Palladium-Catalyzed ortho-Benzoylation of Sulfonamides through C?H Activation: Expedient Synthesis of Cyclic N-Sulfonyl Ketimines

Article abstract of DOI:10.1002/adsc.201900989

The ortho-carbonylation of sulfonylarenes by non-hazardous aryl aldehydes as a carbonyl precursor was reported. In this method, the sulfonamide group serves as a directing group for C?H activation in the presence of a Pd catalyst under ligand-free conditions. The scope of this strategy has been extended to the one-pot two-step synthesis of cyclic N-sulfonyl ketimines under mild reaction conditions. Our approach could be considered as an alternative by circumventing the use of highly reactive organolithium or Grignard reagents to access a wide range of biologically potent cyclic N-sulfonyl ketimines. (Figure presented.).

Full text of DOI:10.1002/adsc.201900989

Title: Palladium-catalyzed ortho-benzoylation of sulfonamides through
C-H activation: Expedient synthesis of cyclic N-sulfonyl ketimines
Authors: Subhadra Ojha and Niranjan Panda
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201900989
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10.1002/adsc.201900989
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Palladium-Catalyzed ortho-Benzoylation of Sulfonamides through C–H
Activation: Expedient Synthesis of Cyclic N-Sulfonyl Ketimines
Subhadra Ojhaa and Niranjan Pandaa*
a
Department of Chemistry, National Institute of Technology Rourkela, Odisha 769008, India
Email: npanda@nitrkl.ac.in; niranjanpanda@gmail.com
ORCID: Niranjan Panda (0000-0002-7431-8826)
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. The ortho-carbonylation of sulfonylarenes by non-
hazardous arylaldehydes as a carbonyl precursor is reported.
In this method the sulfonamide group serves as the directing
group for C–H activation in the presence of a Pd catalyst
under ligand-free conditions. The scope of this strategy has
been extended to the one-pot two-step synthesis of cyclic N-
sulfonyl ketimines under mild reaction conditions.
Our approach could be considered as an alternative by
circumventing the use of highly reactive organolithium or
Grignard reagents to access a wide range of biologically
potent cyclic N-sulfonyl ketimines.
Keywords: ortho-carbonylation; C–H activation; arene
sulfonamide; aryl aldehyde; cyclic N-sulfonyl ketimines
H carbonylation reaction to synthesize saccharine
Introduction
derivatives
using
expensive
diisopropyl
azodicarboxylate (DIAD) as carbonyl surrogate.
Recently, Sundararaju[8b] et al. employed a Co-
catalyzed two-chambered tandem reaction pathway
for the incorporation of a carbonyl group between N–
H and ortho-C–H bonds of arenesulfonamides having
an 8-aminoquinoline directing group. Although above
methods are proficient for ortho-C–H carbonylation,
the use of gaseous carbon monoxide as a carbonyl
precursor is indeed technically challenging. On the
other hand, with the growing demand for sustainable
Owing to its atom and step economy, transition-metal
(TM) catalyzed C–H activation/functionalization
reactions have stood out as a powerful and versatile
method for the construction of C–C and C–X bonds.
Since the pioneering work of Fujiwara[1] and Murai,[2]
a vast number of innovative developments have been
made in this field. Activation of electronically
deficient aromatic C–H bonds are traditionally more
difficult than activation of electron-rich aromatic C–H
bonds. Nevertheless, introduction of directing groups
(DGs)[3] involving nitrogen and oxygen atoms (e.g.,
pyridyl, amino, azo, amido, thio, hydroxy, carbonyl,
ester, aldehyde, and carboxyl groups) facilitates such
C–H activation by enhancing the catalytic efficiency
of the transition metal through chelation.
chemical
synthesis,
direct
catalytic
C–H
carbonylation of electronically deficient aromatic ring
by employing non-hazardous and less expensive
acylating reagent under mild reaction conditions is
often intriguing.[9] In this context, it occurred to us
that the commercially available carbaldehyde could
serve as a reliable handle for C–H carbonylation
reaction. Though the N-acylation of sulfonamide
using aldehyde has already been delineated;[10] to the
best of our knowledge,[5,8] sulfonamide directed
ortho-carbonylation using carbaldehyde precursor has
remained elusive in the literature. In continuation of
our current research on TM-catalyzed cross-coupling
reactions,[11] we became interested to develop an
efficient method for ortho-carbonylation of
sulfonamides through C–H bond activation. Herein,
we report the Pd-catalyzed dehydrogenative coupling
of N-methoxy sulfonamides with aryl aldehydes to
produce o-keto sulfonamides. Besides, the tandem
ortho-carbonylation of sulfonamides (ArSO2NH2) and
Being an ubiquitous motif in numerous
pharmaceuticals and biologically potent molecules,[4]
a great deal of attention has been paid to C–H
functionalization of sulfonylarenes. In particular, C–
H
olefination and arylation reactions of
sulfonylarenes with amide,[5] acid[6] and imine[7]
functionalities have been reported extensively. In
contrast, direct carbonylation of sulfonylarenes to
ortho-keto sulfonylarenes is relatively less explored.
In 2011, ligand (i.e., Ac-Leu-OH) mediated Pd-
catalyzed ortho-carbonylation of N-aryl sulfonamides
using carbon monoxide as the carbonyl source was
reported by Yu and co-workers (Scheme 1).[5b]
Daugulis and co-workers[8a] developed an interesting
Co-catalyzed protocol for aminoquinoline-directed C–
1
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10.1002/adsc.201900989
Advanced Synthesis & Catalysis
subsequent intramolecular annulation to afford cyclic mixture) only in trace amount. We anticipated that,
the presence of an electron-rich substituent at the
nitrogen atom may chelate the TM[20] effectively, and
thus, the carbonylation would be facilitated.
Gratifyingly, when N-methoxy-4-methylbenzene-
sulfonamide (2a) and benzaldehyde (1a) were treated
under similar reaction conditions in 1,4-dioxane for
16 h, the desired benzoylated product 3a was isolated
in 41% yield.
N‐sulfonyl ketimines was also performed. Evidently,
the cyclic N‐sulfonyl ketimines are privileged
structural motifs that show a broad range of biological
activities.[12] These have also found applications in
organic synthesis, as building blocks,[13] chiral
auxiliaries,[14] and directing groups for C–H
functionalization.[15] Furthermore, cyclic N‐sulfonyl
ketimines serve as a versatile synthon to access a
myriad of S- and N-containing molecules.[16] As such,
the methods to obtain cyclic N‐sulfonyl ketimines
mostly involve the reaction of organolithium
compound/Grignard reagent with saccharin or
pseudosaccharin chloride;[17] and the cyclization of
benzophenone with chlorosulfonyl isocyanate.[18] We
were unaware of any report in the literature in which
the cyclic N‐sulfonyl ketimines have been synthesized
directly from the readily available arenesulfonamides
and aryl aldehydes.
Scheme 2. ortho-Carbonylation of sulfonamides
O
O
O
O
Pd(OAc)2 (10 mol%)
TBHP (2 equiv)
S
O
S
R
R
N
H
N
H
+
H
Ph
1,4-dioxane, 100 °C
16 h
Me
COPh
Me
3a, R = OMe (41%)
O
HO
R =
Me
OMe
CH3
N
N
S6
2a
S5
S3
S4
S1
S2
Inspired by these results, we screened different
oxidants, solvents, reaction temperatures, and
additives in the presence of Pd(OAc)2 (10 mol%)
catalyst (Table 1). Notably, when 2a was treated with
1a in the presence of TBHP for 16 h at room
temperature in 1,4-dioxane, no reaction occurred with
the recovery of starting material (Table 1, entry 1).
However, with the increase in reaction temperature to
Scheme
1.
C–H
activation/functionalization
of
sulfonylarenes
Previous work
O
S
O
O
O
O
O
S
R
C6F5
NAc
S
NAc
N
H
O
R
O
CO2Et
ref. 5g
S
ref. 5a
[Pd]
CO2Et
[
N
C6F5
ref. 5b
R
]
h
h
R
[
]
]
d
50°C,
the
desired
2-benzoyl-N-methoxy-4-
P
O
[
O
O
S
O
O
ref. 5b
C
methylbenzenesulfonamide (3a) was produced in
52% yield (Table 1, entry 2) with remaining
unreacted starting material. Further rise of reaction
temperature to 90°C gave 3a in 64% yield with the
recovery of starting material 20% (Table 1, entry 4).
However, at 120°C, 25% of 3a was isolated with the
appearance of several unwanted spots in TLC from
the decomposition of the product (entry 6). The
optimum yield of 68% was also obtained even when
the reaction mixture [TBHP (2 equiv), Pd(OAc)2 (10
mol%) in dioxane] was heated at 100 °C for 15 min
(entry 16). However, by increasing the reaction time,
the yield of 3a was subsided due to the formation of
several uncharacterized byproducts (entries 5, 14 &
15). The yield of the 3a was also not improved
appreciably by increasing the concentration of
catalyst (20 mol%, 69% yield) or oxidant (4 equiv.).
