Y. Luo et al.
H215N
15NH2
15NH2
N
Cl
N
15NH2
Cl
N
Cl
Cl
N
15NH3
15NH3
0-5
15NH3
N
N
N
N
N
N
C
80
N
N
30-50 C
C
15NH2
15NH2
Cl
Cl
1
2
3
4
Scheme 1. Synthesis of [15N3]melamine.
HO
N
OH
We found that when the reaction was carried out under reduced
pressure and sulfolane as solvent, [13C3]cyanuric acid was
obtained with satisfying yield up to 88.4% based on [13C]urea
consumed.
O
solvent
13C
N
N
NH2
H2N
13C3
OH
5
6
Scheme 2. Synthesis of [13C3]cyanuric acid.
Results and discussion
References
Although the manufacture of melamine and cyanuric acid are
fairly common on industrial scale, reports of the preparation of
isotopically labelled melamine and cyanuric acid are very rare.
Previously Varelis described the synthesis of [13C3]melamine and
[13C3]cyanuric acid in which [13C3]cyanuric chloride reacted with
ammonia and formic acid, respectively, to give [13C3]melamine
and [13C3]cyanuric acid in moderate yields. In order to improve
the synthesis of both standards, we developed a new synthetic
method with satisfying labeling yields with the common
substrates [15N]NH4Cl and [13C]urea.12
As shown in Scheme 1, multi-step ammonization of cyanuric
chloride could stop at the one or two substitution stage by
controlling the reaction temperature and the dosage of
ammonia properly. In this article, [15N3]melamine was synthe-
sized via a one-pot method and solvent played an important
role in the reaction. By using dioxane as the solvent,
[15N3]melamine could be synthesized with higher than 99.4%
chemical purity. [15N]NH4Cl in the filtrate could be recycled
quantitatively and the yield of 4 was better than 97.0% based on
labeled-substrate consumed. Other attempts using water,
acetonitrile, and acetone as solvent were made and 2,4-
diamine-6-chloride-1,3,5-triazine was found to be the main
products under the same reaction conditions.
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Copyright r 2010 John Wiley & Sons, Ltd.
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