Ionic liquids as an alternative reaction medium for HMDST based synthesis of thioaldehydes

Article abstract of DOI:10.1080/10426507.2015.1114487

Reaction of bis(trimethylsilyl)sulfide (HMDST) with aldehydes can be efficiently carried out in various ionic liquids, under CoCl₂.6H₂O or TfOTMF catalysis, leading to the formation of thioaldehydes, which are trapped as Diels-Alder

Full text of DOI:10.1080/10426507.2015.1114487

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
Ionic liquids as an alternative reaction medium for
HMDST based synthesis of thioaldehydes
Damiano Tanini, Andrea Angeli & Antonella Capperucci
To cite this article: Damiano Tanini, Andrea Angeli & Antonella Capperucci (2016) Ionic
liquids as an alternative reaction medium for HMDST based synthesis of thioaldehydes,
Phosphorus, Sulfur, and Silicon and the Related Elements, 191:2, 156-158, DOI:
10.1080/10426507.2015.1114487
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Date: 14 March 2016, At: 16:54

PHOSPHORUS, SULFUR, AND SILICON
, VOL. , NO. , –
http://dx.doi.org/./..
Ionic liquids as an alternative reaction medium for HMDST based synthesis of
thioaldehydes
Damiano Tanini, Andrea Angeli, and Antonella Capperucci
Dipartimento di Chimica “Ugo Schiff,”Università di Firenze, Sesto Fiorentino, Italy
ABSTRACT
ARTICLE HISTORY
Received  August 
Accepted  November 
Reaction of bis(trimethylsilyl)sulfide (HMDST) with aldehydes can be efficiently carried out in various ionic
liquids, under CoCl2.6H2O or TfOTMF catalysis, leading to the formation of thioaldehydes, which are trapped
as Diels-Alder cycloadducts. When 1,3-cycloheaxadiene was used, a stereoselective entry to the endo isomer
was always obtained.
KEYWORDS
Thioaldehydes; ionic liquids
(ILs); silyl sulfide; Diels-Alder
cycloadditions
GRAPHICAL ABSTRACT
elucidated their behaviour as heterodienophiles with acyclic and
cyclic dienes.
Introduction
Organic sulfur compounds play an important role in different
fields. They represent very reactive and efficient intermediates in
many chemical processes for the synthesis, for instance, of phar-
maceutically active compounds.1 Very recently, phenyl propyl
thioketone has been isolated from seagrasses and identified as a
novel antibacterial compound.2 They participate also in obtain-
ing molecules used in food chemistry as additives and aromas.3
In fact it is well known that chemicals which contain sulfur
atoms often have a peculiar odour, depending on the nature of
the sulfurated functional groups, i.e. sulfide, di- or higher sul-
fides, thiol, heterocyclic systems or thiocarbonyl derivatives.
In addition, it has been well established that the hetero Diels-
Alder reaction is a very useful method for the preparation of
six-membered heterocycles containing different heteroatoms,
including sulfur and selenium. In fact carbon-chalcogen dou-
ble bonds have been recognized as reactive groups, and in
particular thiocarbonyl derivatives represent very valuable com-
pounds to react as efficient heterodienophiles in cycloaddi-
tion reactions, including 1,3-dipolar cycloadditions.4 During
the course of our studies in the chemistry of thiocarbonyl
derivatives, we reported an efficient and direct conversion of a
carbonyl function into a thiocarbonyl group through the
reactivity with bis(trimethylsilyl)sulfide, (Me3Si)2S (HMDST).5
Using this procedure, we have successfully obtained a wide series
of thioaldehydes, thioketones and thioacylsilanes, and we have
Although other efficient methods for the direct conversion
6
=
=
of a C O into a C S group are described, such as for instance
the use of Lawesson’s reagent or H2S/HCl, the n-BuLi catalyzed
reaction of a silyl sulfide, to date the conversion of a carbonyl
group into a thiocarbonyl moiety in room temperature ionic liq-
uids (RTILs) has not been yet reported. Thus, the development
=
of new, alternative methodologies to access C S containing sys-
tems under mild conditions, using non hazardous materials, is
highly desirable.
In this context, a growing interest has been focused in the
use of ionic liquids as solvents or catalysts in different chemical
reactions.7 They are salts that are liquids at room temperature or
below. RTILs found wide application because of their negligible
vapor pressure, lack of inflammability, chemical stability, good
solvating ability and recyclability. They are made of positive and
negative ions, and each ionic liquid shows peculiar chemical
and physical properties depending on the kind of cation and
anion. The most commonly used cations are based on N,N’-
dialkylimidazolium species, and they show a different behaviour
as a function of the nature of the relative anion. Reactions per-
formed in ionic liquids often show higher yields, rate enhance-
ment and selectivity with respect to traditional solvents.7 Some
papers dealing with the synthesis of organochalcogenides in ILs
are also reported.8 To the best of our knowledge no example is
described for thionation reactions using ionic liquids as solvents.
CONTACT Antonella Capperucci
Fiorentino (Firenze) , Italy.
antonella.capperucci@unifi.it
Dipartimento di Chimica “Ugo Schiff,” University of Florence, Via della Lastruccia, -, Sesto
Dedicated to Professor B. S. (Raj) Thyagarajan for his retirement from the Editorial Board of Phosphorus Sulfur and Silicon and the Related Elements
©  Taylor & Francis Group, LLC

