Selective 1,2,4-triazole

Table 1 Selected triazole derivatives and their corresponding mass spectral data. H NMR data supplied by author...

Anastrozole is a potent and selective triazole AI. It, like letrozole, binds competitively and specifically to the heme of the CYP19. Anastrozole 1 or 10 mg administered once daily for 28 days reduces total body aromatization by 96.7 and 98.1%, respectively. In addition, anastrozole reduces local aromatization in large, ER-positive breast tumors. 

Several thiadiazolo-triazoles 43 have been synthesized that show antifungal and cytotoxic properties. hiadiazoles 45 were prepared from hydrazones 44 by treating them neat with thionyl chloride at room temperatures. The thiadiazoles were formed regio-selectively on the methyl group of the hydrazone. 

Reduction of the 1//-1,2-benzodiazepines 6 with lithium aluminum hydride results in the dihydro compounds 8, which are dehydrogenated to the 3H-1,2-benzodiazepines 9 by 4-phenyl-4//-l,2,4-triazole-3,5-dione.123 The products readily revert to the 1//-tautomers in the presence of sodium methoxide. 3//-1,2-Benzodiazepines react with 3-chloroperoxybenzoic acid to give mixtures of 1- and 2-oxides, 10 and 11, in which the latter predominate. Treatment of the 2-oxides 11 with nucleophiles provides 3-substituted H- 1.2-benzodiazepines 12. Selected examples are given.124... 

In a similar fashion, the C - C hnked pyrazinone-triazoles were reacted with an excess of DMAD (3.5 equiv) under microwave irradiation conditions at a pre-selected temperature of 190 °C (Scheme 29). The reactions proceeded smoothly in o-DCB in 10-20 min, using a maximum irradiation power of 200 W. Differing from the C - O analogues, the C - C linked pyrazinone-triazoles generated the corresponding pyridinones as the exclusive products. 

These triazolo-pyrazinones were reacted with DMAD under microwave irradiation (Scheme 32). The reactions were carried out in o-DCB at a slightly elevated temperature of 200 °C for 15 min. Interestingly, the opposite selectivity to the C-C linked analogues was observed during the Diels-Alder reactions of C - N linked pyrazinone-triazoles with DMAD, as pyridines were found to prevail over the corresponding pyridinones. These compounds were isolated in combined yields of 39-68%. 

The preparation of novel triazole-containing 20-22 membered macrocyclic azacrown ether-thioethers was reported <96JCR(S)182> and the first selective synthetic method fra the synthesis of dicyanotriazolehemiporhyrazines was published <96JOC6446>. 1,2,4-Triazole-containing polyimide beads were prepared and employed as Mo(VI) epoxidation catalyst supports, liie 1,2,4-nitronyl nitroxide 29 was also synthesized and found to have remarkable magnetic properties <96AM60>. 

Diacetylcyclopropane reacts with 3-amino-l, 2,4-triazole in acetic acid (either aqueous or glacial) to give triazolopyrimidines 28 <%1ZV1322>, whilst a selection of fiised-ring pyrimidines, for example the l,2,3-triazolo[4,S-prepared using amino hetmoarenecarboxamides and esters <96H(42)691 >. 

Under microwave irradiation and applying MCM-41-immobilized nano-iron oxide higher activity is observed [148]. In this case also, primary aliphatic alcohols could be oxidized. The TON for the selective oxidation of 1-octanol to 1-octanal reached to 46 with 99% selectivity. Hou and coworkers reported in 2006 an iron coordination polymer [Fe(fcz)2Cl2]-2CH30H with fez = l-(2,4-difluorophenyl)-l,l-bis[(l//-l,2,4-triazol-l-yl)methyl]ethanol which catalyzed the oxidation of benzyl alcohol to benzaldehyde with hydrogen peroxide as oxidant in 87% yield and up to 100% selectivity [149]. An alternative approach is based on the use of heteropoly acids, whereby the incorporation of vanadium and iron into a molybdo-phosphoric acid catalyst led to high yields for the oxidation of various alcohols (up to 94%) with molecular oxygen [150]. 

