Triazine , intramolecular cyclization

When a tautomeric equilibrium is possible, neutral dihydro-1,3,5-triazines exist predominantly or exclusively in their 1,2-dihydro forms. Thus, the formation of 1-substituted 1,2-dihydro-l,3,5-triazines 104 was reported on intramolecular cyclization of imidoylcarbodiimides (86CB3737). No corresponding 1,4-dihydro tautomers were observed by H, NMR, or IR spectroscopy in solution. 

FVP of Tacylnaphtho[l,8- ( ][l,2,3]triazines 575 gave exclusively the corresponding 2-substituted-naphth[l,8- ][l,3]oxazines 576 (Equation 69). The reaction was presumed to start with the elimination of N2 to give l-(acylamino)naphthalene diradicals, which then underwent intramolecular cyclization to give the oxazines 576 <2005T10507>. 

Alkyl-hexahydro-l,3,5-triazin-2-ones are prepared by the reaction between urea, formaldehyde and primary amines (73S243). The intermediate polycondensate (87) undergoes intramolecular cyclization on heating to yield the desired product (Scheme 52). By using substituted ureas (or thioureas) and/or different aldehydes, a wide variety of N-substituted 5-alkyl-hexahydro-l,3,5-triazin-2-ones (or 2-thiones) may be prepared. 

The exploitation of intramolecular Diels-Alder reactions has included synthetic applications in the thienopyrimidine series as well. Thus, the 1,2,4-triazine with a tethered alkyne (276) participates in an intramolecular cyclization, with concomitant loss of RCN, to produce the thienopyrimidine (277) (Equation (97)) <87JOC4287>. A similar reaction occurs with oxygen analogues. 

A series of condensed 1,2,4-triazines have been obtained from nitroarenes and guanidines or other TV-nucleophiles as exemplified in Schemes 241243 <1999JOC3361, 2002J(P1)696, 2006RCB1243, CHEC-III(9.02.7.1)158>. The key step in these reactions involves nucleophilic displacement of hydrogen ortho to a nitro group by the action of the iV-nucleophile followed by intramolecular cyclization to the 1,2,4-triazine system. 

Formation of imidazo[4,5-e]-1,2,4-triazines 119 has been observed to occur when 6-ethylamino-5-methylamino-1,2,4-triazines 118 react with benzamidine. However, in this case only the methylamino group at C-5 is substituted by the amidine, while the ethylamino group at C-6 participates itself as a nucleophile in an intramolecular cyclization reaction (Scheme 68) (78CPB3154). 

Intramolecular cyclization of 3-(acylhydrazino)pyridin-2-amines with polyphosphoric acid affords pyrido[2,3-c]-l, 2,4-triazines 7.144 This reaction is an extension of the Bischler synthesis of 1,2,4-benzotriazines.149... 

These are the only examples to date of a furan reacting as a diene with a cyano dienophile. Taylor and French have recently reported two intramolecular cyclizations of nitrile dienophiles with triazines to give fused heterocycles [Eq. (8)] in modest yields.12b... 

A practical synthesis of 2//-pyrimido[4,5-e]ll,2,4]triazin-3-ylidenecyanamides 106 has been developed. The key step is the coupling reaction of an aryldiazonium salt with l-cyano-3-(2,6-dioxo-l,2,3,6-tetrahydropyrimidin-4-ylamino)-2-methylisothiourea 105, obtained from uracil 104, followed by an intramolecular cyclization <04TL931ft>. 

There are several types of intramolecular cyclizations in which the 1,2,4-triazine skeleton is obtained due to the formation of a new C-N bond. For instance, the cyclization of hydrazones of cyanoacetyl carbamates 286 takes place under basic conditions, thus leading to azauracils 287 (Scheme 175) <2001JHC1465, 2002JHC357, 2005ARK30, 2005JME2167>. 

Another pattern for the synthesis of 1,2,4-triazines from [6+0] fragments is the intramolecular Cs-Nj bond formation which takes place in the intramolecular cyclization of hydrazones 290 derived from the reaction of... 

A few papers report on use of the N1-N2 bond formation for closure of the 1,2,4-triazine ring. For instance, pyrazolo[5,l-c]-l,2,4-triazine 5-oxides have been obtained through the intramolecular cyclization of l-(2 -nitroaryl)-5-aminopyrazoles under alkaline conditions (Scheme 181) <1996EJM259, 1997S556, 1999JME2218,... 

Several examples of intramolecular Boger reactions toward the synthesis of pyridine-containing heterocyclic systems were reported by the Taylor group and the Snyder group, For instance, intramolecular cyclization of triazine 219, after loss of nitrogen, afforded 220. Alternatively, triazine 221 generated bicyclic systems 222, which was then oxidized to 223. ... 

In the field of bioactive agents, the DNA-binding capability of newly synthesized benzothieno[3,2-(/]-l,2,3-triazines 9 was evaluated. For the synthesis, a well-known synthetic route was applied by coupling diazonium salt 10 derived from amine 11 with primary amines 12 and subsequent intramolecular cyclization of the resulting triazines 13. The synthesized... 

An attempt to isolate the tetrahydro (246) or dihydro (247) derivatives of the pyrido[3,4-e]-1,2,4-triazine ring system from the cyclization of the pyridine (248) failed in that the only isolable product was the aminoimidazolone (249). This product (249), however, is postulated to be derived from the desired compound (246) via an intramolecular reaction (Scheme 20) <76JHC60l>. 

Syntheses of pyrimido[4,5-e]-1,2,4-triazines (6-azapteridines) by [6 + 0] component cyclization of pyrimidine precursors are uncommon. Two examples, however, are the preparation of compounds (410) and (414) (Equations (69) and (70)). Formation of the latter is interesting in that it involves an intramolecular acyl transfer of the ester group from one nitrogen atom to an adjacent one <65JA1976, 75JOC2329). 

The cyclization kinetics of 11 model l-[2-(methoxycarbonyl)phenyl]-3-(2-substitut-ed phenyl)triazenes (177) have been examined in aqueous methanolic buffer solutions at various pH values. 3-(2-Substituted phenyl)benzo[fi ][l,2,3]triazin-4(3 f)-ones (178) were identified as the cyclization products. The log fcobs vs pH plot was linear with a slope of unity. The assumed and confirmed Bac2 mechanism involving specific base catalysis begins by deprotonation of the triazene giving rise to the conjugate base, continues with formation of a tetrahedral intermediate, and ends with elimination of the methanolate ion (Scheme 32). Desilylation with methanolic HCl of the substituted anilide (179), a compound formed by a Ugi reaction, led to a facile intramolecular conversion to an ester (180). This reaction was the key step in a... 

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