PHOSPHORUS, SULFUR, AND SILICON
157
Table . Synthesis of thioaldehydes in ionic liquids and their trapping by ,-
dimethyl-,-butadiene.
Yield
%
b
Entry
Ionic Liquid
Aldehyde
Adducta

[bmim][BF]
[bmim][BF]
[bmim][BF]
[bmim][BF]
[emim][TfO]
[emim][TfO]
[bmim][BF]
[bmim][BF]
CHCHO
a
b
c
d
e
c










p-CFCHCHO
o-CFCHCHO
p-NOCHCHO
p-CHOCHCHO
p-CHOCHCHO
CHCHCHO


—
—
d
—
—
d

CHCH(Ph)CHO
aProducts 2a, 2e, 3 have been previously reported in the literature.c For 2b,c see
ref. .
bIsolated products.
cBisadduct
3 [,-bis(,-dihydro-,-dimethyl-H-thiopyranyl)benzene] was
obtained with a ratio aldehyde:HMDST:diene = ::.
dTrimers were formed as major products.
Scheme 
(Table 1, entries 7, 8), thus confirming their low reactivity in
Diels-Alder reactions.
Even though it is reported that ionic liquids usually are
effective in promoting cycloadditions of carbon or nitrogen
Results and discussion
In order to develop a clean thionation method, in this commu- containing dienophiles,11 in our case alkanethials proved to be
nication we would like to report the use of ionic liquids as novel unreactive, as already observed in traditional solvents.5c
reaction media for the conversion of aldehydes into thioaldehy-
des, which reacted as heterodienophiles in Diels-Alder cycload- cyclohexadiene in order to evaluate the stereochemical out-
ditions.
come of the cycloaddition. The reaction with thiobenzaldehyde,
Then we turned our attention towards the reaction with 1,3-
As a model substrate to evaluate the best reaction conditions, generated under CoCl2·6H2O or TfOTMS catalysis with alde-
we performed a set of experiments using benzaldehyde and hyde:HMDST ratio of 1:2, occurs with a high preference for the
bis(trimethylsilyl)sulfide 1 under CoCl2·6H2O or silyl triflate formation of the endo adduct 4 (Scheme 2, R = Ph), as previ-
(TfOTMS) catalysis and 2,3-dimethyl-1,3-butadiene as trapping ously observed by us in acetonitrile.5c
agent (Scheme 1).9 We considered different ionic liquids, which
When PhCHO and HMDST were reacted in equimolar ratio
are liquid at room temperature and stable under the used con- in the presence of TfOTMS as catalyst, the endo adduct was
ditions. All imidazolium derivatives, with different alkyl chains again the major isomer isolated. This result was different from
(butyl-methyl [bmim], ethyl-methyl [emim] and hexyl-methyl what we obtained in CH3CN, where the exo adduct was pre-
[hmim]) and various counter ions were efficient in promoting dominant when aldehydes/HMDST were used in 1:1 molar ratio
the thionation of PhCHO and the cycloaddition of the tran- under TfOTMS catalysis.5c This behaviour was observed with a
sient thioaldehyde with the diene (Scheme 1, entries 1–5), as representative series of differently substituted aromatic and het-
demonstrated by the good yields of the corresponding dihydro- eroaromatic aldehydes (Scheme 2).
thiopyran derivative 2a. When the reaction was performed in
Finally, in order to verify whether ionic liquids could behave
pyrrolidinium derivatives, only in [bmpl][N(Tf)2] was observed also as catalysts, aldehydes were treated with HMDST and the
the formation of the cycloadduct (Scheme 1, entry 6), while diene in different ILs. Whilst it is reported that Diels-Alder
in [bmpl][N(CN)2] any amount of the desired product was cycloadditions can be performed under ionic liquids catalysis,11
observed (Scheme 1, entry 7). This result can suggest the influ- no example is described of thionation induced by ILs.
ence of the cation in such reactions. The ionic liquids used can
A series of imidazolium derivatives were then used to study
the effect of changing the alkyl chain and the nature of the anion,
be potentially recycled up to three times.10
These findings point out that the use of ionic liquids to pro- but only [emim][TfO] was able to promote the conversion of
mote this thionation is suitable, and that the conditions are mild PhCHO and p-CF3C6H4CHO into the corresponding thioalde-
enough to trap thiobenzaldehyde with the diene. With the aim hydes, isolated as cycloadducts with cyclohexadiene, even in a
of evaluating the generality of this new protocol, differently sub- little bit lower yield with respect to the catalyzed reaction.
stituted aromatic and aliphatic aldehydes were reacted under
Theoretically, different interactions have to be considered for
CoCl2·6H2O catalysis in selected ionic liquids. The results are reactions in ILs, like for example the ability of the cation to act
summarized in Table 1.
All aromatic aldehydes react smoothly, and the reaction
appears to be general (Table 1, entries 2–6). The yields were gen-
erally good, comparable with those obtained in traditional sol-
vents, and a rate enhancement was observed in ionic liquids.
Also aliphatic thioaldehydes were formed under the present
conditions, but they demonstrated unreactive towards the diene,
leading to the formation of trimers and oligomeric material Scheme 

