A novel practical preparation of methyl methanethiosulfonate from dimethyl sulfoxide initiated by a catalytic amount of (COCl)2 or anhydrous HCl

Article abstract of DOI:10.1080/17415993.2021.1932887

A novel practical preparation method for methyl methanethiosulfonate (MMTS) has been developed. Dimethyl sulfoxide was converted to MMTS in the presence of a catalytic amount of oxalyl chloride or anhydrous HCl in acetonitrile under reflux in an ideal yield. Methanesulfenic acid was proposed to be the key intermediate for the formation of MMTS.

Full text of DOI:10.1080/17415993.2021.1932887

Journal of Sulfur Chemistry
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/gsrp20
A novel practical preparation of methyl
methanethiosulfonate from dimethyl sulfoxide
initiated by a catalytic amount of (COCl) or
2
anhydrous HCl
Shuai Huang, Hao Wang, Yongguo Liu, Baoguo Sun, Hongyu Tian & Sen Liang
To cite this article: Shuai Huang, Hao Wang, Yongguo Liu, Baoguo Sun, Hongyu Tian & Sen
Liang (2021): A novel practical preparation of methyl methanethiosulfonate from dimethyl sulfoxide
initiated by a catalytic amount of (COCl) or anhydrous HCl, Journal of Sulfur Chemistry, DOI:
2
10.1080/17415993.2021.1932887
To link to this article: https://doi.org/10.1080/17415993.2021.1932887
View supplementary material
Published online: 30 May 2021.
Submit your article to this journal
Article views: 25
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
https://www.tandfonline.com/action/journalInformation?journalCode=gsrp20

JOURNAL OF SULFUR CHEMISTRY
https://doi.org/10.1080/17415993.2021.1932887
A novel practical preparation of methyl
methanethiosulfonate from dimethyl sulfoxide initiated by a
catalytic amount of (COCl) or anhydrous HCl
2
Shuai Huang, Hao Wang, Yongguo Liu, Baoguo Sun, Hongyu Tian and Sen Liang
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Key Laboratory of Flavor
Chemistry, Beijing Technology and Business University, Beijing, People’s Republic of China
ABSTRACT
ARTICLE HISTORY
Received 13 April 2021
Accepted 16 May 2021
A novel practical preparation method for methyl methanethiosul-
fonate (MMTS) has been developed. Dimethyl sulfoxide was con-
verted to MMTS in the presence of a catalytic amount of oxalyl chlo-
ride or anhydrous HCl in acetonitrile under reflux in an ideal yield.
Methanesulfenic acid was proposed to be the key intermediate for
the formation of MMTS.
KEYWORDS
Methyl
methanethiosulfonate;
dimethyl sulfoxide; oxalyl
chloride; methanesulfenic
acid;
methoxydimethylsulfonium
salt
Introduction
Thiosulfonates, which are very useful sulfenylating or sulfonylating reagents in organic
synthesis, have attracted much attention among the organic community during recent
years [1]. In this compound class, methyl methanethiosulfonate (MMTS) is one of the
most widely employed thiosulfonates. It is commonly used as a sulfenylating reagent, more
reactive than the commonly utilized dimethyl disulfide, and more stable than the highly
reactive methanesulfenyl chloride [2]. It is broadly applied in the methylsulfenylation of
mercapto groups in enzymes and other biologically active compounds [3–6]. Moreover,
a variety of sulfenylated intermediates in organic syntheses can be prepared with MMTS.
Substrates with acidic protons, such as 1,3-dicarbonyl compounds [7,8] or lactones [9],
can be methylsulfenylated with MMTS after deprotonation in the presence of a base. It can
also serve as a protective reagent for amino groups [10]. A methylthio group can be intro-
duced into different heterocycles with MMTS via metalation [11–13]. It can be used to
convert 1-alkenylalumiunum derivatives into sulfides efficiently [14]. In addition, MMTS
was reported to exist in various vegetables, such as broccoli [15], mushroom [16], cabbage
CONTACT Hongyu Tian
tianhy@btbu.edu.cn
Beijing Advanced Innovation Center for Food Nutrition and
Human Health, Beijing Key Laboratory of Flavor Chemistry, Beijing Technology and Business University, Beijing 100048,
People’s Republic of China
©
2021 Informa UK Limited, trading as Taylor & Francis Group

2
S. HUANG ET AL.
Scheme 1. Preparation of MMTS from DMSO with a catalytic amount of (COCl)2.
