Cantillo et al.
JOCArticle
hydrogen sulfide anion,4 or the treatment with Lawesson’s
reagent,5 have been so far described for the conversion of
mesoionic olates into mesoionic thiolates. In this context
we have recently reported the conversion of imidazo-
[2,1-b]thiazolium-3-olate systems (1 and 3) into the cor-
responding imidazo[2,1-b]thiazolium-3-thiolate derivatives
(2 and 4) by reaction with aryl isothiocyanates, and proving
unequivocally that this thionation does actually proceed via a
domino mechanism.6
Results and Discussion
Syntheses and Reactivity. The reaction of monocyclic
€
3-aryl-2-dialkylaminothioisomunchnones with aryl isothiocya-
nates leads to 3-aryl-2-dialkylamino-1,3-thiazolium-4-thiolates.
This O/S exchange occurs through two competitive reaction
pathways, a thionation process similar to that described for the
synthesis of 2 and 4, which retains the aryl group on N-3, and a
domino cycloaddition-retrocycloaddition process that adds
the aryl group from isothiocyanate to the new mesoionic
structure. Obviously, only one thiolate system is obtained when
the aryl groups of both reaction partners are identical.
Thus, mesoionic heterocycles 5-77 react with phenyl,
4-methoxyphenyl, and 4-nitrophenyl isothiocyanates (8-10) to
afford the corresponding mixtures of 3-aryl-2-(N-methylbenzyl-
amino)-5-phenyl-1,3-thiazolium-4-thiolate systems 11-13. Initi-
ally, such reactions were carried out in CH2Cl2 at room tem-
€
perature by using a 1:5 ratio of thioisomunchnone-isothio-
cyanate, and compounds 11-13 could be isolated by column
chromatography by using benzene-acetonitrile gradients after
no more than 48 h. The low yields thus obtained were increased
when DMF was used as solvent (Table 1). A further improve-
ment was achieved by conducting these transformations in DMF
at 100 °C (oil bath) leading to completion in less than 40 min.
To delineate the scope of this methodology, it is conve-
nient to move it from fused and polycyclic systems to the
more readily available monocyclic 1,3-thiazolium-4-thio-
lates. Furthermore, this study should allow us to disentangle
the fate of two competing processes, i.e., thionation and the
expected cycloaddition of the masked dipole with the hetero-
cumulenic partner. In the course of this theoretical research,
we came across a simple and intuitive protocol for the
location of all stationary points along the potential surface.
This methodology is described in detail and we judge many
synthetic chemists will find it both useful and computation-
ally inexpensive, thus overcoming the fears in moving from
the bench to virtual chemistry.
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To find the optimal conditions for the syntheses of 11-13, the
above-mentioned reactions were alternatively attempted under
microwave irradiation, using a multimode microwave instru-
ment (maximum power: 300 W; temperature: 100 °C measured
with use of an internal fiber-optic probe) in DMF as solvent, a
polar medium suitable for dielectric heating.8 Under these con-
ditions, transformations are complete within 5 min. This accel-
eration causes energy savings but it does not substantially affect
the chemoselectivity of either of the global yields with respect to
the conventional heating for the same time.9 Although the
conventionally heated reaction, conducted in the identical reac-
tion vessel at 100 °C, usually requires 10-40 min for completion,
we deliberately stopped these protocols after 5 min and evaluated
both overall yields and selectivities (Table 1), which show a close
similarity to those completed after 5 min of irradiation.
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