Rh(III)-Catalyzed Oxidative Annulation of Sulfoximines with Arylalkynyl Silanes via Desilylation

Article abstract of DOI:10.1021/acs.joc.9b00743

Rh(III) catalyzed oxidative synthesis of 1,2-benzothiazine derivatives using sulfoximine as a directing group under C-H activation strategy is reported. In this study, we utilized arylalkynyl silanes as an alternate for terminal alkynes to obtain the 1,2-

Full text of DOI:10.1021/acs.joc.9b00743

Note
pubs.acs.org/joc
Cite This: J. Org. Chem. XXXX, XXX, XXX−XXX
Rh(III)-Catalyzed Oxidative Annulation of Sulfoximines with
Arylalkynyl Silanes via Desilylation
Vinayak Hanchate, Nachimuthu Muniraj, and Kandikere Ramaiah Prabhu*
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, Karnataka, India
S
* Supporting Information
ABSTRACT: Rh(III) catalyzed oxidative synthesis of 1,2-
benzothiazine derivatives using sulfoximine as a directing
group under C−H activation strategy is reported. In this
study, we utilized arylalkynyl silanes as an alternate for
terminal alkynes to obtain the 1,2-benzothiazine derivatives
via desilylation pathway. The developed methodology shows a
good range of functional group tolerance and furnished the
products in moderate yields.
ulfoximines are important structural scaffolds found in
many natural products and medicinally important
Scheme 1. Comparison with Previous Work
S
compounds.1 1,2-Benzothiazines can also be described as
cyclic sulfoximines, which are useful synthetic scaffolds found
in many medicinally important molecules.2 1,2-Benzothiazines
are nonaromatic benzofused heterocyclic compounds contain-
ing sulfur, nitrogen, and a stereogenic center. High molecular
complexity and the presence of stereogenic atom in 1,2-
benzothiazines is responsible for their medicinal activities.3
This class of compounds acts as peptido mimetic inhibitors.
They can inhibit Calpain-I enzyme, which is responsible for
neurodegenerative disorders including stroke, traumatic brain
injury, spinal cord trauma, Alzheimer’s disease, Parkinson’s
disease, multiple sclerosis, motor neuron damage, and
muscular dystrophy (Figure 1).4 Despite such profound
Figure 1. Selected examples of medicinally important molecules
having 1,2-benzothiazine scaffold.
unfunctionalized sulfoximines (Scheme 1).7 In this report, they
have utilized internal alkynes as coupling partners to obtain the
corresponding 1,2-benzothiazines derivatives. This C−H
activation strategy to obtain 1,2-benzthazine derivatives finds
a greater attention in the field of organic synthesis. However,
many groups, including Bolm’s group, have utilized sulfoximine
as a directing group under C−H activation strategy for
annulation reactions for constructing 1,2-benzothiazene
derivatives using internal alkynes,7 diazo compounds,8a,b allyl
medicinal importance, meager attention has been paid to
these molecules since their discovery in 1973 by Williams and
Cram due to the synthetic challenges associated with them.5
Harmata’s group used Pd-catalyzed Sonogashira cross-
coupling reaction between 2-bromo sulfoximines and terminal
alkynes followed by cyclization to obtain the 1,2-benzothia-
zine.6 Although this is an efficient strategy, prefunctionalized
sulfoximines such as bromosulfoximines were necessary for this
transformation (Scheme 1). To avoid prefunctionalization,
simplified and step economical methods are desired. Bolm’s
group addressed this problem using Rh-catalyzed C−H
activation method for synthesizing 1,2-benzthiazenes using
Received: March 15, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.9b00743
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
Table 1. Optimization Studies
b
NMR yield (%)
entry
Rh catalyst (5 mol %)
silver salt (20 mol %)
oxidant (20 mol %)
additive (equiv)
solvent (2 mL)
3aa
3aa′
nd
7
8
3
8
5
4
4
6
trace
3
10
6
7
5
8
6
9
c
1
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*(MeCN)3][SbF6]2
[Cp*Rh(CH3CN)3][BF4]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
none
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Fe(OAc)2
none
none
none
none
none
none
none
none
DCE
DCE
toluene
TFE
nd
49
55
35
54
48
42
49
51
38
26
58
25
65
48
56
35
50
20
nd
39
2
3
4
5
6
7
8
9
10
11
12
13
14
1,4-dioxane
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
none
AgBF4
AgNTf2
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
none
none
none
none
AgOAc
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
none
NaOAc (1)
AcOH (1)
H2O (10)
H2O (10)
H2O (10)
H2O (10)
H2O (10)
H2O (10)
H2O (10)
H2O (10)
d
15
16
17
18
e
f
g
19
20
21
2
nd
7
Cu(OAc)2·H2O
Cu(OAc)2·H2O
h
AgSbF6
a
Reaction conditions: 1a (0.2 mmol), 2a (0.24 mmol), [RhCp*Cl2]2 (5 mol %), AgSbF6 (20 mol %), Cu(OAc)2·H2O (20 mol %), solvent (2 mL)
b
c
d
at 100 °C for 4 h. 1H NMR yield (using terephthalaldehyde as an internal standard). Phenylacetylene was used instead of 2a. 1 equiv of
Cu(OAc)2·H2O. 7.5 mol % of [RhCp*Cl2]2. At 80 °C. At 120 °C. In open air.
e
f
g
h
carbonates,8c sulfoxonium ylides8d,e (Scheme 1), and pyrido-
triazoles8f as coupling partners. The use of internal alkyne as
coupling partner is very common with Rh(III) catalyst system
but terminal alkynes are scant.9 It is believed that terminal
alkynes are less compatible with Rh(III) catalyst because of
acidic terminal proton leading to homocoupling under
oxidative conditions. This creates a hurdle for the applicability
of directing group strategy in synthesizing many important
structural moieties. To solve this pitfall, recently Li, Glorius,
Loh, and Chang have independently reported Rh(III)
catalyzed C−H functionalization for the direct construction
of versatile disubstituted alkynes by using prefunctionalized
hypervalent iodine-alkynes as powerful alkynylating reagents.10
Very recently, we have shown an approach using arylalkynyl
silanes as an alternate to terminal alkynes for the ortho-
alkenylation of secondary benzamides using Co(III)-catalyst.11
In continuation of our efforts on C−H activation studies,12
herein we report the synthesis of 1,2-benzothiazines that are
substituent-free at the C-4 position using sulfoximine as a
directing group and trimethylsilylacetylene derivatives as a
coupling partner through desilylation pathway using the
Rh(III) catalytic system (Scheme 1).
failed to give the desired product, indicating the non-
compatibility of terminal alkynes for this reaction. Inspired
by our previous work,10 we performed the same reaction with
arylalkynyl silane 2a instead of phenyl acetylene, which
afforded the corresponding annulated products 3aa and 3aa′
in 49 and 7% yields, respectively (entry 2). Solvent screening
revealed that toluene is the best solvent for this reaction
(entries 3−5). Performing the reaction with different cationic
species of rhodium catalyst and the acetate complex of
rhodium species did not bring any significant improvement to
the outcome of the reaction (entries 6 and 7). Changing the
silver salts from AgSbF6 to AgBF4 or AgNTf2 was not helpful
(entries 8 and 9). Performing the reaction with Fe(OAc)2 or
AgOAc as an oxidant instead of Cu(OAc)2·H2O also was not
useful in improving the yield of 3aa (entries 10 and 11).