[
17,18] and cauliflower [19], which was claimed to possess antibacterial activity [17,18]
and antimutagenic activity [19].
Some strategies for thiosulfonate synthesis have been developed due to increasing inter-
est in this class of compounds, which can be prepared from various chemical feedstocks,
such as disulfides, thiosulfinates, thiols, sulfenyl halides, sulfonyl halides, alkali metal
thiosulfonates or sulfinates, or sulfonyl hydrazides [1]. To the best of our knowledge, no
economically attractive synthetic methods have been described for methyl methanesul-
fonate. Traditional preparation methods of MMTS include hydrolysis of methanesulfenyl
chloride made by oxidation of dimethyl disulfide with chlorine [20,21], silver-assisted
displacement on sulfur of disulfide with sodium methanesulfinate [22], reduction of sul-
fonyl halides with potassium iodide [23] or activated zinc powder [24–27], or oxidation
of dimethyl disulfide with microwave-supported permanganate or hydrogen peroxide in
AcOH [28,29]. In addition, Laszlo and Mathy accidentally discovered that dimethyl sul-
foxide (DMSO) can be converted into MMTS by treatment with chlorotrimethylsilane and
ethylene glycol [30].
DMSO is a versatile source for various synthons including methyl, methylene, methine,
methylthio, methylthiomethyl, methyl sulfinyl, methylsulfinylmethyl etc [31–33]. Our
recent work has focused on the application of combination reagents containing sulfoxide
and oxalyl halide [34] in various chemical transformations, including sulfenyllactonization
[
[
[
34] or chlorolactonization [35] of alkenoic acids, bromination [36], sulfenylchlorination
37] or oxysulfenylation [38] of alkenes, dehydration of primary amides or aldoximes
39], sulfenyletherification of alkenols [40], and the preparation of unsaturated lactones
from 3-alkenoic acids [41,42]. During the investigation of alkene oxysulfenylation with
DMSO/(COCl) [38], we fortuitously discovered that MMTS can be obtained cleanly from
2
DMSO with a catalytic amount of (COCl) (Scheme 1) [43].
2
Results and discussion
Originally, methyl methanethiosulfonate was found in our work on the oxysulfenylation
of alkenes, which involved treating an alkene with DMSO/(COCl) followed by reacting
2
with p-cresol in the presence of K CO [38] Stimulated by the results, a series of experi-
2
3
ments were conducted to investigate its formation in this reaction system. Several control
experiments were carried out by modifying the conditions in oxysulfenylation of alkenes
without the addition of alkene and p-cresol [38]. MMTS produced in the reaction mixture
was analyzed semiquantitatively by GC/MS with an internal standard (Table 1).
The typical procedure is as follows: to a solution of dimethylsulfoxide (DMSO, 30 mmol,
2
equivalents) in acetonitrile cooled at 0°C was added dropwise a solution of oxalyl chlo-
ride (15 mmol, 1 equivalent) in acetonitrile. Then K CO (2 equivalents) was added and
2
3
the reaction mixture was allowed to warm to room temperature and then heated to reflux.
The reaction was shown to be complete after refluxing for 2 h by GC/MS analysis. The

JOURNAL OF SULFUR CHEMISTRY
3
Table 1. Investigation on the conditions for the formation of MMTS.
Entry
Reagents (equiv.)
Conditions
Yield (%)a
1
2
3
4
5
6
7
8
DMSO/(COCl)2/K2CO3(2/1/2)
DMSO/K2CO3(1/1)
CH3CN, 0°C-reflux, 2 h
CH3CN, 0°C-reflux, 8 h
CH3CN, 0°C-reflux, 2 h
CH3CN, 0°C-reflux, 2.5 h
CH2Cl2, 0°C-reflux, 8 h
CH3CN, 0°C-reflux, 3.5 h
CH3CN, 0°C-reflux, 6 h
CH3CN, 0°C-reflux, 10.5 h
9
0
8
10
5
19
19
19
DMSO/(COCl)2(2/1)
DMSO/(COCl)2(3/1)
DMSO/(COCl)2(3/1)
DMSO/(COCl)2(10/1)
DMSO/(COCl)2(20/1)
DMSO/(COCl)2(30/1)
aGC yields. The amount of MMTS in the reaction mixture was determined using n-pentyl acetate as an internal standard via
GC/MS. The yields were calculated based the amount of MMTS formed from one equivalent of DMSO.
content of MMTS in the reaction mixture was determined by the internal standard method.
