Ullmann procedures

Fig. 16.5. Biaryl synthesis via arylcopper compounds II— in-situ preparation of the nucleophile with the classical Ullmann procedure ("variant 1"), with a procedure that may also be applied to aryl bromides ("variant 2") and with a crossed classical Ullmann coupling (bottom-most reaction example).

Fig. 13.4. Biaryl syntheses via arylcopper compounds II in situ preparation of the nucleophile in the Ullmann procedure.

Halo ethers are prepared by adding an alcoholic solution of the sodium alkoxide to the polymethylene halide, X(CHj) X, in anhydrous ether or benzene, as illustrated by the preparation of l-bromo-6-methoxyhexane (47%). In a somewhat different manner, an aromatic halo ether such as y-phenoxypropyl bromide is synthesized by the action of phenol and the dihalide in the presence of hot aqueous sodium hydroxide (85%). The syntheses of o- and p-chlorophenyl phenyl ethers have been successfully accomplished by the Ullmann procedure (40-55%), whereas chlorination of diphenyl ether yields an inseparable mixture of isomers. ... 

Aromatic and aliphatic amino ethers have been synthesized by this method. An example of the formation of a cyano ether is the preparation of p-cyano benzyl methyl ether from the substituted benzyl bromide and sodium methoxide (84%). Also, certain aryloxyacetonitriles, AtOCHjCN, are made by the condensation of chloroacetonitrile with sodium phenoxides in a solution of methyl ethyl ketone containing a small amount of sodium iodide (70-80%). Aromatic nitro ethers, like o- and p-nitrodiphenyl ether, have been prepared by the Ullmann procedure (84%). The synthesis of alkyl p-nitrophenyl ethers has also been accomplished with good yields (55-92%). ... 

Certain diethers of the type ROCHaCH OR have been prepared by adding alkyl halides to a solution of sodium in excess ethylene glycol monoalkyl ether, as in the preparation of ethylene glycol dimethyl ether (78%). Chloromethyl methyl ether and alcohols react to give an acetal derivative of formaldehyde, CHjOCHjOR the reaction is carried out in the presence of pyridine. Aromatic diethers such as 2-methoxydiphenyl ether have been prepared by the Ullmann procedure. ... 

The bisbenzylisoquinoline (205) has been synthesized from 6-bromolaudanosine and armepavine by an improved Ullmann procedure, using pentafluorophenylcop-per in dry pyridine. ... 

A comprehensive study of the decoration of polymer-bound 2(lH)-pyrazinone scaffolds, by means of a variety of transition metal-catalyzed transformations, has been described [40]. The readily prepared pyrazinone was specifically decorated at the C3 position by use of microwave-mediated Suzuki, Stille, Sonogashira, and Ullmann procedures (Scheme 16.17) to introduce additional diversity. In all these... 

Ullmann coupling reactions of iodothiophenes were referred to in CHEC-I <84CHEC-I(4)741>. This procedure has been made use of in the synthesis of cyclobuta [1,2-c 3,4-c ]dithiophene <85CC880>. The first step in the synthesis is the Cornforth modification of the Ullmann procedure (MeCN, Me2CO, aq. NH3, Cu, CUSO4 25 °C) (Equation (58)). The Ullmann reaction has also been used for the synthesis of several substituted phenylthiophene derivatives <85JHC1667>. 

Some of the optimized procedures for Stille and Sonogashira reactions involve the addition of copper cocatalysts to accelerate the cross-coupling procedures. A word of caution should be provided on the role of these additives in Pd-catalyzed amination procedures. Beletskaya and Davydov have reported the arylation of benzotriazole and of diary-lamines in polar organic or aqueous organic solvents using a combination of palladium and copper as catalyst.The arylation of amino acids has been reported under similar conditions.However, these reaction conditions are similar to classic Ullmann procedures for the synthesis of arylamines, except for the addition of palladium to the reaction mixture. In one case, subsequent work showed that the palladium species was not an essential component and that copper alone was the true catalyst in their reactions. An unusual accelerating effect of amino acid coordination to copper was used to explain the low-temperature Ullmann conditions. Beletskaya, however, showed that lower yields and a mixture of N1 and N2 arylation products were observed from the reactions of benzotriazole in the absence of copper and no reaction was observed in the absence of palladium. The conditions for this chemistry are, however, distinct enough from those of the majority of the aryl halide aminations to support the idea that a different mechanism may operate. 

