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References and notes
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Scheme 2.
amine in a model reaction. On the basis of the product yield it was
clear that EDC hydrochloride and HgCl2 were the optimal reagents
for this reaction. We studied the generality of both the thiophiles
for the synthesis of desired triazines. EDC hydrochloride failed to
yield triazines when acetamidine hydrochloride was used as a
binucleophile, but HgCl2 gave the desired product. Therefore, HgCl2
was selected as a general thiophile for all other reactions.
All the reactions between isothiocyanates, N,N-diethylamidines,
and carbamidines with systematic variations of R1, R2, and R3 pro-
ceeded smoothly to afford the corresponding 1,3,5-triazines in
good to moderate yields (Scheme 1). The generality of this new
synthetic method for the efficient construction of 1,3,5-triazines
was investigated by employing HgCl2 as a thiophile using THF as
a solvent at room temperature.16 The results are summarized in
Table 1. The generality of this method for the synthesis of 2,5-dia-
mino-1,3,5-triazines was also studied by reacting isothiocyanates
with tetramethylguanidine followed by condensation with carb-
amidines in the presence of HgCl2 (Scheme 2, Table 1, entries
10–13).
In conclusion, we have reported a convenient one-pot synthesis
of biologically important trisubstituted 1,3,5-triazine derivatives
from readily available starting materials under mild conditions.
The reaction is applicable to a wide range of substituted isothiocy-
anates, N,N-diethylamidines, and carbamidines.
15. Linton, B. R.; Carr, A. J.; Orner, B. P.; Hamilton, A. D. J. Org. Chem. 2000, 65,
1566–1568.
16. General experimental procedure for the preparation of trisubstituted 1,3,5-
triazines: To a stirred solution of isothiocyanate 1 (1 mmol) in THF (5 mL),
N,N-diethylamidine 2 (1 mmol) was added at room temperature and allowed
to stir for 2 h. To the stirred reaction mixture triethylamine (15 mmol) and
carbamidine hydrochloride 4 (1.2 mmol) were added at room temperature.
Mercury(II) chloride (1 mmol) was added slowly to the reaction mixture (slight
exothermic) and the mixture was allowed to stir for another 4 h at room
temperature. Initiation of the desulfurization was observed by the formation of
black HgS precipitate. Progress of the reaction was monitored by TLC using
ethyl acetate/hexane (3:7) as a mobile phase. After the completion of the
reaction, the reaction mixture was diluted with THF (5 mL) and filtered
through a Celite bed to remove the black precipitate of HgS. The filtrate was
concentrated in vacuum and purified by silica gel (60–120 mesh) column
chromatography using 12% ethyl acetate in hexane as a mobile phase to give
triazines 5. The same experimental protocol was followed for the preparation
of 2,5-diamino-1,3,5-triazines (Scheme 2, Table 1, entries 10–13) using
tetramethylguanidine instead of N,N-diethylamidines.
Acknowledgments
We thank Professor Harish Padh and Professor C. J. Shisoo,
Directors, B.V. Patel PERD centre, for their constant encouragement
and support.
Supplementary data
Supplementary data (general experimental procedure and spec-
tral data for representative compounds) associated with this article