1,3,5-Trithianes and sulfur monochloride/sodium sulfide: an alternative route to 3,5-disubstituted 1,2,4-trithiolanes

Article abstract of DOI:10.1080/17415993.2020.1810251

Treatment of substituted 1,3,5-trithianes with S₂Cl₂ and Na₂S under mild conditions provides 3,5-disubstituted 1,2,4-trithiolanes, as mixture of diastereoisomers.

Full text of DOI:10.1080/17415993.2020.1810251

Journal of Sulfur Chemistry
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/gsrp20
1,3,5-Trithianes and sulfur monochloride/sodium
sulfide: an alternative route to 3,5-disubstituted
1,2,4-trithiolanes
Damiano Tanini , Francesca Trapani & Antonella Capperucci
To cite this article: Damiano Tanini , Francesca Trapani & Antonella Capperucci (2020) 1,3,5-
Trithianes and sulfur monochloride/sodium sulfide: an alternative route to 3,5-disubstituted 1,2,4-
trithiolanes, Journal of Sulfur Chemistry, 41:6, 635-644, DOI: 10.1080/17415993.2020.1810251
To link to this article: https://doi.org/10.1080/17415993.2020.1810251
Published online: 26 Aug 2020.
Submit your article to this journal
Article views: 18
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
2020, VOL. 41, NO. 6, 635–644
https://doi.org/10.1080/17415993.2020.1810251
1,3,5-Trithianes and sulfur monochloride/sodium sulfide: an
alternative route to 3,5-disubstituted 1,2,4-trithiolanes
Damiano Tanini, Francesca Trapani and Antonella Capperucci
Department of Chemistry ‘Ugo Schiff’, University of Florence, Sesto Fiorentino (Firenze), Italy
ABSTRACT
ARTICLE HISTORY
Received 26 June 2020
Accepted 7 August 2020
Treatment of substituted 1,3,5-trithianes with S2Cl2 and Na2S under
mild conditions provides 3,5-disubstituted 1,2,4-trithiolanes, as mix-
ture of diastereoisomers.
KEYWORDS
1,3,5-trithianes; sulfur
monochloride; α,α’-dichloro
sulfides; sodium sulfide;
3,5-disubstituted
1,2,4-trithiolanes
1. Introduction
A large number of sulfurated moieties are present in many organic compounds, which
possess a variety of different properties. Together with their wide use in organic synthesis,
sulfurated molecules find application in different fields, as pharmaceutical [1–5], agro-
chemical [6,7], food [8–10], materials and polymer chemistry [11,12]. Despite the high
variety of linear and cyclic sulfurated structures, the methods for their synthesis are often
limited by the availability of sulfur reagents and by the harsh conditions. Additionally,
various reaction steps and the use of expensive, or hardly to access, reagents are often
required.
During our investigation on the synthesis of chalcogen-containing derivatives [13–19]
we became interested in the study of new convenient methods to prepare polysulfurated
heterocycles. Five membered systems, such as 1,2,4-trithiolanes, as well as six and seven
membered derivatives, namely tetrathianes and trithiepanes, represent interesting com-
pounds both for their organoleptic properties and for their use as precursors of other
polysulfurated compounds. In particular, as has been very recently reported by Mloston
and coworkers [20], trithiolanes and their oxides take part in a variety of organic and
organometallic transformations. Furthermore, several trithiolanes are present in nature,
and are responsible of the typical flavorings and fragrances of various foods and plants, such
CONTACT Antonella Capperucci
antonella.capperucci@unifi.it
Department of Chemistry ‘Ugo Schiff’,
University of Florence, Sesto Fiorentino (Firenze), Italy
© 2020 Informa UK Limited, trading as Taylor & Francis Group

636
D. TANINI ET AL.
as garlic, onion, mushrooms, meat [21]. Some of them, as 1- and 4-oxo-1,2,4-trithiolanes,
isolated together with other cyclic polysulfides from the marine alga Chondria californica,
also exhibited antibiotic activity [22].
