1.4- Diaryl-l,2,3-triazoles

The synthesis of 4-amino-3,5-diaryl-l,2,4-triazoles is well documented but deamination using sodium nitrite in aqueous nitric acid typically gives low yields and is restricted in its scope. A more efficient method of deamination using aqueous hypophophorous acid has been reported the intermediate diazonium salt formed in this reaction is reduced quickly within the reaction mixture, leading to high yields (Equation 29 and Table 10) <2002JHC93>. 

N-Amino groups are replaced by hydrogen on treatment with phosphorus trichloride (l,2,4-triazole-4-acylimines are converted into triazoles) or with nitrous acid (e.g., 824 825). 4-Amino-3,5-diaryl-l,2,4-triazoles are deaminated efficiently by reduction of the diazonium salt with aqueous hypophosphorous acid <2002JHC93>. AAAlkylaminoazoles form stable N-nitroso compounds, normally existing as a mixture of E- and Z-rotamers. 

Various synthetic protocols were available for the preparation of 1,2,4-triazoles and derivatives thereof Efhcient synthesis of 3,4,5-tri-substituted 1,2,4-triazoles 171 was accompHshed from the reaction of guanidines 169 with 2,2,2-tri-chloroethylimidates 170 in PEG-400 (14TL177). 3,5-Diaryl-l,2,4-triazoles 173 were synthesized from a domino nucleophilic substitution/ oxidative cycfr-zation sequence from 2 equivalents of amidines 172 with copper catalyst, sodium bicarbonate as base, 1,10-phenanthroline as an additive, and K3[Fe(CN)6]/air as the oxidant (14T1635). Sulfur-substituted 1,2,4-triazoles... 

JCS(C)171l), s-triazolo[3,4-6][l,3,4]oxadiazoles (71TL1729), 3,5-diaryl-s-triazolo[3,4-c]-s-triazoles (76ACS(B)463) and pyrazolo[l,5-c][l,2,4]triazoles (77JHC227). 

Syntheses of quaternary l-alkyl-3-perfluoroalkyl-4,5-dimethyl-l,2,4-triazolium iodides have led to the disclosure of a variety of new quaternary salts <04JOC1397>. Arylation of 3-alkylthio-5-aryl-l,2,4-triazoles under basic conditions gave 5-alkylthio-l,3-diaryl-l,2,4-triazoles in moderate yields <04JHC201>. Acyl hydrazides 155 reacted with imidates 156 to yield 1,2,4-triazoles 157 followed by Mitsunobu reactions with amino alcohols 158 to give regioisomeric... 

A possibility of formation of 5,7-diaryl-4,7-dihydro-1,2,4-triazolo[l,5-a]pyr-imidines 182 in reactions of 3-amino-l,2.4-triazole 147 with synthetic precursors of unsaturated ketones—aldehydes 179 and ketones 180—or in condensation of acetophenones 180 and azomethynes 183 was established in [176, 177]. It was shown that in the first case the multicomponent procedure was not an independent method but resulted in the initial formation of unsaturated ketones 181 themselves and their further reaction with aminoazol (Scheme 3.53). 

Imidoyl chlorides (303) react with primary aromatic amines to give 2,3-diaryl-5-phenyl-3//-imidazo[l,2-i][l,2,4]triazoles (304) (Equation (88)) <89JCR(S)262>. 

Among (halkyl and diaryl (3-methylthio-l,2,4-triazol-5-yl)iminodithiocar-bonates prepared from 5-amino-1,2,4-triazoles, carbon disulfide, and an excess of potassium hydroxide with 2 mol equivalents of the corresponding alkyl or aralkyl hahdes, dimethyl (3-methylthio-l,2,4-triazole-5-yl)imino-dithiocarbamate 18 was isolated in both desmotropic forms. The form 18a crystaUized from hot acetonitrile, while the form 18b crystallized slowly from dilute ethanol. Both forms are stable enough in fresh -heptane and benzene-d solutions to give a possibility to differentiate them by UV and NMR (Scheme 12) (1990JHC1689). 