Introduction of the additives such as NaOAc to this reaction
brought an incremental improvement in the yield of 3aa (58%,
entry 12), whereas the addition of AcOH as an acid additive
resulted in lowering the yield of 3aa to 25% (entry 13).
Performing the reaction of 1a with 2a using 10 equiv of H2O as
an additive enhanced the yield of the product 3aa to 65%
(entry 14). Increasing the Cu(OAc)2·H2O loading or Rh
catalyst loading did not improve the yield of 3aa (entries 15
and 16). Decreasing or increasing the reaction temperatures
was not useful in improving the yield of 3aa (entries 17 and
18). Reactions in the absence of AgSbF6 or Cu(OAc)2·H2O
furnished the product 3aa in lower yields (entries 19 and 20).
Performing the reaction in open air instead of oxygen
We initiated the optimization studies by checking the
compatibility of terminal alkynes. Therefore, we performed the
reaction of sulfoximine 1a (0.2 mmol) with phenyl acetylene
(0.24 mmol) using [RhCp*Cl2]2 (5 mol %), AgSbF6 (20 mol
%), and Cu(OAc)2·H2O (20 mol %) in DCE (2 mL) in an
oxygen atmosphere for 4 h (entry 1, Table 1). This reaction
B
DOI: 10.1021/acs.joc.9b00743
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a−c
Scheme 2. Substrate Scope for Sulfoximine Derivatives
a
Reaction conditions: 1 (0.2 mmol), 2a (0.24 mmol), [Cp*RhCl2]2 (5 mol %), AgSbF6 (20 mol %), Cu(OAc)2·H2O (20 mol %), H2O (10 equiv),
b
c
toluene (2 mL) at 100 °C for 4 h under O2. Isolated yield. NMR yields are in parentheses. 2 mmol scale.
a−c
Scheme 3. Substrate Scope for Arylalkynyl Silane Derivatives
a
Reaction conditions: 1a (0.2 mmol), 2 (0.24 mmol), [Cp*RhCl2]2 (5 mol %), AgSbF6 (20 mol %), Cu(OAc)2·H2O (20 mol %), H2O (10 equiv),
b
c
toluene (2 mL) at 100 °C for 4 h under O2. Isolated yield. NMR yields are in the parentheses. 2 mmol scale.
atmosphere decreased the yield of 3aa to 39%, indicating that
oxygen is necessary for this transformation (entry 21). It is
noteworthy to mention that the optimal yield of this reaction
(entry 14) is moderate; other modifications resulted either in
no reaction or reduced yield of 3aa due to the degradation of
the sulfoximine 1a under the reaction conditions. Therefore,
further studies were continued using the conditions mentioned
in entry 14 for exploring the scope of the reaction.
Having optimal conditions in hand (entry 14, Table 1), we
explored the scope of the reaction with various sulfoximine
derivatives (Scheme 2). Thus, methyl and tert-butyl sub-
stitution on the various positions of the aryl ring of sulfoximine
reacted with 2a under the optimal conditions, affording the
products 3ba−3da in 50−58% yields. Electron-donating group
such as methoxy at the para-position of the aryl ring furnished
the product 3ea in 48% yield. Halogenated aryl sulfoximine
underwent a smooth reaction with 2a forming the correspond-
ing annulated products 3fa−3ha in 40−63% yields. Unsym-
metrical sulfoximine such as isopropyl aryl sulfoximine reacted
with 2a and rendered the corresponding product 3ia in only
32% yield. A scale-up experiment of sulfoximine 1a (2 mmol,
434 mg) with 2a under optimal reaction conditions afforded
the corresponding product 3aa in 58% yield.13
Next, we explored the scope of the arylalkynyl silane
derivatives (Scheme 3). Thus, methyl, tert-butyl, methoxy, and
phenyl groups on the para-position of arylalkynyl silanes
reacted with 1a and afforded the products 4aa−4ad in 42−
54% yields. 4-Fluoro arylalkynyl silane reacted with 1a under
the optimal conditions, furnishing the annulated product 4ae
in 43% yield, whereas 4-chloro arylalkynyl silane provided the
corresponding annulated product 4af in only 26% yield.
Electron-withdrawing groups such as cyano, nitro, and
carbonyl groups on para-position of 2 displayed a good
reactivity with 1a and delivered the products 4ag−4ai in 42−
58% yields. Similarly, when arylalkynyl silane such as
trimethyl(prop-1-yn-1-yl)silane was treated with 1a under
optimal conditions, the corresponding annulated product 4ak
was delivered in only 28% yield.13
To gain insight into the reaction mechanism, a few control
experiments were performed. Thus, sulfoximine 1a was reacted
with 10 equiv of D2O under the optimal reaction conditions,
which led to 80% deuterium incorporation at the ortho-carbons
of the sulfoximine (Scheme 4, eq 1). This experiment indicates
that C−H activation might be a reversible process. The
reaction of 1a, 1a-d2, and 2a under optimal conditions
furnished a mixture of products 3aa and deuterio-3aa in 52%
C
DOI: 10.1021/acs.joc.9b00743
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
̅
desilylation of intermediate C can be promoted by the SbF6
and H2O, which is present in the medium.
Scheme 4. Control Experiments
In conclusion, we developed a method for synthesizing 1,2-
benzothiazine derivatives using Rh(III) catalyst under
oxidative conditions. In this report, we utilized arylalkynyl
silane as an alternate for terminal alkylation via the desilylation
pathway. Interestingly, the obtained 1,2-benzothiazine deriva-
tives have the substituent free at the C-4 position, which can be
further functionalized at that position. Degradation of the
sulfoximine under the reaction conditions could be the reason
for obtaining moderate yields of 1,2-benzothiazine derivatives.
EXPERIMENTAL SECTION
■
General Information. All reactions were carried out using
distilled solvents. Reactions were monitored by using precoated silica
TLC plates. Mass spectra were recorded on EI and ESI (TOF)
modes. NMR spectra were recorded at 400 MHz spectrometers in
CDCl3 or DMSO-d6; tetramethylsilane (TMS; δ = 0.00 ppm) served
as an internal standard for 1H NMR. The corresponding residual
nondeuterated solvent signal (CDCl3; δ = 77.16 ppm and DMSO-d6;
δ = 39.52 ppm) was used as an internal standard for 13C NMR.
Column chromatography was carried out on silica gel 230−400 mesh
or 100−200 mesh (Merck), and thin-layer chromatography was
carried out using silica gel GF-254. Chemicals obtained from
commercial suppliers were used without further purification. All
sulfoximine derivatives,14 arylalkynyl silane derivatives,15 and silver
phenylacetylide16 were synthesized according to reported literature
procedure.
Experimental Procedures and Data. A. General Experimental
Procedure to Prepare Sulfoximines. In a 50 mL round bottomed
flask with a magnetic bar was suspended sulfoxide derivative (4.0
mmol) in methanol (25 mL). (Diacetoxyiodo)benzene (10.0 mmol)
and ammonium acetate (8 mmol) were added and stirred for 12 h at
room temperature. After completion of the reaction (monitored by
TLC), solvent was removed by distillation under reduced pressure.
The crude products were purified by flash column chromatography
using ethyl acetate and petroleum ether mixture.
yield with KIE value of 3.54, indicating that the C−H
activation step may be a rate-determining step (eq 2). We
hypothesized that arylalkynyl silane 2a could form silver
phenylacetylide 5 in the presence of AgSbF6. Therefore, we
performed a reaction of 1a with silver phenylacetylide 5, which
failed to afford the product 3aa, indicating that silver
phenylacetylide 5 may not be an intermediate in this reaction.
