The fluoride anion-catalyzed sulfurization of thioketones with elemental sulfur leading to sulfur-rich heterocycles: First sulfurization of thiochalcones ?

Article abstract of DOI:10.3390/molecules26040822

Fluoride anion was demonstrated as a superior activator of elemental sulfur (S8) to perform sulfurization of thioketones leading to diverse sulfur-rich heterocycles. Due to solubility problems, reactions must be carried out either in THF using tetrabutylammonium fluoride (TBAF) or in DMF using cesium fluoride (CsF), respectively. The reactive sulfurizing reagents are in situ generated, nucleophilic fluoropolysulfide anions FS(8?x)?, which react with the C=S bond according to the carbophilic addition mode. Dithiiranes formed thereby, existing in an equilibrium with the ring-opened form (diradicals/zwitterions) are key-intermediates, which undergo either a step-wise dimerization to afford 1,2,4,5-tetrathianes or an intramolecular insertion, leading in the case of thioxo derivatives of 2,2,4,4-tetramethylcyclobutane-1,3-dione to ring enlarged products. In reactions catalyzed by TBAF, water bounded to fluoride anion via H-bridges and forming thereby its stable hydrates is involved in secondary reactions leading, e.g., in the case of 2,2,4,4-tetramethyl-3-thioxocyclobutanone to the formation of some unexpected products such as the ring enlarged dithiolactone and ring-opened dithiocarboxylate. In contrast to thioketones, the fluoride anion catalyzed sulfurization of their α,β-unsaturated analogues, i.e., thiochalcones is slow and inefficient. However, an alternative protocol with triphenylphosphine (PPh3) applied as a catalyst, offers an attractive approach to the synthesis of 3H-1,2-dithioles via 1,5-dipolar electrocyclization of the in situ-generated α,β-unsaturated thiocabonyl S-sulfides. All reactions occur under mild conditions and can be considered as attractive methods for the preparation of sulfur rich heterocycles with diverse ring-size.

Full text of DOI:10.3390/molecules26040822

molecules
Article
The Fluoride Anion-Catalyzed Sulfurization of Thioketones
with Elemental Sulfur Leading to Sulfur-Rich Heterocycles:
First Sulfurization of Thiochalcones †
*
, Jakub Wre˛czycki 2,*, Katarzyna Urbaniak 1, Dariusz M. Bielin´ski 2
1,
Grzegorz Mloston´
and Heinz Heimgartner 3
1
2
3
Department of Organic and Applied Chemistry, Faculty of Chemistry, University of Lodz, 12 Tamka Street,
91-403 Lodz, Poland; katarzyna.urbaniak@chemia.uni.lodz.pl
Institute of Polymer and Dye Technology, Faculty of Chemistry, Lodz University of Technology,
12/16 Stefanowskiego Street, 90-924 Lodz, Poland; dariusz.bielinski@p.lodz.pl
Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland;
heinz.heimgartner@chem.uzh.ch
*
Correspondence: grzegorz.mloston@chemia.uni.lodz.pl (G.M.); jakub.wreczycki@dokt.p.lodz.pl (J.W.);
Tel.:+48-42-635-57-61 (G.M.)
†
Dedicated to Professor Janusz Jurczak (Warsaw) on the occasion of his 80th birthday.
Abstract: Fluoride anion was demonstrated as a superior activator of elemental sulfur (S8) to perform
sulfurization of thioketones leading to diverse sulfur-rich heterocycles. Due to solubility problems,
reactions must be carried out either in THF using tetrabutylammonium fluoride (TBAF) or in DMF
using cesium fluoride (CsF), respectively. The reactive sulfurizing reagents are in situ generated,
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
−
nucleophilic fluoropolysulfide anions FS(8−x) , which react with the C=S bond according to the car-
ꢀꢁꢂꢃꢄꢅꢆ
bophilic addition mode. Dithiiranes formed thereby, existing in an equilibrium with the ring-opened
form (diradicals/zwitterions) are key-intermediates, which undergo either a step-wise dimerization
to afford 1,2,4,5-tetrathianes or an intramolecular insertion, leading in the case of thioxo derivatives of
2,2,4,4-tetramethylcyclobutane-1,3-dione to ring enlarged products. In reactions catalyzed by TBAF,
water bounded to fluoride anion via H-bridges and forming thereby its stable hydrates is involved
in secondary reactions leading, e.g., in the case of 2,2,4,4-tetramethyl-3-thioxocyclobutanone to the
formation of some unexpected products such as the ring enlarged dithiolactone and ring-opened
dithiocarboxylate. In contrast to thioketones, the fluoride anion catalyzed sulfurization of their α,β-
unsaturated analogues, i.e., thiochalcones is slow and inefficient. However, an alternative protocol
with triphenylphosphine (PPh3) applied as a catalyst, offers an attractive approach to the synthesis
Citation: Mloston´, G.; Wre˛czycki, J.;
Urbaniak, K.; Bielin´ski, D.M.;
Heimgartner, H. The Fluoride
Anion-Catalyzed Sulfurization of
Thioketones with Elemental Sulfur
Leading to Sulfur-Rich Heterocycles:
First Sulfurization of Thiochalcones .
Molecules 2021, 26, 822. https://
doi.org/10.3390/molecules26040822
Academic Editor: Oleg A. Rakitin
Received: 18 January 2021
Accepted: 2 February 2021
Published: 5 February 2021
of 3H-1,2-dithioles via 1,5-dipolar electrocyclization of the in situ-generated α,β-unsaturated thio-
cabonyl S-sulfides. All reactions occur under mild conditions and can be considered as attractive
methods for the preparation of sulfur rich heterocycles with diverse ring-size.
Keywords: thioketones; thiochalcones; fluoride anion; elemental sulfur; sulfur heterocycles
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1. Introduction
It is a well-known fact that large amounts of elemental sulfur (S8) are available as a side
product of diverse technological processes, and its further usage in a sustainable cycle of
conversions leading to useful, organic compounds represents an important and challenging
Copyright:
© 2021 by the authors.
problem for chemical industry and related branches [1]. Sulfurization reactions performed
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
with elemental sulfur and leading to cyclic or acyclic organic compounds constitute an
interesting and practically relevant topic in the current organic chemistry of sulfur. Results,
which were mainly published in the recent two decades, are summarized and compared in
an excellent, comprehensive review [2].
Reactions of thiocarbonyl compounds with elemental sulfur and their conversion into
sulfur-rich heterocycles attract attention since many decades. Aromatic, aliphatic/aromatic
Molecules 2021, 26, 822. https://doi.org/10.3390/molecules26040822
https://www.mdpi.com/journal/molecules

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or cycloaliphatic thioketones
1, and
2, e.g., thiobenzophenone (1a) and (tert-butyl) phenyl
thioketone (1b), as well as cycloaliphatic analogues such as 2,2,4,4-tetramethylcyclobutane-
1,3-dithione (2a), 2,2,4,4-tetramethyl-3-thioxocyclobutanone (2b) or adamantanethione (2c
are known to undergo sulfurization in the presence of a nucleophilic catalyst or upon
heating without a catalyst in an appropriate organic solvent [ ] (Figure 1). On the other
hand, sulfurization of thiochalcones -unsaturated thioketones) as substrates for the
preparation of sulfur-rich heterocycles has not yet been reported.
)
3–8
3 (α,β
Figure 1. Aromatic and cycloaliphatic thioketones
1 and 2, and thiochalcones 3 applied in the study.
In many cases, the mechanistic interpretation of the observed reactions course was
based on the assumption that the transient thiocarbonyl S-sulfides (thiosulfines) ],
4 [9
generated via the transfer of a sulfur atom to the C=S bond, and considered as ‘sulfur-
rich’ representatives of so called ‘sulfur-centered 1,3-dipoles’, play the crucial role in
the formation of sulfur heterocycles, such as the corresponding 1,2,4-trithiolanes
(Figure 2). On the other hand, the larger rings, e.g., 1,2,4,5-tetrathianes or 1,2,3,5,6-
pentathiepanes , are formed via more complex processes, but the reaction mechanisms are
not fully rationalized to date and require further studies [3,4,11].
5 [10]
6
7
Figure 2. Thiocarbonyl S-sulfides
4, the sulfur-rich heterocycles 1,2,4-trithiolanes 5, 1,2,4,5-
tetrathianes 6, and 1,2,3,5,6-pentathiepanes 7, as well as phenylpolysulfide anions 8A.
For example, in some instances, sulfurization of thioketones performed in the pres-
ence of a nucleophilic catalyst, e.g., sodium or potassium thiophenolate, were explained
via involvement of in situ-generated, reactive polysulfide anions of type 8A [3,4]. Thus,
Huisgen and Rapp reported that elemental sulfur reacts with thiobenzophenone (1a) in
boiling acetone, in the presence of catalytic amounts of sodium thiophenolate, yielding
3,3,6,6-tetraphenyl-1,2,4,5-tetrathiane (6a) (R = Ph) as the exclusive product [
authors demonstrated that 3-thioxo-2,2,4,4-tetramethyl-cyclobutanone (2b) [ ] and adaman-
tanethione (2c) [ ] also undergo sulfurization under the same conditions. However, the
isolated products are either the bis-spirocyclic 1,2,4,5-tetrathianes 6b 6c (R,R = 6b: spiro-
2,2,4,4-tetramethyl-3-oxocyclobutyl; 6c: spiro-2-adamantyl) or 1,2,3,5,6-pentathiepanes 7a 7b
(R,R = 7a: spiro-2,2,4,4-tetramethyl-3-oxocyclobutyl; 7b: spiro-2-adamantyl), respectively.
3]. The same
4
3
/
/
Okuma also studied reactions of 2c with elemental sulfur in the presence of cat-
alytic amounts of triphenylphosphine sulfide (Ph3P=S) in boiling CHCl3 and isolated

