Acid-mediated sulfonylation of arylethynylene bromides with sodium arylsulfinates: Synthesis of (: E)-1,2-bis(arylsulfonyl)ethylenes and arylacetylenic sulfones

Article abstract of DOI:10.1039/c7ra07105a

A solvent-dependent sulfonylation of arylethynylene bromides with sodium arylsulfinates has been developed. The (E)-1,2-bis(arylsulfonyl)ethylenes were formed in DMSO, while the arylacetylenic sulfones were obtained in toluene. Utilizing simple and readily available starting materials, the sulfonylation products were generated with good selectivities and yields without the need for a metal catalyst or oxidant.

Full text of DOI:10.1039/c7ra07105a

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Acid-mediated sulfonylation of arylethynylene
bromides with sodium arylsulfinates: synthesis of
(E)-1,2-bis(arylsulfonyl)ethylenes and
arylacetylenic sulfones†
Cite this: RSC Adv., 2017, 7, 36112
*
Chenshu Dai, Junqi Wang, Siqi Deng, Candong Zhou, Wenhe Zhang, Qiuhua Zhu
*
and Xiaodong Tang
Received 27th June 2017
Accepted 13th July 2017
A solvent-dependent sulfonylation of arylethynylene bromides with sodium arylsulfinates has been
developed. The (E)-1,2-bis(arylsulfonyl)ethylenes were formed in DMSO, while the arylacetylenic sulfones
were obtained in toluene. Utilizing simple and readily available starting materials, the sulfonylation
products were generated with good selectivities and yields without the need for a metal catalyst or oxidant.
DOI: 10.1039/c7ra07105a
rsc.li/rsc-advances
Organosulfone compounds are of great importance in organic bis(arylsulfonyl)ethylenes by nucleophilic vinylic substitutions
chemistry, due to their widely existing in natural products and with sodium arylsulnates. Except the multi-step preparation of
drug molecules.1 Meanwhile, the sulfonyl group is also exten- vinyl-iodonium salts, stoichiometric amount of iodine benzene
sively used as versatile synthon for other organosulfur as a by-product placed this method in an unfavourable position
compounds synthesis.2 1,2-Bis(arylsulfonyl)ethylenes are (Scheme 1c).6c Kataoka et al. also developed a method for 1,2-
important organosulfone compounds and widely studied in bis(phenylsulfonyl)ethylene via the reaction of alkynylseleno-
synthetic applications. Firstly, they can act as p-decient nium salt with sodium benzenesulnate (Scheme 1d).6d–f In the
alkenes for cycloaddition reaction to synthesize cyclic above methods, all have some obvious disadvantages such as
compounds.3 Secondly, they play the role as leaving group in multi-step processes, strong oxidants, unavailable starting
radical alkenylation reaction, in which various radicals add into materials, toxic by-products and so on. Hence, it is attractive
the C–C double bond and then eliminate a sulfonyl radical.4 and meaningful to develop a new method for synthesis of 1,2-
Thirdly, in the presence of organocatalyst, they are able to bis(arylsulfonyl)ethylenes in a direct, simple and green way.
undergo 1,2-sulfone rearrangement to form various other
Haloalkynes are easily available building blocks which can
organosulfone compounds.5 Due to their importance, synthetic be prepared in quantitative yield in mol-scale on the bench top.
chemists have exploring their synthetic methods. However, the Due to the electron-deciency of haloalkyne, it usually used as
methods for synthesis of 1,2-bis(arylsulfonyl)ethylenes are still an activated alkyne for addition reaction to give the sole regio-
rarely. The most common method was the reaction of the 1,2- selectivity.7 In recent years, some practical synthetic methods
dichloroethylene with phenylthiolate to give 1,2-bis(arylthio)
ethylene which was followed by oxidation to furnish 1,2-
bis(arylsulfonyl)ethylenes (Scheme 1a).6a While those multi-step
synthesis was even impeded by limited symmetric 1,2-bis(ar-
ylsulfonyl)ethylenes formation. Reddy et al. reported a one-pot
method, through the condensation of 1-arylsulfonyl-2,2-
dichloroethanes with sodium sulnates in aqueous alcohol
(Scheme 1b).6b The b-((phenylsulfonyl)alkenyl)iodonium tetra-
fIuoroborates were used as starting materials to form (Z)-1,2-
Guangdong Provincial Key Laboratory of New Drug Screening, School of
Pharmaceutical Sciences, Southern Medical University, 1023 South Shatai Road,
Baiyun District, Guangzhou 510515, P. R. China. E-mail: zhuqh@smu.edu.cn;
tangxdong@smu.edu.cn
† Electronic supplementary information (ESI) available: Experimental section,
characterization of all compounds, Fig. S1, copies of 1H and 13C NMR spectra
for all target compounds. CCDC 1502249. For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/c7ra07105a
Scheme 1 Synthetic methods for 1,2-bis(arylsulfonyl)ethylenes.
