Nano copper catalyzed synthesis of symmetrical/unsymmetrical sulfones from aryl/alkyl halides and p-toluenesulfonylmethylisocyanide: TosMIC as a tosyl source

Article abstract of DOI:10.1016/j.tet.2020.131263

A magnetically induced nano copper-catalyzed efficient and mild route for the synthesis of diaryl and alkyl/aryl sulfones from aryl/alkyl halides and tosylmethyl isocyanide (TosMIC) has been developed. A variety of aryl and alkyl sulfones have been obtained in very good to excellent yields. Sulfones containing molecules have medicinal relevance as they are known to possess various activities such as antifungal, anti-HIV, antitumor, and anticancer. Herein, a magnetically induced nano copper-catalyzed efficient and mild route for the synthesis of biaryl and alkyl/aryl sulfones from aryl/alkyl halides and tosylmethyl isocyanide (TosMIC) has been developed. A variety of aryl and alkyl sulfones have been obtained in very good to excellent yields. In this newly developed protocol TosMIC acts as sulfonyl source. The catalyst can magnetically be recovered and recycled five times without significant loss in activity.

Full text of DOI:10.1016/j.tet.2020.131263

Tetrahedron xxx (xxxx) xxx
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Nano copper catalyzed synthesis of symmetrical/unsymmetrical
sulfones from aryl/alkyl halides and p-
toluenesulfonylmethylisocyanide: TosMIC as a tosyl source
Mandalaparthi Phanindrudu c, Pogula Jaya b c, Pravin R. Likhar b c,
Dharmendra Kumar Tiwari
a
b
,
,
,
a, *
Molecular Synthesis and Drug Discovery Laboratory, Center of Biomedical Research, Sanjay Gandhi Post-Graduate Institute of Medical Sciences Campus,
Raebareli Road, Lucknow, 226014, India
Catalysis and Fine Chemicals Department, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India
b
c
Academy of Scientific & Innovative Research (AcSIR), New Delhi, 110001, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 February 2020
Received in revised form
A magnetically induced nano copper-catalyzed efficient and mild route for the synthesis of diaryl and
alkyl/aryl sulfones from aryl/alkyl halides and tosylmethyl isocyanide (TosMIC) has been developed. A
variety of aryl and alkyl sulfones have been obtained in very good to excellent yields. Sulfones containing
molecules have medicinal relevance as they are known to possess various activities such as antifungal,
anti-HIV, antitumor, and anticancer. Herein, a magnetically induced nano copper-catalyzed efficient and
mild route for the synthesis of biaryl and alkyl/aryl sulfones from aryl/alkyl halides and tosylmethyl
isocyanide (TosMIC) has been developed. A variety of aryl and alkyl sulfones have been obtained in very
good to excellent yields. In this newly developed protocol TosMIC acts as sulfonyl source. The catalyst can
magnetically be recovered and recycled five times without significant loss in activity.
1
April 2020
Accepted 5 May 2020
Available online xxx
Keywords:
Copper nano particle
Aryl-aryl
Aryl-alkyl sulfones
TosMIC
© 2020 Elsevier Ltd. All rights reserved.
Tosyl source
1. Introduction
Sulfones are key structural unit frequently encountered in
numerous bioactive natural products, pharmaceuticals, agro-
chemicals, drug candidates (Figure 1, A-F) and polymer materials
[
1e3]. Sulfone containing molecules possess a broad range of bio-
logical activities such as cyclooxygenase-2 (COX-2) inhibitor, anti-
fungal, antimicrobial, anti-inflammatory, anti-HIV, antitumor, and
anticancer activities [4]. Besides, they are also known to display
interesting chemical properties and are useful intermediates in
organic synthesis [5]. Owing to their remarkable biological impor-
tance, considerable attention has been paid to develop an efficient
and mild protocol for aryl sulfone synthesis and as a result,
numerous new synthetic methodologies have appeared in the
literature [6].
Fig. 1. Biologically active molecules substituted aryl sulfones.
halide with thiol followed by the oxidation or the reaction of either
organomagnesium halides or organolithiums with sulfonate esters
7]. But the use of foul-smelling thiols and a stoichiometric amount
Conventionally, biaryl sulfones can easily be accessed by sulfo-
nylation of an aromatic ring or nucleophilic substitution reaction of
[
of aluminium chloride are the few drawbacks associated with these
classical methods.
*
Corresponding author.
E-mail addresses: dkt80.org@gmail.com, dktiwari@cbmr.res.in (D.K. Tiwari).
In the recent past, the transition metal-mediated cross-coupling
https://doi.org/10.1016/j.tet.2020.131263
040-4020/© 2020 Elsevier Ltd. All rights reserved.
0
Please cite this article as: M. Phanindrudu et al., Nano copper catalyzed synthesis of symmetrical/unsymmetrical sulfones from aryl/alkyl
halides and p-toluenesulfonylmethylisocyanide: TosMIC as a tosyl source, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131263

2
M. Phanindrudu et al. / Tetrahedron xxx (xxxx) xxx
reaction, however, recently we and few other groups have used
TosMIC as a tosyl source in different organic transformations [13].
In the frame of our continuing research program towards the
development of new methodologies for the synthesis of various
biologically important heterocycles [14], herein, we report an effi-
cient and mild method for the synthesis of biaryl sulfones from
tosylmethyl isocyanide and aryl iodides in the presence of
0
magnetically recoverable and reusable Cu /Fe
3
O
4
. Notably, the re-
action also worked well with alkyl iodides to give corresponding
alkyl-aryl sulfones in good yields [10]. Furthermore, the magnetic
separation of catalysts from the reaction medium makes this
strategy more convenient and practical to access.
3 4
Fig. 2. Recycle potential diagram of Cu(0)/Fe O for the preparation of biaryl sulfone.
Reaction conditions: 1a (1.0 mmol), 2 (1.2 mmol), cat. (Cu 8 wt%, 30 mg) and K
2
CO
3
ꢀ
2. Results and discussion
(
2.0 mmol) at 90 C for 12 h.
We have chosen phenyl iodide (1a) and tosylmethyl isocyanide
(2) as model substrates for this investigation. Our first attempt by
treating phenyl iodide (1a, 1.0 mmol), tosylmethyl isocyanide (2,
reactions of sulfinic acid salts with aryl halides have emerged as
powerful tools to access biaryl sulfones. In this context, Suzuki and
co-workers have reported the cross-coupling of aryl iodides and
sulfinic acid in the presence of the stoichiometric amount of CuI (1.5
1.2 mmol), and K
presence of Cu /Fe O under nitrogen condition at room temper-
2
CO
3
(2.0 mmol) in dry DMSO (3.0 mL) in the
0
3 4
ꢀ
equiv.) in DMF at 110 C (scheme 1, eq.-a) [8]. Furthermore, Wang
ature for 12 h was found to be unsuccessful (Table 1, entry-1).