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1,2,4-trithiolane 5c (R,R = spiro-2-adamantyl) in 59% yield [
5
]. In the same publication, sul-
furization of 1a with elemental sulfur in boiling xylene, in the presence of maleic anhydride
as a trapping reagent for the postulated, intermediate thiobenzophenone S-sulfide (4a) (R1
= R2 = Ph), was also described, and the expected [3+2]-cycloadduct, i.e., 5,5-diphenyl-1,2-
dithiolane-3,4-dicarboxylic acid anhydride, was obtained in 74% yield [5].
Nakayama et al. performed sulfurization of the cycloaliphatic thioketone 1b with
elemental sulfur without a nucleophilic catalyst using DMF or toluene as a solvent. De-
pending on the solvent, either a mixture of the isomeric 1,2,4-trithiolanes cis- and trans-5a
(boiling toluene) or cis-5a as the sole product (DMF, rt), were obtained [6,7]. In these reac-
tions, a plausible mechanistic explanation comprised the in situ-formation of thiocarbonyl
S-sulfide 4b and its subsequent stereoselective [3+2]-cycloaddition onto the unconverted
thioketone 1b (Scheme 1).
Toluene
reflux
S
S
S
S
S
Ph
+
S
+ 1b
Ph
Ph
Ph
+ S8
_
+
or
DMF, rt
Ph
S
S
S
Ph
4b
1b
trans-
5a
cis-5a
Scheme 1. Reaction of tert-butyl phenyl thioketone (1b) with elemental sulfur S8 in boiling toluene or in DMF at rt (ref. [6,7]).
A similar reaction performed with tert-butyl 4-methylphenyl ketone in boiling pyri-
dine and using tetraphosphorus decasulfide (P4S10) as a thionating and sulfurizing reagent,
was described by Okuma et al. [8].
In spite of the fact that the fluoride anion is well known as a useful reagent acting
not only as a unique catalyst for nucleophilic trifluoromethylation reactions [12], as a
desilylating agent [13], but also as a strong base [14], its exploration as an activating
reagent for elemental sulfur in the sulfur transfer reactions is limited to two reports only,
which are known to date [15,16]. In one of them, Petrov and Marshall demonstrated
the utility of the fluoride anion as a potent activator of elemental sulfur used for in situ-
generation of reactive hexafluorothioacetone S-sulfide, which subsequently was trapped
by ethylenic dipolarophiles yielding corresponding bis-trifluoromethylated 1,2-dithioles
in high yields [15]. In the second publication, sulfurization of cyclopropenethione 2d
and its oxo-analogues with elemental sulfur in DMF solution at room temperature was
described [16] (Scheme 2). In this study, potassium fluoride was used in two-fold excess as
activator and the molar ratio of reagents 2d/[S]/KF was optimized to 1:2:2. Under these
conditions, 3-thioxo-1,2-dithiole 9 was obtained as the product of a cascade reaction and
isolated in good yield (84%). A series of analogous Se-heterocycles was also obtained using
elemental selenium instead of sulfur [16].
Scheme 2. Fluoride anion-catalyzed sulfurization of diphenylcyclopropenethione (2d) (ref. [16]).
Unlike thioketones, similar sulfurization of α,β-unsaturated thioketones 3 (thiochalkones)
with S8 are almost unknown. In an earlier publication, however, sulfurization of rather
complex thiochalcones 11, prepared in situ from corresponding ketones 10, was carried out
in non-polar xylene by treatment with S8. These reactions led to the polycyclic products
12, which were formed as minor products, exclusively [17] (Scheme 3). The formation
of the latter heterocycles was explained via a multi-step mechanism with the respective
α
,β-unsaturated thiocarbonyl S-sulfides 4c as the reactive intermediates in the postulated
intramolecular [5+2]-cycloaddition reactions.

Molecules 2021, 26, 822
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Scheme 3. Reaction of thiochalcones 11 with sulfur yielding 1,2-dithiepanes 12 via intramolecular
[5+2]-cycloaddition of intermediate thiocarbonyl S-sulfides 4c (ref. [17]).
The main goal of the present study was examination of the utility of the fluoride anion
as a new type of a catalyst for sulfurization of thiobenzophenone (1a) and cycloaliphatic
thioketones 2a
selected thiochalcones 3a
–
2c. In extension of the study with thioketones, first sulfurization reactions of
3d were carried out by using elemental sulfur (S8) in the presence
–
of a nucleophilic catalyst. Elucidation of the mechanisms of the studied reactions, leading
to the formation of sulfur-rich heterocycles with diverse ring size, was of primary interest.
2. Results and Discussion
2.1. Conversions of Thioketones 2a and 2b upon Tretament with Catalytic Amounts of TBAF in the
Absence of Elmental Sulfur
In an earlier publication, unexpected conversions of thiobenzophenone (1a) and cy-
cloaliphatic thioketones 2a–2c upon treatment with catalytic amounts of TBAF in THF
solution were reported [18]. The obtained results demonstrated that the type of products
formed in each reaction strongly depended on the type of thioketone used in the studied
experiment. Interestingly enough, two structurally similar cycloaliphatic thioketones 2a
and 2b—derived from 2,2,4,4-tetramethylcyclobutane-1,3-dione (13)—gave completely dif-
ferent sets of products. Whereas in the case of dithione 2a the only product was the isomeric
thiolactone 14, the monothione 2b afforded a mixture of the unusual dithiocarboxylate 15
and the parent dione 13 (Scheme 4).
Scheme 4. Comparison of unusual conversions of thioketones 2a and 2b upon treatment with catalytic amounts of TBAF in
THF solution at rt in the absence of S8.
Due to the importance of this observation, both experiments were repeated in the
initial stages of the present study. The already described isomerization of 2a leading to 14
as the sole product was fully confirmed. However, in the experiment with 2b we found
that along with 13 and 15 also the ring-enlarged five-membered dithiolactone 16b was
present in the crude mixture. Moreover, the molar ratio of dione 13 and dithiolactone 16b

Molecules 2021, 26, 822
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was ca. 1:1 and this finding suggests that the monothione 2b can be an actual source of
sulfur incorporated into the four-membered ring of another molecule of the same substrate.
The mechanism of the isomerization of 2a induced by fluoride anion presented in [18
]
is a plausible explanation of this conversion. On the other side, the formation of dithioester
15, which requires reduction of the C=S bond of 2b, as well as the intermolecular transfer
of the sulfur atom from one molecule of 2b to another one in the formation of 16b, has
not convincingly been rationalized yet. Searching for a correct explanation, an additional
experiment with attempted conversion of 2b using catalytic amounts of flame-dried CsF
in dry DMF has also been performed. To our surprise, no effect was observed even after
ca. 2 h at rt. This situation changed immediately after addition of a drop of water to the
solution, which rapidly changed the color to orange indicating thereby conversion of 2b
.
Subsequent control of the composition of products by means of 1H-NMR spectroscopy
confirmed the formation of the mixture of three known products, namely 13, 15, and 16b.
This result clearly demonstrated that the unexpected conversion of 2b can be performed
only in the presence of water and the involvement of the hydrated fluoride anion in the
reaction solution plays a crucial role in the formation of 15 and 16b. Notably, TBAF is
known to exist as a hydrated complex and the complete removal of water requires a special
procedure [19].
2.2. Activation of Elemental Sulfur with Fluoride Anion
It is very likely that the activation of elemental sulfur with fluoride anion comprises
cleavage of the S8-ring leading to a mixture of red-colored, highly nucleophilic fluoropoly-
sulfide anions 8B with variable length of the sulfur chain Sx (Scheme 5).
Scheme 5. Ring cleavage of the S8 crown and formation of a mixture of fluoropolysulfide anions 8B
.
It is worth of mentioning that in the case of TBAF complete removal of water forming
‘fluoride anion hydrates’ is a difficult problem and some amounts of water are still present
in the solution [20]. In contrast, cesium fluoride, which can be used alternatively as a source
of the fluoride anion, can be prepared as a water-free salt. However, due to solubility
problems reactions with CsF have to be performed in dry DMF solution. In the sulfurization
reaction of a thioketone, the C=S bond is believed to react with anions 8B according to the
‘carbophilic’ mode of the initial nucleophilic attack.
2.3. Sulfurization of Thioketones with Elemental Sulfur
All experiments were carried out using optimized protocols elaborated in a series of
preliminary test reactions. Magnetically stirred suspension of elemental sulfur in THF at
rt dissolved immediately after addition of catalytic amounts of TBAF, and the obtained
solution was colored red or olive-green, thereby indicating formation of fluoropolysufide
anions 8B with variable length of the Sx chain. Addition of a thioketone led to the change of
the color within a few minutes, and the completion of the reaction was established by TLC
(see Tables 1 and 2). After pre-purification by column chromatography aimed at separation
of the catalyst, the crude mixtures were analyzed in the 1H-NMR spectra with weighted
standard (1,2-dichloroethane; Method A), and pure products were isolated on preparative
plates (Method B). Alternatively, selected reactions were performed in DMF solution using
pre-dried CsF as a catalyst.

