Solvent-catalyzed umpolung carbon–sulfur bond-forming reactions by nucleophilic addition of thiolate and sulfinate ions to in situ–derived nitrosoalkenes in deep eutectic solvents

Article abstract of DOI:10.1016/j.crci.2017.01.008

The low transition temperature mixture formed by lactic acid and choline chloride proved to be effective for an umpolung carbon–sulfur bond formation at the α-position of α-chloro oximes. Aliphatic, aromatic, and heteroaromatic thiolate and sulfinate ions

Full text of DOI:10.1016/j.crci.2017.01.008

C. R. Chimie xxx (2017) 1e7
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Full paper/Memoire
Solvent-catalyzed umpolung carbonesulfur bond-forming
reactions by nucleophilic addition of thiolate and sulfinate
ions to in situederived nitrosoalkenes in deep eutectic
solvents
Giuseppe Dilauro, Luciana Cicco, Filippo Maria Perna, Paola Vitale,
Vito Capriati*
ꢁ
Dipartimento di FarmaciaeScienze del Farmaco, Universita degli Studi di Bari “Aldo Moro”, Consorzio C.I.N.M.P.I.S., Via Edoardo Orabona,
4, 70125 Bari, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
The low transition temperature mixture formed by lactic acid and choline chloride proved
Received 7 November 2016
Accepted 19 January 2017
Available online xxxx
to be effective for an umpolung carbonesulfur bond formation at the
a-position of a-
chloro oximes. Aliphatic, aromatic, and heteroaromatic thiolate and sulfinate ions can be
smoothly added to in situederived nitrosoalkenes affording the corresponding sulfeny-
lated or sulfonylated adducts, respectively, in a very good yield (up to >98%). This meth-
odology offers the advantage of working at room temperature and under air in
biodegradable and cost-effective reaction mixtures, which can be used both as solvents
and catalysts (20 mol %), thereby avoiding the use of anhydrous, hazardous volatile organic
solvents and an inert atmosphere.
Keywords:
Deep eutectic solvents
a
-Chloro oximes
Nitrosoalkenes
Umpolung
© 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Sulfenylation
Sulfonylation
Green chemistry
1. Introduction
against a variety of diseases [5]. Significant progress has
been achieved throughout the years in forging CeS bonds
The carbonesulfur (CeS) bond formation holds
a
mainly exploiting metal-catalyzed and asymmetric orga-
nocatalytic strategies which, however, still make use of
toxic and hazardous volatile organic solvents (e.g., benzene,
toluene, THF, CH2Cl2, MeCN, Et2O, and so forth) with critical
issues from an environmental point of view [6]. On the
other hand, small organic molecules (e.g., secondary and
tertiary amines, thiourea derivatives, phosphines, and so
forth) have proven to be effective in promoting non-
enantioselective organocatalytic CeS bond formation such
as sulfa-Michael additions [7], thiolysis of epoxides and
aziridines [8], and thioesterification reactions [9] also in
ionic liquids, in water, and under solvent-free conditions.
Recently, Coltart et al. [10] have reported an interesting
prominent position in the preparation of valuable and
attractive synthetic intermediates, because many sulfeny-
lated compounds are known to play a crucial role in pri-
mary metabolism of a wide range of living organisms [1]
and are, at the same time, privileged structural motifs in
many synthetic drugs [2], bioactive natural products [3],
and functional materials [4]. Sulfenylated heterocycles have
also attracted considerable attention from both industry
and academia because of their presence in many biologi-
cally active small molecules and their therapeutic value
asymmetric organocatalytic
a-sulfenylation of ketones that
* Corresponding author.
E-mail address: vito.capriati@uniba.it (V. Capriati).
proceeds in an umpolung fashion relative to conventional
http://dx.doi.org/10.1016/j.crci.2017.01.008
1631-0748/© 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: G. Dilauro, et al., Solvent-catalyzed umpolung carbonesulfur bond-forming reactions by
nucleophilic addition of thiolate and sulfinate ions to in situederived nitrosoalkenes in deep eutectic solvents, Comptes Rendus
Chimie (2017), http://dx.doi.org/10.1016/j.crci.2017.01.008

2
G. Dilauro et al. / C. R. Chimie xxx (2017) 1e7
enolate/azaenolate methods [10]. In this transformation,
simple thiols have been added in the presence of a catalyst
to in situederived nitrosoalkenes 2, generated by treating
2. Results and discussion
We initiated our study by investigating, as a model re-
the corresponding
a-chlorinated oximes 1 with a base, to
action, the one-pot sulfenylation of cyclic
a-chloro oxime
give -sulfenylated oximes 3, which could be finally elabo-
a
1a with sodium thiophenolate 4a for the preparation of a-
rated to the corresponding sulfenylated ketones or undergo
other transformations (Scheme 1). The nature of the solvent
was proven to be crucial for final product yield, and the best
results were achieved using anhydrous CH2Cl2 and carrying
out the reaction under a slight static pressure of argon.
Natural deep eutectic solvents (DESs) represent an
emerging generation of green and unconventional reaction
media generally composed of two or three safe and inex-
pensive components, which are able to engage in hydrogen-
bond interaction with each other to form a eutectic mixture
with a melting point much lower than that of either of the
individual components [11]. They are also known as “low
transition temperature mixtures” (LTTMs) because many of
them do not exhibit clear eutectic melting points, but
glass transitions [11f]. Thanks to their extraordinarily biode-
gradability, biocompatibility, negligible vapor pressure,
nonflammability, high thermal stability, tunable physico-
chemicalproperties,andtheeasinessofpreparationbygentle
thermal mixing, which requires no further purification, they
are progressively replacing volatile organic solvents in many
fields of science with interesting and somewhat unexpected
results [11len], and thus they are capturing more and more
the interest of academic and industrial community.