On the basis of the control experiments, literature
precedence,8 and our previous work on desilylation,10
a
plausible reaction mechanism is proposed in Scheme 5.
Scheme 5. Proposed Mechanism
B. General Experimental Procedure for Synthesizing 1,2-
Benzothiazine Derivatives. In an 8 mL screw cap reaction vial,
sulfoximine derivatives (0.2 mmol), arylalkynyl silane derivative (0.24
mmol), Cu(OAc)2·H2O (8 mg, 20 mol %), rhodium catalyst (6.2 mg,
5 mol %), and AgSbF6 (13.8 mg, 20 mol %) were added followed by
the addition of toluene (2 mL) and water (36 mg, 2.0 mmol). This
vial was sealed with a screw cap after flushing with oxygen and placed
in a preheated metal block at 100 °C, and the reaction mixture was
stirred at the same temperature for 5 h. After completion of the
reaction (monitored by TLC), the reaction mixture was cooled to
room temperature and filtered through silica gel bed (100−200
mesh), and the resulting filtrate was concentrated under reduced
pressure. The crude products were purified by flash column
chromatography using an ethyl acetate and petroleum ether mixture.
C. Experimental Procedure for Scale-Up Reaction. In a 50 mL
pressure tube, diphenylsulfoximine (2.29 mmol, 500 mg), 1-phenyl-2-
trimethylsilylacetylene (2.74 mmol, 477 mg), Cu(OAc)2·H2O (91
mg, 20 mol %), rhodium catalyst (70.7 mg, 5 mol %), and AgSbF6
(157.6 mg, 20 mol %) were added followed by the addition of toluene
(25 mL) and water (360 mg, 20 mmol). This tube was sealed with a
screw cap after flushing with oxygen and placed in a preheated oil
bath at 100 °C, and the reaction mixture was stirred at the same
temperature for 5 h. After completion of the reaction (monitored by
TLC), the reaction mixture was cooled to room temperature and
filtered through silica gel bed (100−200 mesh), and the resulting
filtrate was concentrated under reduced pressure. The crude products
were purified on a column using ethyl acetate and petroleum ether
mixture.
Initially, [RhCp*Cl2]2 reacts with AgSbF6 and Cu(OAc)2·
H2O, forming an active catalyst A. Further, the active catalyst A
reacts with 1a, forming the rhodacycle B through a concerted
metalation and deprotonation pathway, followed by the
insertion of arylalkynyl silane 2a to form the 7-membered
intermediate C. The intermediate C under goes a reductive
elimination, affording the product 3aa along with RhICp*. The
active catalyst A was regenerated by the reoxidation of copper
salt and oxygen. As described in our earlier work,10 the
Sulfonimidoyldibenzene (1a). Prepared as shown in General
Experimental Procedure to Prepare Sulfoximines (A). Purified by flash
chromatography on 100−200 mesh silica gel using EtOAc:petroleum
D
DOI: 10.1021/acs.joc.9b00743
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The Journal of Organic Chemistry
Note
ether (20:80 v/v) as eluent to obtain a white solid. Isolated yield: 82%
(0.71g); mp: 102−104 °C (lit.8a −102.5−104.4 °C); IR (Neat,
cm−1): 3275, 3059, 2920, 1445, 1227, 1129, 1061; 1H NMR (CDCl3,
400 MHz): δ 8.08−8.02 (m, 4H), 7.56−7.43 (m, 6H), 2.95 (s, 1H);
13C{1H} NMR (CDCl3, 100 MHz): δ 143.4, 132.6, 129.2, 128.0;
HRMS (ESI) (m/z): Calcd for C12H11NOSH [M + H]+: 218.0640,
found [M + H]+: 218.0639.
4,4′-Sulfonimidoylbis(Bromorobenzene) (1g). Prepared as shown
in General Experimental Procedure to Prepare Sulfoximines (A).
Purified by flash chromatography on 100−200 mesh silica gel using
EtOAc:petroleum ether (15:85 v/v) as eluent to obtain a white solid.
Isolated yield: 81% (1.25 g); mp: 138−140 °C (lit.8a −137.9−139
°C); IR (Neat, cm−1): 3270, 3085, 1571, 1469, 1235, 1129, 1064; 1H
NMR (CDCl3, 400 MHz): δ 7.87 (d, J = 8.6 Hz, 4H), 7.62 (d, J = 8.6
Hz, 4H), 2.44 (s, 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 132.7,
129.6, 128.3; HRMS (ESI) (m/z): Calcd for C12H9Br2NOSH [M +
H]+: 373.8850, found [M + H]+: 373.8850
(Propan-2-ylsulfonimidoyl)benzene (1i). Prepared as shown in
General Experimental Procedure to Prepare Sulfoximines (A).
Purified by flash chromatography on 100−200 mesh silica gel using
EtOAc:petroleum ether (20:80 v/v) as eluent to obtain a colorless
liquid. Isolated yield: 44% (0.32 g); IR (Neat, cm−1): 3273, 3061,
2978, 1444, 1213, 1102; 1H NMR (CDCl3, 400 MHz): δ 7.95 (d, J =
7.7 Hz, 2H), 7.62 (dd, J = 10.5, 4.2 Hz, 1H), 7.55 (dd, J = 8.1, 7.1 Hz,
2H), 3.25 (dt, J = 13.6, 6.8 Hz, 1H), 2.58 (s, 1H), 1.32 (d, J = 6.8 Hz,
3H), 1.27 (d, J = 6.8 Hz, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ
139.9. 133.1, 129.4, 129.0, 56.6, 16.4, 16.1; HRMS (ESI) (m/z):
Calcd for C9H13NOSH [M + H]+: 184.0796, found [M + H]+:
184.0793.
1,3-Diphenylbenzo[e][1,2]thiazine 1-oxide (3aa). Prepared as
shown in General Experimental Procedure for Synthesizing 1,2-
Benzothiazine Derivatives (B). Purified by flash chromatography on
230−400 mesh silica gel using EtOAc:petroleum ether (3:97 v/v) as
eluent to obtain a yellow solid. Isolated yield: 62% (39 mg); mp:
129−131 °C; Rf (25% EtOAc-Pet. ether) = 0.6; IR (Neat, cm−1):
3060, 3024, 1582, 1219, 1112; 1H NMR (CDCl3, 400 MHz): δ 8.06−
7.93 (m, 4H), 7.67−7.60 (m, 1H), 7.57 (t, J = 7.4 Hz, 2H), 7.51−
7.45 (m, 1H), 7.45−7.38 (m, 3H), 7.34 (dd, J = 14.1, 7.5 Hz, 2H),
7.24−7.19 (m, 1H), 6.81 (s, 1H); 13C{1H} NMR (CDCl3, 100
MHz): δ 147.3, 140.6, 138.9, 136.62, 133.5, 132.2, 129.4, 129.1,
128.9, 128.5, 127.0, 126.7, 126.4, 125.0, 119.7, 98.3; HRMS (ESI)
(m/z): Calcd for C20H15NOSH [M + H]+:318.0953, found [M +
H]+: 318.0952.
4,4′-Sulfonimidoylbis(methylbenzene) (1b). Prepared as shown in
General Experimental Procedure to Prepare Sulfoximines (A).
