Copper Ullman reaction

Ullman reaction The synthesis of diaryls by the condensation of aromatic halides with themselves or other aromatic halides, with the concomitant removal of halogens by a metal, e.g. copper powder thus bromobenzene gives diphenyl. The reaction may be extended to the preparation of diaryl ethers and diaryl thio-ethers by coupling a metal phenolate with an aryl halide. 

The Ullman reaction has long been known as a method for the synthesis of aromatic ethers by the reaction of a phenol with an aromatic halide in the presence of a copper compound as a catalyst. It is a variation on the nucleophilic substitution reaction since a phenolic salt reacts with the halide. Nonactivated aromatic halides can be used in the synthesis of poly(arylene edier)s, dius providing a way of obtaining structures not available by the conventional nucleophilic route. The ease of halogen displacement was found to be the reverse of that observed for activated nucleophilic substitution reaction, that is, I > Br > Cl F. The polymerizations are conducted in benzophenone with a cuprous chloride-pyridine complex as a catalyst. Bromine compounds are the favored reactants.53,124 127 Poly(arylene ether)s have been prepared by Ullman coupling of bisphenols and... 

The procedure described here is by far the most efficient synthesis of terpyridine. Previous preparations include the dehydrogenation of pyridine with ferric chloride, the Ullman reaction of 2-bromopyrid1ne and 2,6-dibromopyridine,5 the action of copper on 2-bromopyridine and 6-bromo-2,2 -... 

Ullman reaction conditions have also been used in the synthesis of biflavanoids. Heating of 3-haloflavones in the presence of copper powder provided biflavones in good yield <1993SC1075>. Isoflavone and derivatives, for example 425, can be prepared efficiently by the Suzuki cross-coupling of 3-bromo and 3-iodochromones 424 with arylboronic acids (Scheme 71) <1988BCJ3008, 1989CPB529>. 

The mixed Ullman reaction in which two haloarenes couple in the presence of copper powder is still commonplace in industrial process, but the catalyzed cross-coupling reactions appear to be more productive and provide reliable results in synthesis of unsymmetrical biaryls (Scheme 30). The isomeric michel-... 

Ullman reaction. Synthesis of biaryls by copper-induced coupling of aryl halides. Similar coupling of aryl halides with aroxides yields diaryl ethers. (A modification of the Fittig synthesis in which copper powder is used instead of sodium.)... 

Copper mediated Ullman reaction, usually requires harsh conditions. Wipf and Lynch reported arelatively mild biaryl ether synthesis via an SnAt (nucleophUic aromatic substimtion)... 

Although not frequently used directly for reduction to hydrocarbons, aryl iodides (e.g., iodobenzene, CeHsI) on treatment with activated copper (Cu) apparently form arylcuprates, which, in a subsequent step, react with a second equivalent of aryl iodide to produce a biaryl. Equation 7.24 is an example of the production of biphenyl by this coupling process (known as the Ullman reaction). ... 

Comparison of the effects of different sources of ultrasound are few and far between. An exception is a study of the copper-catalysed Ullman coupling of 2-iodonitrobenzene in DMF [45] (Scheme 3). The original reaction was first described by Rausch in 1961 [46] and uses a highly activated substrate, such that the thermal reaction only takes 60 h at 60 °C. It should be noted that this represents one of the lowest temperatures and highest yields reported for a classical Ullman reaction. 

In a procedure recommended for the preparation of iodo[U- C]benzene, a mixture of [U- C]benzene and 1.8 equivalents of iodine in 45% nitric acid was heated at 85 °C for 1.5 h. Vacuum distillation of the reaction product furnished a 4 1 mixture of iodo[U- C]-benzene and [U- C]benzene in almost quantitative radiochemical yield. Without separation into its components, the mixture was subjected to a copper catalyzed Ullman reaction at 288-290 °C to give [U- C]biphenyl in 65% overall radiochemical yield. ... 

Ullman condensation of m-trifluoromethylaniline (13) with o-iodobenzoic acid in the presence of copper-bronze affords flu-fenamic acid (14). An analogous reaction of o-chlorobenzolc acid with 2,3-dimethylaniline (15) gives mefenamic acid (16) meclofenamic acid (18) is obtained by Ullman condensation employing 2,6-dlchloro-3-methylaniline (17). 

This instant invention represents an improvement in the Ullman coupling reaction. This investigation represents the first general method for coupling electron deficient phenols and unactivated aryl halides (1,2,3,4). The basis of the improvement lay in the high solubility of (CuOTf)2 benzene and cesium phenolate or copper phenolate in the reaction solvent, toluene. 

Aminobenzimidazoles undergo copper-catalyzed Ullman-type reaction with 2-chloropyridine-... 

The prevalence of the aniline functional group in alkaloid natural products of medicinal interest has inspired a number of metal-catalyzed strategies for the preparation of substituted anilines. One classical method, a variation of the Ullman aryl ether synthesis, features copper catalysis. This method generally suffers from harsh reaction conditions and limited substrate scope. Nonetheless, the simplicity of the transformation and the inexpensiveness of copper catalysis has prompted additional development of this strategy. For instance, cyclohexylphenylamine is formed in excellent yield from the copper(I) iodide-catalyzed amination of iodobenzene. ... 

The Ullman coupling reaction is known to proceed via arylcopper intermediates. Pertinent reviews have appeared on this subject (Bacon and Hill, 1965 Fanta, 1964, 1974). Copper-induced coupling of vinyl halides has been found to occur with retention of configuration (Cohen and Poeth, 1972). 

Various attempts have been made to use cheaper chloromonomers. ICI patented an Ullman ether condensation route in which copper is used to catalyse the halide displacement. However copper residues had to be carefully removed since they were detrimental to the thermal stability of the polymer. It also seems possible that the balance of side reactions is such that PAEK produced from chloromonomers will be somewhat different to PAEK produced by more conventional routes. More recently Gharda Chemical has filed patents [8] on a route to PEK from a chloromonomer. The low cost monomer (hydroxychlorobenzophenone) is prepared by reaction of 4-chlorobenzoylchloride with phenol. 

Organocopper intermediates are involved in another broad class of reactions which accomplish the coupling of two organic substrates. The classical example of this type of reaction is the Ullman coupling of aryl halides, which is usually done with a copper-bronze alloy. Good yields in this reaction are limited to halides with electron-attracting substituents. Mechanistic and synthetic work has revealed the... 

As a metal-mediated approach, intramolecular Ullman-type reaction of 2-(2-haloaryl)phenols with copper salts has been used for dibenzofuran synthesis [35]. However, harsh reaction conditions are generally required. On the other hand, Liu et al. developed the copper-mediated intramolecular O-arylation of 2-(2-haloaryl)phenols under milder and neutral conditions [36]. The reaction of 2-(2-chloroaryl)phenols 65 with electron-withdrawing substituent(s) gave the corresponding dibenzofurans 66 in high yields (Scheme 23.25). They also demonstrated the... 

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