To the best of our knowledge, there are only a few ex-
amples of sulfenylation reactions run in DESs reported in
the literature: (1) a CeS bond formation via a one-pot re-
action of alkyl halides, thiourea, and electron-deficient
olefins using the choline chloride (ChCl)eurea DES both
as the reaction medium and catalyst [12], (2) the ring
opening of a variety of epoxides by thiols (and other nu-
cleophiles) using the eutectic mixture ChCleSnCl2 as a
solvent and a catalyst [13], and a catalyst-free multicom-
ponent synthesis of various sulfenylated 4H-chromenes in
a ChCl-ureaebased DES [14].
sulfenylated adduct 3a (Table 1). A preliminary reaction run
in CH2Cl2 was done for comparison. After stirring a mixture
of 1a (1.0 mmol), Et3N (1.1 mmol), and 4a (2.0 mmol) in
CH2Cl2 (1.5 mL) at RT and under air, followed by quenching
after 1.5 h with a saturated aqueous NH4Cl solution, the
desired adduct 3a was formed in 75% yield. Under these
conditions, however, a
noted to compete, and
b
-elimination reaction was also
-unsaturated oxime 5 could be
a
,b
additionally isolated as a byproduct (20% yield) (Table 1,
entry 1). Disappointedly, when the aforementioned
mixture was vigorously stirred at RT and under air in a type
III archetypal DES [11c], namely ChCleglycerol (Gly) (1:2)
(1.5 g per 1.0 mmol of 1a), the reaction resulted in only
formation of 5 (50% yield; the remaining being starting
material only), either after 1.5 h or after a prolonged reac-
tion time of 24 h (Table 1, entries 2,3).
As pointed out in Section 1, DESs are unconventional
fluids characterized by strong intermolecular hydrogen-
bonding interactions between their components. We
anticipated that hydrogen bond catalysis provided by sol-
vents with stronger H-bond donors might contribute to
better increase the electrophilic character at the a-carbon of
the in situeformed nitrosoalkenes. Thus, a second set of
experiments was performed in more acidic DES mixtures
[11b]. After mixing the aforementioned reagents thor-
oughly in a L-tartaric acideChCl (1:2) DES mixture for 24 h
at 100 ꢀC (because of the high-viscosity medium), sulfeny-
lated oxime 3a was formed in 10% yield but as the sole
product (Table 1, entry 4). Such a percentage could be pro-
gressively increased up to 49% using
LTTMs in combination with -glucose,
L
-lactic acidebased
D
L-alanine, and ChCl,
and working at RT (Table 1, entries 5e7). On the other hand,
a higher temperature (50 ꢀC) proved to be strongly detri-
mental for the chemical yield of 3a (10%) (Table 1, entry 8).
Remarkably, upon switching from Et3N to NaHCO3 as the
base, the desired adduct 3a could be isolated in 90% yield
Inspired by the results of Coltart et al. [10], and building
on our recent findings in using DESs as nonconventional
reaction media for exploring novel paradigms in fields of
organometallics, catalysis, and solar technologies [15], in
from a L-lactic acideChCl (2:1) LTTM [11g] working at RT
and after a reaction time of only 1.5 h (Table 1, entry 9); no
other byproducts could be detected. It is worth noting that
by replacing 4a with simple thiophenol, a significant drop in
the formation of 3a was noticed: 43% (Table 1, entry 10). By
reacting 1a with 4a (2 equiv) without any base, the expected
adduct 3a was again formed, albeit in a slightly reduced
yield (80%) (Table 1, entry 11). A similar result in terms of
yield was obtained upon switching to a more basic eutectic
mixture, such as ChCleurea (2:1) (Table 1, entry 12). By
running the reaction with an equimolar amount of both
NaHCO3 (1 equiv) and 4a (1 equiv), adduct 3a was formed in
44% yield only. The latter yield could be increased to 54% by
increasing the amount of base up to 2 equiv (Table 1, entries
13,14). Thus, both the electrophilic character of the sub-
strate and the nucleophilicity/amount of the thiolate, jointly
with the correct choice/amount of the base to generate the
putative nitrosoalkene, are all important factors to allow the
sulfenylation reaction to take place in high yields in an
this report we establish that sulfenylation of a-chlorinated
oximes can be safely and conveniently carried out also using
DESs as privileged and environmentally friendly solvents in
reactions run at room temperature (RT) and under air.
Scheme 1. Catalytic umpolung sulfenylation of
a-chloro oximes.
acidic L-lactic acidebased LTTM at RT and under air.
Please cite this article in press as: G. Dilauro, et al., Solvent-catalyzed umpolung carbonesulfur bond-forming reactions by
nucleophilic addition of thiolate and sulfinate ions to in situederived nitrosoalkenes in deep eutectic solvents, Comptes Rendus
Chimie (2017), http://dx.doi.org/10.1016/j.crci.2017.01.008

G. Dilauro et al. / C. R. Chimie xxx (2017) 1e7
3
Table 1
Survey of conditions for a-sulfenylation of a
-chloro oxime 1aa.
