molecules
Article
Article
Synthesis of
of Alkyl
Alkyl Aryl
Aryl Sulfones
Sulfones via
via Reaction
Reaction of
of
Synthesis
N-Arylsulfonyl Hydroxyamines
with
N-Arylsulfonyl
Hydroxyamines with
Electron-Deficient Alkenes
Alkenes
Electron-Deficient
Yunhui Bin and Ruimao Hua *
Yunhui Bin and Ruimao Hua *
Department of Chemistry, Tsinghua University, Beijing 100084, China; [email protected]
Department of Chemistry, Tsinghua University, Beijing 100084, China; [email protected]
* Correspondence: [email protected]; Tel.: +86-10-6279-2596
* Correspondence: [email protected]; Tel.: +86-10-6279-2596
Academic Editor: Roman Dembinski
Academic Editor: Roman Dembinski
Received: 4 December 2016; Accepted: 26 December 2016; Published: date
Received: 4 December 2016; Accepted: 26 December 2016; Published: 28 December 2016
reaction of
of N-arylsulfonyl
N-arylsulfonyl
Alkyl aryl
aryl sulfones
sulfones were prepared in high yields via the reaction
Abstract: Alkyl
hydroxylamines with electron-deficient alkenes. These
These reactions
reactions have
have the
the advantages
advantages of
of simplicity,
simplicity,
easily available starting materials and mild reaction
reaction conditions.
conditions.
hydroxylamines
Keywords: alkyl aryl sulfones; electron-deficient alkenes; N-arylsulfonyl hydroxylamines
1. Introduction
Sulfones
Sulfones are important
important starting compounds
compounds in the
the synthesis
synthesis of
of different
different sulfur-containing
sulfur-containing
compounds
Sulfones also
also exist
exist in
in a wide range of
compounds and natural products [1]. Sulfones
of biologically
biologically active
active
molecules, such as oxycarboxin (a highly efficient agricultural fungicide)
fungicide) [2],
[2], fipronil (a pesticide)
pesticide) [3],
and benzobicyclon (a herbicide) [4]. In addition, the structures of alkyl aryl sulfones are well known
as the core structural
structural unit
unit in
in pharmaceutical
pharmaceutical molecules. For instance, eletriptan is an efficient drug
for early migraine [5], and bicalutamide is used for the treatment of advanced prostate cancer [6]
(Figure 1). Therefore,
Therefore, aa variety
variety of synthetic approaches have been developed for the synthesis of
alkyl aryl sulfones,
coupling reaction
reaction of
of alkyl halides with vinyl
sulfones, including
including the
the Zn/CuI-mediated
Zn/CuI-mediated coupling
arylsulfones [7],
[7],FeCl
FeCl3/TMSCl-catalyzed
β-sulfonation
of α,β-unsaturated
carbonyl
compounds
β-sulfonation
of α,β-unsaturated
carbonyl
compounds
with
3 /TMSCl-catalyzed
with
p-toluenesulfinates
[8], aerobic
the aerobic
oxysulfonylation
alkenes
withvarious
varioussulfinic
sulfinicacids
acids [9],
[9],
p-toluenesulfinates
[8], the
oxysulfonylation
of of
alkenes
with
Cu(OAc)22-catalyzed
-catalyzed direct
direct oxysulfonylation
oxysulfonylation of
of alkenes
alkenes with
with dioxygen
dioxygen and sulfonylhydrazides
sulfonylhydrazides [10],
the reaction of alkenes with sodium
sodium arylsulfinates catalyzed by molecular iodine under aerobic
oxidative conditions [11], sulfonylation of activated alkenes with sulfonylhydrazides [12], the direct
sulfonylation of 2-methylquinolines
with sodium
sodium aryl
aryl sulfinates
sulfinates mediated
mediated by
by KI in the presence of
2-methylquinolines with
nickel-catalyzed hydroxysulfonylation
oxidant [13], nickel-catalyzed
hydroxysulfonylation of
of alkenes using sodium sulfinates [14], and
oxygen-mediated reaction of diethyl 1-arylvinyl phosphates with arylsulfinic acid [15]. Recently, He
and co-workers reported the preparation of α-sulfonylethanone oximes from the reaction of styrenes
of tetrabutylammonium
tetrabutylammonium periodate
with substituted N-arylsulfonyl hydroxylamines in the presence of
(n-Bu44NIO44)) (Scheme
N-arylsulfonyl
as oxidant (n-Bu
(Scheme 1)
1) [16]. In
In this
this paper,
paper, we
we report the reaction of N-arylsulfonyl
hydroxylamines with electron-deficient alkenes to provide an alternative procedure for the synthesis
(Scheme 1).
1).
of alkyl aryl sulfones under mild conditions (Scheme
Figure
with structural
structural unit
unit of
of alkyl
alkyl aryl
aryl sulfone.
sulfone.
Figure 1.
1. Examples
Examples of
of pharmaceutical
pharmaceutical molecules
molecules with
Molecules 2017, 22, 39; doi:10.3390/molecules22010039
Molecules 2017, 22, 39; doi:10.3390/molecules22010039
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Molecules 2017, 22, 39
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Molecules 2017,
2017, 22,
22, 39
39
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22 of
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Scheme
1. Synthesis
of alkyl
aryl sulfones
from N-arylsulfonyl
hydroxylamines with
Scheme
with alkenes.
alkenes.
Scheme 1.
1. Synthesis
Synthesis of
of alkyl
alkyl aryl
aryl sulfones
sulfones from
from N-arylsulfonyl
N-arylsulfonyl hydroxylamines
hydroxylamines with
alkenes.