Trithiolanes, therefore, represent an interesting class of compounds and the develop-
ment of alternative and convenient methods for their preparation is highly desirable. To
the best of our knowledge, a rather limited number of synthetic protocols are reported,
through a multistep reaction by chlorination of disulfides, followed by treatment with
sodium sulfide, where the final cyclization to 1,2,4-trithiolanes has low yields, also because
of the formation of polysulfides [23]. Treatment of ketones or aldehydes with hydrogen sul-
fide led to bis(1-mercaptoalkyl)sulfides, which can be oxidized to 3,5-disubstituted-1,2,4-
trithiolanes [24,25]. Reaction of aldehydes with (NH4)2S [26,27] or treatment with H2S in
the presence of ammonia [28], or α,ω-diamines [29] allowed the isolation of substituted
1,3,5-dithiazines as precursors of trithiolanes after suitable elaboration. Thioketones as well
behaved as convenient reagents to prepare substituted trithiolanes in the presence of oxi-
dizing agents [30,31]. In particular, [3 + 2] cycloadditions of aryl, heteraryl and cycloalkyl
thioketones with organic azides represent an efficient way to provide sterically crowded
unsymmetrical and symmetrical disubstituted-spiro- or dispiro-1,2,4-trithiolanes, likely
via a thiocarbonyl-S-sulfide intermediate [32–34]. However, these methods frequently
lead to the target heterocycles in complex mixtures, with a variety of sulfurated com-
pounds and often in rather low yields. In fact, some synthetic procedures provide 1,2,4-
trithiolanes as minor products together with other thiaheterocycles, as tetrathianes [26,27],
penthathiepanes [26–29], thiadiazepines [29], or in some cases trithiolanes are formed as
side products in the preparation of pentathianes [31]. On the other hand, slightly bet-
ter yields were observed when 3,3,5,5-tetrasubstituted trithiolanes were prepared through
thionation of carbonyl derivatives [24,25,30,32].
In this context, we became interested in developing an alternative synthetic approach
to 1,2,4-trithiolanes. During the course of our studies on the thionation of car-
bonyl compounds [35–37] we found that a direct conversion of aldehydes, ketones
and acylsilanes to the corresponding thiocarbonyl derivatives was accomplished with
bis(trimethylsilyl)sulfide (HMDST) under Lewis acid catalytic conditions. However, for
their well-known tendency to oligomerize, thioaldehydes were in situ trapped with 1,3-
dienes to afford the Diels–Alder cycloadducts. On the other hand, when the reaction
was carried out without any trapping agent, the corresponding trimers, namely 2,4,6-
trisubstituted 1,3,5-trithianes, were isolated in high yields. We then envisaged that these
six-membered thia-heterocycles could be regarded as potential starting compounds to pre-
pare trithiolanes. We report in this communication an alternative synthetic approach to
this class of pentatomic sulfurated molecules under mild conditions.
2. Results and discussion
Following the retrosynthetic approach, trithiolanes might be prepared from the parent
1,1’-bis(mercapto)-dialkyl sulfides, which could be accessible from α,α’-(dichloro)dialkyl
sulfides after chlorination of the appropriate dialkyl sulfides (Scheme 1).
Several drawbacks are nevertheless linked to the use of the most common chlorinated
reagents. In fact, the reaction of dialkylsulfides with N-chlorosuccinimide (NCS) leads
primarily to mono-chloro sulfides (RCH(Cl)SCH2R), instead of the desired α,α’-dichloro

JOURNAL OF SULFUR CHEMISTRY
637
S
S
SH SH
X
X
R
S
R
R
R
R
S
R
R
S
R
S
Scheme 1. Retrosynthetic approach to 1,2,4-trithiolanes.
Me
Cl
Cl
solvent
T(°C), time
S
S
+
S2Cl2
Me
S
Me
Me
S
Me
2
3a
1a
Entry
Solvent
T (°C)
Time (min) Yield (%)a
1
2
3
THF
rt
60
rt
120
90
--
THF
--
< 5b
CH2Cl2
120
4
5
6
7
8
CH2Cl2
H2O
H2O
--
35
100
50
90
30
60
90
60
< 5b
15c
< 5b
34d
65e
rt
--
100
a Isolated yield
b Determined by H-NMR
c ca. 50% of sulfurated side productsb
d ca. 30% of sulfurated side productsb
e ca. 10% of sulfurated side products
Scheme 2. Optimization of the chlorination reaction to synthesize dichlorosulfide 3a.
sulfides [38,39]. Indeed, dichloro sulfides were prepared through multistep reactions from
α-chloro vinylsulfides/HCl [40], or by reaction of ethanal with H2S/HCl [41]. Time ago was
likewise reported the synthesis of α-dihalogeno sulfides upon treatment of 1,3,5-trithianes
with bromine [42]. In this connection, searching for a convenient synthetic route to trithi-
olanes, our attention was focused to the behavior of 1,3,5-trithianes, prepared following
our reported procedure [35–37] from aldehydes and HMDST under catalytic conditions
.
