Triazolo pyridine ring system

Pyrazolo[l,5-fc]-l,2,4-triazole 154 " and l,2,4-triazolo[l,5-a]pyridine 156 ring systems were successfully obtained from the corresponding formamidoximes or related ami-doximes 153 and 155, respectively, and acylating agent (TsCl or TFAA) (equations 67 and 68). Similarly, l,2,4-triazolo[l,5-a]pyrimidines were obtained from pyrimidine formamidoximes . 

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>. 

When the six-membered ring is strongly activated, e.g. by a 6-nitro substituent, nucleophilic attack by alcoholic alkali may lead to rearrangement as in Scheme 15 (81T3423). These reactions are analogous to those occurring in the corresponding 1,2,4-triazolo-pyridine and -pyrimidine systems. 

In the following presentation, structures (l)-(62) will be used, as is customary, to represent the parent heterocycle of the derivative under discussion. It should also be noted that the structures are all drawn (with several exceptions) using [l,2,4]triazolo[4,3-a]pyridine (1) as the prototype. Thus, the focus of visual orientation will be a bridgehead nitrogen in the lower center part of the ring system. This had been done not out of disrespect for the recognized molecular orientations but in an effort to simplify the relationships of these diverse systems to one another. 

An example of this ring system was prepared (78USP4I08860) through cyclization of 3-hydrazido-l,2-benzothiazole-i,l-dioxide (91) with phos-phoryl chloride in dimethylformamide (DMF). 3-Methyl-l,2,4-triazolo-[4,3-fe]1,2-benzothiazole-5,5-dioxide (95) was obtained (79USP4140693) when 3-chloro-l,2-benzothiazole-l,l-dioxide (93) was treated with 3-methyltetrazole (94) in the presence of pyridine. 

Finally, 96 (and its 2-methyl analog), when heated in pyridine with carbon disulfide and triethylamine (bath at 115°C, 6 h), yielded 95% of 7- and 8-methyl-1,6-dihydro-8-azapurine-2-thione. Derivatives of a new ring system were produced instead of azapurines when the 3-methyl and 3-benzyl analogs of 96 were treated similarly, giving 3-alkyl-3,7-dihydro-3//-1,2,3-triazolo[4,5-[Pg.169]

Hiickel molecular orbital calculations have shown that the 5-position in this ring system has associated with it a greater tt-electron density than is present in the corresponding positions in s-triazolo[4,3-a]pyridine, s-triazolo[4,3-a]pyrimidine, and s-triazolo[4,3-c]pyrimidine. This fact has been used to rationalize the difficulty in rearranging this heterocycle to its s-triazolo[l,5-a] analogue, in contrast to the ease with which the other s-triazolo systems rearrange. 

Ultraviolet absorption data in either ethanol or cyclohexane have been tabulated for ten derivatives of the ring system. In ethanol, s-triazolo[4,3-a]pyrazine has three main bands, at 206, 253, and 292 nm, and the spectrum is very similar to that of s-triazolo[4,3-a]pyrimidine and the corresponding fused pyridine. Replacement of CH by N in the pyridine ring of s-triazolo[4,3-a]pyridine results in only small shifts in the... 

The chemical behaviour of IPs is determined not only by the chemical properties of the imidazole and pyridine rings separately, but also by intramolecular interaction effects (electronic and steric) that arise between the rings in the fused systems. These effects strongly depend both on the electronic condition of the substrate (neutral molecule, cation or anion) and on the geometrical orientation of the rings. IP s behaviour in various reactions will be considered below. We will also examine the behaviour of related heterocycles (for example, pyridine, isoquinoline or triazolo [4,5-c]pyridine, etc.) to illustrate the general or particular character of the IP s properties. 

Reaction of heterocycles with a hydrazine residue at the a-position with sugars gave the respective hydrazones whose oxidative heterocyclization gave the 1,2,4-triazolo ring fused to the heterocycle. A variety of fused heterocycles such as pyridines, quinolines, triazines, and fused ring systems were prepared as acycHc nucleosides [2-5,109-111]. 

Unusual heterocyclic systems can be obtained by photodimerizations and for five-membered heterocycles with two or more heteroatoms such dimerizations need be effected on their ring-fused derivatives. Cyclobutanes are usually obtained as in the photodimerization of the s-triazolo[4,3-a]pyridine (540) to the head-to-head dimer (541). These thermally labile photodimers were formed by dimerization of the 5,6-double bond in one molecule with the 7,8-double bond in another (77T1247). Irradiation of the bis( 1,2,4-triazolo[4,3-a]pyridyl)ethane (542) at 300 nm gave the CK0ifused cyclobutane dimer (543). At 254 nm the cage-like structure (544) was formed (77T1253). 

Cycloadditions are in general an effective way of constructing cyclobutane rings. A wide variety of heterocyclic systems dimerize in this way. 1,3-Diacetylindole, for example, affords the head-to-tail dimer 242 on irradiation in ethanol.185 Ethyl 2-ethoxy-l,2-dihydroquinoline-l-carboxy-late is similarly converted in diethyl ether into the trans head-to-head dimer.186 Notable among many analogous photodimerizations are those reported in 1,4-dihydropyridines,187 in furo[3,2-b]pyridin-2(4//)-ones,188 in 8-methyl-s-triazolo[4,3-a]pyridine,189 and in 2H-2-benzazepine-1,3-diones.190 The [ 2 + 2] dimerization of amidopyrine is the first reported example of a photocycloaddition in a 4-pyrazolin-3-one.191... 

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