0872; found:
322.0871.
13C NMR (100 MHz, CDCl3): δ = 159.7, 134.7, 132.9, 132.6, 131.6,
131.0, 128.7, 128.0, 125.5, 124.7, 124.5, 114.3, 55.5, 52.2, 36.5.
(4Z)-2-Ethyl-4-(4-methylbenzylidene)-3,4-dihydro-2H-1,2-benzo-
thiazine 1,1-Dioxide (17bb)
HRMS (ESI+): m/z [M + Na]+ calcd for C17H17NNaO3S: 338.0821; found:
Prepared following the typical procedure for 17aa using 16bb (100
mg, 0.25 mmol), sodium formate (26 mg, 0.38 mmol), and Pd(PPh3)4
(12 mg, 4 mol%) in DMF–H2O (7:3, 3 mL) at 100 °C for 1 h. The product
was purified by column chromatography (10% EtOAc–PE) to yield
17bb (74 mg, 93%) as white solid; mp 109–111 °C; Rf = 0.30 (10%
EtOAc–PE).
338.0825.
(4Z)-4-(4-Ethoxybenzylidene)-2-methyl-3,4-dihydro-2H-1,2-ben-
zothiazine 1,1-Dioxide (17ad)
Prepared following the typical procedure for 17aa using 16ad (100
mg, 0.24 mmol), sodium formate (25 mg, 0.37 mmol), and Pd(PPh3)4
(11 mg, 4 mol%) in DMF–H2O (7:3, 3 mL) at 100 °C for 1 h. The product
was purified by column chromatography (10% EtOAc–PE) to yield
17ad (75 mg, 91%) as a reddish gummy liquid; Rf = 0.25 (10% EtOAc–
PE).
IR (KBr): 1614, 1159, 1028 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.86–7.77 (m, 2 H), 7.57–7.52 (m, 1 H),
7.46–7.38 (m, 2 H), 7.26–7.17 (m, 4 H), 4.69 (d, J = 1.0 Hz, 2 H), 3.05 (q,
J = 7.2 Hz, 2 H), 2.39 (s, 3 H), 0.98 (t, J = 7.2 Hz, 3 H).
IR (KBr): 1595, 1170, 1049 cm–1
.
13C NMR (100 MHz, CDCl3): δ = 138.5, 134.8, 134.5, 132.7, 132.4,
131.6, 129.6, 129.3, 128.7, 125.9, 125.2, 124.8, 48.2, 43.2, 21.4, 13.4.
HRMS (ESI+): m/z [M + Na]+ calcd for C18H19NNaO2S: 336.1029; found:
336.1028.
1H NMR (400 MHz, CDCl3): δ = 7.85 (dd, J = 7.8, 1.2 Hz, 1 H), 7.80 (d, J =
8.1 Hz, 1 H), 7.57–7.53 (m, 1 H), 7.46–7.42 (m, 1 H), 7.38 (s, 1 H),
7.23–7.19 (m, 2 H), 6.95–6.91 (m, 2 H), 4.68 (d, J = 1.0 Hz, 2 H), 4.08 (q,
J = 7.0 Hz, 2 H), 2.69 (s, 3 H), 1.44 (t, J = 7.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.1, 134.7, 133.0, 132.5, 131.7,
(4Z)-2-Ethyl-4-(4-methoxybenzylidene)-3,4-dihydro-2H-1,2-ben-
zothiazine 1,1-Dioxide (17bc)
131.0, 128.6, 127.9, 125.5, 124.7, 124.4, 114.8, 63.7, 52.3, 36.5, 14.9.
HRMS (ESI+): m/z [M + Na]+ calcd for C18H19NNaO3S: 352.0978; found:
352.0980.