ꢀ
and co-workers have developed an efficient and catalytic meth-
odology to access biaryl sulfones from aryl iodides and sulfinic acid
However, when the reaction mixture was heated at 50 C, the
desired product was obtained albeit in very low yield (12%) (Table 1,
0
in the presence of a copper catalyst and N, N -dimethylethylene-
entry-2). The desired biaryl sulfone 3a was obtained in 25% yield
ꢀ
diamine (DMEDA) as an additive (scheme-1, eq.-b) [9]. On the other
when the reaction mixture was heated at 70 C for 12 h under
hand, Ma and co-workers have demonstrated
L-proline-promoted
oxygen (Table 1, entry-3). To our delight, the desired 3a was ob-
ꢀ
and copper iodide catalyzed coupling reaction of aryl halides and
sulfinic acid salt (scheme 1,-eq.-c) [10]. Although all these beautiful
methods allow convenient access to aryl sulfones the requirements
of a stoichiometric amount of copper salts, additives, amino acids
and recovery and reusability of catalysts is the major drawback
associated with these methods. It is important to mention here that
most of the methods reported in the literature are limited to only
biaryl sulfones whereas the syntheses of alkyl-aryl sulfones are not
much explored. In the recent past, tosylmethyl isocyanide (TosMIC)
has emerged as a privileged reagent that undergoes into various
organic transformations reactions including [3 þ 2]-cycloaddition
with the substrates containing C]O, C]N, C]C, and C^C groups
to offer a large number of value-added heterocycles [11]. Further-
more, they have also been employed in the synthesis of natural
products such as variolin B, halichondrin B, attenol A, and man-
souramycin B [12]. From the literature reports it is evident that the
ToSMIC is mostly used as a 1,3-dipole in various cycloaddition
tained in 54% yield when the reaction was performed at 90
C
(Table 1, entry-4). Further increasing the reaction temperature
(120 C) leads to an inferior yield of the desired product (Table 1,
ꢀ
entry-5). A better yield of the required 3a was obtained when the
reaction was carried out under air (Table 1, entry-6). A substantial
increase in the yield (83%) was observed when the reaction was
performed under an oxygen atmosphere (Table 1, entry-7). At this
stage, the product 3a was characterized by various spectroscopic
1
13
techniques such as H NMR, C NMR, and HRMS. The spectral data
of 3a is exactly matched with the previously reported compound in
literature [6b]. During our investigations, we also screened various
0
0
nano-catalysts such as Cu /Al
the inferior yields of the desired product (Table 1, entries 8e9). The
homogeneous catalysts such as CuI, Cu(OTf)2, and Cu(OAc) were
2 3
O , Cu /rGO but all of them furnished
2
also investigated but all of them were found to be unsuccessful to
give the desired product (Table 1, entries 10e12). To further
improve the yield of desired 3a, various organic and inorganic bases
3 2 3 2 3
such as Et N, Na CO and Cs CO were also tested but all of them
furnished the required 3a (Table 1, entries 14e15) in lower yield.
We next screened various solvents such as DMF, DME, and toluene
but all of them furnished the inferior yields of aimed product 3a
(
Table 1, entries 16e18).
Reaction conditions: [ Phenyl iodide 1a (1.0 mmol), TosMIC 2,
a]
0
(1.2 mmol), K
2
CO
3
(2.0 mmol) and Cu /Fe
3
O
4
(Cu 8 wt%, 30 mg) at
ꢀ
[b]
[c]
[d]
9
0
C for 12 h, under N
2
;
under air
under oxygen;
When Phenylchloride was used;
When
[e]
[f]
Phenylbromide was used,
when 2.0 equivalents of TosMIC was used; rGO ¼ reduced graphene
oxide N. O. ¼ not observed.
Instead of phenyl iodide (1a) we also employed phenyl bromide
00
1′a) and phenyl chloride (1 a) into this reaction. Gratifying, reac-
(
tion worked well with phenyl bromide and furnished the desired
product in slightly lower yield (75%) (Table 1 entry-19). On the
other hand, only a trace amount of the desired product was ob-
tained with phenyl chloride (1′b) (Table 1 entry-20). Using 2.0
equivalents of TosMIC also furnished lower yield of desired product
(Table 1, entry-21).(See Table 2)
The optimized reaction conditions in hand (Table 1, entry 6), we
Scheme 1. Previous approaches for the synthesis of useful aryl sulfones along with the
current work.
next turned our attention towards the substrate scope of the
Please cite this article as: M. Phanindrudu et al., Nano copper catalyzed synthesis of symmetrical/unsymmetrical sulfones from aryl/alkyl
halides and p-toluenesulfonylmethylisocyanide: TosMIC as a tosyl source, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131263

M. Phanindrudu et al. / Tetrahedron xxx (xxxx) xxx
3
Table 1
Optimization of reaction conditions. .
a
Entry
Catalyst
Base
Solvent
Temp
Yield
ꢀ
/[ C]
0
1
2
3
4
5
6
7
8
9
Cu /Fe
3
3
3
3
3
3
3
O
O
O
O
O
O
O
4
4
4
4
4
4
4
K
K
K
K
K
K
K
K
K
K
K
K
2
2
2
2
2
2
2
2
2
2
2
2
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
3
3
3
3
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
Rt
N$O.
12
25
0
Cu /Fe
50
70
90
120
90
90
90
90
90
90
90
90
90
90
90
90
90
90
90
90
0
Cu /Fe
0
Cu /Fe
54
0
Cu /Fe
19
0
b
Cu /Fe
71
0
c
Cu /Fe
83
45
0
c
Cu /Al
2
O
3
0
c
Cu /rGO
CuI
17
c
1
1
1
1
1
1
1
1
1
1
2
2
0
1
2
3
4
5
6
7
8
9
0
1
N$O.
Cu(OTf)
2
N$O.c
c
Cu(OAc)
2
N$O.
0
c
Cu /Fe
3
3
3
3
3
3
3
3
3
O
O
O
O
O
O
O
O
O
4
4
4
4
4
4
4
4
4
Et
Na
Cs
3
N
21
0
c
Cu /Fe
2
CO
CO
3
71
0
c
Cu /Fe
2
3
73
0
c
Cu /Fe
K
2
K
2
K
2
K
2
K
2
K
2
CO
3
CO
3
CO
3
CO
3
CO
3
CO
3
65
0
c
Cu /Fe
DME
13
0
c
Cu /Fe
Toluene
DMSO
DMSO
DMSO
28
0
d
Cu /Fe
75
0
e
Cu /Fe
Trace
0
80f
Cu /Fe
present methodology concerning various aryl and alkyl halides
1a,1′a - 1u, 1′u) and TosMIC (2). The aryl halides containing both
electron-donating (EDG) and electron-withdrawing (EWG) groups
smoothly underwent this transformation to furnish the desired
products in very good yields. Various functional groups such as
methoxy (1e & 1f), hydroxyl (1g), halo (1h & 1i), cyano (1j), ester
sulfone (3t) were obtained in 81% and 69% yields respectively.
(
Next, a recyclability test of the catalyst was performed under
optimized conditions using phenyl iodide and ToSMIC. After each
catalytic cycle, the catalyst was separated from the reaction
mixture, washed by ethanol, dried at room temperature under
vacuum, and subjected to the next run. Only slight changes in the.
yield of desired sulfone conversion was detected upon three
consecutive runs. However, a slight drop in the conversion (74-70%)
from the 4th to 5th cycles is observed it may be due to the clogging
of some catalytic active sites with organic reagents during the
reaction.
