| Ullmann condensation | |
|---|---|
| Named after | Fritz Ullmann |
| Reaction type | Coupling reaction |
| Identifiers | |
| Organic Chemistry Portal | ullmann-reaction |
| RSC ontology ID | RXNO:0000081 |
TheUllmann condensation orUllmann-type reaction is the copper-promoted conversion ofaryl halides to aryl ethers, aryl thioethers, aryl nitriles, and aryl amines. These reactions are examples ofcross-coupling reactions.[1]
Ullmann-type reactions are comparable toBuchwald–Hartwig reactions but usually require higher temperatures. Traditionally, these reactions require high-boiling, polar solvents such asN-methylpyrrolidone,nitrobenzene, ordimethylformamide and high temperatures (often in excess of 210 °C) withstoichiometric amounts of copper. Aryl halides are required to be activated byelectron-withdrawing groups. Traditional Ullmann style reactions used "activated" copper powder, e.g. prepared in situ by thereduction ofcopper sulfate byzinc metal in hot water. The methodology improved with the introduction of soluble copper catalysts supported bydiamines and acetylacetonate ligands.[1]
Illustrative of the traditional Ullmann ether synthesis is the preparation of p-nitrophenyl phenyl ether from4-chloronitrobenzene andphenol.[2]
Copper is used as a catalyst, either in the form of the metal or copper salts. Modern arylations use soluble copper catalysts.[3]
A traditionalGoldberg reaction involves reaction of ananiline with an aryl halide. The coupling of2-chlorobenzoic acid and aniline is illustrative:[4]
A typical catalyst is formed fromcopper(I) iodide andphenanthroline. The reaction is an alternative to theBuchwald–Hartwig amination reaction.
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]
The nucleophile can also be carbon includingcarbanions as well ascyanide. In the traditionalHurtley reaction, the carbon nucleophiles were derived frommalonic ester and other dicarbonyl compounds:[6]
More modern Cu-catalyzed C-C cross-couplings utilize soluble copper complexes containing phenanthroline ligands.[7]
The arylation of alkylthiolates proceeds by the intermediacy of cuprous thiolates.[8]
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:
In the case of C-N coupling, kinetic studies implicateoxidative addition reaction followed by reductive elimination from Cu(III) intermediates (Ln = one or morespectator ligands):[9]
The Ullmann ether synthesis is named after its inventor,Fritz Ullmann.[10] The corresponding Goldberg reaction, is named afterIrma Goldberg.[11] The Hurtley reaction, which involves C-C bond formation, is similarly named after its inventor.[6]
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