594
H. Weinmann et al. / Tetrahedron Letters 43 (2002) 593–595
Scheme 2.
Scheme 3.
Experiments to precipitate the salt from the aqueous
solution by adding water-miscible organic solvents like
THF or DMF were not successful. To our great sur-
prise we then found that by slowly (over 1 h) dropping
the reaction mixture at 0–5°C into ice-cold ethanol,
2-amino-imidazole-hemisulfate was obtained as a white
crystalline precipitate in 86% yield.9 This result was
even more surprising as Storey, Sullivan and Moyer
had used ethanol as a solvent in their work-up proce-
dure. Therefore, it seems that the solubility of 2-amino-
imidazole-hemisulfate strongly depends on the
temperature.
strated that amines can be reacted with O-methyl-
isourea-sulfate for the preparation of monosubstituted
guanidines.8 However, to the best of our knowledge,
2-amino-acetaldehyde-acetals have not been used so
far. Surprisingly, we found that at 50°C in an aqueous
solution after 4 h a complete transformation to the
guanidine derivative is achieved (Scheme 3).
The reaction can be performed with 2-amino-acetalde-
hyde diethylacetal as well as with 2-amino-acetaldehyde
dimethylacetal. As the latter is cheaper, we preferred
the dimethylacetal. Both the 2-amino-acetaldehyde-
dimethylacetal and the O-methyl-isourea are cheap
commodities and therefore this process has economic
advantages and is environmentally more friendly as
only methanol is released as a by-product during the
reaction.
In summary we have developed a new procedure for the
preparation of 2-amino-imidazole which besides a very
good yield and quality of the product has several other
advantages related to technical, safety and environmen-
tal aspects. By using the new one-pot procedure not
only a higher yield is obtained but also the work-up is
drastically simplified.
Unfortunately, our attempts to isolate the guanidine
derivative were not successful. Therefore, we developed
a one-pot procedure. The transformation of O-methyl-
isourea to the guanidine is followed immediately by the
sulphuric acid-catalysed cyclisation to 2-amino-imida-
zole-hemisulfate. A pH of 2.5 was found to be optimal
as no deterioration or polymerisation occurred under
these conditions. After 2 h at 100°C a complete trans-
formation was reached. Due to the extremely good
solubility of 2-amino-imidazole in water as a salt or free
base, it was impossible to isolate the product from the
reaction mixture by the usual extraction with organic
solvents. On the other hand, removal of the water
through distillation resulted in partial deterioration of
the product. It was possible to isolate the product by
freeze-drying but, from a technical point of view, this
was not an economical method for isolation. Concen-
tration of the solution and crystallisation attempts were
also unsuccessful.
Acknowledgements
We thank the Schering Spectroscopic and Analytical
Departments for their excellent support.
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