(1k), and nitro (1l & 1n) groups were well tolerated under the
optimized reaction conditions and furnished the corresponding
biaryl sulfones in very good yields. Surprisingly, 4-iodophenol (1g)
also effectively reacted with TosMIC (2) to form the desired product
(3g) in 62%. Furthermore, various heterocyclic aromatic iodides
such as 3-iodopyridine (1n), 2-iodothiophene (1o), 3-
iodoisoquinoline (1p) were also reacted with TosMIC under opti-
mized reaction conditions leading to the formation of desired
To further understand the radical reaction mechanism, we car-
ried out two different control experiments (Scheme-4). Initially,
when the reaction was performed in the presence of TEMPO, only a
trace amount of desired product (3a) was obtained it indicates the
involvement of the radical mechanism. On the other hand, when
reaction was performed in the absence of aryl halide (1a) under
products (3n-3p) in very good yields. Moreover,
naphthyl aryl iodides ((1q-1r) also produced the desired product
3q-3r) in good yield. We next evaluated the substrate scope of
a-naphthyl and b-
(
present methodology with respect to aliphatic iodides. To our
delight, various alkyl halides such as benzyl iodide (1s), 1-
iodobutane (1t), 1-iodoheptane (1u), and 3-ethyl-1-iodopentane
standard
conditions
it
gave
S-(p-tolyl)
4-
methylbenzenesulfonothioate (3w) in 24% yield (Scheme-4, eq.-
b). The formation of 3w, clearly suggests that the reaction going
through radical mechanism [16].
(1v) effectively underwent this catalytic transformation to furnish
the corresponding alkyl-aryl sulfones (3s-3v) in good yields.
Based on controlled experiments and previous literature reports
[13], a plausible mechanism is proposed (Scheme-4). The catalytic
cycle started with oxidative addition of Cu to organo halides to form
intermediate “A”. From this intermediate halide get replaced by
Tosyl radical which is in-situ generated from TosMIC, furnishing
intermediate “B” [13c]. Finally through reductive elimination in-
termediate “B” give rise to desired product 3a and completing a
catalytic cycle by producing a catalyst for the next cycle.
[
a]
Reaction conditions:
Aryl/Alkyl halides (1a, 1′a -1x, 1′v;
0
1
(
.0 mmol); TosMIC 2, (1.2 mmol), K
2
CO
Cu 8 wt%, 30 mg) at 90 C for 12 h under O
The selective tosylation of 1,4-diiodobenzene was also investi-
gated under the standard reaction conditions (Scheme-2). When
,4-diiodobenzene was treated with TosMIC under the optimized
3 3 4
(2.0 mmol) and Cu /Fe O
ꢀ
2
.
1
conditions it furnished the mono tosylated product (3i) in 65% yield
along with a trace amount of ditosylated product (3v). On the other
hand, when 1,4-diiodobenzene (1i) was treated with 2.4 equiva-
lents of TosMIC under optimized reaction conditions it furnished
only ditosylated product (3j) in 69% yield.
To further expand the synthetic proficiency of this present
methodology, a gram-scale synthesis for both aryl-aryl (3a) and
alkyl-aryl (3t) sulfones were performed under the optimized con-
ditions (Scheme-3). Delightfully, biaryl sulfone (3a) and alkyl/aryl
3. Conclusion
In summary, we have developed a catalytic, mild and efficient
method for the synthesis of unsymmetrical aryl sulfones from
readily available starting materials in very good yields. Further-
more, the nanocatalyst was magnetically separated and reused
without any obvious loss of activity. In this newly developed
Please cite this article as: M. Phanindrudu et al., Nano copper catalyzed synthesis of symmetrical/unsymmetrical sulfones from aryl/alkyl
halides and p-toluenesulfonylmethylisocyanide: TosMIC as a tosyl source, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131263

4
M. Phanindrudu et al. / Tetrahedron xxx (xxxx) xxx
Table 2
Substrate scope with different halides and TosMIC.
Scheme 4. (a)Controlled experiments, (b)Possible reaction pathway.
on the wider applications of the current methodology is in progress
in our laboratory.
4. Experimental section
4.1. General information
All reagents were purchased from commercial suppliers and
used without further purification. All experiments were carried out
under nitrogen atmosphere. All the solvents used for the reaction
were distilled before use. The product purification by column
chromatography was accomplished using silica gel 100e200 mesh.
Analytical TLC was performed with Merck silica gel 60 F254 plates,
1
13
and the products were visualized by UV detection. H and C NMR
spectra were recorded with 300, 400 and 500 MHz NMR in-
struments with tertramethylsilane (TMS) as an internal standard.
High-resolution mass spectra (ESI-HRMS) were recorded on ESI-
QTOP mass spectrometer. Chemical shifts (
ppm using TMS as an internal standard, and spin-spin coupling
constants (J) are given in Hz. Multiplicities in the H NMR spectra
d
¼ ) are reported in
1
are described as: s ¼ singlet, d ¼ doublet, t ¼ triplet, q ¼ quartet,
m ¼ multiplet, bs ¼ broad singlet; coupling constants are reported
in Hz. Low (MS) and high (HRMS) resolution mass spectra were
recorded on a Waters 2695 and Thermo Scientific Exactive spec-
trometer respectively and mass/charge (m/z) ratios are reported as
values in atomic mass units.
4.2. General experimental procedure for the synthesis of aryl/aryl
and alkyl/aryl sulfones (3a) [6b]
Scheme 2. Selective sulfonylation of diiodobenzene
A mixture of aryl halides (1a-1r) or alkyl halides (1s - 1v)
(
1.0 mmol), Tosylmetylisocyanide (1.2 mmol), K
2
3
CO (1.0 mmol)
and Cu(0)/Fe
3
O
4
(30 mg) in distilled DMSO (4.0 mL) was heated at
ꢀ
90 C for 10 h under oxygen atmosphere. The stirring was stopped
and mixture allows attain room temperature. Catalyst was sepa-
rated with the help of external magnate and water (10.0 mL) was
added to the reaction mixture. The aqueous layer was further
washed with ethyl acetate (3 ꢁ 10 mL). The organic layer was
washed with brine (10.0 mL) and dried over anhydrous sodium
sulphate. The solvent was removed under reduced pressure to give
crude 3a which was Purified by column chromatography on silica
gel (petroleum ether/ethyl acetate ¼ 88/12) to afford 3a as a white
Scheme 3. Gram scale synthesis of Tosyl sulfone (3a) and alkyl/aryl sulfone (3v).
ꢀ
1
solid (193 mg, 83%), m. p. 129e130 C.; H NMR (500 MHz, CDCl
3
)
protocol TosMIC acts as a source of the sulfonyl group. The ready
availability of starting materials, broad substrate scope, and oper-
ational simplicity makes the present method an attractive option
for the synthesis of the unsymmetrical aryl sulfones. Further study
d
¼ 7.95e7.91 (m, 2H), 7.83 (d, J ¼ 8.3 Hz, 2H), 7.57e7.45 (m, 1H),
13
7
.50e7.47 (m, 2H), 7.29 (d, J ¼ 8.0 Hz, 2H), 2.39 (s, 3H); C NMR
75 MHz, CDCl
¼ 144.1, 142.0, 138.6, 133.0, 130.9, 129.9, 129.5,
29.0, 127.6, 21.5. HRMS (ESI, Orbitrap) calcd for C13
S [MþH]
(
1
3
) d
13 2
H O
Please cite this article as: M. Phanindrudu et al., Nano copper catalyzed synthesis of symmetrical/unsymmetrical sulfones from aryl/alkyl
halides and p-toluenesulfonylmethylisocyanide: TosMIC as a tosyl source, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131263

M. Phanindrudu et al. / Tetrahedron xxx (xxxx) xxx
5
is 233.0631 and found 233.0632.
