Triazine method

One can use s-triazine (163) as a source of formamidrazones that react with more triazine (56JOC1037) or undergo self-condensation in the presence of acid (62CB2546, 66CB3734). In the absence of acid the acylic dihydrazone (164) is formed and can be cyclized to 4-aminotriazole. Scheme 74 illustrates some applications of the triazine method (57JA2839) and Scheme 75 the use of trichloro-s-triazine (60AG956). 

Cyanogen bromide, triazine method, cychc trani-2,3-carbonate reaction, carbonylation, periodate oxidation, epoxide activation Curtis azide rearrangement, coupling reagent method, acid anhydride reaction Schiff base formation reaction... 

The synthesis of heterocycles 4 can be achieved in high yield by reaction of 1,3,5-triazine (1) with primary diamines 3 under moderate reaction conditions. Ammonia is again formed as the byproduct and the 1,3,5-triazine acts as a methine precursor.19 In contrast to other methods of preparing these heterocycles, the triazine method gives better yields and purer products.18... 

Starting triazine Method applied Electrophile Products and yields i%)... 

Manufacture. Dicyandiamide is converted into melamine by heating. Simple pyrolysis above the melting point leads to an exothermic reaction however, deammoniation occurs, forming products containing two or three triazine rings as well as melamine. After it was discovered in 1940 that deammoniation can be counteracted by conducting the reaction under ammonia pressure, various methods were developed to control the exothermic reaction on an industrial scale. 

This paper deseribes a rapid and versatile on-line-SPE LC-MS/MS method developed for the determination of various pestieides and tlieir metabolites in water. 28 pestieides, ineluding various triazines, phenylureas, organophosphorous eompounds and other speeies, were seleeted for systematie investigations. 

The metal chelating 2,2"-bipyridines, useful in material science, can be obtained by this method.For example, bis-triazines 92, in the presence of two equivalents of enamine 67, will produce bipyridines 93. 

Microwave irradiation generates pyridine 98 from triazine 97 and enamine 67. Again, the new technology reduces reaction time and the alternative conditions provide reaction manifolds not obtainable using traditional methods. ... 

The common method of preparation of 6-alkyl-2,4-dioxotetrahydro-triazines is the cyclization of acyl-biurets by aqueous hydroxide. Formyl biuret which should by analogy 3deld 5-azauracil had not been known until recently. Its transient formation can be expected during further synthesis of 5-azauracil. Piskala and GuP achieved... 

The chemistry of the 6-aza analogs of pyrimidine bases which has been developed from the biochemical aspect since about 1956 was based on work reported in relatively numerous older papers. In spite of the fact that 6-azauracil was prepared only in 1947 and suitable syntheses were described only quite recently, substances of this type and methods of their preparation had been known for a long time. The chemistry of 6-aza analogs of pyrimidine bases is therefore relatively closely linked with the chemistry of the 1,2,4-triazine derivatives. 

Substances of this type have hitherto received little attention. One of the reasons appears to be the limited possibilities of preparation. The only known method of preparation, described by Woolley et ai./ proceeds from the derivatives of 4-aminoimidazole-5-carboxylic acid. The amide of this acid (142) is treated with nitrous acid to yield 4-hydroxyimidazo [4,5-d]-i -triazine (2-azahypoxanthine) (143), the amidine (144) yielding the 4-amino derivative (2-azaadenine) (145) under the same conditions. 2-Azahypoxanthine was probably obtained in the same way earlier but was not identified. ... 

The infrared spectral method has been used to show that certain amino-l,2,4-triazines exist as such (Table VI). Although the separate isolation of 263 and 264 was claimed in 1940, this report is probably erroneous,... 

This review deals with methods for the synthesis of 1,2,4-triazine mono-lV-oxides and their reactivity. The interest in 1,2,4-tiiazines is due to their incorporation in many natural and artificial compounds, their biological activity, and other useful properties. 

It is useful to compare the spectroscopic data of 1,2,4-triazine mono-A-oxides with the data for the corresponding 1,2,4-triazines. Introduction of an A-oxide group in the 1,2,4-triazine ring changes its physicochemical properties dramatically, and the analysis of these changes allows one to determine which of three nitrogens is oxidized. The most useful method in this case is NMR spectroscopy, including H, C, and N NMR. 