Moreover, the reaction did not proceed in the absence
of oxidant (e.g., TBHP). Use of other solvents such as
DMSO, toluene, DCE, CH3CN, THF, t-BuOH could
not improve the yield (entries 7-12) with an exception
to DME, which delivered 3a in comparable yield
(entries 13, 16 &18). Replacement of TBHP by other
oxidants such as H2O2, DTBP, BQ, K2S2O8, oxone,
AgOAc and Cu(OAc)2 did not afford the required
product 3a with complete recovery of 2a (for details:
see supporting information). Addition of 1 equiv. of
acids or bases [e.g., AcOH, PTSA, TFA, PivOH,
O
NHAc
Ar / Alk
ref. 5c-f
[Rh]
S
X
O
[
O
N
C
N
H
o
]
/
[
M
n
]
S
]
n
M
[
H
/
]
o
C
[
O
O
ArCHO
O
N
S
N
Pd(OAc)2
TBHP
ref. 8
N
R
O
O
O
R
O
S
S
NHOMe
ref. 5h-k
N
O
Ar
Ar
Present work
Results and Discussion
At the outset, the ortho-carbonylation reaction
was performed with the Pd-catalyzed coupling of
benzaldehyde (1a) and N-acylated sulfonamide, S1
(Scheme 2). Though, the TM-catalyzed C–H
functionalization of N-acyl arenesulfonamides[5b,5d,19]
is well precedent; unfortunately, for the present case
the benzoylation reaction under Pd-catalyzed
condition [Pd(OAc)2 (10 mol%), TBHP (2 equiv),
1,4-dioxane (2 mL) at 100°C for 16h] failed with
complete recovery of the starting material. The
required benzoylation reaction with other potential
DGs (e.g., S2-S5) under similar reaction conditions
was also unfruitful. Incidentally, when N-methyl
tosylamide (S6) was treated with benzaldehyde, the
corresponding o-benzoylated product was identified
(from TLC and 1H NMR of the crude reaction
2
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10.1002/adsc.201900989
Advanced Synthesis & Catalysis
t
NaOAc, BuOK, K2CO3] as additives inhibited the corresponding carbonylated products in poor yield
benzoylation and 2a was recovered. Among the tested (entries 20 and 21). Again, aliphatic aldehydes such
Pd-catalysts
[Pd(OAc)2, PdCl2,
Pd(PPh3)2Cl2, as hexanal and octanal were also found to be reactive
Pd(CH3CN)2Cl2, Pd(OCOCF3)2, Pd(PPh3)4, Pd(dba)2] to this Pd-catalysis to afford the o-carbonylated
Pd(OAc)2 enabled the ortho-benzoylation product 3a product 3s and 3t respectively (entries 18 & 19).
(see supporting information) in maximum yield.
However, when cinnamaldehyde was employed as a
carbonylating agent, the corresponding ortho-
carbonylated product 3u was not formed; rather, 3a
was isolated in 35% yield (entry 22). Probably, under
our reaction conditions, cinnamaldehyde underwent
Pd-catalyzed C-C cleavage[21] to benzaldehyde; which
could couples with 2a to afford 3a.
Table 1. Optimization of reaction conditions[a]
O
O
O
O
S
O
S
H
Pd(OAc)2 (10 mol%)
TBHP (2 equiv)
NHOMe
O
NHOMe
+
Ph
1a
H
Me
Me
Ph
2a
3a
Entry
temperature
time
solvent
yield(%)
Table 2. C–H benzoylation of N-methoxysulfonamides
O
O
O
O
S
1
2
3
4
5
6
7
8
rt
16 h
16 h
16 h
16 h
16 h
16 h
16 h
16 h
16 h
16 h
16 h
16 h
16 h
4 h
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
Toluene
DCE
CH3CN
DMSO
t-BuOH
THF
DME
1,4-dioxane
1,4-dioxane
DME
NR
52
59
64
41
25
32
28
NR
NR
NR
22
59
48
63
61
68
64
Pd(OAc)2 (10 mol%)
S
NHOMe
O
NHOMe
R1CHO
+
50 °C
65 °C
90°C
TBHP (2 equiv)
1,4-dioxane (2 mL)
100 °C, 15 min
R
H
R
R1
1, (0.75 mmol)
2 ( 0.5 mmol)
3
100 °C
120 °C
90 °C
90 °C
90 °C
90 °C
90 °C
90 °C
90 °C
100 °C
100 °C
100 °C
100 °C
100 °C
Entry Aldehyde
Sulfonamide
Product yield
(3) (%)b
3a 68
(1)
(2)
1
2
3
4
5
6
7
8
9
1a, R1 = C6H5-
2a, R = 4-CH3
2b, R = H
1a
1a
1a
1a
1a
1a
1a
1a
3b 66
3c 64
3d 48
3e ND
3f 66
9
2c, R = 4-Cl
2d, R = 4-Br
2e, R = 4-I
2f, R = 4-Et
2g, R = 4-OMe
10
11
12
13
14
15
16
17
18
3g 49
2h, R = 3,4-(OMe)2 3h 53
1h
1 h
2i, R = 3,4-(Me)2
2j, R = 3,4-(Cl)2
2k, R = -NO2
3i 57
3j 49
3k NR
3l 67
3m 63
3n 64
3o NR
3p 63
3q 57
3r 31
3s 29
3t 28
3u 33
3v 0(35)c
10 1a
11 1a
15 min 1,4-dioxane
15 min DME
12 1b, R1 = 4-MeC6H4- 2a
13 1c, R1 = 4-ClC6H4- 2a
14 1d, R1 = 4-BrC6H4- 2a
15 1e, R1 = 4-NO2C6H4-2a
16 1f, R1 = 4-FC6H4- 2a
17 1g, R1 = 2-BrC6H4- 2a
[a] Reaction conditions: 1a (40 mg, 0.37 mmol), 2a (50 mg,
0.25 mmol), Pd(OAc)2 (10 mol %), TBHP (70% in decane)
(2 equiv) in 2 mL of the solvent. rt: room temperature.
Having the optimized reaction conditions in hand, we
examined the substrate scope by varying the
substituents at the aryl group of sulfonamides (Table
2). Pd-catalyzed C–H functionalization of N-methoxy
sulfonamides having various substituents, such as -
Me, -Cl, -Br, -OMe, enabled the corresponding ortho-
benzoylated products in moderate yields (Table 2,
entries 1-10). Unfortunately, the Pd-catalyzed C–H
activation failed with N-methoxy-4-nitrobenzene-
sulfonamide (2k) with complete recovery of starting
material, probably due to ring deactivation by the
nitro group (Table 2, entry 11). Further, by extending
the substrate scope of the carbonylation reaction with
differently substituted aryl aldehydes gave the
corresponding benzoylated derivatives in moderate
yields (entries 12-21). Interestingly, the halogen-
substitutions in the aldehydes as well as sulfonamides
were compatible to the optimal reaction conditions
and exhibit the desired product in appreciable yield.
Notably, coupling of 2a with aryl aldehydes featuring
cyano- and ester group (e.g., 1j and 1k) resulted in the
18 1h, R1 = n-hexyl-
19 1i, R1 = n-octyl-
2a
2a
20 1j, R1 = 4-CNC6H4- 2a
21 1k, R1 = 4-CO2MeC6H4-2a
22 1l, R1 = Ph-CH=CH- 2a
[a] Reaction conditions: A mixture of 1 (0.75 mmol), 2 (0.5
mmol), Pd(OAc)2 (10 mol%), TBHP (1 mmol) in 1,4-
dioxane (2 mL) was heated at 100°C for 1 h. [b]Isolated
yield. c 3a was isolated in 35% yield.
To elucidate the reaction pathway, an H/D
exchange experiment was performed. Under the
standard reaction conditions, when N-methoxy-4-
methylbenzenesulfonamide (2a) was treated with 20
equiv. of D2O in the absence of benzaldehyde (1a),
low inclusion of deuterium (7% from 1H NMR) in the
aryl ring (i.e., of [D]-2a) was observed (Scheme 3a).
This result indicates that the initial cleavage of the
ortho C−H bond generates aryl−Pd intermediate
species and this is an irreversible process. Further,
kinetic isotope effects (KIE) experiment was
3
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10.1002/adsc.201900989
Advanced Synthesis & Catalysis
performed by reacting equivalent amounts of 2b and
[D]-2b with benzaldehyde under standard reaction
conditions (Scheme 3b). The resulting kH/kD (= 3.3)
suggests that the initial C–H activation step is the
rate-determining step in the overall transformation.
Scheme 4. Plausible reaction pathway
O
O
O
O
S
S
NHOMe
NHOMe
O
Me
2a
Me
Pd(OAc)2
Ph
3a
Scheme 3. Deuterium labelling experiment
AcOH
AcOH
a) Deuterium exchange experiment
O
O
O
O
O
O
S
O
O
O
O
NHOMe
S
S
S
S
NHOMe
NHOMe
NHOMe
NHOMe
IV
Pd(OAc)2 (10 mol%)
III
Pd
OAc
OAc
Me
Pd
O
Pd
O
D2O
2
+
Me
Me
Ac
TBHP (2 equiv)
1,4-dioxane (2 mL)
100 °C, 15 min
Me
H
O
Me
D(H)
I
2
Ph
Ph
O
Ac
(20 equiv)
III
[D]-2ab (90% recovery)
2a (0.5 mmol)
II
t-BuO
O
7% deuterium inclusion
H
Ph
Ph
O
b) Kinetic Isotope Effect (KIE)
t-BuOH
1a
O
O
O
O
S
S
NHOMe
NHOMe
An increase in reaction time to 4 h could not improve
the yield (58%). Unlike the former, decomposition
did not occur even on heating for 12 h. Interestingly,
by changing the solvent to DME, 5a was obtained in
optimum yield (70%) over a period of 12 h. Here, we
presumed that -SO2NH2 serves as a directing group
for the ortho-benzoylation of sulfonylarene and the
resulting intermediate undergoes intramolecular
annulation to afford the cyclic N-sulfonyl ketimines.
Notably, both the steps (i.e., ortho-benzoylation and
intramolecular annulation) occur sequentially and the
attempts to isolate the intermediate were unsuccessful.
