Ullmann condensation
Ullmann condensation | |
---|---|
Named after | Fritz Ullmann |
Reaction type | Coupling reaction |
Identifiers | |
Organic Chemistry Portal | ullmann-reaction |
RSC ontology ID | RXNO:0000081 |
The Ullmann condensation or Ullmann-type reaction is the copper-promoted conversion of aryl halides to aryl ethers, aryl thioethers, aryl nitriles, and aryl amines. These reactions are examples of cross-coupling reactions.[1]
Ullmann-type reactions are comparable to
Ullmann ether synthesis: C-O coupling
Illustrative of the traditional Ullmann ether synthesis is the preparation of p-nitrophenyl phenyl ether from
- O2NC6H4Cl + C6H5OH + KOH → O2NC6H4O−C6H5 + KCl + H2O
Copper is used as a catalyst, either in the form of the metal or copper salts. Modern arylations use soluble copper catalysts.[3]
Goldberg reaction: C-N coupling
A traditional Goldberg reaction involves reaction of an aniline with an aryl halide. The coupling of 2-chlorobenzoic acid and aniline is illustrative:[4]
- C6H5NH2 + ClC6H4CO2H + KOH → C6H5N(H)−C6H4CO2H + KCl + H2O
A typical catalyst is formed from
Aryl iodides are more reactive arylating agents than are aryl chlorides, following the usual pattern. Electron-withdrawing groups on the aryl halide also accelerate the coupling.[5]
Hurtley reaction: C-C coupling
The nucleophile can also be carbon including
- Z2CH2 + BrC6H4CO2H + KOH → Z2C(H)−C6H4CO2H + KBr + H2O (Z = CO2H)
More modern Cu-catalyzed C-C cross-couplings utilize soluble copper complexes containing phenanthroline ligands.[7]
C–S coupling
The arylation of alkylthiolates proceeds by the intermediacy of cuprous thiolates.[8]
Mechanism of Ullmann-type reactions
In the case of Ullmann-type reactions (aminations, etherifications, etc. of aryl halides), the conversions involve copper(I) alkoxide, copper(I) amides, copper(I) thiolates. The copper(I) reagent can be generated in situ from the aryl halide and copper metal. Even copper(II) sources are effective under some circumstances. A number of innovations have been developed with regards to copper reagents.[1]
These copper(I) compounds subsequently react with the aryl halide in a net metathesis reaction:
- Ar−X + CuOR → Ar−OR + CuX
- Ar−X + CuSR → Ar−SR + CuX
- Ar−X + CuNHR → Ar−NHR + CuX
In the case of C-N coupling, kinetic studies implicate oxidative addition reaction followed by reductive elimination from Cu(III) intermediates (Ln = one or more spectator ligands):[9]
- ROCuAr(X)Ln → RO−Ar + CuLn
History
The Ullmann ether synthesis is named after its inventor, Fritz Ullmann.[10] The corresponding Goldberg reaction, is named after Irma Goldberg.[11] The Hurtley reaction, which involves C-C bond formation, is similarly named after its inventor.[6]
References
- ^ PMID 19681081.
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- doi:10.15227/orgsyn.093.0163.)
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: CS1 maint: multiple names: authors list (link - PMID 29224350.
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