Entry
Solvent
T (ꢀC)
t (h)
Base
Yield (%) 3ab
1
2
3
4
5
6
7
8
CH2Cl2
25
25
25
100
25
25
25
50
25
25
25
25
25
25
25
1.5
1.5
24
24
24
24
24
24
1.5
1.5
1.5
1.5
1.5
1.5
1.0
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
75c
NRe,f
NRe,f
10
30
35
ChCl/Glyd
ChCl/Glyd
L
L
L
L
L
L
L
L
-Tartaric acid/ChClg
-Lactic acid/
-Lactic acid/
D
-glucoseh
-alaninei
L
-Lactic acid/ChClj
-Lactic acid/ChClj
-Lactic acid/ChClj
-Lactic acid/ChClj
-Lactic acid/ChClj
49
10
9
NaHCO3
NaHCO3
el
90
10
11
12
13
14
15
43k
80
Urea/ChClj
el
80
44
-Lactic acid/ChClj
-Lactic acid/ChClj
-Lactic acid/ChClj
NaHCO3
NaHCO3
NaHCO3
m
n
L
L
L
54
>98o
a
Reaction conditions:
a
-chloro oxime 1a (1.0 mmol), base (1.1 mmol), sodium thiophenolate 4a (2.0 mmol); DES mixture: 1.5 g per 1.0 mmol of 1a.
b
Isolated yield by column chromatography on silica gel.
Compound 5 was also isolated in 20% yield.
1:2 mol/mol.
c
d
e
f
No reaction.
Compound 5 was isolated in 50% yield as the sole product.
1:2 mol/mol.
5:1 mol/mol.
9:1 mol/mol.
2:1 mol/mol.
Thiophenol was used in place of 4a.
Sodium thiophenolate 4a: 2 equiv.
Sodium thiophenolate 4a: 1 equiv, NaHCO3: 1 equiv.
Sodium thiophenolate 4a: 1 equiv, NaHCO3: 2 equiv.
In this reaction, only 20 mol % DES was used under sonication.
g
h
i
j
k
l
m
n
o
With the optimized conditions in hand, we next turned
our attention to investigate the scope of this atom-
economy reaction with various combinations of thiolates
and a-chloro oxime 1a, and results are reported in Scheme
2. We were pleased to find that assorted aliphatic and
heteroaromatic thiolates 4bee all proved to be competent
sonicating bath [17]. The complete disappearance of the
starting oxime took place after 1 h of stirring, as revealed by
GCeMS analysis. Pleasingly, the desired adduct 3a could be
isolated in almost quantitative yield (>98%) by simple
dilution of the mixture with equal volume mixture of water
and Et2O, followed by separation of the organic layer and
removal of the solvent under reduced pressure (Table 1,
entry 15). It is worth noting that the same reaction run
without the aforementioned LTTM, under solvent-free
conditions, gave only starting materials after 1 h. This
observation is consistent with the catalytic effect provided
by LTTM in this reaction. A plausible mechanism of forma-
partners straightforwardly providing the expected
a-sul-
fenylated adducts 3bee in very good yields (70e90%) at RT
and under air (Scheme 2).
Recently, there has been a growing interest in finding
novel applications of DESs both as sustainable media and
catalysts for organic transformations [11j,k]. Indeed,
hydrogen bond catalysis promoted by “noninnocent” DESs
has been proven to be responsible for the increase in reac-
tion rate observed in several multicomponent and hetero-
cyclodehydration processes as well as in conjugate addition
reactions [16]. Thus, we next investigated the possibility of
tion of compounds 3 from a-chloro oximes 1 and thiolates 4,
highlighting the active role played by LTTM components in
increasing the electrophilic character of the in situ-formed
nitrosoalkenes 2, is depicted in Scheme 3.
With the aim to extend the scope of this protocol even
conducting
a
one-pot sulfenylation by considerably
more, thiolates 4aee were also reacted with the acyclic a-
reducing the amount of the aforementioned DES. On the
basis of this, the formation of 3a was reinvestigated by using
only 20 mol % of L-lactic acideChCl (2:1) and without any
additional cosolvent. Because of the high viscosity of the
reaction medium at RT, the reactionwas runwith the aid of a
chloro oxime1b exposingthe mixture tothe aforementioned
catalytic sulfenylation conditions, under sonication at RTand
under air for 1 h. All reactions proved to be extraordinarily
clean affording the anticipated adducts 3fej in very good
yields (60e90%) and with no other byproducts (Scheme 4).
Please cite this article in press as: G. Dilauro, et al., Solvent-catalyzed umpolung carbonesulfur bond-forming reactions by
nucleophilic addition of thiolate and sulfinate ions to in situederived nitrosoalkenes in deep eutectic solvents, Comptes Rendus
Chimie (2017), http://dx.doi.org/10.1016/j.crci.2017.01.008

4
G. Dilauro et al. / C. R. Chimie xxx (2017) 1e7
Scheme 2. Scope of the
a-sulfenylation reaction with various thiolates.
Scheme 3. Plausible mechanism for the formation of sulfenylated products 3 under LTTM catalysis.
Scheme 4. Scope of the a-sulfenylation reaction under catalytic conditions.
Please cite this article in press as: G. Dilauro, et al., Solvent-catalyzed umpolung carbonesulfur bond-forming reactions by
nucleophilic addition of thiolate and sulfinate ions to in situederived nitrosoalkenes in deep eutectic solvents, Comptes Rendus
Chimie (2017), http://dx.doi.org/10.1016/j.crci.2017.01.008

G. Dilauro et al. / C. R. Chimie xxx (2017) 1e7
5
Scheme 5. Direct sulfonylation of a-chloro oximes under catalytic conditions.