To a side note, sulfonamide (-SO2NH2) directed C–H
activation/functionalization has not been reported yet.
To extend the scope of the reaction, a series of
differently substituted cyclic N-sulfonyl ketimines (5)
were synthesized following the same C–H activation
strategy (Scheme 5). Gratifyingly, a series of
sulfonamides with a range of substituents were
amenable to the reaction conditions and the respective
cyclic N-sulfonyl ketimines (5) were produced in
moderate yields. Although the coupling reactions of
sulfonamides featuring keto and ester functionalities
delivered the cyclic ketimines, similar reaction of
sulfonamides having CN and NO2 substituents failed.
Additionally, the 4-nitrobenzaldehyde also did not
couple under the optimized reaction conditions to
afford 5r with the recovery of 2a. Notably, the halo-
substitutions to the aryl ring of the sulfonamide as
well as the aryl ring of aldehyde were found to be
tolerant to the reaction conditions and the desired
ketimines were produced in appreciable yield. In
particular, the sustained bromo-functionality in the
resulting cyclic ketimines, e.g., 5d, 5q, 5s and 5u
allow for further cross-coupling reactions to be
performed on the products. On the other hand,
preparation of such derivatives by other means (i.e.,
with use of organolithium or Grignard reagent) is not
possible. Notably, the ortho-substituted aldehydes
afforded poor yield of ketimine (5s and 5t) probably
due to steric reason. Interestingly, when benzyl
O
O
2b (0.25 mmol)
Pd(OAc)2 (10 mol%)
Ph
3b (46%)
+
+
Ph
H
TBHP (2 equiv)
1,4-dioxane (2 mL)
100 °C, 15 min
D
D
1a (0.75 mmol)
O
O
O
O
D
D
S
D
D
S
D
NHOMe
O
NHOMe
D
Ph
D
kH / kD = 3.3
[D]-2b (0.25 mmol)
[D]-3b (14%)
In line with the above observation and earlier
literature precedence,[20] we proposed a mechanism
(Scheme 4) in which Pd(OAc)2 initially chelates to
the electronically rich –NHOMe group effectively and
induces ortho C–H activation through the formation
of cyclopalladated intermediate I[22] by releasing one
equivalent of AcOH. As addition of 1 equiv. of
radical inhibitor (i.e., TEMPO) to the optimized
reaction condition results in lower yield of 3a (12%),
we believed that the reaction follows a radical
pathway to afford the benzoylated product. From the
decomposition of TBHP, tBuO· radical thus generates
would react with the aldehyde to afford the reactive
benzoyl radical by hydrogen abstraction.[22f] It may be
hypothesized that the benzoyl radical would add to
the palladacycle I oxidatively with the formation of
putative intermediate II[22d] or III[22e]. Finally, by
reductive depalladation, the desired ortho-
benzoylated sulfonamide forms with the regeneration
of Pd(OAc)2 for subsequent catalytic cycle (Scheme
4).
Next, we became interested in exploiting the C–
H carbonylation of aryl sulfonamides (ArSO2NH2)
with an aim to achieve ortho-benzolylated
sulfonamide, which could undergo intramolecular
annulation to afford the biologically potent cyclic N-
sulfonyl ketimines. Pleasantly, when tosylamide (4a)
was treated with benzaldehyde (1a) under the similar
reaction conditions, cyclic N-sulfonyl ketimine 5a
was isolated directly in 58% yield over a period of 1 h.
4
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10.1002/adsc.201900989
Advanced Synthesis & Catalysis
sulfonamide was treated with aryl aldehyde, the C–H benzoylated product. Deuterium labeling experiment
benzoylation followed by annulation occurs at 100°C and KIE study indicates that the initial C–H activation
and the corresponding six-membered cyclic N- step is irreversible process and is also the rate
sulfonyl ketimines (6a & 6b) occurred.[23]
determining step. Additionally, this strategy has been
extended for the one-pot two-step synthesis of a wide
range of synthetically important cyclic N-sulfonyl
ketimines. Mild reaction conditions and the simple
experimental procedure for C–H activation make the
process interesting and could be a preferred route to
access cyclic N-sulfonyl ketimines over the reported
multistep approaches.
Scheme 5. Synthesis of cyclic N-sulfonyl ketimines [a]
O
O
O
O
O
O
S
S
S
NH2
NH2
Pd(OAc)2 (10 mol%)
N
R1CHO
+
O
H
TBHP (2 equiv)
DME (2 mL)
R
R
R
R1
R1
100 °C, 12 h
5
4 (0.5 mmol)
1 (0.75 mmol)
O
O
N
O
S
O
O
O
O
N
O
N
S
S
S
N
Me
Cl
Br
Experimental Section
5a, 70%
5b, 68%
5c, 64%
5d, 57%
O
O
O
O
N
O
O
N
O
O
S
N
General Experimental Information. All the solvents for
routine isolation of products and chromatography were
reagent grade. Column chromatography was performed
using silica gel (100−200 mesh) and mixture of ethyl
acetate−petroleum ether (60−80 °C) as eluent. Melting
points are uncorrected. FTIR spectrophotometer (IR
Affinity 1S W/L with quest ATR) was used to record the
MeO
MeO
S
S
S
N
Et
H3CO
I
5f, 74%
5g, 62%
5e, 0%
5h, 57%
Me
O
O
O
O
O
S
N
O
O
S
N
O
Cl
Me
Me
S
N
S
N
1
IR spectra. H NMR and 13C NMR spectra were recorded
O
Cl
Me
Me
Me
on 400 MHz (1H NMR) and 100 MHz (13C NMR)
spectrometers using CDCl3 as the solvent and TMS as the
Me
1
5i, 63%
5j, 55%
5k, 61%
5l, 40%
internal standard. The H NMR data are reported as the
chemical shift in parts per million, multiplicity (s, singlet; d,
doublet; t, triplet; q, quartet; m, multiplet), coupling
constant in hertz (Hz), and number of protons. High-
resolution mass spectra were obtained using a high-
resolution ESI-TOF mass spectrometer. The used
O
O
S
N
O
O
O
O
O
O
N
S
N
S
S
N
O
Me
Me
OMe
5m, 39%
F
Me
Cl
5n, 69%
aldehydes (1) are of commercial grade. N-methoxy
5o, 58%
5p, 59%
[24]
sulfonamides
(2) and sulfonamides[25] (4) are known
O
O
S
N
O
O
O
S
O
O
S
N
O
N
S
compounds and were prepared by following the similar
literature procedure.
N
Me
Me
Me
Br
Cl
General procedure for the synthesis of N-
methoxysulfonamides [24] (2)
Br
CN / NO2
5r,trace only
5q, 56%
5t, 41%
5s, 41%
To a stirred solution of arenesulfonyl chloride (1.05 mmol)
in DCM (5.0 ml), pyridine (2.0 equiv) was added slowly at
0°C. After 15 minutes, N-methoxyamine hydrochloride
(1.2 equiv) was added, and then the reaction mixture was
allowed to attain room temperature slowly. After 4h, the
reaction mixture was acidified with 2N HCl solution and
triturated with EtOAc (20 mL). The organic layer was
separated and washed with H2O, brine and dried over
anhydrous Na2SO4. The filtrate was evaporated under
reduced pressure and the corresponding pure N-methoxy
sulfonamide was obtained by recrystallization from ethanol.
O
O
O
O
N
S
S
N
Me
Me
Br
5v, 57%
5u, 54%
[a]Reaction conditions: Sulfonamide(0.5 mmol), aldehyde
(0.75 mmol), Pd(OAc)2 (10 mol%), TBHP (1 mmol) in
DME (2 mL) was heated at 100 °C for 12 h.
[25]
General procedure for the synthesis of sulfonamides
(4)
Conclusion
To a stirred solution of arylsulfonyl chloride (1.05 mmol)
in DCM (5.0 ml), pyridine (2.0 equiv) was added slowly at
0°C. After 15 minutes, 25% aqueous ammonia solution (4
equiv) was added, and then the reaction mixture was
allowed to attain room temperature slowly. After 4h, the
reaction mixture was acidified with 2N HCl solution and
triturated with EtOAc (20 mL). The organic layer was
separated and washed with H2O, brine and dried over
In summary, a simple method for the sulfonamide
directed ortho-carbonylation of arenes has been
developed. Non-hazardous arylaldehydes was
successfully employed as a carbonylating precursor in
the presence of Pd-catalyst. The reaction procedure is
very simple and does not require any ligand or
additive or inert atmosphere to enable the ortho-
5
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10.1002/adsc.201900989
Advanced Synthesis & Catalysis
anhydrous Na2SO4. The filtrate was evaporated under 3H), 2.35 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 143.6,
reduced pressure and the corresponding pure sulfonamide 137.9, 133.6, 130.2, 129.2, 126.0, 65.0, 20.0, 19.7.
was obtained by recrystallization from ethanol.
4-(Methoxycarbonyl)benzenesulfonamide. A mixture of
tosylamide (2a) (1gm, 0.58 mmol) and KMnO4 (2.0 equiv,
General procedure for the synthesis of 2-benzoyl-N-
methoxy-arylsulfonamide (3). To a mixture of aldehyde 1.17 mmol) in 10 ml H2O was heated at reflux for 12h.
