Functionalization of Alkynes and Alkenes Using a Cascade Reaction Approach: Synthesis of β-Keto Sulfones under Metal-free Conditions

Article abstract of DOI:10.1021/acs.joc.9b02779

Here, we are reporting a multicomponent cascade reaction approach for the synthesis of β-keto sulfones by exploiting differential reactivity pattern of substrates under open-atmosphere and metal-free conditions. The coupling partners are aryldiazonium salts, unsaturated compounds, and DABSO. The optimized conditions worked well with both alkenes and alkynes. Moreover, the reaction also works with metabisulfite for the source of sulfone. The controlled liquid chromatography-mass spectrometry and ¹⁸O-labelled experiments suggested that air is a source of the incoming oxygen atom of the keto group of β-keto sulfones.

Full text of DOI:10.1021/acs.joc.9b02779

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Article
Functionalization of alkynes and alkenes using cascade reaction
approach: Synthesis of #-keto sulfones under metal-free conditions
Mukesh Kumar, Riyaz Ahmed, Maninder Singh, Shweta
Sharma, Thanusha Thatikonda, and Parvinder Pal Singh
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02779 • Publication Date (Web): 12 Dec 2019
Downloaded from pubs.acs.org on December 17, 2019
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Functionalization of alkynes and alkenes using cascade reaction approach:
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Synthesis of β-keto sulfones under metal-free conditions
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Mukesh Kumar,a Riyaz Ahmed,a Maninder Singh,a Shweta Sharma,a Thanusha Thatikonda,b and
Parvinder Pal Singh*a
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aMedicinal Chemistry Division, Academy of Scientific and Innovative Research, CSIR-Indian Institute
of Integrative Medicine, Canal Road, Jammu-180001, India
bDepartment Of Chemistry, CSIR-National Chemical Laboratory, Pune-411008, India.
* E-mail: ppsingh@iiim.ac.in
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N2BF4
R
6
7
8
9
R1
R2
"SO2"
O
S
O
O
S
O
Air, MeCN
R1
R1 = Ph
R1
R1 = Ph
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R
O
O
R
25 examples
8 examples
"SO2" =
*Metal-free *Multi-component *Cascade reactions *Open atmosphere
DABCO(SO2)2 and Na2S2O5
Abstract:
Here, we are reporting a multi-component cascade reaction approach for the synthesis of β-keto
sulfones by exploiting differential reactivity pattern of substrates under open-atmosphere and metal-free
conditions. The coupling partners are aryldiazonium salts, unsaturated compounds, and DABSO. The
optimized conditions worked well with both alkenes and alkynes. Moreover, the reaction also works
with metabisulfite for the source of sulfone. The controlled LC-MS and 18O-labelled experiments
suggested that air is a source of incoming oxygen atom of keto group of β-keto sulfones.
.
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Introduction:
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The β-Keto sulfones represents an important core in the area of synthetic and medicinal
chemistry because of unique reactivity.1 β-Keto sulfones also possessed biological activity in the
number of disease areas such as anti-infective,2 anti-fungal3 and inhibitor of 11-HSD1 (Hydroxysteroid
dehydrogenase type I) inhibitor,4 bacterial quorum sensing antagonists.5 Considering the synthetic and
biological potential of β-keto sulfones, number of approaches has been developed. Initially, it was
generated by the i) oxidation of β-keto sulfides,6 ii) coupling between α-halo ketones7 or α-tosyloxy
ketones8 and sodium sulfonates, iii) coupling between diazo sulfones and aldehydes,9 and iv) coupling
between (methylsulfonyl)arenes and acyl chlorides. All these methods required pre-functionalized
coupling partners. In the last decade, with the advancement in the radical chemistry, the synthesis of β-
ketosulfones was also achieved by the reaction between phenylsulfonyl radical and alkenes/alkynes,
which in turn was generated from diverse sulfonyl containing precursors such as phenyl sulfonyl
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halides,10 sodium phenyl sulfinates,10a,
phenylsulfinic acids,12 phenylsulfonyl hydrazides,10a,
benzenesulfonothioate13e under diverse reaction conditions ranging from photo-catalyst to metal to
metal-free (Fig 1). The generation of phenylsulfonyl radicals using sulfone surrogate and aryl radicals,
providing an effective alternative approach and is being exploited for diverse coupling reactions.14 In
this direction, Jie Wu made an attempt and was successful to coupled phenylsulfonyl radical (generated
from aryldiazonium salts and DABSO) with functionalized alkenes (silyl enol ethers) and alkynes (3-
arylpropiolic acids) (Fig 1).15a-c On the other hand, considering the readily availability of
phenylacetylenes and styrenes, their use in this transformation would be more valuable and diverse,
however, no such report is available. Considering our interest in radical chemistry,16 we started an
investigation toward the search of suitable conditions for the cascade reactions to functionalized
alkynes and alkenes using aryldiazonium tetrafluoroborates and DABSO as coupling partners. Here, we
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are reporting an approach for the synthesis of β-keto sulfones through the cascade reaction between
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aryldiazonium tetrafluoroborates, DABSO and alkynes/alkenes under metal-free conditions.
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8
Previous reports: Using PhenylSulfonyl-containing precursors
O
S
O
9
R4
R2
Photo-catalysts or Metal or
Metal-free
X
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R2
O
+
R5 R3
R3
R1
R1
X = SO2Cl, SO2Na, SO2H, SO2NH2NH2, SO2SR
Jie Wu work: 15a-c
O
O
R4
S
R2
Photo-catalysts or Metal or
X
R2
O
+
R3
Metal-free
R3
R1
R1
DABSO
X = I or N2BF4
Our work
X
R1
DABSO
N BF
2 4
X =
Metal-free
O
O
O
O
S
S
R
R
O
O
Figure 1: Previous and present approaches
Results and discussion:
Initially, we examine the reaction between 4-nitrobenzenediazonium tetrafluoroborate 1a,
phenylacetylene 2a and DABSO as model substrates for the optimization of reaction conditions (Table
1).
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Table 1: Optimization studies.
5
6
7
O
S
O
N2BF4
Solvents, oC
8
9
O
Air
O2N
O2N
DABSO
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1a
2a
3a
Temp (oC)
rt
b
entries
3a
Solvent
Yield %
NR
DABSO
2
1
2
DMSO
DMSO
<10
2
2
2
2
100
100
100
H2O
NR
NR
NR
NR
3
4
5
6
DMF
THF
80
1,4-Dioxane
2
2
100
100
NR
DMA
7
8
9
2
2
MeCN
MeCN
MeCN
MeCN
62
100
80
78
1.5
80
10
11
12
64
38
80
80
1
0.5
MeCN
<10
a
Reaction conditions
1
2 (
:
Reactions were carried out using (1equiv.), 1.2
b
)
(
equiv and DABSO 2 equiv) 8mL of solvent; isolated yields; 6-12 hrs.
In the first experiment, 4-nitrobenzenediazonium tetrafluoroborate 1a (1 mmol), DABSO (2
mmol) phenylacetylene 2a (1.5 mmol) were dissolved in DMSO and stirred at the room temperature
under open atmosphere, no desired product formation was observed (entry 1). In the next experiment,
o
the reaction was heated at 80 C, the formation of desired β-keto sulfones 3a was observed with very
low yields (entry 2) giving a positive indication towards the working of the concept. In further
experiments, a range of solvents such as H2O, DMF, THF, 1,4-Dioxane, DMA and MeCN were
screened (entries 3-8) and surprisingly MeCN gave the desired product with 62% yields and none of the
others gave the desired product. The decrease in the temperature from 100 oC to 80 oC further enhanced
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the yields to 78% (entry 9) and further fall in temperature also decreased the yields. In further attempts,
a varied amount of DABSO was also studied which found to affect the yields (entries 10-12). After
trying the number of optimization experiments, reaction conditions of entry 9 is found to be best.