(CoCl2 6H2O or TfOTMS), in the presence of S2Cl2, which is commonly used as powerful
sulfurating agent in the synthesis of heterocycles, and only rarely as chlorinating reagent
[43,44]. In order to search for chlorination conditions, a first screening was performed
investigating the reaction of trithiane 1a (R = Me) with S2Cl2 2 under different conditions
(Scheme 2).
We found that when the reaction was carried out in THF or CH2Cl2, at room tem-
perature or by heating, the desired α,α’-dichloro sulfide 3a was not formed, or it was
observed in traces amount (Scheme 2, entries 1–4). When trithiane 1a was heated in water
with S2Cl2, polysulfurated compounds were obtained as predominant products, however
3a was obtained, albeit in low yield (Scheme 2, entry 5). Prompted by this result, 1a was

638
D. TANINI ET AL.
R
Cl
Cl
S
S
+
S2Cl2
R
S
R
100°C, 60 min
R
S
R
3a-d
2
1a-d
a
b
R = Me (65%);
R = i-Pr (49);
R = Et (53%)
d
R = Ph (48%)
c
Scheme 3. Synthesis of 1,1’-dichlorosulfides 3.
Cl
Cl
SH SH
S
DMF
S
S
.
S
+
S
+ Na2S 9H2O
-10°C
10h
R
S
R
R
S
R
R
R
S
R
S
R
3a-d
4
a
5a
5b
5c
5d
(67%)
6a
(54%)
(60%)
(53%)
a
c
b
d
R = Me;
R = i-Pr;
R = Et
R = Ph
Scheme 4. Synthesis of 3,5-disubstituted 1,2,4-trithiolanes 5a–d. a5a was isolated in 22% yield per-
forming the reaction at r.t. or in the presence of TBAB.
reacted with 2 at lower temperature, leading to traces of the desired α,α’-dichlorosulfide 3a,
whereas trithiane and polysulfides were still present as main products (Scheme 2, entry 6).
An interesting result was indeed achieved performing the reaction at room temperature in
neat S2Cl2: a better yield of 3a was achieved, even if polysulfurated products were observed
together with unreacted trithiane (Scheme 2, entry 7). Finally, when 1a was heated in neat
sulfur monochloride, we were pleased to observe the formation of the dichloro deriva-
tive 3a as major compound, along with a reduced amount of polysulfides (Scheme 2,
entry 8).
Other substituted trithianes 1b–d were reacted under these conditions, providing α,α’-
dichlorosulfides 3b–d bearing aliphatic and aromatic groups (Scheme 3).
Subsequently, 3a was reacted in DMF at ambient temperature with hydrate sodium sul-
fide (Scheme 4), which is used in the reaction with halides to form symmetrical disulfides
[45], and indeed the trithiolane 5a was isolated, even if in moderate yield (22%), together
with other sulfurated products, amongst which the 1,2,3,5-tetrathiane 6a was the major
compound. Under these conditions the parent 1,1’-bis(mercapto)-dialkyl sulfide interme-
diate 4 was not isolated, being quickly oxidized to provide a direct access to 5a from 3a.
In order to increase the yield of 5a the reaction was carried out in the presence of TBAB
(tetrabutylammonium bromide) as phase transfer catalyst, but no considerable increase in
yield was observed. On the contrary, when the reaction was performed at lower tempera-
ture (−10°C) the trithiolane 5a was achieved in higher yield (67%) as equimolar mixture of
stereoisomers, and tetrathiane 6a was observed as minor compound (<5%) (Scheme 4).
The reaction was also efficient with differently substituted trithianes, leading to variously
3,5-disubstituted 1,2,4-trithiolanes 5b–d under mild conditions (Scheme 4).
A better result was achieved when performing a one-pot reaction, to avoid any manip-
ulation of the dichlorosulfide intermediate 3a. After the formation of 3a as previously

JOURNAL OF SULFUR CHEMISTRY
639
R
S
1. S2Cl2
90 min
S S
S
S
R
R
S
2. Na2S.9H2O
DMF, -10°C
10h
R
R
5a
5b
5c
(73%)
(51%)
(58%)
1a-c
Scheme 5. Direct synthesis of 3,5-dialkyl 1,2,4-trithiolane 5a–c from 1a–c.
described, the mixture was cooled and diluted with DMF. After that, sodium sulfide was in
situ added. Under these conditions the desired trithiolane 5a was isolated as almost pure
compound in 73% yield (cis:trans 55:45) (Scheme 5).
Likewise, the reaction can be extended to synthesize trithiolanes 5b,c under similar
conditions, as a 1:1 mixture of stereoisomers (Scheme 5).
