2.4.6- Trichloro-l ,3,5-triazine

Direct bromination readily yields the 6-bromo derivative (111), just as with uracil. Analogous chlorination and iodination requires the presence of alkalies and even then proceeds in low yield. The 6-chloro derivative (113) was also obtained by partial hydrolysis of the postulated 3,5,6-trichloro-l,2,4-triazine (e.g.. Section II,B,6). The 6-bromo derivative (5-bromo-6-azauracil) served as the starting substance for several other derivatives. It was converted to the amino derivative (114) by ammonium acetate which, by means of sodium nitrite in hydrochloric acid, yielded a mixture of 6-chloro and 6-hydroxy derivatives. A modified Schiemann reaction was not suitable for preparing the 6-fluoro derivative. The 6-hydroxy derivative (115) (an isomer of cyanuric acid and the most acidic substance of this group, pKa — 2.95) was more conveniently prepared by alkaline hydrolysis of the 6-amino derivative. Further the bromo derivative was reacted with ethanolamine to prepare the 6-(2-hydroxyethyl) derivative however, this could not be converted to the corresponding 2-chloroethyl derivative. Similarly, the dimethylamino, morpholino, and hydrazino derivatives were prepared from the 6-bromo com-pound. ... 

On reaction with aged phosphoroxychloride, 6-azauracil formed 3,5-dichlorotriazine (117) in only a 10% yield. " A somewhat higher yield (30%) was obtained from the reaction of 6-bromodioxotriazine which gave 3,5,6-trichloro-l,2,4-triazine. Similar reactions take place much more readily with uracil and in better yield. " Thus,... 

Trichloro-l,2,4-triazine was reacted with menthanol and subsequently crystallized from w ater to yield 5-chloro-6-azauracil. A chloro-dimethoxy derivative appears to be an intermediate product, this being further cleaved by hydrogen chloride. No 2,4-dimethoxy derivatives have been prepared so far. 

Addition of cyclopentene to trifluoro-1,2,4-triazine gave products arising from addition of a second molecule of olefin. This was in contrast to trichloro-l,2,4-triazine where the eventual products were predominantly pyridine derivatives [82JCS(P1)1245]. 

Trichloro-l,2,4-triazine reacts with cycloheptene and cyclododecene to give 2,6-dichloropyridine derivatives (e.g., 10) via an intermediate dihydropyridine formed by Diels-Alder addition and loss of Nj <96JCS(P1)519>. 

Trichloro-l,2,4-triazine (73) reacts with potassium fluoride to give the trifluoro compound (325). This reacts with hexafluoropropene to give 5-heptafluoroisopropyl-3,6-difluoro- (326), 3,5-bis(heptafluoroisopropyl)-6-fluoro- (327) and a small amount of 5,6-bis(heptafluoroisopropyl)-3-fluoro-l,2,4-triazine (328) and finally to the... 

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). 

Trichloroethylene, 479-480 Trichloro-l,2,4-triazine, 480 Tricyclo-cfta-santalol, 37 Triethoxydiiodophosphorane, 480-481 Triethylamine, 481... 

Frequencies and intensities of bands in the IR spectra of 1,2,4-triazines have been calculated by the 4-31G method50 and by ab initio Hartree-Fock level with 6-31G, 6-31G, U-9 and 3-21G methods.51 The shifts for the protons in the parent 1,2,4-triazine have been predicted and are in reasonable agreement with the observed values.52 The shifts of the 13C NMR signals for 3,5,6-trichloro-l, 2,4-triazine have been calculated by the first and second order SCS method and compared with the experimental values.53 The nature of lone pair effects of heteroatoms on direct 13C — H spin coupling constants has been calculated by the AMI method54 and the nuclear shielding tensors of 15N and 1 C nuclei by the SOLO (second-order corrected localized orbital-local origin method) ab initio method.55 14N Shifts have been predicted.75 The electron distribution of 1,2,4-triazines has been estimated from the observed NMR shifts.76... 

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... 

Pyrolysis of 3,5,6-trichloro-l,2,4-triazine (t) at660 °C affords trichloroacrylonitrile, tetra-chloroethene and nitrogen. The formation of the nitrile is explained by the intermediate formation of trichloroazete, ring opening and migration of chlorine from C2 to C4.431... 

The shifts of the C NMR signals of 3,5,6-trichloro-l,2,4-triazine have been compared with the calculated values obtained by first and second order SCS methods 3= 160.8 (C-3 157.7, 163.4),... 

Several pyridine syntheses involving [4 + 2] cycloaddition reactions have been reported. Thus when trichloro-l,2,4-triazine (18) is heated with alkenes, 2,6-dichloropyridines (19) are formed in 75-80% yield (Scheme 9). ... 

The isolation of a 45% yield of trichloroacrylonitrile (296) upon thermolysis (at 600 °C) of trichloro-l,2,4-triazine (295) may implicate an azete intermediate (Scheme 116). ... 

Armstrong et al. (07JOC8019) investigated a synthetic approach to (+ )-epibatidine 128 from 3,5,6-trichloro-l,2,4-triazine 124 (Scheme 43). However, the approach was abandoned due to the poor selectivity in the flZfl-Diels-Alder reaction and the anticipated difficulty in the selective removal of the extra chlorine from 127. The authors did note the utility of this approach as a convenient means of varpng the heteroaromatic portion of epibatidine in analogue synthesis. 

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. 

Scheme 12 Displacement of chlorine atoms in 3,5,6-trichloro-l,2,4-triazine...

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