Convenient method for preparation of aryl sulfinates from arenes and DABSO as the SO2 surrogates

Article abstract of DOI:10.1016/j.tetlet.2018.01.081

A safe and efficient protocol for the synthesis of aryl sulfinates from arenes and 1,4-diazabicyclo[2,2,2]octane bis(sulfur dioxide) (DABSO) under mild conditions is described. Through in situ infrared spectroscopic studies, a plausible mechanism for the sulfination reaction is proposed as well.

Full text of DOI:10.1016/j.tetlet.2018.01.081

Accepted Manuscript
Convenient method for preparation of aryl sulfinates from arenes and DABSO
as the SO2 surrogates
Tianlei Wang, Fumin Wang, Jinghua Shen, Tianting Pang, Yanfei Ren, Botao
Wu, Xubin Zhang
PII:
S0040-4039(18)30126-6
https://doi.org/10.1016/j.tetlet.2018.01.081
TETL 49668
DOI:
Reference:
Tetrahedron Letters
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Revised Date:
Accepted Date:
13 November 2017
24 January 2018
26 January 2018
Please cite this article as: Wang, T., Wang, F., Shen, J., Pang, T., Ren, Y., Wu, B., Zhang, X., Convenient method
for preparation of aryl sulfinates from arenes and DABSO as the SO2 surrogates, Tetrahedron Letters (2018), doi:
https://doi.org/10.1016/j.tetlet.2018.01.081
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Graphical Abstract
Convenient method for preparation of aryl
sulfinates from arenes and DABSO as the
SO2 surrogates
Leave this area blank for abstract info.
Tianlei Wang, Fumin Wang, Jinghua Shen, Tianting Pang, Yanfei Ren, Botao Wu, and Xubin Zhang

Tetrahedron Letters
Convenient method for preparation of aryl sulfinates from arenes and DABSO
as the SO2 surrogates
Tianlei Wang a, Fumin Wang a,*, Jinghua Shena, Tianting Pang a, Yanfei Ren a, Botao Wu a, and Xubin
Zhang a,*
aSchool of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A safe and efficient protocol for the synthesis of aryl sulfinates from arenes and 1,4-
diazabicyclo[2,2,2]octane bis(sulfur dioxide) (DABSO) under mild conditions is
described. Through in situ infrared spectroscopic studies, a plausible mechanism for
the sulfination reaction is proposed as well.
Available online
2017 Elsevier Ltd. All rights reserved.
Keywords:
Aryl sulfinates
DABSO
Sulfination
In situ IR
Synthetic methods
Santos in 1987.12 Willis et al. reported the palladium-
catalyzed aminosulfonylation process with DABSO,13 the
Introduction
As the valuable and pivotal intermediates for the
preparation of sulfoxides, sulfonamides and other organic
compounds which have sulfonyl motifs(-SO2-), sulfinic
acids and their salts should not be ignored. They were first
reported in the 1860s1 and started to be extensively
developed over the last decade. The commonly used
method is the reduction of the corresponding sulfonyl
chlorides.2 Other strategies for the preparation of sulfinates
include the reaction between organometallic agent and
SO2, 3 Pd-catalyzed coupling of diazonium
synthesis of sulfinates from DABSO and organometallic
agent,14 and another way to access sulfinates is from
DABSO and boronic acids.15 Wu et al. studied the
formation of sulfonamides with DABSO and arylboronic
acids,16 metal-free aminosulfonylation of aryldiazonium
tetrafluoroborates with DABSO and hydrazines17 and other
related reactions with insertion of sulfur dioxide.18
Furthermore, there have been many other researches on the
use of DABSO in the synthesis of related substances in the
recent years.19 Considering the wide application of
DABSO in organosulfur chemistry, we envisioned that
DABSO might be employed in the Friedel-Crafts
sulfination as well. Herein, we report the simple
preparation of aryl sulfinates from arenes and DABSO as
the SO2 surrogates.
tetrafluoroborates with SO2 and H2,4 and the oxidation of
thiols.5 In recent years, some new advances have been
made in the synthesis of sulfinates, such as iron-catalyzed
reaction of diphenyliodonium salts and rongalite
(HOCH2SO2Na·2H2O),6 palladium-catalyzed sulfination of
aryl halides and K2S2O5,7 gold(I)-catalyzed synthesis of
8
O
sulfinates from aryl boronic acid derivatives and K2S2O5
OH
O
H2N
S
and so on.9,10
O
O
S
O
The most straightforward approach to sulfinates is the
Friedel-Crafts sulfination.11 However, the use of toxic and
irritative SO2 gas and HCl gas is cumbrous and it requires
careful handling. Therefore, we were attracted to use the
SO2 surrogates for the Friedel-Crafts sulfination reaction.
DABSO (1,4-diazabicyclo [2.2.2] octane bis (sulfur
dioxide) adduct), as a bench-stable colorless solid, has
been proved that it can be applied to various reactions
instead of SO2 gas. It was first found and characterized by
Parabase ester
Figure 1. A key intermediate of reactive dyes.
Results and discussion
We started our initial studies with acetanilide (1a),
which could be the starting material for parabase ester [2-
(p-aminophenylsulfonyl)ethyl hydrogen sulfate] (Figure 1).
*Corresponding authors. E-mail addresses: wangfumin@tju.edu.cn, tjzxb@tju.edu.cn.