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Table 1. Sulfurization conditions of thioketones 2a and 2b and yields of the products.
Thioketone
Entry
RT [h], rt
Product
Yield (%)
14
16a
63 a
A
1
11 a
8 b
16a
6e
B
1.5
15 b
43 b
meso-17,D,L-17
14
16a
18
9 a
8 b
C
2
5 a
2a
23 b
7c
0
54 b
C
24
7c
14
16a
18
7c
19
3 a
5 a
2 a
D
A
2
46 b
4 b
15
16b
6b
30 a
10 a
12 a
20 a
23 a
40 a
1.5
3
15
16b
6b
B
2b
34 b
43 b
52 b
60 b
C
48
24
22
6
7a
7a
7a
7a
0
C
D
E
a
Method A (1H-NMR); b Method B (isolated products).
Table 2. Sulfurization conditions of thioketones 2c and 1b and yields of the products (isolated amounts).
Yield
(%)
ThioketoneEntry
RT (h)
Product
Yield (%)
59
-
-
Product
A
72
46
24
24
5c
-
-
7b
7b
7b
-
37
47
51
-
B
2c
1a
C
0
C
5c
59
B
72
72
48
6a
6a
6a
28
52
56
-
-
-
-
-
-
C
0
C
2.3.1. Sulfurization of ‘Dithione’ 2a and ‘Monothione’ 2b
A series of experiments aimed at determination of the impact of the molar ratio of 2a
to sulfur on the structure of the formed products, was performed starting with 1:0.5, 1:1,
1:2, 1:4 or 1:8 (Entries A–E) mixtures of the two reagents. In the obtained crude mixtures
both, known and hitherto unknown sulfur-rich heterocycles were initially identified by
1H-NMR spectroscopy (see Supplementary Materials part) and subsequently isolated as
pure compounds (Figure 3).
In the first experiment, the reaction with a 1:0.5 molar ratio of 2a and atomic [S]
(Entry A) led to a mixture of the isomeric thiolactone 14 (63% yield) and the ring enlarged
five-membered thiolactone 16a (11%) (Figure 3, Table 1).

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Figure 3. Products of sulfurization of thioketones 2a and 2b with elemental sulfur in the presence of
TBAF in THF solution.
Enhancement of the sulfur amount in the 1:1 experiment (Entry B) resulted in a drastic
change of composition of the products in the reaction mixture. The main component
isolated as the most polar fraction showed in the 1H-NMR spectrum eight signals with
approximately the same intensities located at 1.32, 1.35, 1.51, 1.51, 1.69, 1.71, 1.74, and
1.75 ppm. More important information was found in the 13C-NMR spectrum, which
revealed the presence of two isomeric compounds with very similar patterns of absorptions.
The most characteristic ones were those found at 248.18 and 248.39 ppm, which were
attributed to two C=S groups of the dithiocarboxylate type. In addition, two signals at
78.54 and 78.71 ppm corresponded to non-equivalent Csp3 atoms connected with two sulfur
atoms. In analogy to the 1H-NMR, eight signals between 26.32 and 30.66 ppm suggested
the presence of structurally similar 16 Me groups. The elemental analysis confirmed the
molecular formula C16H24S6, which can be attributed to a 1:1-mixture of the isomeric
bis-spiro-1,3-dithietane derivatives meso- and d,l-17. All attempts to separate this mixture
to obtain pure diastereoisomers, either by chromatography or fractional crystallization,
were unsuccessful.
The less polar fraction formed a yellowish oil, which in the 1H-NMR spectrum showed
the presence of only two broadened singlets located at 1.42 and 1.69 ppm. More infor-
mation delivered the 13C-NMR spectrum with two low field absorptions at 243.0 and
216.6 ppm. Whereas the first signal could be attributed to the C=S group incorporated in
the four-membered ring of cyclobutane, the second one was identified as the C=O unit of
a cyclobutane moiety. In addition, two closely located signals with low intensity, found
at 79.86 and 79.91 ppm, respectively, revealed the presence of two Csp3-atoms attached
to two S-atoms like in the molecule of a 1,2,4,5-tetrathiane. As a matter of fact, elemental
analysis confirmed the molecular formula C16H24OS5, which corresponds to the structure
of the ‘non-symmetric’ dispiro-1,2,4,5-tetrathiane 6e (Figure 3, Table 1). Apparently, the ini-
tially formed ‘symmetric’ analogue 6d (not isolated) underwent hydrolysis in the reaction
solution and one C=S group was converted into the C=O moiety.
Finally, the smallest and least polar fraction isolated after chromatography was identi-
fied as the known [4], five-membered dithiolactone 16a (8%) (Table 1).
Increase of the molar excess of sulfur to 4 mol-equiv. (Entry D) changed dramatically
the composition of the product mixture, and in this case the major fraction consisted of
an orange oil, which in the 1H-NMR spectrum showed a complicated pattern of signals

Molecules 2021, 26, 822
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located in the 1.30–2.00 ppm region. In the spectrum registered at 90 ◦C in CHCl2–CHCl2
solution, four broadened signals emerged at 1.92, 1.98. 2.08, and 2.20 ppm, respectively,
indicating thereby the existence of dynamic phenomena, like in the case of pentathiepane
7a described by Huisgen et al. [4]. Elemental analysis confirmed the molecular formula
C16H24S7 expected for the new pentathiepane 7c and allowed to determine the yield of the
isolated product to 46%. In another experiment carried out with 2a and [S] in a ratio 1:2
(Entry C), pentathiepane 7c was isolated in a lower yield (23%) and the already described
sulfur heterocycles 14 (9%), 16a (8%), and 18 (5%) were formed as side products.
Two more sulfur-rich heterocycles were separated as minor products. One of them
was identified as the known five-membered dithiolactone 18 [21], and the structure of
the second one was elucidated based on spectroscopic data and elemental analysis as
hitherto unknown spirocyclic 1,2,3,4,5,6-hexathiepane 19 being a thioxo analogue of the
corresponding oxo derivative, which was described in our earlier work [22]. Both com-
pounds revealed very similar chemical shifts for the spiro-C-atoms: 95.6 (for 19) and 92.2
(for the oxo analogue [22]) ppm, respectively.
Notably, the same pentathiepane 7c was isolated chromatographically in 54% yield as
the sole product when the sulfurization of 2a was carried out in DMF solution using dried
0
CsF as a catalyst (Entry C ). In that experiment the molar ratio of 2a and [S] was calculated
to 1:2.
In contrast to the hitherto unexplored dithione 2a, its monothione analogue 2b was
studied extensively by Huisgen and Rapp in sulfurization reactions with elemental sulfur
using potassium thiophenolate as a catalyst [4]. The main goal of that study was the
elucidation of the mechanism of the dimerization of in situ-generated intermediates leading
to 1,2,4,5-tetrathiane 6b. In our hands, reactions of 2b with variable amounts of sulfur and
performed with TBAF as a catalyst led virtually to similar products. Thus, in experiments
starting with 2b and [S] in a molar ratio 1:0.5 (Entry A) or 1:1 (Entry B), the only sulfur-rich
compound identified in the crude mixture of products was 6b accompanied by the above
reported 3-oxopentanedithioate 15 and dithiolactone 16b. In the 1:1 experiment, the yield
of tetrathiane 6b was higher (40%) (Table 1). Further enhancement of the amounts of sulfur
to 1:2 (Entry C), 1:4 (Entry D), and finally 1:8 (Entry E) molar ratio suppressed completely
the formation of other products and nothing but 1,2,3,5,6-pentathiepane 7a was isolated in
acceptable yields of 34%, 52%, and 60%, respectively. In a test experiment using pre-dried
CsF (instead of TBAF) in DMF solution and starting with a 1:2 ratio of 2b and atomic [S],
the latter heterocycle was isolated in 43% yield (Entry C0). Spectroscopic and physico-
chemical data of 7a fitted well with those reported earlier [4]. In addition, the crystal
structure of this compound showing a complex conformation of this seven-membered,
sulfur-rich hetererocycle has also been reported in another publication [22]. In the present
study, the structure of 7a was redetermined by X-ray analysis and the crystallographic
characterization of this sulfur-rich heterocycle could be refined thereby.
2.3.2. Formation of Sulfur-Rich Heterocycles from Thioketones 2a and 2b; Mechanistic
Interpretations
It has to be underlined that in both series of experiments performed either with 2a or
2b and starting with a 1:0.5 molar ratio of a thioketone
at all of the corresponding 1,2,4-trithiolane of type
of products. These findings allow to exclude participation of thiocarbonyl S-sulfides
(thiosulfines) 4A derived from the studied thioketones as reactive intermediates in the
2
and elemental sulfur [S], no traces
5
could be detected in the mixtures
–
C
2
herein presented sulfurizations. Instead, these observations suggest to consider dithiiranes
21 and their ring opened forms, i.e., diradicals 22 (or zwitterions 23), as elusive species
involved in the formation of the isolated sulfur-rich heterocycles (Scheme 6). The parent
dithiirane and its isomerization to dithioformic acid can serve as a model system helpful
in the formulation of experimentally well founded rational description of the complex
conversions observed in the present study [23].
It seems a plausible explanation that in situ-generated fluoropolysulfide anions 8B
undergo the carbophilic addition to the C=S bond forming the intermediate anion 20. The

