Aromatic Coupling Reactions

The most classical reaction of this type is the Ullmann coupling of aromatic halides in the presence of copper(O). 

This reaction has received some improvements. For example, highly reactive metal powders are obtained from Co, Ni and Fe halides and Li metal. Copper powder in DMF is used to couple polychloroaromatics, but pentachloropyridines are reduced and do not couple (for example [18]). 

Cross coupling of aryl halides involves one metallation step (e.g. with Li) followed by exchange with copper halide and reaction with Ar iodide [19]. 

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Success of the reactions depends considerably on the substrates and reaction Conditions. Rate enhancement in the coupling reaction was observed under high pressure (10 kbar)[l 1[. The oxidative addition of aryl halides to Pd(0) is a highly disfavored step when powerful electron donors such as OH and NHt reside on aromatic rings. Iodides react smoothly even in the absence of a... 

Other typical electrophilic aromatic substitution reactions—nitration (second entry) sul fonation (fourth entry) and Friedel-Crafts alkylation and acylation (fifth and sixth entnes)—take place readily and are synthetically useful Phenols also undergo elec trophilic substitution reactions that are limited to only the most active aromatic com pounds these include mtrosation (third entry) and coupling with diazomum salts (sev enth entry)... 

Polymerization by G—G Goupling. An aromatic carbon—carbon coupling reaction has been employed for the synthesis of rigid rod-like polyimides from imide-containing dibromo compounds and aromatic diboronic acids ia the presence of palladium catalyst, Pd[P(CgH )2]4 (79,80). 

Azo Coupling. The coupling reaction between an aromatic diazo compound and a coupling component is the single most important synthetic route to azo dyes. Of the total dyes manufactured, about 60% are produced by this reaction. Other methods iaclude oxidative coupling, reaction of aryUiydraziae with quiaones, and oxidation of aromatic amines. These methods, however, have limited iadustrial appHcations. 

The azo coupling reaction proceeds by the electrophilic aromatic substitution mechanism. In the case of 4-chlorobenzenediazonium compound with l-naphthol-4-sulfonic acid [84-87-7] the reaction is not base-catalyzed, but that with l-naphthol-3-sulfonic acid and 2-naphthol-8-sulfonic acid [92-40-0] is moderately and strongly base-catalyzed, respectively. The different rates of reaction agree with kinetic studies of hydrogen isotope effects in coupling components. The magnitude of the isotope effect increases with increased steric hindrance at the coupler reaction site. The addition of bases, even if pH is not changed, can affect the reaction rate. In polar aprotic media, reaction rate is different with alkyl-ammonium ions. Cationic, anionic, and nonionic surfactants can also influence the reaction rate (27). 

Basic Red 22 (134), which contains 1 part ia 7 of the yellowish red 1,4-dimethyl isomer, Basic Red 29 (135), and Basic Yellow 25 (136) are all examples of delocalized cationic azo dyes. Dyes of this type can also be synthesized by Hbnig s oxidative coupling reaction of heteroaromatic hydrazones with tertiary aromatic amines. 

An azo coupling reaction of primary aromatic and aliphatic amines with diazotized 4-nitroaniline in water-organic solutions has been investigated. It has been demonstrated that depending on the nature of an organic solvent different azo derivatives are formed in neutral medium. 

Cross-coupling reactions of aromatic or vinylic halides and olefins catalyzed by palladium. 

In general, imines are too reactive to be used to protect carbonyl groups. In a synthesis of juncusol, however, a bromo- and an iodocyclohexylimine of two identical aromatic aldehydes were coupled by an Ullman coupling reaction modi-fied by Ziegler. The imines were cleaved by acidic hydrolysis (aq. oxalic acid, THF, 20°, 1 h, 95% yield). Imines of aromatic aldehydes have also been prepared... 

The true, all-aromatic system (see 18, below) described by Kime and Norymberski is unusual in the sense that all of the ether linkages bridge aromatic carbons ". Synthesis of 18, therefore, required extensive use of copper mediated coupling reactions. As expected for such reactions, yields were generally low. The aromatics such as 18 were ineffective at binding either alkali metal or ammonium cations ". ... 

Trifluoromethylalion of aryl iodides was carried out by the fluoride ion in duced cross-coupling reaction of aromatic iodides with tnfluoromethyltnalkyl-silanes in the presence ofcopper(I) salts [219 (equation 147) Some pentafluoro- ethyl derivative was also formed This methodology was extended to pentafluoroethyl-and heptafluoropropyltriethylsilanes [2/9]... 

Aromatic carbon-heteroatom coupling reactions with participation and formation of heterocycles 98JCS(P1)2615. 

Coupling reaction of diazoniutn ions with electron-rich aromatic compounds... 

Arenediazonium ions 1 can undergo a coupling reaction with electron-rich aromatic compounds 2 like aryl amines and phenols to yield azo compounds 3. The substitution reaction at the aromatic system 2 usually takes place para to the activating group probably for steric reasons. If the para position is already occupied by a substituent, the new substitution takes place ortho to the activating group. 

The optimal pH-value for the coupling reaction depends on the reactant. Phenols are predominantly coupled in slightly alkaline solution, in order to first convert an otherwise unreactive phenol into the reactive phenoxide anion. The reaction mechanism can be formulated as electrophilic aromatic substitution taking place at the electron-rich aromatic substrate, with the arenediazonium ion being the electrophile ... 

Diazonium salts are important intermediates in organic synthesis, e.g. for the Sandmeyer reaction. The most important use is the coupling reaction with phenols or aromatic amines to yield azo dyes (see Diazo coupling). 

With a substituted aromatic ring compound 2, mixtures of isomeric coupling products may be formed the ort/zo-product usually predominates. The rules for regiochemical preferences as known from electrophilic aromatic substitution reactions (see for example Friedel-Crafts acylation), do not apply here. 