Kellum [115] has described a class-selective oxidation chemistry procedure for the quantitative determination of secondary antioxidants in extracts of PE and PP with great precision (better than 1 %). Diorgano sulfides and tertiary phosphites can be quantitatively oxidised with /-chloropcroxybenzoic acid to the corresponding sulfones and phosphates with no interference from other stabilisers or additives. Hindered phenols, benzophenones, triazoles, fatty acid amides, and stearate... 

Bis-l,2,4-triazole-3,5-diones such as 110 have also been used in Diels-Alder reactions, and give bispyridazines.171 The pyridazine derivative 111 is formed in quantitative yield from PTAD and 2,7-dimethyl-2,3,5,6-octatetraene,172 and the azadiene, 4-aza-l,3,5-triphenylpenta-2,4-diene, also reacts readily with PTAD to give 112.173 There are many other examples of Diels-Alder additions of ADC compounds to simple acyclic dienes which proceed entirely as expected the above selection has been limited to reactions of synthetic potential and with novel features. 

More recently, Somfai and coworkers have reported on the efficient coupling of a set of carboxylic acids suitable as potential scaffolds for peptide synthesis to a polymer-bound hydrazide linker [24]. Indole-like scaffolds were selected for this small library synthesis as these structures are found in numerous natural products showing interesting activities. The best results were obtained using 2-(7-aza-l H-benzo-triazol-l-yl)-l,l,3,3-tetramethyluronium hexafluoride (HATU) and N,N-diisopropyl-ethylamine (DIEA) in N,N-dimethylformamide as a solvent. Heating the reaction mixtures at 180 °C for 10 min furnished the desired products in high yields (Scheme 7.4). In this application, no Fmoc protection of the indole nitrogen is required. 

Loupy et al. [70] have studied the effect of solvent on the selectivity of the alkylation of 1,2,4-triazole 62 by 2,2, 4 -trichloroacetophenone 63 (Scheme 4.31) under MW and conventional heating. The reactions were all performed at 140 °C. 

Pyridones were studied for N- and C-alkylation reactions by de la Hoz et al. [100] as already mentioned for 1,2,4 triazoles, the selectivity of the alkylation is highly dependent on the activation technique (microwave or conventional heating). 

Experimental dipole moments and acidities of azoles, including 1,2,3-triazole, show linear correlations with their Jt-electron excess calculated by the semiempirical AMI method <2003CHE71>. Experimental dipole moments of azoles agree well with those calculated by the DFT program ALLCHEM <2003PCA4172>. Calculated dipole moments t (in units of Debye,D) of a few selected azoles are listed below ... 

Table 1 Selected bond lengths (in A) for 1,2,3-triazole derivatives 5-12...

Reactions of salts of 1,2,3-triazole with electrophiles provide an easy access to 1,2,3-triazol-jV-yl derivatives although, usually mixtures of N-l and N-2 substituted triazoles are obtained that have to be separated (see Section 5.01.5). Another simple method for synthesis of such derivatives is addition of 1,2,3-triazole to carbon-carbon multiple bonds (Section 5.01.5). N-l Substituted 1,2,3-triazoles can be selectively prepared by 1,3-dipolar cycloaddition of acetylene or (trimethylsilyl)acetylene to alkyl or aryl azides (Section 5.01.9). 

Abstract In this chapter, selected results obtained so far on Fe(II) spin crossover compounds of 1,2,4-triazole, isoxazole and tetrazole derivatives are summarized and analysed. These materials include the only compounds known to have Fe(II)N6 spin crossover chromophores consisting of six chemically identical heterocyclic ligands. Particular attention is paid to the coordination modes for substituted 1,2,4-triazole derivatives towards Fe(II) resulting in polynuclear and mononuclear compounds exhibiting Fe(II) spin transitions. Furthermore, the physical properties of mononuclear Fe(II) isoxazole and 1-alkyl-tetrazole compounds are discussed in relation to their structures. It will also be shown that the use of a,p- and a,C0-bis(tetrazol-l-yl)alkane type ligands allowed a novel strategy towards obtaining polynuclear Fe(II) spin crossover materials. 

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