The yield was about 9% based on the amount of DMSO (entry 1). An experiment was
carried out in the absence of (COCl) with the other conditions the same as those in
2
entry 1. GC/MS analysis showed that DMSO was unchanged without MMTS formed after
refluxing for 8 h (entry 2). The reaction of DMSO with (COCl) also produced MMTS
2
in about 8% yield in the absence of K CO with the other conditions the same as those
2
3
in entry 1 (entry 3). The following reaction was carried out with an increased ratio of
DMSO/(COCl) 3/1 and the yield of MMTS increased slightly to 10% (entry 4). Whereas
2
when the reaction was carried out in CH Cl , about half of DMSO remained after reflux-
2
2
ing for 8 h with a 5% yield (entry 5). We observed that no DMSO was left in the reaction
of entry 4 even though the amount of DMSO was excess compared with that in the reac-
tion of entry 3. Therefore, we wondered whether stoichiometric amount of (COCl) was
2
necessary in this reaction. Subsequently, a reaction was carried out with a DMSO/(COCl)2
ratio of 10/1 and monitored by GC/MS. It was found that DMSO disappeared completely
in 3.5 h and the yield of MMTS increased to 19% (entry 6). This result suggested that the
formation of MMTS did not require a stoichiometric amount of (COCl) . The reaction
2
can occur as well when the ratio of DMSO/(COCl) increased further to 20/1, affording
2
MMTS in about 19% yield within 6 h (entry 7). Impressively, MMTS was still able to be
produced even with a DMSO/(COCl) ratio of 30/1. However, the reaction seemed to
2
slow down in that approximately 2/3 of the DMSO remained unreacted after refluxing
for 4 h. The reaction was accomplished in 10.5 h with a final yield approaching about 19%
(
entry 8).
Initially, the formation of MMTS was merely analyzed by GC/MS without separation for
calculating yields. Further experiments with different DMSO/(COCl) ratios were done
2
on a larger scale with 0.1 mol of DMSO and the products were purified by column chro-
matography (Table 2). The reaction was complete after refluxing for 2.5 h when the ratio
of DMSO/(COCl) was 4/1, affording MMTS in 11% yield (entry 1, Table 2). When the
2
amount of (COCl) was reduced (DMSO/(COCl) = 10/1), the yield of MMTS increased
2
2
to 16% (entry 2, Table 2). In contrast, the reaction took longer time to complete with a 18%
yield when the amount of (COCl) was reduced further (DMSO/(COCl) = 20/1) (entry
2
2
3
, Table 2). Considering the time cost, a 10/1 ratio of DMSO/(COCl) is more reasonable
2
for the practical production of MMTS. Thus, the preparation of MMTS was performed
on a large scale of 1 mol DMSO with a 10/1 ratio of DMSO/(COCl) and the product was
2
purified by vacuum distillation with a 16% average yield.

4
S. HUANG ET AL.
Table 2. Investigation of MMTS formation on a larger scale.
Entry
Reagents (equiv.)
Conditions
Yield (%)a
1
2
3
DMSO/(COCl)2(4/1)
DMSO/(COCl)2(10/1)
DMSO/(COCl)2(20/1)
CH3CN, 0°C-reflux, 2.5 h
CH3CN, 0°C-reflux, 3.5 h
CH3CN, 0°C-reflux, 7 h
11
16
18
aSeparation yields based on column chromatography.
Scheme 2. A proposed mechanism for the formation of methanesulfenic acid from DMSO initiated by
COCl)2.
(
From above results, methanesulfenic acid (1) is proposed to be formed initially as the
key precursor for MMTS formation (Scheme 2). It is well known that the reaction of
DMSO with (COCl) rapidly generates chlorodimethylsulfonium salt (2) as an interme-
2
diate, which is the key active species in Swern oxidation. DMSO attacks the methyl group
of chlorodimethylsulfonium salt via nucleophilic substitution leading to the formation of
methanesulfenyl chloride and methoxydimethylsulfonium salt (3), which was reported by
Bellesia et al [44] and also observed in our previous work [34]. The methoxydimethyl-
sulfonium salt (3) further decomposes to dimethyl sulfide, formaldehyde, and a proton
+
(
H ). The transfer of this proton to DMSO produces hydroxydimethylsulfonium salt (4),
which is subsequently attacked by DMSO on the methyl group via nucleophilic substitu-
tion to regenerate methoxydimethylsulfonium salt (3) and release methanesulfenic acid
(
CH SOH, 1). In our previous work, formaldehyde formed in this regeneration cycle of
3
methoxydimethylsulfonium salt (3) was utilized for the preparation of N-acylbenzoxazines
from phenols and nitriles [45].