Purified by flash chromatography on 100−200 mesh silica gel using
EtOAc:petroleum ether (20:80 v/v) as eluent to obtain a pale brown
solid. Isolated yield: 76% (0.74 g); mp: 101−103 °C; IR (Neat,
cm−1): 3274, 3059, 1595, 1491, 1240, 1136, 1094; 1H NMR (CDCl3,
400 MHz): δ 7.90 (d, J = 8.2 Hz, 4H), 7.25 (d, J = 8.1 Hz, 4H), 2.79
(s, 1H), 2.37 (s, 6H); 13C{1H} NMR (CDCl3, 100 MHz): δ 143.3,
140.8, 129.8, 127.9, 21.5; HRMS (ESI) (m/z): Calcd for
C14H15NOSH [M + H]+: 246.0953, found [M + H]+: 246.0952.
4,4′-Sulfonimidoylbis(tert-butylbenzene) (1c). Prepared as shown
in General Experimental Procedure to Prepare Sulfoximines (A).
Purified by flash chromatography on 100−200 mesh silica gel using
EtOAc:petroleum ether (10:90 v/v) as eluent to obtain a white solid.
Isolated yield: 63% (0.82 g); mp: 111−113 °C (charred) ; IR (Neat,
1
cm−1): 3303, 2959, 2853, 1587, 1467, 1231, 1136, 1084; H NMR
(CDCl3, 400 MHz): δ 7.95 (d, J = 8.6 Hz, 4H), 7.48 (d, J = 8.6 Hz,
4H), 1.30 (s, 18H), 1.25 (s, 1H); 13C{1H} NMR (CDCl3, 100 MHz):
δ 156.4, 140.5, 127.9, 126.3, 35.2, 31.2; HRMS (ESI) (m/z): Calcd
for C20H27NOSH [M + H]+: 330.1892, found [M + H]+: 330.1893.
4,4′-Sulfonimidoylbis(1,2-dimethylbenzene) (1d). Prepared as
shown in General Experimental Procedure to Prepare Sulfoximines
(A). Purified by flash chromatography on 100−200 mesh silica gel
using EtOAc:petroleum ether (20:80 v/v) as eluent to obtain a white
solid. Isolated yield: 49% (0.53 g); mp: 121−123 °C; IR (Neat,
1
cm−1): 3272, 3050, 1449, 1226, 1113, 1088; H NMR (CDCl3, 400
MHz): δ 7.79−7.72 (m, 4H), 7.21 (d, J = 7.9 Hz, 2H), 2.59 (s, 1H),
2.28 (s, 6H), 2.27 (s, 6H); 13C{1H} NMR (CDCl3, 100 MHz): δ
142.0, 141.0, 137.9, 130.3, 128.7, 125.4, 20.0, 19.9; HRMS (ESI) (m/
z): Calcd for C16H19NOSNa [M + Na]+: 296.1085, found [M + Na]+:
296.1086.
4,4′-Sulfonimidoylbis(methoxybenzene) (1e). Prepared as shown
in General Experimental Procedure to Prepare Sulfoximines (A).
Purified by flash chromatography on 100−200 mesh silica gel using
EtOAc:petroleum ether (30:70 v/v) as eluent to a pale brown solid.
Isolated yield: 75% (0.83 g); mp: 137−139 °C (lit.8a −137.5−138.2
°C); IR (Neat, cm−1): 3326, 3064, 2947, 1593, 1495, 1257, 1132,
1097; 1H NMR (CDCl3, 400 MHz): δ 7.94 (d, J = 9.0 Hz, 4H), 6.92
(d, J = 8.9 Hz, 4H), 3.82 (s, 6H), 2.79 (s, 1H); 13C{1H} NMR
(CDCl3, 100 MHz): δ 162.8, 135.6, 129.8, 114.4, 55.7; HRMS (ESI)
(m/z): Calcd for C14H15NO3SNa [M + Na]+: 300.0670, found [M +
Na]+: 300.0667
4,4′-Sulfonimidoylbis(fluorobenzene) (1f). Prepared as shown in
General Experimental Procedure to Prepare Sulfoximines (A).
Purified by flash chromatography on 100−200 mesh silica gel using
EtOAc:petroleum ether (10:90 v/v) as eluent to obtain a colorless
liquid. Isolated yield: 60% (0.6 g); IR (Neat, cm−1): 3275, 3103,
3067, 1589, 1489, 1244, 1130, 1094; 1H NMR (CDCl3, 400 MHz): δ
8.04 (dd, J = 7.9, 5.6 Hz, 4H), 7.16 (t, J = 8.4 Hz, 4H), 2.82 (s, 1H);
13C{1H} NMR (CDCl3, 100 MHz): δ 165.33 (d, JC−F = 255.37 Hz),
139.4, 130.7 (d, J = 9.5 Hz), 116.5 (d, J = 22.5 Hz); HRMS (ESI)
(m/z): Calcd for C12H9F2NOSH [M + H]+: 254.0451, found [M +
H]+: 254.0451
4,4′-Sulfonimidoylbis(Chlorobenzene) (1g). Prepared as shown in
General Experimental Procedure to Prepare Sulfoximines (A).
Purified by flash chromatography on 100−200 mesh silica gel using
EtOAc:petroleum ether (15:85 v/v) as eluent to obtain a white solid.
Isolated yield: 62% (0.7 g); mp: 107−109 °C (lit.8a −108.7−110.1
°C); IR (Neat, cm−1): 3273, 3088, 1576, 1473, 1239, 1133, 1089; 1H
NMR (CDCl3, 400 MHz): δ 7.95 (d, J = 8.5 Hz, 4H), 7.45 (d, J = 8.4
Hz, 4H), 2.94 (s, 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 141.7,
139.6, 129.6, 129.5; HRMS (ESI) (m/z): Calcd for C12H9Cl2NOSH
[M + H]+: 285.9860, found [M + H]+: 285.9863
(Z)-3-Benzylidene-1-phenylbenzo[d]isothiazole 1-oxide (3aa′).
Prepared as shown in General Experimental Procedure for Synthesiz-
ing 1,2-Benzothiazine Derivatives (B). Purified by flash chromatog-
raphy on 230−400 mesh silica gel using EtOAc:petroleum ether (3:97
v/v) as eluent to obtain a yellow solid. Isolated yield: 6% (3.8 mg);
mp: 144−146 °C; Rf (25% EtOAc-Pet. ether) = 0.5; IR (Neat, cm−1):
1
3059, 3018,1591,1219; H NMR (CDCl3, 400 MHz): δ 8.16 (d, J =
7.4 Hz, 2H), 7.92 (dd, J = 7.4, 1.4 Hz, 3H), 7.68−7.57 (m, 3H), 7.52
(t, J = 7.7 Hz, 2H), 7.39 (dt, J = 13.9, 7.8 Hz, 3H), 7.21 (t, J = 7.4 Hz,
1H), 6.54 (s, 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 13C NMR
(101 MHz, CDCl3) δ 143.60 (s), 141.1, 138.7, 136.8, 135.4, 133.8,
132.8, 129.6, 129.5, 128.9, 128.4, 126.5, 122.5, 121.6, 108.1; HRMS
(ESI) (m/z): Calcd for C20H15NOSH [M + H]+:318.0953, found [M
+ H]+: 318.0952.