After the optimization, the scope of the reaction with respect to different diazonium salts and
acetylenes were investigated (Scheme 1). The reaction of 4-nitrobenzenediazonium tetrafluoroborate 1a
with phenyl acetylenes having electron-donating (4-Me, 4-t-butyl, 4-O-n-propyl, 4-O-n-pentyl, 4-OMe,
3-Me) and electron-withdrawing groups (4-CF3, 4-F, 4-Br, 4-Ph) on attempt underwent smoothly and
gave the corresponding products (3a−3k) in good yields (78-56%). When bisubstituted
phenylacetylenes were tried, the corresponding β-keto sulfone (3l) was observed in a yield of 48%.
After this, (4-bromo and 4-methoxy) substituted benzenediazonium tetrafluoroborate salts were also
tried to examine its diversification. All the tried reactions underwent smoothly and gave their
corresponding products (3m-3w) with good to moderate yields (73-52%).
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Scheme 1. Substatre scopesa
5
6
O
S
O
N2BF4
Air, MeCN
7
O
8
9
R1
Reflux, 6 -12 hrs
R
R
R1
DABSO
3, (Yield %)b
1
2
10
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O
S
O
O
S
O
O
S
O
O
O
O
O2N
O2N
O2N
3c, (
67%)
3b,
(53%)
O
3a,
(78%)
O
S
O
O
S
O
S
O
O
O
O
n-pentyl
O2N
OMe
O2N
O2N
O
3f, (
66%)
O2N
n-propyl
3e
O
S
, (66%)
O
3d,
(67%)
O
S
O
O
O
S
Me
O
O
O
O2N
F
CF3
O2N
3i, (
67%)
3h, (
57%)
3g,
(
56%)
O
S
O
O
S
O
O
S
O
O
O
O
O2N
F
O2N
Ph
3l,
(48%)
O
O2N
Br
3k,
(73%)
O
3j,
(63%)
O
O
S
O
S
O
S
O
O
Br
n-propyl
O
Br
3o, (
58%)
3n,
(68%)
O
Br
Br
3m
, (66%)
O
S
O
O
S
O
S
O
O
O
Br
F
O
3r, (
57%)
n-pentyl
Br
O
3q,
3p
(54%)
O
, (52%)
O
O
S
O
O
S
O
S
O
O
O
MeO
3u, ( %)
64
MeO
Ph
MeO
Br
3t
3s
, (69%)
, (73%)
MeO
O
S
O
O
S
O
O
O
MeO
n-propyl
3v,
(64%)
3w,
(62%)
a
Reaction conditions
6-12 hrs; bisolated yields.
1
2 (
)
2
:
Reactions were carried out using (1equiv.), 1.2 equiv and DABSO equiv 8-10 mL of solvent,
In the next attempts, we also explored the optimized conditions for alkenes as unsaturated
coupling partner, which worked nicely and afforded the β-keto sulfones 5 in a good to excellent yields.
4-Nitrobenzenediazonium tetrafluoroborate 1a, when treated with phenyl styrene gave the
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corresponding β-keto sulfones 5a in a yield of 68%. In the next attempts, mono- and bi-substituted
styrenes were tried which gave the corresponding β-keto sulfones (5a-5h) in a yield of 68-34%
(Scheme 2). When sodium metabisulphite (Na2S2O5) was tried in place of DABSO for the source of
sulfone, we feel happy to report that the reaction between benzenediazonium tetrafluoroborate salts 1
and phenyl acetylenes 2 underwent smoothly at room temperature and gave the corresponding β-keto
sulfone (6a-6f) in a yield of 63-43% (Scheme 3). We also carried out the reaction of benzenediazonium
tetrafluoroborate with phenyl styrene which gave the corresponding β-keto sulfones (7a-7c) in a yield
of 39-48% (Scheme 4). Sodium metabisulphite being an inexpensive source of sulfone providing an
additional advanatge to the present methdology. When we carried out this reaction on a large scale (1
gm, 4.23 mmol) it gave the corresponding β-keto sulfones product 3a with a (68% yield) (Scheme 5).
Scheme 2. Substatre scopesa
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O
S
O
N2BF4
Air, MeCN
O
Reflux, 6 -12 hrs
R
R1
R
DABSO
R
4
5 (yield %)b
1
O
S
O
O
S
O
O
S
O
CF3
O
O
O
O
O2N
O2N
O2N
Br
O2N
5b, (
42%)
O
5c
, (37%)
O
5a,
(68%)
O
CF3
O
S
O
S
O
Me
S
O
O
O
O
Br
Br
F
Br
5e
, (63%)
O
5d, (
34%)
O
5f,
(46%)
Me
Me
O
S
O
S
O
O
Me
5h, (
42%)
5g, (
38%)
a
Reaction conditions
1
4 (
)
2
:
Reactions were carried out using (1equiv.), 1.2 equiv and DABSO equiv 8mL of solvent;
bisolated yields; 6-12 hrs.
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Scheme 3. Reaction of phenyl acetylenes with another sulfone sourcea
5
6
7
8
O
S
O
N2BF4
Air, MeCN
O
9
rt, 12-24 hrs
R1
R
R1
R
10
11
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3/6, (yield %)b
Na2S2O5
2
1
O
S
O
O
S
O
O
S
O
O
O
O
O2N
OMe
O2N
O2N
3f/6c, (
47%)
O
3b/6b,
(47%)
O
3a/6a, (
63%)
O
O
S
O
S
O
S
O
O
O
O2N
CN
Br
CN
O2N
Ph
6f,
(43%)
6e,
(46%)
3k/6d,
(49%)
a
Reaction conditions
12-24 hrs; bisolated yields.
1
2 (
)
:
Reactions were carried out using (1equiv.), 1.2 equiv and Na2S2O5 (2 equiv.), 8-10 mL of solvent,
Scheme 4. Recation of phenyl styrene with another sulfone sourcea
O
S
O
N2BF4
Air, MeCN
O
rt, 12-24 hrs
R1
R
R1
R
3/7, (yield %)b
Na2S2O5
4
1
O
S
O
O
S
O
O
S
O
O
O
O
O2N
MeO
O2N
OMe
3a/7a, (
48%)
3f/7b
, (41%)
3u/7c
, (39%)
a
Reaction conditions
12-24 hrs; bisolated yields.
1
4 (
)
:
Reactions were carried out using (1equiv.), 1.2 equiv and Na2S2O5 (2 equiv.), 8-10 mL of solvent,
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Scheme 5. Reaction in gram scalea
O
S
O
6
7
8
9
N2BF4
Air, MeCN
O
Reflux, 12 hrs
R1
R
R1
R
10
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b
DABSO
1
2
3a,
(68%)
a
Reaction conditions
1
2 (
)
:
Reactions were carried out using ( 1 equiv., 4,23 mmol), 1.2 equiv, 6.83 mmol and DABSO
(2 equiv, 8.47 mmol), bisolated yields.
Scheme 6. Controlled experiments.
O
S
O
N2BF4
TEMPO (2 Equiv.)