2.
and Discussion
2. Results
Results
2.
Results and
and Discussion
Discussion
We
initiated
our
the
reaction
of
N-phenylsulfonyl
We
initiated
our study
study on
on the
the reaction
reaction of
of N-phenylsulfonyl
N-phenylsulfonyl hydroxylamine
hydroxylamine (1a)
(1a) with
with methyl
methyl
We initiated our
study
on
hydroxylamine
(1a)
with
methyl
acrylate
(2a)
to
optimize
the
reaction
conditions.
As
summarized
in
Table
1,
when
a
mixture
of 1a
acrylate (2a)
(2a) to
tooptimize
optimizethe
thereaction
reactionconditions.
conditions.AsAs
summarized
Table
1, when
a mixture
1a
acrylate
summarized
in in
Table
1, when
a mixture
of 1aofand
and
2a
(2.0
equiv.)
in
CH
3CN was heated with stirring at 60 °C for 18 h, not any product was formed
and
2a
(2.0
equiv.)
in
CH
3CN was heated with stirring at◦60 °C for 18 h, not any product was formed
2a (2.0 equiv.) in CH3 CN was heated with stirring at 60 C for 18 h, not any product was formed by
by
analyses
of
the
mixture
by
and
both 1a
and
were
(entry 1).
by the
the
analyses
ofreaction
the reaction
reaction
mixture
by GC-MS,
GC-MS,
and
1a were
and 2a
2a
were recovered
recovered
1).
the
analyses
of the
mixture
by GC-MS,
and both
1aboth
and 2a
recovered
(entry 1). (entry
However,
However,
in
the
presence
of
NaOAc
(1.0
equiv.),
repeating
the
same
reaction
gave
the
desired
However,
in the
of equiv.),
NaOAc repeating
(1.0 equiv.),
repeating
the gave
samethe
reaction
the desired
in
the presence
of presence
NaOAc (1.0
the same
reaction
desiredgave
compounds
3aa
compounds
3aa
in
39%
GC
yield
(entry
2)
[17],
indicating
that
the
presence
of
base
is
crucial
for the
compounds
3aa
in
39%
GC
yield
(entry
2)
[17],
indicating
that
the
presence
of
base
is
crucial
the
in 39% GC yield (entry 2) [17], indicating that the presence of base is crucial for the formationfor
of 3aa.
formation
of
3aa.
In
addition,
when
CH
3OH was used as solvent to replace CH3CN, 3aa was formed
formation
of
3aa.
In
addition,
when
CH
3OH was used as solvent to replace CH3CN, 3aa was formed
In addition, when CH3 OH was used as solvent to replace CH3 CN, 3aa was formed in 98% GC yield
in
GC
(entry
3).
of
employed,
the
the
in 98%
98%3).
GCInyield
yield
(entry
3). In
In the
the case
case
of acrylonitrile
acrylonitrile
employed,
the yield
yield of
of product
the corresponding
corresponding
(entry
the case
of acrylonitrile
employed,
the yield
of the corresponding
3af is also
product
3af
is
also
greatly
depending
on
the
solvents
used,
and
CH
3OH is the best choice (entries
product
3af
is
also
greatly
depending
on
the
solvents
used,
and
CH
3OH is the best choice (entries
greatly depending on the solvents used, and CH3 OH is the best choice (entries 4–6). Increasing the
4–6).
4–6). Increasing
Increasing the
the amount
amount of
of NaOAc
NaOAc (from
(from 1.0
1.0 equiv.
equiv. to
to 2.0
2.0 equiv.)
equiv.) afforded
afforded 3af
3af in
in the
the same
same yield
yield
amount of NaOAc (from 1.0 equiv. to 2.0 equiv.) afforded 3af in the same yield (entry 7), but the
(entry
7),
but
the
decreasing
amount
of
NaOAc
(from
1.0
equiv.
to
0.5
equiv.)
resulted
in
the
considerable
(entry
7),
but
the
decreasing
amount
of
NaOAc
(from
1.0
equiv.
to
0.5
equiv.)
resulted
in
the
considerable
decreasing amount of NaOAc (from 1.0 equiv. to 0.5 equiv.) resulted in the considerable decrease of
decrease
decrease of
of the
the yield
yield of
of 3af
3af (entry
(entry 8).
8). Moreover,
Moreover, the
the use
use of
of Na
Na22CO
CO33 as
as base
base led
led to
to 44%
44% of
of 3af
3af (entry
(entry 9),
9),
the yield of 3af (entry 8). Moreover, the use of Na2 CO3 as base led to 44% of 3af (entry 9), and the use
and
the
use
of
1,4-diazabicyclo[2.2.2]octane
(DABCO),
1,8-diazabicyclo[5.4.0]-undec-7-ene
(DBU)
and
the use of 1,4-diazabicyclo[2.2.2]octane
(DABCO), 1,8-diazabicyclo[5.4.0]-undec-7-ene
(DBU)
of
1,4-diazabicyclo[2.2.2]octane
(DABCO), 1,8-diazabicyclo[5.4.0]-undec-7-ene
(DBU) and pyridine
as
and
and pyridine
pyridine as
as base,
base, or
or without
without the
the use
use of
of base
base led
led to
to no
no formation
formation of
of 3af
3af at
at all
all (entries
(entries 10–13).
10–13).
base, or without the use of base led to no formation of 3af at all (entries 10–13).
a
Table
1.
conditions
Table 1.