.3. 1-Methyl-2-tosylbenzene (3b)
b as white solid was prepared by following the procedure
4.9. 1-Chloro-4-tosylbenzene (3h)
3h as white solid was prepared by following the procedure
4
described for 3a in 78% yield (225 mg). TLC: R
f
(3h) ¼ 0.43 (pe-
ꢀ
1
troleum ether/ethyl acetate ¼ 9:1); M. P. 115e117 C.; H NMR
3
(
7
500 MHz, CDCl
3
)
d
d
¼ 7.86 (d, J ¼ 8.6 Hz, 2H), 7.81 (d, J ¼ 8.3 Hz, 2H),
described for 3a in (195 mg) 79% yield. TLC: R
f
(3b) ¼ 0.5 (petroleum
13
.46 (d, J ¼ 8.6 Hz, 2H), 7.31 (d, J ¼ 8.2 Hz, 2H), 2.40 (s, 3H); C NMR
ꢀ
1
ether/ethyl acetate ¼ 9:1). M. P. 119e121 C.; H NMR (400 MHz,
(125 MHz, CDCl
3
)
¼ 144.53, 140.56, 139.69, 138.27, 130.07, 129.57,
CDCl
3
)
d
¼ 8.19 (d, J ¼ 7.7 Hz, 1H), 7.75 (d, J ¼ 8.1 Hz, 2H), 7.46 (t,
1
28.99, 127.73, 77.30, 77.05, 76.79, 21.61; HRMS (ESI, Orbitrap) calcd
J ¼ 7.2 Hz, 1H), 7.38 (t, J ¼ 7.5 Hz, 1H), 7.29 (d, J ¼ 7.9 Hz, 2H), 7.22 (d,
for C13
H11ClO
2
S [MþNa] is 289.0060 and found 289.0067.
13
J ¼ 7.4 Hz, 1H), 2.44 (s, 3H), 2.41 (s, 3H); C NMR (100 MHz, CDCl
3
)
d
¼ 143.9, 139.2, 138.3, 137.9, 133.4, 132.6, 129.6, 129.3, 127.7, 126.4,
4.10. 1-Iodo-4-tosylbenzene (3i)
2
2
1.6, 20.2; HRMS (ESI, Orbitrap) calcd for C14
H
15
O
2
S [MþH] is
47.0787 and found 247.0790.
3
i as white sticky solid was prepared by following the procedure
described for 3a in 65% yield (232 mg). TLC: R
(3i) ¼ 0.50 (petro-
leum ether/ethyl acetate ¼ 9:1); H NMR (400 MHz, CDCl ¼ 7.84
d, J ¼ 8.5 Hz, 2H), 7.80 (d, J ¼ 8.3 Hz, 2H), 7.63 (d, J ¼ 8.6 Hz, 2H),
f
1
4.4. 1-Methyl-3-tosylbenzene (3c)
3
) d
(
13
3
c as white solid was prepared by following the procedure
7.30 (d, J ¼ 8.1 Hz, 2H), 2.40 (s, 3H); C NMR (125 MHz, CDCl
3
)
described for 3a in 80% yield (197 mg). TLC: R
f
(3c) ¼ 0.5 (petroleum
d
¼ 144.54, 141.78, 138.52, 138.20, 130.07, 128.91, 127.74, 100.75,
ꢀ
ꢀ
1
ether/ethyl acetate ¼ 9:1). M.P. 118e120 C.; (Lit. 120e122 C); H
21.62; Data in accordance with the literature.[(15a)].
NMR (500 MHz, CDCl
H), 7.39e7.32 (m, 2H), 7.29 (d, J ¼ 8.1 Hz, 2H), 2.39 (s, 6H); C NMR
125 MHz, CDCl
¼ 144.0, 141.8, 139.4, 138.8, 133.8, 129.9, 129.1,
27.7, 124.7, 21.5, 21.3; HRMS (ESI, Orbitrap) calcd for C14
MþH] is 247.0787 and found 247.0791.
3
)
d
¼ 7.82 (d, J ¼ 8.3 Hz, 2H), 7.73 (d, J ¼ 7.1 Hz,
13
2
4.11. 4-Tosylbenzonitrile (3j)
(
3
) d
1
H
15
O
2
S
3j as white solid was prepared by following the procedure
described for 3a in 72% yield (201 mg). TLC: R
(3d) ¼ 0.43 (petro-
leum ether/ethyl acetate ¼ 9:1); M. P. 130e132 C.; H NMR
(400 MHz, CDCl
¼ 8.03 (d, J ¼ 8.6 Hz, 2H), 7.83 (d, J ¼ 8.3 Hz, 2H),
7.78 (d, J ¼ 8.6 Hz, 2H), 7.34 (d, J ¼ 8.0 Hz, 2H), 2.42 (s, 3H); C NMR
(100 MHz, CDCl
¼ 146.30, 145.28, 137.16, 133.04, 130.31, 128.15,
128.08, 117.21, 116.75, 77.36, 77.04, 76.72, 21.68; HRMS (ESI, Orbi-
[
f
0
ꢀ
1
4
.5 4,4 -Sulfonylbis(methylbenzene (3d): 3d as white solid was
prepared by following the procedure described for 3a in 82% yield
3
) d
13
(
202 mg). TLC: R
f
(3d) ¼ 0.50 (petroleum ether/ethyl acetate ¼ 9:1).
ꢀ
M. P. 133e135 C.; 1H NMR (400 MHz, CDCl3)
4
d
d
¼ 7.81 (d, J ¼ 8.3 Hz,
3
) d
13
H), 7.28 (d, J ¼ 8.1 Hz, 4H), 2.38 (s, 3H); C NMR (100 MHz, CDCl3)
¼ 143.9, 139.0, 129.8, 127.5, 21.5; HRMS (ESI, Orbitrap) calcd for
trap) calcd for C14
280.0406.
H11NO
2
SNa [MþNa] is 280.0403 and found
C
14
H
15
O
2
S [MþH] is 247.0787 and found 247.0790.
4
.6 1-Methoxy-4-tosylbenzene (3e): 3e as yellow solid was pre-
pared by following the procedure described for 3a in 74% yield
4.12. Methyl 4-tosylbenzoate (3k)
(
194 mg). TLC: R
f
(3e) ¼ 0.50 (petroleum ether/ethyl acetate ¼ 9:1).
1
ꢀ
M. P. 97e98 C.; H NMR (400 MHz, CDCl
2
3
)
d
¼ 7.86 (d, J ¼ 8.7 Hz,
3k as white solid was prepared by following the procedure
H), 7.80 (m, J ¼ 8.5 Hz, 2H), 7.26 (d, J ¼ 7.9 Hz, 2H), 6.95 (J ¼ 8.9 Hz,
described for 3a in 76% yield (221 mg). TLC: R
leum ether/ethyl acetate ¼ 9:1); m. p. 124e125 C.; H NMR
(400 MHz, CDCl
¼ 8.14 (d, J ¼ 8.6 Hz, 2H), 7.99 (d, J ¼ 8.6 Hz, 2H),
7.83 (d, J ¼ 8.3 Hz, 2H), 7.32 (d, J ¼ 8.0 Hz, 2H), 3.93 (s, 3H), 2.41 (s,
f
(3k) ¼ 0.43 (petro-
13
ꢀ
1
2
1
(
2
H), 3.83 (s, 3H), 2.38 (s, 3H); C NMR (125 MHz, CDCl
43.7, 139.4, 133.5, 130.9, 129.7, 128.8, 127.3, 114.4, 55.6, 21.5; HRMS
ESI, Orbitrap) calcd for C14
S [MþH] is 263.0736 and found
3
)
d
¼ 163.2,
3
) d
15 3
H O
13
63.0743.
