Imidazol 1,2-6 11,2,4 triazines synthesis

Construction of the imidazole ring onto a triazine has been also used for the synthesis of this group of compounds. The reaction of 3-aminobenzofl, 2,4]triazine with a-bromoacetaldehyde acetal gave the [1,2-b] linear isomer. On the other hand, the similar reaction on 1-oxide 461... 

Some of the ring expansion reactions discussed in Section 2.03.3.3.1 can be extended to five-membered heterocycles containing two or more heteroatoms. Reaction of imidazoles and pyrazoles with dichlorocarbene, for example, gives chloropyrimidines together with small amounts of chloro-pyrazines or -pyridazines, and oxidative ring expansion of 1-aminopyrazole with nickel peroxide gives 1,2,3-triazine (this, in fact, constitutes the only known synthesis of the unsubstituted triazine). There are, however, a number of interesting and useful transformations which are unique to five-membered polyheteroatom systems. 

The presence or absence of the dioxolane protecting group in dienes dictates whether they participate in normal or inverse-electron-demand Diels-Alder reactions.257 The intramolecular inverse-electron-demand Diels-Alder cycloaddition of 1,2,4-triazines tethered with imidazoles produce tetrahydro-l,5-naphthyridines following the loss of N2 and CH3CN.258 The inverse-electron-demand Diels-Alder reaction of 4,6-dinitrobenzofuroxan (137) with ethyl vinyl ether yields two diastereoisomeric dihydrooxazine /V-oxide adducts (138) and (139) together with a bis(dihydrooxazine A -oxide) product (140) in die presence of excess ethyl vinyl ether (Scheme 52).259 The inverse-electron-demand Diels-Alder reaction of 2,4,6-tris(ethoxycarbonyl)-l,3,5-triazine with 5-aminopyrazoles provides a one-step synthesis of pyrazolo[3,4-djpyrimidines.260 The intermolecular inverse-electron-demand Diels-Alder reactions of trialkyl l,2,4-triazine-4,5,6-tricarboxylates with protected 2-aminoimidazole produced li/-imidazo[4,5-c]pyridines and die rearranged 3//-pyrido[3,2-[Pg.460]

In, this mini book we have focused our attention to the application of micro-wave irradiation in synthesis of various important heterocyclic organic compounds viz. pyrazoles, imidazoles, oxazoles, thiazoles, oxadiazoles, oxazolines, triazoles, triazines, benzimidazoles, benzoxazoles and benzthiazoles. The selected heterocyclic moieties are synthetically important due to their interesting pharmacological properties (anti-HIV, anti-parasitic, anti-histaminic, anti-cancer, anti-malarial etc.). 

Imidazo[l,2-a][l,3,5]triazines have been prepared by annulation of the imidazole onto an existing triazine as well as by annulation of the triazine onto an imidazole precursor. Depending upon the desired substituent pattern, both routes allow effective preparation of variously substituted heterocycles. Research on this ring system has been minimal until recently, when several papers have focused on the synthesis of nucleoside derivatives, which can be thought of as 5-aza-7-deazapurine nucleosides. 

The scope of direct amination reactions is not too great in comparison with all other methods for synthesizing simple N-aminoimidazoles. Probably the first specific example of N-amination of imidazoles was the synthesis of l-tosylamino-2,4,5-triphenylimidazole on treatment of the lophine anion with tosylazide [Eq. (9)] (72BCJ306). However, the yield of 35 was small because of the side formation of 2,4,6-triphenyl-l,3,5-triazine and diphenyl acetylene. 

The susceptibility of 1,3,5-triazine to nucleophilic attack with ring opening makes it a synthetically useful equivalent of formate, or formamide, particularly for the synthesis of other heterocycles, such as imidazoles and triazoles (see above). Despite the high susceptibility of 1,2,4-triazines to nucleophilic addition, 3-substituted-6-methoxy-l,2,4-triazines can be successfully lithiated. ... 

Preparation of 5-amino-6-oxo-l,6-dihydro-1,2,4-triazine-3-carboxylic acid derivatives and the synthesis of compound libraries thereof have been reported <04TL2791>. Intramolecular inverse electron demand Diels-Alder reactions of imidazoles with 1,2,4-triazines have been described as a new route to obtain l,2,3,4-tetrahydro-l,5-naphthyridines and related heterocycles... 

A novel synthesis of imidazo[l,2-fi ][l,2,4]triazines has been realized by the ring closure of the imidazole compound (151) with urethane to yield the fused triazinone (152) (Equation (43)) (89JCR(S)206>. Other approaches to this ring system have also been published (84CCC275, 88JIC784>. 

The strategies described in Schemes 4.6.S-4.6.9 thus combine efficiently a novel sulfur-based safety-catch linker strategy, multigeneration construction of thio-linked pyrimidines with a multidirectional cleavage procedure. This approach should prove successful for the solid-phase synthesis of a whole range of nitrogen-containing heterocycles such as pyrimidines, triazines, imidazoles, benzimidazoles. 

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