158
D. TANINI ET AL.
as hydrogen bond donor and the counter anion as hydrogen
acceptor, solvent effects, as well as their basic or acid charac-
ter.12 Therefore various factors can affect either thionation and
cycloaddition, as well as the behaviour of ILs as promoters of
such reactions. These effects are at present not fully understood,
and further investigations will be necessary.
(c) Segi, M.; Nakajima, T.; Suga, S.; Murai, S.; Ryu, L.; Ogawa, A.; Son-
oda, N. J. Am. Chem. Soc. 1988, 110, 1976–1978 and references cited
therein.
7. For some examples: (a) Martins, M. A. P.; Frizzo, C. P.; Tier, A. Z.;
Moreira, D. N.; Zanatta, N.; Bonacorso, H. G. Chem. Rev. 2008, 108,
2015–2050. (b) Wasserscheid, P.; Welton, T. (eds.) Ionic Liquids in Syn-
thesis, Wiley-VCH, 2nd Edition, 2007. ISBN: 978-3-527-31239-9 and
references cited. (c) Sheldon, R. Chem. Commun. 2001, 2399–2407. (d)
Wasserscheid, P.; Keim, W. Angew. Chem. Int. Ed. 2000, 39, 3772–3789.
(e) Welton, T. Chem. Rev. 1999, 99, 2071–2083.
Conclusions
8. For some examples of organochalcogens in ILs: (a) Zimmermann, E.
G.; Thurow, S.; Freitas, C. S.; Mendes, S. R.; Perin, G.; Alves, D.; Jacob,
R. G.; Lenardão, E. J. Molecules 2013, 18, 4081–4090. (b) Thurow,
S.; Ostosi, N. T.; Mendes, S. R.; Jacob, R. G.; Lenardão, E. J. Tetra-
hedron Lett. 2012, 53, 2651–2653. (c) Lenardão, E. J.; Borges, E. L.;
Mendes, S. R.; Perin, G.; Jacob, R. G. Tetrahedron Lett. 2008, 49, 1919–
1921.
In summary, we have shown that direct formation of thioalde-
hydes, and their trapping with dienes, are possible using ionic
liquids as solvents under mild conditions, through reaction of
silyl sulfide with aldehydes. Further studies to extend the thion-
ation to different carbonyl compounds and to try to elucidate the
interaction between the ionic liquids and the substrates are now
under investigation.
9. Typical procedure. A mixture of 0.5 mL of ionic liquid (maintained
under high vacuum prior to use), benzaldehyde (30 mg, 0.28 mmol)
and 2,3-dimethyl-1,3-butadiene (46 mg, 0.56 mmol) was treated
under inert atmosphere at room temperature with HMDST (100 mg,
0.56 mmol) and CoCl2·6H2O (14 mg, 0.056 mmol) (or TfOTMS,