3H); C NMR (100 MHz, CDCl
30.42, 130.11, 127.94, 127.56, 52.68, 21.63; HRMS (ESI, Orbitrap)
calcd for C15
S [MþH] is 291.0686 and found 291.0685.
3
)
d
¼ 165.56, 145.91, 144.74, 134.12,
1
15 4
H O
4.7. 1-Methoxy-2-tosylbenzene (3f)
4
.13. 1-Methyl-4-((4-nitrophenyl)sulfonyl)benzene (3l)
3
f as white solid was prepared by following the procedure
described for 3a in 71% yield (186 mg). TLC: R
(3f) ¼ 0.43 (petro-
leum ether/ethyl acetate ¼ 9:1); M. P. 105e106 C.; H NMR
400 MHz, CDCl
f
3
l as white solid was prepared by following the procedure
described for 3a in 69% yield (207 mg). TLC: R
(3l) ¼ 0.43 (petro-
leum ether/ethyl acetate ¼ 9:1); M. P. 163e165 C.; H NMR
400 MHz, CDCl
¼ 8.33 (d, J ¼ 9.0 Hz, 2H), 8.11 (d, J ¼ 9.0 Hz, 2H),
.85 (d, J ¼ 8.4 Hz, 2H), 7.35 (d, J ¼ 8.0 Hz, 2H), 2.43 (s, 3H); C NMR
125 MHz, CDCl
¼ 150.25, 147.80, 145.41, 137.05, 130.36, 128.83,
28.12, 124.49, 21.68; HRMS (ESI, Orbitrap) calcd for C13 SNa
MþNa] is 300.0301 and found 300.0307.
ꢀ
1
f
(
3
)
d
¼ 8.14 (dd, J ¼ 7.9, 1.6 Hz, 1H), 7.85 (d, J ¼ 8.2 Hz,
ꢀ
1
2
6
H), 7.57e7.49 (m,1H), 7.27 (d, J ¼ 7.5 Hz, 2H), 7.09 (t, J ¼ 7.5 Hz,1H),
(
7
(
1
3
) d
13
.89 (d, J ¼ 8.3 Hz, 1H), 3.77 (s, 3H), 2.41 (s, 3H); C NMR (75 MHz,
¼ 157.0, 143.7, 138.5, 135.3, 129.7, 129.1, 128.4, 120.5, 55.8,
1.6; HRMS (ESI, Orbitrap) calcd for C14H15O3S [MþH] is 263.0736
and found 263.0744.
1
3
3
CDCl ) d
3
) d
2
H11NO
4
[
4.8. 4-Tosylphenol (3g)
4.14. 1-Nitro-2-tosylbenzene (3 m)
3
g as white solid was prepared by following the procedure
described for 3a in 62% yield (154 mg). TLC: R
(3g) ¼ 0.43 (petro-
leum ether/ethyl acetate ¼ 9:1); M. P. 140e142 C.; H NMR
400 MHz, CDCl
¼ 8.33 (d, J ¼ 9.0 Hz, 2H), 8.11 (d, J ¼ 9.0 Hz, 2H),
.85 (d, J ¼ 8.4 Hz, 2H), 7.35 (d, J ¼ 8.0 Hz, 2H), 2.43 (s, 3H); C NMR
125 MHz, CDCl
3 m as white solid was prepared by following the procedure
described for 3a in 77% yield (231 mg). TLC: R
(3 m) ¼ 0.43 (pe-
troleum ether/ethyl acetate ¼ 9:1); M. P. 170e172 C.; H NMR
(400 MHz, CDCl
¼ 8.36e8.30 (m, 1H), 7.86 (d, J ¼ 8.4 Hz, 2H),
7.73 (dd, J ¼ 6.7, 1.7 Hz, 3H), 7.35 (d, J ¼ 8.0 Hz, 2H), 2.44 (s, 3H);
NMR (100 MHz, CDCl
¼ 148.50, 145.05, 137.45, 134.98, 134.38,
132.42, 131.48, 129.79, 128.44, 124.67, 21.72; HRMS (ESI, Orbitrap)
calcd for C13
SNa [MþNa] is 300.0301 and found 300.0307.
f
f
ꢀ
1
ꢀ
1
(
7
(
3
)
d
3
) d
1
3
13
C
3
)
d
¼ 150.25, 147.80, 145.41, 137.05, 130.36, 128.83,
3
) d
1
28.12, 124.49, 77.31, 77.05, 76.80, 21.68; HRMS (ESI, Orbitrap) calcd
for C13
H
13
O
3
S [MþH] is 249.0580 and found 249.0586.
H11NO
4
Please cite this article as: M. Phanindrudu et al., Nano copper catalyzed synthesis of symmetrical/unsymmetrical sulfones from aryl/alkyl
halides and p-toluenesulfonylmethylisocyanide: TosMIC as a tosyl source, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131263

6
M. Phanindrudu et al. / Tetrahedron xxx (xxxx) xxx
4
.15. 3-Tosylpyridine (3n)
(s, 2H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl
30.8, 129.5, 128.9, 128.3, 62.9, 21.66. Data in accordance with the
literature.[(15b)].
3
)
d
¼ 144.6, 135.0,
1
3
n as white solid was prepared by following the procedure
described for 3a in 68% yield (159 mg). TLC: R
(3n) ¼ 0.43 (petro-
leum ether/ethyl acetate ¼ 9:1); M. P.; 160e161 C.; H NMR
500 MHz, CDCl
¼ 9.08 (s, 1H), 8.72 (s, 1H), 8.14 (d, J ¼ 7.8 Hz,
H), 7.78 (d, J ¼ 8.2 Hz, 2H), 7.38 (s, 1H), 7.27 (d, J ¼ 8.0 Hz, 2H), 2.35
f
ꢀ
1
4.21. 1-(Butylsulfonyl)-4-methylbenzene (3t)
(
1
3
) d
3
t as sticky solid was prepared by following the procedure
described for 3a in 75% yield (159 mg). TLC: R
(3t) ¼ 0.43 (petro-
¼ 7.78
d, J ¼ 6.9 Hz,1H), 7.36 (d, J ¼ 7.3 Hz,1H), 3.07 (t, J ¼ 7.8 Hz, 2H), 2.45
s, 3H), 1.74e1.60 (m, 2H), 1.38 (dd, J ¼ 14.6, 7.3 Hz, 2H), 0.92e0.84
13
(
s, 3H); C NMR (100 MHz, CDCl
35.18, 130.25, 127.89, 77.37, 77.05, 76.73, 21.65; HRMS (ESI, Orbi-
trap) calcd for C12
S [MþH] is 234.0583 and found 234.0589.