Two pathways are proposed for the conversion of methanesulfenic acid (1) to MMTS
Scheme 3). The first mechanism involves oxygen as an oxidant, since the reactions
(
were carried out under an air atmosphere. It abstracts a hydrogen atom from methane-
sulfenic acid (1) via homolytic bond cleavage to yield a methylsulfinyl radical (5).
It can combine with its resonance structure (an O-centered radical, 6) to give labile

JOURNAL OF SULFUR CHEMISTRY
5
Scheme 3. Two possible pathways for the generation of MMTS from methanesulfenic acid (1).
OS-methanesulfenyl methanesulfinate (7). Subsequently, this unstable intermediate col-
lapses to a methanesulfonyl radical (8) and a methanesulfenyl radical (9), which can
recombine at the sulfur atoms to yield MMTS. In the other pathway, methanesulfenic acid
(1) undergoes self-condensation to generate methyl methanethiosulfinate (10) followed
by disproportionation to yield MMTS with dimethyl disulfide. Both pathways can be sup-
ported by literature. Sulfenic acids have been taken as the precursors for thiosulfinates
and thiosulfonates [46–51], which are very common in the organosulfur chemistry of the
genus Allium [52–54]. It was reported that t-butylsulfenic acid was converted to S-t-butyl
t-butanethiosulfonate in the presence of di-t-butyl peroxide via a sulfenyl sulfonate [46],
which is similar to the first pathway we proposed in Scheme 3. In addition, Pratt et al.
established that sulfenic acids have among the weakest O-H bonds known (ca. 70 kcal
−
1
mol ) and demonstrate high radical-trapping activity, which accounts for antioxidant
activity of extracts of garlic and petiveria [55]. Obviously, this kind of antioxidant activity
exploits autoxidation of sulfenic acids involving oxygen. On the other hand, the formation
of MMTS from methanesulfenic acid via disproportionation of methyl methanethiosulfi-
nate was reported to occur in garlic [52]. It was also reported methyl methanethiosulfinate
(
10) could be as the precursor of MMTS [56]. In addition, Wen et al. proposed that MMTS
derived from DMSO was the possible active species in acid promoted direct cross-coupling
of methyl ketones with dimethyl sulfoxide [57].
Which pathway methanesulfenic acid (1) would take to produce MMTS in this present
work? If the formation of MMTS occurred through the first pathway, four equivalents of
DMSO would produce one equivalent of MMTS theoretically; in comparison, the forma-
tion of one equivalent of MMTS would require eight equivalents of DMSO by the second
pathway. Generally, the separated yield under optimized conditions in our work is about
1
6%, based on which it was calculated that about six equivalents of DMSO produce one
equivalent of MMTS. The average yield we obtained was between the theoretical yields of
two possible pathways. The H NMR spectrum of the crude product indicated that it is a
1
very clean conversion of DMSO to MMTS. Therefore, we deduce that these two pathways
could coexist in the formation of MMTS in our work.

6
S. HUANG ET AL.
In addition, the presence of dimethyl disulfide can corroborate the second pathway.
Indeed, it was detected in the reaction mixture by GC/MS. Moreover, reactions under a
nitrogen atmosphere also formed MMTS in similar yields compared to reactions in air.
These results implied that the second pathway we proposed does exist. However, appar-
ently the second pathway is not the only mechanism for the formation of MMTS since
the amount of dimethyl disulfide observed is much less than MMTS formed in the reac-
tion mixture. Oddly, the amount of dimethyl disulfide did not increase significantly as we
expected when the reactions were carried out under a nitrogen atmosphere. This remains
elusive and further investigations are required.
The fact that yield of MMTS increases with reduced amount of (COCl) can be inter-
2
preted reasonably by the mechanism proposed above. The reaction of (COCl) with DMSO
2
generates methoxydimethylsulfonium salt (3), which decomposes to provide protons as
catalyst for the formation of the key active species methanesulfenic acid (1). More (COCl)2
would consume more DMSO, which reduces the yield of MMTS. On the other hand, it is
logical that a too small amount of (COCl) retards the reaction since the amount of protons
2
produced in situ depends on the (COCl) loading.
