Triazines and tetrazines

Bettinetti, E. Fasani, G. Minoli, and S. Pietra, Gazz. Chim. ItaL, 1979,109, 175. 

A simple, high-yield, preparation of 1,3,5-triazine by heating formamidinium acetate with triethyl orthoformate has been reported. Lewis-acid-catalysed condensation of two molecules of a cyanogen halide with one of a trihalogenomethyl compound, e.g. PhCCL, results in the formation of a 4,6-dihalogeno-triazine, e.g. (304).  

Reagents i, PhClNHjlNX, CHCI3, pyridine ii, chloranil, PhH, heat 

Hexahydrotriazines (312) react rapidly with acid chlorides to give the N-(chloromethyl)carboxamides (313) in good yield. This is a considerable 

The novel l,2,3,6-tetrahydro-l,2,3,4-tetrazines (314) have been prepared by the cycloaddition of azoalkenes with azodicarbonyl compounds yields are good, and the structure has, in one case, been confirmed by X-ray crystallography. The dihydrotetrazine (315) is converted into the aromatic system (316) (98%) simply by heating (at 150—155 °C, for 30 min) the thermolability of the dihydrocompound may be attributable to its Stt system. 

The first reported synthesis of 1,2,3-triazine involves the oxidation of 1-aminopyrazole with nickel peroxide other oxidants, such as lead tetraacetate, are ineffective, although they can be used to prepare substituted 

The generality of the synthesis of 1,3,5-triazines from 7V-cyano-amidines and amide chlorides that was reported last year has been further developed this route allows the preparation of s-triazines with a wide variety of substi- 

Reagents i, syw-triazine, HOAc, ACjO, BF3 EtjO, reflux 

2-dibromoethane enolizable ynones e.g. MeCOC=CSiMe3) give mixtures of products, cycloaddition occurring either across the triple bond [giving acyl-pyridazines, e.g. (158 R = COMe)] or across the enol double bond [giving (after loss of water) alkynylpyridazines, e.g. (159)]. In similar fashion, the 

Seven-membered heterocycles containing at least two heteroatoms  

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Although all the rings in Figure 1 contain six tt-electrons, the accumulation of electronegative nitrogen atoms in the polyaza structures leads to hydrolytic as well as thermal instability. This is noticeable in pyrimidine, and marked in the triazines and tetrazine. Some stability can be conferred by appropriate substitution, as we shall outline later. 

The 27T-electrons of the carbon-nitrogen double bond of 1-azirines can participate in thermal symmetry-allowed [4 + 2] cycloadditions with a variety of substrates such as cyclo-pentadienones, isobenzofurans, triazines and tetrazines 71AHC(13)45). Cycloadditions also occur with heterocumulenes such as ketenes, ketenimines, isocyanates and carbon disulfide. It is also possible for the 27r-electrons of 1-azirines to participate in ene reactions 73HCA1351). 

Another type of special diene, the polyaza benzene heterocyclics, such as triazines and tetrazines, is discussed in Section 6.6.2. 

Elimination of nitrogen from D-A adducts of certain heteroaromatic rings has been useful in syntheses of substituted aromatic compounds.315 Pyrazines, triazines, and tetrazines react with electron-rich dienophiles in inverse electron demand cycloadditions. The adducts then aromatize with loss of nitrogen and a dienophile substituent.316... 

Many reports have dealt with stmctures which can be included under this heading and so, only examples bearing triazine and tetrazine rings will be highlighted. 

Extrapolation from benzene through pyridine to the diazines and then to the triazines and tetrazines delineates the main trends of azine chemistry. 

Under the alternative low-temperature procedure, animation is conducted in liquid ammonia. The use of KNH2, which is more soluble than NaNH2 in this solvent, is preferable. The reaction occurs under homogeneous conditions and does not show the previous dependence on substrate basicity. Diazines, triazines, and tetrazines, which usually undergo destruction in the high temperature process, are aminated successfully in liquid ammonia. 

In the diazines, triazines and tetrazines, the effects of the additional nitrogen atom(s) are roughly additive. In Table 4 the positions of substituents in the common azine ring systems are listed in order of increasing reactivity. The limit is reached in 2-, 4- or 6-substituted 1,3,5-triazines for which the reactivity approximates to that in the corresponding carbonyl compound (559). 

Cycloaddition reactions of the C = N bond of azirines are common, e.g. Scheme 31 (71AHC(13)45, B-83MI 101-03, 84CHEC(7)47). Azirines can also participate in [4 + 2] cycloadditions with cyclopentadie-nones, isobenzofurans, triazines, and tetrazines. 

Pyrimidines are expected to be much less reactive in cycloadditions of this type than triazines and tetrazines. Normally, the presence of electron-withdrawing substituents on the pyrimidine ring is essential. The best results are obtained with a nitro group in position 5. Reaction of 5-nitropyrimidine with various enamines affords fused nitropyridines (82TL3965 89T2693) (Scheme 59). The mechanism (89T2693) is in agreement with the usual expectations. 

The monocyclic diazines, triazines, and tetrazines are all theoretically subject to electrophilic attack at one or more of their annular nitrogen atoms by protons alkylating, acylating, and aminating reagents and peracids. Coordination with metals could also be classified under this heading. 

Cyclic, electron-deficient diaza-1,3-butadienes, e. g. pyrimidines, pyridazines, triazines and tetrazines have proved to be an extremely versatile synthetical tool. Extensive studies aimed at the use of these dienes in the synthesis of natural products stem from Boger s group [11]. 

Conversely, nucleophilic attack is increasingly easier than in pyridine. Nucleophiles which react only with quaternized pyridines will sometimes react with the parent diazines. Triazines and tetrazines are even attacked by weak nucleophiles. 

Successive introduction of nitrogen atoms into benzene causes a gradual reduction in aromatic stabilization. The diazines still show typical aromatic behavior in that in most of their reactions they revert to type. However, with the triazines and tetrazines, decreasing aromaticity increases the ease of both thermal and photochemical fragmentations and rearrangements, and of cyclic transition state reactions with other reagents. 

Successive substitution of carbon by nitrogen lowers the energy of the LUMO. As a consequence, the ease of reduction and the stability of radical anions are increased from benzene to pyridine, diazines, triazines, and tetrazines. 

The basicities of triazines and tetrazines are undoubtedly considerably lower than those of the diazines, but few quantitative data are available. 

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