NJC
Letter
aldehyde 4 via b-hydride elimination.9–12 The aldehyde 4 is much
more reactive toward biguanide 2, and the dihydro-triazine 5 is
formed under the reaction conditions.4 Finally, the desired
product 3 is formed via dehydrogenative aromatization of 5
by the ruthenium catalyst or air oxidation.15 In all reaction,
aldehydes as intermediates could be detected.
In summary, we have developed a simple and efficient protocol
for the synthesis of tri-substituted 1,3,5-triazines via ruthenium
catalyzed reaction of alcohols with biguanides. The method
employs readily available reagents and has a broad scope and
high functional group tolerance. Detailed mechanistic studies and
scope expansion work are currently underway in our laboratory.
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Experimental
General remarks
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Unless otherwise noted, materials were obtained from commer-
cial suppliers and used without further purification. t-BuOK (98%
purity) was purchased from Aladdin Industrial Corporation.
Thin layer chromatography (TLC) was performed using silica
gel 60 F254 and visualized using UV light. Column chromato-
graphy was performed with a silica gel (mesh 300–400).
1H NMR and 13C NMR spectra were recorded on a Bruker
Avance 500 MHz spectrometer in CDCl3 with Me4Si as an
internal standard. Data were reported as follows: chemical shift
in parts per million (d), multiplicity (s = singlet, d = doublet,
t = triplet, q = quartet, br = broad, and m = multiplet), coupling
constant in Hertz (Hz) and integration.
General procedure for the synthesis of 1,3,5-triazines
To a mixture of alcohols (1.0 mmol), biguanide hydrochloride
(1.0 mmol), and t-BuOK (2.0 mmol) in dioxane (5 mmol),
Ru(COD)Cl2 (2 mol%) was added. The resulting mixture was
then sealed and stirred for 12 h at 100 1C. After completion of
the reaction, the reaction mixture was cooled to room tem-
perature and extracted with ethyl acetate. The organic phase
was dried over anhydrous Na2SO4. The crude residue was
obtained after evaporation of the solvent in vacuum, and the
residue was purified by flash chromatography with CH2Cl2 and
CH3OH as eluents to give the pure product.
Acknowledgements
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NMR analysis was performed at the Research Center of Analysis
& Measurement, Zhejiang University of Technology Center.
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