2
Based upon the aforementioned mechanisms, it appears that DMSO could be converted
to MMTS in the presence of a protic acid without needing (COCl) . Nevertheless, no
2
MMTS was detected when DMSO was treated with 0.1 equivalent of TsOH, CF COOH or
3
TfOH after refluxing in CH CN for 8 h. Conversely, a trace amount of MMTS was detected
3
after refluxing in CH CN for 8 h in the presence of 0.1 equivalent of hydrochloric acid
3
aqueous solution. Moreover, comparable yield of MMTS was obtained when the reaction
was carried out in the presence of about 0.1 equivalent of anhydrous hydrogen chloride
instead of (COCl) . These results indicated that a protic acid with enough acidity is nec-
2
essary for the generation of methanesulfenic acid (1). In addition, water has an adverse
effect on the reaction since only a trace amount of MMTS was detected when hydrochlo-
ric acid aqueous solution was used. Thus, it can be concluded from these results that the
mechanisms we proposed are reasonable.
There are two known preparation methods of MMTS involving DMSO. One was
reported by Laszlo and Mathy [30], who discovered it accidentally when preparing
formaldehyde acetals from alcohols and chlorotrimethylsilane in the presence of DMSO.
As pointed out by Maes et al., this method is unpractical in terms of atom economy, reaction
mass efficiency, and reaction process mass intensity [1]. The other method was reported by
Rätz and Sweeting in which MMTS was obtained as a byproduct without yield given [58].
Evidently, the synthesis of MMTS in this present work is distinct from those reported in the
literature. Compared with the existing methods, our method is much more advantageous
from the following aspects: (1) Clean conversion under benign experimental conditions
within a short reaction time; (2) Low synthetic cost and high reproducibility. In practice,
producing 1 equivalent of MMTS requires about 6 equivalents of DMSO and less than 0.6
equivalents of (COCl) or HCl. The reactions have been repeated many times with high
2
reproducibility. The reagents are cheap and the solvent can be recycled. Among all the exist-
ing methods, it is worth noting that Maddaluno et al. reported that MMTS was obtained
in 86% yield by the oxidation of dimethyl disulfide with hydrogen peroxide in AcOH [29].
Although it took 24 h to complete the reaction without large scale data, it looks quite practi-
cal. Compared with this method, our method has several advantages, such as short reaction
time, catalytic amount of reagent, and recyclable solvent.

JOURNAL OF SULFUR CHEMISTRY
7
In addition, the transformation of methylphenyl sulfoxide to phenyl benzenethiosul-
fonate was also explored under the above optimized conditions. Unfortunately, only a
small amount of phenyl benzenethiosulfonate was detected. This transformation should
be achievable according to the mechanisms we proposed. Further study about this trans-
formation and other sulfoxides is currently underway.
Conclusion
In summary, MMTS can be prepared in an ideal yield from DMSO with a catalytic
amount of (COCl) or anhydrous HCl after simple operations. Possible mechanisms are
2
proposed, in which methanesulfenic acid is generated as the key species which either
undergoes radical reactions via OS-methanesulfenyl methanesulfinate or intermolecular
condensation to produce methyl methanethiosulfinate intermediate to afford MMTS. It
is easy to scale up and quite suitable for the industrial production of MMTS. This prac-
tical approach has the potential to replace the current preparation method for MMTS in
industry.
Experimental
General procedures for preparation of methyl methanethiosulfonate from DMSO and
(
(
COCl) or anhydrous HCl. To a solution of DMSO (78 g, 1.0 mol, 1 equiv.) in CH CN
200 mL) cooled at 0°C was added dropwise a solution of oxalyl chloride (8.7 mL, 0.1 mol,
2
3
0
.1 equiv.) in CH CN (50 mL) under an air atmosphere (DMSO and CH CN were used
3
3
directly without treatment with drying agents). When anhydrous HCl was used, a solution
of anhydrous HCl in CH CN was prepared as follows. To concentrated H SO (30 mL)
3
2
4
was added dropwise concentrated HCl. The HCl gas generated passed through a water trap
filled with conc. H SO and a column of blue silica gel sel, then was bubbled into CH CN
2
4
3
in a round-bottom flask with a known weight at room temperature. After about 3.6 g of HCl
0.1 equiv.) was absorbed by CH CN, DMSO (1 equiv.) was added. The mixture was then
(
3
allowed to warm up to reflux. The reaction was monitored by GC/MS and was complete
in 3.5 h. The mixture was concentrated with a rotary evaporator under reduced pressure.