3
)
d
¼ 153.37,148.51, 145.04,137.76,
f
1
1
leum ether/ethyl acetate ¼ 9:1). H NMR (500 MHz, CDCl
3
) d
H12NO
2
(
(
(
5
[
ꢀ
.16. 2-Tosylthiophene (3 )
13
4
m, 3H); C NMR (100 MHz, CDCl
6.1, 24.7, 21.5, 13.5; HRMS (ESI, Orbitrap) calcd for C11
MþH] is 213.0944 and found 213.0948.
3
)
d
¼ 144.5, 136.2, 129.8, 128.0,
17 2
H O S
ꢀ
3
as white solid was prepared by following the procedure
ꢀ
described for 3a in 64% yield (152 mg). TLC: R
f
(3 ) ¼ 0.43 (petro-
ꢀ
1
leum ether/ethyl acetate ¼ 9:1); M. P. 118e120 C.; H NMR
500 MHz, CDCl
¼ 7.87 (d, J ¼ 8.4 Hz, 2H), 7.67 (dd, J ¼ 3.8,1.4 Hz,
H), 7.62 (dd, J ¼ 5.0, 1.4 Hz, 1H), 7.31 (d, J ¼ 8.0 Hz, 2H), 7.06 (dd,
4.22. 1-(Hexylsulfonyl)-4-methylbenzene (3u)
(
1
3
) d
3u as a thick oil was prepared by following the procedure
13
J ¼ 5.0, 3.8 Hz, 1H), 2.41 (s, 3H); C NMR (100 MHz, CDCl
¼ 144.3, 143.5, 139.1, 133.5, 133.0, 129.9, 127.7, 127.4, 21.6; Data in
accordance with the literature [(15c)].
3
)
described for 3a in 71% yield (171 mg). TLC: R
f
(3u) ¼ 0.43 (petro-
d
1
leum ether/ethyl acetate ¼ 9:1); H NMR (500 MHz, CDCl3)
d
¼ 7.82e7.74 (m, 2H), 7.40e7.31 (m, 2H), 3.11e3.00 (m, 2H), 2.43 (s,
3
4
1
H), 1.72e1.65 (m, 2H), 1.34 (d, J ¼ 5.1 Hz, 2H), 1.24 (d, J ¼ 2.5 Hz,
4.17. 3-Tosylquinoline (3p)
13
H), 0.85 (t, J ¼ 6.5 Hz, 3H); C NMR (125 MHz, CDCl
3
)
d
¼ 144.5,
36.3, 129.8, 128.0, 56.4, 31.1, 27.9, 22.7, 22.3, 21.6, 13.9; HRMS (ESI,
3
p as white solid was prepared by following the procedure
described for 3a in 78% yield (221 mg). TLC: R
(3p) ¼ 0.43 (petro-
leum ether/ethyl acetate ¼ 9:1); M. P. 166e167 C.; H NMR
500 MHz, CDCl
Orbitrap) calcd for C13
21 2
H O
S [MþH] is 241.1257 and found
f
241.1260.
ꢀ
1
(
1
2
3
)
d
¼ 9.30 (s, 1H), 8.82 (s, 1H), 8.18 (d, J ¼ 8.3 Hz,
H), 8.04e7.86 (m, 4H), 7.68 (t, J ¼ 7.6 Hz, 1H), 7.33 (d, J ¼ 8.2 Hz,
H), 2.40 (s, 3H). 13C NMR (125 MHz, CDCl
¼ 149.2, 147.0, 144.9,
4.23. 1-((2-Ethylhexyl)sulfonyl)-4-methylbenzene (3v)
3
) d
3
v as white solid was prepared by following the procedure
described for 3a in 77% yield (207 mg). TLC: R
(3v) ¼ 0.43 (petro-
¼ 7.79
144.2,138.0,136.7,132.7,130.2,129.5,129.2,128.3,127.8, 21.6. HRMS
f
(
ESI, Orbitrap) calcd for C16
H
14NO
2
S [MþH] is 284.0740 and found
1
leum ether/ethyl acetate ¼ 9:1); H NMR (500 MHz, CDCl
3
) d
2
84.0749.
(
2
d, J ¼ 8.1 Hz, 2H), 7.35 (d, J ¼ 7.9 Hz, 2H), 3.00 (dd, J ¼ 5.9, 2.6 Hz,
H), 2.45 (s, 3H), 1.94e1.86 (m, 1H), 1.49e1.40 (m, 2H), 1.37 (dd,
4.18. 1-Tosylnaphthalene (3q)
J ¼ 14.8, 6.4 Hz, 2H), 1.22 (dd, J ¼ 13.5, 6.8 Hz, 2H), 1.16 (dd, J ¼ 14.2,
1
3
6
.4 Hz, 2H), 0.84 (t, J ¼ 7.2 Hz, 3H), 0.81 (t, J ¼ 7.4 Hz, 3H). C NMR
3
q as white solid was prepared by following the procedure
described for 3a in 68% yield (192 mg). TLC: R
(3q) ¼ 0.50 (petro-
leum ether/ethyl acetate ¼ 9:1); M. P. 101e102 C.; H NMR
400 MHz, CDCl
¼ 8.64 (d, J ¼ 8.4 Hz, 1H), 8.49 (d, J ¼ 6.6 Hz, 1H),
.08 (d, J ¼ 8.2 Hz, 1H), 7.92e7.78 (m, 4H), 7.57 (d, J ¼ 31.8 Hz, 3H),
.27 (s, 1H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl
¼ 143.9,138.8,
35.0, 134.2, 129.8, 129.0, 128.3, 127.5, 126.8, 124.4, 21.57; HRMS
ESI, Orbitrap) calcd for C17
S [MþH] is 283.0787 and found
(100 MHz, CDCl
3
) d
¼ 144.42, 137.26, 129.84, 127.93, 77.37, 77.05,
f
7
6.73, 60.01, 34.41, 32.40, 28.19, 25.74, 22.68, 21.63, 13.99, 10.19;
ꢀ
1
HRMS (ESI, Orbitrap) calcd for C15
found 269.1568.
25
H O
2
S [MþH] is 269.1570 and
(
8
7
1
(
2
3
) d
3
) d
0
4
.24. 1,4-Ditosylbenzene (3 i)
15 2
H O
0
3
i as white solid was prepared by following the procedure
83.0793.
0
described for 3a in 69% yield (266 mg). TLC: R
f
(3 i) ¼ 0.43 (petro-
1
leum ether/ethyl acetate ¼ 9:1); H NMR (400 MHz, CDCl
s, 4H), 7.83e7.77 (m, 4H), 7.31 (d, J ¼ 7.9 Hz, 4H), 2.41 (s, 6H);
NMR (100 MHz, CDCl
¼ 152.1, 146.3, 145.1, 141.8, 137.2, 130.2,
30.13, 128.3, 128.0, 21.6. Data in accordance with the
literature.[(15b)].
3
)
d
¼ 8.01
4
.19. 2-Tosylnaphthalene (3r)
13
(
C
3
) d
3
r as white solid was prepared by following the procedure
described for 3a in 76% yield (215 mg). TLC: R
(3r) ¼ 0.43 (petro-
leum ether/ethyl acetate ¼ 9:1); M. P. 127e128 C.; H NMR
400 MHz, CDCl
¼ 8.64 (d, J ¼ 8.7 Hz,1H), 8.50 (dd, J ¼ 7.4,1.2 Hz,
H), 8.08 (d, J ¼ 8.2 Hz, 1H), 7.92e7.79 (m, 3H), 7.56e7.45 (m, 3H),
1
f
ꢀ
1
(
1
3
) d
4.25. S-(p-tolyl) 4-methylbenzenesulfonothioate (3w)
13
7
(
1
.27 (dd, J ¼ 7.3, 2.5 Hz, 1H), 7.25 (s, 1H), 2.36 (s, 3H). C NMR
100 MHz, CDCl
¼ 143.9, 138.8, 136.1, 135.0, 134.2, 129.7, 129.0,
28.3, 127.5, 126.8, 124.4, 21.5. HRMS (ESI, Orbitrap) calcd for
S [MþH] is 277.06931 and found 283.07928.