1. Optimizing
Optimizing the
the reaction
reaction conditions
conditions aa...
Table
Optimizing
the
reaction
b
b
Entry
Solvent
Base
(Equiv.)
(%)
Entry
RR
Solvent
(Equiv.) Yield
Entry
R
Solvent
BaseBase
(Equiv.)
YieldYield
(%) b(%)
1
COOMe
CH
3CN
-00
COOMe
CH
3CN
-- –
1 1
COOMe
CH
0
3 CN
2
CH
3CN
NaOAc
(1)
39
CH
3CN
NaOAc
(1) (1)
39 39
2 2
CH
NaOAc
3 CN
3OH
NaOAc
(1)
98(93)
CH
3 33
CH
NaOAc
98(93)
3OH
NaOAc
(1) (1)
98(93)
CH
3 OH
CN
toluene
NaOAc
(1)
45
4 44
CN
toluene
NaOAc
(1)
CN
toluene
NaOAc (1)
45 45
5 55
CH
CN
NaOAc
(1)
CH
3CN
NaOAc
(1)
53
3
CH3CN
NaOAc (1)
53 53
6 66
CH
OH
NaOAc
(1)
85(80)
3OH
NaOAc
(1)
85(80)
CH
3
NaOAc (1)
85(80)
CH3OH
7 7
CH
NaOAc
(2)
84
3 OH
CH
3OH
NaOAc
(2)
84
7
CH3OH
NaOAc (2)
84
8 8
CH
OH
NaOAc
(0.5)
67
3
3OH
NaOAc
(0.5)
67
CH
3OH
NaOAc
67 44
CH
9 8
CH
Na(0.5)
3 OH
2 CO3
Na
2
CO
3
44
3OH
9
CH
Na
2
CO
3
44 0
3
OH
9
CH
10
CH3 OH
DABCO (1)
3OH
DABCO
(1)
00
CH
11 10
CH
OH
DBU
(1)
0
DABCO (1)
10
CH3OH
3
CH
3OH
DBU
(1)
0
12 11
CH
OH
pyridine
0
3
11
CH3OH
DBU (1)
0
3OH
pyridine
00
CH
13 12
CH
0
3 OH
3OH
pyridine–
12
CH
a Reactions were 13
3OH
-0
CH
carried
out
using
1.0
mmol
of
1a,
2.0
mmol
of
2a
or
2f,
and
base
in
10.0
mL of solvent in
-0
13
CH3OH
b GC yield based on the amount of 1a used. Number in parenthesis is isolated yield.
a Reactions
a sealed tube.
were
carried
out
using
1.0
mmol
of
1a,
2.0
mmol
of
2a
or
2f,
and
base
a Reactions
were carried out using 1.0 mmol of 1a, 2.0 mmol of 2a or 2f, and base in
in 10.0
10.0 mL
mL of
of
b
solvent
GC yield
yield based
based on
on the
the amount
amount of
of 1a
1a used.
used. Number
Number in
in parenthesis
parenthesis is
is
solvent in
in aa sealed
sealed tube.
tube. b GC
isolated
yield.
isolated yield.
Molecules 2017, 22, 39
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33 of
Under the optimized reaction conditions shown in entries 3 and 6 in Table 1, the generality for the
Under
the
optimized
reaction
conditions
shown
in
entries
3N-arylsulfonyl
and
6 in
in
Table
1,
the
generality
forthe
the
Under
the
optimized
conditions
entries
3of3and
6 6in
Table
1,1,
the
generality
for
formation
ofUnder
alkyl
aryl
sulfonesreaction
was
investigated
byshown
usingin
ain
variety
hydroxylamines
reaction
conditions
shown
entries
and
Table
the
generality
for
the
Molecules
2017,
22,the
39 optimized
3 of 7
formation
of
alkyl
aryl
sulfones
was
investigated
by
using
a
variety
of
N-arylsulfonyl
hydroxylamines
formation
of
alkyl
aryl
sulfones
was
investigated
by
using
a
variety
of
N-arylsulfonyl
hydroxylamines
and alkenes,
and
obtained
results
are investigated
summarized
Tables
2 6and
3.
in Table
2, the
1a
Under
the
optimized
reaction
conditions
shown in entries
3 and
in Table
1,shown
the generality
for
formation
ofthe
alkyl
aryl
sulfones
was
byinusing
a variety
of As
N-arylsulfonyl
hydroxylamines
Under
the
optimized
reaction
conditions
shown
in
entries
3
and
6
in
Table
1,
the
generality
for
the
and
alkenes,
and
the
obtained
results
are
summarized
in
Tables
2
and
3.
As
shown
in
Table
2,1a1a
1a
and
alkenes,
and
the
obtained
results
are
summarized
in
Tables
2
and
3.
As
shown
in
Table
reacted
with
acrylates
2b–e
to
give
the
expected
alkyl
aryl
sulfones
3ab–3ae
in
high
yields.
No
significant
formation
of
alkyl
aryl
sulfones
was
investigated
by
using
a
variety
of
N-arylsulfonyl
hydroxylamines
and alkenes, and the obtained results are summarized in Tables 2 and 3. As shown in Table2,2,
formation
of
alkyl
aryl
sulfones
was
investigated
by
using
a
variety
of
N-arylsulfonyl
hydroxylamines
reacted
with
acrylates
2b–e
to
give
the
expected
alkyl
aryl
sulfones
3ab–3ae
in
high
yields.
No
significant
reacted
with
acrylates
2b–e
to
give
the
expected
alkyl
aryl
sulfones
3ab–3ae
in
high
yields.