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involving haloalkynes have been developed, including nucleo- (3a) was obtained in 60% yield (entry 1). And the structure was
philic addition,8 cross-coupling reactions9 and cycloaddition conrmed by single-crystal X-ray analysis, in which the double
reactions.10 In comparison with sulfonyl chlorides, sodium bond is E-type conguration.12 Aerwards, we examined the
sulnates as mild sulfone moieties have many advantages, such concentration of hydrochloric acid and the results indicated
as low toxicity, ready accessibility and stability. The sodium that the yields increased with higher concentration HCl (entries
sulnates are not only used as the simple nucleophilic reagents 2–5). The yield was raised up to 91% when 12 M HCl was used
but also sulfonyl radicals to participate in the sulfonylation (entry 5). Next, the screening of reaction temperature showed
reaction. Recently, many endeavors have been made towards that neither increasing nor decreasing the temperature led to
utilizing sodium sulnates to synthesize organosulfone a lower yield of product (entries 6–9). Other Brønsted acids such
compounds.11 Based on the reaction development of hal- as H2SO4, TsOH, TfOH, TFA and HOAc were tested to give the
oalkynes and sodium sulnates, we developed a direct synthesis product in decent yields (entries 10–14). Control experiment
of 1,2-bis(arylsulfonyl)ethylenes through tandem reaction indicated that acid was essential for this transformation (entry
between haloalkynes and sodium sulnates under acidic 15). The screening of different solvents showed that the solvents
conditions. Herein, we presented a acid-mediated synthesis of played a critical role, the polar solvents were benecial for the
1,2-bis(arylsulfonyl)ethylenes from bromoalkynes and sodium transformation (entries 16–24).
sulnates (Scheme 1e).
With the optimal reaction condition in hand, we next con-
We used the reaction between phenylethynyl bromide (1a) ducted a survey of various substrates to explore the scope of this
and sodium p-tolylsulnate (2a) as a model to examine various transformation. As listed in Table 2, the reaction had a good
reaction parameters and the results were summarized in substrate suitability and various substituted (E)-1,2-bis(ar-
Table 1. On the rst trial, 1a and 2a (2.5 equiv.) were treated with ylsulfonyl)ethylenes were obtained in moderate to excellent
1 M HCl (1 equiv.) in DMSO as solvent at 60 ꢀC for 12 h. To our yields. We rstly evaluated the scope of bromoalkynes. Various
delight, the target product 1,2-bis(tolylsulfonyl)phenylethene alkyl and halogen substitutions on benzene ring of
Table 2 Substrate scope for the synthesis of substituted (E)-1,2-
Table 1 Optimization of the reaction conditionsa
bis(arylsulfonyl) ethylenesa
Entry
Acid
Solvent
T (ꢀC)
Yield (%)
1
2
3
4
5
6
7
8
1 M HCl
3 M HCl
6 M HCl
9 M HCl
12 M HCl
12 M HCl
12 M HCl
12 M HCl
12 M HCl
H2SO4
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
CH3CN
DMF
60
60
60
60
60
40
rt
80
100
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
68
74
83
91
42
13
80
78
71
58
68
65
10
n.d.
61
50
38
27
15
n.d.
n.d.
n.d.
n.d.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
TsOH
TfOH
TFA
HOAc
—
12 M HCl
12 M HCl
12 M HCl
12 M HCl
12 M HCl
12 M HCl
12 M HCl
12 M HCl
12 M HCl
Acetone
CH3NO2
1,4-Dioxane
CHCl3
EtOAc
Toluene
DCE
a
Reaction were performed with 1a (0.3 mmol), 2a (0.75 mmol), acid (0.3
mmol) in solvent (3.0 mL) for 12 h. Isolated yield. n.d. ¼ not
determined.
a
Reactions were performed with 1 (0.3 mmol), 2 (0.75 mmol), 12 M HCl
(0.3 mmol), and DMSO (3 mL) at 60C for 12 h. Yields was referred to
isolated yields.
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phenylacetylene bromides were tolerated for this reaction. smoothly and afforded the corresponding products in moderate
Strong electron-donating substitute such as methoxyl slightly to good yields (Table 3, 4i–4p). It was a pity that sodium alkyl-
decreased the yield of desired product (Table 2, 3f and 3i). For sulnates was not appropriate for the transformation at this
the substrate scope of sodium sulnates, different para- stage.
substituted sodium phenylsulnates could be converted into
To gain more insight into the mechanism, the control
the corresponding products in moderate to good yields (Table 2, experiments were carried out and shown in Scheme 2. When we
3j–3m). Even the steric hindered ortho-substituted sodium utilized phenylacetylene, phenylethynyl chloride or phenyl-
phenylsulnates also worked efficiently to give the products in ethynyl iodine to react with 2a under the standard conditions.