Further studies on the application of this synthetic approach to differently substituted
1,3,5-trithianes, and to the selenated analogues (1,3,5-triselenanes), are currently under
investigation in our laboratories, in order to study their characteristics and properties as
well as a possible reaction mechanism.
3. Conclusion
We have found an alternative and simple method to prepare 3,5-disubstituted 1,2,4-
trithiolanes under mild conditions by reaction of 1,3,5-trithianes with sulfur monochloride
and sodium sulfide. Trithiolanes can also be prepared in one-pot reaction, by adding
sodium sulfide to the reaction medium, without the isolation of the dichloro sulfide
intermediate.
4. Experimental
4.1. General
All reagents and solvents were purchased from various commercial sources and used
without further purification. Preparative TLC was performed by using silica gel plates
(60 F-254). NMR spectra were recorded in CDCl3 on a Varian Gemini 200 spectrome-
1
ter operating at 200 MHz for H and 50 MHz for 13C. Chemical shifts (δ) are reported
1
in parts per million (ppm) measured relative to the solvent peak (7.26 ppm for H,
77.0 ppm for 13C). Data are reported as follows: chemical shift, multiplicity (s = singlet,
d = doublet, t = triplet, q = quartet, m = multiplet, b = broad), integration and cou-
pling constants. Mass spectra were recorded using ionization potential (EI, 70 eV) and
electrospray ionization (ESI).
4.2. General procedure A
4.2.1. Synthesis of 2,4,6-trisubstituted 1,3,5-trithianes 1 [32,33]
A solution of aldehyde (1 mmol) and bis(trimethylsilyl)sulfide (2 mmol) in CH3CN (1 mL)
.
was treated under inert atmosphere with a solution of CoCl2 6H2O (0.2 mmol) in 1.5 mL

640
D. TANINI ET AL.
of CH3CN (or with TfOTMS, 0.2 mmol), and stirred at room temperature for 4 h. The
reaction mixture was quenched with water (1 mL) and extracted with diethyl ether (2 mL).
The organic layer is separated, washed with water and brine, dried over Na2SO4 and fil-
tered. Evaporation of the solvent afforded the crude product, which was purified on silica
gel (petroleum ether/diethyl ether), leading to a mixture of two stereoisomers.
2,4,6-Trimethyl-1,3,5-trithiane 1a: Yield 73% (petroleum ether/diethyl ether 9:1). Major
isomer (>95:5): 1H NMR (200 MHz, CDCl3): δ (ppm) 4.11 (q, 3H, J = 7.4 Hz), 1.59 (d,
9H, J = 7.4 Hz). 13C NMR (50 MHz, CDCl3): δ (ppm) 40.1, 20.4. MS (m/z %): 180 (M+,
41), 120 (27), 116 (31), 60 (100), 59 (44), 55 (48).
2,4,6-Triethyl-1,3,5-trithiane 1b: Yield 75% (petroleum ether/diethyl ether 9:1). Major
isomer (>95:5): 1H NMR (200 MHz, CDCl3): δ (ppm) 4.07 (t, 3H, J = 6.9 Hz), 1.96–1.85
(m, 6H), 1.06 (t, 9H, J = 7.2 Hz). 13C NMR (50 MHz, CDCl3): δ (ppm) 43.1, 27.4, 10.6.
MS (m/z %): 222 (M+, 15), 106 (21), 74 (100).
2,4,6-Triisopropyl-1,3,5-trithiane 1c: Yield 65%. Major isomer ( >95:5): 1H NMR
(200 MHz, CDCl3): δ (ppm) 4.38 (d, 3H, J = 6.8 Hz), 2.31–2.19 (m, 3H), 1.17 (bd, 18H,
J = 7.3 Hz). 13C NMR (50 MHz, CDCl3): δ (ppm) 51.2, 29.8, 18.6. MS (m/z %): 264 (M+,
15), 144 (21), 88 (100), 87 (92).
2,4,6-Triphenyl-1,3,5-trithiane 1d: Yield 77%. Major isomer ( >95:5): 1H NMR
(200 MHz, CDCl3): δ (ppm) 7.69–7.15 (m, 15H), 5.46 (s, 3H). 13C NMR (50 MHz, CDCl3):
δ (ppm) 137.9, 128.0, 127.5, 126.2, 46.1. MS (m/z %): 366 (M+, 34), 212 (22), 180 (44), 122
(78), 121 (100).
