1.2.3- Triazolo pyridine derivatives

Several heterocyclic hydrazones 32 have been oxidized in CH3CN-O.I mol/1 Et4C104 solution with addition of 60% HCIO4 to s-triazolo[4,3-a]pyridine derivatives 33 in yields ranging from 55 to 92% [56] (Scheme 20). 

A similar series of nucleophilic substitutions has been performed on 4-chloro[l,2,3]triazolo[4,5-c]pyridine (246) and some of its simple substituted derivatives. On compound 246 itself formic acid gives the triazolo-pyridin-4-one,192 ammonia gives the 4-amino compound,192 and hydrazine the 4-hydrazino derivative 245 hydrosulfide gives the 4-thione192 and thiourea in propanol, at first reported151 to give the 4-thione, has subsequently been... 

Phenyl-1,2,4-triazolium dicyanomethylide (399) undergoes with DMAD 1,3-dipolar cycloaddition (83JCS(P2)1317). The primary product of the reaction (400) can be isolated under carefully controlled conditions. On gentle heating it is transformed into a l,2,4-triazolo[3,4-a]pyridine derivative (401). Many other azolium ylides undergo similar reactions. 

The synthesis of the triazolo-pyridine-fused 1,3-diazocine 20a was achieved starting from 56a, which by de-O-benzoylation followed by reaction with NaN3 in DMF afforded the triazolo-pyridine 57. The latter by treatment with a mixture of acetone and 2,2-dimethoxypropane in the presence of acid afforded the O-isopropylidene derivative 60. The Mitsunobu reaction led to the diazocine 19a, which, as mentioned in Section 14.05.2.5 (Scheme 2), afforded 20a in 19% overall yield (Scheme 11) <2005JME6454>. 

Diaminopyridinium salt reacts, in the presence of base, with a variety of a,/J-unsaturated compounds such as benzoylacetylenes, benzalaceto-phenone, ethoxymethylenepentane-2,4-dione, and diethyl ethoxymethyl-enemalonate to give s-triazolo[l,5-a]pyridine derivatives, presumably via l-amino-2-imino-l,2-pyridine (47) (Eq. 24).171 These reactions involve formal cleavage of the carbon-carbon double and triple bonds. 

The ring-chain isomerisation of phosphino-substituted triazolo-pyridines was found to depend on the nature of the phosphine substituent. Conversion of the phosphines to their selenides resulted in a complete shift of the equilibrium towards electron-acceptor structure D (Scheme 10). Acenaphthene and acenaphthylene were converted to polycyclic phosphole derivatives via Ti(II)-mediated cyclization of the corresponding dialkynylated arenas. The related phosphole oxides were stable species (Scheme 11). Asymmetric lithiation of dimethyl-tert-butylphosphine sulfide and trimethylsilylation gave an intermediate that was subjected to a five-step reaction sequence including metallation, P-functionalization (in three steps) and removal of the silyl group to yield the precursor of Mini-PHOS (Scheme 12). ... 

Ballesteros-Garrido R, Abarca B, Ballesteros R, de Arellano CR, Leroux FR, Colobert F, Garcia-Espana E (2009) [l,2,3]Triazolo[l,5-a]pyridine derivatives as molecular chemosensors fin Zinc(II), nitrite and cyanide anions. New J Chem 33 2102-2106... 

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). 

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). 

In all syntheses of [ 1,2,4]triazolo[4,3-a]pyridines it should be remembered that electron withdrawing substituents on the pyridine ring can cause Dimroth rearrangement of the initially formed compounds into derivatives of [l,2,4]tria-zolo[l,5-fl]pyridines (see Section B.2.c). 

It was not possible to brominate the [l,2,4]triazolo[l,5-a]pyridine species (137) directly with bromine or NBS, but the 5- and 8-bromo (66CPB523) and 3-chloro (66JOC265) derivatives were made from the diazonium salts. More recently regiospecific 5-lithiation of 137 has provided access to the 5-bromo derivative in 94% yield (92JOC5538). 

Kinetic studies of base-catalysed hydrogen exchange of heterocyclic compounds have been carried out. Paudler and Helmick515 measured second-order rate coefficients for deuteration of derivatives of imidazo[l,2-a]pyridine(XXXIII), imidazo[l,2-a]pyrimidine(XXXIV), and 1,2,4-triazolo[1,5-a]pyrimidine(XXXV)... 

Cyclization of 776 with ortho-esters gave (83JOC1628) [l,2,4]triazolo-[4,3-fc]pyrimido[5,4-< ][ 1,2,4]triazines 777, whereas reaction with sodium nitrite afforded the corresponding tetrazolopyrimidotriazine 778.3-Azido-pyrimido[4,5-e][l, 2,4]triazine 779 exists in a cyclic form as tetrazolo derivative 780, as shown by X-ray analysis (86KGS114). In solution the position of the 779 780 equilibrium depended on temperature and solvent. Higher temperatures favored 779. Azido compound 779 predominated in water, and tetrazolo compound 780 predominated in pyridine. Addition of sodium azide to the aqueous solution shifted the equilibrium toward 780. The... 

As depicted in Scheme 11, ylides 39 derived from 4-methyl-[l,2,3]triazolo[l,5- ]pyridine react with Michael acceptors, which, upon nucleophilic attack at C3 and ring opening, lead to nucleophilic displacement of nitrogen. The intermediate diradical led to a mixture of compounds, including alkenes and a cyclobutane derivative when methyl acrylate was used, and the indolizine 40 with methyl propiolate as the electrophile <1998T9785>. Heating 4-methyl triazolopyridine with benzenesulfonyl chloride in acetone also confirmed decomposition via a radical pathway. 

Alkyne dipolarophiles such as methyl propiolate or DMAD reacted with ylides derived from [l,2,3]triazolo[l,5-tf]-pyridines, but the mechanism proposed involved a Michael addition and subsequent nucleophilic attack rather than a concerted [4+2] cycloaddition <1996T10519> (see Section 11.13.8). 

Sulfur addition on the ring phosphorus atom of [l,2,4]triazolo[5,l-c][l,4,2]diazabenzophosphinine derivatives 59 was described by Zarudnitskii et al. <2002HAC146> (Scheme 9). The transformations were carried out in pyridine at 85 °C to yield the P-sulfanylene products 60. 

Spickett and Wright investigated the reactions of 4-substituted 3-amino-1,2,4-triazoles and EMME in acetic acid for 24-48 hr [67JCS(C)503]. Generally, they obtained [l,2,4]triazolo[l,5-a]pyrimidine-7-ones (1124) in 38-56% yields. In the case of the benzyl derivative (R = CH2Ph), the isomeric triazolo[l, 5-a]pyrimidin-5-one (1125) was also isolated from the mother liquor, in 5% yield. From the 4-ethyl and 4-phenethyl derivatives (R = Et, CH2CH2Ph), l-(l,2,4-triazol-3-yl)pyridin-2-ones (1126) were also obtained in 1-2% yields. 

Silver 2,4,6-tris(dioxoselena)perhydrotriazine-l,3,5-triide, 0039 Silver trisulfurpentanitridate, 0024 Tetrasilver diimidodioxosulfate, 0043 Tetrasilver diimidotriphosphate, 0042 Tetrasilver orthodiamidophosphate, 0041 Tetrasulfurtetraimide-silver perchlorate, 0029 1,2,4-Triazolo 14.3 -a pyridine - silver nitrate Trisilver tetranitride, 0040 See other heavy metal derivatives... 

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