1.2.4- Triazolones

3-Nitro-l,2,4-triazol-5-one (NTO) (140) is prepared from the nitration of l,2,4-triazol-5-one (139) under a variety of conditions the latter prepared from the condensation of semicarbazide 

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There is a drive to develop insensitive or less sensitive munitions, ie, those less likely to accidental or sympathetic detonation. A leading candidate is 3-nitro-l,2,4-triazolin-5-one [930-33-6] (59), made by the reaction of semicarbazide and formic acid to give l,2,4-triazolin-5-one [932-64-9] foUowed by nitration of the triazolone (218). 

Azolone anions are readily alkylated at nitrogen, e.g. 2-triazolone with methyl iodide gives the 1-methyl derivative. 

FIGURE 10.34 Aerobic degradation of 1,2,4-triazolone herbicides (a) metamitron and (b) metribuzin. 

Dinitroazetidine salts were studied as explosives nitrate, dinitroimidate, 2,4-dinitroimidazolate, 4,4, 5.5 -tctranitro-2.2 -biimidazolate, 5-nitro-l,2,4-triazolonate... 

Figure 18A shows the overlaid multiplicity-edited GHSQC and 60 Hz 1,1-ADEQUATE spectra of posaconazole (47). As will be noted from an inspection of the overlaid spectra, there is an overlap of the C46 and C47 resonances of the aliphatic side chain attached to the triazolone ring that can be seen more clearly in the expansion shown in Figure 18B. In contrast, when the data are subjected to GIC processing with power = 0.5, the overlap between the C46 and C47 resonances is clearly resolved (Figure 18C). In addition, the weak correlation between the C3 and C4 resonances of the tetrahydrofuryl moiety in the structure is also observed despite the fact that this correlation was not visible in the overlaid spectrum shown in A. This feature of the spectrum can be attributed to the sensitivity enhancement inherent to the covariance processing method.50...

Diethyl malonate reacts with azides to form triazolone derivatives, noteworthy because of their interesting tautomeric relationships (Dimroth). 

Methyl 3,3-diazido-2-cyanoacrylate, 1824 Methylenebis(3 -nitramino-4-methylfurazan), 2805 1-Methyl-1,2,3-triazole, 1189 Nitrosyl azide, 4766 3-Nitro-l,2,4-triazolone, 0716 Pentazole, 4443... 

Oxidation of 5-anilino-4-phenyl- -triazole may give a 4 -triazolone derivative as an intermediate (Scheme 39). ... 

The reaction was carried out in refluxing acetic acid and ethyl acetate triazolones 3 were isolated in good yields (Table 1). 

Methoxy-l,2,3,4-thiatriazole, 0773 1-Methyl-l,2,3-triazole, 1189 4-Nitroamino-1,2,4-triazole, 0777 4-Nitro-l-picryl-l,2,3-triazole, 2886 3-Nitro-l,2,4-triazolone, 0716 1-Picryl-l,2,3-triazole, 2893... 

Triazolones are reduced by lithium aliuninum hydride and triazoles can be the product, pre-... 

The oxygen atom of 5-triazolones can be replaced by sulfur by reaction with bis-(tricyclohexyltin) sulfide (64) (Equation (23)) <87S912>. 

The 3-(4-chloro-2-nitrophenyl)triazole derivative (110) undergoes nucleophilic displacement of chloride by azide ion <89JCS(P2)1425>. The thermal and photochemical decomposition of 3-nitro-triazolone have been shown to occur via radical cations <9UPC5509>. 

Thioureas (25) rearrange spontaneously at room temperature to thiadiazoles (26) (Scheme 9) (77JCS(P1)1616>. In contrast, the corresponding ureas (27) require refluxing in aqueous potassium hydroxide in order to be transformed into the triazolones (28) (Equation (8)) <90JCS(P2)1289>. 

Af, A -Disubstituted hydrazones rearrange smoothly to furnish 1,2,3-triazolium salts, hydrazides give triazolones (35), and amidrazones (36) afford (37) (Scheme 12) <91KGS822,92KGS969). 

A ring transformation (49)- (50) has been described (Scheme 18) <91JHC1229>. 3-Arylamino-5-methoxy-1,2,4-oxadiazoles (51) rearrange in the presence of sodium methoxide to triazolones (Equation (11)) <82JOCl969>. 

As a consequence of its high lipophilicity and low aqueous solubility, gastric acidity is also required for itraconazole absorption (Haria et al., 1996). It is best absorbed when administered with food, although there is considerable interpatient variabihty. The oral bioavailability or itraconazole from a 100-mg solution dose was 55%. Like ketoconazole, its bioavailability and half-life are dose-dependent, indicating saturable metabolism. Once absorbed, itraconazole is highly plasma protein bound (99.8%) and widely distributed (10.7 L/kg). Although itraconazole is widely metabolized, it does produce an active metabolite by hydroxylation of the triazolone side-chain. 

Brand Name(s) Emend, Emend 3-Day Chemical Class Triazolone derivative... 

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