1,2,4-Triazole tertiary alcohols

Fluconazole. This substance (19) is a water-soluble bis-triazole tertiary alcohol (33). Fluconazole [86586-75-4] h.3.s a broad spectmm, but has httie activity in vitro. However, animal experiments reveal a broad spectmm and a potent effect. 

Synthesis and Fungicidal Activity of Triazole Tertiary Alcohols... 

Imidazole- and Triazole-Transfer Reactions to Tertiary Alcohols, Halides, and Acetates... 

Table 20-1. N-Substituted imidazoles and triazoles prepared by transfer reactions of azolides A—F with tertiary alcohols of the triphenylmethanol type and analogues.

Table 20-2. Imidazoles and triazoles prepared through transfer reactions of azolides to secondary and tertiary alcohols.

A number of other 1,2,4-triazole containing tertiary alcohols (Figure 13) are being developed for crop protection e.g. BAY HWG 1608( 2) and SAN 619F(ni), and fluconazole( M) is in clinical trials for the oral treatment of human fungal infections. 

It is possible to construct tertiary alcohols in a one-step process from an a-1,2,4-triazol-1-yl ketone with a suitable carbanion (Figure 22). In this case the ester enolate generated using lithium diisopropylamide gives a much better yield than the product of the Reformatsky reaction. 

Other 1,2,4-triazole containing tertiary alcohols are being developed as fungicides, and it is likely that further compounds from this family, with useful biological properties, will be discovered. 

A review of the asymmetric Stetter and asymmetric benzoin reactions focuses mainly on two classes of highly successful catalysts NHCs and metallophosphites. A new NHC, pyrido[l,2-a]-2-ethyl[l,2,4]triazol-3-ylidene (99), is a powerful catalyst of benzoin condensation in the presence of potassium f-butoxide. A DFT study of the mechanism suggests that the f-butanol solvent is explicitly involved. o-Phthalaldehyde chalcones (100) undergo intramolecular aldehyde-ketone crossed-benzoin condensation to naphthalenone tertiary alcohols (101) in yields up to 94%, in 20 min, using NHC catalysis. ... 

When treated with a mixture of triphenylbismuth dibromide (Ph3BiBr2) and iodine, tertiary and secondary alcohols are converted to the corresponding most stable alkenes under mild conditions. Sesquiterpinic alcohol is dehydrated to cedrene by this binary system (Equation (143)).236 Irradiation of tri(/>-tolyl)bismuth diazide in benzene in the presence of acetylenes results in the transfer of one of the azido ligands to the triple bond, affording 1,2,3-triazoles in moderate yields (Equation (144)).237... 

After the occurrence of some decomposition the free heterocycles formed, pyrazole, imidazole, or triazole, may take part in the reaction. Since they are more acidic than ethyl alcohol (47) they may protonate the tertiary nitrogen atom of the unreacted molecules, thus facilitating the nucleophilic substitution at the germanium atom by the ethoxy group. An autocatalytic effect therefore might be operative in these reactions. 

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