(1, 0.75 mmol), N-methoxy sulfonamide (2, 0.5 mmol) and Then, the reaction mixture was cooled to 00C and few
Pd(OAc)2 (11 mg, 10 mol%) in 1,4-dioxane (2 mL), TBHP drops of conc. H2SO4 were added during which precipitate
(70% in decane) (1 mmol) was added dropwise keeping the was formed. The precipitate was filtered out, washed with
oil bath temperature 100°C. After 15 min, the reaction cold water (2 x 10 mL), dried on air and then recrystallized
mixture was cooled to room temperature and filtered over a from methanol to get 775 mg of
methyl 4-
short pad of celite. The filtrate was eluted with 3x 10 mL of sulfamoylbenzoic acid in 66% yield as a white solid, which
ethyl acetate. The combined organic layer was washed with was used as it is for the preparation of methyl 4-
dilute (10%) NaHCO3 solution (3 x 10 mL). Then the sulfamoylbenzoate without further purification. A solution
organic layer was dried over anhydrous Na2SO4 and of 4-sulfamoylbenzoic acid (700 mg, 3.48 mmol.) in dry
concentrated under reduced pressure. The crude reaction methanol (10mL) was refluxed in the presence of 10 drops
mixture was purified by column chromatography to afford of conc. H2SO4 for 12ꢀh. After completion of the reaction,
the o-benzoylated sulfonyl arenes (3).
the mixture was poured into ice cold water during which
precipitate was formed. The precipitate was filtered and
dried to give 666 mg of 4-(methoxycarbonyl)-
General procedure for the synthesis of cyclic N-sulfonyl
ketimines (5 & 6). To a mixture of aldehyde (1, 0.75 benzenesulfonamide in 89% yield as a white crystalline
mmol), sulfonamide (4, 0.5 mmol) and Pd(OAc)2 (11 mg, solid. M. P. 115°C; 1H NMR (400 MHZ, CDCl3): δ 8.13 (d,
10 mol%) in DME (2 mL), TBHP (70% in decane) (1 2H, J = 8.4 Hz), 7.97 (d, 2H, J = 8.0 Hz), 7.56 (s, 2H), 3.88
mmol) was added dropwise keeping the oil bath (s, 3H); 13C NMR (100 MHz, CDCl3): δ 170.5, 153.2,
temperature 100 °C. After 12 h, the reaction mixture was 137.5, 135.0, 131.2, 57.7.
cooled to room temperature and filtered over a short pad of
celite. The filtrate was eluted with 3x 10 mL of ethyl
acetate. The combined organic layer was washed with (3a). Following the general procedure, reaction of 1a and
2-Benzoyl-N-methoxy-4-methylbenzenesulfonamide
[24]
dilute (10%) NaHCO3 solution (3 x 10 mL). Then the 2a
gave 103 mg (68% yield) of 3a as a white solid.
organic layer was dried over anhydrous Na2SO4 and M.P.: 73-74 °C. IR: 3547, 3219, 3072, 2988, 2939, 1927,
concentrated under reduced pressure. The crude reaction 1662, 1591, 1382, 1320, 1151, 719, 544 cm-1.1H NMR (400
mixture was purified by column chromatography to afford MHZ, CDCl3): δ 8.23 (s, 1H), 8.09 (d, 1H, J = 8.4 Hz), 7.85
the desired cyclic N-sulfonyl ketimines (5). Six-membered (d, 2H, J = 7.6 Hz), 7.65 (d, 1H, 7.6 Hz), 7.50 (t, 3H, J =
cyclic N-sulfonyl ketimines were also prepared following 7.6 Hz), 7.24 (s, 1H), 3.86 (s, 3H), 2.47 (s, 1H); 13C NMR
the similar procedure with only change in reaction time (100 MHz, CDCl3): 197.6, 143.9, 138.2, 135.8, 134.2,
from 1h to 2h.
133.6, 132.8, 132.3, 130.8, 130.7, 130.1, 128.5, 128.4, 64.9,
21.5. HRMS (ESI) m/z [M+Na]+ calcd for C15H15NNaO4S+
328.0619; found 328.0614.
Synthesis
and
Characterization
4-Iodo-N-
methoxybenzenesulfonamide (2e). Following the general
procedure, the reaction of 4-iodo benzenesulfonylchloride 2-Benzoyl-N-methoxybenzenesulfonamide
(3b).
[24]
with N-methoxylamine hydrochloride gave 902 mg (87% Following the general procedure, reaction of 1a and 2b
1
yield) of 2e as a white solid. M.P. 95 °C; H NMR (400 gave 95 mg (66% yield) of 3b as a colorless gummy liquid.
MHZ, CDCl3): δ 7.92 (d, 2H, J = 8.4 Hz), 7.63 (d, 2H, J = IR: 2982, 2817, 2360, 2325, 1654, 1599, 1549, 1501, 1445,
1
8.4 Hz), 7.34 (s, 1H), 3.80 (s, 3H); 13C NMR (100 MHz, 1145, 998, 705, 614 cm-1. H NMR (400 MHZ, CDCl3): δ
CDCl3): δ138.4, 136.1, 129.8, 101.8, 65.2.
8.30 (s, 1H), 8.25-8.19 (m, 1H), 7.88-7.82 (m, 2H), 7.74-
7.66 (m, 2H), 7.68-7.62 (m, 1H), 7.54-7.43(m, 3H), 3.87 (s,
4-Ethyl-N-methoxybenzenesulfonamide (2f). Following 3H); 13C NMR (100 MHz, CDCl3): 197.5, 138.3, 135.9,
the general procedure, the reaction of 4-ethyl 135.8, 134.4, 132.7, 132.4, 130.8, 130.4, 129.6, 128.6, 65.0.
benzenesulfonylchloride
with
N-methoxylamine HRMS (ESI) m/z [M+H]+
calcd for C14H14NO4S+
hydrochloride gave 970 mg (92% yield) of 2f as a white 292.0644; found 292.0639.
1
solid. M. P. 75°C; H NMR (400 MHZ, CDCl3): δ 7.85 (d,
2H, J = 8.4 Hz), 7.38 (d, 2H, J = 8.4 Hz), 7.23 (s, 1H), 3.80 2-Benzoyl-4-chloro-N-methoxybenzenesulfonamide (3c).
(s, 3H), 2.75 (q, 2H, J = 7.6 Hz), 1.28 (t, 3H, J = 7.6 Hz); Following the general procedure, from the reaction of 1a
[24]
13C NMR (100 MHz, CDCl3): δ 151.0, 133.6, 128.6, 128.6, and 2c,
3c was isolated in 64% yield (104 mg) as a
65.0, 28.9, 15.0.
white solid. M.P.: 88-89 °C. IR: 3743, 3645, 3219, 2974,
2925, 2855, 2360, 2318, 1662, 1605, 1543, 1445, 1382,
1
N-Methoxy-3,4-dimethylbenzenesulfonamide
(2i). 1348, 1278, 1159, 816,705,558 cm-1. H NMR (400 MHZ,
Following the general procedure, the reaction of 3,4- CDCl3): δ 8.16 (d, 1H, J = 3.2 Hz), 8.13 (s, 1H), 7.85 (d,
dimethylbenzenesulfonylchloride with N-methoxylamine 2H, J = 8.4 Hz), 7.73-7.64 (m, 2H), 7.57-7.49 (m, 2H),
hydrochloride gave 938 mg ( 89% yield) of 2i as a white 7.42 (d, 1H, J = 2 Hz), 3.86 (s, 3H); 13C NMR (100 MHz,
1
solid. M. P.: 72 °C; H NMR (400 MHZ, CDCl3): δ 7.69 (s, CDCl3): 195.9, 139.7, 139.6, 135.0, 134.6, 134.1, 133.6,
1H), 7.67 (d, 1H, J = 8.0 Hz), 7.34-7.23 (m, 2H), 3.79 (s, 130.6, 130.2, 129.3, 128.7, 65.0. HRMS (ESI) m/z
6
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10.1002/adsc.201900989
Advanced Synthesis & Catalysis
[M+Na]+ calcd for C14H12ClNNaO4S+ 348.0073; found 1H NMR (400 MHZ, CDCl3): δ 8.37 (s, 1H), 7.97 (s, 1H),
348.0068.
7.85 (d, 2H, J = 7.6 Hz), 7.65 (t, 1H, J = 7.6 Hz), 7.50 (t,
2H, J = 7.6 Hz), 7.21 (s, 1H), 3.87 (s, 3H), 2.44 (s, 3H),
2-Benzoyl-4-bromo-N-methoxybenzenesulfonamide (3d). 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3): 197.7, 142.4,
Following the general procedure, from the reaction of 1a 139.8, 136.2, 135.7, 134.1, 133.3, 133.1, 131.2, 130.8,
and 2d,[24] 3d was isolated in 48% yield (88 mg) as a white 128.5, 65.0, 19.9, 19.8. HRMS (ESI) m/z [M+H]+ calcd for
crystalline solid. M.P.: 120-121 °C. IR: 2928, 2855, 1732, C16H18NO4S+ 320.0957; found 320.0954.
1668, 1577, 1459, 1396, 1340, 1284, 1165, 1047, 1012,
725, 572 cm-1. 1H NMR (400 MHZ, CDCl3): δ 8.16 (s, 1H),
2-Benzoyl-4,5-dichloro-N-methoxybenzenesulfonamide
8.06 (d, 1H, J = 8.4 Hz), 7.88-7.81 (m, 3H), 7.69 (t, 1H, J = (3j). Following the general procedure, reaction of 1a and
7.6 Hz), 7.58 (s, 1H), 7.53 (t, 2H, J = 8.0 Hz), 3.86 (s, 3H); 2j[24] gave the desired compound in 49% yield (88 mg) as a
13C NMR (100 MHz, CDCl3): 195.9, 139.8, 135.2, 134.8, white solid. M.P.: 104 °C. IR: 3205, 3100, 2982, 2932,
133.7, 133.4, 132.2, 130.8, 128.6, 128.1, 65.1. HRMS 2855, 2346, 1654, 1599, 1543, 1452, 1389, 1348, 1278,
(ESI) m/z [M+H]+ calcd for C14H13BrNO4S+ 369.9749; 1165, 956, 894, 725, 565, 516 cm-1. .1H NMR (400 MHZ,
found 369.9745.
