1.2.4- Triazines with amines

Table. 2. Products from the reaction of trichloro triazine with amines.

Scheme 10.4 Sequential substitution of triazines with amine nucleophiles.

Furalazine, Acetylfuratrizine, Panfuran-S. Heating nitrovin in butanol or dimethylformamide at 100—130°C affords furalazine, 6-[2-(5-nitro-2-furanyl)ethenyl]-l,2,4-triazine-3-amine (34). An improved synthesis originates with 5-nitro-2-furancarboxaldehyde and acetone, proceeds through 4-(5-nitro-2-furanyl)-3-buten-2-one followed by a selenium dioxide oxidation to the pymvaldehyde hydrate, and subsequent reaction with aininoguariidine (35). Furalazine, acetylfuratrizine (36), and the A[-A/-bis(hydroxymethyl) derivative, Panfuran-S, formed from the parent compound and formaldehyde (37), are systemic antibacterial agents. 

Triazines substituted with amines are generally less reactive as the amine becomes more basic, and more reactive as the amine becomes less basic. The chromophore may be sufficientiy electron withdrawing or donating to affect reactivity of the dye. 

The highly activated 2,4,6-trichloro-s-triazine with excess amines at... 

Another pathway for the aromatization of the cr -adducts was found in the reactions of 3-pyrrolidino-l,2,4-triazine 4-oxide 81 with amines. Thus the treatment of 1,2,4-triazine 4-oxide 81 with ammonia leads to 5-amino-1,2,4-triazine 4-oxides 54—products of the telesubstitution reaction. In this case the cr -adduct 82 formed by the addition of ammonia at position 5 of the heterocycle undergoes a [l,5]sigmatropic shift resulting in 3,4-dihydro-1,2,4-triazine 83, which loses a molecule of pyrrolidine to yield the product 54. This mechanism was supported by the isolation of the key intermediates for the first time in such reactions—the products of the sigmatropic shift in the open-chain tautomeric form of tiiazahexa-triene 84. The structure of the latter was established by NMR spectroscopy and X-ray analysis. In spite of its open-chain character, 84 can be easily aromatized by refluxing in ethanol to form the same product 54 (99TL6099). 

The increase in thermodynamic stability of 85 is achieved by easy ring opening (01H127). This knowledge allows one to control the regioselectivity of the oxidative amination of the 6-aryl-l,2,4-tiiazine 4-oxides 53, obtaining either (i) the 5-amino-1,2,4-triazine 4-oxides 56 in the reaction of 53 with amines at low temperature in the presence of the oxidant or (ii) the 3-amino-1,2,4-triazine 4-oxides 88, provided the reaction is carried out in two steps (addition and oxidation) at room temperature or higher. 

Peroxides oxidize TPDD to Wurster s blue, a product with a semiquinone diimine structure [1]. Similarly Wurster s blue is also produced from TPDD by reaction with halogen-containing substances produced by the reaction of aromatic amines and triazines with chlorine gas. 

Hydroxy leuco bases can be converted into the corresponding amino leuco bases by allowing the leuco compound to react with a secondary amine in the presence of acetic acid.78 Examples, 54, of amine bases utilized in this manner are imidazole, 1,2,4-triazine, aryl amine, and cyclohexayl amine. 

Kreuxzberger, A. Reactions of Trichloromethyl-1.3.5-triazine Derivatives with Amines. J. Amer. chem. Soc. 79, 2629 (1957). 

Reactive halogen crosslinkers are mainly specific for sulfhydryl groups at physiological pH, however at more alkaline pH values they can readily cross-react with amines and the imidazole nitrogens of histidine residues. Some reactivity with hydroxyl-containing compounds also may be realized, particularly with dichloro-s-triazine derivatives under alkaline conditions. 

Formation of some mesoionic [ 1,3,4]rhiazolo[3,2-z/ [1,3,5]triazines 303 and related [l,2,4]triazolo[2,3- ][l,3,5]tri-azines 305 has been observed by Anders et al. <2005T673>, as shown in Scheme 60. These authors reported that the quaternary salts 302 and 304 containing polyfused delocalized cations easily react with amines to result in ring opening to 303 and 305, respectively. 

Alternatively, diazopyrazole (86) reacted with amines to yield triazines which, when treated with activated carbonic acid derivatives, e.g., phosgene, afforded derivatives of 161 (87CB1375). 

Condensation of l-[4,6-bis(allylamino)-l,33-triazin-2-yl]-4-piperidone (32) with amines 30 and 31 afforded the verapamil-like analogs 33 and 34 which were synthesized as potential drugs able to revert multidrug resistance (MDR). Both compounds show chemosensitizing activity but maintain some cardiovascular action <99JMC1687>. 

Electron transfer to the xanthenes, particularly reduction with amines, has been used for a number of years to initiate acrylate polymerization. A typical system is that reported to form volume holograms—lithium or zinc acrylate, triethanolamine and Eosin, Erythrosin, or Rose Bengal [290], Similar mixtures are used to form printing plates photoreducible dye, phenylac-ridine, and acrylate monomer [292], A recent patent application discloses aryl iodonium salts, Rose Bengal, and oxidizable triazines such as 2-methyl-4,6-bis(trichloromethyl)-s-triazine to polymerize acrylates [292],... 

The reaction of 1,2,4-triazines with ketene derivatives such as the 0,0-acetals (42la), 0,iV-acetals (421b), Af,Af-aminals (421c) and (V.S-aminals (421d) has been studied extensively. In all cases pyridines (422) were isolated (Scheme 14). These reactions follow the usual cycloaddition route. Again it is found that the orientation is dominated by secondary... 

These compounds are more stable than the alkyl derivatives. They do not undergo thermal isomerization, and hydrolysis requires very severe conditions. The aryl cyanurates react smoothly with amines to yield 2,4,6-triamino-l,3,5-triazines. It is possible to effect electrophilic substitution of the aryl rings <59HC(l3)l,p.l7). Aryl cyanurates are hydrogenated to form cyanuric acid and the arene (equation 22) (74RTC204). 

Formaldehyde reacts with amines to yield the 1,3,5-trisubstituted hexahydro-1,3,5-triazines and with nitriles to form the acyl derivatives (Scheme 90) (59HC(13)1, p. 486, B-61MI22000, p. 658). Hexamethylenetetramine (70) is prepared by heating an ammoniacal solution of formaldehyde (B-61MI22000, p. 688). 

Some heteroarylamines have been prepared by aromatic nucleophilic substitution of suitable support-bound arylating agents with amines (Table 3.27). This technique has been successfully employed in the synthesis of 2-(alkylamino)pyrimidines [507,508], 2-(arylamino)pyrimidines [509], aminopurines [510-512], and 1,3,5-triazines [513]. When the heteroarene is bound to the support as a thioether, nucleophilic clea-... 

Compounds (83) and (85) were oxidized to the corresponding 1,4-dioxides (94) and (95) and treatment of these with amines led to a variety of products. For example, compound (94) gave products such as the 3-morpholinyl derivative (96) or the 3-benzylpyrido[4,3-e]-l,2,4-triazine (97) <76MI 717-01). 

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