Epoxides reaction with triazole

Acyl substituents at the 3- and/or 4-positions result in decreased hydrolytic stability compared with the alkyl and aryl derivatives described above. Despite this constraint most of the usual reactions of the carbonyl group are possible. Aldehydes <9ILA1211> and ketones are oxidized to the carboxylic acid, borohydride reduction affords the expected alcohols, and epoxides are formed on reaction with diazomethane. Oximes and arylhydrazones are formed with hydroxylamine and arylhydrazines, and the products may subsequently undergo monocyclic rearrangement involving the oxadiazole to give the corresponding isomeric furazans and 1,2,3-triazoles (Section 4.05.5.1.4). 

A modern example of an agent used against human fungal infections is Pfizer s fluconazole, which actually contains two triazoles. The first is added as the anion to an a-chloroketone and the second is added to an epoxide made with sulfur ylid chemistry (you will meet this in Chapter 46). Note that weak bases were used to catalyse both of these reactions. Triazole is acidic enough for even... 

Reactions with aldehydes and ketones in the 1,2-dimethylimidazole series. Side-chain lithiation of a 2-chloro-methylthiazole 574 leads to epoxides 575 (Scheme 122) <2003T1381>. Exposure of triazole 576 to LDA and then benzonitrile generates the bicyclic 577 <2003EJM959>. 

The epoxide 38 derived from tetrafluoromethylenecyclopentadiene has been utilized as the diene in a [4 + 2]-cycloaddition reaction with the 1,2,4-triazole 36 to form the interesting adduct... 

Acid 121 can be converted to acid chloride 126 with either thionyl chloride [46] or oxalyl chloride [49]. Friede 1-Crafts acylation on m-difluorobenzene with 126 gives the (i )-chlor-oketone 127 (97% ee) in 80% overall yield from 121. Epoxidation of 127 affords 128 with > 95% diastereoselectivity. Reaction of the epoxide with triazole furnishes ra 5-epoxide (2S, 35)-129, an isomer of an important intermediate for the preparation of a class of triazole antifungal agents (Scheme 19). 

The synthesis of triticonazole is only described in patents as a one-pot sequence [57] Knoevenagel condensation of 4-chlorobenzaldehyde on 2,2-dimethylcyclopentanone gives the a,) -unsaturated ketone, which enters a Corey-Chaykovsky epoxidation reaction to afford the epoxide which in turn is opened with the potassium salt of 1,2,4-triazole (Scheme 17.10). 

Synthesis of Triazoles A number of MCRs that use an epoxide-azide-alkyne Cu(I)-catalyzed cycloaddition sequence to provide substituted p-hydroxy-l,2,3-triazoles 70 (Scheme 3.36) have been recently developed. The azida-tion of an epoxide with sodium azide to give 2-azidoalcohols and subsequent reaction with a terminal alkyne have been carried out under mild conditions in environmentally friendly solvents, such as water, using the catalytic system CuSO sodium ascorbate [65] (see the example depicted in Scheme 3.36) [65a] or a porphyrinatocopper(II) complex... 

Cyclobutanones are susceptible to Baeyer-Villiger oxidation. The epoxide (186) cannot be prepared by reacting the ketoalkene (185 equation 67) with MCFBA. Moderate, chemoselective epoxidation has been observed in the reaction of (185 equation 68) with ( -trichloroethylperoxycaib(Miic acid (190) prepared in situ from the triazole (189) and H2O2. ... 

The 1,2 dione and 1,2 diol were prepared starting from 2,4-dichlorobenzyl propyl ketone using a modification of the Mannich reaction and epoxidising the intermediate enone with basic hydrogen peroxide. Opening of the epoxide with 1,2,4-triazole followed by reduction completes the synthesis. (Figure 23). 

The additive reaction of oxiranes was also utilized for the preparation of SMP networks with covalent crosslinks. The crosslinking of 3-amino-1,2,4-triazole with epoxidized natural rubber catalyzed by bisphenol-A resulted in polymer networks having shape-memory capability with Ti ms = Tg [82]. The Tg could be controlled by the 3-amino-1,2,4-triazole content in the range between 29 and 64 °C. Recently, the crosslinking reaction of oxiranes and amines was systematically investigated in two polymer systems based on the reaction of the diglycidyl ether of bisphenol A epoxy monomer cured with the bifunctional poly(propylene glycol)bis(2-aminopropyl)... 

The addition of dichloromethyllithium to methyl 4,6-0-benzylidene-2-0-benzoyl- and 2-0-methyl-a-D-ri o-hexopyranosid-3-ulose affords branched derivatives 8 which, on treatment with caesium acetate-crown ether, affords compounds 9. The latter derivatives are drought to be formed via an intermediate f/>iro-chloroepoxide in a similar way to that described in Vol. 25, p. 162, ref. 9. In a somewhat analogous reaction, spiro-tosyl epoxide 10 is formed when the anion derived from chlorotosyl methane (TSCH2CI) reacts with methyl 4,6-0-benzylidene-a-D-ery/ o-hexopyranosid-3-ulose. Compound 10 can be caused to react with a wide range of nucleophiles affording a wide range of branched-derivatives. The synthesis of l-(P-D-apiofuranosyl)-l,2,3-triazoles is mentioned in Chapters 10 and 20. 

Pathak et al. developed a metal-free route to 1,5-disubstituted 1,2,3-triazolylation at Cl, C2, C3, C4, andC6 of pyranosidesgenerating 1,5-triazolylated monosaccharides and 1,5-triazole-linked disaccharides for the first time. Exo-cyclic vinyl sulfones 117 and 118 derived from styrene epoxide and monotosylated glycerol were reacted with six different azidopyranosides 116 to generate 1,5-disubstituted 1,2,3-triazoles 119 and 120 (Scheme 4.45) [46]. The reaction was... 

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