3w Purified by column chromatography on silica gel (petroleum
3
) d
ether/ethyl acetate ¼ 88/12) to afford 3w as white solid a (122 mg,
1
4
4%), H NMR (400 MHz, CDCl
3
)
d
¼ 7.46 (d, J ¼ 8.4 Hz, 2H), 7.23 (d,
17 14 2
C H O
J ¼ 8.3 Hz, 2H), 7.21 (d, J ¼ 8.0 Hz, 2H), 7.14 (d, J ¼ 7.9 Hz, 2H), 2.42
13
(
1
d, J ¼ 5.3 Hz, 3H), 2.38 (s, 3H). C NMR (126 MHz, CDCl
3
)
d
¼ 144.6,
4.20. 1-(Benzylsulfonyl)-4-methylbenzene (3s)
42.0, 140.5, 136.5, 130.2, 129.3, 127.6, 124.6, 21.7, 21.5. Data in
accordance with the literature [16].
3
s as white solid was prepared by following the procedure
described for 3a in 81% yield (199 mg). TLC: R
(3s) ¼ 0.50 (petro-
leum ether/ethyl acetate ¼ 9:1); M. P. 141e142 C.; H NMR
500 MHz, CDCl
7.50 (d, J ¼ 8.3 Hz, 2H), 7.34e7.30 (m, 1H),
.28e7.25 (m, 2H), 7.25e7.22 (m, 2H), 7.09 (d, J ¼ 8.2 Hz, 2H), 4.29
f
ꢀ
1
Declaration of competing interest
(
7
3
) d
The authors declare that they have no known competing
Please cite this article as: M. Phanindrudu et al., Nano copper catalyzed synthesis of symmetrical/unsymmetrical sulfones from aryl/alkyl
halides and p-toluenesulfonylmethylisocyanide: TosMIC as a tosyl source, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131263

M. Phanindrudu et al. / Tetrahedron xxx (xxxx) xxx
7
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
(2004) 4587e4612.
6] (a) H. Yue, C. Zhu, M. Rueping, Angew. Chem. Int. Ed. 57 (2018) 1371e1375;
[
(
(
b) S. Cacchi, G. Fabrizi, A. Goggiamani, L.M. Parisi, R. Bernini, J. Org. Chem. 69
2004) 5608e5614;
Acknowledgments
(c) M. Yang, H. Shen, Y. Li, C. Shena, P.d. Zhang, RSC Adv.
6295e26300;
4 (2014)
2
(
(
d) B.P. Bandgar, S.V. Bettigeri, J. Phopase, Org. Lett. 6 (2004) 2105e2108;
e) C. Beaulieu, D. Guay, Z. Wang, D.A. Evans, Tetrahedron Lett. 45 (2004)
The Science and Engineering Research Board (SERB), New Delhi
India, is thanked for the financial support. M.P. is thankful to the
University Grants Commission (UGC) India for his fellowship. M. P.
and P. J. gratefully acknowledge the Academy of Scientific and
Innovative Research (AcSIR) for PhD registration. The authors are
grateful to the Director, CSIR-IICT and director CBMR Lucknow for
providing the necessary infrastructure.
3233e3236;
(
(
f) N. Umierski, G. Manolikakes, Org. Lett. 15 (2013) 1188e1191;
g) M.L. Kantam, B. Neelima, B. Sreedhar, R. Chakravarti, Synlett (2008)
1
455e1460;
(h) P. Bisseret, N. Blanchard, Org. Biomol. Chem. 11 (2013) 5393e5398.
7] (a) K. Schank, in: S. Patai, Z. Rappoport, C.J.M. Stirling (Eds.), The Chemistry of
Sulfones and Sulfoxides, Wiley, New York, 1988 (Chapter 7);
[
(
(
b) R.P. Greenhalgh, Synlett (1992) 235e247;
c) R.S. Reddy, J.S. Reddy, R. Kumar, P. Kumar, J. Chem. Soc., Chem. Commun.
8
4 (1992) 85;
Appendix A. Supplementary data
(
(
d) B.M. Graybill, J. Org. Chem. 32 (1967) 2931e2933;
e) M. Ueda, K. Uchiyama, T. Kano, Synthesis (1984) 323e325;
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2020.131263.
(f) W.E. Truce, T.C. Klinger, W.W. Brand, in: S. Oae (Ed.), Organic Chemistry of
Sulfur, Plenum Press, New York, 1977;
(
(
g) S.J. Nara, J.R. Harjani, M.M. Salunkhe, J. Org. Chem. 66 (2001) 8616e8620;
h) H. Gilman, N.J. Beaver, C.H. Meyers, J. Am. Chem. Soc. 47 (1925)
References
2047e2052;
(i) W.H. Baarschers, Can. J. Chem. 54 (1976) 3056e3059.
[
1] (a) Y. Harrak, G. Casula, J. Basset, G. Rosell, S. Plescia, D. Raffa, M.G. Cusimano,
[8] H. Suzuki, H. Abe, Tetrahedron Lett. 36 (1995) 6239e6242.
[9] J.M. Baskin, Z. Wang, Org. Lett. 4 (2002) 4423e4425.
[10] W. Zhu, D. Ma, J. Org. Chem. 70 (2005) 2696e2700.
[11] (a) T. Kaur, P. Wadhwa, A. Sharma, RSC Adv. 5 (2015) 52769e52787;
(b) A.V. Lygin, Angew. Chem. Int. Ed. 49 (2010) 9049e9052.
[12] (a) A. Baeza, J. Mendiola, C. Burgos, J.A. Builla, J. Vaquero, J. Eur. J. Org. Chem.
(2010) 5607e5618;
R. Pouplana, M.D. Pujol, J. Med. Chem. 53 (2010) 6560e6571;
(
(
b) D.A. Smith, R.M. Jones, Curr. Opin. Drug Discovery Dev. 11 (2008) 72e79;
c) R. Silvestri, G. De Martino, G. La Regina, M. Artico, S. Massa, L. Vargiu,
M. Mura, A.G. Loi, T. Marceddu, P. La Colla, J. Med. Chem. 46 (2003)
482e2493.
2
[2] (a) N.S. Simpkins, in: J.E. Baldwin (Ed.), Sulfones in Organic Synthesis, Perga-
mon Press, Oxford, 1993;
(b) J.S. Yadav, C.N. Reddy, G. Sabitha, Tetrahedron Lett. 53 (2012) 2504e2507;
(c) J.S. Yadav, P.A.N. Reddy, Y.J. Reddy, S. Meraj, A.R. Prasad, Eur. J. Org Chem.
