Ullmann condensation

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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]

Contents

Ullmann-type reactions are comparable to Buchwald–Hartwig reactions but usually require higher temperatures. Traditionally, these reactions require high-boiling, polar solvents such as N-methylpyrrolidone, nitrobenzene, or dimethylformamide and high temperatures (often in excess of 210 °C) with stoichiometric amounts of copper. Aryl halides are required to be activated by electron-withdrawing groups. Traditional Ullmann style reactions used "activated" copper powder, e.g. prepared in situ by the reduction of copper sulfate by zinc metal in hot water. The methodology improved with the introduction of soluble copper catalysts supported by diamines and acetylacetonate ligands. [1]

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. [2]

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 copper(I) iodide and phenanthroline. The reaction is an alternative to the Buchwald–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]

Hurtley reaction: C-C coupling

The nucleophile can also be carbon including carbanions as well as cyanide. In the traditional Hurtley reaction, the carbon nucleophiles were derived from malonic ester and other dicarbonyl compounds: [6]

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]

Related Research Articles

In organic chemistry, an aryl halide is an aromatic compound in which one or more hydrogen atoms, directly bonded to an aromatic ring are replaced by a halide. The haloarene are different from haloalkanes because they exhibit many differences in methods of preparation and properties. The most important members are the aryl chlorides, but the class of compounds is so broad that there are many derivatives and applications.

The Suzuki reaction or Suzuki coupling is an organic reaction that uses a palladium complex catalyst to cross-couple a boronic acid to an organohalide. It was first published in 1979 by Akira Suzuki, and he shared the 2010 Nobel Prize in Chemistry with Richard F. Heck and Ei-ichi Negishi for their contribution to the discovery and development of noble metal catalysis in organic synthesis. This reaction is sometimes telescoped with the related Miyaura borylation; the combination is the Suzuki–Miyaura reaction. It is widely used to synthesize polyolefins, styrenes, and substituted biphenyls.

The Sonogashira reaction is a cross-coupling reaction used in organic synthesis to form carbon–carbon bonds. It employs a palladium catalyst as well as copper co-catalyst to form a carbon–carbon bond between a terminal alkyne and an aryl or vinyl halide.

The Corey–House synthesis (also called the Corey–Posner–Whitesides–House reaction and other permutations) is an organic reaction that involves the reaction of a lithium diorganylcuprate () with an organic halide or pseudohalide () to form a new alkane, as well as an ill-defined organocopper species and lithium (pseudo)halide as byproducts.

The Ullmann reaction or Ullmann coupling, named after Fritz Ullmann, couples two aryl or alkyl groups with the help of copper. The reaction was first reported by Ullmann and his student Bielecki in 1901. It has been later shown that palladium and nickel can also be effectively used.

<span class="mw-page-title-main">Diazonium compound</span> Group of organonitrogen compounds

Diazonium compounds or diazonium salts are a group of organic compounds sharing a common functional group [R−N+≡N]X− where R can be any organic group, such as an alkyl or an aryl, and X is an inorganic or organic anion, such as a halide.

<span class="mw-page-title-main">Palladium(II) acetate</span> Chemical compound

Palladium(II) acetate is a chemical compound of palladium described by the formula [Pd(O2CCH3)2]n, abbreviated [Pd(OAc)2]n. It is more reactive than the analogous platinum compound. Depending on the value of n, the compound is soluble in many organic solvents and is commonly used as a catalyst for organic reactions.

<span class="mw-page-title-main">Grignard reagent</span> Organometallic compounds used in organic synthesis

Grignard reagents or Grignard compounds are chemical compounds with the general formula R−Mg−X, where X is a halogen and R is an organic group, normally an alkyl or aryl. Two typical examples are methylmagnesium chloride Cl−Mg−CH3 and phenylmagnesium bromide (C6H5)−Mg−Br. They are a subclass of the organomagnesium compounds.

<span class="mw-page-title-main">Finkelstein reaction</span> Chemistry

The Finkelstein reaction, named after the German chemist Hans Finkelstein, is a type of SN2 reaction that involves the exchange of one halogen atom for another. It is an equilibrium reaction, but the reaction can be driven to completion by exploiting the differential solubility of various halide salts, or by using a large excess of the desired halide.

<span class="mw-page-title-main">Organocopper chemistry</span> Compound with carbon to copper bonds

Organocopper chemistry is the study of the physical properties, reactions, and synthesis of organocopper compounds, which are organometallic compounds containing a carbon to copper chemical bond. They are reagents in organic chemistry.

In organic chemistry, the Buchwald–Hartwig amination is a chemical reaction for the synthesis of carbon–nitrogen bonds via the palladium-catalyzed coupling reactions of amines with aryl halides. Although Pd-catalyzed C–N couplings were reported as early as 1983, Stephen L. Buchwald and John F. Hartwig have been credited, whose publications between 1994 and the late 2000s established the scope of the transformation. The reaction's synthetic utility stems primarily from the shortcomings of typical methods for the synthesis of aromatic C−N bonds, with most methods suffering from limited substrate scope and functional group tolerance. The development of the Buchwald–Hartwig reaction allowed for the facile synthesis of aryl amines, replacing to an extent harsher methods while significantly expanding the repertoire of possible C−N bond formations.

The Castro–Stephens coupling is a cross coupling reaction between a copper(I) acetylide and an aryl halide in pyridine, forming a disubstituted alkyne and a copper(I) halide.

<span class="mw-page-title-main">Tripotassium phosphate</span> Chemical compound

Tripotassium phosphate, also called tribasic potassium phosphate is a water-soluble salt with the chemical formula K3PO4.(H2O)x (x = 0, 3, 7, 9). Tripotassium phosphate is basic.