Moist MeCN
eq. 1
O
O2N
O2N
DABSO
1a
2a
Reflux, 6 -12 hrs
open atmosphere
3a, 0%
O
S
O
O
N2BF4
O
Moist MeCN
Reflux, 6 -12 hrs
open atmosphere
eq. 2
O2N
O2N
DABSO
3a, 0%
1a
2a
O
S
O
N2BF4
X
+
Unidentified products
O
O2N
eq. 3
MeCN, Argon
Reflux, 6 -12 hrs
DABSO
O2N
2a
3a, 14%
1a
In order to confirm the proposed mechanistic pathway, a number of confirmatory controlled
experiments have been performed. In the first instance, the reaction was performed in the presence of
free-radical scavenger TEMPO, no desired product was formed (eq. 1, Scheme 6) confirmed the radical
pathway. In the literature reports, it is known that phenyl acetylenes hydrated to acetophenone,17 and
also suggested its involvement under present conditions. In order to rule out this assumption, the
reaction was performed with acetophenone under optimized conditions, no desired product formation
was formed, ruled out its involvement (eq. 2, Scheme 6). To know the source of incoming oxygen in
the β-keto sufones, when the reaction was performed under an argon atmosphere, the formation of
desired product 3a was significantly suppressed (eq. 3, Scheme 6) suggested that oxygen may be source
of incoming oxygen atom in β-keto sulfones. In the next attempts, the reaction of 4-
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nitrobenzenediazonium tetrafluoroborate 1a with phenyl acetylene 2a and styrene 4a, respectively,
were conducted and studied in a LC-MS at different interval of times (Figure 2, and details provided in
page no.s S2-S7 of Supporting Information (SI)). The LC-MS study revealed the formation of phenyl
sulfone radical III and peroxy radical intermediate (X). The existence of peroxy radical intermediate
(X) suggested that oxygen is the source of incoming oxygen. Next, we conducted the reaction in the
presence of 18O-labelled oxygen gas (Fig 3), wherein LC−MS analysis showed 81% presence of 18O in
the product, confirmed the source of incoming oxygen is air.
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O
S
O
N2BH2F4
DABSO
Moist MeCN, Air
Reflux, 6 -12 hrs
O
O2N
O2N
3a
1a
2a
4
-ESI Scan (10.24 min) Frag=135.0V E736-15MIN.d
x10
(a)
(b)
1.2
1.1
1
O
4
-ESI EIC(184.0000-186.0000) Scan Frag=135.0V E736-15MIN.d
x10
S
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
O
1
1
O
S
1.5
1
O2N
III
O
Mass: 185.9861 (M)
O2N
III
0.5
0
Exact Mass: 185.9861
* 10.26
10
1
2
3
4
5
6
7
8
9
11
12
150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950
Counts vs. Mass-to-Charge (m/z)
Counts vs. Acquisition Time (min)
(d)
x10
5
-ESI EIC(185.9000) Scan Frag=135.0V 15MINE790neg.d
1
1
1.75
1.5
1.25
1
O
S
O
N2BF4
* 10.32
Moist MeCN, Air
Reflux, 6 -12 hrs
O
O
S
O2N
O
O2N
DABSO
0.75
0.5
0.25
0
5a
1a
4a
O2N
III
Exact Mass: 185.9861
(f)
1
2
3
4
5
6
7
8
9
10
11
12
Counts vs. Acquisition Time (min)
4
-ESI Scan (8.45 min) Frag=135.0V 15MINE790neg.d
x10
(e)
x10
O
O
5
-ESI Scan (10.34 min) Frag=135.0V 15MINE790neg.d
O
6
5
4
3
2
1
0
S
O
S
O
1.4
1.2
1
O
X
III
O2N
Mass: 322.0385 (M)
O2N
0.8
0.6
0.4
0.2
0
Mass: 185.9861 (M)
100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950
Counts vs. Mass-to-Charge (m/z)
150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950
Counts vs. Mass-to-Charge (m/z)
Figure 2. LC-MS analysis regarding intermediates capturing; a-b) analysis of reaction with
phenylacetylene, d-f) analysis of reaction with styrene.
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O
O
N2BF4
S
Moist MeCN, Air
Reflux
O
O2N
O2N
DABSO
3a
1a
2a
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(a)
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O
S
O18
MeCN, 18O2
Reflux
N2BF4
b
(
)
O
O2N
O2N
81% of O18 product
DABSO
1a
4a
3a

Figure 3. a) LC-MS Chromatogram of reaction mixture under air; b) LC-MS Chromatogram of
reaction mixture conducted under 18O-labeled oxygen.
Based on the controlled experiments and literature precedents,15a, 18 the following plausible
mechanistic pathway is proposed (Fig 4). The diazonium salt 1 on reaction with DABSO (A) generates
phenyl radical (I), sulfur dioxide (II) and DABCO-based cation radical (B). The formed phenyl radical
(I) immediately react with sulfur dioxide (II) to from phenylsulfonyl radical (III).14a The intermediate
(III) attack on the unsaturated partner and give radical based intermediates (IV and IX) which attack by
12b
the oxygen10d, 12b and then formed dimer (VI and XI)
followed by homolytic cleavage into oxy-
radical based intermediates (VII and XII). The intermediate VII undergoes single-electron transfer
reaction12b, 15a with DABSO to hydroxylated intermediates VIII, which immediately isomerizes to β-
keto sulfones 3. Moreover, in case of alkenes, the oxy-radical based intermediate XII undergoes proton
abstraction reaction10d, 12b with B to give β-keto sulfones 3.
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Figure 4. Plausible mechanism
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6
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9
R
S
O
O
N2 BF4
O
R
O
O
S
O
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11
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S
O
3
1
N
O
O
O
O
O
R
S
OH
N
S N
N
S
S N
N
O
S
3
O
O
B
O
O
O
A
A
O
O
S
O
R
O
N
O
O
NH
R
S
VIII
S
S
O
SO2
II
+
+
C
O
O
O
N
O
S N
N
S
I
O
O
N
O
B
D
XII
VII
O
S
R
O
S
O
O
R
O
O
O
S
O
O
O
R
XI
O
S
O
R
S
O
O
VI
Confirmed by
LC-MS
O
O
O
O
III
R
R
O
O
R
R
S
S
O2
O
O
O2
O
O
S
S
O
V
X
O
R
R
2
Confirmed by
LC-MS
IX
IV
In conclusion, a metal-free multi-component cascade reaction approach has been developed for
the synthesis of β-keto sulfones using commercially available arenediazonium salt and alkyns/alkenes
as a starting materials, while DABSO as a source of sulfur dioxide. The examples collected in Scheme
1−2 demonstrate the broad scope and high functional group tolerance of the optimized conditions.
Regarding the source of sulfone, the optimized conditions work with inexpensive reagent sodium
metabisulfite at room temperature and provided additional advantages in contrast to previous methods
(Scheme 3-4).
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EXPERIMENTAL SECTION
General Information
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8
9
All reactions were conducted under condenser fitted round bottom flask in open atmosphere and
reaction mixture was monitored by thin-layer chromatography (TLC). TLC pre-coated silica gel 60
F254 (20 × 20 cm). TLC plates were visualized by exposing UV light or by iodine vapors or immersion
in staining solution of cerric ammonium sulfate and anisaldehyde. Organic solvents were evaporated on
rotary evaporator and all the compounds were purified on flash Column chromatography (230−400
mesh size). Mass spectra were obtained using an Agilent 6540 accurate mass Q-TOF LC/MS (135 eV)
spectrometer, using electrospray ionization (ESI). 1H NMR spectra were recorded on 400 and 500 MHz
NMR instruments. Chemical data for protons are reported in parts per million (ppm, scale) downfield
from tetramethylsilane as referenced to the residual proton in the NMR solvent (CDCl3: δ 7.26, 1.56
CDCl3 moister and 1.25 grease peak or other solvents as mentioned). All the NMR spectras were
processed with MestReNova software. The coupling constant (J) are in Hz. ESI-MS and HRMS spectra
were recorded on LC-Q-TOF machines.