Prepared following the typical procedure for 17aa using 16bc (100
mg, 0.24 mmol), sodium formate (25 mg, 0.37 mmol), and Pd(PPh3)4
(11 mg, 4 mol%) in DMF–H2O (7:3, 3 mL) at 100 °C for 1 h. The product
was purified by column chromatography (10% EtOAc–PE) to yield
17bc (72 mg, 89%) as white solid; mp 108–110 °C; Rf = 0.30 (10%
EtOAc–PE).
(4Z)-4-[4-(Benzyloxy)benzylidene]-2-methyl-3,4-dihydro-2H-1,2-
benzothiazine 1,1-Dioxide (17ae)
Prepared following the typical procedure for 17aa using 16ae (100
mg, 0.21 mmol), sodium formate (22 mg, 0.32 mmol), and Pd(PPh3)4
(10 mg, 4 mol%) in DMF–H2O (7:3, 3 mL) at 100 °C for 1 h. The product
was purified by column chromatography (10% EtOAc–PE) to yield
17ae (73 mg, 88%) as a white solid; mp 123–125 °C; Rf = 0.30 (10%
EtOAc–PE).
IR (KBr): 1595, 1163, 1006 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.84 (d, J = 7.6 Hz, 1 H), 7.77 (d, J = 8.0
Hz, 1 H), 7.53 (t, J = 7.3 Hz, 1 H), 7.43 (t, J = 7.5 Hz, 1 H), 7.36 (s, 1 H),
7.26–7.23 (m, 2 H), 6.95 (d, J = 8.5 Hz, 2 H), 4.70 (s, 2 H), 3.85 (s, 3 H),
3.05 (q, J = 7.1 Hz, 2 H), 0.99 (t, J = 7.2 Hz, 3 H).
IR (KBr): 1600, 1165, 1005 cm–1
.
13C NMR (100 MHz, CDCl3): δ = 159.7, 135.0, 134.3, 132.4, 131.3,
130.9, 128.5, 128.1, 125.2, 125.1, 124.8, 114.3, 55.5, 48.3, 43.2, 13.4.
HRMS (ESI+): m/z [M + Na]+ calcd for C18H19NNaO3S: 352.0978; found:
352.0981.
1H NMR (400 MHz, CDCl3): δ = 7.87–7.79 (m, 2 H), 7.58–7.53 (m, 1 H),
7.47–7.35 (m, 7 H), 7.26–7.22 (m, 2 H), 7.05–7.00 (m, 2 H), 5.11 (s, 2
H), 4.68 (s, 2 H), 2.70 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.9, 136.7, 134.6, 133.0, 132.5,
131.5, 131.0, 128.8, 128.6, 128.3, 127.6, 125.5, 124.7, 124.5, 115.2,
70.2, 52.2, 36.5, 29.8.
(4Z)-4-(4-Ethoxybenzylidene)-2-ethyl-3,4-dihydro-2H-1,2-benzo-
thiazine 1,1-Dioxide (17bd)
HRMS (ESI+): m/z [M + Na]+ calcd for C23H21NNaO3S: 414.1134; found:
414.1134.
Prepared following the typical procedure for 17aa using 16bd (100
mg, 0.24 mmol), sodium formate (24 mg, 0.35 mmol), and Pd(PPh3)4
(11 mg, 4 mol%) in DMF–H2O (7:3, 3 mL) at 100 °C for 1 h. The product
was purified by column chromatography (10% EtOAc–PE) to yield
17bd (75 mg, 92%) as white solid; mp 97–100 °C; Rf = 0.30 (10%
EtOAc–PE).
(4Z)-4-Benzylidene-2-ethyl-3,4-dihydro-2H-1,2-benzothiazine
1,1-Dioxide (17ba)
Prepared following the typical procedure for 17aa using 16ba (100
mg, 0.26 mmol), sodium formate (27 mg, 0.40 mmol), and Pd(PPh3)4
(12 mg, 4 mol%) in DMF–H2O (7:3, 3 mL) at 100 °C for 1 h. The product
was purified by column chromatography (10% EtOAc–PE) to yield
17ba (71 mg, 90%) as white solid; mp 112–115 °C; Rf = 0.30 (10%
EtOAc–PE).
