Aromatic rings, arylation reactions

A reaction of aryl diazonium salts that does not involve loss of nitrogen takes place when they react with phenols and arylamines Aryl diazonium ions are relatively weak elec trophiles but have sufficient reactivity to attack strongly activated aromatic rings The reaction is known as azo coupling two aryl groups are joined together by an azo (—N=N—) function... 

The Suzuki reaction97 allows tire coupling of two aromatic rings by reaction of an arylboronic compound with a iodo or bromo aryl derivative. The tetrakis (U iphenylphosphine) Pd is the catalyst working in the basic medium. This reaction was recently used98 in aqueous media for the preparation of different isomers of diphenyldicarboxylic acids (Fig. 5.21) but also for the synthesis of soluble rodlike polyimides99 by coupling the 3,6-diphenyl- V, V,-bis(4-bromo-... 

Another catalytic methodology that is widely used for C-C bond formation is the Heck and related coupling reactions [86, 87]. The Heck reaction [88] involves the palladium-catalysed arylation of olefinic double bonds (Fig. 1.31) and provides an alternative to Friedel-Crafts alkylations or acylations for attaching carbon fragments to aromatic rings. The reaction has broad scope and is currently being widely applied in the pharmaceutical and fine chemical industries. For example, Albemarle has developed a new process for the synthesis of the anti-in-... 

Intramolecular anodic coupling of diaryl amides is a synthetically interesting reaction that may be applied to the synthesis of alkaloidal structures [210]. However, this aryl coupling is initiated by the oxidation of an aromatic ring (aryl ether or phenol) and not by oxidation of the nitrogen. Therefore, it is not discussed further in this chapter. 

Compounds in which the halogen atom is attached directly to an aromatic ring (aryl halides, e.g., bromobenzene) differ so much from the alkyl halides in their preparations and properties that they will be taken up in a separate chapter (Chap. 25). For the present we need to know that—in the kinds of reaction typical of alkyl halides—most aryl halides are extremely mreactive. 

Some metallocenes, such as ferrocene, undergo a wide variety of aromatic ring substitution reactions, including Friedel-Crafts acylation, arylation, and sulfonation a few such as nickelocene and cobalto-cene are too unstable to be directly substituted. 

CHEMICAL PROPERTIES stable under ordinary conditions of use and storage hazardous polymerization has not been reported organic portions of compound have typical aromatic chemical properties chemical activity is intermediate between phenol and anisole undergoes a wide variety of aromatic ring substitution reactions, including Friedel-Crafts acylation, arylation and sulfonation sublimes above 100°C (212°F) resists pyrolysis at 400°C (752°F) molecule is diamagnetic dipole moment is effectively zero not decomposed by high temperature, air, water, dilute acids or bases, when the central metal atom is in a stable oxidation state FP (data not available) LFL/UFL (data not available) AT (data not available) HC (data not available),... 

The transmetallation of various organometallic compounds (Hg, Tl, Sn, B, Si, etc.) with Pd(II) generates the reactive cr-aryl, alkenyl, and alkyl Pd compounds. These carbopalladation products can be used without isolation for further reactions. Pd(II) and Hg(II) salts have similar reactivity toward alkenes and aromatic compounds, but Hg(II) salts form stable mercuration products with alkenes and aromatic rings. The mercuration products are isolated and handled easily. On the other hand, the corresponding palladation products are too reactive to be isolated. The stable mercuration products can be used for various reactions based on facile transmetallation with Pd(II) salts to generate the very reactive palladation products 399 and 400 in rim[364,365]. 

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... 

Arenediazonium salts are also used for the couplina[563], (Z)-Stilbene was obtained unexpectedly by the reaction of the ti-stannylstyrene 694 by addition-elimination. This is a good preparative method for cu-stilbene[564]. The rather inactive aryl chloride 695 can be used for coupling with organostannanes by the coordination of Cr(CO)3 on aromatic rings[3.565]. 

Hydrogenolysis of aryl and alkenyl halides and triflates proceeds by the treatment with various hydride sources. The reaction can be explained by the transmetallation with hydride to form palladium hydride, which undergoes reductive elimination. Several boro hydrides are used for this purpose[680], Deuteration of aromatic rings is possible by the reaction of aryl chlorides with NaBD4681]. 

Aromatic Ring Fluorination. The formation of an aryl diazonium fluoride salt, followed by decomposition, is a classical reaction (the Schiemaim reaction) for aryl fluoride preparation (21). This method has been adapted to the production-scale manufacture of fluorobenzene [462-06-6]... 

