Communication
vent ethanol was replaced by a non-polar (e.g., toluene,
chloroform) or a slightly polar aprotic solvent (e.g., tetrahydro-
furan (THF)), no reaction was observed and the starting nitrile
agent was fully recovered.
Table 2. Synthesis of 5-aryl-1,2,3,4-thiatriazoles TT1-TT9.[a]
When the highly polar aprotic solvent acetonitrile was used,
we isolated 16% of unsymmetrical 3-(4-bromophenyl)-6-
methyl-1,2,4,5-tetrazine T2, because acetonitrile acts as both
solvent and second nitrile precursor in the reaction. In addition
to the tetrazine, the unusual 1,2,3,4-thiatriazole TT1 was also
obtained with a 9% yield. More interestingly, when using di-
methylformamide (DMF) as a solvent, the yield of TT1 signifi-
cantly increased to 41%.[18] And remarkably, when the even
more polar solvent dimethyl sulfoxide (DMSO) was employed,
the yield was optimized to as high as 74%. These findings are
remarkably interesting because this is the first time that the
1,2,3,4-thiatriazole has been isolated using “Pinner synthesis”.
All the reactions were performed in a one-pot procedure with-
out isolating any thioacylating agents. It is worth noting that
in the case of all three polar solvents (acetonitrile, DMF and
DMSO) only a trace amount (yield below 1%) of symmetrical
tetrazine T1 could also be observed.
[a] Reactions were carried out on a 0.5 mmol scale in 2 mL DMSO. Yields
(isolated) based on the starting nitrile.
Formation of 1,2,3,4-thiatriazole in this reaction is assumed
to process through diazotization of a thiohydrazide intermedi-
ate, formed in the first step, by the nitrous acid used in the
second step. However, the detailed mechanism of formation of
these thiohydrazide intermediates is still under investigation
and it is not clear if small amounts of hydrogen sulfide are
formed or not.
to instability of the thioacylating intermediates which have
been described previously.[3]
With our convenient one-pot synthetic approach in hand,
we hypothesized that it could be used to prepare donor-ac-
ceptor type thiatriazole derivatives using an appropriate nitrile
precursor. More importantly, we also believed that 1,2,3,4-thia-
triazole could act as a novel electron acceptor for efficient
TADF emitters. Indeed one-pot or multicomponent synthesis of
functional chromophores has received considerable interest
both in academia and industry.[19] To our delight, the donor-ac-
ceptor thiatriazole derivative using phenoxazine as a donor
motif, TT9, was easily prepared in a high yield (70%) using our
approach. TT9 easily forms yellow crystals, which are stable
and could be stored at room temperature for several months
without noticeable degradation. The single-crystal structure
(Figure 1) shows a large twisting angle (678) between the
planes of donor and acceptor, which is desired to achieve
small HOMO–LUMO overlap and to realize a small DEST, and
therefore efficient TADF characteristics.[4]
The reaction with DMSO as a solvent became the most inter-
esting to us because it provides a novel, convenient pathway
to 1,2,3,4-thiatriazoles directly from commercially available ni-
trile reagents in an excellent yield. The reaction conditions
were optimized by changing the amount of sulfur and reaction
temperature. Probably acting both as an inducer and reactant
in the reaction, the amount of sulfur is crucial in this reaction.
Theoretically, one equivalent of sulfur should be enough to
obtain the thiatriazole product. In those conditions the reac-
tion already led to a reasonable yield (53%, Table S1 in Sup-
porting Information), while slight excesses (1.3 equiv) of sulfur
could still improve the yield and 1.5 equiv of sulfur gave the
best yield (74%). The reaction temperature and time were op-
timized to 908C for 1 hour, because decreasing the reaction
temperature only resulted in prolonged reaction times to
reach similar yields (Table S2). We used microwave heating
throughout, but we have verified that running the reaction in
a sealed tube with conventional heating worked fine as well,
resulting in a similar yield (72%).
TT9 was further characterized by electrochemistry (Fig-
ure S8). The cyclic voltammogram in DCM displays a reversible
oxidation wave for the phenoxazine, and an irreversible reduc-
tion one corresponding to the thiatriazole. The HOMO and
LUMO energies were determined to be 5.35 and 3.41 eV from
the onset of the respective waves.
To extend the scope of this synthetic approach, we engaged
a series of nitrile substrates in our new one-pot synthetic ap-
proach. Thus, a series of 5-aryl-1,2,3,4-thiatriazoles were suc-
cessfully prepared in good to high yields (51–80%, Table 2),
among which many were previously complicated to prepare.[3]
The reactions are simple and efficient, and the nitrile substrate
can contain different functional groups such as halogens and
hydroxyl groups. Although the reaction is versatile, unfortu-
nately, preparation of 5-alkyl-1,2,3,4-thiatriazoles using benzyl
cyanide or tert-butyl cyanide was not successful, probably due
Figure 1. Crystal structure of TT9. Hydrogen atoms are omitted for clarity.
Chem. Eur. J. 2019, 25, 1 – 7
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