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 reaction In organic chemistry, a cross-coupling reaction is a reaction where two fragments are joined together with the aid of a metal catalyst. In one important reaction type, a main group organometallic compound of the type R-M (R = organic fragment, M = ...

s. Ullmann-type reactions are comparable to Buchwald–Hartwig reactions but usually require higher temperatures. Traditionally these reaction requires high-boiling polar solvents such as ''N''-methylpyrrolidone, nitrobenzene, or

dimethylformamide Dimethylformamide is an organic compound with the formula ( CH3)2NC(O)H. Commonly abbreviated as DMF (although this initialism is sometimes used for dimethylfuran, or dimethyl fumarate), this colourless liquid is miscible with water and the maj ...

and high temperatures (often in excess of 210 °C) with

stoichiometric Stoichiometry refers to the relationship between the quantities of reactants and products before, during, and following chemical reactions. Stoichiometry is founded on the law of conservation of mass where the total mass of the reactants equ ...

amounts of copper. Aryl halide were required to be activated by

electron-withdrawing group In chemistry, an electron-withdrawing group (EWG) is a substituent that has some of the following kinetic and thermodynamic implications: *with regards to electron transfer, electron-withdrawing groups enhance the oxidizing power tendency of the ...

s. Traditional Ullmann style reactions used "activated" copper powder, e.g. prepared in situ by the reduction of

copper sulfate Copper sulfate may refer to: * Copper(II) sulfate, CuSO4, a common compound used as a fungicide and herbicide * Copper(I) sulfate Copper(I) sulfate, also known as cuprous sulfate, is an inorganic compound with the chemical formula Cu2 SO4. It ...

zinc Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...

metal in hot water. The methodology improved with the introduction of soluble copper catalysts supported by

diamine A diamine is an amine with exactly two amino groups. Diamines are used as monomers to prepare polyamides, polyimides, and polyureas. The term ''diamine'' refers mostly to primary diamines, as those are the most reactive. In terms of quantities p ...

s and acetylacetonate ligands.

Ullmann ether synthesis: C-O coupling

Illustrative of the traditional Ullmann ether synthesis is the preparation of p-nitrophenyl phenyl ether from 4-chloronitrobenzene and

phenol Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it ...

. : Copper is used as a catalyst, either in the form of the metal or copper salts. Modern arylations use soluble copper catalysts.

Goldberg reaction: C-N coupling

A traditional Goldberg reaction involves reaction of an

aniline Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine. It is an industrially significant commodity chemical, as well as a versatile starti ...

with an aryl halide. A typical catalyst is formed from

copper(I) iodide Copper(I) iodide is the inorganic compound with the formula CuI. It is also known as cuprous iodide. It is useful in a variety of applications ranging from organic synthesis to cloud seeding. Copper(I) iodide is white, but samples often appe ...

and

phenanthroline 1,10-Phenanthroline (phen) is a heterocyclic organic compound. It is a white solid that is soluble in organic solvents. The 1,10 refer to the location of the nitrogen atoms that replace CH's in the hydrocarbon called phenanthrene. Abbreviated ...

. The reaction is an alternative to the Buchwald–Hartwig amination reaction. The scope is includes

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...

s in place of amines.The coupling of

2-chlorobenzoic acid 2-Chlorobenzoic acid is an organic compound with the formula ClC6H4CO2H. It is one of three isomeric chlorobenzoic acids, the one that is the strongest acid. This white solid is used as a precursor to a variety of drugs, food additives, and dye ...

and aniline is illustrative: : 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. BuchwaldAmidationReaction

Hurtley reaction: C-C coupling

The nucleophile can also be carbon including carbanions as well as

cyanide Cyanide is a naturally occurring, rapidly acting, toxic chemical that can exist in many different forms. In chemistry, a cyanide () is a chemical compound that contains a functional group. This group, known as the cyano group, consists of ...

. In the traditional Hurtley reaction, the carbon nucleophiles were derived from malonic ester and other dicarbonyl compounds: : (Z = CO₂H) More modern Cu-catalyzed C-C cross-couplings utilize soluble copper complexes containing phenanthroline ligands.

C–S coupling

The arylation of alkylthiolates proceeds by the intermediacy of cuprous thiolates.

Mechanism of Ullmann-type reactions

In the case of Ullmann-''type'' reactions (aminations, etherifications, etc. of aryl halides), the conversions involves 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. These copper(I) compounds subsequently react with the aryl halide in a net metathesis reaction: : : : In the case of C-N coupling, kinetic studies implicate

oxidative addition Oxidative addition and reductive elimination are two important and related classes of reactions in organometallic chemistry. Oxidative addition is a process that increases both the oxidation state and coordination number of a metal centre. Oxid ...

reaction followed by reductive elimination from Cu(III) intermediates ( = one or more

spectator ligand In coordination chemistry, a spectator ligand is a ligand that does not participate in chemical reactions of the complex. Instead, spectator ligands (vs "actor ligands") occupy coordination sites. Spectator ligands tend to be of polydentate, such ...

s): :

History

The Ullmann ether synthesis or is named after its inventor,

Fritz Ullmann Fritz Ullmann (July 2, 1875 in Fürth – March 17, 1939 in Berlin) was a German chemist. Ullmann was born in Fürth and started studying chemistry in Nuremberg, but received his PhD of the University of Geneva for work with Carl Gräbe in 18 ...

. The corresponding Goldberg reaction, is named after Irma Goldberg. The Hurtley reaction, which involves C-C bond formation, is similarly named after its inventor.

References

{{DEFAULTSORT:Ullmann Condensation Carbon-heteroatom bond forming reactions Condensation reactions Name reactions