CH Cl (100 mL) was added to the residue and washed with saturated aqueous NaHCO
2
2
3
and brine successively. The organic layer was dried over anhydrous MgSO , filtered, and
4
concentrated in vacuum. Distillation under reduced pressure afforded 20.5 g of MMTS as a
1
colorless oil (16% yield, bp 69–72°C/0.4 mm). H NMR (300 MHz, CDCl ) δ 3.31 (s, 3 H),
3
1
3
2
.70 (s, 3 H). C NMR (75 MHz, CDCl ) δ 48.8, 18.3. All measured values were identical
3
to those in the literature [30].
Disclosure statement
No potential conflict of interest was reported by the author(s).
Funding
Financial support from the National key research and development program [grant numbers
2
017YFB0307502, 2016YFD0400801].

8
S. HUANG ET AL.
References
[
[
[
[
[
[
[
[
1] Mampuys M, Clark CR. Thiosulfonates as emerging reactants: synthesis and applications. Adv
Synth Catal. 2020;362:3–64.
2] Takeuchi K. Methyl methanethiosulfonate. e-EROS Encylcopedia of Reagents for Organic
Synthesis. 2001; 1-3.
3] Sheppard JG, McAleer JP, Saralkar P, et al. Allicin-inspired pyridyl disulfides as antimicrobial
agents for multidrug-resistant Staphylococcus aureus. Eur J Med Chem. 2018;143:1185–1195.
4] Zheng Y, Yu B, Li Z, et al. An esterase-sensitive prodrug approach for controllable delivery of
persulfide species. Angew Chem Int Ed. 2017;56:11749–11753.
5] Karala A-R, Ruddock LW. Does S-methyl methanethiosulfonate trap the thiol–disulfide state
of proteins? Antioxid Redox Sign. 2007;9:527–531.
6] Ryu EK, Choe YS, Byun SS, et al. Synthesis of radioiodine labeled dibenzyl disulfide for
evaluation of tumor cell uptake. Bioorgan Med Chem. 2004;12:859–864.
7] Wladislaw B, Marzorati L, Biaggio FC. Novel uncatalyzed thermal Pummerer rearrangements.
J Org Chem. 1993;58:6132–6134.
8] Mikolajczyk M, Midura WH. α-Phosphoryl sulfoxides. XI. Sulfenylation of α-phosphoryl
sulfoxides and a general synthesis of optically active ketene dithioacetal mono-S-oxides.
Tetrahedron. 1997;53:2959–2972.
[9] Ishigami K, Kitahara T. Synthesis of all the four possible stereoisomers of acaterin, naturally
occurring ACAT inhibitor, and the determination of its absolute configuration. Tetrahedron.
1
995;51:6431–6442.
[
10] Petrone DA, Franzoni I, Ye J, et al. Palladium-catalyzed hydrohalogenation of 1,6-enynes:
hydrogen halide salts and alkyl halides as convenient HX surrogates. J Am Chem Soc.
2
017;139:3546–3557.
[
[
11] Balkenhohl M, Jangra H, Lenz T, et al. Lewis acid directed regioselective metalations of
pyridazine. Angew Chem Int Ed. 2019;58:9244–9247.
12] Nafe J, Auras F, Karaghiosoff K, et al. Selective functionalization of tetrathiafulvalene using Mg-
and Zn-TMP-bases: Preparation of mono–, di–, tri–, and tetrasubstituted derivatives. Org Lett.
2
015;17:5356–5359.
[
[
[
[
[
[
[
[
[
[
13] Haas D, Mosrin M, Knochel P. Regioselective functionalization of the oxazole scaffold using
TMP-bases of Mg and Zn. Org Lett. 2013;15:6162–6165.
14] Kadikova RN, Ramazanov IR, Vyatkin AV, et al. Zirconocene catalysis in organoaluminum
synthesis of 1-alkenyl sulfones and sulfides. Synthesis. 2017;49:1889–1897.
15] Wu Y, Shen Y, Wu X, et al. Hydrolysis before stir-frying increases the isothiocyanate content of
broccoli. J Agric Food Chem. 2018;66:1509–1515.
16] Nosaka S, Miyazawa M. Characterization of volatile components and odor-active compounds
in the oil of edible mushroom Boletopsis leucomelas. J Oleo Sci. 2014;63:577–583.