IR (KBr): 1600, 1160, 1016 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.84 (dd, J = 7.7, 1.2 Hz, 1 H), 7.77 (d, J =
7.9 Hz, 1 H), 7.53 (td, J = 7.6, 1.4 Hz, 1 H), 7.42 (td, J = 7.6, 0.8 Hz, 1 H),
7.35 (s, 1 H), 7.22 (d, J = 8.7 Hz, 2 H), 6.94 (dt, J = 8.7, 1.9 Hz, 2 H), 4.67
(d, J = 1.4 Hz, 2 H), 4.08 (q, J = 7.0 Hz, 2 H), 3.05 (q, J = 7.3 Hz, 2 H), 1.44
(t, J = 7.0 Hz, 3 H), 0.99 (t, J = 7.2 Hz, 3 H).
IR (KBr): 1577, 1163, 1032 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 710–722

720
S. Debnath, S. Mondal
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Synthesis
13C NMR (100 MHz, CDCl3): δ = 159.1, 135.0, 134.3, 132.4, 131.4,
130.9, 128.5, 128.0, 125.2, 124.9, 124.8, 114.7, 63.7, 48.2, 43.2, 14.9,
13.4.
13C NMR (100 MHz, CDCl3): δ = 138.4, 135.0, 134.6, 132.6, 132.5,
132.4, 129.4, 129.2, 129.1, 128.8, 128.5, 127.8, 125.5, 125.3, 125.0,
51.9, 47.4, 21.4.
HRMS (ESI+): m/z [M + Na]+ calcd for C19H21NNaO3S: 366.1134; found:
HRMS (ESI+): m/z [M + Na]+ calcd for C23H21NNaO2S: 398.1185; found:
366.1134.
398.1185.
(4Z)-4-(4-Benzoxybenzylidene)-2-ethyl-3,4-dihydro-2H-1,2-ben-
(4Z)-2-Benzyl-4-(4-methoxybenzylidene)-3,4-dihydro-2H-1,2-
zothiazine 1,1-Dioxide (17be)
benzothiazine 1,1-Dioxide (17cc)
Prepared following the typical procedure for 17aa using 16be (100
mg, 0.21 mmol), sodium formate (21 mg, 0.31 mmol), and Pd(PPh3)4
(9 mg, 4 mol%) in DMF–H2O (7:3, 3 mL) at 100 °C for 1 h. The product
was purified by column chromatography (10% EtOAc–PE) to yield
17be (73 mg, 87%) as a white solid; mp 102–105 °C; Rf = 0.35 (10%
EtOAc–PE).
Prepared following the typical procedure for 17aa using 16cc (100
mg, 0.21 mmol), sodium formate (22 mg, 0.32 mmol), and Pd(PPh3)4
(10 mg, 4 mol%) in DMF–H2O (7:3, 3 mL) at 100 °C for 1 h. The product
was purified by column chromatography (10% EtOAc–PE) to yield
17cc (73 mg, 88%) as a white solid; mp 99–101 °C; Rf = 0.35 (10%
EtOAc–PE).
IR (KBr): 1590, 1160, 1019 cm–1
.
IR (KBr): 1599, 1160, 1030 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.85 (dd, J = 7.8, 1.3 Hz, 1 H), 7.77 (d, J =
7.8 Hz, 1 H), 7.53 (td, J = 7.4, 1.3 Hz, 1 H), 7.47–7.33 (m, 7 H), 7.26–
7.22 (m, 2 H), 7.03 (dt, J = 8.8, 2.0 Hz, 2 H), 5.11 (s, 2 H), 4.70 (d, J = 1.4
Hz, 2 H), 3.05 (q, J = 7.1 Hz, 2 H), 1.00 (t, J = 7.3 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.91 (dd, J = 7.8, 1.2 Hz, 1 H), 7.80 (d, J =
8.0 Hz, 1 H), 7.56 (td, J = 7.8, 1.2 Hz, 1 H), 7.46 (td, J = 7.6, 0.8 Hz, 1 H),
7.39 (s, 1 H), 7.17–7.09 (m, 5 H), 7.06–7.04 (m, 2 H), 6.85 (dt, J = 8.8,
1.7 Hz, 2 H), 4.51 (d, J = 0.9 Hz, 2 H), 4.13 (s, 2 H), 3.82 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.9, 136.7, 134.9, 134.3, 132.4,
131.2, 130.9, 128.8, 128.5, 128.4, 128.3, 127.6, 125.2, 124.8, 115.2,
70.3, 48.3, 43.3, 13.5.
