Mercuration of arenes

The direct mercuration of arenes is widely used for the synthesis of arylmercurials. The reaction is particularly efficient for activated arenes (such as phenols, anilines, and aryl ethers), while deactivated arenes require the use of stronger electrophiles and higher reaction temperatures. A recent example of the latter is the mercuration of terephthaldehyde reported by Vicente (equation 6) ... 

As a preparative route mercuration of arenes suffers from a lack of selectivity often all possible ring substitution products are formed. The directing influences of substituents operate, but selectivity is poor. The initial products can isomerize. Isomer distributions in mercuration of toluene under different conditions are given in Table 3. These effects coupled with the ease of polymercuration can be disadvantagous. Mild conditions must be used to limit the extent of mercuration of five-membered heterocyclic aromatics such as pyrrole, thiophene, selenophen and furan. These are among the most reactive aromatics toward Hg salts use of HgCl2 in the presence of Na02CCH3 at RT is... 

The direct mercuration of arenes by electrophilic attack with Hg(OAc)2 or HgCl2 is perhaps the most useful synthetic route. 

Mercuration.—particularly effective mercurating system for perfluoro-aromatics, RpH, is the combination Hg(0C0CFs)2,CF3S03H in CF3CO2H. Treatment in situ of the mercurated products, RpHgOSOgCFs, with HCl or KBr provide the isolatable RpHgCl and (RF)aHg, respectively (Rf = XCeF, X = F, MeO, H, NOa, Br, HO ere.). The active species in these electrophilic reactions is Hg(OSOaCF3)2. Jr-Complexes have frequently been invoked in mercurations of arenes now a series has been prepared by Dean. Interaction... 

The hemidecarboxylation of sodium phthaiate on reaction with mercuric acetate in boiling water [Eq. (82), X = H] (90) was the first reported thermal decarboxylation. The reaction has been observed for a number of arenes with two adjacent carboxylate groups (1-4,91) and has been named the Pesci reaction (91). Studies of 3-substituted sodium phthalates or of preformed mercuric 3-substituted phthalates have shown that the sterically hindered carboxyl group (the 2-carboxyl) is preferentially eliminated whether X is electron-donating or electron-withdrawing [Eq. (82), X = Me (91), Cl, N02 (91,93), Br (93), or C02H (94)]. A similar conclusion was drawn from the decomposition of mercuric 1,2-naph-thalenedicarboxylate and 3,4-phenanthrenedicarboxylate (91). 

Another instructive scenario may be found when considering the metalation of arenes. There are two distinct mechanisms for the metalation of aromatic C-H bonds - electrophilic substitution and concerted oxidative addition (Box2). The classical arene mercuration, known for more than a century, serves to illustrate the electrophilic pathway whereas the metal hydride-catalyzed deuterium labeling of arenes document the concerted oxidative addition mechanism [8, 17]. These two processes differ both in kinetic behavior and regioselectivity and thus we may appreciate the need to differentiate these two types of process. However, the choice of C-H bond activation to designate only one, the oxidative addition pathway, creates a similar linguistic paradox. Indeed, it is hard to argue that the C-H bond in the cationic cr-complex is not activated. 

Kinetic experiments have demonstrated that the mercuration of benzene with mercury acetate or nitrate is second order, first order in each of the mercury salt and the arene [7]. Electron-donating substituents on the ring increase mercuration rates, whereas electron-withdrawing groups slow down the reaction [7-11]. For example, mercuration of nitrobenzene requires 150 °C to occur and reaction of benzene with Hg(OAc)2 in AcOH takes hours at 90-120 °C whereas N,N-dimethy-laniline readily reacts with Hg(OAc)2 in aqueous EtOH at room temperature within a few minutes [7]. 

Perchloric acid increased the electrophilicity of Pd(II). A strong parallel between palladation and mercuration of aromatic hydrocarbons was drawn.568 (The effect of strong acids in increasing the electrophilicity of metal acetates has been discussed earlier.) Arylmercury complexes are relatively stable and do not afford biaryl readily. Analogous arylthallium(III) complexes only afford biaryls on photolysis in the presence of arenes via the following sequence ... 

Figure 6 Direct relationship of the relative reactivities (Jt i) of arenes in mercuration and thallation...

The study of mercuration and thallation provides a shaip focus on the experimental delineation of stepwise and concerted mechanisms for arene activation. Thus the unequivoc demonstration of arene radical cations as key intermediates in thallation, particularly of durene and pentamethylbenzene, is consistent with a stepwise (electron-transfer) mechanism for arene activation (compare Scheme 6 and equation 39). 

To date the mercurated arene radical cation is known for biphenylene [87], ace-naphthene, pyracene, hexahydropyrene, triptycene, p-terphenyl, tetramethylnaph-thopyran, anthracene, dibenzodioxin [89], and 4-tert-butylanisole [88]. In certain cases multiple mercuration is observed, for example in case of diphenylene [87] and dibenzodioxin [89]. Mercuration causes a decrease in -value and always occurs at the site where the local coefficient of the Huckel HOMO of the hydrocarbon is greatest, and there is a constant ratio of about 20.6 between the hyperfine couplings by the Hg [l, abundance 16.84 %) which has been introduced, and by the proton which has been displaced [89]. EPR spectroscopic evidence is reported for 8, 9, 10, 11, 12, 13, 14, 15 and 16 as new examples of recently recognized alternative mechanism of arene mercuration in which collapse of ArH +Hg(TFA)2 radical ion pair leads to arylmercury trifluoroacetate ArHg(TFA) + [90]. 

In this way an aromatic amine is converted regiospecifically into the corresponding mercurial. An alternative method of preparation, electrophilic mercuration of an arene, however, leads to a mixture of position isomers (p. 62). 

Aromatic compounds undergo electrophilic mercuration. The old method involved heating the arene with mercury(II) acetate under reflux in acetic acid or in ethanol. Recently it has been found that mercury(II) trifluoroacetate in trifluoroacetic acid reacts at room temperature. The reactions are reversible the isomer ratios depend on time, tending towards the statistical. The mechanism shown above has been proposed. The equilibrium constant K for Tc-complex formation has been estimated from changes in the UV spectra of arenes which occur on addition of HgfOCOCFj). For benzene in CF3CO2H at 25°C, K = 8.2mo Mm ... 

The high reactivity of ferrocene toward electrophilic substitution was described earlier. Similar reactions of arene Ti-complexes result in the cleavage of the complexed bonds. For example, Friedel-Crafts acylation, metalation with butyllithium, mercuration, or nitration of ditoluenechromium, which is more soluble in organic solvents than the slightly soluble dibenzenechro-mium, failed to give any substitution products. 

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