Diazine ring reactivity

Reactions of benzodiazines show no exceptional features compared with the simple diazines. Reactivity towards electrophiles is less than in quinoline and isoquinoline. If S Ar reactions take place, they lead to substitution of the benzene ring. As a rule, nucleophilic substitution of benzodiazines occur in the diazine ring, particularly if substituted by halogen. The quinazoline system displays C-4 regioselectivity, e.g. in the reactions of 2,4-dichloroquinazoline with amines or alcohols ... 

No kinetic data or semi-quantitative comparisons among themselves or with other diazines are available. The most reactive derivative is expected to be the 4-substituted-l,6-naphthyridine (425), with 2-substituted-1,6- and l-substituted-2,7-naphthyridines (426) somewhat less reactive, all three positions being activated by two ring-nitrogens by resonance. Other positions also activated in this way... 

The reactivity of 1,8-naphthyridine (27) is greater than expected.61,79 Here, unlike the diazines, the two heteroatoms with their unshared electron pairs are in separate rings. After correction for the two kinetically equivalent reactive sites, the rate constant for 27 is nearly the same as that for pyridine and four times larger than that for quinoline. These results are surprising, especially when it is remembered that the diaza substrate is substantially less basic than the comparison compounds. Correcting for the diminished nucleophilicity expected to be associated with the lower basicity of 27 serves to make the reactivity comparisons even more striking.61... 

Diazines are considerably more reactive toward nucleophiles than pyridines and as the number of ring nitrogens increases the propensity for nucleophilic addition reactions increases still more. Many 1,2,4-triazines give addition products with various nucleophiles which are formally dihydrotriazines. 

In the diazines, triazines and tetrazines, the effects of the additional nitrogen atom(s) are roughly additive. In Table 4 the positions of substituents in the common azine ring systems are listed in order of increasing reactivity. The limit is reached in 2-, 4- or 6-substituted 1,3,5-triazines for which the reactivity approximates to that in the corresponding carbonyl compound (559). 

Oxazine, azine and thiazine dyes are named for the characteristic heterocyclic ring systems 1,4-oxazine, 1,4-diazine, and 1,4-thiazine. The dyes are generally cationic (basic) or acid dyes. They also can be reduced to colorless forms, then oxidized back to the dye, as in vat dyeing. The dyes also have been used to a limited extent in disperse and fiber reactive applications. They are used as titration indicators and may be applied to acrylic fibers and leather. 

The aza substituent constants (vide supra) reflect the fact that electron-withdrawing annular nitrogens decrease the reactivity of any other ring nitrogen in the order ortho meta < para. For this reason, pyrazines should quaternize more readily than pyrimidines and pyridazines, and all three diazines should react faster than triazines. When the diazines are included in a Hammett plot for the methylation of substituted pyridines (p = —2.3), the positive deviations showed that they were all more reactive than indicated by their pK values. Relative rates compared with pyridine were pyridazine, 0.25 pyrimidine, 0.044 and pyrazine, 0.036 (72JA2765). Pyridazine in particular appears to be much more reactive than one would expect. (See Section III, A below). 

By analogy with 4- and 2-chloropyrimidines, it is reasonable to predict the relation 5-as-triazinyl > 3-os-triazinyl. The substantial activation by additional ring-nitrogens, especially in the optimal 1,3,6 arrangement, is evident in the fact that chloro-s-triaasines, even when deactivated by one or two substituents, are equally or more reactive than many chloro-azines or chloro-diazines. For example, 2,4,6-trichloro-s-triazine reacts with various nucleophiles to give monosubstituted derivatives at 0-10°, disubstituted at 20-30°, and trisubstituted at... 

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