Ullmann substitution

A halogen atom directly attached to a benzene ring is usually unreactive, unless it is activated by the nature and position of certain other substituent groups. It has been show n by Ullmann, however, that halogen atoms normally of low reactivity will condense with aromatic amines in the presence of an alkali carbonate (to absorb the hydrogen halide formed) and a trace of copper powder or oxide to act as a catalyst. This reaction, known as the Ullmant Condensation, is frequently used to prepare substituted diphenylamines it is exemplified... 

Aromatic haUdes do not react easily with phenoxide ions to produce diaryl ethers unless the aromatic haUde is substituted with one or more electron-withdrawing groups, eg, nitro or carboxyl groups. The Ullmann reaction uses finely divided copper or copper salts to cataly2e the reaction of phenoxides with aromatic haUdes to give diaryl ethers. 

ULLMANN GOLDBERG Aromatic substitution Cu catalyzed substitution of aromatic halides in the synthesis of disryls, diaiyl ethers, diaryl amines, phenols... 

The extension of the method to the synthesis of y-carboline from 1-y-pyridylbenztriazole (199) and of a 3,4-benz-y-carboline from a l-(4-quinolyl)benztriazole proceeded smoothly. In an alternative approach excellent yields of y-carboline were obtained by heating l-phenylpyrido[3,4-d] -triazole (200) at 320-350°. The synthesis of halogeno-substituted j8- and y-carbolines via the Graebe-Ullmann reaction has been reported. ... 

It has been shown that the imidoyl chloride moiety of 2(lff)-pyrazinones can imdergo an easy addition/elimination reaction with alkyl amines [24], while reactions with anilines proceed under harsher conditions. Ullmann coupling [109-113] of 2(lff)-pyrazinones with substituted anilines could open the way to the libraries of physiologically active compounds useful in inhibiting HIV replication [7]. Polymer-bound pyrazinone was successfully... 

Asymmetric syntheses of warfarin <96TL8321> and the axially chiral bicoumarin, isokotanin A <96TL3015> have been reported. The former is based on a Rh-catalysed asymmetric hydrogenation of a 3-(a,P-unsaturated ketone) substituted coumarin, whilst the key steps of the latter are an asymmetric Ullmann coupling and a selective demethylation. The stereochemistry of the fused dihydrocoumarin resulting from Li/NHs reduction of... 

To investigate the possibility of preparing uniquely substituted hexa-chlorodibenzo-p-dioxins, several experiments were performed under Ullmann conditions. Although condensation of potassium 2-bromo-4-chlorphenate occurred readily, several 2,6-substituted phenates failed to... 

As seen in the retro-synthetic Scheme 5.3, intermediate 15 is useful for both routes. The choice of benzyl protection group was made based on the robust stability of benzyl phenol ethers toward most reactions and several possible avenues to remove it, although it was reported from Medicinal Chemistry that benzyl group removal via hydrogenolysis posed challenges in this compound. The choice of iodide substitution was born out of the known high reactivity of iodides in the Ullmann-type coupling reaction with alcohols and the robust stability of aryl iodides in many other common reactions. 

When subjected to Ullmann biaryl reactions, 8-bromo-l-oxazolinylnaph-thalene (,S)-27 can be converted to the 8,8 -substituted binaphthyl 28 in high diastereomeric excess (another isomer, the (a/ ,b )-diastcrcomer, is less than 3%).40... 

A larger blue shift in fluorescence was observed for alkoxycarbonyl-substituted PTs 400 and 401. The polymers were prepared from 2,5-dibromo-substituted monomers by two methods (i) Ullmann reaction with Cu powder and (ii) Ni(0)-mediated polymerization (Scheme 2.63) [485]. Both polymers have similar molecular weights (Mn 3000), although the Cu-prepared polymers showed higher quality and lower polydispersity. PL emission maxima for the Cu-prepared polymers 400 and 401 were red-shifted, compared to the Ni-prepared polymers (by 13-15 nm ( 0.05 0.06 eV) in solution and 25-30 nm ( 0.08 O.lOcV) in films, Table 2.4). This demonstrates that the properties of the polymer depend on the preparation method and, consequently conclusions from small shifts of 0.05-0.1 eV in PL EL energies of the materials, prepared by different methods, should be made with care. 

Dichloro-2,2 -dimethyl-1,1 -dianthraquinonyl can be synthesized by Friedel-Crafts reaction from phthalic anhydride and 2,6-dichlorotoluene. Subsequent cyclization of the resulting substituted benzoylbenzoic acid 102 in sulfuric acid affords the corresponding anthraquinone derivative 103, which is dimerized by Ullmann reaction ... 

The reaction sequence used to synthesize these flexible systems involved four steps which are outlined in Figure 1. The first of these was an aromatic nucleophilic substitution, a polymer forming reaction in which 4,4 -dichlorodiphenyl sulfone reacts with various diols. The second step, an Ullmann ether reaction, gives bromine terminated products in which the bromines can be replaced by ethynyl end groups in the final stages. 

Both the substitution and Ullmann reactions provide sources of oligomers, making the final product a mixture of monomeric and oligomeric Bpecies. While this was desirable for the overall objective of the work, increasing chain length between crosslink sites, the presence of oligomers did complicate characterization of the products obtained from the various reactions. For this reason, a reaction scheme which would give a pure monomeric product was formulated and used for all of the diol systems to do preliminary evaluations. 

R = CHj, R = and adenocarpine(16 R = CH=CHPh, R = H) ° are likewise dehydrogenated to 2,3 -bipyridine, and related dehydrogenation reactions afford substituted 2,3 -bipyridines. Ullmann and Grignard reactions have been used to synthesise 2,3 -bipyridine, whereas the Gomberg reaction of 3-pyridinediazonium chloride with pyridine and alkyl pyridines affords 2,3 -bipyridine, along with other isomeric bipyridines, and alkyl substituted 2,3 -bipyridines, respectively. " Photolysis of 3-... 

Several of the methods of synthesis of 2,2 -bipyridines have their counterpart in the preparation of 4,4 -bipyridine. The Ullmann reaction has been used to prepare 4,4 -bipyridine. Thus 4-halogenated pyridines afford 4,4 -bipyridine. Dehalogenation and dimerization of 4-bromopyridine may be accomplished too with hydrazine and alkali at 65°C in the presence of a palladium catalyst, whereas 4-chloropyridine is converted to 4,4 -bipyridine in 46% yield by reaction with alkaline sodium formate in the presence of palladium on charcoal and a surfactant. Several extensions of the Ullmann reaction have recently been reported, especially for the synthesis of substituted 4,4 -bipyridines. Thus 4-iodo-2-methylpyridine gives 2,2 -dimethyl-4,4 -bipyridine, 3-nitro-4-chloropyridine affords 3,3 -dinitro-4,4 -bipyridine, 4-bromo- or 4-iodotetrafluoropyridine gives octafluoro-4,4 -bipyridine, and 4-iodo- or 4-bromotetrachloropyridine gives octachloro-4,4 -bipyridine. Related syntheses have been de-... 

For a review of copper-assisted aromatic nucleophilic substitution, sec Lindley Tetrahedron 1984, 40. 1433-1456. "For a review of the Ullmann ether synthesis, see Moroz Shvartsbcrg Russ. Chem. Rev. 1974, 43. 679-689. Wcingarten J. Org. Chem. 1964, 29. 977. 3624. 

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