Triazole moieties

An alternative pathway to impart diversity at the C-3 position of the pyrazinone scaffold is possible via the hnkage of the triazole moiety to the core using a C - C bond (Scheme 27). The C-3 acetylenic pyrazinone... 

The 1,2,4-triazole moiety was featured in the structures of several medicinal agents whose synthesis was reported during the year. Notable among these reports was the preparation of the... 

In yet another approach towards the synthesis of cyclocarbons by cycloreversion, Adamson and Rees [71] prepared the 1,2,3-triazole-fused dehydroannulenes 42 - 44, as mixtures of regioisomers in ca. 30 % overall yield, by oxidative Hay coupling of the protected 4,5-diethynyl-l,2,3-triazole 41 (Scheme 7). No investigations have yet been reported on the thermal or mass spectrometric [3-1-2] cycloreversions of 42-44, with loss of the triazole moieties and ultimate formation of the cyclocarbons Cis, C24, and C30, respectively. 

In view of the nature of this edition as a whole, the content of this chapter is restricted to describing the chemistry of monocyclic 1,2,4-triazole systems. Readers are directed to the relevant chapters elsewhere in this edition for details of the chemistry of fused heterocyclic systems that contain a 1,2,4-triazole moiety examples of fused systems are only cited in this chapter where relevant. 

The characterization of molecular systems containing 1,2,4-triazole moieties has continued to employ familiar spectroscopic techniques, supplemented by more recent developments in the field. Other techniques, including electrochemistry, have also been described for triazoles that have been designed for or deployed in specific, applied environments such functional molecules are described later in this chapter. 

Chloromethyl-l,2,4-triazoles can be valuable intermediates in the synthesis of more complex compounds containing a 1,2,4-triazole moiety, and they can be accessed using a number of established methods for the synthesis of the triazole ring system. However, these processes often give variable yields and require much work to construct the starting material. A more convenient procedure has been developed, by which a hydroxymethyl-1,2,4-triazole is converted to the chloromethyl derivative by reaction with thionyl chloride (Equation 20 and Table 6) <2006S156>. 

As part of a program directed toward the synthesis of dendrimeric structures containing the 1,2,4-triazole moiety, 3,5-dichloro-4(4-methoxyphenyl)-4/7-l,2,4-triazole 69 was reacted with phenol 77 under basic conditions to give the dendron 78 in a yield of 80% (Equation 28) <2006T2677>. 

Subsequent efforts focused on reducing hERG inhibition. This goal was successfully accomplished using the triazole moiety instead of benzimidazole in... 

The Chichibabin reaction for the synthesis of indolizines has been revisited and some variations have been proposed. The modified benzotriazole 168 reacted with substituted pyridines 167 in refluxing dimethylformamide (DMF). The indolizine 169 bears a triazole moiety that proved useful for the construction of benzo-annulated indolizines <2000JOC8059>. Also, cyclic iminium ylides like 170 can be used in the Chichibabin reaction. Their solvolysis produced the corresponding indolizinones 171 (Scheme 40). 

X-Ray elucidation provided a final proof for the structure elucidation of 8-(4-chlorophenyl)-8-hydroxy-5-methyl-8/f-[l,4]thiazino[3,4-H[l,2,4]oxadiazol-3-one 49, which was obtained as a product of ring-transformation reaction <1997J(P2)2407>. This analysis revealed that the oxadiazole ring is planar, whereas the thiazine ring is in a distorted half-chair conformation with a displacement asymmetry parameter AC2 (S—G(3)) = 0.031. The structure analysis represents the first X-ray elucidation of a [l,4]thiazine ring fused to a [l,2,4]triazole moiety. 

Scheme 47 contains syntheses of [l,2,4]triazolo[4,3- ]pyridazine derivatives by ring closure of the triazole moiety. Kozhevnikov et al. reported <2005MC31> an interesting ring transformation treatment of the... 

Synthesis was directed towards metabolic stability and this was found in the bis-triazole series of compounds. Metabolic stability is achieved by the relative resistance of the triazole moiety to oxidative attack, the presence of halogen functions on the phenyl grouping, another site of possible oxidative attack, and steric hindrance of the hydroxy function, a site for possible conjugation. 

The IR and Raman spectra of benzotriazole, benzotriazole anion and its Cu(I) complex have been measured. The characteristic peaks in the IR spectrum of the triazole moiety in benzotriazole anion occur at 1163 cm , 1134 cm , and 1115 cm . A broad band with a main peak at 1151 cm occurs in the spectrum of the Cu(I)-BTA complex <85JST(l00)57i>. The chemisorption of benzotriazole on clean copper and cuprous oxide surfaces is investigated by combining XPS, UV-PE and IR reflection absorption spectroscopy (IRAS). Coordination geometry including the triazole-... 

The 1,2,4-triazole moiety, like the 1,2,4-oxadiazole and 1,3,4-oxadiazole discussed in Section 11.2.5, has been used extensively as an ester or amide bioisostere but has rarely been inserted into peptide segments 109-112 1,2,4-Triazoles are complementary to the 1,2,4- and 1,3,4-oxadiazoles due to their ability to donate a hydrogen bond as well as accept a hydrogen bond. 

The iV-4-(benzotriazolylmethyl)-tetrahydro-l,4-benzodiazepine 59 reacted smoothly with Grignard reagents in THF to provide convenient access to substituted homologues in good yield (Scheme 25) <2002J(P1)592>. The benzo-triazole moiety can be removed reductively with NaBFLr to provide the simple jV-methyl compound, while reaction with triethyl phosphite and ZnBr2 in dry THF gave the diethylphosphonate derivative. 

Fig. 13 Chemical structure of indole derivatives containing a triazole moiety [130,131]...

To build up the desired cyclic key precursors, containing an amide bond as an anchor to connect the triazole moiety, different strategies can be pursued. Cyclization of y-amino acids directly yields pyrroli-dones, whereas P-amino alcohols allow access to two different chiral bicyclic frameworks. They can form either oxazolidin-2-ones (Enders and Kallfass 2001) or morpholinones upon treatment with phosgene or chloro acetylchloride, respectively (Scheme 3). 

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