Pteridin-2-ones, covalent hydration

Considering the four potential monohydroxypteridines, pteridin-4- and -7-one 56JCS3443) behave normally whereas pteridin-2- and -6-one (25) form covalent hydrates. The reversible hydration of nitrogen heterocycles was actually discovered with pteridin-6-one (52JCS1620),... 

As is pointed out in the introduction to Section II, the presence or absence of water in the solid state gives no indication as to whether or not covalent hydration occurs in aqueous solution. However, many examples are known of substances which hydrate strongly in solution and also in the solid state. Thus, 2-hydroxy- and 6-hydroxy-pteridine crystallize with one molecule of water. On heating, the former loses water rapidly only at 180°, whereas the latter retains all of the water up to 180° where it begins to darken. ... 

The most common ester used for pteridine synthesis is ethyl glyoxylate which is commercially available as the ethyl hemiacetal (ethyl 2-ethoxy-2-hydroxyacetate) or as the diethylsulfanyl derivative. Both the pteridin-6-one and the pteridin-7-one may be obtained, and the ratio of isomers can be controlled to some extent by the choice of reaction conditions. This is well illustrated by condensations of pyrimidine-4,5-diamine with ethyl 2-ethoxy-2-hydroxyacetate. At pH 6 a mixture of products is obtained with the 7-isomer predominating. The products may be separated at pH 2 at which pteridin-7(8/7)-one is insoluble and may be collected, whilst the pteridin-6(5//)-one remains in solution as the 7,8-hydrate cation. If the condensation is carried out at pH 10 (2 M sodium carbonate under reflux), the 7-isomer is formed, almost exclusively, as the sodium salt.79 However, if the reaction is carried out at pH 0 (1 M sulfuric acid, 37 °C), the 6-isomer, as its stable covalent hydrate, is formed almost exclusively.80... 

The effect of covalent hydration on the properties of pteridines is well illustrated by the facile oxidation of pteridin-6(5//)-one (10) to ptcridine-6,7(5/7,8//)-dione (12) which proceeds via the adduct 11.240... 

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