In the iavestigation of the decomposition reaction of aryldia2onium tetrafluoroborates ia nitroben2ene, it was found that ia addition to uoroben2ene, 3,3 -dinitrobiphenyl was formed (67). An ionic type of arylation reaction seems to take place. Decomposition of aryldia2onium tetrafluoro-, tetrachloro-, and tetrabromoborates ia aromatic solvents leads to electrophilic ring arylation (68). 

An aryl methane- or toluenesulfonate ester is stable to reduction with lithium aluminum hydride, to the acidic conditions used for nitration of an aromatic ring (HN03/H0Ac), and to the high temperatures (200-250°) of an Ullmann reaction. Aryl sulfonate esters, formed by reaction of a phenol with a sulfonyl chloride in pyridine or aqueous sodium hydroxide, are cleaved by warming in aqueous sodium hydroxide. ... 

Protection of primary aryl amines as the triazene is accomplished by diazotiza-tion of the amine followed by reaction with pyrrolidine in aq. KOH. This group is stable to metalation of the aromatic ring by metal halogen exchange. The amine is recovered by reductive cleavage with Ni-Al alloy (aq. KOH, rt, 37-68% yield). ... 

A variety of aryl systems have been explored as substrates in the Knorr quinoline synthesis. Most notable examples are included in the work of Knorr himself who has demonstrated the high compatibility of substituted anilines as nucleophilic participants in that reaction. In the case of heteroaromatic substrates however, the ease of cyclization is dependent on the nature and relative position of the substituents on the aromatic ring." For example, 3-aminopyridines do not participate in ring closure after forming the anilide... 

The results are consistent with the rate-determining step being addition of the aryl radical to the aromatic ring, Eq. (9). Support for this mechanism is derived from the results of three other studies (a) When A -nitrosoacetanilide is decomposed in pyridine, the benzene formed by abstraction of hydrogen from pyridine by phenyl radical accounts for only 1 part in 120 of the reaction leading to phenyl-pyridines. (b) 9,9, 10,lCK-Tetrahydro-10,10 -diphenyl-9,9 -bianthryl is formed in the reaction between phenyl radicals and anthracene, probably by the addition mechanism in Eq. (11). Adducts are also formed in the reactions of benzyl radicals with anthracene- and acridine. ... 

For the in situ preparation of the required arenediazonium salt from an aryl amine by application of the diazotization reaction, an acid HX is used, that corresponds to the halo substituent X to be introduced onto the aromatic ring. Otherwise—e.g. when using HCl/CuBr—a mixture of aryl chloride and aryl bromide will be obtained. The copper-(l) salt 2 (chloride or bromide) is usually prepared by dissolving the appropriate sodium halide in an aqueous solution of copper-(ll) sulfate and then adding sodium hydrogensulfite to reduce copper-(ll) to copper-(1). Copper-(l) cyanide CuCN can be obtained by treatment of copper-(l) chloride with sodium cyanide. 

Pyridinium chloride ([PyHjCl) has also been used in a number ofcyclization reactions of aryl ethers (Scheme 5.1-4) [4, 18]. Presumably the reaction initially proceeds by deallcylation of the methyl ether groups to produce the corresponding phenol. The mechanism of the cyclization is not well understood, but Pagni and Smith have suggested that it proceeds by nucleophilic attack of an Ar-OH or Ar-0 group on the second aromatic ring (in a protonated form) [4]. 

How- does this reaction take place Although it appears superficially similar to the SN1 and S 2 nucleophilic substitution reactions of alkyl halides discussed in Chapter 11, it must be different because aryl halides are inert to both SN1 and Sj 2 conditions. S l reactions don t occur wdth aryl halides because dissociation of the halide is energetically unfavorable due to tire instability of the potential aryl cation product. S]sj2 reactions don t occur with aryl halides because the halo-substituted carbon of the aromatic ring is sterically shielded from backside approach. For a nucleophile to react with an aryl halide, it would have to approach directly through the aromatic ring and invert the stereochemistry of the aromatic ring carbon—a geometric impossibility. 

The benzylic position of an alkylbcnzene can be brominated by reaction with jV-bromosuccinimide, and the entire side chain can be degraded to a carboxyl group by oxidation with aqueous KMnCfy Although aromatic rings are less reactive than isolated alkene double bonds, they can be reduced to cyclohexanes by hydrogenation over a platinum or rhodium catalyst. In addition, aryl alkyl ketones are reduced to alkylbenzenes by hydrogenation over a platinum catalyst. 

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