1.2- Dihydro- 1,3,5-triazines, formation

The observations suggest that the two condensations are direct and distinct. Had the base-catalysed reaction first given the aryl-dihydro-triazine (CXXXIV) which, under the prevailing basic conditions rearranged to the anilino-dihydro-triazine (CXXXV), an equilibrium mixture of the two would have been expected. Since, however, the pure anilino-dihydrotriazine (CXXXV) was isolated, its formation is considered to be direct and independent of that of its isomer (ffS). The formation of (CXXXIII) from 1-aryl-l-alkylbiguanides (see preceding Section), which cannot proceed by way of an aryl-dihydrotriazine, bears out this conclusion. 

Moreover, considering the mechanistic similarities between dihydro-1,2-triazine formation via ylide thermolysis and the condensation of aryl aldehydes with benzamidine or IV-alkylbenzamidines, the [4 + 2] cycloaddition... 

The first systematic theoretical study on dihydro-1,2,4-triazines was recently carried out (98JOC5824) the stabilities of all the possible unsubstituted dihydro-1,2,4-triazines were calculated using various theoretical methods, all reliable calculation methods consistently show that the 2,5-dihydro isomer 98 is the most stable. This is in perfect agreement with the experimental observations all the synthetic methods used for the preparation of dihydro-1,2,4-triazines result in 2,5-dihydro isomer 98, provided the structures of the reactants and the reaction mechanism allow its formation. Thus, although Metze and Scherowsky (59CB2481) claimed the formation of 1,2-dihydro-1,2,4-triazine 92 (R = = Ph) in the reduction... 

If the formation of a 2,5-dihydro isomer 98 is not allowed, other dihydro-1,2,4-triazines are formed aeeording to their order of stability ealeulated by various theoretieal methods (see Table III) (98JOC5824). 

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. 

Base-catalyzed Dimroth rearrangements of l-aryl-4,6-diamino-1,3,5-triazines or triflic acid-induced decomposition of 6-anilino-1,3,5-triazines led to the formation of the corresponding substituted 1,2-dihydro-l,3,5-triazines, whose structure was established on the basis of H NMR spectra (93JHC849). 

Refluxing of hydrazine 60 in acetic acid in the presence of sodium acetate resulted in the formation of 6-methyl-3-oxo-8-phenyl-3,4-dihydro-2/7-pyrimido[6,l-r-][l,2,4]triazine-9-carbonitrile 61 in good yield <1997IJB269> (Equation 2). 

Refluxing of benzo[l,2,4]triazine-3-thione 86 with epichlorohydrin in the presence of triethylamine in methanol for 14 h resulted in the formation of 3,4-dihydro-2H,97/-l-thia-4a,9,10-triaza-phenanthren-3-ol 87 <2003PS797> (Equation 7). 

Two types of addition to pyrimidine bases appear to exist. The first, the formation of pyrimidine photohydrates, has been the subject of a detailed review.251 Results suggest that two reactive species may be involved in the photohydration of 1,3-dimethyluracil.252 A recent example of this type of addition is to be found in 6-azacytosine (308) which forms a photohydration product (309) analogous to that found in cytosine.253 The second type of addition proceeds via radical intermediates and is illustrated by the addition of propan-2-ol to the trimethylcytosine 310 to give the alcohol 311 and the dihydro derivative 312.254 The same adduct is formed by a di-tert-butyl peroxide-initiated free radical reaction. Numerous other photoreactions involving the formation by hydrogen abstraction of hydroxyalkyl radicals and their subsequent addition to heterocycles have been reported. Systems studied include 3-aminopyrido[4,3-c]us-triazine,255 02,2 -anhydrouri-dine,256 and sym-triazolo[4,3-fe]pyridazine.257 The photoaddition of alcohols to purines is also a well-documented transformation. The stereospecific addition of methanol to the purine 313, for example, is an important step in the synthesis of coformycin.258 These reactions are frequently more... 

Some 4,5-dihydro[l,2,4]triazolo[3,4-r-]benzo[l,2,4]triazines 57 easily reacted with aromatic aldehydes to result in the formation of synthetically valuable azomethine imines 58 <2005EJO3553>. The transformation took place at room temperature in the presence of tetrafluoroboric acid in 10 min in high yields. The product 58 was conveniently prepared and stored in the form of tetrafluoroborate salt, and was subjected to further reactions (e.g., 1,3-dipolar cycoadditions see Section 11.19.5.4.) by in situ liberation of the free base prior to transformation. 