No
significant
electron
effect
was
observed,
and
when
R
are
both
electron-donating
and
electron-withdrawing
groups,
and alkenes,
theacrylates
obtained
results
are summarized
in Tables
and 3. As
shownininhigh
Table
2, 1a No
reacted
reactedand
with
2b–e
to give
the expected alkyl
aryl 2sulfones
3ab–3ae
yields.
significant
and
alkenes,
and
theobserved,
obtained
results
arethe
summarized
in Tablessmoothly
2 and 3.and
As
shown
in Table
2, 1a groups,
electron
effect
was
observed,
and
when
R
are
both
electron-donating
and
electron-withdrawing
groups,
effect
was
and
when
R
are
both
electron-donating
electron-withdrawing
N-arylsulfonyl
hydroxylamines
underwent
present
reaction
to
afford
the
corresponding
with electron
acrylates
2b–e
to
give
the
expected
alkyl
aryl
sulfones
3ab–3ae
in
high
yields.
No
significant
electron effect was observed, and when R are both electron-donating and electron-withdrawing groups,
reacted
with acrylates
2b–e to give theunderwent
expected alkyl
aryl
sulfones
3ab–3aesmoothly
in high yields.
No significant
N-arylsulfonyl
hydroxylamines
the
present
reaction
to
afford
the
corresponding
N-arylsulfonyl
hydroxylamines
underwent
the
present
reaction
smoothly
to
afford
the
corresponding
alkyl
aryl
sulfones
3ba,
3bb,
3ca,
and
3da–fa
in
good
yields.
electron
effect
was
observed,
and
when
R
are
both
electron-donating
and
electron-withdrawing
groups,
N-arylsulfonyl
underwent
the present reaction
smoothly to afford groups,
the corresponding
electron
effect was hydroxylamines
observed, and when
R are both electron-donating
and electron-withdrawing
alkylaryl
arylsulfones
sulfones3ba,
3ba,3bb,
3bb,
3ca,and
and3da–fa
3da–fa
ingood
good
yields.
alkyl
3ca,
inin
yields.
N-arylsulfonyl
hydroxylamines
underwent
the
present
reaction
smoothly to afford the corresponding
alkyl
aryl
sulfones
3ba,
3bb,
3ca,
and
3da–fa
good
yields.
N-arylsulfonyl hydroxylamines underwent the present reaction smoothly to afford the corresponding
Table
2. Synthesis
of alkyl
aryl sulfones a.
alkylalkyl
aryl aryl
sulfones
3ba,3ba,
3bb,
3ca,
and
yields.
sulfones
3bb,
3ca,
and3da–fa
3da–fain
in good
good yields.
a. a.
Table
2.
Synthesis
of
alkyl
aryl
sulfones
Table
2.2.
Synthesis
ofof
alkyl
aryl
sulfones
a.
Table
Synthesis
alkyl
aryl
sulfones
a.
a
Table
2.
Synthesis
of
alkyl
aryl
sulfones
Table 2. Synthesis of alkyl aryl sulfones .
a Reactions were carried out using 1.0 mmol of 1, 2.0 mmol of 2, and 1.0 mmol of NaOAc in 10.0 mL
Reactions
were carried
carried out
1.01.0
mmol
of 1,of
2.01,mmol
of 2, and
1.0and
mmol
NaOAc
10.0 mLin
of 10.0
MeOH
Reactions
were
outusing
using
mmol
2.0 mmol
of 2,
1.0ofmmol
ofinNaOAc
mL
◦ C for 18 h. All the yields are isolated yields.
at
60
aMeOH
a Reactions
of
at
60
°C
for
18
h.
All
the
yields
are
isolated
yields.
Reactions
were
carried
out
using
1.0
mmol
of
1,
2.0
mmol
of
2,
and
1.0
mmol
of
NaOAc
in
10.0
mL
carried
out
using
1.0
mmol
of
1,
2.0
mmol
of
2,
and
1.0
mmol
of
NaOAc
in
10.0
mL
of MeOH
at 60 °Cwere
for
18
h.
All
the
yields
are
isolated
yields.
a Reactions
were carried out using 1.0 mmol of 1, 2.0 mmol of 2, and 1.0 mmol of NaOAc in
10.0
mL
of
MeOH
at
60
°C
for
18
h.
All
the
yields
are
isolated
yields.
ofof
MeOH
at
60
°C
for
18
h.
All
the
yields
are
isolated
yields.
MeOH at
60also
°C for
18 h. All to
theprepare
yields are
yields.
In addition,
it is
interesting
theisolated
multi-sulfur
atom-bearing compounds, thus we
In addition, it is also interesting to prepare the multi-sulfur atom-bearing compounds, thus we
performed the reactions of 1a and 1c with phenyl vinyl sulfone (2g). As shown in Table 3, the
In
addition,
is
also
interesting
prepare
the
multi-sulfur
atom-bearing
compounds,
thuswe
we
addition,
it itis
also
interesting
totoprepare
the
multi-sulfur
compounds,
thus
performedInthe
the
reactions
of
1a
and
with
phenyl
vinyl
sulfone
As shown
in
3, the
reactions
ofis
1a
and
1c 1c
with
phenyl
vinyl
sulfone
(2g). (2g).
Asatom-bearing
shown
in Table
3,Table
the desired
addition,
also
interesting
the
multi-sulfur
atom-bearing
compounds,
thus
we
desiredIn
products
3agitand
3cg were
isolatedto
in prepare
good yields.
a a
performed
thereactions
reactions
of1a1a
1a
and1c1c
1c
withphenyl
phenyl
vinylsulfone
sulfone(2g).
