Triazolo pyridine, arylation

Oxidation of 5-arylazo-6-aminoquinoline 146 with copper sulfate in pyridine gave the corresponding 2-aryltriazolo[4,5-/]quinolines 147. Condensation of halo-genated nitrobenzenes with triazolo[4,5-/]quinoline 145 yielded the appropriate 2H- and 3//-aryl derivatives. The nitration of 3-phenyl-3//-triazolo[4,5-/]quino-line 147 occurred at position 4 of the phenyl ring (Scheme 46) (73T221). 

The only examples of ring oxidation are the one-electron anodic oxidation of Nl-aryl[l,2,4]triazolo[4,3-a]pyridines such as compound 143 to give quaternary salts (88ZC187), and the voltammetric oxidation of the anti-depressant Trazodone (Section V.A) (87MI1). 

Zinc chloride-doped natural phosphate was shown to have catalytic behavior in the 1,3-dipolar cycloadditions of nucleoside acetylenes with azides to form triazolonucleosides <99SC1057>. A soluble polymer-supported 1,3-dipolar cycloaddition of carbohydrate-derived 1,2,3-triazoles has been reported <99H(51)1807>. 2-Styrylchromones and sodium azide were employed in the synthesis of 4(5)-aryl-5(4)-(2-chromonyl)-1,2,3-triazoles <99H(51)481>. Lead(IV) acetate oxidation of mixed bis-aroyl hydrazones of biacetyl led to l-(a-aroyloxyarylideneamino)-3,5-dimethyl-l,2,3-triazoles <99H(51)599>. Reaction of 1-amino-3-methylbenzimidazolium chloride with lead(fV) acetate afforded l-methyl-l/f-benzotriazole <99BML961>. Hydrogenation reactions of some [l,2,3]triazolo[l,5-a]pyridines, [l,2,3]triazolo[l,5-a]quinolines, and [l,2,3]triazolo[l,5-a]isoquinolines were studied <99T12881>. 

Trudell and co-workers reported the N-arylation with 2-chloro-3-nitropyridine of [l,2,3]triazolines fused onto [4,5-dpyridazine (Scheme 5) and [4,5-,yjpyrimidine (Scheme 6) <2000JHC1597>. Substitution at the 2-position of the pyridine ring was confirmed by X-ray crystallographic analysis of products 8 and 9. Similarly, [l,2,3]triazolo[4,5-,yjpyrimidine gave 10 in low yield, after nucleophilic substitution of the chloro substituent activated by the nitro group in 2-chloronitrobenzene (Scheme 6). 

Of the condensed heterocycles containing a bridgehead nitrogen atom that have been subjected to the Anil Synthesis, the 2-arylimidazo[l,2-a]-pyridine system exhibits good alkali stability, whereas the 2-aryl-j-triazolo[l,5-a]pyridine system may only be reacted below 45°C.19,78... 

The 2-aryl-l,2,3-triazolo[4,5-d]pyrimidines 68 were prepared by coupling diazotized p-anisidine with 4-amino-2-(dimethylamino)-6-methoxypyrimi-dine (66) to give the azo intermediate 67, which upon heating in pyridine containing CuSC>4 5H20 gave 68 (80GEP3001424) (Scheme 12). 

In contrast to the ease of N-functionalization, shown in Scheme 1, the triazolopyridine nucleus is resistant to direct nuclear oxidation or electrophilic additions. Electrophilic additions will occur on aryl substituents for example, nitration of l-phenyltriazolo[4,5-c]pyridine (26) and sulfonation of 2-phenyl-2i/-triazolo[4,5-6]pyridine (28) occur exclusively in the para position of the phenyl ring <34LA(514)279, 38MI 710-01). Nuclear functionalization was observed when l-( -butyl)-5-methyl-tri-azolo[4,5-c]pyridinium iodide (30) was treated with potassium ferricyanide to afford triazolopyridin-4-one (31), as shown in Scheme 2. Similarly, the iodide (30) is converted by either phosphorus oxychloride-phosphorus pentachloride, or bromine or nitric acid to 7-substituted triazolopyridin-4-ones (32) <37LA(529)288>. 

Examples of either the dihydro or tetrahydro analogues of the heterocycles in this chapter are rare. A synthesis of 3-aryl-4-methyl-4,5,6,7-tetrahydro-3/7-l,2,3-triazolo[4,5-6]pyridines was reported (see Section 7.10.9.1.1), but its chemistry was not discussed <86CB359i>. 

Several unique heterocyclic fused-1,2,4-triazole structures have been published. Pyridine amination of 216 with O-mesitylenesulfonylhydroxylamine followed by condensation with various aryl and heterocyclic aldehydes and subsequent cyclization and oxidation gave triazolopyridines 217 <03TL1675>. Triazolopyridines 217 were utilized in the direct conversion to the triazolopyridine amides 218 with methylaluminoxane premixed with amines in a combinatorial library synthesis. A convenient synthesis of novel 4-(l,2,4-triazol-l-yl)-2-pyrazolines and their derivatives has been reported <03SC1449>. A novel triheterocyclic ring system, thieno[2,3-y][l,2,4]triazolo[l,5-a]azepines, has been published <03S1231>. 

The 3-aryl-[l,2,4]triazolo[4,3-a]pyridines are best prepared by heating the hydrazinopyridine with an equimolar amount of the appropriate acid or ester or, in the... 

Table 8 Examples of 3-Alkyl- and 3-Aryl-[l,2,4]triazolo[4,3-a]pyridines Prepared from 2-Hydrazinopyridines and Carboxylic Acids, Anhydrides, Esters or Ortho Esters <66JOC25i, 78JHC439.7OJHC703,70JHC1019)...

Flash thermolysis of 3-aryl[l,2,3]triazolo[l,5-a]pyridines (277) under mild conditions (380-500°C, 10-3 torr) affords carbazoles (279, 280) in nearly quantitative yields.232 The triazoles exist as the valence tautomeric diazo compounds 278 in the gas phase.189 The substitution patterns in the products (279 and 280) demonstrate that the reactions take place exclusively by a carbene-nitrene rearrangement in which the pyridylcarbenes insert into the 2,3-bond in pyridine (Scheme 52). 

Dehydrogenation of a-pyridinealdehyde hydrazone (251) yields not a-pyridyldiazomethane (252) but the cyclic isomer l,2,3-triazolo[3,4-a]pyridine (253).1 A similar ring closure is observed in diazo group transfers onto alkyl or aryl(2-pyridyl)methyl ketone (254) in MeOH/KOEt.1 The diazo intermediate could not be isolated but 3-acyl[l,2,3]triazolo[3,4-a]pyridine (255) is obtained.1... 

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