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General Procedure
In a 50 ml Round bottom flask, to a solution of substituted diazonium tetrafluoroborate salt 1 (237 mg,
1equiv., 1 mmol) dissolved in MeCN (8-10 ml) and then sulfur source{DABSO (480 mg, 2 mmol) or
Na2S2O5 (950 mg, 5 mmol) and phenylacetylene or alkene 2 or 4 (130 μl, 1.2 mmol) were stirred at
80 °C (temperature of oil bath) for 6 -12 h under an open atmosphere. After completion of the reaction,
reaction was monitored by TLC, the reaction mixture was cooled to room temperature and MeCN was
evaporated. The dried reaction mixture was admixed with ethyl acetate. The organic layer was washed
with water (3 × 30 mL). The organic layer was dried over anhydrous Na2SO4and evaporated under
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vacuum. The crude product was obtained then purified by flash column chromatography using EtOAc
and hexane to give required products 3a-w, 5a-5h, 6a-6f and 7a-7c.
General Procedure for gram scale reaction
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In a 250 ml Round bottom flask, to a solution of substituted diazonium tetrafluoroborate salt 1 (1 gm,
4.23 mmol) dissolved in MeCN (20 ml) and then DABSO (2.02 gm, 8.47 mmol) and phenylacetylene 2
(566 μl, 6.83 mmol) were stirred at 80 °C (temperature of oil bath) for 6 -12 h under an open
atmosphere. After completion of the reaction, reaction was monitored by TLC, the reaction mixture was
cooled to room temperature and MeCN was evaporated. The dried reaction mixture was admixed with
ethyl acetate. The organic layer was washed with water (3 × 200 mL). The organic layer was dried over
anhydrous Na2SO4and evaporated under vacuum. The crude product was obtained then purified by
flash column chromatography using EtOAc and hexane to give required product 3a with a (68% yield,
874 mg).
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Experimental Data:
5
6
7
8
2-((4-Nitrophenyl)sulfonyl)-1-phenylethan-1-one (3a/7a, Scheme 1):10a TLC (Hexane/EtOAc, 7:3)
Rf = 0.4; Yield 78% (238 mg); Yellow solid; m.p.: 166 oC; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J =
8.8 Hz, 2H), 8.12 (d, J = 8.8 Hz, 2H), 7.95 – 7.90 (m, 2H), 7.66 (s, 1H), 7.51 (t, J = 7.8 Hz, 2H), 4.82
9
10
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59
60
13
(s, 2H); C{1H} NMR (101 MHz, CDCl3) δ 187.6, 151.1, 144.1, 135.4, 134.8, 130.3, 129.2, 129.1,
124.3, 63.1; HRMS (ESI-TOF) calcd. for: C14H10NO5S 304.0280 [M-H]-, found 304.0303.
2-((4-Nitrophenyl)sulfonyl)-1-(p-tolyl)ethan-1-one (3b, Scheme 1):10d TLC (Hexane/EtOAc, 7:3) Rf
1
= 0.4; Yield 53% (168 mg); Yellow gummy; H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.8 Hz, 2H),
8.11 (d, J = 8.8 Hz, 2H), 7.82 (d, J = 8.2 Hz, 2H), 7.32 (s, 2H), 4.78 (s, 2H), 2.44 (s, 3H); 13C{1H}
NMR (101 MHz, CDCl3) δ 187.8, 150.9, 144.1, 139.1, 135.6, 135.42, 130.3, 129.5, 128.9, 126.5,
124.2, 63.0, 21.3; HRMS (ESI-TOF) calcd. for: C15H12NO5S 318.0436 [M-H]-, found 318.0462.
1-(4-(tert-Butyl)phenyl)-2-((4-nitrophenyl)sulfonyl)ethan-1-one
(3c,
Scheme
1):
TLC
1
(Hexane/EtOAc, 7:3) Rf = 0.3; Yield 67% (241 mg); Gummy dark reddish; H NMR (400 MHz,
CDCl3) δ 8.39 (d, J = 8.8 Hz, 2H), 8.11 (d, J = 8.9 Hz, 2H), 7.86 (d, J = 8.6 Hz, 2H), 7.51 (d, J = 8.5
Hz, 2H), 4.79 (s, 2H), 1.34 (s, 9H); C{1H} NMR (101 MHz, CDCl3) δ 187.1, 159.1, 151.0, 144.1,
13
132.8, 130.3, 129.2, 126.1, 124.2, 115.6, 63.0, 35.4, 30.9; HRMS (ESI-TOF) calcd. for: C18H18NO5S
360.0906 [M-H]-, found 360.0926.
2-((4-Nitrophenyl)sulfonyl)-1-(4-propylphenyl)ethan-1-one (3d, Scheme 1): TLC (Hexane/EtOAc,
7:3) Rf = 0.3; Yield 67% (203 mg); Yellow crystalline solid; m.p.: 125 oC; 1H NMR (400 MHz, CDCl3)
δ 8.39 (d, J = 8.8 Hz, 2H), 8.11 (d, J = 8.8 Hz, 2H), 7.84 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 8.2 Hz, 2H),
4.79 (s, 2H), 2.68 – 2.64 (m, 2H), 1.66 (dq, J = 14.8, 7.4 Hz, 3H), 0.95 (t, J = 7.3 Hz, 3H); C{1H}
13
NMR (101 MHz, CDCl3) δ 187.1, 167.2, 150.9, 144.1, 133.2, 130.4, 129.4, 129.2, 124.3, 63.0, 38.1,
29.7, 24.1, 13.7; HRMS (ESI-TOF) calcd. for: C17H16NO5S 346.0749 [M-H]-, found 346.0759.
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2-((4-Nitrophenyl)sulfonyl)-1-(4-(pentyloxy)phenyl)ethan-1-one
(3e,
Scheme
1):
TLC
5
6
7
8
(Hexane/EtOAc, 7:3) Rf = 0.4; Yield 66% (211 mg); Dark reddish; m.p.: 116 oC; 1H NMR (400 MHz,
CDCl3) δ 8.36 (t, J = 14.4 Hz, 2H), 8.10 (d, J = 8.9 Hz, 2H), 7.89 (d, J = 8.9 Hz, 2H), 7.08 – 6.80 (m,
2H), 4.75 (s, 2H), 4.04 (t, J = 6.5 Hz, 2H), 1.91 – 1.72 (m, 2H), 1.52 – 1.34 (m, 4H), 0.96 – 0.92(m,
3H); 13C{1H} NMR (101 MHz, CDCl3) δ 185.7, 164.6, 151.0, 144.1, 131.8, 130.3, 128.1, 124.2, 114.7,
68.6, 62.9, 28.7, 28.0, 22.4, 13.9; HRMS (ESI-TOF) calcd. for: C19H20NO6S 390.1011 [M-H]-, found
390.1028.
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1-(3-Methoxyphenyl)-2-((4-nitrophenyl)sulfonyl)ethan-1-one
(3f/7b,
Scheme
1):
TLC
o
1
(Hexane/EtOAc, 6:4) Rf = 0.5; Yield 66% (221 mg); Yellow solid; m.p.: 106 C; H NMR (400 MHz,
CDCl3) δ 8.39 (d, J = 8.7 Hz, 2H), 8.13 (d, J = 8.7 Hz, 2H), 7.50 (d, J = 7.6 Hz, 1H), 7.41 (dd, J = 10.5,
5.0 Hz, 2H), 7.19 (dd, J = 8.0, 2.0 Hz, 1H), 4.80 (s, 2H), 3.84 (s, 3H); 13C{1H} NMR (101 MHz,
CDCl3) δ 187.5, 160.1, 151.1, 144.1, 136.6, 130.4, 130.1, 124.3, 121.9, 121.8, 121.5, 113.0, 63.1, 55.6;
HRMS (ESI-TOF) calcd. for: C15H12NO6S 334.0391 [M-H]-, found 334.0398.