(2g).As
Asshown
showninin
inTable
Table3,3,
3,the
the
performed
ofof
with
desired
products
3ag
and
3cg
were
isolated
in
good
yields.vinyl
products
3ag andthe
3cg
were
isolated
inand
good
yields.
performed
the
reactions
and
with
phenyl
vinyl
sulfone
(2g).
As
shown
Table
the
a.
desired
products
3ag
and
3cg
were
isolated
in
good
yields.
desired
products
3ag
and
3cg
were
isolated
in
good
yields.
Table
3.
Synthesis
of
alkyl
aryl
sulfones
desired products 3ag and 3cg were isolated in good yields.
aa
Table 3. Synthesis of alkyl aryl sulfones . O
O
a a
Table
Synthesis
of
alkyl
aryl
sulfones
Table
3. 3.
Synthesis
ofof
alkyl
aryl
sulfones
NaOAc,
CH
3OH
S O. a..
alkyl
aryl
sulfones
OH + TableR'3. Synthesis
O S
Ar
R'
Ar
N
o
18 3hOH
60 C,CH
NaOAc,
O S
O
OO
HO
S OO
OH
R'
+
N O
1 S OH
OH + + 2
O H S
SN N OH
Ar
Ar
Entry Ar1O OH N
2 +
H
1 O H
2
1 2O
11
Entry
1
1a1
Entry
2
1
S
Entry 1 11
Entry
2 22
Entry
Ar
1
O O 2g
1a
S
OO
O
1a O 2g
1 2 1 11 1c1a1a1a
S
2gS S
Ar
R'
o NaOAc,
CH
C, 18 hCH
60NaOAc,
3OH
3OH
SS
NaOAc,
CH
3OH 3 OArAr S
R'
R'R'
o
o
Ar O(%)
18
h
60
C,
hh
60
o C,
360
Yield
O b
C,1818
O
3
O
2
22
3 3 (%) b
3 O
Yield
S
S 3
75 3(%) b
Yield
b b
O
O
Yield
(%)
3 33
Yield
(%)
b
Yield
(%)
OO
S 3ag O O
S
75
O
OO
O O S SO
O
O
S
SS
S
75
7575
S
76 75
R'
R'R'
3agO O
S
O
OO
O
O
3ag O
3cg 3ag
O
O3ag
S
O 1.0 mmol of NaOAc
a Reactions
1c
2g 1.0 mmol of 1, 2.0 mmol of 2,Oand
2 were carried
76 in 10.0 mL
SO
out using
OO
O
O
SOS
S
of MeOH at 60 °C
for 181c
h.1cb Isolated yields.
2g
2
76
2g
2
S
S
3cg O O
O
2g
2 1c 1c
S
2
76 7676
O
O
O
a Reactions were carried out using 1.0 mmol of 1, 2.0 mmol
O mmol of NaOAc in 10.0
3cg 1.0
of 2,3cg
and
OO
3cg
O
O O 2g2g
O 2g
O
mL
b
Reactions
were
carried
out
using
1.0
mmol
of
1,
2.0
mmol
of
2,
and
1.0
mmol
of
NaOAc
in
10.0
mL
Reactions
were
carried
out
using
1.0
mmol
of
1,
2.0
mmol
of
2,
and
1.0
mmol
of
NaOAc
in
10.0
mL
ofaMeOHReactions
at 60 °C for
18 carried
h. Isolatedusing
yields.
were
1.0
of of
1, 2,
2.0and
mmol
of 2, of
and
1.0 mmol
NaOAc
in
10.0
mL
Reactions were carried
out usingout
1.0b mmol of
1, mmol
2.0 mmol
1.0 mmol
NaOAc
in 10.0of
mL
of MeOH
b
of
MeOH
at
60
°C
for
18
h. Isolated
Isolated
yields.
of◦of
MeOH
atat
°C°C
for
1818
h.h.
yields.
b Isolated
b6060
MeOH
for
yields.
a a
a
at 60 C for 18 h.
Isolated yields.
Molecules 2017, 22, 39
Molecules 2017, 22, 39
4 of 7
4 of 7
On the
the basis
basis of
of the
the known
knowndecomposition
decomposition of
of N-arylsulfonyl
N-arylsulfonyl hydroxyamines
hydroxyamines under
under basic
basic conditions
conditions
On
to
nitrosyl
hydride
and
arylsulfinate
[18],
a
proposed
mechanism
for
the
formation
of
alkyl aryl
aryl
to nitrosyl hydride and arylsulfinate [18], a proposed mechanism for the formation of alkyl
sulfones
is
shown
in
Scheme
2.
It
involves
the
formation
of
an
arylsulfinate
anion/arylsulfonyl
anion
sulfones is shown in Scheme 2. It involves the formation of an arylsulfinate anion/arylsulfonyl
intermediate [12], and its Michael addition with an electron-deficient alkene to afford alkyl aryl
anion intermediate [12], and its Michael addition with an electron-deficient alkene to afford alkyl aryl
sulfone 3.
sulfone 3.
O
OH
Ar S N
O H
NaOAc
1
R
Michael addition
O
Ar S
O
HOAc
+
HNO
O
S
Ar
O
Na+
O
Ar S
O
Na+
HOAc NaOAc
R
3
R: electron-withdrawing group
Scheme
2. The
for the
the formation
formation of
of alkyl
alkyl aryl
aryl sulfones.
sulfones.
Scheme 2.