28 (2013) 6317e6324;
(
b) Z.-Y. Sun, E. Botros, A.-D. Su, Y. Kim, E. Wang, N.Z. Baturay, C.-H. Kwon,
J. Med. Chem. 43 (2000) 4160e4168;
c) T. Otzen, E.G. Wempe, B. Kunz, R. Bartels, G. Lehwark-Yvetot, W. H a€ nsel, K.-
J. Schaper, J.K. Seydel, J. Med. Chem. 47 (2004) 240e253;
d) W. Hu, Z. Guo, F. Chu, A. Bai, X. Yi, G. Cheng, J. Li, Bioorg. Med. Chem. Lett
3 (2003) 1153e1160;
e) A.M. Faucher, P.W. White, C. Brochu, C. Grand-Maitre, J. Rancourt, G. Fazal,
(
(d) A. Coppola, D. Sucunza, C. Burgos, J. Vaquero, J. Org. Lett. 17 (2015) 78e81.
[13] (a) H. Bounar, Z. Liu, L. Zhang, X. Guan, Z. Yang, P. Liao, X. Bi, X. Li, Org. Biomol.
Chem. 13 (2015), 8723 e 8278;
(
1
(
(b) J. Liu, Z. Liu, P. Liao, X. Bi, Org. Lett. 16 (2014) 6204e6207;
(c) M. Phanindrudu, D.K. Tiwari, B. Sridhar, P.R. Likhar, D.K. Tiwari, Org. Chem.
Front. 3 (2016) 795e798;
J. Med. Chem. 47 (2004) 18e21.
[
3] (a) K.M. Elattar, A. Fekri, N.M. Bayoumy, A.A. Fadda, Res. Chem. Intermed. 43
(d) Garima, V.P. Srivastava, L.S. Yadav, Tetrahedron Lett. 52 (2011)
4622e4626;
(e) J. Chen, W. Guo, Z. Wang, L. Hu, F. Chen, Y.J. Xia, Org. Chem. 81 (2016)
5504e5512;
(f) L. Kadari, R.K. Palakodety, L.P. Yallapragada, Org. Lett. 19 (2017)
2580e2583;
(
(
(
(
(
(
2017) 4227e4232;
b) F.L. Yang, S.K. Tian, Tetrahedron Lett. 58 (2017) 487e504;
c) S. Shaaban, S. Liang, N.W. Liua, G. Manolikakes, Org. Biomol. Chem. 15
2017) 1947e1955;
d) N.W. Liu, S. Liang, G. Manolikakes, Synthesis 48 (2016) 1939e1973;
e) F. Reck, F. Zhou, M. Girardot, G. Kern, C.J. Eyermann, N.J. Hales, R.R. Ramsay,
(g) X. Chu, D. Ge, T. Loh, Z. Shen, Org. Chem. Front. 6 (2019) 835e840.
[14] (a) D.K. Tiwari, J. Pogula, B. Sridhar, D.K. Tiwari, P.R. Likhar, Chem. Commun.
51 (2015) 13646e13649;
M.B. Gravestock, J. Med. Chem. 48 (2005) 499e506;
f) W.M. Xu, F.F. Han, M. He, D.Y. Hu, J. He, S. Yang, B.A. Song, J. Agric. Food
(
Chem. 60 (2012) 1036e1041.
(b) D.K. Tiwari, M. Phanindrudu, V.K. Aravilli, B. Sridhar, P.R. Likhar,
D.K. Tiwari, Chem. Commun. 52 (2015) 4675e4679;
(c) D.K. Tiwari, M. Phanindrudu, S.B. Wakade, J.B. Nanubolu, D.K. Tiwari,
Chem. Commun. 53 (2017) 5302e5304;
[
4] (a) F. Catella-Lawson, B. Mcadam, B.W. Morrison, S. Kapoor, D. Kujubu,
L. Antes, K.C. Lasseter, H. Quan, B.J. Gertz, G.A. Fitzgerald, J. Pharmacol. Exp.
Ther. 289 (1999) 735e741;
(
b) M.J. Langman, D.M. Jensen, D.J. Watson, S.E. Harper, P.L. Zhao, H. Quan,
(d) S.B. Wakade, D.K. Tiwari, P.S.K.P. Ganesh, M. Phanindrudu, P.R. Likhar,
D.K. Tiwari, Org. Lett. 19 (2017) 4948e4951;
J.A. Bolognese, T.J. Simon, J. Am. Med. Assoc. 282 (1999) 1929e1933;
(
(
(
c) I.C. Richards, P.S. Thomas, Pestic. Sci. 30 (1990) 275e284;
d) W.M. Wolf, J. Mol. Struct. 474 (1999) 113e124;
e) C.J. Dinsmore, T.M. Williams, T.J. O’Neill, D. Liu, E. Rands, J.C. Culberson,
(e) M. Phanindrudu, S.B. Wakade, D.K. Tiwari, P.R. Likhar, D.K. Tiwari, J. Org.
Chem. 16 (2018) 9137e9143;
(f) D.K. Tiwari, R.A. Maurya, J.B. Nanubolu, Chem. Eur J. 22 (2016) 526e530;
(g) M. Phanindrudu, D.K. Tiwari, V.K. Aravilli, K.C. Bhardwaj, G. Sabapathi,
P.R. Likhar, D.K. Tiwari, Eur. J. Org Chem. (2016) 4629e4634;
(h) D.K. Tiwari, J. Pogula, D.K. Tiwari, RSC Adv. 5 (2015) 53111e53116.
[15] R.B. Kamble, S.S. Chavanb, New J. Chem. 43 (2019) 1632e1636;
(b) Y. Fu, W. Zhu, X. Zhao, H. Hugel, Z. Wu, Y. Su, Z. Du, D. Huang, Y. Hu, Org.
Biomol. Chem. 12 (2014) 4295e4299;
R.B. Lobell, K.S. Koblan, N.E. Kohl, J.B. Gibbs, A.I. Oliff, S.L. Graham,
G.D. Hartman, Biorg. Med. Chem. Lett. 9 (1999) 3301e3306;
(
f) J.B. McMahon, R.J. Gulakowsky, O.S. Welslow, R.J. Schoktz, V.L. Narayanan,
D.J. Clanton, R. Pedemonte, F.W. Wassmundt, R.W. Buckheit, W.D. Decker,
E.L. White, J.P. Bader, M.R. Boyd, Antimicrob. Agents Chemother. 37 (1993)
7
54e760;
(
g) T.M. Williams, T.M. Ciccarone, S.C. MacTough, C.S. Rooney, S.K. Balani,
(c) S. Cacchi, G. Fabrizi, A. Goggiamani, L.M. Parisi, Org. Lett. 4 (2002)
4719e4721.
[16] L. Cao, S.H. Luo, K. Jiang, Z.F. Hao, B.W. Wang, C.M. Pang, Z.Y. Wang, Org. Lett.
20 (2018) 4754e4758.
J.H. Condra, E.A. Emini, M.E. Goldman, L.W.J. Greenlee, R. Kauffman,
J.A. O’Bnen, V.V. Sardana, W.A. Schleif, A.D. Theoharides, P.S. Anderson, J. Med.
Chem. 36 (1993) 1291e1294.
[5] M.A. Hickner, H. Ghassemi, Y.S. Kim, B.R. Einsla, J.E. McGrath, Chem. Rev. 104
Please cite this article as: M. Phanindrudu et al., Nano copper catalyzed synthesis of symmetrical/unsymmetrical sulfones from aryl/alkyl
halides and p-toluenesulfonylmethylisocyanide: TosMIC as a tosyl source, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131263