2-((4-Nitrophenyl)sulfonyl)-1-(m-tolyl)ethan-1-one (3g, Scheme 1): TLC (Hexane/EtOAc, 7:3) Rf =
o
1
0.4; Yield 56% (169 mg); Yellow Solid; m.p.: 130 C; H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.5
Hz, 2H), 8.12 (d, J = 8.1 Hz, 2H), 7.72 (d, J = 6.5 Hz, 2H), 7.52 – 7.33 (m, 2H), 4.80 (s, 2H), 2.41 (s,
3H); 13C{1H} NMR (101 MHz, CDCl3) δ 187.8, 150.9, 144.1, 139.1, 135.6, 135.42, 130.3, 129.5,
128.9, 126.5, 124.2, 63.0, 21.3; HRMS (ESI-TOF) calcd. for: C15H12NO5S 318.0442 [M-H]-, found
318.0450.
2-((4-Nitrophenyl)sulfonyl)-1-(4-(trifluoromethyl)phenyl)ethan-1-one (3h, Scheme 1): TLC
1
(Hexane/EtOAc, 7:3) Rf = 0.4; Yield 57% (156 mg); Yellow gummy; H NMR (400 MHz, CDCl3) δ
8.43 (d, J = 8.7 Hz, 2H), 8.10 (dd, J = 13.9, 8.5 Hz, 4H), 7.80 (d, J = 8.2 Hz, 2H), 4.83 (s, 2H); 13C{1H}
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NMR (101 MHz, CDCl3) δ 186.9, 151.2, 143.7, 138.0, 136.0 (d, J = 41.58 Hz), 129.5 (d,= J = 127.226
Hz), 129.6, 129.0, 126,2 (q = J = 5.04 Hz), 124.46 (d = J = 4.28 Hz), 124.29, 121.91, 63.28; HRMS
(ESI-TOF) calcd. for: C15H9F3NO5S 372.0154 [M-H]-, found 372.0156.
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1-(4-Fluorophenyl)-2-((4-nitrophenyl)sulfonyl)ethan-1-one
(3i,
Scheme
1):10d
TLC
o
1
(Hexane/EtOAc, 6:4) Rf = 0.4; Yield 67% (216 mg); yellow solid; m.p.: 120 C; H NMR (400 MHz,
CDCl3) δ 8.42 (d, J = 8.4 Hz, 2H), 8.11 (d, J = 8.4 Hz, 2H), 8.00 (dd, J = 8.3, 5.3 Hz, 2H), 7.20 (t, J =
8.3 Hz, 2H), 4.78 (s, 2H); 13C{1H} NMR (101 MHz, CDCl3) δ 186.2, 165.3, 143.7, 137.0, 136.8, 132.2
(d, J = 9.09 Hz), 130.3, 124.4, 116.4 (d, J = 25.25 Hz) 63.1; HRMS (ESI-TOF) calcd. for: C14H9FNO5S
322.0191 [M-H]-, found 322.0227.
1-(4-Bromophenyl)-2-((4-nitrophenyl)sulfonyl)ethan-1-one
(3j,
Scheme
1):10d
TLC
(Hexane/EtOAc, 7:3) Rf = 0.4; Yield 63% (241 mg); Yellow crystalline solid; m.p.: 170 C;1H NMR
(400 MHz, CDCl3) δ 8.41 (d, J = 8.3 Hz, 2H), 8.11 (d, J = 8.3 Hz, 2H), 7.81 (d, J = 8.1 Hz, 2H), 7.67
(d, J = 8.1 Hz, 2H), 4.77 (s, 2H); 13C{1H} NMR (101 MHz, CDCl3) δ 186.7, 151.0, 143.8, 134.1, 132.1,
131.6, 130.6, 130.3, 124.3, 63.1; HRMS (ESI-TOF) calcd. for: C14H9BrNO5S 383.9364 [M-H]-, found
383.9381.
o
1-([1,1'-Biphenyl]-4-yl)-2-((4-nitrophenyl)sulfonyl)ethan-1-one
(3k,
Scheme
1):
TLC
(Hexane/EtOAc, 6:4) Rf = 0.6; Yield 73% (381mg); Crystaline solid.; m.p.: 158oC; H NMR (400
1
MHz, CDCl3) δ 8.40 (d, J = 8.8 Hz, 2H), 8.14 (d, J = 8.7 Hz, 2H), 8.01 (d, J = 8.3 Hz, 1H), 7.73 (d, J =
8.4 Hz, 2H), 7.63 (d, J = 7.2 Hz, 2H), 7.46 (dt, J = 22.6, 7.1 Hz, 3H), 4.85 (s, 2H); C{1H} NMR
13
NMR (101 MHz, CDCl3) δ 187.2, 151.1, 147.6, 139.1, 133.9, 130.4, 129.9, 129.1, 128.8, 127.7, 127.7,
124.4, 63.1; HRMS (ESI-TOF) calcd. for: C20H14NO5 S 380.0593 [M-H]-, found 380.0591.
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1-(4-Fluoro-3-methylphenyl)-2-((4-nitrophenyl)sulfonyl)ethan-1-one (3l, Scheme 1): TLC
5
6
o
1
(Hexane/EtOAc, 7:3) Rf = 0.4; Yield 48% (161 mg); Yellow crystalline; m.p.: 125 C; H NMR (400
7
8
9
MHz, CDCl3) δ 8.41 (d, J = 8.8 Hz, 2H), 8.11 (d, J = 8.8 Hz, 2H), 7.93 – 7.67 (m, 2H), 7.85 – 7.71 (m,
13
2H), 7.13 (t, J = 8.7 Hz, 1H), 4.77 (s, 2H), 2.34 (s, 3H); C{1H} NMR (101 MHz, CDCl3) δ 186.3,
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165.5 (d,J = 258.56 Hz) 151.1, 143.9, 133.2 (d, J = 1.01 Hz), 133.1 (d, J = 2.02Hz), 131.6 (d, J = 3.03
Hz), 130.3, 129.6 (d, J = 10.1 Hz), 126.5, 126.3, 126.1, 116.1 (d, J = 5.05 Hz) 115.8 (d, J = 4.04 Hz),
63.0, 14.6; HRMS (ESI-TOF) calcd. for: C15H11FNO5S 336.0342 [M-H]-, found 336.0359.
2-((4-Bromophenyl)sulfonyl)-1-(p-tolyl)ethan-1-one (3m, Scheme 1): TLC (Hexane/EtOAc, 7:3) Rf
= 0.4; Yield 66% (222 mg); Yellow solid; m.p.: 142 oC; 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.2
Hz, 2H), 7.74 (d, J = 8.6 Hz, 2H), 7.68 (d, J = 8.6 Hz, 2H), 7.28 (d, J = 8.1 Hz, 2H), 4.71 (s, 2H), 2.43
(s, 3H); C{1H} NMR (101 MHz, CDCl3) δ 187.4, 145.8, 137.7, 133.2, 132.5, 130.2, 129.7, 129.6,
13
129.4, 63.3, 21.8; HRMS (ESI-TOF) calcd. for: C15H12BrO3S 350.9691 [M-H]-, found 350.9696.
2-((4-Bromophenyl)sulfonyl)-1-phenylethan-1-one (3n, Scheme 1):11b TLC (Hexane/EtOAc, 7:3) Rf
1
= 0.4; Yield 68% (230 mg); Yellow gummy; H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 7.7 Hz, 2H),
7.76 (d, J = 8.5 Hz, 2H), 7.69 (d, J = 8.5 Hz, 2H), 7.51 (d, J = 7.7 Hz, 2H), 4.74 (s, 2H); HRMS (ESI-
TOF) calcd. for: C14H10BrO3S 338.9519 [M-H]-, found 338.9526.