Molecules 2021, 26, 822
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latter extrudes a new fluoropolysulfide anion with a shortened sulfide chain yielding the
elusive dithirane 21, which may exist in an equilibrium with ring opened reactive species
22 and/or 23 (Scheme 6).
Scheme 6. Initial, nucleophilic attack of fluoropolysulfide anion 8B onto the C=S bond and subse-
quent ring closure leading to dithiiranes 21 as elusive intermediates.
In the reaction performed with equimolar amounts of thioketone and sulfur, step-
wise dimerization of the latter species leads to the formation of the 1,2,4,5-tetrathiane
6. Alternatively, the intermediate species 22 undergo ring-expansion via intramolecular
insertion of the S-atom into a C–C bond to form dithiolactones 16. However, if there is
a source of sulfur and fluoropolysulfide 8B exists in the system, it can transfer one more
sulfur atom to the intermediate 24 yielding finally 1,2,3,5,6-pentathiepanes 7 (Scheme 7).
Scheme 7. Step-wise formation of 1,2,4,5-tetrathianes 6 and 1,2,3,5,6-pentathiepanes 7.
This interpretation seems to be more likely than an alternative pathway via a secondary
ring opening/ring closure reaction sequence of the initially formed 1,2,4,5-tetrathiane
derivative, after reaction with a polysulfide anion, leading either to 1,2,4-trithiolanes or
1,2,3,5,6-pentathiepanes. This pathway has been suggested in an earlier publication, dealing
with similar problems of sulfurization reactions of some aromatic aldehydes [11].
The unexpected formation of diastereoisomeric dispiro-1,3-dithietane 17 deserves
also a comment. It seems likely that in analogy to the earlier observed BTAF/TMSCF3
induced dimerization of dithione 2a [18] affording 1,3-dithietane 25, also fluoropolysulfide
anions 8B can catalyze an analogous reaction. Now, each of the C=S bonds can react with
8B and via addition/ring expansion sequence is converted in mixtures of isomeric, spiro-
heterocycles 17 (Scheme 8). Alternatively, dimerization of the initially formed dithiolactone
16a, induced by fluoride anion can be postulated. Notably, no formation of corresponding
products of type 17, starting with monothione 2b was observed and this is one more feature,
which differs behavior of both cycloaliphatic thioketones in sulfurization reactions.

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Scheme 8. Postulated mechanism of the formation of diastereoisomeric bis-spiro-1,3-dithianes 17 via
initial dimerization of the starting thioketone 2a.
An alternative cyclization pathway of the initial anionic adduct 20, formed via attack
of anions 8B onto the C=S group, leading to the hexathiepane 19, is presented in Scheme 9.
It demonstrates the known tendency for the formation of seven-membered rings consisting
of sulfur and carbon atoms [22].
Scheme 9. Mechanistic explanation of the formation of 1,2,3,4,5,6-hexathiepane 19.
2.3.3. Sulfurization of ‘Adamantanethione (2c) and Thiobenzophenone (1a)
In extension of the study performed with cycloaliphatic thioketones 2a and 2b, derived
from the sterically crowded and ring congested 2,2,4,4-tetramethylcyclobutane-1,3-dione
(
13), sulfurization reactions of easily available thioketones, such as the cycloaliphatic
adamantanethione (2c) and the aromatic thiobenzophenone (1a), were also tested in the
fluoride anion catalyzed sulfurization reactions. In both cases, the reactions were carried
out with TBAF as a catalyst in THF at rt, and required remarkably longer times for com-
pletion (see Table 2, Figure 4). Analysis of the crude mixtures of products by 1H-NMR
spectroscopy and separation by preparative thin-layer chromatography led to the iden-
tification and isolation of three types of sulfur-rich heterocycles. Thus, in the case of 2c
,
irrespective of the molar ratio of thioketone and sulfur, 1:1 (Entry B) or 1:2 (Entry C),
only the symmetric 1,2,3,5,6-pentathiepane 7b was obtained in moderate yields (37–51%).
However, in the experiment with a 1:0.5 molar ratio (2c: [S], Entry A), 1,2,4-trithiolane 5c
was found in the mixture of products as the major component (59%). The same product
was formed in DMF solution at rt exclusively, when the reaction was performed with CsF
(Entry C0). Its presence suggests the appearance of adamantane-2-thione S-sulfide and
subsequent trapping by another molecule of 2c according to the [3+2]-cycloaddition mode
as suggested in our earlier study [24]. Limited amounts of elemental sulfur available in
the first experiment (Entry A) can suggest that the reaction leading to 5c follows a hitherto
unknown mechanism of the reaction of fluoride anion with 2c mentioned in our earlier
publication [18]. Nevertheless, formation of 7b can results from the mechanism initiated
by the attack of fluoropolysulfide anion onto the C=S bond according to the pathways
presented in Scheme 7. Notably, no symmetric 1,2,4,5-tetrathiane derived from 2c and
obtained by Huisgen and Rapp [
3] via sulfurization of the latter in reactions catalyzed with
potassium thiophenolate, was observed in our experiments.

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Figure 4. Three types of sulfur-rich heterocycles obtained by sulfurization of adamantanethione (2c
)
and thiobenzophenone (1a) with sulfur, catalyzed with fluoride anion.
The fluoride anion catalyzed sulfurization of thiobenzophenone (1a) was performed
starting with 1:1 or 1:2 molar ratio of 1a to [S] (Entry B or Entry C, respectively). In both
cases colorless products precipitated from THF solution, and the analysis of the obtained
crude mixtures demonstrated that the literature known, symmetric 3,3,6,6-tetraphenyl-
1,2,4,5-tetrathiane (6a) [3] was the sole product in both reactions, isolated in 28% and
52% yield, respectively. Remarkably, no ring expansion to the corresponding 1,2,3,5,6-
pentathiepane in the experiment with molar excess of sulfur (1:2; Entry C) was observed.
This observation suggests that this could be the effect of the limited solubility of 6a, which
precipitated from the THF solution in the course of the reaction. Notably, Huisgen and Rapp
did not observe formation of this 1,2,3,5,6-pentathiepane either [3]. In the present study,
along with 1a, other well-known aromatic thioketones such as xanthione, thioxanthione
and dibenzosuberenethione, which have been frequently applied in our studies, were tested
in the fluoride anion catalyzed sulfurization, but in all cases no reaction was observed at rt,
even after longer reaction time (up to one week). Particularly, thiofluorenone (9H-fluorene-
9-thione) converted rapidly into the dimeric fluorenyliden-9-ene (tetrabenzo[5.5]fulvalene)
in analogy to the result described in [18]. Thus, thiobenzophenone (1a) should be con-
sidered as an exceptional case showing superior tendency to undergo the reaction with
fluoropolysulfide anion 8B with subsequent ‘head-to-head’ dimerization of a reactive
intermediate leading to tetrasubstituted 1,2,4,5-tetrathiane 6a.
In accordance with the proposal presented in Scheme 9, a plausible mechanistic
interpretation of this multi-step reaction is the initial formation of the unstable 3,3-diphenyl
dithiirane (21c). The latter, after spontaneous cleavage of the S–S bond, converts into a
reactive intermediate of type 24, which undergoes step-wise dimerization leading to the
1,2,4,5-tetrathiane ring (Scheme 7).
2.4. Sulfurization of Thiochalcones 3
In contrast to thioketones
1/2, the α,β-unsaturated analogues, i.e., diaryl thiochal-
cones , are much less investigated as potentially useful reagents in the cycloaddition
3
chemistry. In fact, thiochalcones exhibit a far more complex nature in comparison with
thioketones, which comprises their tendency to form two dimeric molecules existing in
an equilibrium with the monomeric ones. The equilibrium concentration of monomeric
and dimeric forms depends on the solvent polarity that makes thiochalcones difficult to be
tamed in [3+2]-cycloadditions [25], Diels-Alder- [26], and hetero-Diels-Alder-reactions [27].
Correctly, the fraction containing only the monomeric form is often described as ‘thiochal-
cone fraction’ [25,27]. As mentioned in the ‘Introduction’, the single experiment reporting
sulfurization of a rather complex, in situ-generated thiochalcone relates to harsh reaction
conditions with heating of the reaction mixture in boiling xylene [17].
The goal of the present study was to verify whether sulfurization of typical thiochal-
cones
3 can be performed under mild conditions using elemental sulfur activated by TBAF
in THF at room temperature. The test experiment performed with 3a and elemental sulfur
(molar ratio of 3a to [S] was 1:2) according to the protocol described above for thioketones
2a,b (Entry C), was unsuccessful, however. In that case, no conversion of 3a occurred
even after three days of stirring at rt. Instead, slow decomposition of the starting 3a was
observed by TLC.

