1.3.5- Triazine, trifluoro-, reaction with

Condensed pyridines were obtained when 1,2,4-triazines reacted with cyclic alkenes. Trichloro-l,2,4-triazine (73) afforded the condensed pyridines (370a, b) in high yield with cyclopentene and (Z)-cyclooctene, respectively. In the reaction with cyclopentene the bis adduct (371) was isolated in small amount but the bis adduct (372a) is the sole reaction product when (73) is treated with norbornene. The more reactive trifluoro-1,2,4-triazine (325) affords bis adducts (371b, c 372b) with cyclopentene and (Z)-cyclooctene as well as with norbornene (79CC658). 

Thus, 3,5,6-trichloro-l,2,4-triazine affords the condensed pyridines 6 in high yield when reacted with cyclopentene (77%) or (Z)-cyclooctene (80%), respectively387 (see Houben-Weyl, Vol. E7b, p 476 ff). In the reaction with cyclopentene the bisadduct 7 is isolated in small amounts. The bisadduct is the sole product when the trichloro compound is reacted with bicyclo[2.2.1]hept-2-ene. The more reactive 3,5,6-trifluoro-l,2,4-triazine affords the bisadducts with cyclopentene and (Z)-cyclooctenc as well as with bicyclo[2.2.1]hept-2-ene, e.g. formation of 8 (X = F).385... 

Cyanuric halides also react with other organornetallic compounds. Thus, 2,4,6-trifluoro-l,3,5-triazine (2) on reaction with lithium (trimethylsilyl)acetylide forms the compound 2,4,6-tris[(trimethylsilyl)ethynyl]-l, 3,5-triazine (36).129... 

Microwave assisted reaction of 2-diazo, 4,4-trifluoro-3-oxobutanoate 37 with aryl hydrazides in the presence of copper(II)acetate, followed by reaction with ammonium acetate in acetic acid gave the 1,2,4-triazines 38 in modest yield (Scheme 17) [27],... 

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. 

The first examples of formation of a or-complex between a polyfluoro-aromatic compound and F have been reported trifluoro-5-triazine and CsF in tetra-methylene sulphone formed a o--complex which could be isolated and characterized by F n.m.r. spectroscopy. Analogous reactions with perfluoro-mono-and -di-isopropyl-s-triazines gave analogous complexes containing—CF2—, but they were not isolated. 

Method A 4 Cl2 was passed through SbF3 (100g, 0.54mol) at 100"C until no more Cl2 was absorbed. The SbF3Cl2 which formed was allowed to cool to rt and 2,4,6-trichloro-l, 3,5-triazine (1 50 g. 0.26 mol) was added. The reaction flask was fitted with a 30-cm Vigreux column and the flask was heated until all the liquid product had distilled. Redistillation of the liquid product gave 2,4,6-trifluoro-l, 3,5-triazine (2) as a colorless liquid yield 26.1 g (71 %) bp 74 C. 

Thus reactions of perfluoro-2-methylpent-2-ene and perfluoro-5-azanon-4-ene with urea in the presence of triethylamine in dipolar aprotic solvents (MeCN, DMF) form 6-fluoro-4-pentafluoroethyl-5-trifluoro-methyl-l//-pyrimidin-2-one 93 and an s-triazine derivative, respectively (00JFC(103)105, 80/82JAP(K)85377). 

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. ... 

The chlorine substituents of cyanuric chloride can be exchanged with other halogen and pseudohalogen substituents.96,133 140 2,4,6-Trifluoro-l,3,5-triazine (2) (see also p 683) is formed by the reaction of cyanuric chloride (1) with sodium fluoride.133... 

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... 

The reaction of 4,5,6-trichloro-l,2,3-triazine 4 with potassium fluoride at an elevated temperatures provides fully substituted 4,5,6-trifluoro-l,2,3-triazine 2 in addition to compounds 5 and 6 with partial displacement of chlorine atoms (Scheme 7) [11], It is clear that yields of fluorinated products depend on the reaction conditions (Table 3) [11]. At temperatures of 150-200 °C replacement of one or two chlorine atoms take place. The polyfluorinated 1,2,3-triazines 2, 5 were obtained when using two-step process in 55-69 % yields. 

Another example illustrating utility of this approach is displacement of chlorine atoms in 3,5,6-trichloro-l,2,4-triazine which does occur in a melt of compound 17 with dry KF (Scheme 12) [20]. The conversion degree depends on the reaction conditions at450 °C the dominantproduct of the reaction proved to be 3,5,6-trifluoro-1,2,4-triazine 18, while 3-chloro-5,6-difluoro-l,2,4-triazine 19 was isolated as a minor product. 

Incorporation of perfluoroisopropyl groups into trifluoro-l,2,4-triazine takes place smoothly in the reaction of 18 with hexafluoropropene and cesium fluoride without of any solvent [12], When the reaction is carried out at 125 °C for 25 min amixture of 5-perfluoroisopropyl-derivative 100 and 3,5-di- and 3,5,6-tri (perfluoroisopropyl)-1,2,4-triazines 101,102 are formed (Scheme 43), while the formation of tiisubstituted derivative 102 (yield 52 %) takes place on heating at 110 °C for 2 h. 

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). 

Reaction of 2,4,6-trifluoro-l,3,5-triazine 55 with l-amino-8-naphthol-3,6-disulfonic acid provides l-(4, 6 -difluoro-r,3, 5 -triazyn-2 -yl)amino-8-naphthol-3,6-disulfonicacidm95 % yield [90], Substitution of fluorine atoms in fluorotriazine dye 148 with the alkoxides, generated from tetrahydropyran-2-methanol, a- and p-methylglucopyranoside, D-sorbitol, D-mannitol and D-glucose, has been found to lead to the corresponding conjugates 149 (Schane 62) [91],... 

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