Occurrence of Covalent Hydration in Heteroaromatic Substances

Covalent hydration has been demonstrated in the following families of compounds 1,6-naphthyridines, quinazolines, quinazoline 3-oxides, foiu families of l,3,x-triazanapththalenes, both l,4,x-triazanaphthalenes, pteridines and some other tetraazanaphthalenes, and 8-azapurines these compounds are discussed in that order. In general, for any particular compound (e.g. 6-hydroxypteridine) the highest ratio of the hydrated to the anhydrous species follows the order cation neutral species anion. In some cases, however, anion formation is possible only when the species are hydrated, e.g. pteridine cf. 21 andN-methyl-hydroxypteridines (Section III, E, 1, d). Table V in ref. 10 should be consulted for the extent of hydration in the substances discussed here. 

The physical properties of four of the six possible naphthyridines have been examined in some detail, and hydration could not be demonstrated in the neutral species and cations of 1,5-, 1,6-, 1,7-, and 

8-napththyridine. The principal evidence against hydration was the similarity between the ultraviolet spectra measured in cyclohexane, in water at near neutral pH, and in dilute aqueous acid. The ionization constants also showed no apparent anomaly. 1,6-Naphthyridine is of particular interest because water could add at two different sites, 

6- (10) or 1,2- (11), to form cations which are stabilized by resonance (see Section IV for a discussion of this factor in stabilization). However, 

8-nitro-l,6-napththyridines in which the electron-deficiency on C-2 and C-5 in 1,6-naphthyridine is reinforced. The neutral molecules of both nitro compounds are predominantly anhydrous, but the cations are largely hydrated. The anomalous behavior of the cations was revealed by ultraviolet spectroscopy. Spectra determined in strong sulfuric acid and anhydrous dichloroacetic acid indicated that water-addition was involved, and using rapid-reaction techniques the presence of the unstable hydrated neutral species was detected. Hydration was absent from both the neutral species and the cation of 

Hydration in quinazolines has been discussed in an earlier review and will be only briefly reported here. Recent findings are considered in more detail. 

The anomalous behavior of quinazoline was first discovered by Albert et who made the surprising observation that 4-methyl-quinazoline 2.5) was a weaker base than quinazoline (pA 3.5). Mason then observed that the ultraviolet spectrum of the quinazoline cation was abnormal but that the spectrum of 4-methylquin-azoline was normal (see Fig. 2). These anomalies led to the suggestion that water adds covalently to the cation of quinazoline to give 12 (R = H). The occurrence and position of hydration were confirmed by a detailed study of the ultraviolet and infrared spectra of the anhydrous and hydrated hydrochlorides and by mild oxidation of the cation to 4(3 )-quinazolinone. Using the rapid-reaction technique (the continuous-flow method), the spectrum of the unstable 

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