2-((4-Bromophenyl)sulfonyl)-1-(4-propylphenyl)ethan-1-one
(3o,
Scheme
1):
TLC
o
1
(Hexane/EtOAc, 7:3) Rf = 0.4; Yield 58% (196 mg); Yellow solid; m.p.: 114 C; H NMR (400 MHz,
CDCl3) δ 7.84 (d, J = 8.3 Hz, 2H), 7.75 (d, J = 8.6 Hz, 2H), 7.75 (d, J = 8.6 Hz, 2H), 7.68 (d, J = 8.7
Hz, 2H), 7.28 (d, J = 8.2 Hz, 2H), 4.71 (s, 2H), 2.83 – 2.53 (m, 2H), 1.67 (dq, J = 14.8, 7.4 Hz, 2H),
0.93 (dd, J = 21.6, 14.2 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 187.4, 150.4, 137.7, 133.4,
130.2, 129.2, 129.4, 129.0, 63.3, 38.1, 24.0, 13.7; HRMS (ESI-TOF) calcd. for: C17H16BrO3S 380.9989
[M-H], found 380.9992.
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2-((4-Bromophenyl)sulfonyl)-1-(4-(pentyloxy)phenyl)ethan-1-one (3p, Scheme 1): TLC
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o
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(Hexane/EtOAc, 7:3) Rf = 0.4; Yield 52% (184 mg); Yellow solid; m.p.: 121 C; H NMR (400 MHz,
CDCl3) δ 7.90 (d, J = 8.9 Hz, 2H), 7.74 (d, J = 8.6 Hz, 2H), 7.67 (d, J = 8.6 Hz, 2H), 6.93 (d, J = 8.9
Hz, 2H), 4.67 (s, 2H), 4.03 (t, J = 6.5 Hz, 2H), 1.87 – 1.78 (m, 2H), 1.48 – 1.36 (m, 4H), 0.94 (t, J = 7.0
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Hz, 3H); C{1H} NMR (101 MHz, CDCl3) δ 186.0, 164.4, 137.7, 132.5, 131.9, 130.2, 129.7, 128.7,
114.6, 68.5, 63.3, 28.7, 28.1, 22.4, 13.9; HRMS (ESI-TOF) calcd. for: C19H21BrO4S 425.0245 [M-H]-,
found 425.0253.
2-((4-Bromophenyl)sulfonyl)-1-(4-(tert-butyl)phenyl)ethan-1-one (3q, Scheme 1): TLC
(Hexane/EtOAc, 7:3) Rf = 0.4; Yield 54% (213 mg); Yellow crystalline solid; m.p.: 162oC; H NMR
1
(400 MHz, CDCl3) δ 7.86 (d, J = 8.6 Hz, 2H), 7.74 (d, J = 8.7 Hz, 2H), 7.68 (d, J = 8.7 Hz, 2H), 7.49
(d, J = 8.6 Hz, 2H), 4.71 (s, 2H), 1.34 (s, 9H); 13C{1H} NMR (101 MHz, CDCl3) δ 187.3, 158.7, 137.7,
133.1, 132.4, 130.23, 129.6, 129.2, 125.9, 63.3, 35.3, 30.9; HRMS (ESI-TOF) calcd. for: C18H18BrO3S
395.0146 [M-H]-, found 395.0152.
2-((4-Bromophenyl)sulfonyl)-1-(4-fluorophenyl)ethan-1-one (3r, Scheme 1): (Hexane/EtOAc, 7:3)
Rf = 0.4; Yield 57% (203 mg); Crystalline solid; m.p.: 95 oC; H NMR (400 MHz, CDCl3) δ 8.00 (dd, J
1
= 7.7, 5.5 Hz, 2H), 7.72 (dd, J = 17.2, 8.1 Hz, 4H), 7.18 (t, J = 8.1 Hz, 2H), 4.70 (s, 2H); 13C{1H} NMR
(101 MHz, CDCl3) δ 186.2, 171.2, 167.6 (d, J = 258.56 Hz), 137.5, 132.8, 132.6, 132.2 (d, J = 7.07
Hz), 130.2, 129.9, 129.6, 116.3 (d, J = 22.22 Hz) 63.5; HRMS (ESI-TOF) calcd. for: C14H9BrFO3S
354.9440 [M-H]-, found 354.9468.
1-(4-Bromophenyl)-2-((4-methoxyphenyl)sulfonyl)ethan-1-one
(3s,
Scheme
1):19
TLC
(Hexane/EtOAc, 6:4) Rf = 0.5; Yield 73% (267 mg); Yellow solid; m.p.: 115 oC; 1H NMR (400 MHz,
CDCl3) δ 7.78 (dt, J = 24.9, 12.3 Hz, 5H), 7.63 (d, J = 8.5 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 4.66 (s,
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2H), 3.88 (s, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ 187.4, 164.2, 134.5, 132.2, 130.9, 129.96, 129.8,
114.4, 63.9, 55.7; HRMS (ESI-TOF) calcd. for: C15H12BrO4S 368.9619 [M-H]-, found 368.9628.
1-([1,1'-Biphenyl]-4-yl)-2-((4-methoxyphenyl)sulfonyl)ethan-1-one (3t, Scheme 1): TLC
(Hexane/EtOAc, 7:3) Rf = 0.4; Yield 69% (253 mg); Reddish brown solid; m.p.: 96 oC; 1H NMR (400
MHz, CDCl3) δ 8.03 (d, J = 8.2 Hz, 2H), 7.82 (d, J = 8.8 Hz, 2H), 7.70 (d, J = 8.2 Hz, 2H), 7.63 (d, J =
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7.3 Hz, 2H), 7.52 – 7.41 (m, 3H), 7.00 (d, J = 8.8 Hz, 2H), 4.74 (s, 2H), 3.87 (s, 3H); C{1H} NMR
(101 MHz, CDCl3) δ 187.8, 164.2, 147.0, 139.4, 134.5, 130.9, 130.2, 130.0, 129.0, 128.6, 127.4, 127.3,
114.4, 63.9, 55.7; HRMS (ESI-TOF) calcd. for: C21H17O4S 365.0848 [M-H]-, found 365.0862.
2-((4-Methoxyphenyl)sulfonyl)-1-phenylethan-1-one (3u/7c, Scheme 1):11d TLC (Hexane/EtOAc,
1
7:3) Rf = 0.5; Yield 64% (185 mg); Yellow solid; m.p.: 98oC; H NMR (400 MHz, CDCl3) δ 7.98 –
7.92 (m, 2H), 7.80 (d, J = 9.0 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.8 Hz, 2H), 6.99 (d, J = 9.0
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Hz, 2H), 4.71 (s, 2H), 3.88 (s, 3H); C{1H} NMR (101 MHz, CDCl3) δ 188.3, 164.2, 135.9, 134.3,
130.9, 130.3, 129.4, 128.7, 114.4, 63.8, 55.7; HRMS (ESI-TOF) calcd. for: C15H13O4S289.0535 [M-H]-
, found 289.0540.