Finally, we have also briefly explored the feasibility of
(1.35 mmol) was added at RT, under air, and vigorous stir-
ring. After 1.5 h, saturated aqueous NH4Cl (3 mL) was added
and the reaction mixture was extracted with Et2O
(3 ꢁ 5 mL), and the combined organic extracts were
washed with brine, dried over anhydrous Na2SO4, filtered,
and concentrated in vacuo. The crude product was purified
by chromatography over silica gel using 20:80 EtOAc/hex-
using sulfinate ions, which are ambident nucleophiles but
with a reactivity much smaller than that of thiolates, as
partners in CeS bond-forming reactions [18]. They are
known to react with various electrophiles either at the
sulfur atom (soft nucleophilic center) to give sulfonyl de-
rivatives or at the oxygen end (hard nucleophilic center) to
lead to sulfinate esters. Thus, sulfinate ion 6 was reacted at
ane as the solvent to give the desired a-sulfenylated oximes
RT and under air with
combining ultrasound and the LTTM
a
-chloro oximes 1a,b synergistically
-lactic acideChCl
3aej.
L
(2:1) (20 mol %) in the presence of NaHCO3. Both reactions
occurred at the sulfinate sulfur, thereby providing sulfone
derivatives 7a,b in high yields (72% to >98%) (Scheme 5). As
far as we are aware, these represent the first examples of
direct sulfonylation of organic substrates performed in low
melting mixtures under catalytic conditions.
4.2. Ultrasound-mediated synthesis of a-sulfenyl oximes
under solvent-free conditions: general procedure
a
-Chlorinated oxime (0.7 mmol), NaHCO3 (0.77 mmol),
sodium thiolate (1.4 mmol), and 20 mol % of DES or LTTM
were mixed in a 10 mL round-bottomed flask. The reaction
mixture was irradiated in a water bath of an ultrasonic
cleaner (frequency, 40 kHz; nominal power, 50 W) for 1 h at
RT, and saturated aqueous NH4Cl (3 mL) was added. The
reaction mixture was extracted with Et2O (3 ꢁ 5 mL), and
the combined organic extracts were washed with a satu-
rated aqueous solution of NaCl, dried over anhydrous
Na2SO4, filtered, and concentrated in vacuo. The crude
product was purified by chromatography over silica gel
using 20:80 EtOAc/hexane as the solvent to give the desired
3. Conclusions
In this work, we report a simple and effective green
protocol to perform a direct addition of thiolates, at RT and
under air, to in situederived nitrosoalkenes from a-chloro
oximes using, for the first time, an LTTMformed bylactic acid
and ChCl as an environmentally friendly unconventional
solvent. This umpolung sulfenylation reaction, which can
also be carried out under catalytic conditions (20 mol %
LTTM) with the aid of ultrasound, allows the preparation in
a
-sulfenylated oximes 3a,3fej.
very good yields (up to >98%) of a variety of a-sulfenylated
4.3. Synthesis of -sulfonylated oxime 7a: typical procedure
a
oximes (aliphatic, aromatic, and heteroaromatic) starting
from cyclic and acyclic scaffolds. Furthermore, this proced-
ure also offers a new scope for umpolung sulfonylation at the
a
-Chlorinated oxime 1a (148 mg, 1 mmol), NaHCO3
(92 mg, 1.1 mmol), sodium benzenesulfinate (328 mg,
2 mmol), and -lactic acideChCl (1:2 mol/mol) (64 mg,
a-carbon position of carbonyl compounds. Studies of the
L
development of an asymmetric carbonesulfur bond forma-
tion using eutectic mixtures as eco-friendly and sustainable
solvent/catalyst systems in organic transformations are un-
derway and results will be reported in due course.
0.2 mmol) were mixed in a 10 mL round-bottomed flask.
The reaction mixture was irradiated in a water bath of
an ultrasonic cleaner (frequency, 40 kHz; nominal
power, 50 W) for 1 h at RT, and then saturated aqueous
NH4Cl (3 mL) was added. The reaction mixture was
extracted with Et2O (3 ꢁ 5 mL), and the combined
organic extracts were washed with a saturated aqueous
solution of NaCl, dried over anhydrous Na2SO4, filtered,
and concentrated in vacuo. The crude product was pu-
rified by chromatography over silica gel using 20:80
4. Experimental section
4.1. Synthesis of
procedure
a-sulfenyl oximes in DESs or LTTMs: general
EtOAc/hexane as the solvent to give the desired
a
-sul-
To a mixture of
a-chlorinated oxime (0.67 mmol) and
fonylated oxime 7a in a quantitative (>98%) yield
NaHCO3 (0.74 mmol) in 1 g of DES or LTTM, sodium thiolate
(271 mg, 0.985 mmol).
Please cite this article in press as: G. Dilauro, et al., Solvent-catalyzed umpolung carbonesulfur bond-forming reactions by
nucleophilic addition of thiolate and sulfinate ions to in situederived nitrosoalkenes in deep eutectic solvents, Comptes Rendus
Chimie (2017), http://dx.doi.org/10.1016/j.crci.2017.01.008

6
G. Dilauro et al. / C. R. Chimie xxx (2017) 1e7
4.4. Spectroscopic data
4.4.5. (Z)-2-(Benzo[d]thiazol-2-ylthio)-1-phenylethanone
oxime (3h)
White solid, mp 176e178 ꢀC, 60% yield. 1H NMR
(600 MHz, CDCl3): 4.83 (s, 2H), 7.10e7.12 (m, 2H), 7.26
e7.28 (m, 2H), 7.44e7.48 (m, 3H), 7.77e7.79 (m, 2H). 13C
NMR (125 MHz, CDCl3): 26.9, 112.2, 121.4, 124.6, 126.8,
a
-Chlorinated oximes 1a,b [19] and a-sulfenylated ox-
imes 3a [19a], 3b [20], and 3d [19a] had analytical and
spectroscopic data identical to those previously reported.
d
Configuration of
a-sulfenylated and
a
-sulfonylated oximes
d
was determined by FT-IR experiments run in CHCl3 at a
variable concentration of oxime. In the case of Z-isomers,
the intramolecular hydrogen bonding stretching band with
the sulfur atom did not change its position significantly
even at high dilution, and thus was not altered by a change
in concentration.