2
Tetrahedron
Initially, we performed the reaction between acetanilide
b HPLC yield relative to an internal standard. N.R.= No reaction.
1a and DABSO (1.0 equiv) at 20 oC, using AlCl3 (4 equiv)
as the catalyst and DCE as the solvent, respectively.
However, only a trace amount of the desired product was
obtained (Table 1, entry 1). Then we increased the amount
of catalyst. To our delight, the reaction occurred smoothly
to give the desired product with 83% yield when the
amount of AlCl3 was increased to 8 equiv (Table 1, entry
3). Further investigation on the effect of reaction
Then we investigated the scope of our reaction, and the
results were summarized in Table 2. Interestingly,
compared to acetanilide, using only 4 equiv of AlCl3, the
reaction could be carried out with a series of substituted
arenes, affording the corresponding products in good yields
(75-98%) in several hours.
Table 2. Scope of Friedel-Crafts sulfination of arenes and
temperature was conducted and at 25 oC the reaction
produced the highest yield (91%, Table 1, entry 6). The use
of different solvents also strongly influenced the reaction.
When the reaction was carried out in DCM, MeNO2, CS2
or PhNO2, the yield of the desired product decreased
dramatically (Table 1, entries 7-10). Reaction was not
observed when using FeCl3, ZnCl2 and TiCl4 as catalyst
(Table 1, entries 11-13). The “SO2” precursor also played a
vital role in this reaction. We tried another two tertiary
amine-SO2 complexes. The SO2 adduct of quinuclidine
(ABSO) gave a low yield (Table 1, entry 14), and the SO2
adduct of hexamethylenetetramine (HMTA·2SO2) gave a
moderate yield (Table 1, entry 15), while DABSO gave the
best result in terms of yield. Therefore, the optimal
conditions were established as: using AlCl3 (8 equiv) as the
catalyst and DABSO as the “SO2” precursor to perform the
reaction in DCE at 25 oC.
DABSOa
Table 1. Optimization of reaction conditionsa
aConditions: arene (2.0 mmol), DABSO (1.0 equiv), AlCl3 (4.0
equiv), solvent (10 mL). bIsolated yields.
As shown in detail in Table 2, the introduction of
electron-donating groups, such as alkyl and alkoxy group
(1b-e) could cause high yields. While the presence of
electron-withdrawing groups could lead to different results:
the halides (1g-i) gave good to excellent yields (70-98%),
but the nitro group (1j) failed. It was noteworthy that for
anisole (1d), nitrobenzene was more appropriate than DCE
or DCM as the solvent in this reaction. But for other
substrates listed in table 2, the corresponding product
cannot be observed when the nitrobenzene was used as
solvent. Presumably due to the interaction of AlCl3 and
nitrobenzene, which weaken its catalytic effect, the
extremely electron-donating effect of methoxyl group
makes the reaction proceed smoothly.
Various methods including in situ IR were used to study
the possible mechanisms.20 But to our knowledge, no
detailed mechanistic study of Friedel-Crafts sulfination
a Reaction conditions: acetanilide (2.0mmol), “SO2” precursors
(1.0 equiv), solvent (10 mL),