Lam discovered that imidazoles and pyrazoles underwent N-arylation with 2.0 equiv. of p-tolylboronic acid under typical conditions (Scheme 5.15) [9]. Electron-poor azoles such as triazoles and tetrazole gave poor yields. Recently, dark and co-workers [30] reported N-arylation at the N-2 position of 4,5-diaryl-l,2,3-triazole (no specified yield) (Scheme 5.15). This is in contrast to the results on the parent 1,2,3-triazole where N-arylation occurs on N-1 [9j. The r ochemical preference of Clark s system can be explained by the high sensitivity to steric hindrance of these cross<oupling reactions (vide infra). 

In an effort to synthesize fused 7/5 heterocyclic ring system to obtain boosted bioactivity, Gupta et al. [102] condensed two heterocyclic systems, triazole and triazepine, into a single framework by the cyclocondensation of 5-aryl-3,4-diamino-l,2,4-triazoles with p-chlorocinnamaldehydes in the presence of catalytic amount of p-TsOH in DMF xmder microwave irradiation (also conventional oil bath heating) to afford 3,6-diaryl-5H-[l,2,4] triazolo[4,3-fc]-l,2,4-triazepines (103). Both the heterocyclic motifs (triazepine and triazole) are well-known core units of several drugs and bioactive compoxmds (Scheme 34). 

Cyclocondensation of aminoazoles and a,(3-unsaturated carbonyl compounds or Mannich bases is the most common method for the synthesis of dihydroa-zolopyrimidines [99, 155, 156, 157]. Various alkyl- and aryl-substituted dihy-dropyrimidines were prepared in this way. For example, cyclocondensation of 3-amino-1,2,4-triazole 147 with chalcones 148 leads to 5,7-diaryl-4,7-dihydro-l,2,4-triazolo[l,5-a]pyrimidines 149 [158], while reaction with hydrochlorides of Mannich bases 150 leads to heterocycles 151 (Scheme 3.46). 

Cycloaddition reactions of l,3,4-oxadiazin-6-ones 97 (R = Ph, R = Ar), via their 2,3-diaza-l,3-diene functionality, are observed by treatment with dipolarophiles. Thus, 2,5-diaryl-l,3,4-oxadiazines 97 react with diaryl nitrilimines 115, which are liberated in situ from the corresponding hydrazonoyl chlorides 114 and triethylamine, to give 1//-1,2,4-triazole A -imines 118 and open-chain products 119 <1996JHG591>. It is reasonable to conclude that intermediates 116 are formed initially from cycloaddition across the adjacent carbonyl-carbon nitrogen double bond and that subsequent CO abstraction gives 177-1,2,4-triazole A -imine derivatives 118. The open-chain adducts 119 are formed from intermediates 117, which result from the reaction of 115 at the carbonyl double bond of the oxadiazinones 97 (Scheme 15). 

Cyano-l,5-diaryl-A -l,2,3-triazolines (385), obtained by addition of diazoacetonitrile to AT-benzylideneanilines, have been decomposed to aziridines (386) and enamines (387) with migration of the 5-aryl substituent (78x2229). Thermolysis of 4,4-dimethyl-l-(l-phenyl-vinyl)-5-(l-pyrrolidinyl)-4,5-dihydro-li/-l,2,3-triazole (388) gives 2-methyl-iV-(l-... 

Photochemically induced ring contraction of novel 4-iminodi-hydro-1,2,3-triazoles to the corresponding ( )- and (Z)-aziridin-imines has also been reported. A different pathway is followed in the 6-(l -triazolyl)uracils (24) which on irradiation in acetonitrile were converted into the pyrrolo[2,3-d]pyrimidines (25) via triplet biradical intermediates a novel cyclisation leading to the formation of pyrimido[4,5-c]isoquinolines is observed, however, when C-5 phenyl substituents are present on the triazole ring. Rate constants for the cycloaddition f diarylnitrilimines, generated by photoelimination of nitrogen from diaryl 2H-tetra-zoles, to various dipolarophiles have been determined experiment-... 

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