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Prompted by Okuma’s report [5], we decided to use PPh3 in boiling acetone solution
as a nucleophilic activator of sulfur (Procedure I, Table 3). In the cited study, comparable
results were obtained using either PPh3 or S=PPh3. In our hands, under these conditions a
part of 3a, consisting of monomeric thiochalcone and its dimer (dithiine derivative, under-
went dissociation) reacted with sulfur yielding an orange-red colored, crystalline product.
In the 1H-NMR spectrum (see Supplementary Materials part), along with absorptions of
aromatic H atoms, a characteristic set of two doublets with 3JH,H = 3.0 Hz was found at
5.87 and 6.19 ppm, respectively. In addition, 13C-NMR revealed a signal of a Cq atom at
63.7 ppm and two other signals located at 120.7 and 132.9 ppm, respectively, with clearly
different intensities, which could be attributed to a CH=C unit. The elemental analysis
confirmed the molecular formula C15H12S2 expected for a product of monosulfurization of
3a. Based on the collected spectroscopic data, the structure of the obtained product was
established as 3,5-diphenyl-3H-1,2-dithiole (26a, Scheme 10).
Scheme 10. Synthesis of 3H-1,2-dithioles 26a
3a–3d.
–26d via PPh3-catalyzed sulfurization of thiochalcones
Table 3. Sulfurization conditions of thiochalcones 3a–3d and yields of products.
Thiochalcone
Procedure
RT [h]
Product
Yield (%)
40 a (63 b)
15 a
3a
3a
3a
3a
3b
3c
3c
3d
I
II
III
IV
I
I
IV
I
3.5
4.0
0.5
72
4.0
3.5
72
26a
26a
26a
26a
26b
26c
26c
26d
41 a
15 a
15 a
20 a
17 a
3.0
12 a
a
Method A (isolated product); b Method B (1H-NMR).
It has to be underlined that the 1H-NMR analysis of the crude mixture revealed the presence
of the non-reacted thiopyran as one of the dimers of the starting thiochalcone [25 27]. Apparently,
–
this dimer is stable under the reaction conditions and does not undergo dissociation
leading to new portions of the monomeric form. This fact must be taken into account while
calculating the yield of the obtained sulfurization product.
An analogous procedure has been applied to perform sulfurization of three other
thiochalcones 3b–d, which have also been converted into the desired 3H-1,2-dithioles
26b , albeit in all cases the yields of the isolated products were rather low. The results of
–
d
all experiments aimed at the synthesis of heterocycles 26 are summarized in Table 3.
For comparison reasons, two modifications of the applied procedure were tested in
reactions with 3a. In the first case, potassium thiophenolate was used as a catalyst, but
after 4 h reaction time the product 26a was isolated in lower yield (15%) (Procedure II). The
second modification comprised replacement of acetone by higher boiling butanone, and in
this case, the reaction was finished after only 30 min, yielding 26a in the comparable yield
of 41% (Procedure III, Table 3).

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The alternative procedure with pre-dried CsF in DMF solution (Procedure IV) was
also tested in reactions with 3a and 3c. After 3d at rt the reactions were finished and the
1H-NMR analysis of the crude mixtures indicated the presence of the expected 3H-1,2-
dithioles 26a and 26c, which were isolated by column chromatography in 15% and 17%
yields, respectively.
Notably, no formation of a corresponding 1,2,4-trithiolane was observed in any experi-
ment performed with thiochalcones 3.
A feasible reaction mechanism is presented in Scheme 10. The PPh3 catalyzed sulfur-
ization of thiochalcones involves α,β-unsaturated thiocarbonyl S-sulfides 4 as plausible
intermediates. They are formed via sulfur transfer from in situ-generated, neutral (and
therefore less nucleophilic) triphenylphosphine polysulfides to the C=S group. In reactions
catalyzed with CsF (Procedure IV), participation of fluoropolysulfide anion 8B in the trans-
fer of the sulfur atom is likely. In that case, however, the intermediate dithiirane of type
21, derived from the respective thiochalcone
the C–S bond yielding the respective 1,3-dipole [22
from chalcones belong to the group of -unsaturated 1,3-dipoles and, therefore, they
3, is belived to undergo ring opening along
,
23,28]. Thiocarbonyl S-sulfides derived
α,β
can undergo 1,5-electrocyclization [29] leading to the formation of 3H-1,2-dithioles, which
apparently is a faster intramolecular process than the competitive [3+2]-cycloaddition
with a ‘non-sulfurized’ molecule of the starting thiochalcone. Therefore, in none of the
experiments formation of a respective 1,2,4-trithiolane was observed. Participation of
thiocarbonyl S-sulfides in the [3+2]-cycloaddition with thiocarbonyl dipolarophiles is an
important method for the synthesis of sulfur-rich heterocycles and diverse methods for the
generation of this type of ‘sulfur-centered 1,3-dipoles’ are known [28]. Most importantly,
the described 1,5-dipolar electrocyclization found for the first time in sulfurization reactions
of thiochalcones offers a convenient method for the preparation of useful, five-membered
3H-1,2-dithioles 26.
3. Materials and Methods
3.1. Materials
Elemental sulfur (S8) in the form of a powder (99.98% purity), molecular sieves
4Å (mesh 8–12), tetrabutylammonium fluoride (TBAF, 1.0 M solution in THF) and ben-
zophenone (99%) were purchased from Merck (Sigma-Aldrich, Darmstadt, Germany).
Triphenylphosphine (Ph3P) (>95%), cesium fluoride (CsF) and 1,1,2,2-tetrachloroethane,
used as internal standard in NMR analysis, were received from Tokyo Chemical Industry
(TCI, Tokyo, Japan). Organic solvents were purchased from the following companies:
tetrahydrofuran (99.9%) from Chemsolve (Witko, Lodz, Poland), dichloromethane (99.9%)
from Honeywell (Charlotte, NC, USA), anhydrous N,N-dimethylformamide (99.8%) from
Merck (Sigma-Aldrich), methanol (99.8%), acetone (99.5%) and petroleum ether 40/60 from
´
Chempur (Piekary Sla˛skie, Poland). THF was dried over sodium (Na) with an addition
of benzophenone, and acetone was distilled before its usage. Starting thioketones were
obtained following reported procedures: thiobenzophenone (1b) from benzophenone by
treatment with Lawesson’s reagent in toluene solution [18]; 2,2,4,4-tetramethylcyclobutane-
1,3-dithione (‘dithione’) (2a), 2,2,4,4-tetramethyl-3-thioxocyclo-butanone(‘monothione’)
(
2b), and admantanthione (2c) from 2,2,4,4-tetramethylcyclobutane-1,3-dione (13) and
adamantane-2-one, respectively, by treatment with P4S10 in pyridine solution [18]. Thiochal-
cones were prepared from the corresponding chalcones by thionation with Lawesson’s
3
reagent and subsequently purified by column chromatography on silica gel [25,26].
3.2. Analytical Methods and Equipment
The nuclear magnetic resonance (NMR) spectra were measured using a Bruker Avance
III instrument (Bruker, Billerica, MA, USA) at 600 MHz (1H-NMR) and at 151 MHz (13C-
NMR), respectively. Unless otherwise indicated the measurements were carried out in
deuterochloroform (CDCl3), using solvent signals as a reference (1H-NMR,
δ
= 7.26 ppm
(CDCl3); 13C-NMR,
δ = 77.0 ppm (CDCl3)). Chemical shifts (δ) were presented in ppm