6-Methyl-3-phenyl-1-(p-tolyl)benzo[e][1,2]thiazine 1-oxide
(3ba). Prepared as shown in General Experimental Procedure for
Synthesizing 1,2-Benzothiazine Derivatives (B). Purified by flash
chromatography on 230−400 mesh silica gel using EtOAc:petroleum
ether (4:96 v/v) as eluent to obtain a yellow solid. Isolated yield: 58%
(40 mg); mp: 134−136 °C; Rf (25% EtOAc-Pet. ether) = 0.6; IR
1
(Neat, cm−1): 2923, 2853,1591, 1223, 1107; H NMR (CDCl3, 400
MHz): δ 7.99 (d, J = 7.6 Hz, 2H), 7.85 (d, J = 8.2 Hz, 2H), 7.40 (t, J
= 7.5 Hz, 2H), 7.37−7.31 (m, 3H), 7.23 (d, J = 8.0 Hz, 2H), 7.03 (d,
J = 8.6 Hz, 1H), 6.73 (s, 1H), 2.44 (s, 3H), 2.39 (s, 3H); 13C{1H}
NMR (CDCl3, 100 MHz): δ 147.3, 144.4, 142.7, 139.1, 137.9, 136.7,
129.7, 129.3, 128.8, 128.4, 127.8, 126.7, 126.6, 125.0, 117.7, 98.1,
21.8, 21.7; HRMS (ESI) (m/z): Calcd for C22H19NOSH [M + H]+:
346.1266, found [M + H]+: 346.1268.
6-(tert-Butyl)-1-(4-(tert-butyl)phenyl)-3-phenylbenzo[e][1,2]-
thiazine 1-oxide (3ca). Prepared as shown in General Experimental
Procedure for Synthesizing 1,2-Benzothiazine Derivatives (B).
Purified by flash chromatography on 230−400 mesh silica gel using
EtOAc:petroleum ether (2:98 v/v) as eluent to obtain yellow solid.
Isolated yield: 52% (44 mg); mp: 190−192 °C; Rf (20% EtOAc-Pet.
E
DOI: 10.1021/acs.joc.9b00743
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
ether) = 0.7; IR (Neat, cm−1): 3060, 3025, 2962, 1591, 1221, 1120,
1097; 1H NMR (CDCl3, 400 MHz): δ 8.01 (d, J = 7.9 Hz, 2H), 7.90
(d, J = 8.2 Hz, 2H), 7.56 (d, J = 6.5 Hz, 2H), 7.46−7.31 (m, 4H),
7.29 (d, J = 0.5 Hz, 2H), 6.80 (s, 1H), 1.34 (d, J = 2.7 Hz, 18H);
13C{1H} NMR (CDCl3, 100 MHz): δ 157.2, 155.5, 147.1, 139.2,
6-Bromo-1-(4-bromophenyl)-3-phenylbenzo[e][1,2]thiazine 1-
oxide (3ha). Prepared as shown in General Experimental Procedure
for Synthesizing 1,2-Benzothiazine Derivatives (B). Purified by flash
chromatography on 230−400 mesh silica gel using EtOAc:petroleum
ether (2:98 v/v) as eluent to obtain a yellow solid. Isolated yield: 63%
(60 mg); mp: 159−161 °C; Rf (20% EtOAc-Pet. ether) = 0.8; IR
137.8, 136.5, 129.2, 128.7, 128.4, 126.7, 126.1, 124.8, 124.6, 123.02,
117.5, 98.6, 35.3, 35.2, 31.2, 31.1; HRMS (ESI) (m/z): Calcd for
C28H31NOSH [M + H]+: 430.2205, found [M + H]+: 430.2204.
1-(3,4-Dimethylphenyl)-6,7-dimethyl-3-phenylbenzo[e][1,2]-
thiazine 1-oxide (3da). Prepared as shown in General Experimental
Procedure for Synthesizing 1,2-Benzothiazine Derivatives (B).
Purified by flash chromatography on 230−400 mesh silica gel using
EtOAc:petroleum ether (5:95 v/v) as eluent to obtain a yellow solid.
Isolated yield: 50% (44 mg); mp: 191−193 °C; Rf (30% EtOAc-Pet.
ether) = 0.6; IR (Neat, cm−1): 2921, 2856, 1688, 1587, 1485, 1220,
1
(Neat, cm−1): 3080, 3024, 1569, 1224, 1069; H NMR (CDCl3, 400
MHz): δ 7.96 (d, J = 7.0 Hz, 2H), 7.80 (d, J = 8.5 Hz, 2H), 7.70 (d, J
= 8.5 Hz, 2H), 7.60 (s, 1H), 7.47−7.36 (m, 3H), 7.32 (dd, J = 8.5, 1.3
Hz, 1H), 7.16 (d, J = 8.5 Hz, 1H), 6.72 (s, 1H); 13C{1H} NMR
(CDCl3, 100 MHz): δ 148.7, 140.7, 139.0, 138.7, 138.2, 138.2, 130.7,
129.5, 129.4, 128.6, 126.8, 126.8, 126.6, 126.2, 117.4, 97.6; HRMS
(ESI) (m/z): Calcd for C20H13Br2NOSH [M + H]+: 473.9163, found
[M + H]+: 473.9167.
1-Isopropyl-3-phenylbenzo[e][1,2]thiazine 1-oxide (3ia). Pre-
pared as shown in General Experimental Procedure for Synthesizing
1,2-Benzothiazine Derivatives (B). Purified by flash chromatography
on 230−400 mesh silica gel using EtOAc:petroleum ether (4:96 v/v)
as eluent to obtain a yellow semisolid. Isolated yield: 32% (19 mg); Rf
(30% EtOAc-Pet. ether) = 0.7; IR (Neat, cm−1): 3058, 2976, 2930,
1
1098; H NMR (CDCl3, 400 MHz): δ 7.98 (d, J = 7.4 Hz, 2H),
7.77−7.65 (m, 2H), 7.39 (t, J = 7.4 Hz, 2H), 7.32 (t, J = 8.4 Hz, 2H),
7.20 (s, 1H), 7.08 (s, 1H), 6.71 (s, 1H), 2.34 (s, 3H), 2.30 (s, 6H),
2.19 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 146.2, 143.0,
142.1, 139.2, 138.2, 137.9, 136.0, 134.7, 130.2, 130.1, 128.5, 128.4,
127.2, 126.9, 126.6, 124.8, 117.9, 97.7, 20.3, 20.1, 20.0, 19.9; HRMS
(ESI) (m/z): Calcd for C24H23NOSH [M + H]+: 374.1579, found [M
+ H]+: 374.1575.
1
1583, 1207, 1105; H NMR (CDCl3, 400 MHz): δ 8.01−7.94 (m,
2H), 7.73 (d, J = 8.0 Hz, 1H), 7.56−7.50 (m, 1H), 7.43−7.39 (m,
2H), 7.38−7.30 (m, 3H), 6.54 (s, 1H), 3.84 (hept, J = 6.8 Hz, 1H),
1.57 (d, J = 6.9 Hz, 3H), 1.19 (d, J = 6.7 Hz, 3H); 13C{1H} NMR
(CDCl3, 100 MHz): δ 148.1, 138.9, 138.8, 132.9, 128.9, 128.4, 127.1,
126.5, 126.1, 124.5, 114.8, 97.2, 58.0, 17.5, 13.7; HRMS (ESI) (m/z):
Calcd for C17H17NOSH [M + H]+: 284.1109, found [M + H]+:
284.1109.
