So far, the main approaches to these compounds reported in literatures include: 1) addition of 1,2,3-thiadiazol-5-amine to isocyanates
(Scheme 1, route a) [7]; 2) addition of amines to 5-isocyanato-1,2,3-thiadiazole generated in situ via Curtius rearrangement of 1,2,3-
thiadiazole-5-carbonyl azide which is obtained from 1,2,3-thiadiazole-5-carbohydrazide [13] or 1,2,3-thiadiazole-5-carboxylic acid [8]
by multi-step reactions (Scheme 1, route b); 3) addition of amines to 5-isocyanato-1,2,3-thiadiazole generated in situ by the reaction of
1,2,3-thiadiazol-5-amine with diphosgene (Scheme 1, route c) [14]. However, there are many drawbacks associated with these methods
such as complex structure and inconvenient sources of the raw materials, tedious synthetic route, cumbersome operations, low atomic
economy, high cost and generation of corrosive acid wastes.
As the most important C1 building block, CO has been employed extensively for various carbonylation transformations in the presence
of catalysts [15-20]. Over the past decades, cheap and readily available nonmetal selenium has been found and applied as an effective
catalyst for the carbonylation reaction with CO to prepare many valuable carbonyl-containing compounds such as ureas [21-23],
carbamates [21,24,25], thiocarbamates [21,26] and carbonates [21,27] with high atom economy in one-pot manner. Recently, Se-
carbonylation reaction has also been developed for the preparation of 1,3-selenazolidin-2-ones [28]. However, no example has so far
been found in literatures on the synthesis of 1,2,3-thiadiazol-5-ylureas with Se/CO catalytic system. Herein, we wish to report a facile
and economical approach to these target compounds via one-pot selenium-catalyzed oxidative carbonylation of 1,2,3-thiadiazol-5-amine
with various amines in the presence of CO and O2 (Scheme 1, route d).
Initially, the oxidative carbonylation of 1,2,3-thiadiazol-5-amine with aniline (1a) was chosen as a model reaction to optimize the
reaction conditions (Table 1). For safety reason, the ratio of CO to O2 was designated as 9:1 during the selenium-catalyzed oxidative
o
carbonylation reaction. To our delight, the reaction could proceed smoothly at 80 C and afforded the target product 1-phenyl-3-(1,2,3-
thiadiazol-5-yl)urea (2a) in 63% yield (Table 1, entry 1) accompanied with a small amount of diphenylurea and di(1,2,3-thiadiazol-5-
yl)urea, suggesting that accompanying by the cross carbonylation reaction there existed the competitive carbonylation of 1,2,3-thiadiazol-
5-amine and aniline themselves. When the temperature was raised to 100 oC, higher product yield could be obtained (Table 1, entry 2).
Further increase of the temperature to 120 oC failed to gain the beneficial result (Table 1, entry 3). Generally, a proper alkaline condition
is believed to be necessary for the generation of the active specie carbonyl selenide (COSe) in the selenium-catalyzed carbonylation
reactions [21,29]. Thus, the common alkalis such as NaOH, K2CO3, Pyridine and Et3N were screened (Table 1, entries 2, 4-6) and the
results indicated that the organic alkalis (Table 1, entries 2,6) were more effective than those inorganic ones (Table 1, entries 4,5). Among
them, Et3N worked best. Finally, the effect of solvents on the carbonylation reaction was also studied (Table 1, entries 2,7-9). According
to the results, strong polar solvents worked better (Table 1, entries 2,7) than the weak ones (Table 1, entries 8,9). So, DMF was chosen
ultimately as the solvent in this carbonylation system for convenience purpose.
With the optimized reaction conditions in hand, we next investigated the scope and efficiency of the selenium-catalyzed oxidative
carbonylation of 1,2,3-thiadiazol-5-amine with a series of amines (Table 2). Experimental details and characterization data of the target
compounds are presented in Supporting information. The results indicated that most of the amines could tolerate the carbonylation
reaction, affording the corresponding 1,2,3-thiadiazol-5-ylureas in moderate to good yields. Firstly, aromatic amines were applied in the
carbonylation reaction and the results revealed that the reaction was very sensitive to both electronic effect and steric effect of the
aromatic amines. For example, the anilines bearing electron-donating group (Table 2, entries 2-4,8) such as 4-methylbenzenamine and
4-methoxylbenzenamine (Table 2, entries 4 and 8) were more effective than those with electron-withdrawing group (Table 2, entries 5-
7 and 9) such as 4-cholrobenzenamine and 4-nitrobenzenamine (Table 2, entries 7 and 9), resulting in the higher product yields of the
former than the latter. As for steric effect, ortho-substituted anilines (Table 2, entries 2,5) were less effective than those meta-substituted
or para-substituted ones (Table 2, entries 3,4,6,7), resulting in the lower product yields of the former than the latter. As the examples of
The results indicated that both of them could tolerate the carbonylation reaction, affording the corresponding product in yield of 46%
(Table 2, entry 11) and 40% (Table 2, entry 12), respectively. Next, the substrate scope of the carbonylation reaction was extended to
aliphatic amines. On the whole, aliphatic amines worked less efficiently (Table 2, entries 13-19) than those aromatic ones most probably
due to their weak reactivities. Steric effect seemed to affect the carbonylation reaction significantly. Less hindered aliphatic amines such
as propan-1-amine and butan-1-amine worked more efficiently (Table 2, entries 13,14) than those more hindered ones such as 2-
methylpropan-1-amine and cyclohexanamine (Table 2, entries 15,17). The greater the steric hindrance of the aliphatic amines is, the
lower their reactivity becomes. Thus, it was understandable that no desired products were obtained when the carbonylation reaction
proceeded with the highly hindered 2-methylpropan-2-amine (Table 2, entry 16) as well as two secondary amine examples of
diethylamine and piperidine (Table 2, entries 17,18).
Compared with other catalytic systems, one remarkable characteristic of this selenium-catalyzed carbonylation system is that it has
the function of phase-transfer catalysis. In particular, selenium powder is insoluble in solvent prior to the carbonylation reaction; then it
can react with CO in proper alkaline condition to form soluble carbonyl selenide (SeCO) in situ, which initiate the subsequent
homogeneous carbonyaltion reaction to form the target product during the reaction process; upon the completion of the reaction, insoluble
selenium power can be precipitated from the reaction mixture after sufficient oxidation and can be easily recovered by suction filtration.
Thus, the reaction system can change reciprocally between heterogeneous and homogeneous systems during the whole reaction process,
which can not only realize the efficient catalytic reaction, but also facilitate the separation and recovery of the catalyst selenium. The
reusability of the recovered selenium was tested via the model carbonylation reaction of 1,2,3-thiadiazol-5-amine with aniline. The yield