CDCl3): δ 8.28 (s, 1H), 8.25 (s, 1H), 7.84 (d, 2H, J = 8.4
Hz), 7.71 (t, 1H, J = 7.6 Hz), 7.58-7.50 (m, 3H), 3.88 (s,
2-Benzoyl-4-ethyl-N-methoxybenzenesulfonamide (3f). 3H); 13C NMR (100 MHz, CDCl3): 195.2, 137.9, 137.4,
Following the general procedure, from the reaction of 2f 135.6, 135.3, 135.1, 134.9, 134.1, 131.2, 130.7, 128.9, 65.2.
and 1a, 3f was isolated in 66% yield (104 mg) as a white HRMS (ESI) m/z [M-NHOMe]+ calcd for C13H7Cl2O3S+
solid. M.P.: 76-78 °C. IR: 3743, 3651, 2974, 2925, 2855, 312.9493; found 312.9507.
2367, 2318, 1710, 1585, 1515, 1438, 1292, 1151, 852, 725,
650, 544, 502 cm-1. 1H NMR (400 MHZ, CDCl3): δ 8.24 (S, N-Methoxy-4-methyl-2-(4-methylbenzoyl)benzenesulfo-
1H), 8.12 (d, 1H, J = 8.0 Hz), 7.86 (d, 2H, J = 8.4 Hz), 7.66 namide (3l). Following the general procedure, reaction of
(t, 1H, J = 7.6 Hz), 7.51 (t, 3H, J = 8.0 Hz), 7.26 (s, 1H), 1b and 2a gave 107 mg of 3l as a white solid (67% yield).
3.87 (s, 3H), 2.76 (q, 2H, 7.6 Hz) 1.27 (t, 3H, J = 7.6 Hz); M.P.: 126-127 °C. IR: 3012, 2909, 2312, 1678, 1612, 1503,
13C NMR (100 MHz, CDCl3): 197.7, 149.9, 138.4, 135.9, 1498, 1352, 1298, 1232, 1056, 922 cm-1.1H NMR (400
134.3, 133.1, 132.5, 130.8, 129.6, 129.2, 128.6, 65.0, 28.7, MHZ, CDCl3): δ 8.25 (s, 1H), 8.08 (d, 1H, J = 8 Hz), 7.75
14.9. HRMS (ESI) m/z [M+Na]+ calcd for C16H17NNaO4S+ (d, 2H, J = 8.4 Hz), 7.48 (d, 1H, J = 8.0 Hz), 7.30 (d, 2H, J
342.0776; found 342.0770.
= 8.0 Hz), 7.24 (s, 1H), 3.85 (s, 3H), 2.46 (s, 3H), 2.45 (s,
3H); 13C NMR (100 MHz, CDCl3): 197.2, 145.5, 143.8,
(3g). 138.4, 133.3, 132.3, 130.9, 130.6, 130.1, 129.3, 64.9, 21.8,
2-Benzoyl-4,N-dimethoxybenzenesulfomide
Following the general procedure, the reaction of 1a and 21.5. HRMS (ESI) m/z [M+Na]+ calcd for C16H17NNaO4S+
2g,[24] gave 79 mg of 3g as a white solid in 49% yield. 342.0776; found 342.0770.
M.P.: 85-87 °C. IR: 37365, 3645, 3219, 2967, 2939, 2897,
2360, 2325, 1647, 1577, 1459, 1389, 1334, 1242, 1165,
2-(4-Chlorobenzoyl)-N-methoxy-4-methylbenzenesulfo-
1061, 1026, 928, 852, 705, 551 cm-1. H NMR (400 MHZ, namide (3m). Following the general procedure, reaction of
CDCl3): δ 8.14 (d, 1H, J = 8.8 Hz), 8.11 (s, 1H), 7.87 (d, 1c and 2a gave 107 mg of 3m as a white solid (63% yield).
2H, J = 7.6 Hz), 7.66 (t, 1H, J = 7.6 Hz), 7.50 (t, 2H, J = M.P.: 107 °C. IR: 3212, 2982, 2932, 2367, 2324, 1647,
7.6 Hz), 7.13(d, 1H, J = 8.8 Hz), 6.92 (s, 1H), 3.89 (s, 3H), 1525, 1389, 1340, 1292, 1173, 1089, 949, 725, 530 cm-1.
3.86 (s, 3H); 13C NMR (100 MHz, CDCl3): 197.0, 162.7, 1H NMR (400 MHZ, CDCl3): δ 8.13(s, 1H), 8.09 (d, 1H, J =
140.2, 135.6, 134.6, 134.3, 130.8, 128.6, 127.1, 116.1, 8.0 Hz), 7.79 (d, 2H, J = 8.4 Hz), 7.53-7.45 (m, 3H), 7.21
114.1, 64.9, 55.9. (ESI) m/z [M+H]+ calcd for (s, 1H), 3.86 (s, 3H), 2.48 (s, 3H); 13C NMR (100 MHz,
1
C15H16NO5S+ 322.0749; found 322.0749.
CDCl3): 196.4, 144.0, 140.9, 137.8, 134.1, 132.8, 132.4,
132.0, 131.0, 129.7, 129.0, 65.0, 21.5. HRMS (ESI) m/z
(3h). [M+Na]+ calcd for C15H14ClNNaO4S+ 362.0230; found
2-Benzoyl-4,5,N-trimethoxybenzenesulfonamide
Following the general procedure, reaction of 1a and 2h
[24]
362.0224.
gave 94 mg of 3h as a gummy liquid in 53% yield. IR:
2982, 2905, 2360, 2325, 1654, 1599, 1501, 1452, 1340,
2-(4-Bromobenzoyl)-N-methoxy-4-methylbenzenesulfo-
1
1256, 1207, 1165, 1068, 1019, 866, 711 cm-1. H NMR namide (3n). Following the general procedure, reaction of
(400 MHZ, CDCl3): δ 8.38 (s, 1H), 7.85 (d, 2H, J = 8 Hz), 1d and 2a gave 122 mg of 3n as a white crystalline solid
7.64 (d, 2H, J = 8.8 Hz), 7.50 (t, 2H, J = 7.6 Hz), 6.88 (s, (64% yield). M.P.: 83 °C. IR: 2982, 2905, 2367, 2318,
1H), 4.05 (s, 3H), 3.86 (s, 3H), 3.86 (s, 3H); 13C NMR (100 1654, 1585, 1508, 1466, 1340, 1256, 122, 1165, 1068,
MHz, CDCl3): 196.8, 151.5, 149.6, 136.0, 134.1, 131.5, 1012, 705, 537, cm-1. H NMR (400 MHZ, CDCl3): δ 8.12
1
130.6, 128.5, 114.6, 112.4, 64.9, 56.4, 56.3. HRMS (ESI) (s, 1H), 8.09 (d, 1H, J = 8.4 Hz), 7.71 (d, 2H, J = 8.8 Hz),
m/z [M+Na]+ calcd for C16H17NNaO6S+ 374.0674; found 7.65 (d, 2H, J = 8.4 Hz), 7.50 (d, 1H, J = 8.0 Hz), 7.21(s,
374.0669.
1H), 3.86 (s, 3H), 2.47 (s, 3H); 13C NMR (100 MHz,
CDCl3): 196.5, 144.0, 137.7, 134.5, 132.8, 132.3, 132.0,
131.9, 130.9, 129.7, 129.7, 64.9, 21.4. HRMS (ESI) m/z
2-Benzoyl-4,5-dimethyl-N-methoxybenzenesulfonamide
(3i). Following the general procedure, reaction of 1a and 2i [M+H]+ calcd for C15H15BrNO4S+ 383.9905; found
gave 88 mg of 3i (57% yield) as a white solid. M.P.:108- 383.9901.
109 °C. IR: 3212, 3065, 2982, 2925, 2318, 1654, 1591,
1452, 1389, 1340, 1278, 1173, 1019, 886, 719, 586 cm-1.
7
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10.1002/adsc.201900989
Advanced Synthesis & Catalysis
129.5, 117.7, 117.3, 65.1, 21.5. HRMS (ESI) m/z [M+H]+
2-(4-Fluorobenzoyl)-N-methoxy-4-methylbenzenesulfo-
namide (3p). Following the general procedure, reaction of calcd for C16H15N2O4S+ 331.0757; found 331.0753.
1f and 2a gave 102 mg of 3p as a white crystalline solid
(63% yield). M.P.: 132-133°C. IR: 3212, 3107, 3079, 2982,
4-(2-Methoxysulfamoyl-5-methylbenzoyl)benzoic acid
2919, 2855, 1654, 1585, 1501, 1466, 1389, 1278, 1229, methyl ester (3u). Following the general procedure,
1
1159, 1047, 942, 705, 544 cm-1. H NMR (400 MHZ, reaction of 1k and 2a gave 60 mg of 3u as a white solid
CDCl3): δ 8.15(s, 1H), 8.09 (d, 1H, J = 8Hz), 8.01-7.85 (m, (33% yield). M.P.: 77-79°C. IR: 3219, 2932, 2849, 1724,
2H), 7.50 (d, 1H, J = 8.0 Hz), 7.19 (q, 2H, J = 9.4 Hz), 3.86 1662, 1563, 1501, 1438, 1410, 1348, 1278, 1165, 1109,
1
(s, 3H), 2.48 (s, 3H); 13C NMR (100 MHz, CDCl3): 196.1, 956, 830, 747, 565 cm-1. H NMR (400 MHz, CDCl3): δ
167.7, 165.2, 144.1, 138.0, 133.6, 133.5, 132.8, 132.4, 8.18-8.07 (m, 4H), 7.90 (d, 2H, J = 8.4 Hz), 7.52 (d, 1H, J
132.3, 130.9, 129.8, 116.0, 115.8, 65.0, 21.5. HRMS (ESI) = 8 Hz), 7.21 (s, 1H), 3.98 (s, 3H), 3.86 (s, 3H), 2.47 (s,
m/z [M+H]+ calcd for C15H15FNO4S+ 324.0706; found 3H); 13C NMR (100 MHz, CDCl3): 197.0, 166.0, 144.1,
324.0694.