4.3. General procedure B
4.3.1. Synthesis of α,α’-dichloro sulfides 3
Trithiane 1 (1 mmol) was slowly added under nitrogen with sulfur monochloride
(1.1 mmol) and heated at 100°C for 60 min. After cooling, the solution was filtered and
evaporated under reduced pressure to afford sulfides 3, which were used without further
purification.
Bis(1-chloroethyl)sulfane 3a: Yield 65%. 1H NMR (200 MHz, CDCl3): δ (ppm) 5.46 (q,
2H, J = 6.6 Hz), 1.86 (d, 6H, J = 6.6 Hz). 13C NMR (50 MHz, CDCl3): δ (ppm) 56.4, 22.3.
MS (m/z %): 162 (M++4, 1.4), 160 (M++2, 8.9), 158 (M+,14), 125 (23), 123 (65), 95 (10),
65 (14), 63 (49), 61 (100), 60 (48), 59 (40).
Bis(1-chloropropyl)sulfane 3b: Yield 53%. 1H NMR (200 MHz, CDCl3): δ (ppm) 5.18 (t,
2H, J = 6.9 Hz), 2.25–2.01 (m, 4H), 1.04 (t, 6H, J = 7.0 Hz). 13C NMR (50 MHz, CDCl3):
δ (ppm) 59.6, 30.3, 9.8. MS (m/z %): 190 (M++4, 1.6), 188 (M++2, 9.2), 186 (M+,18), 171
(20), 153 (25), 151 (65), 109 (16), 77 (52), 75 (96), 74 (100).
1
Bis(1-chloro-2-methylpropyl)sulfane 3c: Yield 49%. H NMR (200 MHz, CDCl3): δ
(ppm) 4.98 (d, 2H, J = 7.1 Hz), 2.53–2.24 (m, 2H), 1.11 (bd, 12H, J = 7.3 Hz). 13C NMR
(50 MHz, CDCl3): δ (ppm) 60.4, 33.9, 16.3, 16.2. MS (m/z %): 218 (M++4, 0.9), 216
(M++2, 10), 214 (M+, 14), 199 (26), 181 (23), 179 (59), 123 (13), 91 (58), 89 (83), 88
(100).

JOURNAL OF SULFUR CHEMISTRY
641
Bis(chloro(phenyl)methyl)sulfane 3d: Yield 48%. 1H NMR (200 MHz, CDCl3): δ (ppm)
7.29–7.10 (m, 10H), 5.83 (s, 2H). 13C NMR (50 MHz, CDCl3): δ (ppm) 141.0, 132.5, 131.9,
128.0, 61.6. MS (m/z %): 286 (M++4, 4.6), 284 (M++2, 10), 282 (M+, 45), 249 (26), 247
(72), 205 (48), 157 (26), 125 (60), 122 (100).
4.4. General procedure C
4.4.1. Synthesis of 3,5-disubstituted 1,2,4-trithiolanes 5
(a) A solution of dichloro sulfide (1 mmol) in DMF (1.5 mL) was cooled at −10°C
and then slowly treated with hydrate sodium sulfide (2 mmol). The reaction was
stirred overnight. After extraction with hexane, the mixture was washed with water
(3 × 1 mL) and dried over Na2SO4. Evaporation of the solvent afforded the trithiolane
(mixture of cis/trans stereoisomers ∼1:1), which was purified on TLC (petroleum
ether). The stereochemistry of trithiolanes (cis/trans) was assigned by comparison
with literature reported data [23].
(b) One-pot synthesis: Sulfur monochloride (1.1 mmol) was slowly added to trithiane 1
(1 mmol) and stirred for 60 min at 100°C. The dark yellow oil was cooled to room
temperature and diluted with DMF (2 mL). Sodium sulfide (2 mmol) was then added
portionwise at −10°C with stirring (10 h). After addition of dichlorometane, the mix-
ture was washed with water (3 × 1 mL) and dried over Na2SO4. Filtration, evaporation
of the solvent and purification on silica gel afforded the product 5 as cis/trans isomers
(ca. 1:1).
3,5-Dimethyl-1,2,4-trithiolane 5a [23]: Yield 67%. Diastereoisomer cis: 1H NMR
(200 MHz, CDCl3): δ (ppm) 5.04 (q, 2H, J = 6.6 Hz), 1.65 (d, 6H, J = 6.6 Hz). 13C NMR
(50 MHz, CDCl3): δ (ppm) 55.7, 21.4. Diastereoisomer trans: 1H NMR (200 MHz, CDCl3):
δ (ppm) 4.86 (q, 2H, J = 6.6 Hz), 1.77 (d, 6H, J = 6.6 Hz). 13C NMR (50 MHz, CDCl3): δ
(ppm) 56.9, 22.3. MS (m/z %): 154 (9), 152 (M+, 76), 92 (58), 88 (48), 64 (61), 60 (55), 59
(100).