2-((4-Methoxyphenyl)sulfonyl)-1-(4-propylphenyl)ethan-1-one
(3v,
Scheme
1):
TLC
1
(Hexane/EtOAc, 7:3) Rf = 0.4; Yield 64% (185 mg); Gummy dark reddish; H NMR (400 MHz,
CDCl3) δ 7.85 (d, J = 8.3 Hz, 2H), 7.83 – 7.77 (m, 2H), 7.32 – 7.23 (m, 2H), 6.98 – 6.93 (m, 2H), 4.68
(s, 2H), 3.86 (s, 3H), 2.82 – 2.50 (m, 2H), 1.78 – 1.54 (m, 2H), 1.01 – 0.84 (m, 3H); 13C{1H} NMR
(101 MHz, CDCl3) δ 187.8, 164.1, 150.1, 133.6, 130.8, 130.3, 129.5, 128.9, 128.7, 114.3, 63.7, 55.7,
38.0, 24.0, 13.7; HRMS (ESI-TOF) calcd. for: C18H21O4S 333.1161 [M+H]+, found 333.1139.
1-(4-(tert-Butyl)phenyl)-2-((4-methoxyphenyl)sulfonyl)ethan-1-one (3w, Scheme 1): TLC
1
(Hexane/EtOAc, 7:3) Rf = 0.4; Yield 62% (214 mg); Gummy dark reddish; H NMR (400 MHz,
CDCl3) δ 7.88 (d, J = 8.3 Hz, 2H), 7.80 (d, J = 8.6 Hz, 2H), 7.48 (d, J = 8.3 Hz, 2H), 6.98 (d, J = 8.7
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Hz, 2H), 4.69 (s, 2H), 3.87 (s, 3H), 1.34 (s, 9H); 13C{1H} NMR (101 MHz, CDCl3) δ 187.8, 164.1,
158.3, 133.3, 130.9, 130.3, 129.3, 125.8, 114.3, 63.7, 55.6, 35.3, 31.0; HRMS (ESI-TOF) calcd. for:
C19H21O4S 345.1161 [M+H]+, found 345.1136.
2-((4-Nitrophenyl)sulfonyl)-1-phenylethan-1-one (5a/3a, Scheme 2):10a TLC (Hexane/EtOAc, 7:3)
Rf = 0.4; Yield 68% (207 mg); Yellow solid; m.p.: 166 oC; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J =
8.8 Hz, 2H), 8.12 (d, J = 8.8 Hz, 2H), 7.95 – 7.90 (m, 2H), 7.66 (s, 1H), 7.51 (t, J = 7.8 Hz, 2H), 4.82
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(s, 2H); C{1H} NMR (101 MHz, CDCl3) δ 187.6, 151.1, 144.1, 135.4, 134.8, 130.3, 129.2, 129.1,
124.3, 63.1; HRMS (ESI-TOF) calcd. for: C14H10NO5S 304.0280 [M-H]-, found 304.0303.
1-(4-Acetylphenyl)-2-((4-nitrophenyl)sulfonyl)ethan-1-one (5b, Scheme 2): TLC (Hexane/EtOAc,
o
1
7:3) Rf = 0.4; Yield 42% (145mg); Yellow solid; m.p.: 125 C; H NMR (400 MHz, CDCl3) δ 8.36 –
8.29 (m, 2H), 8.05 (t, J = 7.7 Hz, 2H), 7.90 (d, J = 8.6 Hz, 2H), 7.18 (d, J = 8.7 Hz, 2H), 4.72 (s, 2H),
13
2.27 (s, 3H); C{1H} NMR (101 MHz, CDCl3) δ 186.4, 168.5, 155.7, 143.9, 132.8, 130.9, 130.3,
124.4, 122.3, 122.3, 63.1, 21.1; HRMS (ESI-TOF) calcd. for: C16H12NO6S 346.0385 [M-H]-, found
346.0394, 304.0280 [M-COCH3]; 185.9872 [M-CH2COPhCOCH3].
1-(3,5-Bis(trifluoromethyl)phenyl)-2-((4-nitrophenyl)sulfonyl)ethan-1-one (5c, Scheme 2): TLC
1
(Hexane/EtOAc, 6:4) Rf = 0.3; Yield 37% (113 mg); Yellow crystalline solid; m.p.: 155oC; H NMR
(400 MHz, CDCl3) δ 8.57 – 8.29 (m, 4H), 8.27 – 8.04 (m, 3H), 4.87 (s, 2H); 13C{1H} NMR (101 MHz,
CDCl3) δ 185.5, 151.4, 151.3, 143.5, 136.8, 133.5, 133.2, 132.9, 130.3, 129.2 (d,J = 3.03 Hz) 127.9 (q,
J = 3.03 Hz), 124.6, 123.9 (q, J = 18.18 Hz), 121.2, 63.1; HRMS (ESI-TOF) calcd. for:
C16H8F6NO5S440.0027 [M-H]-, found 440.0057.
1-(3,5-Dimethylphenyl)-2-((4-nitrophenyl)sulfonyl)ethan-1-one
(5d,
Scheme
2):
TLC
1
(Hexane/EtOAc, 6:4) Rf = 0.6; Yield 34% (113 mg); Dark Brownish gummy; H NMR (400 MHz,
CDCl3) δ 8.39 (d, J = 8.8 Hz, 2H), 8.11 (d, J = 8.7 Hz, 2H), 7.47 (s, 1H), 7.16 (d, J = 7.7 Hz, 2H), 4.77
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(s, 2H), 2.39 (s, 3H), 2.36 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 189.9, 144.5, 137.2, 135.8,
135.2, 134.1, 132.5, 130.7, 130.3, 124.2, 65.1, 21.1, 20.9; HRMS (ESI-TOF) calcd. for: C16H14NO5S
332.0598 [M-H]-, found 332.0631.
2-((4-Bromophenyl)sulfonyl)-1-(4-fluorophenyl)ethan-1-one (5e/3r Scheme 2):10d (Hexane/EtOAc,
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7:3) Rf = 0.4; Yield 63% (184 mg); Yellow solid; m.p.:121 oC; H NMR (400 MHz, CDCl3) δ 8.00 (dd,
J = 7.7, 5.5 Hz, 2H), 7.72 (dd, J = 17.2, 8.1 Hz, 4H), 7.18 (t, J = 8.1 Hz, 2H), 4.70 (s, 2H); 13C{1H}
NMR (101 MHz, CDCl3) δ 186.2, 171.2, 167.6 (d, J = 258.56 Hz), 137.5, 132.8, 132.6, 132.2 (d, J =
7.07 Hz), 130.2, 129.9, 129.6, 116.3 (d, J = 22.22 Hz) 63.5; HRMS (ESI-TOF) calcd. for:
C14H9BrFO3S 354.9440 [M-H]-, found 354.9468.
1-(4-Acetylphenyl)-2-((4-bromophenyl)sulfonyl)ethan-1-one (5f, Scheme 2): TLC (Hexane/EtOAc,
6:4) Rf = 0.6; Yield 46% (175 mg); Yellow solid; m.p.: 124 oC; 1H NMR (400 MHz, CDCl3) δ 7.98 (d,
13
J = 8.6 Hz, 2H), 7.82 – 7.60 (m, 4H), 7.35 – 7.16 (m, 2H), 4.71 (s, 2H), 2.33 (s, 3H); C{1H} NMR
(101 MHz, CDCl3) δ 186.6, 168.5, 155.5, 137.5, 133.1, 132.6, 131.0, 130.2, 122.2, 63.4, 21.1;HRMS
(ESI-TOF) calcd. for: C16H10BrO4S 376.9478 [M-H]-, found 376.9444.