13C NMR (100 MHz, CDCl3): δ = 159.7, 135.1, 135.0, 134.4, 132.5,
132.1, 130.8, 129.1, 128.6, 128.5, 128.1, 127.9, 125.3, 124.9, 124.6,
114.2, 55.5, 51.9, 47.5.
HRMS (ESI+): m/z [M + Na]+ calcd for C24H23NNaO3S: 428.1291; found:
HRMS (ESI+): m/z [M + Na]+ calcd for C23H21NNaO3S: 414.1134; found:
428.1290.
414.1135.
(4Z)-2-Benzyl-4-benzylidene-3,4-dihydro-2H-1,2-benzothiazine
(4Z)-2-Benzyl-4-(4-ethoxybenzylidene)-3,4-dihydro-2H-1,2-ben-
1,1-Dioxide (17ca)
zothiazine 1,1-Dioxide (17cd)
Prepared following the typical procedure for 17aa using 16ca (100
mg, 0.23 mmol), sodium formate (23 mg, 0.34 mmol), and Pd(PPh3)4
(10 mg, 4 mol%) in DMF–H2O (7:3, 3 mL) at 100 °C for 1 h. The product
was purified by column chromatography (10% EtOAc–PE) to yield
17ca (78 mg, 95%) as a white solid; mp 85–88 °C; Rf = 0.35 (10%
EtOAc–PE).
Prepared following the typical procedure for 17aa using 16cd (100
mg, 0.21 mmol), sodium formate (21 mg, 0.31 mmol), and Pd(PPh3)4
(9 mg, 4 mol%) in DMF–H2O (7:3, 3 mL) at 100 °C for 1 h. The product
was purified by column chromatography (10% EtOAc–PE) to yield
17cd (78 mg, 93%) as a white solid; mp 80–83 °C; Rf = 0.35 (10%
EtOAc–PE).
IR (KBr): 1586, 1162, 1101 cm–1
.
IR (KBr): 1589, 1163, 1039 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.92 (dd, J = 7.8, 1.3 Hz, 1 H), 7.84 (d, J =
7.9 Hz, 1 H), 7.59 (td, J = 7.6, 1.4 Hz, 1 H), 7.52–7.47 (m, 2 H), 7.34–
7.26 (m, 3 H), 7.17–7.07 (m, 5 H), 7.04–7.01 (m, 2 H), 4.50 (d, J = 1.3
Hz, 2 H), 4.13 (s, 2 H).
1H NMR (400 MHz, CDCl3): δ = 7.90 (dd, J = 7.7, 1.0 Hz, 1 H), 7.80 (d, J =
8.0 Hz, 1 H), 7.56 (td, J = 7.4, 1.2 Hz, 1 H), 7.46 (td, J = 7.6, 0.7 Hz, 1 H),
7.39 (s, 1 H), 7.18–7.04 (m, 7 H), 6.83 (d, J = 8.7 Hz, 2 H), 4.51 (s, 2 H),
4.12 (s, 2 H), 4.04 (q, J = 7.0 Hz, 2 H), 1.43 (t, J = 7.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 135.4, 134.8, 134.7, 132.6, 132.3,
129.2, 129.1, 129.0, 128.7, 128.5, 128.4, 127.9, 126.2, 125.3, 125.0,
51.9, 47.3.