17] Kyung KH, Han DC, Fleming HP. Antibacterial activity of heated cabbage juice, S-methyl-L-
cysteine sulfoxide and methyl methanethiosulfonate. J Food Sci. 1997;62:406–409.
18] Kyung KH, Fleming HP. Antimicrobial activity-of sulfur compounds derived from cabbage. J
Food Protect. 1997;60:67–71.
19] Nakamura Y, Matsuo T, Shimoi K, et al. S-Methyl methane thiosulfonate, a new antimutagenic
compound isolated from Brassica oleracea L. var. botrytis. Biol Pharm Bull. 1993;16:207–209.
20] Douglass IB. Some new reactions of methanesulfenyl chloride. J Org Chem. 1959;24:2004–
2
006.
21] Slusarchyk WA, Applegate HE, Funke P, et al. Synthesis of 6-methylthiopenicillins and 7-
heteroatom – substituted cephalosporins. J Org Chem. 1973;38:943–950.
22] Bentley MD, Douglass IB, Lacadie JA. Silver-assisted displacements on sulfur. A new thiolsul-
fonate ester synthesis. J Org Chem. 1972;37:333–334.
[23] Palumbo G, Caputo R. A facile way to thiosulfonic S-esters. Synthesis. 1981;13:888–890.
24] Freeman F, Keindal MC. A facile synthesis of symmetrical alkanesulfonothioic S-alkyl ester
[
(
S-alkyl alkanethiosulfonates). Synthesis. 1983;15:913–915.

JOURNAL OF SULFUR CHEMISTRY
9
[
[
[
[
25] Freeman F, Bartosik LG, Bui NV, et al. Preparation and spectral properties of symmetrical S-
aryl arenesulfonothioates (thiosufonates). Phosp Sulf. 1988;35:375–386.
26] Chemla F. An easy and practical synthesis of symmetrical thiosulfonic S-esters. Synthesis. 1998:
8
94–896.
27] Chemla F, Karoyan P. Reduciton of sulfonyl halides with zinc powder: S-methyl methanethio-
sulfonate. Org Syn. 2002;78:99–101.
28] Luu TXT, Nguyen T-TT, Le TN, et al. Fast and efficient green synthesis of thiosulfonate S-esters
by microwave-supported permanganate oxidation of symmetrical disulfides. J Sulfur Chem.
2
015;36:340–350.
[
29] Ahmad M, Gaumont AC, Durandetti M, et al. Direct syn addition of two silicon atoms to a
C(C triple bond by Si-Si bond activation: access to reactive disilylated olefins. Angew Chem
Int Ed. 2017;56:2464–2468.
[
[
[
[
[
[
[
[
[
[
[
[
[
[
30] Laszlo P, Mathy A. A novel, useful, and inexpensive preparation of S-methyl methanesulfonoth-
ioate. J Org Chem. 1984;49:2281–2281.
31] (Tashrifi Z, Khanaposhtani MM, Larijani B, et al. DMSO: yesterday’s solvent, today’s reagent.
Adv Synth Catal. 2020;362:65–86.
32] Wu X-F, Natte K. The applications of dimethyl sulfoxide as reagent in organic synthesis. Adv
Synth Catal. 2016;358:336–352.
33] Jones-Mensah E, Karki M, Magolan J. Dimethyl sulfoxide as a synthon in organic chemistry.
Synthesis. 2016;48:1421–1436.
34] Zhang T, Dai Y, Cheng S, et al. A facile method for the sulfenyllactonization of alkenoic acids
using dimethyl sulfoxide activated by oxalyl chloride. Synthesis. 2017;49:1380–1386.
35] Ding R, Lan L, Li S. A Novel method for the chlorolactonization of alkenoic acids uUsing
diphenyl sulfoxide/oxalyl chloride. Synthesis. 2018;50:2555–2566.
36] Ding R, Li J, Jiao W. A highly efficient method for bromination of alkenes, alkynes, and ketones
using dimethyl sulfoxide and oxalyl bromide. Synthesis. 2018;50:4325–4335.
37] Lan L, Gao Y, Ding R. A facile sulfenylchlorination of alkenes with Me2SO/(COCl)2. Synth
Commun. 2019;49:539–549.
38] Liu Y, Gao Y, Wang Z. The oxysulfenylation of alkenes with dimethyl sulfoxide/oxalyl chloride.
Synth Commun. 2019;49:2662–2670.
