Pyridines, synthesis from triazines

Reactions involving the [4 + 1 + 1] principle, an example of which is shown in equation (136), are rather uncommon and of strictly limited utility [3 + 2 + 1] and [2 + 2 + 2] processes, on th,e other hand, are well known. Representative [3 + 2+1] three-bond formation processes are given in equations (137)—(141), from which it can be seen that the common situation is where ammonia, a substituted amine or formamide constitutes the one-atom fragment. Many [2 + 2 + 2] atom fragment syntheses are known and some are familiar reactions. Thus, the cobalt(I)-catalyzed condensation of nitriles and isocyanates with alkynes gives pyridines and 2-pyridones, often in excellent yield (e.g. equation 142), while the cyclotrimerizations of nitriles, imidates, isocyanates, etc., are well established procedures for the synthesis of 1,3,5-triazine derivatives (e.g. equation 143). Further representative examples are given in equations (144)-(147), and the reader is referred to the monograph chapters for full discussion of these and other [2 + 2 + 2] processes. Examination of the... 

Isoxazole can be fused with pyridine in nine different ways the section on synthesis has been organized accordingly. Further fused systems arise from the diazines, the triazines and their areno and heteroareno homologues. 

Heterocyclic azadienes like di- and triazines have been used in the synthesis of pyridine rings. In general terms the reaction involves a regiospecific inverse electron demand Diels-Alder cycloaddition between the heterocycle and the enamine 280 followed by elimination of HCN (diazines) or N2 (triazines) and an amine from the primary cycloadduct 281 or 283, respectively, to give pyridines 282 and 284 (equation 61). At least in one case the latter type of intermediate has been isolated and fully characterized148. 

The overall sequence of carbenoid generation/ylide formation/[3-l-2]-cycloaddition or rearrangement was explored in the synthesis of a series of 1,3-triazine derivatives. Thus, 1,3-dipolar cycloaddition of the pyridinium ylide derived from 2-(3-diazo-2-oxopropylthio)pyridine gives a 1,3-thiazine ring incorporated into the polycyclic system (Scheme 21) (93JOC1144). 

One synthesis of isoxazolo[5,4-Z>]pyrimidines from 4-unsubtituted 5-AI has been reported (Section III.C.2). As discussed above for isoxazolo[3,4-Z>]pyridines, the reaction of 3-amino-5-methylisoxazole with carbamate 44 does not produce isoxazolo [3,4-7>]pyrimidines, isoxazolo[2,3-a] 1.3.5-triazines 45 being formed as the only products. Meanwhile, the condensation of 5-amino-3-methylisoxazole with the same carbamate yielded isoxazolo[5,4-Z>]pyrimidine 46 (04KGS496) (Scheme 20). 

A new, mild and general method for the synthesis of aryl-substituted-1,3,5-triazines from aromatic aldehydes and ammonia has been found. Treatment of a 1 1 pyridine, concentrated ammonia solution of aromatic aldehyde with excess of Fremy s salt at room temperature gave a readily separable mixture of a primary amide and 1,3,5-triazine (189). A,A-Dibenzylidenephenyl-methanediamine (190) on similar treatment produced almost identical results (Scheme 56) <85S95>. Extension of the reaction to aliphatic aldehydes does not appear to be possible as attempts to oxidize 2,4,6-trimethyl-hexahydro-1,3,5-triazine with Fremy s salt gave rise to complex mixtures, in low yield. 

Cyclocondensation between l,2-dihydroquinoxalin-2-ones and l,2,4-triazine-3,5-dione derivatives involves the carbonyl group of the 1,2,4-triazinedione and not the carbonyl group of the quinoxalinones <04JHC597>. New examples of the synthesis of pyridine and 2,2 -bipyridine derivatives from a variety of substituted 1,2,4-triazines through Diels-Alder reactions have been described <04T8893>. 

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... 

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