1.3.5- Triazine 2- -, ring synthesis

Sojitra, P. N. Patel, K. C.and Patel, H. S., high performance polyamides based on s-triazine ring synthesis and characterization. High Perform. Polym., 22, 974-988 (2010), DOI 10.1177/0954008310378054. 

Because of the ease of ring synthesis, symmetrically trisubstituted s-triazines have been more thoroughly studied, but a few nucleophilic substitutions of derivatives bearing a single leaving group are known. 2-Chloro-4,6-diphenyl- and 2-chloro-4,6-dimethyl-s-triazines (318) undergo facile nucleophilic displacements with ammonia, amines, and hydrazine, with alkoxide, or with hydrosulfide... 

Replacement of heterocyclic rings in nucleosides by ring systems which do not occur in nature represents another approach to compounds which may have activity against viral and neoplastic diseases. One of the early successes in this category involves replacement of a pyrimidine ring by a triazine. The synthesis starts with a now classical glycosidation of a heterocycle as its silylated derivative (146) with a protected halosugar (145), in this case a derivative of arabinose... 

The synthesis of this ring system was achieved by the reaction of the ketene aminal 79 with 3-morpholino-l-ethyl-l,2,4-triazinium tetrafluoro-borate 78 to give 80 (89IZV494). Cyclization of 78 with the bifunctional nucleophile 81 gave the pyrrolo[3,2-e][l,2,4]triazinones 82 (88TL1431). This reaction represents the first example of orthocyclization onto the 1,2,4-triazine ring by the addition of dienophiles at C-5,6 (Scheme 20). 

The synthesis has been described mainly by building the thiadiazole onto a triazine ring. However, one report has used thiadiazole 981 as starting material. Reaction of 981 with ethyl pyruvate gave 982 that was... 

In addition to the synthesis of industrially important azo dyes using heteroaromatic diazo components, intramolecular azo coupling reactions of heterocyclic diazonium ions also have interesting synthetic uses, because they lead to new fused-ring heterocycles, as shown by the diazotization of 2-amino-3-arylbenzimidazoles (12.7) in which, without isolation of the diazonium ion, a 1,2,4-triazine ring is formed (Kolodyazhnaya et al., 1973). Further examples of intramolecular azo couplings were reviewed by Tisler and Stanovnik (1980), and very extensively (403 references ) by Kishimoto et al. (1990). 

Several interesting analogues of structure 11.23 were synthesised recently. These derivatives of 4 methoxynaphthalimide contained a triazine ring with an unsaturated polymerisable substituent capable of addition copolymerisation with other vinyl or acrylic monomers. Such brighteners can be incorporated into the synthesis of polymeric finishes and show exceptional durability to organic solvents and wet treatments [42-44]. 

An alternative synthesis of this ring system involved the construction of the triazine ring at the first stage. Thus, the reaction of diethyl oxomalo-nate either with thiosemicarbazide followed by methylation or with S-... 

Results concerning these ring systems are summarized in Scheme 52. Synthesis of a benzologue of the [l,2,3]tri-azolo[4,3-triazine ring system has been published by Abbott et al. <2002T3185>. The essence of the cyclization procedure is diazotation of the zwitterionic aminoaryltriazole compound 261, whereupon an internal azo coupling takes place to yield the fused triazine 262 in low yield (24%). 

Research work in this area was concentrated to synthesis of thiazolo[3,2-A][l,2,4]triazine ring system and its selenazole analogue. While only three such procedures were discussed in CHEC-II(1996) <1996CHEC-II(8)445, 1984J(P1)2707, 1985KGS1497, 1987KGS554>, quite substantial new literature data have appeared in recent years. Two typical synthetic approaches are shown in Scheme 43, and reference to six further derivatives is also provided. 

A fairly substantial amount of preparative work on the title ring systems has been published in the recent years. Some procedures are closely related to earlier elaborated methods reviewed in CHEC-II(1996) <1996CHEC-II(8)445>, but some new approaches have also been recognized. The majority of the available literature relates to one ring system, thiazolo[2,3-c][l,2,4]triazine, whereas synthesis of four others have also been reported. Synthetic routes to these four outstanding ring systems are discussed first and shown in Schemes 46 and 47. 

The 1,2,3-triazine ring was constructed from o-aminophenyl oximes in the conditions of nitrosation (NaN02/HCl) , while hydrazinooximes were used for the synthesis of the 1,2,4-triazine ring Thus, cyclization of a-hydrazinooxime 342 with Pb304 in the presence of acetic acid afforded 1,2,4-triazines 343 in 44-54% yields (equation 149) . Interaction of oxime 344 with hydrazine leads to the spiro compound product 345 in 73% yield (equation 150) °. 

The synthesis of the novel [l,2]thiaphospholo[43-c][l,2>4]triazine ring system, exemplified by derivatives 20, has been accomplished by the action of Lawesson s reagent on 13,4-triazin-6-ones 19 <99T13457>. 

Most ring synthesis methods focus on formation of the five-membered pyrazole through cyclizations involving condensation of hydrazine with carbonyl moieties attached to the [l,2,4]triazine <1996CHEC-II(7)489>. A typical synthesis of the pyrazole ring to give various pyrazolo[4,3-< ][l,2,4]triazines 84 was reported by Rykowski eta/, using a... 

Cyclization of the urido-l,2,4-trizine derivatives (634) to the 1,2,4-triazino[2,3-c]quinazoline (635) by heating with polyphosphoric acid has already been discussed (see Section XVI.B.7) (74JHC747). However, pyrolytic cyclization of 634 by heating at 200° afforded the 1,2,4-triazino[4,3-c]quinazoline (638) as a result of eliminative cyclization between the urido function and N-4 of the 1,2,4-triazine ring (74JHC747). The structure of 638 was confirmed by an unequivocal synthesis from 2-oxo-4-thioxoquinazoline (639) (74JHC747). 

Asymmetric synthesis of primary amines by nucleophilic 1,2-addition of alkyl-lithiums to aldehyde SAMP/RAMP hydrazones has been reported in detail.105 On reaction with a range of lithium alkyls, 1,3,5-triazinc has been found to form 1,4-adducts which yield 1,4-dihydrotriazines on hydrolysis 106 in contrast LiNR2 or LiCR3(thf)2 promote 1,3,5-triazine ring-opening reactions. 

So we were induced to try this approach, too, and we started synthesis work in the field of s-triazines. The result of our primary working hypothesis was disappointing derivatives bearing anilino radicals showed no herbicidal effects. Surprisingly, however, the herbicidal activity reappeared in the structure 2-chloro-4,6-bis-diethylamino-s-triazine, compound G-25804 shown previously. The awareness that we were confronted with a completely new herbicidal matrix with apparently superior usefulness led us to intensive work around the s-triazine ring system. 

In 1977, when the above review was presented and published, the history of the s-triazine herbicides was already 25 years old, with the first synthesis of these chemicals completed in 1952. The filing of the first basic triazine patent case in Switzerland was on August 16, 1954, and the first commercial products appeared on the market in 1956, following the approval of simazine for use in corn by federal authorities in Switzerland on December 3, 1956. Several other agrochemical companies started immediately to work with their own s-triazine variations, using other radicals or amino-functions on the s-triazine ring. This further research was also briefly reviewed in Knusli s 1977 paper. 

As the polyol-based char formers needs to be substituted, Li and Xu40 reported the synthesis of a novel char former for intumescent system based on triazines and their derivatives. It is a macromo-lecular triazine derivative containing hydroxyethylamino, triazine rings and ethylenediamino groups (Figure 6.7). They showed that the new char former in an intumescent formulation containing APP... 

---