A new cyclization method for [l,2,4]triazolo[5,l-c]triazines (ring system 26) starting from trifluoromethylated 1,2,3-triketones and resulting in formation of 4,7-dihydro derivatives has recently been published <2005JFC1230>. The structure of one representative derivative has also been investigated by X-ray crystallography. 

From the reaction of 6-phenyl-l,2,4-triazine-3,5-dione (157) with phenylmagnesium bromide, 5,6-diphenyl-1,2,4-triazin-3-one (27), 3,5,6-triphenyl-l,2,4-triazine (147), 3,3,5,6-tetraphenyl-2,3-dihydro-l,2,4-triazine (158), 2,4,6-triphenyl-l,3,5-triazine (148) and 2,4,4,5-tetraphenylimidazole (149) were isolated (71JPR699). From the results obtained in the reaction of 3,5,6-triphenyl-l,2,4-triazine (147) with phenylmagnesium-bromide it can be supposed that the last two compounds were formed via the intermediate formation of (147). 

Aromatic aldazines when treated in boiling toluene with potassium r-butoxide, furnished 3,5,6-triaryl-l,2,4-triazines (632) and their 2,5-dihydro (633) and 1,2,5,6-tetrahydro derivatives (634), besides triazoles, which were the major products (76JCS(Pl)207). The formation of the triazines is best explained by a [4+2] cycloaddition or a two-step process via the carbanion (631) and elimination of benzalimine to give (633), which can be oxidized to (632 Scheme 21). TTie formation of (634) is still in doubt. 

Interaction of 1,3,5-triazine (241) with hydrazine affords 1,2-diformylhydrazine dihy-drazone (242) which is a light-sensitive compound which turns pink, especially in the presence of air. The color is attributed to the formation of 1,2,4,5-tetrazine (38) but due to its high volatility the tetrazine could not be isolated. Heating (242) for two hours with acetic anhydride again affords an unisolated red, volatile product formulated as (38), and 1,2-diacetyl-l,2-dihydro-1,2,4,5-tetrazine (243). Since compound (242) is prepared from hydrazine and (241) this preparation is in the final analysis a [2+ 1+ 2 + 1] method (57JA2839). 

Catalytic hydrogenation of 3-phenylpyrido[3,4-e]-l,2,4-triazine (45b) over a palladium catalyst gave the 1,4-dihydro compound (29) in a 90% yield this is an unusual result as the position of the pyridine nitrogen atom does not seem to affect the formation of 1,4-dihydro derivatives (see also Section 7.17.5.4). Electrochemical reduction of the pyrido-l,2,4-triazine (45b) in both protic and... 

When the dihydro-1,2,4-triazinone (194) is heated at 180 °C under reducing conditions there is rupture of the 1,2-bond followed by ring closure, producing 4,5-diphenyl-imidazolinone (195). Such reductive ring closures of benzotriazine 1-oxides (196) can give benzimidazoles, in particular 2-(4-thiazolyl)benzimidazoles (197) ( thiabendazole ). Similar reactions take place with 1,3,5-triazines. In fact, primary amines cleave the compounds completely with evolution of ammonia and formation of iV.iV -disubstituted formamidines. With suitable primary amines, though, this reaction can be designed to produce imidazolines or benzimidazoles (Scheme 113). 

When the dihydro-1,2,4-triazinone 76 is heated at 180°C with red phosphorus and hydroiodic acid, there is rupture of the 1,2-bond and subsequent ring closure to give 4,5-diphenylimidazolin-2-one (77) (see Scheme 17) and reductive ring contractions to imidazoles (81) have also been reported " in the 1,3,5-triazine series. A further interesting ring contraction is that which occurs when 4H-l,3,5-thiadiazines (78) are treated with aliphatic amines at room temperature. The triarylimidazoles (81) may be formed by initial formation of the 1,3,5-thiadiazine anion (79) which probably loses sulfur... 

Diaryl-1,2,4-triazines (360), containing a 3-methoxy or 3-methylthio substituent, give rise to the formation of the 2,5-dihydro derivatives 361 on treatment with These dihydro species, trapped with dimethylace-... 

There are only a few examples known of S-adduct formation. They all feature addition at C-5 of the 1,2,4-triazine ring. Thus, 2,5-dihydro-1,2,4-triazines 38 are formed in good yield when sulfur dioxide is passed through a solution of 1,2,4-triazine in water (water-methanol) (Scheme 26) (78HC(33)189 86H1243 87CPB1378). 

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