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and coupling constants (J) were calculated in Hz. Integrals are given in accordance with
assignments. Melting points were determined in capillaries with a Melt-Temp II apparatus
(Laboratory Devices, Holliston, MA, USA). Elemental analyses were obtained with a Vario
EL III instrument (Elementar Analysensysteme, Langenselbold, Germany).
3.3. Conversions of Thioketones 2a,2b in the Presence of Fluoride Anion and Absence of S8
3.3.1. Procedure I: TBAF/THF
To a stirred solution of pre-dried TBAF (0.1 mL of 1.0 M solution in THF) in 1.5 mL of
dried THF, 0.5 mmol of the corresponding thioketone 2a or 2b was added at rt under Ar
atmosphere. The solution was stirred and after ca. 5 min the color changed from rubin-red
(
2a) or orange-red (2b) to yellow-orange. Next, the solvent was evaporated in vacuo and
the residue was pre-purified by filtration via a short chromatographic column filled with
SiO2 (ca. 2 cm layer). Crude mixtures were analyzed in the 1H-NMR spectra with weighted
standard (Cl2CH–CHCl2). The products formed were identified by comparison of their
spectroscopic data with reported ones. Yields reported below refer to the analysis of crude
mixtures performed with weighted standard (method A) or to amounts of isolated products
(method B).
3.3.2. Procedure II: CsF/DMF
In an alternative procedure, conversion of thioketone 2b was carried out in dry DMF
(1.5 mL) using cat. amounts of freshly calcined cesium fluoride at rt under Ar atmosphere.
After 2 h of magnetic stirring, the color still remained orange-red and no formation of other
products was observed by TLC control. After that time, a drop of water was added to the
stirred solution and the mixture rapidly changed the color to orange indicating thereby
conversion of 2b. The reaction solution was diluted with a portion of CH2Cl2 (5 mL) and
extracted four times with water (4 mL each). Collected organic fractions were dried over
MgSO4, filtered, and the solvent was evaporated. The mixture of crude products was
analyzed in the 1H-NMR spectrum with weighted standard (Cl2CH–CHCl2); the yields of
identified products 13, 15, and 16b were determined by method A.
3.3.3. Product Characterization
3,3-Dimethyl-4-(propan-2-ylidene)thietane-2-thione (14). Yield: Procedure I—92% (method
1
A); 69 mg (80%) (method B). Yellow oil (ref. [18]). H-NMR:
δ 1.47 (s, 2CH3), 1.73 (s, CH3),
1.86 (s, CH3) ppm. 13C-NMR:
131.0 (=C), 243.5 (C=S) ppm.
δ 20.1 (CH3), 21.9 (CH3), 25.2 (2CH3), 74.2 (C-3), 122.6 (=C),
20,20,40,40-Tetramethyl-30-oxocyclobutyl 2,2,4-trimethyl-3-oxopentanedithioate (15). Yield:
Procedure I—59% (method A), 38 mg (48%) (method B); Procedure II—44% (method A).
◦
◦
1
Yellow solid, m.p. 57–58 C (ref. [18], m.p. 62–63 C). H-NMR:
δ 1.13 (d, J = 6.6 Hz,
2CH3(CH)), 1.21 (s, 2CH3), 1.47 (s, 2CH3), 1.68 (s, 2CH3), 2.91 (sept., J = 6.6 Hz, 2CH3(CH)),
0
4.25 (s,
H
C-1 ) ppm. 13C-NMR: δ 20 0.4 (2CH3), 21.8 (2CH3), 25.0 (2CH3), 26.8 (2CH3), 37.0 (C-
0
0
0
4), 57.7 (C-2 , C-4 ), 61.1, 69.4 (C-1 , C-2), 212.0 (C=O, C-3), 218.9 (C=O, C-3 , cyclobutanone),
241.2 (C=S) ppm. C16H26O2S2 (314.51): calculated, C 61.10, H 8.33, S 20.39; found, C 61.12,
H 8.44, S 20.50.
3,3,5,5-Tetramethyl-2-thioxothiolan-4-one (16b). Yield: Procedure I—13% (method◦A);
9 mg (10%) (method B); Procedure II: 11% (method A). Yellow thick oil (ref. [4], mp 39–41 C).
1H-NMR:
δ δ 27.8, 28.1 (2CH3 each), 61.3
1.44 (s, 2CH3), 1.70 (s, 2CH3) ppm. 13C-NMR:
(C-3), 63.4 (C-5), 216.7 (C=O), 234.1 (C=S) ppm.
2,2,4,4-Tetramethylcyclobutane-1,3-dione (13). Yield: Procedure I—12% (method A);
Procedure II—8% (method A). 1H-NMR: δ 1.34 ppm. (ref. [30]).

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3.4. General Procedures of the Fluoride Anion Catalyzed Sulfurization of Thioketones
Elemental Sulfur (S8)
1 and 2 with
3.4.1. Procedure I: TBAF/THF
To the suspension of elemental sulfur (calculated on atomic [S]) (0.25 mmol, Entry
A; 0.50 mmol, Entry B; 1.00 mmol, Entry C, 2.00 mmol, Entry D, or 4.00 mmol, Entry E)
in 1.5 mL of dried THF, under argon atmosphere, 0.1 mL (0.1 mmol, 20% mol. calculated
on the amounts of thioketone used) of the tetrabutylammonium fluoride solution (TBAF,
1.0 M in THF), pre-dried over molecular sieves, was added dropwise. The mixture became
red (Entries B–D)) or olive green in color (Entry A) and the sulfur has dissolved forming
a homogenous solution. After ca. 10–15 min of magnetic stirring at rt, 0.5 mmol of the
corresponding thioketone 1a or 2a,2c was added in small portions to the solution and
stirring was continued for an appropriate time at rt (see Tables 1 and 2). Next, the solvent
was evaporated in vacuum and the residue was pre-purified by filtration via a short chro-
matographic column filled with SiO2 (ca. 2 cm layer). The crude mixtures were analyzed in
the 1H-NMR spectra with weighted standard (Cl2CH–CHCl2) and subsequently separated
on preparative chromatographic plates coated with silica gel. A mixture of petroleum ether
and dichloromethane (in most cases the ratio of both solvents was 9:1 or 8:2) was used as
an eluent. Yields refer either to analysis with weighted standard (method A) or to isolated
amounts (method B).
3.4.2. Procedure II: CsF/DMF
In an alternative procedure reactions of thioketones 1a and 2a–c with 2.0 mmol of
sulfur (Entry C0) were carried out in dry DMF (2–3 mL) using catalytic amounts of freshly
calcined cesium fluoride (CsF). After completion of the reactions, the mixture was diluted
with dichloromethane and extracted several times with small portions of water to remove
DMF. Following an alternative method for the removal of DMF, toluene (2–3 mL) was added
in small portions and the solutions obtained thereby were warmed in a water bath (55 ◦C)
to evaporate the solvents. Crude products were purified by column chromatography on
silica gel using petroleum ether/dichloromethane mixtures as eluent.
3.4.3. Product Characterization
Dispiro[adamantane-2,30-(1,2,4)-trithiolane-50,2”-adamantane] (5c). Yields: Procedure I—(a)
Entry A: 27 mg (59% based on S/30% based on 1◦c); (b) Procedure II—Entry C0: 54 mg
(59%) (method B). Colorless solid, m.p. 200–201 C (methanol/CH2Cl2) (ref. [31], m.p.
◦
191–192 C). 1H-NMR: 1.75–1.95 (m, 16H), 2.15–2.40 (m, 12H) ppm. 13C-NMR:
δ δ 26.6, 26.9
(4CH), 36.7, 37.2, 37.9 (10CH2, ratio ca. 2:2:1), 39.4 (4CH), 90.3 (C-30, C-50) ppm.
3,3,6,6-Tetraphenyl-1,2,4,5-tetrathiane (6a). Yields: Procedure I—(a) Entry B: 32 mg (28%)
(method B); (b) Entry C: 60 mg (52%) (method B); (c) Procedure II—Entry C0: 65 mg (56%)
◦
(method B). Colorless crystals, m.p. 210–212 C (decomposition, blue) (methanol/CH2Cl2)
(ref. [
3
], mp. 209–209.5 ◦C). 1H-NMR:
δ
7.30–7.36 (m, 12CHarom.), 7.55–7.59 (m, 8CHarom.)
ppm. 13C-NMR: δ 71.4 (C-3, C-6), 127.9, 128.5, 128.6 (20CHarom.), 141.7 (4Carom.) ppm.
1,1,3,3,8,8,10,10-Octamethyl-5,6,11,12-tetrathiadispiro-[3.2.3.3]dodecane-2,9-dione (6b). Yields:
Procedure I—(a) Entry A: 12% (method◦A); (b) Entry B: 40% (method A), 30 mg (32%)
◦
(method B). Colorless solid, m.p. 170–172 C (methanol/CH2Cl2) (ref. [
4
], m.p. 169–170 C).
1H-NMR:
δ
1.39 (s, br, 4CH3), 1.54 (s, br, 4CH3) ppm. 13C-NMR:
δ
20.9, 24.9 (4CH3 each),
67.1 (C-1, C-3, C-8, C-10), 71.5 (C-4, C-7), 217.9 (2C=O) ppm.
1,1,3,3,8,8,10,10-Octamethyl-5,6,11,12-tetrathiadispiro-[3.2.3.3]-9-oxododecane-2-thione (6e).
1
Yield: Procedure I—(a) Entry B: 15 mg (15%) (method B). Orange oil. H-NMR:
δ 1.42 (s, br,
4CH3), 1.69 (s, br, 4CH3) ppm. 13C-NMR:
δ 27.8, 28.1 (4CH3 each), 61.3 (C-1, C-3), 63.4 (C-8,
C-10), 77.86, 77.91 (C-4, C-7), 216.6 (C=O), 243.0 (C=S) ppm.C16H24OS5 (392.69): calculated,
C 48.94, H 6.16, S 40.83; found, C 48.96, H 6.33, S 40.58.
1,1,3,3,8,8,10,10-Octamethyl-5,6,11,12,13-pentathiadispiro-[3.2.3.3]tridecane-2,9-dione (7a).
Yields: Procedure I—(a) Entry C: 35 mg (34%) (method B); (c) Entry D: 53 mg (52%) (method
B); (d) Entry E: 61 mg (60%) (method B); Procedure II—(e) Entry C0: 44 mg (43%) (method

