Pyridines from 1,2,4-triazines

In an effort to address this issue. Raw and Taylor have developed a tethered imine-enamine (TIE) methodology for the s3mthesis of highly substituted pyridines from 1,2,4-triazines 76 (04CC508, 05JOC10086). The rationale is the in situ formation of a zwitterion 80, which, it is postulated, mimics the N-oxide 82 intermediate of the Cope elimination (Scheme 27). Alternatively, the internal base may promote epimerisation and so facilitate elimination through the antiperiplanar configuration. The tethered imine-enamine species (e.g. 77) is produced from N-methy-lethylenediamine and the ketone in situ and the reaction proceeds under mild conditions to furnish the pyridines 81 directly. 

Krayushkin M, Sedishev I, Yarovenko V, Zavarzin I, Kotovskaya S, Kozhevnikov D, Charushin V (2008) Synthesis of pyridines from 1,2,4-triazines under high pressure. Russ J Org Chem 44 407-411... 

Boger [57] has utilized inverse electron-demand Diels-Alder reaction of 3,6-bis(methylthio)-l,2,4,5-tetrazine 150 with electron-rich dienophile 151 to produce 1,2-diazine 152 (Scheme 37). Thermally conducted reaction at atmospheric pressure (xylene, 140 °C, 26h) afforded diazine 152 in lower yield (78%). Similar [4 + 2] cycloaddi-tion/nitrogen elimination methodology followed by aromatization was applied by Boger in the S5mthesis of pyridines from triazine 153 and 151 (Scheme 37) [58]. In classical conditions, pyridine 154 was produced in 72% yield (CHCI3, 22h,60°C). 

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. ... 

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. 

In addition to conventional shell fitting, authors have used Monte Carlo simulation. During MC calculation, the Cm atom was positioned at random position in the 10 A diameter sphere formed by three coordinating BTP molecules, and the corresponding theoretical EXAFS spectra were calculated and compared with the experimental spectrum. From the best agreement between the theoretical and experimental EXAFS spectra, the Cm-N distances equal to 2.52 A and 2.57, 2.59 A for nitrogen atoms of pyridine and triazine rings, respectively, were obtained. 

The full scope of the acid-catalyzed one-step conversion of N-tert-bu-tylmethanimine, generated in situ from 1,3,5-tri-tm-butylhexahydro-1,3,5-triazine, to symmetrical 3,5-disubstituted pyridines employing enamines has been detailed.290 The generation of 2,3,5,6-tetrasubstituted pyridines from the thermal reaction of enolizable ketones with hex-amethylphosphoric triamide has been proposed to proceed by in situ generation and subsequent [4 + 2] cycloaddition of /V-methyl-1 -aza-1,3-butadienes with intermediate dimethylamino enamines.30... 

Seitz et al. prepared various l,2,4-triazine-C -nucleosides 340 via cycloaddition of 3,6-bis(trifluoromethyl)-l,2,4,5-tetrazine 147 to monosaccharide-derived imido esters 339 as intermediates in their quest for new pyridine C-nucleosides <1999ZNB549, 1997ZNB851, 1995AP175>. Similarly, the same group reported the preparation of novel 2-(2 -pyrrolidinyl)pyridines from (3 )- and (R)-proline via cycloaddition of 3,6-bis(trifluoromethyl)-l,2,4,5-tetrazine 147 to heterodienophilic imidates or hydrazones derived from (3)- and (R)-proline <1999TA573>. Reaction of dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate 150 with either 0-methylisourea or cyanamide gave... 

With this foundation, Boger communicated the use of 1,2,4-triazines as a dependable, azadiene equivalent for Diels-Alder approaches to substituted pyridines. Electron rich olefin 19, prepared from the corresponding ketone, was allowed to... 

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]. 

Preparation of this ring system has been performed either from a 1,2,4-triazine or a pyridine precursor. 

Pyridine A-oxides were converted to tetrazolo[l,5-a]pyridines 172 by heating in the presence sulfonyl or phosphoryl azides and pyridine in the absence of solvent <06JOC9540>. 3-R-5-Trinitromethyltetrazolo[l,5-a]-l,3,5-triazin-7-ones 173 have been prepared from the alkylation of 5-trinitromethyltetrazolo[l,5-a]-l,3,5-triazin-7-one silver salt with different alkylation agents <06CHE417>. The use of 2-fluorophenylisocyanide in the combinatorial Ugi-tetrazole reaction followed by a nucleophilic aromatic substitution afforded tricylic tetrazolo[l,5-a]quinoxaline 174 in good yields and with high diversity <06TL2041>. 

Thiadiazolines are less stable compared to 1,2,4-thiadiazoles and this can be attributed to the loss of aromatic character. They are readily cleaved at the N-S bond under fairly mild conditions (H2S in pyridine) in some cases, the product from ring cleavage can recyclize to give new heterocyclic ring systems. The 3-imino-l,2,3-thiadiazoline 24 when reduced with H2S affords the two J-triazine derivatives 25 and 26 (Scheme 3) <1996CHEC-II(4)307>. 

SANEX 3 used the 2,6-Z) -(5,6-dialkyl-1,2,4-triazine-3-yl)pyridine family of extraetants eontaining the propyl group, whieh are able to selectively extract trivalent actinides from Imoldm EINO3 [53,78]. The extractant was 0.04mol dm in a mixture of 70%/30% TPH/octanol. A flow sheet based on this solvent has been tried and is shown schematically in Fig. 12.21 the results are given in Table 12.13. The feed was an... 

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