139.1, 137.8, 134.8, 133.0, 132.5, 131.2, 130.6, 129.9,
129.7, 65.0, 52.6, 21.5. HRMS (ESI) m/z [M+H]+ calcd for
C17H18NO6S+ 364.0855; found 364.0859.
2-(2-Bromobenzoyl)-N-methoxy-4-methylbenzenesulfo-
namide (3q). Following the general procedure, reaction of
1g and 2a gave 109 mg of 3q as a white crystalline solid
5-Methyl-3-phenyl-benzo[d]isothiazole
1,1-dioxide[26]
(57% yield). M.P.: 103-104°C. IR: 3219, 2982, 2919, 2849, (5a). Following the general procedure, the reaction of
2360, 2325, 1662, 1563, 1459, 1424, 1396, 1334, 1306, tosylamide [25a] with benzaldehyde gave 90 mg (70 % yield)
1264, 1207, 1165, 1033, 922, 725, 530 cm-1.1H NMR (400 of 5a as a white solid. M.P.: 84-86 °C. IR: 3365, 3253,
MHZ, CDCl3): δ 8.12-8.06 (m, 2H), 8.02-7.97 (m, 1H), 2982, 2919, 2367, 2318, 1718, 1599, 1529, 1445, 1389,
1
7.81-7.71 (m, 2H), 7.52 (d, 1H, J = 8.0 Hz), 7.39 (t, 1H, J = 1298, 1151, 900, 816, 656, 530 cm-1. H NMR (400 MHZ,
8.0 Hz), 7.21 (s, 1H), 3.86 (s, 3H), 2.49 (s, 3 H). 13C NMR CDCl3): δ 7.97 (d, 2H, J = 7.2 Hz), 7.90 (d, 1H, J = 8.0 Hz),
(100 MHz, CDCl3): δ 196.3, 144.2, 137.6, 137.1, 133.3, 7.75-7.56 (m, 5H), 2.54 (s, 3H); 13C NMR (100 MHz,
132.9, 132.5, 131.2, 130.2, 129.8, 129.4, 123.0, 65.0, 21.6. CDCl3): δ 171.2, 144.9, 138.2, 133.9, 133.3, 131.0, 130.5,
HRMS (ESI) m/z [M+H]+ calcd for C15H15BrNO4S+ 129.4, 129.2, 127.1, 122.8, 21.9.
383.9905; found 383.9901.
3-Phenyl-benzo[d]isothiazole
1,1-dioxide[26]
(5b).
Following the general procedure, the reaction of benzene
2-Hexanoyl-N-methoxy-4-methylbenzenesulfonamide
(3r). Following the general procedure, reaction of 1h and sulfonamide with benzaldehyde gave 82 mg (68 % yield)
2a gave 57 mg of 3r as a gummy liquid (31% yield). IR: of 5b as a white solid. M.P.: 124-126 °C. IR: 3065, 2974,
2960, 2932, 2863, 2367, 2318, 1696, 1557, 1459, 1340, 2360,1746, 1599, 1529, 1445, 1326, 1165, 958, 783, 733,
1165, 1089, 1012, 824, 677, 565 cm-1. 1H NMR (400 MHZ, 696, 663, 530 cm-1.1H NMR (400 MHZ, CDCl3): δ 8.04 (d,
CDCl3): δ 8.31 (s, 1H), 8.01 (d, 1H, J = 8 Hz), 7.46-7.39 1H, J = 6.8 Hz), 7.99 (d, 2H, J = 8.4 Hz), 7.93 (d, 1H, J =
(m, 1H), 7.36 (s, 1H), 3.82 (s, 3H), 2.94 (t, 2H, J = 7.6 Hz), 7.6 Hz), 7.85-7.68 (m, 3H), 7.63 (t, 2H, J = 7.6 Hz); 13C
2.50 (d, 3H, J = 4.4 Hz), 1.74 (t, 2H, J = 7.6 Hz), 1.41-1.33 NMR (100 MHz, CDCl3): δ 171.1, 141.1, 133.6, 133.4,
(m, 4H), 0.92 (t, 3H, J = 7.2 Hz); 13C NMR (100 MHz, 133.4, 130.5, 130.4, 129.5, 129.2, 126.6, 123.1.
CDCl3): δ 206.9, 144.6, 140.1, 132.4, 131.5, 130.9, 128.4,
64.9, 42.5, 31.1, 23.3, 22.4, 21.5, 13.9. HRMS (ESI) m/z 5-Chloro-3-phenyl-benzo[d]isothiazole 1,1-dioxide[18b]
[M+H]+ calcd for C14H22NO4S+ 300.1269; found 300.1264.
(5c). Following the general procedure, the reaction of 4-
chloro phenyl sulfonamide[25a] with benzaldehyde gave 89
mg (64% yield) of 5c as a white solid. M.P.: 129 °C. IR:
3635, 3645, 3072, 2982, 2911, 2360, 1704, 1591, 1522,
N-Methoxy-4-methyl-2-octanoyl-benzenesulfonamide
(3s). Following the general procedure, reaction of 1i and
2a gave 47 mg of 3s as a colourless gummy liquid (47 mg,
1
1438, 1326, 1165, 1075, 970, 816, 802, 683, 544 cm-1. H
NMR (400 MHZ, CDCl3): δ 7.97 (d, 3H, J = 8 Hz), 7.87 (s,
1H), 7.81-7.71 (m, 2H), 7.66 (t, 2H, J = 7.6 Hz); 13C NMR
(100 MHz, CDCl3): δ 169.8, 140.2, 139.3, 133.7, 133.2,
132.4, 129.9, 129.4, 126.7, 124.0.
1
29% yield). H NMR (400 MHZ, CDCl3) δ: 8.01 (d, 1H, J
= 8 Hz), 7.43 (d, 1H, J = 8 Hz), 7.36 (s, 1H), 3.82 (s, 3H),
2.94 (t, 2H, J = 7.2 Hz), 1.77-1.68 (m, 3H), 1.40-1.25 (m,
9H), 0.90 (t, 3H, J = 6.4 Hz); 13C NMR (100 MHz, CDCl3):
206.9, 144.5, 140.2, 132.4, 131.6, 130.9, 128.4, 64.9, 42.5,
31.6, 29.0, 28.9, 23.6, 22.6, 21.5, 14.0. HRMS (ESI) m/z
[M+H]+ calcd for C16H27NO4S+ 329.1661; found 329.1658.
5-Bromo-3-phenyl benzo[d]isothiazole 1,1-dioxide (5d).
Following the general procedure, the reaction 4-bromo
benzenesulfonamide[25a] with benzaldehyde gave 91 mg
(57 % yield) of 5d as a white solid. M. P.: 133 °C. IR: 3735,
3645, 3072, 2982, 2360, 2325, 1591, 1522, 1320, 1165,
1068, 963, 789, 537 cm-1.1H NMR (400 MHZ, CDCl3): δ
8.03 (s, 1H), 8.00-7.87 (m, 4H), 7.75 (t, 1H, J = 7.6 Hz),
7.66 (t, 2H, J = 7.6 Hz); 13C NMR (100 MHz, CDCl3): δ
169.8, 139.8, 136.2, 133.7, 132.4, 129.9, 129.6, 129.4,
128.3, 124.1. HRMS (ESI) m/z [M+H]+ calcd for
C13H9BrNO2S+ 321.9537; found 321.9542.
2-(4-Cyano-benzoyl)-N-methoxy-4-methylbenzenesulfo-
namide (3t). Following the general procedure, reaction of
1j and 2a gave 47 mg of 3t as a white crystalline solid
(28% yield). M.P.: 121-123 °C. IR: 3219, 2974, 2367, 2318,
2241, 1662, 1535, 1396, 1278, 1173, 1054, 949, 963, 852,
725, 530 cm-1. 1H NMR (400 MHZ, CDCl3): δ 8.10 (d, 1H, J
= 8.0 Hz), 8.00 (s, 1H), 7.94 (d, 2H, J = 8.4 Hz), 7.81 (d,
2H, J = 8.4 Hz), 7.54 (d, 1H, J = 8.4Hz), 7.18 (s, 1H), 3.86
(s, 3H), 2.48 (s, 3H); 13C NMR (100 MHz, CDCl3): 196.2,
144.4, 139.0, 137.3, 133.0, 132.6, 132.4, 131.4, 130.9,
8
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Advanced Synthesis & Catalysis
5-Ethyl-3-phenyl-benzo[d]isothiazole-1, 1-dioxide (5f). reaction of 2,4-dimethy benzenesulfonamide[25d] with
Following the general procedure, the reaction of 4-ethyl benzaldehyde gave 82 mg (61 % yield) of 5k as a white
benzenesulfonamide[25b] with benzaldehyde gave 99 mg solid. M.P.:123 °C. IR: 3735, 3651, 2974, 2919, 2855,
(74 % yield) of 5f as a white solid. M.P.: 106-107 °C. IR: 2360, 2325, 1591, 1515, 1438, 1292, 1145, 844, 725, 656
1
3645, 3065, 2967, 2919, 2877, 2360, 2325, 1599, 1535, cm-1. H NMR (400 MHZ, CDCl3): δ 7.95 (d, 2H, J = 7.6
1445, 1312, 1145, 970, 852, 796, 733, 649, 537, 446 cm-1. Hz), 7.70 (t, 1H, J = 7.6 Hz), 7.62 (t, 2H, J = 7.6 Hz), 7.46
1H NMR (400 MHZ, CDCl3): δ 8.00-7.90 (m, 3H), 7.76- (s, 1H), 7.35 (s, 1H), 2.74 (s, 3H), 2.48 (s, 3H); 13C NMR
7.59 (m, 5H), 2.83 (q, 2H, J = 7.6 Hz), 1.31(t, 3H, J = 7.6 (100 MHz, CDCl3): δ 171.3, 144.6, 136.7, 136.0, 135.5,
Hz); 13C NMR (100 MHz, CDCl3): δ 171.2, 151.2, 138.4, 133.0, 131.2, 130.8, 129.4, 129.1, 124.6, 21.6, 17.2.
