Pyridopyrimidines covalent hydration

The physical properties of the pyridopyrimidines closely resemble those of their nearest A-heteroeyclie neighbors the quinazolines and the pteridines. Thus, in common with the pteridines, the presence of groups capable of hydrogen-bonding markedly raises the melting point and lowers the solubility. - The acid dissociation constants (pif a values) and ultraviolet absorption spectra of all four parent pyridopyrimidines have been determined by Armarego in a comprehensive study of covalent hydration in these heterocyclic systems. The importance of these techniques in the study of covalent hydration, and... 

Nuclear magnetic resonance spectra of all four parent compounds have been measured and analyzed.The powerful potentialities of NMR as a tool in the study of covalent hydration, tautomerism, or protonation have, however, as yet received no consideration for the pyridopyrimidines. NMR spectra have been used to distinguish between pyrido[3,2-d]pyrimidines. and isomeric N-bridgehead compounds such as pyrimido[l,2- ]pyrimidines and in several other structural assignments (cf. 74 and 75). 

In common with other fused pyrimidines, the pyridopyrimidines are susceptible to the nucleophilic addition of water across the 3,4-bond. This is the phenomenon of covalent hydration... 

Oxidations of pyridopyrimidines are rare, but the covalent hydrates of the parent compounds undergo oxidation with hydrogen peroxide to yield the corresponding pyridopyrimidin-4(3 T)-ones. Dehydrogenation of dihydropyrido[2,3-(i]pyrimidines by means of palladized charcoal, rhodium on alumina, or 2,3-diehloro-5,6-dicyano-p-benzo-quinone (DDQ) to yield the aromatic derivatives have been reported. Thus, 7-amino-5,6-dihydro-1,3-diethylpyrido[2,3-d]-pyri-midine-2,4(lif,3f/)-dione (177) is aromatized (178) when treated with palladized charcoal in refluxing toluene for 24 hours. 

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