13C NMR (100 MHz, CDCl3): δ = 159.0, 135.1, 134.9, 134.3, 132.5,
132.2, 130.8, 129.1, 128.6, 128.5, 127.9, 125.2, 124.9, 124.3, 114.7,
63.7, 51.9, 47.4, 15.0.
HRMS (ESI+): m/z [M + Na]+ calcd for C22H19NNaO2S: 384.1029; found:
HRMS (ESI+): m/z [M + Na]+ calcd for C24H23NNaO3S: 428.1291; found:
384.1030.
428.1294.
(4Z)-2-Benzyl-4-(4-methylbenzylidene)-3,4-dihydro-2H-1,2-ben-
(4Z)-2-Benzyl-4-(4-benzoxybenzylidene)-3,4-dihydro-2H-1,2-ben-
zothiazine 1,1-Dioxide (17cb)
zothiazine 1,1-Dioxide (17ce)
Prepared following the typical procedure for 17aa using 16cb (100
mg, 0.22 mmol), sodium formate (22 mg, 0.33 mmol), and Pd(PPh3)4
(10 mg, 4 mol%) in DMF–H2O (7:3, 3 mL) at 100 °C for 1 h. The product
was purified by column chromatography (10% EtOAc–PE) to yield
17cb (75 mg, 91%) as a white solid; mp 80–83 °C; Rf = 0.35 (10%
EtOAc–PE).
Prepared following the typical procedure for 17aa using 16ce (100
mg, 0.18 mmol), sodium formate (19 mg, 0.27 mmol), and Pd(PPh3)4
(8 mg, 4 mol%) in DMF–H2O (7:3, 3 mL) at 100 °C for 1 h. The product
was purified by column chromatography (5% EtOAc–PE) to yield 17ce
(77 mg, 90%) as a white solid; mp 119–121 °C; Rf = 0.40 (10% EtOAc–
PE).
IR (KBr): 1589, 1163, 1102 cm–1
.
IR (KBr): 1599, 1167, 1037 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.90 (dd, J = 7.7, 1.2 Hz, 1 H), 7.82 (d, J =
7.9 Hz, 1 H), 7.57 (td, J = 7.6, 1.3 Hz, 1 H), 7.47 (td, J = 7.6, 0.9 Hz, 1 H),
7.43 (s, 1 H), 7.18–7.03 (m, 9 H), 4.51 (d, J = 1.2 Hz, 2 H), 4.13 (s, 2 H),
2.36 (s, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.90 (dd, J = 7.8, 1.3 Hz, 1 H), 7.80 (d, J =
8.0 Hz, 1 H), 7.57 (td, J = 7.7, 1.4 Hz, 1 H), 7.49–7.35 (m, 7 H), 7.15–
7.03 (m, 7 H), 6.92 (dt, J = 8.8, 1.8 Hz, 2 H), 5.09 (s, 2 H), 4.50 (d, J = 1.1
Hz, 2 H), 4.13 (s, 2 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 710–722

721
S. Debnath, S. Mondal
Paper
Synthesis
13C NMR (100 MHz, CDCl3): δ = 158.9, 136.8, 135.1, 134.9, 134.4,
132.5, 132.0, 130.8, 129.1, 128.8, 128.6, 128.5, 128.3, 128.3, 127.9,
127.5, 125.3, 124.9, 124.6, 115.1, 70.2, 51.9, 47.4.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561288.
S
u
p
p
ortiInfogrmoaitn
S
u
p
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f
rmoaitn
HRMS (ESI+): m/z [M + H]+ calcd for C29H26NO3S: 468.1628; found:
468.1630.
References
(4Z)-4-Benzylidene-2-(pyridin-2-ylmethyl)-3,4-dihydro-2H-1,2-
benzothiazine 1,1-Dioxide (17da)
(1) For recent review, see: (a) Majumdar, K. C.; Mondal, S. Chem.
