Triazines reactivity with nucleophiles

Base-catalyzed hydrogen exchange, 16, 1 Basicity and acidity of azoles, 41, 187 Behavior of monocyclic 1,2,4-triazines in reactions with C-, N-, O-, and S-nucleophiles, 46, 73 1-, 2-, and 3-Benzazepines, 17, 45 Benzisothiazoles, 14, 43 38, 105 Benzisoxazoles, 8, 277 29, 1 Benzoazines, reactivity with nucleophiles,... 

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. 

The three reactive chlorines on TsT have dramatically different reactivities toward nucleophiles in aqueous solution. The first chlorine is reactive toward hydroxyls as well as primary and secondary amine groups at 4°C and a pH of 9 (Mumtaz and Bachhawat, 1991 Abuchowski et al., 1977a). Once the first chlorine is coupled, the second one requires at least room temperature conditions at the same pH to efficiently react. If two chlorines are conjugated to nucleophilic groups, the third is even more difficult to couple, requiring at least 80°C. After activation of mPEG with TsT, it is therefore, for all practical purposes, only possible to couple one additional component to the triazine ring. 

Most mono-anchor dyes are derivatives of cyanuric chloride (2,4,6-trichloro-1,3,5-triazine [108-77-0]), a molecule of wide synthetic potential because the three chlorine atoms on the triazine ring differ in their reactivities [12], The first chlorine atom exchanges with nucleophiles in water at 0 - 5 °C, the second at 35 -40 °C, and the third at 80 - 85 °C. A wide variety of triazinyl dyes can thus be prepared by careful selection of the reaction conditions. Condensation of cyanuric chloride with a chromophore ( Chrom. ) containing an amino group yields the highly reactive dichlorotriazinyl dyes 1 [11]. These very reactive dyes are sensitive to hydrolysis, and a suitable buffer is usually added to the powdered dye to increase its stability [13],... 

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... 

The foregoing discussion has outlined principles that can account for very wide differences in reactivities of the C—F bond. For example, while saturated perfluorocar-bons like polytetrafluoroethene are relatively inert to nucleophiles, at the other extreme are perfluoroisobutene, which reacts with neutral methanol, and perfluoro-l,3,5-triazine, which is hydrolysed in moist air. As a note of caution, great care should be taken with the systems that are very reactive to nucleophiles and correspondingly potentially very toxic, although there is no good correlation between toxicity levels and reactivity towards nucleophiles. More will be said about some of these systems in later chapters. 

Indeed, 1,2,4-triazines have a profound tendency to react with nucleophilic reagents. All carbon atoms in 1,2,4-triazines are vulnerable to attack by nucleophiles (78HC(33)189 84MI3, 840PP199) however, reactivities of C-3, C-5, and C-6 positions differ greatly, depending on the substituents present in the ring. 

Trichloro-s-triazine is mono-aminated at temperatures of — 15° to 100°, depending on the nucleophilicity of the amine and on the solvent. With ammonia and alkylamines, one chloro group is replaced at — 15 to 10°, a second at 10—50°, and a third at 20-100°. ° Unsymmetrical triamino derivatives can be prepared by adding one mole of three different amines to the reaction mixture at each of the three temperatures. The tribromo analog is stated to react more rapidly than cyanuric chloride with ammonia or primary and secondary amines. Toward ammonia, methoxide ion, or water, the trifluoro analog is also qualitatively more reactive with ammonia (0°, 1 hr) mono-amination occurred in ether and di-amination in tetrahydrofuran. ... 

Cyanuric fluoride behaves much the same as cyanuric chloride but its higher reactivity leads to nucleophilic reactions with aromatic amines, which act as carbon nucleophiles. This is a useful advantage for cyanuric fluoride, as a synthetic reagent, for the synthesis of these triazine derivatives with carbon substituents. 

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