127.1, 128.8, 129.9, 130.1, 134.2, 140.2, 155.1, 166.0. FT-IR
(film, cmꢂ1): 3133, 2964, 1596, 1496, 751, 698. HRMS
(ESI): calcd for C15H12N2OS2 [MþH]þ, 301.0464; found,
301.0435.
4.4.6. (Z)-2-(Thiophen-2-ylthio) acetophenone oxime (3i)
White solid mp 79e81 ꢀC, 88% yield. 1H NMR (600 MHz,
4.4.1. (Z)-2-(Benzothiazol-2-ylthio)cyclohexanone oxime (3c)
Yellow solid, mp 168e170 ꢀC, 83% yield. 1H NMR
CDCl3):
d
4.12 (s, 2H), 6.92 (dd, J ¼ 4.8, 3.0 Hz, 1H), 7.12 (dd, J
¼ 3.6, 1.2 Hz, 1H), 7.33e7.39 (m, 4H), 7.57e7.58 (m, 2H),
(600 MHz, CDCl3):
d
1.66e1.69 (m, 1H), 1.83e1.88 (m, 2H),
8.37 (br s, 1H, exchanges with D2O). 13C NMR (125 MHz,
2.09e2.13 (m,1H), 2.30e2.34 (m,1H), 2.47e2.48 (m,1H), 2.68
e2.80 (m, 2H), 4.85 (t, J ¼ 5.4 Hz, 1H), 7.29 (t, J ¼ 7.8 Hz, 1H),
7.37 (t, J ¼ 7.8 Hz,1H), 7.74 (d, J ¼ 7.8 Hz,1H), 7.86 (d, J ¼ 7.8 Hz,
1H), 8.91 (br s, 1H, exchanges with D2O). 13C NMR (125 MHz,
CDCl3): d 32.4, 126.4, 127.5, 128.5, 129.5, 130.5, 132.9, 134.4,
135.4,155.2. FT-IR (film, cmꢂ1): 3228 (OH), 2913,1731,1454,
1417, 1400, 1316, 1301, 1052, 945. HRMS (ESI): calcd for
C
12H11NOS2 [MþH]þ, 250.0355; found, 250.0371.
CDCl3): d 22.8, 23.5, 25.4, 34.2, 49.5,120.9, 121.9, 124.4,125.9,
135.5, 153.1, 158,2, 165.0. FT-IR (film, cmꢂ1): 3274, 2932, 2859,
4.4.7. (Z)-2-[5-(Methylthio)-1,3,4-thiadiazol-2-ylthio]
acetophenone oxime (3j)
2361, 1654, 1455, 1427, 1261, 980. HRMS (ESI): calcd for
C
13H14N2OS2 [MþNa]þ, 301.0440; found, 301.0482.
White solid, mp 160e163 ꢀC, 86% yield. 1H NMR
(400 MHz, CDCl3):
d 2.75 (s, 3H), 4.66 (s, 2H), 7.32e7.41 (m,
4.4.2. (Z)-2-[5-(Methylthio)-1,3,4-thiadiazole-2-ylthio]
cyclohexanone oxime (3e)
3H), 7.63e7.71 (m, 2H), 8.73 (br s, 1H, exchanges with D2O).
13C NMR (125 MHz, CDCl3):
d 16.5, 27.2, 126.4, 128.8, 129.9,
White solid, mp 154e156 ꢀC, 70% yield. 1H NMR
133.7, 154.3, 163.8, 167.3. FT-IR (film, cmꢂ1): 3256 (OH),
2921, 2821, 1638, 1383, 1303, 1043, 948. HRMS (ESI): calcd
for C11H11N3OS3 [MþH]þ, 298.0137; found, 298.0167.
(600 MHz, CDCl3)
d 1.66e1.73 (m, 3H), 1.81e1.86 (m, 1H),
1.96e2.01 (m, 1H), 2.32e2.36 (m, 1H), 2.53e2.57 (m, 1H),
2.77 (s, 3H), 2.79e2.84 (m, 1H), 4.50 (dd, J ¼ 6.6, 4.8 Hz,1H),
7.85 (br s, 1H, exchanges with D2O). 13C NMR (125 MHz,
4.4.8. (Z)-2-(Phenylsulfonyl)cyclohexanone oxime (7a)
White solid, mp 151e154 ꢀC, 98% yield. 1H NMR
(600 MHz, CDCl3): d 1.33e1.41 (m, 1H), 1.67e1.86 (m, 2H),
1.96e1.98 (m, 1H), 2.10e2.18 (m, 1H), 2.30e2.36 (m, 1H),
2.71e2.74 (m, 1H), 3.22e3.24 (m, 1H), 3.76e3.78 (m, 1H)
7.52e7.55 (m, 2H), 7.61e7.65 (m, 1H), 7.80e7.82 (m, 2H),
7.96 (br s, 1H, exchanges with D2O). 13C NMR (125 MHz,
CDCl3): d 16.4, 22.9, 23.6, 25.3, 34.0, 50.6, 158.1, 163.0, 167.5.