3,5-Diethyl-1,2,4-trithiolane 5b [23]: Yield 54%. Diastereoisomer cis: 1H NMR
(200 MHz, CDCl3): δ (ppm) 4.71 (t, 2H, J = 6.9 Hz), 1.98–2.17 (m, 4H), 1.19 (t, 6H,
J = 7.2 Hz). 13C NMR (50 MHz, CDCl3): δ (ppm) 63.5, 30.3, 11.2. Diastereoisomer trans:
1H NMR (200 MHz, CDCl3): δ (ppm) 4.65 (t, 2H, J = 6.9 Hz), 1.98–2.17 (m, 4H), 1.27 (d,
6H, J = 7.1 Hz). MS (m/z %): 182 (11), 180 (M+, 65), 116 (29), 74 (100), 73 (57).
1
3,5-Diisopropyl-1,2,4-trithiolane 5c [23]: Yield 60%. Diastereoisomer cis: H NMR
(200 MHz, CDCl3): δ (ppm) 4.66 (d, 2H, J = 7.3 Hz), 2.12–2.34 (m, 2H), 1.21 (bd, 6H,
J = 6.6 Hz), 1.18 (bd, 6H, J = 6.9 Hz). 13C NMR (50 MHz, CDCl3): δ (ppm) 65.7, 29.6,
1
18.5, 18.2. Diastereoisomer trans: H NMR (200 MHz, CDCl3): δ (ppm) 4.57 (d, 2H,
J = 7.5 Hz), 2.12–2.34 (m, 2H), 1.09–1.17 (m, 6H). MS (m/z %): 208 (M+, 42), 193 (10),
88 (97), 87 (22), 55 (100).
3,5-Diphenyl-1,2,4-trithiolane 5d [46]: Yield 53%. Diastereoisomer A: 1H NMR
(200 MHz, CDCl3): δ (ppm) 6.19 (s, 2H), 7.35–7.56 (m, 10H). 13C NMR (50 MHz, CDCl3):
δ (ppm) 139.2, 129.1, 128.8, 126.9, 67.3. Diastereoisomer B: 1H NMR (200 MHz, CDCl3):
δ (ppm) 6.15 (s, 2H), 7.35–7.56 (m, 10H). MS (m/z %): 276 (M+, 100), 212 (55), 152 (52),
91 (22), 122 (78), 121 (84).

642
D. TANINI ET AL.
Acknowledgements
We thank MIUR-Italy (‘Progetto Dipartimenti di Eccellenza 2018-2022’ allocated to Department of
Chemistry ‘Ugo Schiff’).
Disclosure statement
No potential conflict of interest was reported by the author(s).
ORCID
Antonella Capperucci http://orcid.org/0000-0003-1087-8143
References
[1] Vazquez-Prieto MA, Miatello RM. Organosulfur compounds and cardiovascular disease. Mol
Aspects Med. 2010;31:540–545.
[2] Parcell S. Sulfur in human nutrition and applications in medicine. Altern Med Rev.
2002;7:22–44.
[3] Angeli A, Tanini D, Capperucci A, et al. Synthesis of different thio-scaffolds bearing sul-
fonamide with subnanomolar carbonic anhydrase II and IX inhibitory properties and X-ray
investigations for their inhibitory mechanism. Bioorg Chem. 2018;81:642–648.
[4] Tanini D, Capperucci A, Supuran CT, et al. Sulfur, selenium and tellurium containing amines
act as effective carbonic anhydrase activators. Bioorg Chem. 2019;87:516–522.
[5] Viglianisi C, Vasa K, Menichetti S, et al. Ditocopheryl sulfides and disulfides: synthesis and
antioxidant profile. Chem Eur J. 2019;25:9108–9116.
[6] Devendar P, Yang G. Sulfur-containing agrochemicals. Top Curr Chem. 2017;375:82.
DOI:10.1007/s41061-017-0169-9 and references cited therein.
[7] Liu Y-C, Qu R-Y, Chen Q, et al. Efficient synthesis of functionalized 6-substituted-
thiosalicylates via microwave-promoted Suzuki cross-coupling reaction. Tetrahedron Lett.
2007;48:6048–6050.
[8] Block E. Garlic and other alliums: the lore and the science. Cambridge, U.K.: RSC Publishing;
2010; and references cited therein.
