1,3-AZOLES

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1,3-AZOLES
Reactivity towards E-files
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Reaction with electrophiles on N - Protonation
Taut.
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Reaction with electrophiles on N N-Alkylation
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Reaction with electrophiles on N N-Acylation
Only rel. for imidazole
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Reaction with electrophiles on C - protonation
Slow react Reactivity C-5 gt C4 gt C2
Neutral / basic cond. - Faster excange
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Reaction with electrophiles on C - Nitration
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Reaction with electrophiles on C - Nitration
Reaction with electrophiles on C - Acylation
No Lewis acid cat react. (Friedel Craft, basic N)
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Reaction with electrophiles on C - Condensation
react
Few ex. comp. to pyrrole / thiophene / furan
Reaction with Nucleophiles
No Nu displacement of H (as for pyridines Some
ring opening react. on oxasole
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Deprotonation at N - Furter reactions
C-metallation - Furter reactions

• Transmetallation
• Coupling react

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Cycloaddition
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Alkylazoler
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Quartenary 1,3-Diazolium Salts
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Amino 1,3-azoles
All as aminotautomers, all are protonated in the
ring
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Oxy 1,3-azoles
All as oxo (carbonyl) Generally low aromaticity
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Synthesis of 1,3-azoles
Carbonyl condensations
Strategy A
Strategy B
Especially valuable for oxazoles
JOC 2003, 9093
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Cycloadditions
carbenoid
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Bioactive 1,3-azoles
LO from plants
Epothilone A RH Epothilone B RMe From
myxobacteria Potential anticancer drugs Mechanism
taxol
Pilokarpin (Acetylkolin agonist) Glaukom
Isolert fra Pilocarpus jaborandi (Raintree)
Sør-Amerika
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Chymotrypsin Cleavage of peptides
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1,2-AZOLES
Reaction with electrophiles on N Protonation
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Reaction with electrophiles on N Alkylation and
acylation
Generally more difficult than with 1,3-diazoles
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Reaction with electrophiles on C
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Reaction with nucleophiles
Not replacement of H
Reaction with base
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Reaction of metallated compounds
C-Met Reactivity as expected
Cycloadditions
No ex. Of 1,2-azoles as dienes in DA
Two mechanisms Low yields
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Alkyl 1,2-azoles
Oxy 1,2-diazoles
Amino 1,2-diazoles
-amino form -3 / 5-amino- anilin, diazotation
etc
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Synthesis of 1,2-azoles
Carbonyl condensations
From oximes / hydrazones
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Cycloadditions