A. Ashouri, S. Samadi
nanocatalysts in various organic reactions [13, 14]. Among
them, magnesium oxide nanoparticles, due to the surface
eꢁect (surface/volume ratio) [15], high melting point [16],
and dual character of ions [17] are more reactive to use in
many ꢃelds spatially in organic reactions as a highly eꢁec-
tive heterogeneous basic catalyst, which makes them proper
for synthesizing the desired products with high eꢂciency, in
a short time and mild reaction condition [18–21].
showed that pyridine had better eꢁect on the reaction rate,
but no remarkable eꢁect on the yield of the desired product
(Table 1, compare entries 2 with 3–5). On the other hand,
using various metal oxide nanoparticles as heterogene-
ous catalysts led to good chemical yield and none of the
acyclic product was observed after 10 h. As presented in
Table 1, the rate of cyclization was considerably enhanced
in the presence of diꢁerent metal oxide nanoparticles such
as TiO , SiO , CuO, MgO, Al O , and ZnO in comparison
To the best of our knowledge, the synthesis of symmetric
amino thiadiazoles with aromatic substituted on the amino
groups attached to the ring is limited in the literature. Few
reports are available that they also have some problems
such as using toxic and expensive reagents, low eꢂciency,
long reaction time, and diꢂculty in the products separation
2
2
2
3
with the uncatalyzed reaction which gave acyclic product
also (Table 1, entries 6–11). Among the investigated nano-
catalysts, MgO nanoparticles have shown better eꢂciency
(Table 1, entry 9). On the other hand, according to entry 12,
it is considered that the use of MgO nanoparticles and pyri-
dine as an external base simultaneously gave an insigniꢃcant
increase in the yield. It could be due to the presence of basic
sites in MgO nanoparticles [28] which enable the preforma-
tion of the reaction even in the absence of the external base.
The usage of MgO was also investigated, but the reaction
resulted in lower yields of MgO NPs (entry 13).
[
22–25].
As the biological activity of symmetrical thiadiazoles was
known [26], earlier, Ziyaei group reported the preparation of
some thiadiazole derivatives in water using of dithiocarba-
mate derivatives, hydrazine sulfate, and pyridine as a base
in water, but the uncyclized products were obtained as the
by-products [27]. To overcome this problem, in this work
we attempted to use diꢁerent nanoparticles as heterogeneous
basic catalysts to obtain the mild and green reaction condi-
tion for preparing these thiadiazole derivatives (Scheme 1).
The results presented in Table 2 show that the time and
yield of the reaction were also aꢁected by the amount of
MgO nanoparticles. The best results were obtained when the
loading of MgO NPs was 5 mg (Table 2, entry 2).
Eꢁect of various solvents was also investigated on the
model reaction. The results obtained showed that the yield
was increased with increasing polarity of the solvents. As
shown in Table 3, the eꢁect of water and ethanol was nearly
the same (entries 5 and 6). Due to the green and environ-
mentally friendly and economic purposes, we have selected
water as the best solvent to continue the reaction.
Results and discussion
The catalytic efect oꢀ diferent nanoparticles
on the preparation oꢀ 2,5‑diamino‑1,3,4‑thiadiazole
derivatives
In order to show the generality of the reaction, the scope
of this process was explored under the optimized reaction
conditions (Scheme 2). The starting material was prepared
using a range of aromatic carbamodithioate bearing electron-
donating as well as electron-withdrawing groups and benzyl
halides or acrylonitrile, which reacted quite general with
hydrazine sulfate to aꢁord 2,5-diamino-1,3,4-thiadiazole
derivatives in good-to-high yields (Table 4, 64–95% yields).
The obtained results showed that the –CN group was not
aꢁected in yields remarkably.
The optimized reaction conditions were achieved by per-
forming the reaction of benzyl phenylcarbamodithioate (1a)
and hydrazine sulfate in water under reꢀux as a model reac-
tion by varying factors such as diꢁerent nanoparticles as a
catalyst with the various loading, diꢁerent amount of start-
ing materials, various bases and solvents.
First, we evaluated the eꢁect of diꢁerent bases such as
pyridine, sodium hydroxide, potassium hydroxide, and
triethylamine on the model reaction. The obtained results
Scheme 1
1
3