The proposed
proposed mechanism
mechanism for
3. Materials
3.
Materials and
and Methods
Methods
3.1. General
3.1.
General Methods
Methods
All organic
organic starting
starting materials
materials and
solvents are
are analytically
analytically pure
pure and
and used
used without
without further
further
All
and solvents
purification.
Nuclear
magnetic
resonance
(NMR)
spectra
were
recorded
on
a
JEOL
ECA-300
purification. Nuclear magnetic resonance (NMR) spectra were recorded on a JEOL ECA-300
spectrometer (JEOL,
(JEOL, Tokyo,
Tokyo, Japan)
Japan) using
usingCDCl
CDCl33 as
as aa solvent
solvent at
at 298
298 K.
K. 11H-NMR
H-NMR (300
(300 MHz)
MHz) chemical
chemical
spectrometer
1
13C-NMR (75 MHz)
1
13
shifts
(δ)
were
referenced
to
internal
standard
TMS
(for
H,
δ
=
0.00
ppm).
shifts (δ) were referenced to internal standard TMS (for H, δ = 0.00 ppm). C-NMR (75 MHz) chemical
13 CDCl3 (for 13C, δ = 77.16
1
13 The 1H- and
chemical
were to
referenced
to internal
ppm).
shifts
wereshifts
referenced
internal solvent
CDClsolvent
3 (for C, δ = 77.16 ppm). The H- and C-NMR charts
13C-NMR charts of products are reported as supplementary materials. The high-resolution mass
of products are reported as supplementary materials. The high-resolution mass spectra (ESI) were
spectra (ESI)
obtained with
a micrOTOF-Q
spectrometer
California, CA, USA).
obtained
withwere
a micrOTOF-Q
10142
spectrometer10142
(Agilent,
California,(Agilent,
CA, USA).
3.2. Typical Experiment Procedure
Procedure for
for the
the Reaction
Reaction of
of N-Phenylsulfonyl
N-Phenylsulfonyl Hydroxylamine
Hydroxylamine(1a)
(1a)with
withMethyl
Methyl
Acrylate
(2a)
Affording
Methyl
3-(Phenylsulfonyl)propanoate
(3aa)
(Table
1,
Entry
3)
Acrylate (2a) Affording Methyl 3-(Phenylsulfonyl)propanoate (3aa) (Table 1, Entry 3)
A
hydroxylamine (1a,
(1a, 173.0
173.0 mg,
mg, 1.0
1.0 mmol),
mmol), methyl
methyl acrylate
acrylate (2a)
(2a)
A mixture
mixture of
of N-phenylsulfonyl
N-phenylsulfonyl hydroxylamine
◦C
(172.0
mg, 2.0
2.0 mmol)
mmol)and
andNaOAc
NaOAc(82.0
(82.0mg,
mg,1.0
1.0mmol)
mmol)
was
heated
(10.0
at °C
60 (oil
3 OH
(172.0 mg,
was
heated
in in
CHCH
3OH
(10.0
mL)mL)
at 60
(oil
temperature)
with
stirring
h in
screw-cappedthick-walled
thick-walledPyrex
Pyrextube
tube under
under an
an air
bathbath
temperature)
with
stirring
forfor
18 18
h in
a ascrew-capped
air
atmosphere.
After
the
reaction
mixture
was
cooled
to
room
temperature,
it
was
directly
subjected
atmosphere. After the reaction mixture was cooled to room temperature, it was directly subjected to
to
aa short
chromatography
(2~3(2~3
cm, eluted
with CH
) to2Cl
remove
insoluble
2 Cl2CH
shortsilica
silicacolumn
column
chromatography
cm, eluted
with
2) to the
remove
the materials.
insoluble
To
the collected
n-octadecane
(25.5 mg, 0.1(25.5
mmol
as 0.1
internal
for GC
analysis)
materials.
To thesolution,
collected
solution, n-octadecane
mg,
mmolstandard
as internal
standard
for was
GC
then
added
with
stirring.
After
GC
and
GC-MS
analyses
of
the
mixture,
volatiles
were
then
removed
analysis) was then added with stirring. After GC and GC-MS analyses of the mixture, volatiles were then
under
reduced
and the residue
subjected
to silica to
gelsilica
column
chromatography,
eluted
removed
under pressure,
reduced pressure,
and thewas
residue
was subjected
gel column
chromatography,
with
a
mixture
of
solvents
of
petroleum
ether/acetone
(from
100:0~100:2
in
volume).
3aa
was
obtained
eluted with a mixture of solvents of petroleum ether/acetone (from 100:0~100:2 in volume). 3aa was
in
212.0 mg
93%)
as yellow
GC oil.
analysis
of reaction
mixture
revealed
the formation
obtained
in (0.93
212.0mmol,
mg (0.93
mmol,
93%)oil.
as The
yellow
The GC
analysis
of reaction
mixture
revealed
1 H-NMR (CDCl
of
[19] in 98%
GC[19]
yield.
(m, 2H),
7.56(m,
(m,2H),
3H),7.56
3.56(m,
(s,3H),
3H),3.56
3.39(s,
(t,3H),
2H,
3 ) δ 7.85
the3aa
formation
of 3aa
in 98%
GC yield. 1H-NMR
(CDCl
3) δ 7.85
13 C-NMR (CDCl
13
J3.39
= 7.8
Hz),
2.70
(t,
2H,
J
=
7.8
Hz);
)
δ
170.3,
138.6,
134.1,
129.4,
128.1,
52.2,
51.4,
27.6;
3
(CDCl3) δ 170.3, 138.6, 134.1, 129.4, 128.1, 52.2,
(t, 2H, J = 7.8 Hz), 2.70 (t, 2H, J = 7.8 Hz); C-NMR
+ : 229.0529;
HRMS
(ESI):
Calcd.
for:Calcd.