Tiiazine A-oxides can be obtained by two general methods by direct oxidation of the parent 1,2,4-tiiazines with organic peracids, and by the formation of the A-oxide group of the 1,2,4-triazine ring by cyclization involving nitro, nitroso (isonitroso), or hydroxylamino groups. 

A more useful method for the synthesis of 1,2,4-tiiazine 4-oxides is the cyclization of a-hydrazonooximes 141 with orthocarboxylates or iminoesters. A variety of 1,2,4-triazine 4-oxides 55 were obtained by this methodology (71 LA 12, 73TL1429, 77LA1713, 78JMC623, 86JHC721, 87KGS257). 

The isomer lowest in energy is predicted to be the 2,5-dihydro-1,2,4-triazine 198g. The most stable structures always show two C=N double bonds. Moreover, in polar solvents, 198h should also be a dominant species [00PCCP2187]. The valence and Rydberg excited states of 1,2,3-triazine have been studied by multireference methods (MRD-CI) and the results are compared with experimental spectra [98CP39]. 

The first systematic theoretical study on dihydro-1,2,4-triazines was recently carried out (98JOC5824) the stabilities of all the possible unsubstituted dihydro-1,2,4-triazines were calculated using various theoretical methods, all reliable calculation methods consistently show that the 2,5-dihydro isomer 98 is the most stable. This is in perfect agreement with the experimental observations all the synthetic methods used for the preparation of dihydro-1,2,4-triazines result in 2,5-dihydro isomer 98, provided the structures of the reactants and the reaction mechanism allow its formation. Thus, although Metze and Scherowsky (59CB2481) claimed the formation of 1,2-dihydro-1,2,4-triazine 92 (R = = Ph) in the reduction... 

In the ring-closure reaction of a-acylaminoketones with hydrazines, some dihydro-1,2,4-triazines were obtained. The possible 1,2-, 2,3-, or 5,6-dihydro structures were excluded by IR spectroscopic studies however, this method, as well as the attempted preparation of fixed derivatives, failed to distinguish between... 

If the formation of a 2,5-dihydro isomer 98 is not allowed, other dihydro-1,2,4-triazines are formed aeeording to their order of stability ealeulated by various theoretieal methods (see Table III) (98JOC5824). 

Atrazine is a widely used triazine which can degrade to several products, including deisopropylatrazine (DIA), deethylatrazine (DEA) and hydroxyatrazine (HA). These species are highly polar and their determination by GC requires a derivatiza-tion step. LC methods combined with SPE (off-line or on-line) are therefore the ones which are most commonly used. The LC-LC method proposed in the literature (34) can allow low levels to be detected with a small sample volume. The experimental conditions are shown in Table 13.1. Due to the different polarity between the most... 

Figure 13.10 LC-LC chromatogram of a surface water sample spiked at 2 p.g 1 with ati azine, and its metabolites (registered at 220 nm). Conditions volume of sample injected, 2 ml clean-up time, 2.60 min ti ansfer time, 4.2 min The blank was subtracted. Peak identification is as follows 1, DIA 2, HA 3, DEA 4, atrazine. Reprinted from Journal of Chromatography, A 778, F. Hernandez et al, New method for the rapid detemiination of triazine herbicides and some of thek main metabolites in water by using coupled-column liquid cliromatography and large volume injection , pp. 171-181, copyright 1997, with permission from Elsevier Science.

P. Hernandez, C. Hidalgo, J. V. Sancho and P. J. Lopez, New method for the rapid determination of triazine herbicides and some of their main metabolites in water by using coupled-column liquid cliromatography and large volume injection , 7. Chromatogr. 171-181 (1997). 

A special method, with only two examples, starts from 1,2,4-triazines.20 21 Diels-Alder reaction with the strained dienophile dimethyl tricyclo[4.2.2.02,5]deca-3,7,9-triene-7,8-dicarboxylate (14) is followed by an elimination of nitrogen via a retro-Diels-Alder process. The formed product, however, cannot be isolated, but reacts via another retro-Diels-Alder reaction and an electro-cyclic reaction to provide the azocine derivative 15. The sequence order of the reactions is not clear, but both pathways lead to the same product. 

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