3
was reported. We established the possible mechanism of
Friedel–Crafts sulfination that acetanilide reacted with
DABSO using AlCl3 as catalyst in DCE.
F was the characteristic absorption peak of para
substitution of benzene ring. In the next 30 minutes two
new bands appeared at 1324 cm-1(A) and 1130 cm-1(C),
which were assigned to the antisymmetric and symmetric
S-O stretching vibrations of SO2, respectively.23 The
characteristic band of AlCl3 at 1100 cm-1 increased
gradually, indicating that more and more AlCl3 was
involved in the reaction. It was noteworthy that DABSO
had very little solubility in DCE, but it could dissolve well
when AlCl3 was added. This result indicated the formation
of the AlCl3 adduct of DABSO, which was the
key intermediate of Friedel–Crafts sulfination.
Figure 2. In situ IR spectra of (a)acetanilide and addition of (b) 1,
(c) 2, (d) 4, and (e) 8 equivalents of AlCl3 in DCE, respectively.
The FTIR spectra in the 1800–1400 cm−1 range of
acetanilide and addition of different amounts of AlCl3 in
DCE were compared in Figure 2, which showed the
interaction of acetamido group with AlCl3. The spectrum
of acetanilide (Figure 2a) gave band at 1700 cm−1 from the
band amide I υ(C=O), and the band amide II, involving
δ(NH), appeared at 1525 cm−1, and at 1603 cm−1 from the
υ(C=C) of the aromatic ring.21 When different amounts of
AlCl3 were added (Figure 2b-e), the two bands at 1700 cm-
1 and 1525 cm-1 were almost disappeared, whereas the
band at 1625 cm-1 was observed, indicating the
Figure 3. In situ IR spectra of the reaction of acetanilide with AlCl3
and DABSO in DCE. DABSO was added after the first spectrum was
collected.
disappearance of the N-H and that the vibration frequency
of the C=O was obviously changed.21 It would be taken as
the evidence of the interaction of acetamido group with
AlCl3. Besides, the absorption peak of aromatic ring
appeared red shift, decreasing from 1603 cm-1 to 1592 cm-
1.22 Therefore, these five bands would indicate the
formation of the AlCl3 adduct of acetanilide. It also
suggested why acetanilide required much more AlCl3 than
other substrates. The possible structure was shown in
Scheme 1.
Figure 4 showed the trend of two peaks which were
assigned to the AlCl3 adduct of 4-
acetamidobenzenesulfinic acid. The absorption intensity of
these peaks gradually increased by roughly the same trend,
indicating that the reaction rate was high at the beginning,
and got slower as the reaction proceeded. It was suggested
that the reaction was similar to second order reaction in
kinetics. Then we investigated the kinetics of this reaction
using HPLC.
Scheme 1. Proposed reaction of acetanilide with AlCl3 in DCE
AlCl
3
Cl
Al
O
O
Cl
N
CH
3
HN
CH
+
3
2AlCl
+
HCl
3
Next, in situ infrared experiment of acetanilide with
AlCl3 and DABSO was carried out (Figure 3). Careful
analysis of these spectra revealed that after the addition of
DABSO, five new bands appeared in the range of 1400-
800 cm-1 and the absorption intensity gradually increased
as the reaction went on. Three new peaks appeared
immediately at 1208 cm-1(B), 1048 cm-1(E) and 846 cm-
1(F). Band B was due to DABSO; bands E and F were
assigned to product (the AlCl3 adduct of 4-
Figure 4. In situ IR spectra of two peaks trend. a-Peaks at 1048 cm-1,
b-Peaks at 846 cm-1.
To measure the reaction order, the peak area of product
and acetanilide with different reaction time was
determined, and the peak area represented, to some extent,
the concentration. The ratio of [product]/[acetanilide] as Y
axis and reaction time as X axis, we obtained a fitting
straight line, of which R2 was 0.9996 (Figure 5).
acetamidobenzenesulfinic acid), indicating a very fast
sulfination reaction. Band E could be attributed to the
symmetric S-O stretching vibrations of product. 23-24 Band

4
Tetrahedron
Meanwhile, the reaction mechanism is proposed by in situ
IR.
Acknowledgments
Financial support from the National Basic Research Program of
China (Grant No: 2012CB720302) and the National Key Research
and Development Program of China (2016YFF0102503) are
gratefully acknowledged.
Supplementary data
Experimental procedures and full characterization for all
compounds associated with this article can be found.
Figure 5. Kinetics of sulfination reaction. Conditions: acetanilide
(2.0 mmol), DABSO (0.5 equiv), AlCl3 (8.0 equiv), DCE (10 mL),
25 oC.
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As we known, for the two reactants with the same initial
concentration, if the reaction was a second-order reaction,
the ratio of the product concentration to the reactant
concentration was a linear function of time. We inferred the
essence of this reaction was that under the catalysis of
AlCl3, acetanilide reacted with SO2 to produce sulfinates.
One DABSO was equivalent to two SO2. Our results
coincided with it and concluded that this reaction was
second order, also consistent with the law: Friedel Crafts
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Conclusion
We have described a convenient and safe method for the
preparation of aryl sulfinates from arenes and DABSO
under mild conditions. The reaction proceeds smoothly
from 0 oC to room temperature to afford a number of aryl
sulfinates from inexpensive and commercially available
materials without the need for any ligands and additives.

5
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Highlights
Simple preparation method, mild conditions and
cheap reactants for the synthesis of aryl sulfinates.
In situ infrared spectroscopic studies for this
sulfination reaction and a plausible mechanism is
proposed.
Solid, stable SO2 surrogates are used instead of
toxic gas SO2.