Conversion of 4‐amino‐4H‐1,2,4‐triazole to 1,3‐bis(1H‐azol‐l‐yl)‐2‐aryl‐2‐propanols and 1‐phenacyl‐4‐[(benzoyl or 4‐toluenesulfonyl)‐imino]‐(1H‐1,2,4‐triazolium) Ylides

Abstract

A series of 1,3‐bis(1H‐azol‐1‐yl)‐2‐aryl‐2‐propanols 17 were synthesized in an one‐pot procedure by reacting l‐aryl‐2‐(1H‐1,2,4‐triazol‐l‐yl)‐ or l‐aryl‐2‐(1H‐imidazol‐l‐yl)ethanones with dimethylsulfoxonium methide in the presence of either 1,2,4‐triazole or imidazole. The aromatic groups in 17 were either 4‐bromo‐, 4‐chloro‐, 2,4‐dichloro‐ or 2,4‐difluorophenyl. 4‐Amino‐4H‐1,2,4‐triazole was acylated with either benzoyl or 4‐toluene‐sulfonyl chloride to afford [4‐(benzoyl or 4‐toluenesulfonyl)amino]4H‐1,2,4‐triazole. Subsequent alkylations with 4‐bromo‐ or 4‐chlorophenacyl bromide produced 1‐(4‐bromo‐ or 4‐chlorophenacyl)‐4‐[(benzoyl‐ or 4‐toluenesulfonyl)amino]‐1H‐1,2,4‐triazolium bromides. Neutralizations of these salts provided the corresponding ylides.

1,2,4-Triazoles: Synthetic approaches and pharmacological importance. (Review)

“…Similarly, the N-2 isomer [172] gave the analogue 133 (Scheme 31), while 133a showed a high potency against Mycobacterium tuberculosis growth inhibitor (99%). 2,4]triazole-3-thione 138, by reaction with p-methoxyphenyl isothiocyanate and phenyl isothiocyanate respectively, followed by treatment with sodium hydroxide. Treatment of 135 with carbon disulfide in basic medium resulted [174] in the formation of 5-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-yl)methyl-[1, 3,4]oxadiazole-2-thione 139, while treatment of 135b with cyanobromide afforded the 5-((1,5-diethyl-1H-1,2,4-triazol-3-yl)methyl)-1,3,4-oxadiazole-2-thione 140.…”

“…2,4]triazole-3-thione 138, by reaction with p-methoxyphenyl isothiocyanate and phenyl isothiocyanate respectively, followed by treatment with sodium hydroxide. Treatment of 135 with carbon disulfide in basic medium resulted [174] in the formation of 5-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-yl)methyl-[1, 3,4]oxadiazole-2-thione 139, while treatment of 135b with cyanobromide afforded the 5-((1,5-diethyl-1H-1,2,4-triazol-3-yl)methyl)-1,3,4-oxadiazole-2-thione 140. The alkaline hydrolysis of 135a, followed by acidification with HCl, furnished the 2-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-yl)acetic acid 141.…”

“…Examples of antifungal drugs [1, 2] are fluconazole 1 [3,4], itraconazole 2 [5], ravuconazole 3 [6], voriconazole 4 [7][8][9], ICI 153066 5 [10], and posaconazole 6 [11]. The action of these compounds is based on the inhibition of biosynthesis of ergosterol, the major steroid in fungal membranes, by blocking 14-α-demethylation, which occurs with accumulation of 14-α-methyl-steroids and disruption of the fungal membranes [12][13][14].…”

Isolation and structural identification of an impurity in fluconazole bulk drug substance

“…Fluconazole sample obtained from two synthetic routes were analyzed by HPLC. Three impurities were detected in the sample obtained form synthetic process reported by Narayanan et al [16]. In a prior publication [17] detailed structural elucidation of these impurities was carried out after preparative chromatographic isolation.…”

“…Different methods of synthesis of fluconazole are reported in literature [14][15][16]. Fluconazole sample obtained from two synthetic routes were analyzed by HPLC.…”