FT-IR (film, cmꢂ1): 3323 (OH), 2942, 2864, 1648, 1602, 1387,
1043, 974, 728. HRMS (ESI): calcd for C9H13N3OS3 [MþH]þ,
276.0299; found, 276.0315.
4.4.3. (Z)-2-(Phenylthio)acetophenone oxime (3f)
White solid, mp 77e78 ꢀC, 77% yield. 1H NMR (600 MHz,
CDCl3): d 21.2, 22.2, 24.3, 25.6, 65.2, 128.7, 128.9, 133.7,
CDCl3):
d
4.26 (s, 2H), 7.22e7.24 (m, 1H), 7.26e7.29 (m, 2H),
137.8, 153.8. FT-IR (film, cmꢂ1): 3285, 2941, 2861,1791,1447,
1306, 1084. GCeMS (70 eV): m/z (%) 253 (Mþ, 2) 143 (29),
125 (13), 111 (100), 77 (44). HRMS (ESI): calcd for
7.37e7.41 (m, 3H), 7.42e7.45 (m, 2H), 7.59e7.61 (m, 2H),
8.98 (br s, 1H, exchanges with D2O). 13C NMR (125 MHz,
CDCl3):
d
28.5, 126.5, 127.0, 128.6, 128.9, 129.6, 131.0, 134.4,
C
12H15NO3S [MþH]þ, 254.0845; found, 254.0898.
135.4, 155.3. FT-IR (film, cmꢂ1): 3244, 3062, 2922, 1735,
1583, 1573, 1439, 1407, 950. HRMS (ESI): calcd for
C
4.4.9. (Z)-2-(Phenylsulfonyl)acetophenone oxime (7b)
14H13NOS [MþH]þ, 244.0800; found, 244.0788.
White solid, mp 156e158 ꢀC, 72% yield. 1H NMR
(600 MHz, CDCl3):
e7.46 (m, 2H), 7.55e7.62 (m, 3H), 7.82e7.85 (m, 3H, 1H,
exchanges with D2O). 13C NMR (125 MHz, CDCl3):
52.6,
d 4.73 (s, 2H), 7.33e7.38 (m, 3H), 7.42
4.4.4. 2-(Methylthio)-1-phenylethanone oxime (3g)
Colorless oil, inseparable mixture of diastereoisomers,
d
dr E:Z ¼ 1:1. 1H NMR (600 MHz, CDCl3):
d
2.11 (s, 3H), 2.16
126.6, 128.4, 128.6, 128.8, 129.9, 133.5, 133.8, 139.3, 147.9.
FT-IR (film, cmꢂ1): 3394, 3062, 2924, 1447, 1308, 1157, 1308,
1157, 1134, 1085, 1055, 956, 745, 686. HRMS (ESI): calcd for
(s, 3H), 3.56 (s, 2H), 3.88 (s, 2H), 7.39e7.47 (m, 6H), 7.53
e7.55 (m, 2H), 7.68e7.70 (m, 2H), 8.69 (br s, 1H, exchanges
with D2O), 9.07 (br s, 1 H, exchanges with D2O). 13C NMR
C
14H13NO3S [MþNa]þ, 298.0508; found, 298.0501.
(125 MHz, CDCl3): d 15.1, 15.9, 26.2, 38.0, 126.4, 128.1, 128.3,
128.6, 129.4, 129.6, 132.1, 134.5154.8, 155.6. FT-IR (film,
cmꢂ1): 3303, 2919, 1631, 1435, 1304, 992, 750, 695. GCeMS
(70 eV): m/z (%) diastereoisomer with minor tR 181 (Mþ,
19), 135 (100), 103 (71), 91 (15), 77 (28); GCeMS (70 eV): m/
z (%) diastereoisomer with major tR 181 (Mþ, 35), 135 (100),
103 (95), 91 (17), 77 (36). HRMS (ESI): calcd for C9H11NOS
[MþH]þ, 182.0634; found, 182.0635.
Acknowledgments
This work was financially supported by the University of
Bari within the framework of the Project “Sviluppo di
nuove metodologie di sintesi mediante l'impiego di bio-
catalizzatori e solventi a basso impatto ambientale” (code:
Perna01333214Ricat) and the Interuniversities Consortium
Please cite this article in press as: G. Dilauro, et al., Solvent-catalyzed umpolung carbonesulfur bond-forming reactions by
nucleophilic addition of thiolate and sulfinate ions to in situederived nitrosoalkenes in deep eutectic solvents, Comptes Rendus
Chimie (2017), http://dx.doi.org/10.1016/j.crci.2017.01.008

G. Dilauro et al. / C. R. Chimie xxx (2017) 1e7
7
(b) H. Nambu, K. Hata, M. Matsugi, Y. Kita, Chem. Eur. J. 11 (2005)
719.
CINMPIS. The authors would like to thank Mr. Francesco
Messa for his contribution to the experimental section.
[10] J.M. Hatcher, M.C. Kohler, D.M. Coltart, Org. Lett. 13 (2011) 3810.
[11] For selected papers, see: (a) A.P. Abbott, G. Capper, D.L. Davies,
R.K. Rasheed, V. Tambyrajah, Chem. Commun. (2003) 70;
(b) A.P. Abbott, D. Boothby, G. Capper, D.L. Davies, R.K. Rasheed, J.
