1.2.4- Triazine V-oxides

Chemical Shifts of the Carbons in the C NMR Spectra of 1,2,4-Triazine V-Oxides IN DMSO- Is IN Comparison ( ) with Those of the Parent 1, 2,4-Triazines... 

The specific nature of 1,2,4-triazine /V-oxides discussed in Section II,C is also manifested in the SNH reactions. Treatment of 1,2,4-triazine 2-oxides containing electron-donating groups at C-3 with methanol, ethanol, or isopropanol in the presence of hydrochloric acid results in 6-alkoxy-substituted 1,2,4-triazines 137 (Scheme 77) (77JOC3498). The reaction is proposed to involve the addition of alcohol to C-6 of the hydroxy-1,2,4-triazinium cation 135, followed by elimination of water. The presence of an electron-donating group at C-3 seems also to be important because it contributes considerably to the stabilization of the intermediate cationic species 136 (Scheme 77). 

The oxidation of 1,2,4-triazines may result in the formation of three isomeric V-oxides. 1,2,4-Triazine V-oxides are still electron-deficient aromatic compounds and, due to the electron-withdrawing character of the V-oxide function, the ring carbon atoms are activated for nucleophilic attack. On the other hand, the electron deficiency of the 1,2,4-triazine ring is partially compensated by the back-donation effect of the V-oxide moiety (Scheme 2), which is clearly reflected in H, and NMR spectra (for a detailed discussion, see Section 9.02.3.3) <1989AHC(46)73, 1998RCR633, 2002AHC(82)261>. 

Contrary to the majority of other reactions of A -aminoazoles, oxidation reactions only began to be studied much later, approximately from the 1960s. Since that time, interest has grown, and presently they represent one of the most intriguing and synthetically useful types of N-aminoazole conversions. With the help of these reactions, one can effectively generate cycloalkynes and arynes, synthesize the difficult-to-obtain 1,2,3-and 1,2,4-triazines, /V,N -azoazoles, and other important compounds. 

There are few reports on the reactivity of 1,2,3-triazine V-oxides. Thermolysis of 4-phenyl-... 

Only a few data on the UV spectra of 1,2,4-triazine N-oxides are to be found in the literature. It seems to us that these spectra should allow a determination of the position of the V-oxide function. For instance, 3-amino-5,6-diphenyl-1,2,4-triazine 1-oxide has two absorption bands at 298 (log e = 4.20), and 231 nm (4.44) <65CPB1168>, while the 2-oxide shows three bands, at 365 (3.82), 257... 

Aminopyridine /V-oxides can be diazotized, and the diazonium salts undergo coupling, etc. These diazonium salts are stabilized by mesomerism (728), cf (726). Amino groups in pyridazine /V-oxides can also be diazotized and the diazonium group further replaced by other functionality. Nitrosation of 3-amino-1,2,4-triazine 2-oxides and subsequent thermolysis of the diazonium tetrafluoroborate salts afforded 3-fluoro-1,2,4-triazine 2-oxides (85H(23)1969). 

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]

Deoxygenative v.s vicarious nucleophilic substitution of hydrogen in reactions of 1,2,4-triazine-4-oxides with a-halocarbanions has been described <02EJO1412>. Tandem vicarious nucleophilic substitution of hydrogen/intramolecular Diels-Alder reaction of 1,2,4-triazine (19) into functionalized cycloalkenopyridines 21 has been reported <02CPB463>. 

Table 5. Influence of /V-Oxidation on the HNMR Shifts (<5 values in ppm) of 1,2,4-Triazines...

Oxidation of /V-(l-phenylethylidene)guanidin-2-amine with selenium dioxide leads to the corresponding a-oxoaldehyde derivatives which cyclize to 5-unsubstituted 1,2,4-triazin-3-amines l.115-141... 

Triazine 4-oxide (10 mmol) and triethyl phosphite (tributyl phosphite) (0.2 mol) were heated with stirring to reflux. The V-oxide dissolved and the solution became yellow. The mixture was evaporated to dryness in vacuo and the residue purified by column chromatography on silica gel with Et20 or EtOAc. 

Relatively few reactions of quinoxaline derivatives occur with change of ring size. Isolated examples are noted in the following text. For example, ring contraction to benzimidazole derivatives occurs when 2,3-diphenylquinoxaline (Chapter XV) or 2-halogenoquinoxalines (Chapter X) are treated with potassium amide in liquid ammonia and quinoxalin-2-one is treated with hydrazine (Chapter VX It is also found that oxidation of l-aminoquinoxalin-2-ones with lead tetraacetate give benzo-1,2,4-triazines (Scheme 6) (Chapter V). 

UV irradiation of 3-aminopyrido[4,3-e]-l,2,4-triazine 1-oxides 7 or 1,2,4-triazine 4-oxides 8 leads to deoxygenation, i.e., loss of the /V-oxide function resulting in the corresponding 3-aminopyrido[4,3-e]-l,2,4-triazines 9 and 1,2,4-triazines 10 (76ACH327,76LA153). At the same time, UV irradiation of the 1,2,4-triazine 4-oxides unsubstituted at the 5 position proceeds as a ring contraction to form triazoles 11 (76LA153). 

Neunhoffer and Bbhnisch, V., Reactions of 1,2,4-triazine 4-oxides, Liebigs Ann. Chem., 153, 1976. 

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