133.3, 132.9, 131.1, 130.5, 129.5, 129.2, 126.0, 123.0, 29.1,
15.5. HRMS (ESI) m/z [M+H]+ calcd for C15H14NO2S+
272.0739; found 272.0739.
1-(1,1-Dioxo-3-phenyl-1H-1λ6-benzo[d]isothiazol-5-
yl)ethanone (5l). Following the general procedure, the
reaction of 4-acetyl benzenesulfonamide[25e] with
benzaldehyde gave 56 mg (40% yield) of 5l as a white
[26]
5-Methoxy-3-phenyl-benzo[d]isothiazole-1,1-dioxide
(5g). Following the general procedure, the reaction of 4- solid. M.P.: 143-144 °C. IR: 3735, 3651, 3072, 2982, 2367,
[25a]
methoxybenzenesulfonamide
with benzaldehyde gave 2325, 1690, 1522, 1312, 1242, 1151, 838, 739, 697, 642,
84 mg (62% yield) of 5g as a white solid. M.P.: 104-106 °C. 593 cm-1. H NMR (400 MHZ, CDCl3): δ 8.47 (s, 1H), 8.35
1
IR: 3086, 2974, 2925, 2841, 2360, 2325, 1585, 1306, 1165, (d, 1H, J = 8.0 Hz), 8.13 (d, 1H, J = 7.6 Hz), 8.02 (d, 2H, J
1
1123, 697, 558, 509 cm-1. H NMR (400 MHZ, CDCl3): δ = 7.6 Hz), 7.76 (t, 1H, J = 7.2 Hz), 7.67 (t, 2H, J = 7.6 Hz),
7.99-7.90 (m, 3H), 7.70 (d, 1H, J = 7.2 Hz), 7.63 (t, 2H, J = 2.72 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 195.4, 170.3,
7.6 Hz), 7.32 (s, 1H), 7.25-7.20 (m, 1H), 3.94 (s, 3H); 13C 144.3, 141.5, 133.8, 133.4, 131.4, 130.0, 129.5, 129.4,
NMR (100 MHz, CDCl3): δ 170.2, 164.0, 133.0, 133.0, 125.9, 123.4, 27.0. HRMS (ESI) m/z [M+H]+ calcd for
132.8, 130.6, 129.3, 129.1, 124.2, 117.4, 112.7, 56.2.
C15H12NO3S+ 286.0533; found 286.0533.
5,6-Dimethoxy-3-phenyl-benzo[d]isothiazole-1,1-
1,1-Dioxo-3-phenyl-1H-1λ6-benzo[d]isothiazole-5-
dioxide[27] (5h). Following the general procedure, the carboxylic acid methyl ester (5m). Following the general
[25c]
reaction of 3,4-dimethoxy benzenesulfonamide
with procedure, the reaction of 4-(methoxycarbonyl)-
benzaldehyde gave 86 mg (57 % yield) of 5h as a white benzenesulfonic acid 5m was prepared in 39 % yield (59
solid. M.P.: 222-223 °C. IR: 2925, 2849, 2360, 2318, 1732, mg) of as a white solid. M.P.: 108 °C. IR: 3743, 3648,
1577, 1494, 1312, 1145, 1040, 922, 775, 691, 488 cm-1. 1H 3093, 2988, 2960, 2360, 2318, 1718, 1599, 1535, 1438,
NMR (400 MHZ, CDCl3): δ 7.95 (d, 2H, J = 7.6 Hz), 7.71 (t, 1340, 1284, 1179, 963, 767, 691 cm-1. 1H NMR (400 MHZ,
1H, J = 7.6 Hz), 7.63 (t, 2H, J = 7.6 Hz), 7.50 (s, 1H), 7.22 CDCl3): δ 8.55 (s, 1H), 8.48 (d, 1H, J = 8.0 Hz), 8.11 (d,
(s, 1 H), 4.07 (s, 3H), 3.98 (s, 3H); 13C NMR (100 MHz, 1H, J = 8.0 Hz), 8.03 (d, 2H, J = 7.2 Hz), 7.76 (t, 1H, J =
CDCl3): δ 171.2, 153.7, 152.9, 134.8, 133.1, 130.7, 129.2, 7.6 Hz), 7.67 (t, 2H, J = 7.6 Hz), 4.02 (s, 3H); 13C NMR
123.5, 107.7, 105.4, 56.8, 56.6.
(100 MHz, CDCl3): δ 170.3, 164.6, 144.5, 135.4, 134.6,
133.7, 131.1, 130.0, 129.6, 129.4, 127.5, 123.1, 53.1.
HRMS (ESI) m/z [M+H]+ calcd for C15H12NO4S+
5,6-Dimethyl-3-phenyl-benzo[d]isothiazole 1,1-dioxide
(5i). Following the general procedure, the reaction of 3,4- 302.0487; found 302.0489.
dimethy benzenesulfonamide[25a] with benzaldehyde gave
86 mg (63% yield) of 5i as a white solid. M.P.: 179-180 °C. 5-Methyl-3-p-tolyl-benzo[d]isothiazole-1,1-dioxide[29]
IR: 3735, 3561, 2982, 2367, 2318, 1724, 1522, 1320, 1151, (5n). Following the general procedure, the reaction of
928, 586 cm-1.1H NMR (400 MHZ, CDCl3): δ 7.97 (d, 2H, J tosylamide with 4-methylbenzaldehyde gave 94 mg (69 %
= 7.6 Hz), 7.78 (s, 1H), 7.70 (t, 1H, J = 7.6 Hz), 7.66-7.58 yield) of 5n as a white solid. M.P.: 191 °C. IR: 2982, 2919,
(m, 3H), 2.46 (s, 3H), 2.43 (s, 3H); 13C NMR (100 MHz, 2353, 1920, 1746, 1605, 1508, 1542, 1298, 1151, 1061,
CDCl3): δ 171.2, 143.6, 143.2, 138.9, 133.1, 130.7, 129.4, 963, 866, 810, 747, 677, 544 cm-1.1H NMR (400 MHZ,
129.1, 128.7, 127.2, 124.0, 20.6, 20.4. HRMS (ESI) m/z CDCl3), δ: 7.89 (d, 3H, J = 8 Hz), 7.69 (s, 1H), 7.58 (d, 1H,
[M+H]+calcd for C15H14NO2S+ 272.0740; found 272.0739.
J = 7.6 Hz), 7.43 (d, 2H, J = 7.6 Hz), 2.54 (s, 3H), 2.51 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 170.9, 144.7, 144.4,
138.4, 133.8, 131.2, 129.9, 129.6, 127.8, 127.0, 122.8, 21.8,
5,6-Dichloro-3-phenyl-benzo[d]isothiazole 1,1-doxide
(5j). Following the general procedure, the reaction of 3,4- 21.8.
dichloro benzenesulfonamide[25a] with benzaldehyde gave
85 mg (55% yield) of 5j as a white solid. M.P.: 233 °C. IR:
3-(4-Chlorophenyl)-5-methyl-benzo[d]isothiazole-1,1-
3107, 1585, 1515, 1326, 1151, 1068, 977, 866, 796, 691, dioxide[29] (5o). Following the general procedure, the
579 cm-1. 1H NMR (400 MHZ, CDCl3): δ 8.11 (s, 1H), 8.00- reaction of tosylamide with 4-chlorobenzaldehyde gave 85
7.93 (m, 3H), 7.76 (t, 1H, J = 7.4 Hz), 7.67 (t, 2H, J = 7.6 mg (58 % yield) of 5o as a white solid. M.P.: 223 °C. IR:
Hz); 13C NMR (100 MHz, CDCl3): δ 169.2, 140.3, 139.1, 3086, 2982, 2367, 2318, 1718, 1590, 1515, 1403, 1326,
138.6, 133.9, 130.0, 129.6, 129.5, 129.4, 127.9, 124.9. 1151, 970, 844, 663, 579 cm-1. 1H NMR (400 MHZ,
HRMS (ESI) m/z [M+H]+calcd for C13H8Cl2NO2S+ CDCl3): δ 7.92 (t, 3H, J = 8.8 Hz), 7.65 - 7.58 (m, 4H),
311.9647; found 311.9655.
2.55 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 170.0, 145.0,
139.9, 138.3, 134.1, 130.8, 130.7, 129.6, 128.9, 126.7,
123.0, 21.9.