Am. Chem. Soc. 126 (2004) 9142;
Appendix A. Supplementary data
Supplementary data related to this article can be found
at http://dx.doi.org/10.1016/j.crci.2017.01.008
(c) A.P. Abbott, J.C. Barron, K.S. Ryder, D. Wilson, Chem. Eur. J. 13
(2007) 6495;
€
(d) C. Ruß, B. Konig, Green Chem. 14 (2012) 2969;
ꢀ ^
(e) Q. Zhang, K. De Oliveira Vigier, S. Royer, F. Jerome, Chem. Soc.
References
Rev. 41 (2012) 7108;
(f) M. Francisco, A. van den Bruinhorst, M.C. Kroon, Angew. Chem.,
Int. Ed. 52 (2013) 3074;
(g) M. Francisco, A. van den Bruinhorst, L.F. Zubeir, C.J. Peters,
M.C. Kroon, Fluid Phase Equilib. 340 (2013) 77;
(h) E.L. Smith, A.P. Abbott, K.S. Ryder, Chem. Rev. 114 (2014)
11060;
[1] (a) R.J. Cremlyn, An Introduction to Organosulfur Chemistry, John
Wiley & sons, Chichester, UK, 1996;
(b) J.R. Fraústo da Silva, R.J.P. Williams, The Biological Chemistry of
the Elements, Oxford University Press, New York, 2001.
[2] (a) L.A. Damani, Sulphur-containing Drugs and Related Organic
Compounds, Wiley, New York, 1989;
(b) A.J. Wilson, J.K. Kerns, J.F. Callahan, C.J. Moody, J. Med. Chem. 56
(2013) 7463.
[3] (a) A. Nudelman, The Chemistry of Optically Active Sulfur Com-
pounds, Gordon and Breach, New York, 1984;
(i) A. Paiva, R. Craveiro, I. Aroso, M. Martins, R.L. Reis, A.R.C. Duarte,
A.C.S. Sustain, Chem. Eng. 2 (2014) 1063;
(j) P. Liu, J.-W. Hao, L.-P. Mo, Z.-H. Zhang, RSC Adv. 5 (2015) 48675;
(k) D.A. Alonso, A. Baeza, R. Chinchilla, G. Guillena, I.M. Pastor,
ꢀ
D.J. Ramon, Eur. J. Org. Chem. (2016) 612;
ꢁ
(b) M.C. Qian, X. Fan, K. Mahattanatawee (Eds.), Volatile Sulfur
Compounds in Food, ACS Symposium Series 1068, American
Chemical Society, 2011.
ꢀ
ꢀ
(l) C. Vidal, J. Garcìa-Alvarez, A. Hernan-Gomez, A.R. Kennedy,
E. Hevia, Angew. Chem., Int. Ed. 53 (2014) 5969;
ꢁ
(m) J. Garcìa-Alvarez, E. Hevia, V. Capriati, Eur. J. Org. Chem. (2015)
[4] H. Liu, X. Jiang, Chem. Asian J. 8 (2013) 2546.
[5] For selected papers, see: (a) F. Cianchi, C. Cortesini, L. Magnelli,
E. Fanti, N. Papucci, L. Schiavone, A. Masserini, A. Vannacci,
S. Capaccioli, F. Perna, M. Lulli, V. Fabbroni, G. Perigli, P. Mechi,
E. Masini, Mol. Cancer Ther. 5 (2006) 2716;
6779;
ꢁ
(n) J. Garcìa-Alvarez, Eur. J. Inorg. Chem. (2015) 5147.
[12] N. Azizi, Z. Yadollahy, A. Rahimzadeh-Oskooee, Tetrahedron Lett. 55
(2014) 1722.
[13] N. Azizi, E. Batebi, Catal. Sci. Technol. 2 (2012) 2445.
[14] N. Azizi, M. Mariami, M. Edrisi, Dyes Pigments 100 (2014) 215.
[15] (a) V. Mallardo, R. Rizzi, F.C. Sassone, R. Mansueto, F.M. Perna,
A. Salomone, V. Capriati, Chem. Commun. 50 (2014) 8655;
(b) F.C. Sassone, F.M. Perna, A. Salomone, S. Florio, V. Capriati,
Chem. Commun. 51 (2015) 9459;
(b) G. De Martino, M.C. Edler, G. La Regina, A. Coluccia, M.C. Barbera,
D. Barrow, R.I. Nicholson, G. Chiosis, A. Brancale, E. Hamel,
R.J. Silvestri, J. Med. Chem. 49 (2006) 947;
(c) Y. Cai, J. Li, W. Chen, M. Xie, X. Liu, L. Lin, X. Feng, Org. Lett. 14
(2012) 2726;
(d) E. Marcantoni, R. Cipolletti, L. Marsili, S. Menichetti, R. Properzi,
C. Viglianisi, Eur. J. Org. Chem. (2013) 132;
(c) L. Cicco, S. Sblendorio, R. Mansueto, F.M. Perna, A. Salomone,
S. Florio, V. Capriati, Chem. Sci. 7 (2016) 1192;
(e) C. Viglianisi, E. Marcantoni, V. Carapacchi, S. Menichetti,
L. Marsili, Eur. J. Org. Chem. (2014) 6405;
(d) E. Massolo, S. Palmieri, M. Benaglia, V. Capriati, F.M. Perna,
Green Chem. 18 (2016) 792;
(f) Y. Siddaraju, K.R. Prabhu, J. Org. Chem. 81 (2016) 7838;
(g) J. Shanmugapriya, K. Rajaguru, S. Muthusubramaian,
N. Bhuvanesh, Eur. J. Org. Chem. (2016) 1963.
(e) R. Mancuso, A. Maner, L. Cicco, F.M. Perna, V. Capriati,
B. Gabriele, Tetrahedron 72 (2016) 4239;
(f) M. Capua, S. Perrone, F.M. Perna, P. Vitale, L. Troisi, A. Salomone,
V. Capriati, Molecules 21 (2016) 924;
(g) C.L. Boldrini, N. Manfredi, F.M. Perna, V. Trifiletti, V. Capriati,
A. Abbotto, Energy Technol. 5 (2017) 345;
[6] For selected papers, see: (a) J. Clayden, P. MacLellan, Beilstein J. Org.