C10 H13for:
O4 SC[M
+OH]
found: 229.0528.
51.4, 27.6;
HRMS
(ESI):
10H13
4S [M
+ H]+: 229.0529;
found: 229.0528.
The
following
compounds
were
similar
prepared:
The following compounds were similar prepared:
Ethyl 3-(phenylsulfonyl)propanoate (3ab) [20]: 1 H-NMR: δ 7.80 (m, 2H), 7.57 (m, 3H), 4.04 (dd, 2H,
Ethyl 3-(phenylsulfonyl)propanoate (3ab) [20]: 1H-NMR: δ 7.80 (m, 2H), 7.57 (m, 3H), 4.04 (dd, 2H, J =
J = 7.2 Hz), 3.40 (t, 2H, J = 7.8 Hz), 2.70 (t, 2H, J = 7.8 Hz),1.18 (t, 3H, J = 7.2 Hz); 13 C-NMR: δ 170.0,
7.2 Hz), 3.40 (t, 2H, J = 7.8 Hz), 2.70 (t, 2H, J = 7.8 Hz),1.18 (t, 3H, J = 7.2 Hz); 13C-NMR: δ 170.0, 138.4,
138.4, 134.0, 129.4, 128.1,61.3, 51.4, 27.8, 14.0; HRMS (ESI): Calcd. for: C11 H12 NO4 S [M + H]+ : 254.0482;
134.0, 129.4, 128.1,61.3, 51.4, 27.8, 14.0; HRMS (ESI): Calcd. for: C11H12NO4S [M + H]+: 254.0482; found:
found: 254.0486.
254.0486.
n-Butyl 3-(phenylsulfonyl)propanoate (3ac): pale yellow oil; 1H-NMR: δ 7.89 (m, 2H), 7.63 (m, 3H), 4.03
(m, 2H), 3.45 (t, 2H, J = 7.5 Hz), 2.73 (t, 2H, J = 7.5 Hz), 1.56 (m, 2H), 1.33 (m, 2H), 0.90 (m, 3H);
Molecules 2017, 22, 39
5 of 7
n-Butyl 3-(phenylsulfonyl)propanoate (3ac): pale yellow oil; 1 H-NMR: δ 7.89 (m, 2H), 7.63 (m, 3H), 4.03 (m,
2H), 3.45 (t, 2H, J = 7.5 Hz), 2.73 (t, 2H, J = 7.5 Hz), 1.56 (m, 2H), 1.33 (m, 2H), 0.90 (m, 3H); 13 C-NMR:
δ 169.7, 138.3, 133.8, 129.2, 127.9, 64.9, 51.2, 30.2, 27.6, 18.8, 13.4; HRMS (ESI): Calcd. for: C13 H19 O4 S
[M + H]+ : 271.0999; found: 271.0998.
t-Butyl 3-(phenylsulfonyl)propanoate (3ad): yellow solid, m.p. 46~48 ◦ C; 1 H-NMR: δ 7.91 (m, 2H),7.62 (m,
3H), 3.37 (t, 2H, J = 7.8 Hz), 2.65 (t, 2H, J = 7.8 Hz), 1.38 (s, 9H); 13 C-NMR: δ 169.2, 138.7, 134.0, 129.5,
128.2, 82.0, 51.7, 29.0, 28.1; HRMS (ESI): Calcd. for: C13 H19 O4 S [M + Na]+ : 293.0818; found: 293.0819.
Benzyl 3-(phenylsulfonyl)propanoate (3ae): pale yellow solid, m.p. 61~63 ◦ C; 1 H-NMR: δ 7.89 (m, 2H),
7.59 (m, 3H), 7.32 (m, 5H), 5.05 (s, 2H), 3.43 (t, 2H, J = 7.8 Hz), 2.73 (t, 2H, J = 7.8 Hz); 13 C-NMR:
δ 169.7, 138.3, 135.1, 134.0, 139.4, 128.6, 128.4, 128.3, 128.1, 67.0, 51.3, 27.8; HRMS (ESI): Calcd. for:
C16 H16 NaO4 S [M + Na]+ : 327.0662; found: 327.0666.
3-(Phenylsulfonyl)propanenitrile (3af) [19]: 1 H-NMR: δ 7.94 (m, 2H), 7.69 (m, 3H), 7.32 (m, 5H), 3.40 (t,
2H, J = 7.6 Hz), 2.82 (t, 2H, J = 7.6 Hz); 13 C-NMR: δ 137.5, 134.8, 129.8, 128.3, 116.1, 51.1, 12.1; HRMS
(ESI): Calcd. for: C9 H9 NNaO2 S [M + Na]+ : 218.0246; found: 218.0249.
Methyl 3-tosylpropanoate (3ba) [20]: 1 H-NMR: δ 7.72 (d, 2H, J = 8.2 Hz), 7.31 (d, 2H, J = 8.2 Hz), 3.57 (s,
3H), 3.35 (t, 2H, J = 7.5 Hz), 2.67 (t, 2H, J = 7.5 Hz), 2.39 (s, 3H); 13 C-NMR: δ 170.4, 145, 135.4, 129.9,
128.1, 52.1, 51.4, 27.6, 21.5; HRMS (ESI): Calcd. for: C11 H15 O4 S [M + H]+ : 243.0686; found: 243.0690.