Of particular synthetic importance is the coupling of aryl- and hetarylboronic acids to aryl- and hetaryl halides (or triflates), allowing for a convenient synthesis of biphenyls, even sterically demanding derivatives such as 14, hetaryl phenyls and Zj/ -hetaryls. With appropriately disubstituted aromatic substrates, the Suzuki coupling reaction can be applied in the synthesis of polyphenylene materials. 

In the first of these, the key step in the synthetic sequence involves an oxidative phenol coupling reaction patterned after the biosynthesis of the natural product. Preparation of the moiety that is to become the aromatic ring starts by methyla-tion of phloroglucinol (5) with methanolic hydrogen chloride to give the dimethyl ether (6). Treatment of that intermediate with sulfuryl chloride introduces the chlorine atom needed in the final product (7). 

Arenediazonium salts undergo a coupling reaction with activated aromatic rings such as phenols and arylamines to yield brightly colored azo compounds, Ar—N=N—Ar. ... 

Diazonium coupling reactions are typical electrophilic aromatic substitutions in which the positively charged diazonium ion is the electrophile that reacts with the electron-rich, ring of a phenol or arylamine. Reaction usually occurs at the para position, although ortho reaction can take place if the para position is blocked. 

Copper(ll) chloride, aromatic iodination and, 551 Coproslanol, structure of, 304 Coral, organohalides from, 352 Corn oil, composition of. 1062 Cornforlh. John Warcup. 1085 Coronene, structure of, 532 Cortisone, structure of. 107 Couper, Archibald Scott, 7 Coupled reactions. 1128-1129 ATP and, 1128-1129 Coupling (NMU), 460... 

Aromatic diazonium compounds became industrially very important after Griess (1866a) discovered in 1861/62 the azo coupling reaction, by which the first azo dye was made by C. A. Martius in 1865 (see review by Smith, 1907). This is still the most important industrial reaction of diazo compounds. Hantzsch and Traumann (1888) discovered that a heteroaromatic amine, namely 2-aminothiazole, can also be diazotized. Heteroaromatic diazonium compounds were, however, only used for azo dyes much later, to a small extent in the 1930 s, but intensively since the 1950 s (see Zollinger, 1991, Ch. 7). 

The diazotization of amino derivatives of six-membered heteroaromatic ring systems, particularly that of aminopyridines and aminopyridine oxides, was studied in detail by Kalatzis and coworkers. Diazotization of 3-aminopyridine and its derivatives is similar to that of aromatic amines because of the formation of rather stable diazonium ions. 2- and 4-aminopyridines were considered to resist diazotization or to form mainly the corresponding hydroxy compounds. However, Kalatzis (1967 a) showed that true diazotization of these compounds proceeds in a similar way to that of the aromatic amines in 0,5-4.0 m hydrochloric, sulfuric, or perchloric acid, by mixing the solutions with aqueous sodium nitrite at 0 °C. However, the rapidly formed diazonium ion is hydrolyzed very easily within a few minutes (hydroxy-de-diazonia-tion). The diazonium ion must be used immediately after formation, e. g., for a diazo coupling reaction, or must be stabilized as the diazoate by prompt neutralization (after 45 s) to pH 10-11 with sodium hydroxide-borax buffer. All isomeric aminopyridine-1-oxides can be diazotized in the usual way (Kalatzis and Mastrokalos, 1977). The diazotization of 5-aminopyrimidines results in a complex ring opening and conversion into other heterocyclic systems (see Nemeryuk et al., 1985). 

If an aromatic o-diamine such as 1,2-diaminobenzene (2.24) is diazotized in dilute aqueous acid, the 2-aminobenzene-l-diazonium ion formed first (2.25) undergoes a rapid intramolecular N-azo coupling reaction to give 1,2,3-benzotri-azole (2.26). Both amino groups of 2.24 can, however, be diazotized in concentrated acid (Scheme 2-18), forming the bis-diazonium ion 2.27. 1,3- and 1,4-diamines must also be bisdiazotized in concentrated acids in order to avoid inter-molecular N- or C-coupling. 

C-coupling is of outstanding importance in the azo coupling reaction for the synthesis of azo dyes and pigments. An aromatic or heteroaromatic diazonium ion reacts with the so-called coupling component, which can be an aromatic primary, secondary, or tertiary amine, a phenol, an enol of an open-chain, aromatic, or heteroaromatic carbonyl compound, or an activated methylene compound. These reactions at an sp2-hybridized carbon atom will be discussed in Chapter 12. In the... 

The replacement of an electrofugic atom or group at a nucleophilic carbon atom by a diazonium ion is called an azo coupling reaction. By far the most important type of such reactions is that with aromatic coupling components, which was discovered by Griess in 1861 (see Sec. 1.1). It is a typical electrophilic aromatic substitution, called an arylazo-de-hydrogenation in the systematic IUPAC nomenclature (IUPAC 1989c, see Sec. 1.2). 

There are also some couplings in which hydrazones are formed but for which the azo tautomer is not detectable and probably does not exist. This is the case in some coupling reactions involving methyl groups of aromatic heterocycles (see, for example, 12.48 and 12.49 in Sec. 12.5). Replacement of a methyl proton by an arylazo group (Scheme 12-3) would result in an azo compound containing an sp3-hybridized — CH2 — group (12.1). The latter is less stable than the tautomeric hydrazone (12.2), in which there is a n-n orbital overlap from the heteroaromatic to the aromatic system. 

Most diazotized heteroaromatic amines undergo normal coupling reactions with common aromatic coupling components, as well as with CH acidic compounds (review Butler, 1975). 

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