5,7-Dimethyl-3-phenyl-benzo[d]isothiazole
1,1-
dioxide[28] (5k). Following the general procedure, the
9
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10.1002/adsc.201900989
Advanced Synthesis & Catalysis
122.9, 21.7. HRMS (ESI) m/z [M+H]+ calcd for
3-(4-Fluorophenyl)-5-methyl-benzo[d]isothiazole-1,1-
dioxide (5p). Following the general procedure, the reaction C14H11BrNO2S+ 335.9688; found 335.9695.
of tosylamide with 4-fluorobenzaldehyde gave 82 mg
(59 % yield) of 5p as a white solid. M.P.: 187 °C. IR: 3079,
5-Methyl-3-naphthalen-2-yl-benzo[d]isothiazole-1,1-
1927, 1591, 1494, 1410, 1306, 1229, 1151, 977, 844, 767, dioxide (5v). Following the general procedure, the reaction
663, 544, 488 cm-1.1H NMR (400 MHZ, CDCl3): δ 8.02 (t, of tosylamide with 2-naphthaldehyde gave 83 mg (54%
2H, J = 6.4 Hz), 7.91 (d, 1H, J = 7.6 Hz), 7.65 (s, 1H), 7.60 yield) of 5v as a white solid. M.P.:133-134 °C. IR: 3058,
(d, 1H, J = 7.6 Hz), 7.33 (t, 2H, J = 8.4 Hz), 2.56 (s, 3H); 2974, 2924, 2360, 2311, 1738, 1535, 1452, 1320, 1151,
13C NMR (100 MHz, CDCl3): δ 169.9, 167.1, 164.5, 144.9, 942, 803, 551 cm-1 1H NMR (400 MHZ, CDCl3): δ 8.23 (d,
.
138.4, 134.0, 132.0, 131.9, 130.8, 126.8, 126.7, 126.7, 1H, J = 7.6 Hz), 8.14 (d, 1H, J = 8.0 Hz), 8.0 (d, 1H, J =
122.9, 116.7, 116.5, 21.9. HRMS (ESI) m/z [M+H]+calcd 8.0 Hz), 7.95 (d, 1H, J = 8.0 Hz), 7.83 (d, 1H, J = 7.2 Hz),
for C14H11FNO2S+ 276.0495; found 276.0497.
7.68 (d, 1H, J = 8 Hz), 7.67-7.56 (m, 3H), 7.30 (d, 1H, J =
10.8 Hz), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3): 171.7,
145.0, 137.7, 134.1, 133.9, 132.6, 132.4, 130.6, 128.7,
3-(4-Bromophenyl)-5-methyl-benzo[d]isothiazole-1,1-
dioxide (5q). Following the general procedure, the reaction 128.1, 127.8, 127.3, 127.1, 125.2, 124.6, 122.6, 21.7.
of tosylamide with 4-bromobenzaldehyde gave 94 mg HRMS (ESI) m/z [M+H]+ calcd for C18H14NO2S+
(56 % yield) of 5q as a white solid. M.P.: 227 °C. IR: 3086, 308.0745; found 308.0748.
2974, 2925, 2841, 2367, 2318, 1577, 1522, 1396, 1320,
1159, 977, 830, 656, 537 cm-1. 1H NMR (400 MHz,
4-(4-Chlorophenyl)-1H-isothiochromene-2,2-dioxide
CDCl3): δ 7.91 (d, 1H, J = 7.6 Hz), 7.86 (d, 2H, J = 8.4 Hz), (6a). Following the general procedure, the reaction of
7.78 (d, 2H, J = 8.4 Hz), 7.61 (d, 2H, J = 9.6 Hz), 2.55 (s, benzylsulfonamide with 4-chlorobenzaldehyde gave 51 mg
3H). 13C NMR (100 MHz, CDCl3): δ 170.1, 114.9, 138.4, (36% yield) of 6a as a white solid. M.P.: 200-201 °C. IR:
134.1, 132.6, 130.8, 130.7, 129.4, 128.4, 126.7, 123.0, 21.8. 3072, 2974, 2905, 2855, 2360, 1585, 1529, 1396, 1320,
HRMS (ESI) m/z [M+H]+ calcd for C14H11BrNO2S+ 1137, 1089, 1012, 949, 830, 719, 544, 468 cm-1. 1H NMR
335.9694; found 335.9696.
(400 MHZ, CDCl3): δ 7.75 (d, 2H, J = 8.8 Hz), 7.67 (t, 1H,
J = 7.6 Hz), 7.61-7.48 (m, 4H), 7.47 (d, 1H, J = 7.6 Hz),
4.52 (s, 2H); 13C NMR (100 MHz, CDCl3): 176.1, 139.2,
3-(2-Bromophenyl)-5-methyl-benzo[d]isothiazole-1,1-
dioxide (5s). Following the general procedure, the reaction 134.0, 133.8, 132.7, 132.4, 131.8, 130.7, 129.3, 129.0,
of tosylamide with 2-bromobenzaldehyde gave 69 mg 125.5, 48.7. HRMS (ESI) m/z [M+H]+ calcd for
(41% yield) of 5s as a white solid. M.P.:116-118 °C. IR: C14H11ClNO2S+ 292.0199; found 292.0196.
3079, 2967, 2919, 2855, 2367, 2388, 1710, 1522, 1417,
1
1320, 1173, 810, 753, 691, 544 cm-1. H NMR (400 MHZ,
4-(4-Fluorophenyl)-1H-isothiochromene-2,2-dioxide
CDCl3): δ 8.10 (s, 1H), 7.90 (t, 2H, J = 7.2 Hz), 7.84 (d, 1H, (6b). Following the general procedure, the reaction of
J = 8.0 Hz), 7.61 (d, 2H, J = 5.6 Hz), 7.52 (t, 1H, J = 8.0 benylsulfonamide with 4-fluorobenzaldehyde have 53 mg
Hz), 2.56 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 169.8, (40 % yield) of 6b as a white solid. M.P.: 185 °C. IR: 3749,
145.1, 138.2, 136.1, 134.2, 132.3, 132.1, 130.7, 130.6, 3596, 3079, 2967, 2919, 2855, 2360, 2318, 1704, 1591,
1
127.9, 126.7, 123.3, 123.0, 21.9. HRMS (ESI) m/z [M+H]+ 1515, 1389, 1312, 1229, 1117, 949, 789, 537 cm-1. H
calcd for C14H11BrNO2S+ 335.9688; found 335.9696.
NMR (400 MHZ, CDCl3): δ 7.86-7.79 (m, 2H), 7.67 (t, 1H,
J = 7.6 Hz), 7.58(d, 1H, J = 7.6Hz), 7.53 (d, 1H, J = 7.6
Hz), 7.47 (d, 1H, J = 7.6 Hz), 7.24 (t, 2H, J = 8.0 Hz), 4.51
3-(2-Chlorophenyl)-5-methyl-benzo[d]isothiazole-1,1-
dioxide (5t). Following the general procedure, the reaction (s, 2H); 13C NMR (100 MHz, CDCl3): 176.1, 166.7, 164.2,
of tosylamide with 4-chlorobenzaldehyde gave 60 mg 134.0, 132.9, 132.9, 132.8, 132.5, 131.6, 131.5, 130.7,
(41% yield) of 5t as a white solid. M.P.: 82-84 °C. IR: 129.2, 125.6, 116.0, 115.8, 48.7. HRMS (ESI) m/z [M+H]+
3219, 2982, 2919, 2855, 1742, 1662, 1599, 1543, 1374, calcd for C14H11FNO2S+ 276.0495; found 276.0500.
1180, 1054, 977, 747, 551cm-1. 1H NMR (400 MHZ,
CDCl3): δ 7.88 (d, 1H, J = 8.0 Hz), 7.63-7.54 (m, 4H),
7.56-7.46 (m, 1H), 7.24 (s, 1H), 2.48 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 171.1, 145.1, 137.0, 134.2, 132.7,
Acknowledgements
Authors thank SERB, (No. EMR/2017/002827), and CSIR (Ref. No.
02(0278)/16/EMR-II), Government of India for financial support.
132.5, 131.3, 130.7, 130.3, 129.9, 127.4, 127.0, 122.6, 21.7.
HRMS (ESI) m/z [M+H]+ calcd for C14H11ClNO2S+
292.0199; found 292.0193.
References
3-(3-Bromophenyl)-5-methyl-benzo[d]isothiazole-1,1-
dioxide (5u). Following the general procedure, the reaction
of tosylamide with 3-bromobenzaldehyde gave 90 mg
(54% yield) of 5u as a white solid. M.P.:119 °C. IR: 3065,
2974, 2919, 2849, 1535, 1417, 1320, 1165, 880, 810, 656,
544, 502 cm-1.1H NMR (400 MHZ, CDCl3): δ 8.11 (s, 1H),
7.91 (t, 2H, J = 8.4 Hz), 7.84 (d, 1H, J = 7.6 Hz), 7.61 (d,
[1] a) I. Moritani; Y. Fujiwara, Tetrahedron Lett. 1967, 8,
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C
NMR (100 MHz, CDCl3): δ 169.5, 144.9, 138.6, 135.9,
134.0, 132.5, 132.1, 130.6, 130.5, 127.8, 126.5, 123.3,
10
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10.1002/adsc.201900989
Advanced Synthesis & Catalysis
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Advanced Synthesis & Catalysis
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Advanced Synthesis & Catalysis
FULL PAPER
Palladium-catalyzed
ortho-benzoylation
of
sulfonamides through C–H activation: Expedient
synthesis of cyclic N-sulfonyl ketimines
Adv. Synth. Catal. Year, Volume, Page – Page
Subhadra Ojha and Niranjan Panda*
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