[9] Qian MC, Fan X, Mahattanatawee K. Volatile sulfur compounds in food. ACS symposium
series. Washington (DC): ACS Books; 2011.
[10] Mottram DS, Mottram HR, editors. An overview of the contribution of sulfur-containing com-
pounds to the aroma in heated foods. ACS symposium series. Washington (DC): ACS Books;
2002.
[11] Wang DY, Guo W, Yongzhu F. Organosulfides: an emerging class of cathode materials for
rechargeable lithium batteries. Acc Chem Res. 2019;52:2290–2300.
[12] Mutlu H, Theato P, et al. Sulfur chemistry in polymer and materials science. Macromol Rapid
Commun. 2019;40:1800650. doi:10.1002/marc.201800650.
[13] Capperucci A, Tanini D, Degl’Innocenti A, et al. Thiosilane and organoselenosilane-mediated
novel access to 3,7-disubstituted-1,2,5-trithiepanes and -1,2,5-dithiaselenepanes. Heteroat
Chem. 2014;25:678–683.
[14] Capperucci A, Salles C, Tanini D, et al. Selective access to sulfurated and selenated heterocycles
by intramolecular cyclization ofβ-substituted sulfides and selenides. Phosphorus Sulfur Silicon
Relat Elem. 2017;192:172–174.
[15] Mloston G, Capperucci A, Tanini D, et al. Dialkyl dicyanofumarates as oxidizing reagents
for the conversion of thiols into disulfides and selenols into diselenides. Eur J Org Chem.
2017;2017:6831–6839.
[16] Obijalska E, Pawelec M, Mlostoń M, et al. A remarkable influence of a trifluoromethyl group
on the reactions of β-mercaptoalcohols with fluorinated α-bromoenones. Eur J Org Chem.
2018;2018:3716–3723.

JOURNAL OF SULFUR CHEMISTRY
643
[17] Tanini D, Ermini E, Capperucci A. Seleno-michael reaction of stable functionalised alkyl
selenols: a versatile tool for the synthesis of acyclic and cyclic unsymmetrical alkyl and vinyl
selenides. Adv Synth Catal. 2019;361:2337–2346.
[18] Tanini D, Lupori B, Malevolti G, et al. Direct biocatalysed synthesis of first sulfur-, selenium-
and tellurium- containing L-ascorbyl hybrid derivatives with radical trapping and GPx-like
properties. Chem Commun. 2019;55:5705–5708.
[19] Tanini D, D’Esopo V, Tatini D, et al. Selenated and sulfurated analogues of triacyl glycerols:
selective synthesis and structural characterization. Chem Eur J. 2020;26:2719–2725.
[20] Mlostoń G, Romański J, Weigand W, et al. Organic and coordination chemistry of 1,2,4-
trithiolanes. Eur J Org Chem. 2019;2019:1867–1875.
[21] Berger RG, editor. Flavours and fragrances. Chap. 12.3 and 13.6. Berlin: Springer-Verlag; 2007.
[22] Wratten SJ, Faulkner DJ. Cyclic polysulfides from the red algaChondria californica. J Org Chem.
1976;41:2465–2467.
[23] Tjan SB, Haakmanc JC, Teunis CJ, et al. Synthesis of 3,5-dialkyl-1,2,4-trithiolanes. Assignment
of configuration and conformational analysis by PMR. Tetrahedron. 1972;28:3489–3500 and
references cited therein.
[24] Dorofeev IA, Shagun LG, Tokareva IA, et al. New synthesis of 1,2,4-trithiolane derivatives. Russ
J Org Chem. 2008;44:1403–1405.
[25] Boelens M, Van der Linde LM, De Valois PJ, et al. Organic sulfur compounds from fatty
aldehydes, hydrogen sulfide, thiols, and ammonia as flavor constituents. J Agric Food Chem.
1974;22:1071–1076.
[26] Krafft C, Brennecke S, Weber B, et al. High-impact sulfur compounds: constitutional and con-
figurational assignment of sulfur-containing heterocycles. Chem Biodivers. 2008;5:1204–1212.
[27] Ott F, Kindel G, Ley J, et al. Disubstituted tetrathianes as fragrances of flavourings. Int. Patent
Pub. Num. WO 2006/027352 A1. 2006.
[28] Takikawa Y, Makabe T, Hirose N, et al. A novel method for the generation of thial S-sulfides
from 2,4,6-trisubstituted 5,6-dihydro-1,3,5-dithiazines. Chem Lett. 1988;17:1517–1520.