6-Methoxy-1-(4-methoxyphenyl)-3-phenylbenzo[e][1,2]thiazine
1-oxide (3ea). Prepared as shown in General Experimental Procedure
for Synthesizing 1,2-Benzothiazine Derivatives (B). Purified by flash
chromatography on 230−400 mesh silica gel using EtOAc:petroleum
ether (10:90 v/v) as eluent to obtain a yellow solid. Isolated yield:
48% (37 mg); mp: 172−174 °C; Rf (30% EtOAc-Pet. ether) = 0.5; IR
Phenyl-3-(p-tolyl)benzo[e][1,2]thiazine 1-oxide (4aa). Prepared
as shown in General Experimental Procedure for Synthesizing 1,2-
Benzothiazine Derivatives (B). Purified by flash chromatography on
230−400 mesh silica gel using EtOAc:petroleum ether (5:95 v/v) as
eluent to obtain a yellow solid. Isolated yield: 54% (36 mg); mp:
193−195 °C; Rf (30% EtOAc-Pet. ether) = 0.6; IR (Neat, cm−1):
1
(Neat, cm−1): 2924, 2846, 1589, 1465, 1259, 1107, 1024; H NMR
(CDCl3, 400 MHz): δ 7.99 (d, J = 7.4 Hz, 2H), 7.87 (d, J = 8.8 Hz,
2H), 7.37 (dt, J = 22.0, 7.0 Hz, 3H), 7.28−7.23 (m, 1H), 7.00 (d, J =
8.8 Hz, 2H), 6.79 (d, J = 2.8 Hz, 2H), 6.71 (s, 1H), 3.86 (s, 6H);
13C{1H} NMR (CDCl3, 100 MHz): δ 163.5, 162.1, 147.9, 139.0,
138.8, 132.7, 131.3, 128.8, 128.4, 127.0, 126.8, 115.9, 114.3, 113.4,
107.5, 98.1, 55.8, 55.6; HRMS (ESI) (m/z): Calcd for C22H19NO3SH
[M + H]+: 378.1164, found [M + H]+: 378.1167.
6-Fluoro-1-(4-fluorophenyl)-3-phenylbenzo[e][1,2]thiazine 1-
oxide (3fa). Prepared as shown in General Experimental Procedure
for Synthesizing 1,2-Benzothiazine Derivatives (B). Purified by flash
chromatography on 230−400 mesh silica gel using EtOAc:petroleum
ether (3:97 v/v) as eluent to obtain a yellow solid. Isolated yield: 40%
(29 mg); mp: 148−150 °C; Rf (20% EtOAc-Pet. ether) = 0.7; IR
(Neat, cm−1): 3096, 3064, 3030, 1584, 1228, 1108; 1H NMR (CDCl3,
400 MHz): δ 7.98 (dt, J = 4.8, 2.1 Hz, 4H), 7.47−7.37 (m, 3H), 7.34
(dd, J = 8.9, 5.4 Hz, 1H), 7.25 (t, J = 8.5 Hz, 2H), 7.08 (dd, J = 9.8,
2.4 Hz, 1H), 6.95 (td, J = 8.5, 2.5 Hz, 1H), 6.75 (s, 1H); 13C{1H}
NMR (CDCl3, 100 MHz): δ 165.9 (d, JC−F = 256.8 Hz), 164.6 (d,
JC−F = 253.3 Hz), 148.6, 139.4 (d, JC−F = 10.0 Hz), 138.3, 136.7 (d,
1
3061, 3020, 2922, 2854, 1583, 1219, 1111; H NMR (CDCl3, 400
MHz): δ 7.99 (d, J = 5.6 Hz, 2H), 7.90 (d, J = 6.1 Hz, 2H), 7.58 (dd,
J = 18.8, 5.5 Hz, 3H), 7.51−7.36 (m, 2H), 7.31 (d, J = 6.9 Hz, 1H),
7.21 (d, J = 5.0 Hz, 3H), 6.78 (s, 1H), 2.37 (s, 3H); 13C{1H} NMR
(CDCl3, 100 MHz): δ 147.3, 140.6, 138.9, 136.7, 136.1, 133.4, 132.2,
129.4, 129.2, 129.1, 126.9, 126.6, 126.1, 125.0, 119.5, 97.7, 21.4;
HRMS (ESI) (m/z): Calcd for C21H17NOSNa [M + Na]+: 354.0929,
found [M + Na]+: 354.0925.
3-(4-(tert-Butyl)phenyl)-1-phenylbenzo[e][1,2]thiazine 1-oxide
(4ab). Prepared as shown in General Experimental Procedure for
Synthesizing 1,2-Benzothiazine Derivatives (B). Purified by flash
chromatography on 230−400 mesh silica gel using EtOAc:petroleum
ether (1:99 v/v) as eluent to obtain a yellow solid. Isolated yield: 42%
(32 mg); mp: 177−179 °C; Rf (10% EtOAc-Pet. ether) = 0.8; IR
1
(Neat, cm−1): 3061, 2959, 2926, 2858, 185, 1222, 1113; H NMR
(CDCl3, 400 MHz): δ 7.99 (d, J = 7.3 Hz, 2H), 7.94 (d, J = 8.2 Hz,
2H), 7.61 (d, J = 6.9 Hz, 1H), 7.57 (d, J = 7.5 Hz, 2H), 7.43 (t, J = 7.1
Hz, 4H), 7.32 (d, J = 7.8 Hz, 1H), 7.20 (t, J = 7.1 Hz, 1H), 6.78 (s,
1H), 1.34 (s, 9H); 13C{1H} NMR (CDCl3, 100 MHz): δ 152.1,
147.4, 140.8, 136.8, 136.1, 133.4, 132.2, 129.4, 129.1, 126.9, 126.5,
126.2, 125.4, 125.1, 119.6, 97.7, 34.8, 31.4; HRMS (ESI) (m/z):
Calcd for C24H23NOSH [M + H]+: 374.1579, found [M + H]+:
374.1577.
JC−F = 2.8 Hz), 132.0 (d, JC−F = 9.7 Hz), 129.3, 128.5, 128.1 (d, JC−F
= 10.2 Hz), 126.8, 116.5 (d, JC−F = 22.8 Hz), 115.9, 115.1(d, JC−F
=
24.6 Hz), 111.8 (d, JC−F = 22.22 Hz), 97.9 (d, JC−F = 2.6 Hz); 19F
NMR (CDCl3, 377 MHz): δ −104.0, −105.6; HRMS (ESI) (m/z):
Calcd for C20H13F2NOSH [M + H]+: 354.0764, found [M + H]+:
354.0762.
6-Chloro-1-(4-chlorophenyl)-3-phenylbenzo[e][1,2]thiazine 1-
oxide (3ga). Prepared as shown in General Experimental Procedure
for Synthesizing 1,2-Benzothiazine Derivatives (B). Purified by flash
chromatography on 230−400 mesh silica gel using EtOAc:petroleum
ether (3:97 v/v) as eluent to obtain a yellow solid. Isolated yield: 55%
(45 mg); mp: 146−148 °C; Rf (20% EtOAc-Pet. ether) = 0.7; IR
(Neat, cm−1): 3087, 3061, 3022, 1575, 1220, 1087; 1H NMR (CDCl3,
400 MHz): δ 7.97 (d, J = 6.9 Hz, 2H), 7.88 (d, J = 8.4 Hz, 2H), 7.54
(d, J = 8.4 Hz, 2H), 7.47−7.33 (m, 4H), 7.24 (d, J = 8.3 Hz, 1H),
7.17 (d, J = 8.5 Hz, 1H), 6.73 (s, 1H); 13C{1H} NMR (CDCl3, 100
MHz): δ 148.7, 140.7, 138.8, 138.7, 138.2, 138.2, 130.7, 129.5, 129.4,
128.6, 126.8, 126.8, 126.6, 126.2, 117.4, 97.6; HRMS (ESI) (m/z):
Calcd for C20H13Cl2NOSH [M + H]+: 386.0173, found [M + H]+:
386.0172.