Chem. 7 (2011) 582;
(b) I.P. Beletskaya, V.P. Anakinov, Chem. Rev. 111 (2011) 1596;
(c) T. Toru, C. Bolm (Eds.), Organosulfur Chemistry in Asymmetric
Synthesis, Wiley-VCH, Weinheim, Germany, 2008;
(d) P. Chauhan, S. Mahajan, D. Enders, Chem. Rev. 114 (2014) 8807.
[7] (a) P. Kotrusz, S. Toma, Molecules 11 (2006) 197;
(b) D. Lanari, R. Ballini, S. Bonollo, A. Palmieri, F. Pizzo, L. Vaccaro,
Green Chem. 13 (2011) 3181;
(h) D. Brenna, E. Massolo, A. Puglisi, S. Rossi, G. Celentano,
M. Benaglia, V. Capriati, Beilstein J. Org. Chem. 12 (2016) 2620.
[16] For selected papers, see: (a) B.S. Singh, H.R. Lobo, G. Subray,
S. Shankarling, Catal. Commun. 24 (2012) 70;
(b) S.T. Disale, S.R. Kale, S.S. Kahandal, T.G. Srinivasan, R.V. Jayaram,
Tetrahedron Lett. 53 (2012) 2277;
(c) S. Bonollo, D. Lanari, J.M. Longo, L. Vaccaro, Green Chem. 14
(2012) 164;
(d) A. Sarkar, S.R. Roy, A.K. Chakraborti, Chem. Commun. 47 (2011)
4538;
(c) A.K. Sanap, G.S. Shankarling, Catal. Commun. 49 (2014) 58;
(d) I. Hawkins, S.T. Handy, Tetrahedron 69 (2013) 9200;
(e) J. Lu, X.-T. Li, E.-Q. Ma, L.P. Mo, Z.-H. Zhang, ChemCatChem 6
(2014) 2854;
(e) N. Azizi, E. Saki, M.C.R. Edrisi, C. R. Chim. 14 (2011) 973.
[8] (a) R.-H. Fan, X.-L. Lou, J. Org. Chem. 68 (2003) 726;
(b) F. Fringuelli, F. Pizzo, S. Tortoioli, L. Vaccaro, Tetrahedron Lett.
44 (2003) 6785;
(f) H.-C. Hu, Y.-H. Liu, B.-L. Li, Z.-S. Cui, Z.-H. Zhang, RSC Adv. 5
(2015) 7720;
(g) P. Liu, J.-W. Hao, L.-P. Mo, Z.-H. Zhang, RSC Adv. 5 (2015) 48675.
[17] For recent papers dealing with the combination of DESs with ul-
trasonic radiation in organic synthesis, see: (a) B.S. Singh, H.R. Lobo,
D.V. Pinjari, K.J. Jarag, A.B. Pandit, G.S. Shankarling, Ultrason. Sono-
chem. 20 (2013) 287;
(b) U.N. Yadav, G.S. Shankarling, J. Mol. Liq. 195 (2014) 188.
[18] T. Okuyama, Sulfinate Ions as Nucleophiles, in: S. Patai (Ed.), John
Wiley & Sons Ltd, 1990, p. 639 ch. 22.
[19] (a) J.M. Hatcher, M.C. Kohler, D.M. Coltart, Org. Lett. 13 (2011)
3810;
(b) Y. Zhang, D. Stephens, G. Hernandez, R. Mendoza, O.V. Larionov,
Chem. Eur. J. 18 (2012) 16612.
[20] D.S. Ribeiro, P.R. Olivato, R. Rittner, Magn. Reson. Chem. 38 (2000)
627.
(c) J. Wu, H.-G. Xia, Green Chem. 7 (2005) 708;
(d) J. Wu, X. Sun, Y. Li, Eur. J. Org. Chem. (2005) 4271;
(e) F. Fringuelli, F. Pizzo, C. Vittoriani, L. Vaccaro, Eur. J. Org. Chem.
(2006) 1231;
(f) C.M. Kleiner, P.R. Schreiner, Chem. Commun. (2006) 4315;
(g) B.C. Ranu, T. Mandal, S. Banerjee, S.S. Dey, Aust. J. Chem. 60
(2007) 278;
(h) B.P. Bandgar, N.S. Joshi, V.T. Kamble, S.S. Sawant, Aust. J. Chem.
61 (2008) 231;
(i) M. Shailaja, A. Manjula, B.V. Rao, Synth. Commun. 40 (2010)
3629;
(j) A.K. Singh, R. Chawla, L.D.S. Yadav, Tetrahedron Lett. 54 (2013) 5099.
[9] (a) H. Nambu, K. Hata, M. Matsugi, Y. Kita, Chem. Commun. (2002)
1082;
Please cite this article in press as: G. Dilauro, et al., Solvent-catalyzed umpolung carbonesulfur bond-forming reactions by
nucleophilic addition of thiolate and sulfinate ions to in situederived nitrosoalkenes in deep eutectic solvents, Comptes Rendus
Chimie (2017), http://dx.doi.org/10.1016/j.crci.2017.01.008