[29] Akhmetova VR, Dzhemileva UM, Tyumkina TY, et al. Regiodirected synthesis and stere-
ochemistry of 2,4,8-trialkyl-3-thia-1,5-diazabicyclo[3.2.1]octanes and α,ω-bis(2,4,6-trialkyl-
1,3,5-dithiazinane-5-yl)alkanes. J Heterocycl Chem. 2015;52:1037–1045.
[30] Okuma K, Shibata S, Shioji K, et al. A new simple synthesis of cis- and trans-3,5-di-tert-butyl-
3,5-diaryl-1,2,4-trithiolanes from ketones and tetraphosphorus decasulfide. Chem Commun.
2000;2000(16):1535–1536.
[31] Ishii A, Oshida H, Nakayama J. Structure elucidation of 6-t-butyl-6-phenylpentathiane monox-
ides by X-ray crystallography and DFT calculations. Bull Chem Soc Jpn. 2002;75:319–328.
[32] Mlostoń G, Celeda M, Linden A, et al. Synthesis of hetaryl-substituted 1,2,4-trithiolanes via a
three-component reaction with dihetaryl thioketones, benzyl azide, and 2,2,4,4-tetramethyl-
3-thioxocyclobutanone. J Sulfur Chem. 2016;37:14–22 and references cited therein.
[33] Mlostoń G, Heimgartner H. 103. Bildung von 1,2,4-trithiolanen in dreikomponenten-
gemischen aus phenyl-azid, aromatischen thioketonen und 2,2,4,4-tetramethylcyclobutanthio
nen: eine schwefel-transfer-reaktion unter bildung von ‘thiocarbonylthiolaten’ ((alkylidensul-
fonio)thiolaten) als reaktive zwischenstufen. Helv Chim Acta. 1995;78:1298–1310.
[34] Mlostoń G, Romański J, Heimgartner H. Sulfur centered 1,3-dipoles. An efficient trapping
of adamantanethione-S-sulfide generated in the reaction of adamantanethione with organic
azides. Pol J Chem. 1996;70:437–445.
[35] Capperucci A, Degl’Innocenti A, Ricci A, et al. Silicon assisted synthesis of thiocarbonyl
derivatives and reactivity of dienophilic thioaldehydes. J Org Chem. 1991;56:7323–7328.
[36] Degl’Innocenti A, Capperucci A, et al. Hexamethyldisilathiane based thionation of carbonyl
compounds: a versatile approach to sulfur containing heterocycles. Synlett. 2005:1965–1983.
[37] Tanini D, Angeli A, Capperucci A. Ionic liquids as an alternative reaction medium for HMDST
based synthesis of thioaldehydes. Phosphorus Sulfur Silicon Relat Elem. 2016;191:156–158.
[38] Drabowicz J, Kielbasinski P, Lyzwa P, et al. Alkanesulfonic acids and acyclic derivatives. Sci
Synth. 2007;39:17–122 and references cited therein.

644
D. TANINI ET AL.
[39] Delaney PA, Johnstone RAW. Solvent effects in the chlorination of tetrahydrothiophens with
N-chlorosuccinimide. Tetrahedron. 1985;41:3845–3851.
[40] Amosova SV, Gostevskaya VI, Gavrilova GM, et al. Divinyl sulfide. XI. 1-chlorovinyl- and 1-
chloroethyl sulfides. Zh Org Khim. 1984;20:2521–2526. doi:10.1002/chin.198518147.
[41] Brandsma L, Arens JF. Chemistry of acetylenic ethers XLIX: Vinylthioethyne and some of its
derivatives. Recl Trav Chim Pays Bas. 1961;80:237–240.
[42] Weissflog E, Schmidt M. Synthese von 2.4-dibrom-3-thiapentan. Phosphorus Sulfur.
1978;4:383–384.
[43] Konstantinova LS, Rakitin OA. Sulfur monochloride in organic synthesis. Russ Chem Rev.
2014;83:225–250 and references cited therein.
[44] Mloston G, Majchrzak A, Senning A, et al. Highly sulfurated heterocycles via dithiiranes and
trithietanes as key intermediates. J Org Chem. 2002;67:5690–5695.
[45] Sonavane SU, Chidambaram M, Almog J, et al. Rapid and efficient synthesis of symmetrical
alkyl disulfides under phase transfer conditions. Tetrahedron Lett. 2007;48:6048–6050.
[46] Adesoga K. Trithiolaniacin, a novel trithiolan from Petiveria alliacea. J Chem Soc Chem
Commun. 1974;1974:906–907.