3-(4-Methoxyphenyl)-1-phenylbenzo[e][1,2]thiazine 1-oxide
(4ac). Prepared as shown in General Experimental Procedure for
Synthesizing 1,2-Benzothiazine Derivatives (B). Purified by flash
chromatography on 230−400 mesh silica gel using EtOAc:petroleum
ether (5:95 v/v) as eluent to obtain yellow solid. Isolated yield: 54%
(35 mg); mp: 166−168 °C; Rf (30% EtOAc-Pet. ether) = 0.6; IR
1
(Neat, cm−1): 3063, 2932, 2837, 1593, 1251, 1218, 1110; H NMR
(CDCl3, 400 MHz): δ 7.97 (dd, J = 15.4, 8.1 Hz, 4H), 7.63 (t, J = 7.3
Hz, 1H), 7.57 (t, J = 7.5 Hz, 2H), 7.46 (t, J = 7.8 Hz, 1H), 7.40 (d, J =
7.7 Hz, 1H), 7.31 (d, J = 7.9 Hz, 1H), 7.19 (t, J = 7.5 Hz, 1H), 6.94
(d, J = 8.8 Hz, 2H), 6.72 (s, 1H), 3.84 (s, 3H); 13C{1H} NMR
(CDCl3, 100 MHz): δ 160.5, 140.8, 136.9, 133.4, 132.2, 131.6, 129.4,
129.1, 128.1, 126.8, 125.9, 125.1, 119.4, 113.8, 97.0, 55.5; HRMS
F
DOI: 10.1021/acs.joc.9b00743
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(ESI) (m/z): Calcd for C21H17NO2SH [M + H]+: 348.1058, found
[M + H]+: 348.1059.
100 MHz): δ 147.8, 145.0, 144.5, 139.8, 135.7, 133.9, 132.6, 129.5,
129.3, 127.7, 127.5, 127.3, 125.1, 123.8, 120.5, 100.9; HRMS (ESI)
(m/z): Calcd for C20H14N2O3SNa [M + Na]+: 385.0623, found [M +
H]+: 385.0625.
4-(1-Oxido-1-phenylbenzo[e][1,2]thiazin-3-yl)benzaldehyde
(4ai). Prepared as shown in General Experimental Procedure for
Synthesizing 1,2-Benzothiazine Derivatives (B). Purified by flash
chromatography on 230−400 mesh silica gel using EtOAc:petroleum
ether (12:88 v/v) as eluent to obtain a yellow solid. Isolated yield:
45% (32 mg); mp: 184−186 °C; Rf (30% EtOAc-Pet. ether) = 0.4; IR
(Neat, cm−1): 3062, 2923, 2851, 2727, 1689, 1590, 1228, 1163, 1092;
1H NMR (CDCl3, 400 MHz): δ 10.03 (s, 1H), 8.18 (d, J = 8.1 Hz,
2H), 8.01 (d, J = 7.6 Hz, 2H), 7.91 (d, J = 8.1 Hz, 2H), 7.71−7.64
(m, 1H), 7.60 (t, J = 7.5 Hz, 2H), 7.56−7.46 (m, 2H), 7.35 (d, J = 7.9
Hz, 1H), 7.30 (d, J = 7.3 Hz, 1H), 6.94 (s, 1H); 13C{1H} NMR
(CDCl3, 100 MHz): δ 192.8, 145.5, 144.6, 140.1, 136.3, 135.9, 133.7,
132.4, 129.9, 129.5, 129.2, 127.4, 127.3, 127.1, 125.1, 120.4, 100.4;
HRMS (ESI) (m/z): Calcd for C21H15NO2SH [M + H]+: 346.0902,
found [M + H]+: 346.0905.
3-([1,1′-Biphenyl]-4-yl)-1-phenylbenzo[e][1,2]thiazine 1-oxide
(4ad). Prepared as shown in General Experimental Procedure for
Synthesizing 1,2-Benzothiazine Derivatives (B). Purified by flash
chromatography on 230−400 mesh silica gel using EtOAc:petroleum
ether (10:90 v/v) as eluent to obtain a yellow solid. Isolated yield:
46% (36 mg); mp:175−177 °C; Rf (30% EtOAc-Pet. ether) = 0.6; IR
1
(Neat, cm−1): 3060, 3028, 2923, 2852, 1582, 1219, 1112; H NMR
(CDCl3, 400 MHz): δ 8.09 (d, J = 8.0 Hz, 2H), 8.01 (d, J = 7.4 Hz,
2H), 7.72−7.61 (m, 5H), 7.60−7.53 (m, 2H), 7.52−7.40 (m, 4H),
7.39−7.29 (m, 2H), 7.29−7.17 (m, 1H), 6.86 (s, 1H); 13C{1H} NMR
(CDCl3, 100 MHz): δ 146.9, 141.6, 140.8, 140.6, 137.8, 136.6, 133.5,
132.2, 129.5, 129.1, 128.9, 127.5, 127.2, 127.2, 127.0, 126.4, 125.1,
119.8, 98.3; HRMS (ESI) (m/z): Calcd for C26H19NOSH [M + H]+:
394.1266, found [M + H]+: 394.1265.
3-(4-Fluorophenyl)-1-phenylbenzo[e][1,2]thiazine 1-oxide (4ae).
Prepared as shown in General Experimental Procedure for Synthesiz-
ing 1,2-Benzothiazine Derivatives (B). Purified by flash chromatog-
raphy on 230−400 mesh silica gel using EtOAc:petroleum ether (3:97
v/v) as eluent to obtain a yellow solid. Isolated yield: 43% (28 mg);
mp: 135−137 °C; Rf (20% EtOAc-Pet. ether) = 0.7; IR (Neat, cm−1):
(4-(1-Oxido-1-phenylbenzo[e][1,2]thiazin-3-yl)phenyl)ethanone
(4aj). Prepared as shown in General Experimental Procedure for
Synthesizing 1,2-Benzothiazine Derivatives (B). Purified by flash
chromatography on 230−400 mesh silica gel using EtOAc:petroleum
ether (10:90 v/v) as eluent to obtain a yellow solid. Isolated yield:
58% (38 mg); mp: 167−169 °C; Rf (30% EtOAc-Pet. ether) = 0.4; IR
1
3065, 2924, 2851, 1588, 1341, 1221, 1112; H NMR (CDCl3, 400
MHz): δ 7.99 (t, J = 7.3 Hz, 4H), 7.66 (t, J = 7.3 Hz, 1H), 7.59 (t, J =
7.5 Hz, 2H), 7.50 (t, J = 7.6 Hz, 1H), 7.43 (d, J = 7.9 Hz, 1H), 7.32
(d, J = 8.0 Hz, 1H), 7.22 (d, J = 7.3 Hz, 1H), 7.09 (t, J = 8.7 Hz, 2H),
1
(Neat, cm−1): 3062, 3012, 2922, 1679, 1595, 1267, 1221, 1112; H
6.75 (s, 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 163.4 (JC−F
=
NMR (CDCl3, 400 MHz): δ 8.10 (d, J = 8.3 Hz, 2H), 8.00 (t, J = 5.7
Hz, 4H), 7.67 (t, J = 7.2 Hz, 1H), 7.60 (t, J = 7.6 Hz, 2H), 7.56−7.43
(m, 2H), 7.34 (d, J = 7.9 Hz, 1H), 7.30−7.25 (m, 1H), 6.91 (s, 1H),
2.62 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 198.0, 145.7,
143.3, 140.1, 136.9, 136.0, 133.7, 132.4, 129.5, 129.2, 128.6, 127.3,
127.1, 126.7, 125.0, 120.2, 99.9, 26.9; HRMS (ESI) (m/z): Calcd for
C22H17NO2SNa [M + Na]+: 382.0878, found [M + Na]+: 382.0880.