39] Ding R, Liu Y, Han M. Synthesis of nitriles from primary amides or aldoximes under conditions
of a catalytic Swern oxidation. J Org Chem. 2018;83:12939–12944.
40] Gao Y, Cheng S, Zhang T. Dimethyl sulfoxide/oxalyl chloride: a useful reagent for sulfenylether-
ification. Synth Commun. 2018;48:2773–2781.
41] Ding R, Li Y, Liu Y. Synthesis of butenolides by reactions of 3-alkenoic acids with diphenyl
sulfoxide/oxalyl chloride. Flavour Frag J. 2018;33:397–404.
42] Ding R, Liu Y, Liu L. A facile synthesis of (-butenolides via cyclization of 3-alkenoic acids with
dimethyl sulfoxide and oxalyl bromide. Synth Commun. 2019;49:3001–3007.
43] Tian H, Liu Y, Huang S. Beijing Technology and Business University, assignee. Preparation
method of S-methyl methanesulfonothioate and its application as methylthiolation reagent.
Peop. Rep. China patent CN 111,072,539. 2019 Dec 27.
[
44] Bellesia F, Boni M, Ghelfi F, et al. β-Chloroalkyl sulfides from Me2S/SO2Cl2/Me2SO and
alkenes. Synth Commun. 1992;22:1101–1108.
[45] Wang H, Xi Z, Huang S, et al. Convenient preparation of N–acylbenzoxazines from
phenols, nitriles, and DMSO initiated by a catalytic amount of (COCl)2. J Org Chem
2
021;86:4932–4943.
[
46] Howard JA, Furimsky E. An electron spin resonance study of the tert-butylsulfinyl radical. Can
J Chem. 1974;52:555–556.
[
47] Davis FA, Yocklovich SG, Baker GS. Synthesis of sulfenic acids: Flash vacuum pyrolysis of aryl
and alkyl t-butyl sulfoxides. Tetrahedron Lett. 1978;19:97–100.
[
48] Penn RE, Block E, Revelle LK. Methanesulfenic acid. J Am Chem Soc. 1978;100:3622–3623.
49] Leslie DR. Mechanistic implications of pyrophosphate formation in the oxidation of O,S-
dimethyl phosphoramidothioate. J Org Chem. 1991;56:3459–3462.
[

10
S. HUANG ET AL.
[
[
[
[
50] Gregory DD, Jenks WS. Thermochemistry of sulfenic esters (RSOR(): Not just another pretty
peroxide. J Org Chem. 1998;63:3859–3865.
51] Freeman F, Bui A, Dinh L. Dehydrative cyclocondensation mechanisms of hydrogen thioper-
oxide and of alkanesulfenic acid. J Phys Chem A. 2012;116:8031–8039.
52] Block E. The organosulfur chemistry of the genus allium – implications for the organic
chemistry of sulfur. Angew Chem Int Ed Engl. 1992;31:1135–1178.
53] Block E, Dane AJ, Thomas S. Applications of direct analysis in real time mass spectrometry
(
DART-MS) in Allium chemistry. 2-Propenesulfenic and 2-propenesulfinic acids, diallyl trisul-
fane S-oxide, and other reactive sulfur compounds from crushed garlic and other alliums. J
Agric Food Chem. 2010;58:4617–4625.
[
[
[
54] Seki K, Ishikawa J, Okada Y. Contribution of 2-propenesulfenic acid to the antioxidant activity
of allicin. J Food Sci. 2018;83:1265–1270.
55] Lynett PT, Butts K, Vaidya V, et al. The mechanism of radical-trapping antioxidant activity of
plant-derived thiosulfinates. Org Biomol Chem. 2011;9:3320–3330.
56] Freeman F, Angeletakis CN. Formation of (-disulfoxides, sulfinic anhydrides, and sulfines dur-
ing the m-chloroperoxybenzoic acid oxidation of symmetrical S-alkyl alkanethiosulfinates. J
Am Chem Soc. 1983;105:4039–4049.
[
57] Wen Z-K L, Liu Y-F X-H, et al. Acid promoted direct cross-coupling of methyl ketones
with dimethyl sulfoxide: access to ketoallyl methylsulfides and -sulfones. Org Lett.
2
017;19:5798–5801.
[
58] Rätz R, Sweeting OJ. Reaction of 3,9-dichloro-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]
undecane 3,9-dioxide with dimethyl sulfoxide. J Org Chem. 1963;28:1612–1616.