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B). Colorless crystals, m.p. 146–148 ◦C (methanol/CH2Cl2) (ref. [
4
,
22], m.p. 147–148 ◦C).
1H-NMR: 1.20–1.90 (m, 8CH3) ppm. 13C-NMR:
δ
δ 21.0–26.0 (m, 8CH3), 67.3 (C-1, C-3, C-8,
C-10), 71.5 (C-4, C-7), 216.2 (2C=O) ppm. C16H24O2S5 (408.69): calculated, C 47.02, H 5.92,
S 39.23; found, C 47.13, H 6.07, S 39.34.
Dispiro[adamantane-2,40-(1,2,3,5,6)-pentathiepane-70,2”-adamantane] (7b). Yields: Proce-
dure I—(a) Entry A: 20 mg (37% based on S/19% based on 2c) (method B); (b) Entry B:
50 mg (47%) (method B); (c) Entry C: 55 mg (51%) (method B). Colorless solid, m.p. > 236 ◦C
◦
1
(decomposition) (methanol/CH2Cl2) (ref. [3]; m.p. > 236 C, decomp.). H-NMR: δ 1.55–3.0
(m, 28H) ppm. 13C-NMR:
δ 27.1, 33.7, 34.1, 35.4, 37.6, 38.6 (18C), referred weak signal at
84 ppm (C-40, C-70) is missing (see: ref. [3]).
1,1,3,3,8,8,10,10-Octamethyl-5,6,11,12,13-pentathiadispiro-[3.2.3.3]tridecane-2,9-dithione (7c).
Yields: Procedure I—(a) Entry C: 25 mg (23%) (method B); (b) Entry D: 51 mg (46%) (method
0
1
B); Procedure II—(c) Entry C : 59 mg (54%) (method B); red-orange viscous oil. H-NMR:
1.30–2.00 (m, 8CH3) ppm; 1H-NMR (CCl2=CCl2, D2O, 90 ◦C):
1.92, 1.98, 2.08, 2.20 (4s, br,
2CH3 each) ppm. 13C-NMR:
24.0–29.0 (m, 8CH3), 50.9 (C-1, C-3, C-8, C-10) 53.5 (C-4, C-7),
δ
δ
δ
276.0 (2C=S) ppm. C16H24S7 (440.82): calculated, C 43.59, H 5.49, S 50.92; found, C 43.37, H
5.38, S 50.97.
3,3-Dimethyl-4-(propan-2-ylidene)thietane-2-thione (14). Yields: Procedure I—(a) Entry A:
63% (method A); (b) Entry B: 9% (method A); (c) Entry C: 3% (method A).
20,20,40,40-Tetramethyl-30-oxocyclobutyl 2,2,4-trimethyl-3-oxopentanedithioate (15). Yields:
Procedure I—(a) Entry A: yield: 30% (method A); (b) Entry B: 20% (method A).
3,3,5,5-Tetramethylthiolane-2,4-dithione (16a). Yields: Procedure I—(a) Entry A: 11%
(method A); (b) Entry B: 8 mg (8%) (method B); (c) Entry C: 8% (method A), 8 mg (8%)
(method B); (d) Entry D: 5% (method A); 3 mg (3%) (method B). Red-orange oil (ref. [
b.p. 122 ◦C). 1H-NMR: 1.61 (s, 2CH3), 1.83 (s, 2CH3) ppm. 13C-NMR:
33.5 (2CH3), 33.7
(2CH3), 71.0 (C-3), 77.8 (C-5), 245.3 (S=C-2), 267.4 (S=C-4) ppm.
4]:
δ
δ
3,3,5,5-Tetramethyl-2-thioxothiolane-4-one (16b). Yields: (a) Entry A: 10% (method A); (b)
Entry B: 23% (method A), 16 mg (17%) (method B).
1,1,4,4,8,8,11,11-Octamethyl-2,6,9,12-tetrathiadispiro[4.1.4.1]dodecane-3,10-dithione (meso-
17), and 1,1,4,4,8,8,11,11-Octamethyl-2,6,10,12-tetrathiadispiro[4.1.4.1]dodecane-3,9-di-thione (d,l-
17). ◦Yield: Procedure I—(a) Entry B: 44 mg (43%) (method B). Yellow crystals, m.p. 130–
1
138 C (methanol/CH2Cl2). H-NMR:
δ
1.32 (s, 2CH3), 1.35 (s, 2CH3), 1.51 (s, 2CH3), 1.51 (s,
2CH3), 1.69 (s, 2CH3), 1.71 (s, 2CH3), 1.74 (s, 2CH3), 1.75 (s, 2CH3) ppm. 13C-NMR:
δ 26.32
(2CH3), 26.36 (2CH3), 26.57 (2CH3), 26.61 (2CH3), 29.72 (2CH3), 29.80 (2CH3), 30.66 (4CH3),
58.20 (2C), 58.57 (2C), 64.22 (2C), 64.51 (2C), 78.54 (2C-5), 78.71 (2C-7), 248.18 (2C=S), 248.39
(2C=S) ppm. C16H24S6 (408.75): calculated, C 47.01, H 5.92, S 47.07; found, C 46.91, H 6.15,
S 46.81.
4,4-Dimethyl-5-(propan-2-ylidene)-1,2-dithiolane-3-thione (18). Yields: Procedure I—(a) En-
try C: yield: 5% (method A); (b) Entry D: yield: 2% (method A). Yellow-orange oil (ref. [21],
1
yellow oil). H-NMR:
δ
1.66 (s, 2CH3), 1.99 (s, CH3), 2.02 (s, CH3) ppm. 13C-NMR:
δ
21.4
(CH3), 26.4 (CH3), 29.6 (2CH3), 64.2 (C-4), 128.2 (=C), 137.10 (=C), 247.9 (C=S) ppm.
1,1,3,3-Tetramethyl-5,6,7,8,9,10-hexathiaspiro[3.6]decane-2-thione (19). Yield: Procedure
1
I—(a) Entry D: 7 mg (4%) (method B). Pink solid, m.p. 111-114 ◦C (MeOH/CH2Cl2). H-
NMR:
δ δ 22.5, 28.6 (2CH3 each), 70.6 (C-1, C-3), 95.6
1.54 (s, br, 4CH3) ppm. 13C-NMR:
(C-4), 274.2 (C=S) ppm. C8H12S7 (332.64): calculated, C 28.89, H 3.64, S 67.48; found, C
29.11, H 3.70, S 67.18.
3.5. General Procedures for Sulfurization of Thiochalcones 3 with Elemental Sulfur (S8)
3.5.1. Procedure I: Ph3P/Acetone
In a two-necked round-bottomed flask (10 mL) equipped with a magnetic stirrer
0.5 mmol of the corresponding thiochalcone 3a–d, 0.125 mmol of elemental sulfur (S8)
(1 mmol calculating on atomic [S]) and 0.125 mmol of triphenylphosphine (Ph3P) were
placed and 2 mL of dry acetone were added. The resulting mixture was heated to the
reflux under condenser and under argon and stirred for the appropriate time (discoloring).

