1.2.4- Triazine, trifluoro-, nucleophilic

Trifluoro-l,2,4-triazine (106) behaves similarly to the trichloro compound toward nucleophilic reagents, but is more reactive. When treated with methanol at room temperature it gives a mixture of 5,6-di-methoxy-3-fluoro-l,2,4-triazine (109) and 3,5-dimethoxy-6-fluoro-l,2,4-triazine (110) in the ratio 2 1 (82JCS(P1)1251). Reactions of 106 with di-... 

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. ... 

Nucleophilic aromatic substitution reactions follow the well-established two-step addition-elimination mechanism via a Meisenheimer intermediate (Fig. 8.3). Indeed, reaction of fluoride ion with trifluoro- -triazine, gives the corresponding perfluorocarbanion system that has been directly observed by NMR spectroscopy, supporting this mechanistic rationale. This reactivity has been termed mirror-image chemistry, which contrasts the very well-known chemistry of... 

Barlow, M.G. Haszeldine, R.N. Simon, C. Simpkin, D.J. Preparation and some nucleophilic substitution reactions of trifluoro-l,2,4-triazine. J. Chem. Soc., Perkin Trans. 1 1982, 1251-1254. 

A number of transformations involving the displacement of fluorine atoms in fluorinated 1,2,4-triazines have been described. In case of 3,5,6-trifluoro-l,2,4-triazine 18 the leaving mobility of fluorine atoms in these displacement reactions is decreasing as follows F >F >F . In accordance with this sequence the hydrolysis of 1,2,4-triazine 18 results in the formation of 6-fluoro-l,2,4-triazine-3,5-(2H,4H)-dione 89 (Scheme 40) [20], The reaction of compound 18 with methanol in a sealed tube afforded 3,5-dimethoxy-6-fluoro- and 5,6-dimethoxy-3-fluoro-1,2,4-triazines 90 and 91 in the ratio 1 2 in total yield of 46 % [20]. Reactivity of 3,5,6-trifluoro-l,2,4-triazine 18 towards N-nucleophiles can be illustrated by the reactions with ammonia (leading to 5-amino-3,6-difluoro-l,2,4-triazine 92), diethylamine and 4-chloroaniline. The reaction of 18 with diethylamine affords two products, 5-diethylamino-3,6-difluoro-l,2,4-triazine 93 and 3,5-bis(diethylamino)-6-fluoro-l,2,4-triazine 94 (Scheme 40) [20], while the only compound 95 was obtained from the reaction of 18 with 4-chloroaniline. 

Nucleophilic replacement of fluorine atoms in azaaromatic compounds can be performed under rather mild reaction conditions, and this method is certainly one of the most effective approaches to their functionalization. Incorporation of perfluoroisopropyl groups into 2,4,6-trifluoro-l,3,5-triazine 55 proceeds smoothly... 

It is worth noting that 2,4,6-trifluoro-l,3,5-triazine 55 is less active than cyanuric chloride in the reaction of with aniline (Scheme 49) [84]. N,N-Dimethylaniline and l,8-bis(dimethylamino)naphthalene react with cyanuric fluoride 55 as C-nucleophiles to give 2,4-difluoro-6-(4-dimethylaminophenyl)-l,3,5-triazine 119 and l,8-bis(dimethylamino)-4,5-(2,4-difluoro-l,3,5-triazinyl-6)naphthalene 123 (Scheme 49) [8], Contrary to it, N,N-diethylaniline, and ortho- or para-substituted N,N-dimethylanilines react with trifluoro-l,3,5-triazine 55 as N-nucleophiles. These reactions are accompanied by elimination of N-alkyl group and the formation of 2,4-difluoro-6-arylamino-l,3,5-triazines 120-122 (Scheme 49). 

Barlow M, Haszeldine R, Simon C, SimpMn D, Ziervogel G (1982) Heterocyclic polyfluoro-compounds. Part 39. Preparation and some nucleophilic substitution reactions of trifluoro-1,2,4-triazine. J Chem Soc PerMn Trans 1 1251-1254... 

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