2-((4-Bromophenyl)sulfonyl)-1-(2,4-dimethylphenyl)ethan-1-one
(5g,
Scheme
2):
TLC
1
(Hexane/EtOAc, 6:4) Rf = 0.6; Yield 38%(139 mg); Gummy pinkish; H NMR (400 MHz, CDCl3) δ
7.67 (dt, J = 17.8, 8.2 Hz, 5H), 7.08 (d, J = 9.0 Hz, 2H), 4.68 (s, 2H), 2.42 (s, 3H), 2.37 (s, 3H);
13C{1H} NMR (101 MHz, CDCl3) δ 189.4, 144.1, 140.6, 138.0, 133.3, 132.7, 132.4, 130.9, 130.1,
129.5, 126.6, 65.3, 21.7, 21.5; HRMS (ESI-TOF) calcd. for: C16H14BrO3S 366.9833 [M-H]-, found
366.9866.
2-((4-Bromophenyl)sulfonyl)-1-(4-(tert-butyl)phenyl)ethan-1-one (5h/3q, Scheme 2): TLC
o
1
(Hexane/EtOAc, 7:3) Rf = 0.4; Yield 42% (213 mg); Yellow crystalline solid; m.p.:162 C; H NMR
(400 MHz, CDCl3) δ 7.86 (d, J = 8.6 Hz, 2H), 7.74 (d, J = 8.7 Hz, 2H), 7.68 (d, J = 8.7 Hz, 2H), 7.49
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(d, J = 8.6 Hz, 2H), 4.71 (s, 2H), 1.34 (s, 9H); 13C{1H} NMR (101 MHz, CDCl3) δ 187.3, 158.7, 137.7,
133.1, 132.4, 130.23, 129.6, 129.2, 125.9, 63.3, 35.3, 30.9; HRMS (ESI-TOF) calcd. for: C18H18BrO3S
395.0146 [M-H]-, found 395.0152.
2-((4-Nitrophenyl)sulfonyl)-1-phenylethan-1-one (6a/3a, Scheme 3):10a TLC (Hexane/EtOAc, 7:3)
Rf = 0.4; Yield 63% (191 mg); Yellow solid; m.p.: 166 oC; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J =
8.8 Hz, 2H), 8.12 (d, J = 8.8 Hz, 2H), 7.95 – 7.90 (m, 2H), 7.66 (s, 1H), 7.51 (t, J = 7.8 Hz, 2H), 4.82
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(s, 2H); C{1H} NMR (101 MHz, CDCl3) δ 187.6, 151.1, 144.1, 135.4, 134.8, 130.3, 129.2, 129.1,
124.3, 63.1; HRMS (ESI-TOF) calcd. for: C14H10NO5S 304.0280 [M-H]-, found 304.0303.
2-((4-Nitrophenyl)sulfonyl)-1-(p-tolyl)ethan-1-one (6b/3b, Scheme 3):10d TLC (Hexane/EtOAc, 7:3)
Rf = 0.4; Yield 47% (149 mg); Yellow gummy; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.8 Hz, 2H),
8.11 (d, J = 8.8 Hz, 2H), 7.82 (d, J = 8.2 Hz, 2H), 7.32 (s, 2H), 4.78 (s, 2H), 2.44 (s, 3H); 13C{1H}
NMR (101 MHz, CDCl3) δ 187.8, 150.9, 144.1, 139.1, 135.6, 135.4, 130.3, 129.5, 128.9, 126.5, 124.2,
63.0, 21.3; HRMS (ESI-TOF) calcd. for: C15H12NO5S 318.0436 [M-H]-, found 318.0462.
1-(3-Methoxyphenyl)-2-((4-nitrophenyl)sulfonyl)ethan-1-one
(6c/3f,
Scheme
3):
TLC
o
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(Hexane/EtOAc, 6:4) Rf = 0.5; Yield 47% (156 mg); Yellow solid; m.p.: 106 C; H NMR (400 MHz,
CDCl3) δ 8.39 (d, J = 8.7 Hz, 2H), 8.13 (d, J = 8.7 Hz, 2H), 7.50 (d, J = 7.6 Hz, 1H), 7.41 (dd, J = 10.5,
5.0 Hz, 2H), 7.19 (dd, J = 8.0, 2.0 Hz, 1H), 4.80 (s, 2H), 3.84 (s, 3H); 13C{1H} NMR (101 MHz,
CDCl3) δ 187.5, 160.1, 151.1, 144.1, 136.6, 130.4, 130.1, 124.3, 121.9, 121.8, 121.5, 113.0, 63.1, 55.6;
HRMS (ESI-TOF) calcd. for: C15H12NO6S 334.0391 [M-H]-, found 334.0398.
1-([1,1'-Biphenyl]-4-yl)-2-((4-nitrophenyl)sulfonyl)ethan-1-one (6d/3j, Scheme 3): TLC
1
(Hexane/EtOAc, 6:4) Rf = 0.6; Yield 49% (186 mg); Crystaline solid.; m.p.: 158oC; H NMR (400
MHz, CDCl3) δ 8.40 (d, J = 8.8 Hz, 2H), 8.14 (d, J = 8.7 Hz, 2H), 8.01 (d, J = 8.3 Hz, 1H), 7.73 (d, J =
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8.4 Hz, 2H), 7.63 (d, J = 7.2 Hz, 2H), 7.46 (dt, J = 22.6, 7.1 Hz, 3H), 4.85 (s, 2H); C{1H} NMR
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NMR (101 MHz, CDCl3) δ 187.2, 151.1, 147.6, 139.1, 133.9, 130.4, 129.9, 129.1, 128.8, 127.7, 127.7,
124.4, 63.1; HRMS (ESI-TOF) calcd. for: C20H14NO5 S 380.0593 [M-H]-, found 380.0591.
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4-(2-((4-Nitrophenyl)sulfonyl)acetyl)benzonitrile (6e, Scheme 3):10d TLC (Hexane/EtOAc, 5:5) Rf =
0.4; Yield 46% (151 mg); Yellow Solid; m.p.: 142oC; 1H NMR (400 MHz, DMSO-d6) δ 8.46 (d, J =
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8.8 Hz, 2H), 8.22 (d, J = 8.8 Hz, 2H), 8.12 (d, J = 8.5 Hz, 2H), 8.04 (d, 2H), 5.67 (s, 2H); C{1H}
NMR (101 MHz, DMSO-d6) δ 189.0, 151.0, 145.2, 138.8, 133.0, 129.9, 129.4, 124.8, 118.2, 116.7,
62.6; HRMS (ESI-TOF) calcd. for: C15H9N2O5S 329.0238 [M-H]-, found 329.0265.
4-(2-((4-Bromophenyl)sulfonyl)acetyl)benzonitrile (6f, Scheme 3):14a TLC (Hexane/EtOAc, 6:4) Rf
= 0.3; Yield 43% (149 mg); Yellow Solid; m.p.: 148oC; H NMR (400 MHz, CDCl3) H NMR (400
MHz, CDCl3) δ 8.07 (d, J = 8.2 Hz, 2H), 7.82 (d, J = 8.2 Hz, 2H), 7.69 (d, J = 29.7 Hz, 4H), 4.73 (s,
2H); 13C{1H} NMR NMR (101 MHz, CDCl3) δ 186.7, 138.2, 137.0, 132.7, 132.7, 130.0, 129.6, 117.7,
117.4, 63.3; MS (ESI-TOF) calcd. for: C15H9BrNO3NO5 S 364.2130 [M-H]-, found 364.05
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ASSOCIATED CONTENT:
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Supporting Information Copies of NMRs, HRMS spectras are given.This material is available free of
charge via theInternet at http://pubs.acs.org.
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AUTHOR INFORMATION:
Corresponding Author
* E-mail: ppsingh@iiim.ac.in.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGEMENTS:
We are grateful to the financial support of CSIR through research grants MLP5005 and HCP0008. M.
K. thanks UGC for the award of fellowship, R. A., M. S., S.S and T.T thanks CSIR for the award of
the fellowship. IIIM-communication No. CSIR-IIIM/IPR/00114.
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