Ethyl 3-tosylpropanoate (3bb) [20]: 1 H-NMR: δ 7.74 (d, 2H, J = 7.8 Hz), 7.32 (d, 2H, J = 7.8 Hz), 4.03 (q,
2H, J = 7.1 Hz), 3.36 (t, 2H, J = 7.6 Hz), 2.66 (t, 2H, J = 7.6 Hz), 2.40 (s, 3H), 1.17 (t, 2H, J = 7.1 Hz), 0.90
(m, 3H); 13 C-NMR: δ 170.0, 145.0, 135.5, 130.0, 128.1, 61.3, 51.5, 27.9, 21.6, 14.0; HRMS (ESI): Calcd. for:
C12 H17 O4 S [M + H]+ : 257.0842; found: 257.0844.
Methyl 3-((4-methoxyphenyl)sulfonyl)propanoate (3ca) [20]: 1 H-NMR: δ 7.83 (d, 2H, J = 9.0 Hz), 7.04 (d,
2H, J = 9.0 Hz), 3.89 (s, 3H), 3.64 (s, 3H), 3.41 (t, 2H, J = 7.1 Hz), 2.74 (t, 2H, J = 7.1 Hz); 13 C-NMR:
δ 170.4, 163.9, 130.3, 129.8, 114.5, 55.7, 52.2, 51.6, 27.7; HRMS (ESI): Calcd. for: C11 H15 O5 S [M + H]+ :
259.0635; found: 259.0637.
Methyl 3-((4-chlorophenyl)sulfonyl)propanoate (3da) [21]: 1 H-NMR: δ 7.78 (d, 2H, J = 8.5 Hz), 7.49 (d, 2H,
J = 8.5 Hz), 3.55 (s, 3H), 3.38 (t, 2H, J = 7.6 Hz), 2.67 (t, 2H, J = 7.6 Hz); 13 C-NMR: δ 170.1, 140.5, 136.8,
129.6, 52.2, 51.3, 27.4; HRMS (ESI): Calcd. for: C10 H11 ClNaO4 S [M + Na]+ : 284.9959; found: 284.9962.
Methyl 3-((4-(trifluoromethyl)phenyl)sulfonyl)propanoate (3ea): white solid, m.p. 120~122 ◦ C; 1 H-NMR:
δ 8.06 (d, 2H, J = 8.2 Hz), 7.85 (d, 2H, J = 8.6 Hz), 3.64 (s, 3H), 3.47 (t, 2H, J = 7.5 Hz), 2.77 (t, 2H,
J = 7.5 Hz); 13 C-NMR: δ 170.2, 142.0, 135.7, 128.9, 127.0, 126.6, 52.4, 51.4, 27.4; HRMS (ESI): Calcd. for:
C11 H11 F3 NaO4 S [M + Na]+ : 319.0222; found: 319.0226.
Methyl 3-((4-cyanophenyl)sulfonyl)propanoate (3fa): pale yellow solid, m.p. 119~122 ◦ C; 1 H-NMR: δ 8.03
(m, 2H), 7.87 (m, 2H), 3.64 (s, 3H), 3.46 (t, 2H, J = 7.5 Hz), 2.77 (t, 2H, J = 7.5 Hz); 13 C-NMR: δ 17.02, 142.8,
133.3, 129.1, 118.0, 117.1, 52.6, 51.5, 27.4; HRMS (ESI): Calcd. for: C11 H12 NO4 S [M + H]+ : 254.0482;
found: 254.0486.
1,2-Bis(phenylsulfonyl)ethane (3ag) [22]: 1 H-NMR: δ 7.88 (m, 4H), 7.70 (m, 2H), 7.60 (m, 6H), 3.45 (s, 4H);
13 C-NMR: δ 138.0, 134.6, 129.7, 128.1, 49.5.
1-Methoxy-4-((2-(phenylsulfonyl)ethyl)sulfonyl)benzene (3cg): white solid, m.p. 150~152 ◦ C; 1 H-NMR:
δ 7.87 (d, 2H, J = 7.6 Hz), 7.78 (d, 2H, J = 8.8 Hz, 7.70 (t, 1H, J = 7.4 Hz ), 7.58 (t, 2H, J = 7.7 Hz ), 3.88
(s, 3H), 3.42 (m, 4H); 13 C-NMR: δ 164.4, 138.1, 134.6, 130.4, 129.8, 129.4, 128.1, 114.5, 55.9, 49.8; HRMS
(ESI): Calcd. for: C15 H17 O5 S2 [M + H]+ : 341.0512; found: 341.0515.
Molecules 2017, 22, 39
6 of 7
4. Conclusions
In summary, we have studied the reaction of N-arylsulfonyl hydroxylamines with electron-deficient
alkenes to provide an alternative efficient synthetic method for the formation of alkyl aryl sulfones
in good yields. The present method has the advantages with simple and easily available starting
materials, under mild conditions, with high atom-utilization.
Supplementary Materials: Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/22/
1/39/s1, the charts of 1 H- and 13 C-NMR of products.
Acknowledgments: This project was supported by the National Natural Science Foundation of China (21473097).
Author Contributions: R.H. designed the experiments and wrote the paper; Y.B. performed the experiments and
analyzed the data.
Conflicts of Interest: The authors declare no conflict of interest.
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2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
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13 C-NMR and HRMS. The charts of 1 H- and 13 C-NMR are reported as Supplementary Materials.
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13 C-NMR,
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Sample Availability: Samples of the compounds are not available from the authors.
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