3-Methyl-1-phenylbenzo[e][1,2]thiazine 1-oxide (4ak). Prepared
as shown in General Experimental Procedure for Synthesizing 1,2-
Benzothiazine Derivatives (B). Purified by flash chromatography on
230−400 mesh silica gel using EtOAc:petroleum ether (5:95 v/v) as
eluent to obtain a yellow solid. Isolated yield: 28% (27 mg); mp:
127−129 °C; Rf (30% EtOAc-Pet. ether) = 0.5; IR (Neat, cm−1):
3075, 2951, 1590, 1595, 1219, 1101; 1H NMR (CDCl3, 400 MHz): δ
8.07−7.84 (m, 2H), 7.63 (dd, J = 8.3, 6.3 Hz, 1H), 7.56 (t, J = 7.4 Hz,
2H), 7.45−7.40 (m, 1H), 7.26 (dd, J = 6.8, 3.7 Hz, 2H), 7.16 (t, J =
7.6 Hz, 1H), 6.11 (s, 1H), 2.32 (s, 3H); 13C{1H} NMR (CDCl3, 100
MHz): δ 148.5, 140.5, 136.8, 133.4, 132.2, 129.3, 129.1,125.8, 125.6,
125.02, 118.3, 99.3, 25.6; HRMS (ESI) (m/z): Calcd for
C15H13NOSH [M + H]+: 256.0796, found [M + H]+: 256.0798.
248.39 Hz), 146.3, 140.5, 136.6, 133.6, 132.3, 129.5, 129.1, 128.6,
128.5, 127.0, 126.5, 125.1, 119.7, 115.5, 115.2, 98.0; 19F NMR
(CDCl3, 377 MHz): δ 113.15; 19F NMR (CDCl3, 377 MHz): δ
−103.98, −105.59; HRMS (ESI) (m/z): Calcd for C20H14FNOSH
[M + H]+: 336.0858, found [M + H]+: 336.0855.
3-(4-Chlorophenyl)-1-phenylbenzo[e][1,2]thiazine 1-oxide (4af).
Prepared as shown in General Experimental Procedure for Synthesiz-
ing 1,2-Benzothiazine Derivatives (B). Purified by flash chromatog-
raphy on 230−400 mesh silica gel using EtOAc:petroleum ether (3:97
v/v) as eluent to obtain yellow a solid. Isolated yield: 26% (18 mg);
mp:172−174 °C; Rf (20% EtOAc-Pet. ether) = 0.7; IR (Neat, cm−1):
3060, 2961, 2867, 1584, 1220, 1113; 1H NMR (CDCl3, 400 MHz): δ
7.99 (d, J = 7.5 Hz, 2H), 7.94 (d, J = 8.5 Hz, 2H), 7.65 (t, J = 7.3 Hz,
1H), 7.59 (t, J = 7.5 Hz, 2H), 7.50 (t, J = 7.4 Hz, 1H), 7.44 (d, J = 7.9
Hz, 1H), 7.37 (d, J = 8.5 Hz, 2H), 7.32 (d, J = 8.0 Hz, 1H), 7.28−
7.20 (m, 1H), 6.79 (s, 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ
146.0, 140.3, 137.4, 136.4, 134.8, 133.6, 132.3, 129.5, 129.2, 128.6,
128.0, 127.1, 126.7, 125.1, 119.9, 98.4; HRMS (ESI) (m/z): Calcd for
C20H14ClNOSH [M + H]+: 352.0563, found [M + H]+: 352.0563.
4-(1-Oxido-1-phenylbenzo[e][1,2]thiazin-3-yl)benzonitrile (4ag).
Prepared as shown in General Experimental Procedure for Synthesiz-
ing 1,2-Benzothiazine Derivatives (B). Purified by flash chromatog-
raphy on 230−400 mesh silica gel using EtOAc:petroleum ether (5:95
v/v) as eluent to obtain a yellow solid. Isolated yield: 42% (28 mg);
mp: 154−156 °C; Rf (30% EtOAc-Pet. ether) = 0.6; IR (Neat, cm−1):
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.9b00743.
1
3063, 2922, 2225, 1590, 1471, 1220, 1112; H NMR (CDCl3, 400
Optimization data, 1H and 13C NMR spectral data of all
compounds, and X-ray crystallography data (PDF)
MHz): δ 8.11 (d, J = 8.4 Hz, 2H), 8.00 (d, J = 7.9 Hz, 2H), 7.75−7.65
(m, 3H), 7.61 (dd, J = 7.9, 7.2 Hz, 2H), 7.57−7.51 (m, 1H), 7.48 (d,
J = 8.0 Hz, 1H), 7.40−7.28 (m, 2H), 6.89 (s, 1H); 13C{1H} NMR
(CDCl3, 100 MHz): δ 144.9, 143.2, 140.0, 135.8, 133.8, 132.5, 132.3,
129.5, 129.3, 127.5, 127.4, 127.1, 125.1, 120.4, 112.0, 100.3; HRMS
(ESI) (m/z): Calcd for C21H14N2OSNa [M + Na]+: 365.0725, found
[M + Na]+: 365.0725.
Crystallographic information for compound 4ai (CIF)
AUTHOR INFORMATION
■
Corresponding Author
3-(4-Nitrophenyl)-1-phenylbenzo[e][1,2]thiazine 1-oxide (4ah).
Prepared as shown in General Experimental Procedure for Synthesiz-
ing 1,2-Benzothiazine Derivatives (B). Purified by flash chromatog-
raphy on 230−400 mesh silica gel using EtOAc:petroleum ether
(15:85 v/v) as eluent to obtain a yellow solid. Isolated yield: 51% (51
mg); mp: 232−234 °C; Rf (30% EtOAc-Pet. ether) = 0.6; IR (Neat,
*E-mail: prabhu@iisc.ac.in.
ORCID
Vinayak Hanchate: 0000-0003-0786-2060
Nachimuthu Muniraj: 0000-0003-4728-6141
Kandikere Ramaiah Prabhu: 0000-0002-8342-1534
1
cm−1): 3066, 292, 2851, 1588, 1515, 1341, 1221, 1112; H NMR
(CDCl3, 400 MHz): δ 8.26 (d, J = 7.2 Hz, 2H), 8.17 (d, J = 7.0 Hz,
2H), 8.01 (d, J = 6.4 Hz, 2H), 7.66 (dd, J = 23.3, 6.1 Hz, 3H), 7.59−
7.45 (m, 2H), 7.34 (s, 2H), 6.95 (s, 1H).; 13C{1H} NMR (CDCl3,
Notes
The authors declare no competing financial interest.
G
DOI: 10.1021/acs.joc.9b00743
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
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ACKNOWLEDGMENTS
■
This work was supported by SERB (EMR/2016/006358),
New-Delhi, Indian Institute of Science, and R. L. Fine Chem.
We thank Dr. A. R. Ramesha (R. L. Fine Chem) for useful
discussion. V.H. thanks CSIR and N.M. thanks UGC, New-
Delhi for fellowships.
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