44% to 69% yields (Table 2, 3n–3p). Unfortunately, more steric Phenylethynyl iodide gave the product 4a in 82% yield, while
hindered mesitylenesulnate and electron-decient nitro- phenylacetylene and phenylethynyl chloride were failed to
benzenesulnate were failed to transform into the corre- convert into the product (Scheme 2, eqn (1)). The presence of
sponding products (Table 2, 3q and 3r).
TEMPO or BHT strongly suppressed the product formation,
It was surprising that when 1a and 2a was treated with 12 M respectively gave the product 4a in 0% and 15% yields (Scheme
HCl (1 equiv.) in toluene as solvent at 60 ꢀC for 12 h, the product 2, eqn (2)). These results indicated that a radical pathway may
acetylenic sulfone (4a) was formed in 48% yield.13 Though some be involved. However, we did not detect the additive products of
methods have been reported for the synthesis of acetylenic radicals coupling with TEMPO or BHT. When the 4-methyl-
sulfones, they had some disadvantages such as unavailable benzenesulnic acid 5 reacted with 2a in absence of 12 M HCl,
starting materials and strong oxidant.14 Thus, we optimized the the product 3a was obtained in 45% yield (Scheme 2, eqn (3)).
reaction conditions and the best reaction conditions were as The vinyl sulfone 6 could not transformed into the product with
followed: 1a (0.3 mmol), 2a (0.75 mmol), 1 M HCl (0.3 mmol), 2a under standard reaction condition (Scheme 2, eqn (4)). We
TBAI (20 mol%), in toluene (3 mL) at 60 ꢀC for 12 h (see the ESI† next investigated whether 4a was the reaction intermediate for
for details). Aer establishing the optimized reaction condi- the formation product 3a. Sodium sulnates could add into 4a
tions, the generality and limitations of various substrates were to form 3a in excellent yield in the presence of 12 M HCl
investigated. Firstly, sodium p-tolylsulnate (2a) was treated (Scheme 2, eqn (5)).
with different substituted phenylacetylene bromides. Different
According to previous studies15,16 and our control experi-
para-substituted phenylacetylene bromides including alkyl ments, the proposed mechanisms were shown in Scheme 3. One
group (Me, Et) and halides (F, Cl, Br) were well tolerated under proposed mechanism was a addition–elimination process (path
the optimized condition to afford the products in 57% to 87% a).15 Firstly, the nucleophilic attack of sulnate ion to 1a formed
(Table 3, 4a–4f). Subsequently, the effect of ortho-substituents the intermediate A, which was followed by protolysis to give the
on the phenyl ring of phenylacetylene bromides were investi- intermediate B. Finally, the intermediate
B eliminated
gated. The product 4g and 4h were formed in 77% and 68% hydrogen bromide to produce the product 4a. The other
yields, respectively. Further investigating the scope of this mechanism was a radical process (path b). The p-tolylsulfonyl
transformation included various substitutions effect on sodium radical C could be generated from sodium p-tolylsulnate in
phenylsulnates. Various sodium sulnates could be proceeded acid under heated condition.16a,b Subsequently, a radical
Table 3 Substrate scope for the synthesis of substituted acetylenic
sulfonea
a
Reaction conditions: 1 (0.3 mmol), 2 (0.75 mmol), 1 M HCl (0.3 mmol),
TBAI (20 mol%), and toluene (3 mL) at 60 ꢀC for 12 h. Yields was referred
to isolated yields.
Scheme 2 Control experiments.
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Scheme 3 Possible reaction mechanism.
addition of p-tolylsulfonyl radical to 1a formed a bromovinyl
radical D.16c Then, the product 4a was obtained via bromine
radical elimination from D.16c Finally, the bromine radical
oxidized sodium p-tolylsulnate to afford p-tolylsulfonyl radical
C with releasing NaBr.16c The 4a could be transformed into the
product 3a through nucleophilic addition. The polarity of the
solvent determined the nal product was 4a or 3a. The nal
product was 4a in the low polar solvents such as toluene, CHCl3,
DCE and so on. The high polar solvent was good for nucleo-
philic addition process. So when the high polar solvents such as
DMSO, DMF, CH3CN were used, the nal product was 3a.
In conclusion, we have developed a practical and novel proce-
dure for the synthesis of (E)-1,2-bis(arylsulfonyl)ethylenes and
arylacetylenic sulfones by sulfonylation of arylethynylene bromides
with sodium arylsulnates in different solvents. The method
obviated the need for unavailable starting materials or strong
oxidants with simple operation. Further research for the mecha-
nism and the synthetic applications are ongoing in our laboratory.
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Acknowledgements
The authors thank the High-level Talent Introduction Founda-
tion of Southern Medical University (C1033520), and the
Science and Technology Program of Guangdong Province
(2015A010105015) for nancial support.
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