In a new modification of the Ullmann procedure. Cava and Afzali have found that condensation of equimolar amounts of 5-( + )-6 -bromolaudanosine with iS -(+)-armepavine in pyridine in the presence of pentafluorophenyl-copper (PFPC) gave (-l-)-O-trimethylmagnolamine in 427 yield. This reaction was then extended to the aporphine-benzylisoquinoline series. ... 

The procedure above is a modification of the method of Ullmann and Stein for the same compound. Sartoretto and Sowa used the same general method. The need for a catalyst can be avoided by heating a mixture of guaiacol potassium, guaiacol, and chlorobenzene at 200° under pressure. Ullmann and Stein have prepared the compound by using phenol, o-bromoanisole. 

Therefore, this book is to give the analyst - whether a newcomer wishing to acquaint themself with new methods or a materials analyst needing to inform themself on methods that are not available in their own laboratory - a clue about the principles, instrumentation, and applications of the methods, techniques, and procedures of surface and thin-film analysis. The first step into this direction was the chapter Surface and Thin Film Analysis of Ullmann s Encyclopedia of Industrial Chemistry (Vol. B6, Wiley-VCH, Weinheim 2002) in which practitioners give briefly outline the methods. 

Reduction with zinc dust in aqueous sulfuric acid gives 2-methyl-4-aminothiophenol (28) Condensation with 2-chlorobenzoic acid (Ullmann reaction) leads to 29, which can close to but one thiox-anthone (25) on treatment with sulfuric acid. Although this procedure is longer than the original, the yields are good and the sequence is regioselective. ... 

As an alternative to the Tauber method, 2,2 -diaminobiphenyl (509) was transformed to carbazole (1) using diazotization conditions. This reaction proceeds intra-molecularly by displacement of nitrogen. With this procedure, only moderate yields of carbazoles were obtained. The reaction is mechanistically similar to the Graebe-Ullmann synthesis (494) (Scheme 5.6). 

The above procedure is essentially that of Ullmann and Bleier.2 2-Aminobenzophenone has also been prepared by reduction of 2-nitrobenzophenone,3 by the Hofmann reaction of the amide of o-benzoylbenzoic acid with sodium hypobromite,4 by the action of an excess of benzoyl chloride on aniline at 220°,6 and by hydrolysis of the acetyl derivative which is obtained by the action of phenylmagnesium bromide on 2-methyl-3,l,4-benzoxaz-4-one (from anthranilic acid and acetic anhydride).6 Various methods for the preparation of 2-aminobenzophenones have been summarized critically by Simpson, Atkinson, Schofield, and Stephenson.7... 

Gracbc and Ullmann, Ann., 21)1, 8 (1896). (The submitters have found that the Curtins procedure gives letter results than the met hod of Hofmann cf. I . A. S. 

The procedure given is similar to one described by Ullmann and Miinzhuber, except that one-half as much aniline hydrochloride and two-thirds as much glacial acetic acid are used, and the time of reflux is reduced from 6 to 3 hours. -Aminotetra-phenylmethane also can be prepared from triphenylchlorometh-ane and aniline hydrochloride, following the same procedure outlined for triphenylcarbinol and aniline hydrochloride, except that a reaction time of 1 hour is sufficient.. 

Acetaldol, Analytical Procedures are briefly discussed under Aldol in Ullmann 3(1953), 172... 

The cyclodehydration of o-phenoxybenzoic acids has been widely used to synthesize xanthones carrying variety of substituents. An Ullmann reaction provides a useful route to the required acids a 2-chlorobenzoic acid and a phenol react in an inert solvent such as nitrobenzene in the presence of copper bronze and potassium carbonate (53JCS1348). In a modified procedure sodium methoxide is used without solvent at 200 °C (79JA665). Cyclization is accomplished in concentrated sulfuric acid or in acetyl chloride containing a little sulfuric acid (61JCS2312). 

Acetal, Analytical Procedures are discussed in l)Kirk Othmer 9(1952),607 2)Ullmann 3 (1953),17 3)Organic Analysis, Interscience, NY, 1(1953),309-328... 

A reaction which is reminiscent of the Wurtz coupling procedure, and which is particularly valuable in the syntheiss of biphenyl and its symmetrically substituted derivatives, is that of Ullmann. It involves heating an aryl halide with copper powder, or better, with activated copper bronze. 

The general procedures for the formation of acetates, benzoates and toluene-p-sulphonates are described in Section 9.6.6, p. 1248. Toluene-p-sulphonates are stable to the presence of lithium aluminium hydride, to the acidic conditions used in aromatic nitrations and to the high temperatures that might be necessary in an Ullmann reaction. 

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