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nd
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[13] This isolation protocol was required because the crude salt
mixture gave complex mixtures upon attempted conversion to the 1,5-
disubstituted imidazole. It was found that the presence of small quantities
of HMTA, paraformaldehyde and related impurities in the crude mixture
of 8a and ammonium salts were very detrimental to the subsequent con-
version to the imidazole. The separation of 8a free base from the mixture
via aqueous base extractions and conversion to the corresponding HCl
salt removed the formaldehyde related impurities, thus allowing smooth
conversion to the desired imidazole. Interestingly, the presence of ammo-
nium salts (NH Cl, NH Br, NH H PO ) did not affect the yield or purity
4
4
4
2
4
of the imidazole formation.
[14] The solubility of 8a•H PO is much greater in water than in
3
4
[8] For preparation of 1,5-substituted imidazoles from glycine
derivatives and thiocyanate see: [a] D. J. Carini, J. V. Duncia, A. L.
Johnson, A. T. Chiu, W. A. Price, P. C. Wong and P. B. M. W.
dilute aqueous solutions of ammonium phosphate. Therefore, care should
be exercised during the washing of the filter cake with water, and it is rec-
ommended to use 1-2% aqueous NH H PO rather than pure water to
4
2
4