Molecules 2021, 26, 822
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Then, the solvent was evaporated in vacuo and the residue was purified, firstly by short
column chromatography and afterwards by thin-layer chromatography, by using SiO2 as
the absorbent and a mixture of petroleum ether and dichloromethane (9:1) as the eluent,
yielding the corresponding 3H-1,2-dithiole derivative 26a–d. Reported yields refer either
to isolated amounts of products 26 (Method A) or to amounts calculated on the basis of
standard analysis performed with weighted amounts of Cl2CH–CHCl2 added to the crude
mixture (method B).
3.5.2. Procedure II: PhSK/Acetone
In analogy to Procedure I, thiochalcone 3a was reacted with elemental sulfur in the
presence of cat. amounts (0.06 mol-equiv.) of potassium thiophenolate (PhSK) in boiling
acetone (see ref. [3,4]).
3.5.3. Procedure III: Ph3P/Butanone
In analogy to Procedure I, thiochalcone 3a was reacted with elemental sulfur in the
presence of cat. amounts of PPh3 using butanone as a solvent.
3.5.4. Procedure IV: CsF/DMF
Thiochalcones 3a or 3c, (1 mmol) and 64 mg (2.0 mmol) of sulfur were stirred mag-
netically in dry DMF (2.5 mL) with cat. amounts of freshly calcined cesium fluoride (CsF).
After 72h the reaction solution was diluted with dichloromethane (25 mL) and extracted
several times with small portions of water for removal of DMF. Combined organic layers
were dried over MgSO4, filtered and purified by column chromatography on silica gel
using a 95:5 mixture of petroleum ether and dichloromethane as eluent.
3.5.5. Product Characterization
3,5-Diphenyl-3H-1,2-dithiole (26a). Yields: (a) Procedure I—51 mg (40%) (method A),
63% (method B); (b) Procedure II—53 mg (41%) (method A); (c) Procedure III—19 mg (15%)
(method A); Procedure IV: 38 mg (15%) (method A). Orange-red solid, m.p. 78–81 ◦C. 1H-
NMR:
7.39–7.44 (m, 5H, CHarom.); 7.49–7.53 (m, 2H, CHarom.); 7.57–7.61 (m, 2H, CHarom.) ppm.
13C-NMR:
63.7 (C-3); 120.7 (C-4); 127.4, 127.5, 128.4, 128.8 129.0, 129.3 (10Carom.); 132.9
δ 5.87 (d, J = 3.0 Hz, 1H, CH); 6.19 (d, J = 3.0 Hz, 1H, CH); 7.34–7.38 (m, 1H, CHarom.);
δ
(C-5); 140.8, 145.2 (2Carom.) ppm. C15H12S2 (256.39): calculated, C 70.27, H 4.72, S 25.01;
found: C 70.20, H 4.68, S 25.01.
3-(4-Chlorophenyl)-5-phenyl-3H-1,2-dithiole (26b). Yield: (a) Procedure I—22 mg (15%)
1
(method A). Red oil. H-NMR:
δ
5.80 (d, J = 3.6 Hz, 1H, CH); 6.15 (d, J = 3.6 Hz, 1H, CH);
7.36 (d, J = 9.0 Hz, 2H, CHarom.), 7.39–7.45 (m, 5H, CHarom.), 7.56–7.59 (m, 2H, CHarom.)
ppm. 13C-NMR:
δ
62.7 (C-3); 120.1 (C-4); 127.4, 128.8, 129.1, 129.4 (9Carom.); 132.7 (C-5);
134.2, 139.4, 145.7 (3Carom.) ppm. C15H11S2Cl (290.83): calculated, C 61.95, H 3.81, S 22.05;
found: C 61.68, H 3.85, S 22.01.
3-(4-Methylphenyl)-5-phenyl-3H-1,2-dithiole (26c). Yield: (a) Procedure I—27 mg (20%)
(method A); Procedure IV—46 mg (17%) (method A). Red solid, m.p. 79–82 ◦C. 1H-NMR:
δ 2.39 (s, 3H, CH3); 5.86 (d, J = 3.3 Hz, 1H, CH); 6.18 (d, J = 3.3 Hz, 1H, CH); 7.21, 7.59 (2d,
J = 8.4 Hz, 4H, AB system), 7.38–7.42 (m, 5H, CHarom.) ppm. 13C-NMR:
δ 21.2 (CH3), 63.5
(C-3), 120.9 (C-4), 127.4, 128.7, 129.2, 129.6, (9Carom.); 133.0 (C-5), 137.8 138.3, 145.0 (3Carom.)
ppm. C16H14S2 (270.41): calculated, C 71.07, H 5.22, S 23.72; found: C 70.92, H 5.43, S 23.61.
3-(4-Methoxyphenyl)-5-phenyl-3H-1,2-dithiole (26d). Yield: (a) Procedure I—17 mg (12%)
1
(method A). Red oil. H-NMR:
δ
3.84 (s, 3H, OCH3); 5.87 (d, J = 3.6 Hz, 1H, CH); 6.17 (d,
J = 3.6 Hz, 1H, CH); 6.93 (d, J = 9.0 Hz, 2H, CHarom.), 7.38–7.44 (m, 5H, CHarom.), 7.57–7.60
(m, 2H, CHarom.) ppm. 13C-NMR:
55.4 (OCH3), 63.3 (C-3), 114.3 (C-4), 121.0, 127.4, 127.7,
127.8, 129.21 (9Carom.); 132.9 (C-5), 133.0, 144.8, 159.7 (3Carom.) ppm.
δ

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4. Conclusions
The presented study showed that fluoride anion can be applied as an excellent ac-
tivator of elemental sulfur in sulfurization reactions of easily available cycloaliphatic
thioketones derived from 2,2,4,4-tetramethylcyclobutane-1,3-dione. Depending on the
molar ratio of the starting materials, sulfur-rich heterocycles with variable ring size can
be obtained in satisfactory to good yields. In situ-generated fluoropolysulfide anions act
as powerful sulfurizing reagents. As a key intermediate in the studied reactions, three-
membered, reactive dithiiranes, formed via the addition of the latter to the C=S group, are
postulated for both cycloaliphatic and aromatic thioketones.
In contrast to thioketones, their α,β-unsaturated analogues, i.e., thiochalcones, do not
undergo the sulfurization reaction with sulfur in the presence of fluoride anion. On the
other hand, their sulfurization with elemental sulfur, leading to 3H-1,2-dithiole derivatives,
can be performed using triphenylphosphine (PPh3) as a catalyst. The latter heterocycles
are of interest as unique starting materials for the preparation of sulfur-heterocycles based
persistent radicals [32,33]. However, up to now, methods for the synthesis of 3H-1,2-
dithioles and their conversion into the stable organic radicals are rarely reported and they
are described only in rather remote literature [34].
The developed protocols of sulfurization in the presence of fluoride anion can be of
interest not only for the synthesis of sulfur-rich heterocycles, such as 1,2,4-trithiolanes [28],
1,2,4,5-tetrathianes [35
rich polymers starting with alkyl- [37
,
36] or 1,2,3,5,6-pentathiepanes, but also for the preparation of sulfur-
38] or aryl [39] substituted thiiranes. In the present
,
work, fluoride anion was shown to act as an alternative, nucleophilic catalyst and can
replace smelly and unstable sodium (or potassium) thiophenolate in the activation of
elemental sulfur in reactions with thiiranes. The presented research should be considered
as a new contribution to our continuous studies on exploration of elemental sulfur and
small-ring, congested S-heterocycles (thiaziridiens, thiiranes) in sulfurization reactions of
diverse organic compounds, including stable thioketones [10
,22,24,30] but also transient
nucleophilic heterocyclic carbenes (NHC) [40,41].
Supplementary Materials: The Supplementary Materials are available online and they contain the
scanned 1H- and 13C-NMR spectra for the described and isolated compounds. The re-determined
X-ray crystallography data for compound 7a are deposited as CSD Communication under deposition
number 2056867 (doi:10.5517/ccdc.csd.cc271bk6).
Author Contributions: G.M.—project foundation, laboratory work coordination and consultancy;
founds availability; reference checking and collection; manuscript preparation; J.W.—laboratory
work, collection of spectroscopic data, the manuscript and SI part preparation; K.U.—part of the
laboratory work, manuscript preparation; D.M.B.—consultancy and manuscript control; H.H.—
consultancy, manuscript preparation. All authors have read and agreed to the published version of
the manuscript.
Funding: The work was supported by the National Centre for Research and Development (Warsaw,
Poland) within the Grant InterChemMed (grant # WND-POWR.03.02.00-00-I029/16-01) and in part
by the NSC (GM, Grant Beethoven-2; grant #2016/23/G/ST5/04115/l, National Science Center,
Cracow, Poland).
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: All data supporting the presented study are included into the Supple-
mentary Material part.
Acknowledgments: Re-determination of the X-ray structure of 1,2,3-5,6-pentathiepane 7a by An-
thony Linden (University of Zurich) is acknowledged. The authors also thank Paulina Stefaniak, MSc.
(University of Lodz) for skillful performance of a part of laboratory work related to sulfurization reac-
tions performed in DMF solution. G.M. acknowledges National Science Center (Grant Beethoven-2,
#2016/23/G/ST5/04115/l, Cracow, Poland) for partial support of the presented study relating to

Molecules 2021, 26, 822
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the problem of sulfurization of reactive intermediates using elemental sulfur. J.W. acknowledges
National Centre for Research and Development (Warsaw, Poland) for a stipend.
Conflicts of Interest: Authors do not report any conflict of interest.
Sample Availability: Samples of the compounds 5a
and 26a-26d are available from the authors.
, 6a,b,e, 7a-7c, 13-15, 16a-16b, meso-17, d,l-17, 19,
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