12 mg, 0.056 mmol). The progress of the reaction was monitored by
TLC (petroleum ether/diethyl ether 10:1). After completion of the
reaction (2–3 h), the mixture was diluted with diethyl ether. The
organic phase was then washed with NH4Cl (3×1 mL) and extracted
with diethyl ether (3×2 mL). The combined organic phases were
dried over Na2SO4 and the solvent was evaporated under vacuum.
TLC purification (petroleum ether/diethyl ether 50:1) afforded 44 mg
(78%) of 4,5-dimethyl-2-phenyl-3,6-dihydro-2H-thiopyran 2a.5c 4,5-
dimethyl-2- (4- (trifluoromethyl)-phenyl)-3,6-dihydro-2H-thiopyran
2b. 1H NMR (200 MHz, CDCl3), δ (ppm): 1.73 (3H, s), 1.77 (3H,
s), 2.45–2.55 (2H, m), 2.91 (1H, bd, J = 16.8 Hz), 3.42 (1H, bd, J =
16.8 Hz), 4.02 (1H, dd, J = 8.4 Hz, 4.5 Hz), 7.45 (2H, ap d, J = 8.3 Hz),
7.61 (2H, ap d, J = 8.3 Hz). MS, m/z (Irel, %): 272 (26) [M+], 239 (16),
190 (59), 82 (100). 4,5-dimethyl-2- (2- (trifluoromethyl)phenyl)-3,6-
dihydro-2H-thiopyran 2c. 1H NMR (200 MHz, CDCl3), δ (ppm): 1.72
(3H, s), 1.74 (3H, s), 2.33–2.51 (2H, m), 2.93 (1H, bd, J = 17.0 Hz), 3.44
(1H, d, J = 17.0 Hz), 4.16 (1H, dd, J = 10.0 Hz, 4.5 Hz), 7.30–7.38 (1H,
m), 7.50–7.56 (1H, m), 7.79–7.83 (1H, m), 7.95–8.01 (1H, m). MS, m/z
(Irel, %): 272 (24) [M+], 239 (12), 190 (62), 82 (100).
10. The same thionation reaction was performed using as a medium the
recovered IL/catalyst system just by adding more reagents, without
the addition of more catalyst. Under these conditions the formation
of the product 2a was observed, even if in lower yield.
11. For some examples: (a) Yadav, J. S.; Reddy, B. V. S.; Chetia, L.; Srini-
vasulu, G.; Kunwar, A. C. Tetrahedron Lett. 2005, 46, 1039–1044. (b)
Meracz, I.; Oh, T. Tetrahedron Lett. 2003, 44, 6465–6468. (c) Fisher,
T.; Sethi, A.; Welton, T.; Woolf, J. Tetrahedron Lett. 1999, 40, 793–
796. (d) Earle, M. J.; McCormac, P. B.; Seddon, K. R. Green Chem. 1999,
1, 23–25.
Funding
Financial support from MiUR, National Project PRIN 2010–2011 “Processi
ossidativi e radicalici: aspetti innovativi ed applicazioni allo sviluppo di
biopolimeri melanici e antiossidanti di rilevanza biomedica e tecnologica
(PROxi)” is gratefully acknowledged.
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