In organic chemistry, a cross-coupling reaction is a reaction where two different fragments are joined. Cross-couplings are a subset of the more general coupling reactions. Often cross-coupling reactions require metal catalysts. One important reaction type is this:

<span class="mw-page-title-main">Dichloro(1,3-bis(diphenylphosphino)propane)nickel</span> Chemical compound

Dichloro[1,3-bis(diphenylphosphino)propane]nickel a coordination complex with the formula NiCl2(dppp); where dppp is the diphosphine 1,3-bis(diphenylphosphino)propane. It is used as a catalyst in organic synthesis. The compound is a bright orange-red crystalline powder.

<span class="mw-page-title-main">Metal-phosphine complex</span>

A metal-phosphine complex is a coordination complex containing one or more phosphine ligands. Almost always, the phosphine is an organophosphine of the type R3P (R = alkyl, aryl). Metal phosphine complexes are useful in homogeneous catalysis. Prominent examples of metal phosphine complexes include Wilkinson's catalyst (Rh(PPh3)3Cl), Grubbs' catalyst, and tetrakis(triphenylphosphine)palladium(0).

Decarboxylative cross coupling reactions are chemical reactions in which a carboxylic acid is reacted with an organic halide to form a new carbon-carbon bond, concomitant with loss of CO2. Aryl and alkyl halides participate. Metal catalyst, base, and oxidant are required.

The Chan–Lam coupling reaction – also known as the Chan–Evans–Lam coupling is a cross-coupling reaction between an aryl boronic acid and an alcohol or an amine to form the corresponding secondary aryl amines or aryl ethers, respectively. The Chan–Lam coupling is catalyzed by copper complexes. It can be conducted in air at room temperature. The more popular Buchwald–Hartwig coupling relies on the use of palladium.

Dialkylbiaryl phosphine ligands are phosphine ligands that are used in homogeneous catalysis. They have proved useful in Buchwald-Hartwig amination and etherification reactions as well as Negishi cross-coupling, Suzuki-Miyaura cross-coupling, and related reactions. In addition to these Pd-based processes, their use has also been extended to transformations catalyzed by nickel, gold, silver, copper, rhodium, and ruthenium, among other transition metals.

<span class="mw-page-title-main">2-Bromoanisole</span> Chemical compound

2-Bromoanisole is an organobromide with the formula BrC6H4OCH3. A colorless liquid, it is one of three isomers of bromoanisole, the others being 3-bromoanisole and 4-bromoanisole. It is a standard coupling partner in metal catalyzed coupling reactions. These reactions include Heck reactions, Buchwald-Hartwig coupling, Suzuki couplings, and Ullmann condensations. The corresponding Grignard reagent readily forms. It is a precursor to o-anisaldehyde.

References

  1. 1 2 3 Florian Monnier, Marc Taillefer (2009). "Minireview Catalytic CC, CN, and CO Ullmann-Type Coupling Reactions". Angewandte Chemie International Edition. 48 (38): 6954–71. doi:10.1002/anie.200804497. PMID   19681081.
  2. ↑ Ray Q. Brewster; Theodore Groening (1934). "p-Nitrodiphenyl Ether". Org. Synth. 14: 66. doi:10.15227/orgsyn.014.0066.
  3. ↑ Buck, Elizabeth; Song, Zhiguo J. (2005). "Preparation of 1-Methoxy-2-(4-Methoxyphenoxy)Benzene". Organic Syntheses. 82: 69. doi:10.15227/orgsyn.082.0069.
  4. ↑ C. F. H. Allen, G. H. W. McKee (1939). "Acridone". Organic Syntheses. 19: 6. doi:10.15227/orgsyn.019.0006.
  5. ↑ H.B. Goodbrand; Nan-Xing Hu (1999). "Ligand-Accelerated Catalysis of the Ullmann Condensation: Application to Hole Conducting Triarylamines". Journal of Organic Chemistry . 64 (2): 670–674. doi:10.1021/jo981804o.
  6. 1 2 William Robert Hardy Hurtley (1929). "Replacement of Halogen in ortho-Bromobenzoic Acid". J. Chem. Soc.: 1870. doi:10.1039/JR9290001870.
  7. ↑ Antoine Nitelet, Sara Zahim, Cédric Theunissen, Alexandre Pradal, Gwilherm Evano (2016). "Copper-catalyzed Cyanation of Alkenyl Iodides". Org. Synth. 93: 163. doi: 10.15227/orgsyn.093.0163 .{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ↑ Roger Adams, Walter Reifschneider, Aldo Ferretti (1962). "1,2-Bis(N-butylthio)benzene". Org. Synth. 42: 22. doi:10.15227/orgsyn.042.0022.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ↑ Ramesh Giri; Andrew Brusoe; Konstantin Troshin; Justin Y. Wang; Marc Font; John F. Hartwig (2018). "Mechanism of the Ullmann Biaryl Ether Synthesis Catalyzed by Complexes of Anionic Ligands: Evidence for the Reaction of Iodoarenes with Ligated Anionic CuI Intermediates". J. Am. Chem. Soc. 140 (2): 793–806. doi:10.1021/jacs.7b11853. PMC   5810543 . PMID   29224350.
  10. ↑ Fritz Ullmann, Paul Sponagel (1905). "Ueber die Phenylirung von Phenolen". Berichte der deutschen chemischen Gesellschaft . 38 (2): 2211–2212. doi:10.1002/cber.190503802176.
  11. ↑ Irma Goldberg (1906). "Ueber Phenylirungen bei Gegenwart von Kupfer als Katalysator". Berichte der deutschen chemischen Gesellschaft . 39 (2): 1691–1692. doi:10.1002/cber.19060390298.
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