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(c) McReynolds, M. D.; Dougherty, J. M.; Hanson, P. R. Chem.
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78, 1387.
Prepared following the typical procedure for 17aa using 16da (100
mg, 0.23 mmol), sodium formate (23 mg, 0.34 mmol), and Pd(PPh3)4
(10 mg, 4 mol%) in DMF–H2O (7:3, 3 mL) at 100 °C for 1 h. The product
was purified by column chromatography (20% EtOAc–PE) to yield
17da (71 mg, 87%) as a reddish gummy liquid; Rf = 0.30 (30% EtOAc–
PE).
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IR (KBr): 1587, 1163, 1082 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.33 (d, J = 4.4 Hz, 1 H), 7.90 (d, J = 7.5
Hz, 1 H), 7.80 (d, J = 8.0 Hz, 1 H), 7.60–7.52 (m, 2 H), 7.48 (t, J = 7.6 Hz,
1 H), 7.41 (s, 1 H), 7.37–7.23 (m, 4 H), 7.18 (d, J = 7.2 Hz, 2 H), 7.10–
7.07 (m, 1 H), 4.63 (d, J = 0.6 Hz, 2 H), 4.31 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 155.8, 149.2, 136.8, 135.5, 134.9,
134.5, 132.7, 132.1, 129.3, 128.8, 128.6, 128.2, 126.3, 125.2, 122.8,
122.7, 54.2, 49.1.
HRMS (ESI+): m/z [M + Na]+ calcd for C21H18N2NaO2S: 385.0981;
found: 385.0983.
(4Z)-4-(4-Benzoxybenzylidene)-2-(pyridin-2-ylmethyl)-3,4-dihy-
dro-2H-1,2-benzothiazine 1,1-Dioxide (17de)
Prepared following the typical procedure for 17aa using 16de (100
mg, 0.18 mmol), sodium formate (19 mg, 0.27 mmol), and Pd(PPh3)4
(8 mg, 4 mol%) in DMF–H2O (7:3, 3 mL) at 100 °C for 1 h. The product
was purified by column chromatography (20% EtOAc–PE) to yield
17de (73 mg, 85%) as a reddish gummy liquid; Rf = 0.40 (30% EtOAc–
PE).
IR (KBr): 1598, 1163, 1017 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.35–8.32 (m, 1 H), 7.88 (dd, J = 7.8, 1.2
Hz, 1 H), 7.77 (d, J = 7.9 Hz, 1 H), 7.58–7.52 (m, 2 H), 7.47–7.32 (m, 8
H), 7.16–7.11 (m, 2 H), 7.10–7.06 (m, 1 H), 6.91 (dt, J = 8.7, 1.9 Hz, 2
H), 5.07 (s, 2 H), 4.64 (d, J = 1.3 Hz, 2 H), 4.29 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 158.6, 155.7, 149.1, 136.7, 136.6,
135.2, 134.1, 132.5, 131.6, 130.8, 128.7, 128.3, 128.2, 128.1, 127.4,
125.0, 124.6, 122.7, 122.6, 114.8, 70.0, 54.1, 49.3.
HRMS (ESI+): m/z [M + Na]+ calcd for C28H24N2NaO3S: 491.1400;
found: 491.1402.
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Acknowledgement
DST, Government of India, is greatly acknowledged for a research
grant to S.M. through INSPIRE Faculty Award (No. IFA12/CH/56) and
S.D. thanks DST for a junior research fellowship under the same proj-
ect. We again thank the DST (New Delhi) for providing Single Crystal
XRD under the DST-FIST program in our department. We also thank
Md. Asif Amin (Indian Association for the Cultivation of Science) for
HRMS data collection.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 710–722

722
S. Debnath, S. Mondal
Paper
Synthesis
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(17) The CCDC reference number for the CIF file of compound 17aa:
CCDC 1412489.
(18) The CCDC reference number for the CIF file of compound 17ab:
CCDC 1412488.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 710–722