Thallation of aromatic compounds

Thallation of aromatic compounds with thallium tris(trifluoroacetate) proceeds more easily than mercuration. Transmetallation of organothallium compounds with Pd(II) is used for synthetic purposes. The reaction of alkenes with arylthallium compounds in the presence of Pd(Il) salt gives styrene derivatives (433). The reaction can be made catalytic by use of CuCl7[393,394], The aryla-tion of methyl vinyl ketone was carried out with the arylthallium compound 434[395]. The /9-alkoxythallium compound 435, obtained by oxythallation of styrene, is converted into acetophenone by the treatment with PdCh[396]. 

Isomer Distributions in the Thallation of Aromatic Compounds at Room Temperature... 

Table 2. Yields from the Direct Thallation of Aromatic Compounds with Thallium(III) Tri-fluoroacetate...

Thallation of aromatic compounds with thallium tris(trifluoroacetate) proceeds more readily than mer-curation and in many instances more selectively. Ortho derivatives are obtained frequendy when functional groups with unshared electron pairs are present to direct the metallation.39... 

A very large number of other arylthallium bistrifluoroacetates have been obtained by the direct thallation of aromatic compounds 40, 168,169,170, 203) (see Section VIII, B). 

The colorless, photosensitive, hygroscopic solid, T1(02CCF3)3 is conveniently prepared by heating under reflux a suspension of TI2O3 in trifluoroacetic acid. A solution of this salt in the acid constitutes a powerful reagent for the direct thallation of aromatic compounds [Eq. (11)] (J6S). Such products are usually soluble in most organic solvents... 

Electrophilic mercuration and thallation of aromatic compounds, alkenes and alkynes are considered in Chapter 3. 

Mercuration of aromatic compounds can be accomplished with mercuric salts, most often Hg(OAc)2 ° to give ArHgOAc. This is ordinary electrophilic aromatic substitution and takes place by the arenium ion mechanism (p. 675). ° Aromatic compounds can also be converted to arylthallium bis(trifluoroacetates), ArTl(OOCCF3)2, by treatment with thallium(III) trifluoroacetate in trifluoroace-tic acid. ° These arylthallium compounds can be converted to phenols, aryl iodides or fluorides (12-28), aryl cyanides (12-31), aryl nitro compounds, or aryl esters (12-30). The mechanism of thallation appears to be complex, with electrophilic and electron-transfer mechanisms both taking place. 

A simple, high-yield procedure for the conversion of ArTlXj into ArjTlX compounds has recently been described 90). This symmetrization reaction, the mechanism of which is not known, can be effected by treatment of the ArTlX2 compound either with triethyl phosphite or with hot aqueous acetone. As a wide variety of ArTlXj compounds can now be easily prepared by electrophilic thallation of aromatic substrates with thallium(III) trifluoroacetate (q. v.), symmetrization represents the method of choice for the preparation of the majority of ArjTlX compounds. Only about twenty mixed compounds, RR TIX, have been prepared so far, and the only general synthetic procedure available consists of a disproportionation reaction between an RTIX2 species and another organometallic reagent [e.g., Eqs. (5)-(7)]. 

Mercuration of aromatic compounds comparison with thallation... 

Aromatic thallation has been shown to be a reversible electrophilic substitution reaction with an energy of activation of approximately 27 kcal/mole and an extremely large steric requirement 153). The consequence of the latter feature of aromatic thallation is that there is a significant preference for para substitution in thallation of simple monosubstituted benzeno id compounds. It will be seen by examination of Table VI that the amount of para substitution increases as the size of the substituent increases (for... 

From the point of view of the synthetic organic chemist, the importance of aromatic thallation, and the remarkable degree of orientation control which can be exercised over this process, lies in the ease with which the resulting ArTlXj compounds can be converted into substituted aromatic derivatives in which the new substituent group has entered the ring at the position to which thallium was originally attached. Syntheses of phenols, nitroso compounds, biaryls, aromatic nitriles, thiophenols, and deuterated aromatic compounds have all been achieved these results are summarized briefly below. 

The aryl-thallium bond is thus apparently capable of displacement either by electrophilic or by suitable nucleophilic reagents. Coupled with its propensity for homolytic cleavage (spontaneous in the case of ArTlIj compounds, and otherwise photochemically induced), ArTlXj compounds should be capable of reacting with a wide variety of reagents under a wide variety of conditions. Since the position of initial aromatic thallation can be controlled to a remarkable degree, the above reactions may be only representative of a remarkably versatile route to aromatic substitution reactions in which organothallium compounds play a unique and indispensable role. 

Tl(III) trifluoroacetate, sometimes with the requirement that boron trifluoride etherate should be present, causes fast dehydrodimerization of many aromatic compounds to give biaryls and/or diphenylmethanes in competition with thallation (McKillop et al., 1980). This system thus seems to be a typical exponent of (96). Table 16, entry no. 16, presents a crude estimate of the possibility of non-bonded electron transfer between Tl(III) trifluoroacetate and naphthalene, showing that it indeed appears to be feasible. Note however that both observed and estimated rate constants are based upon rather uncertain... 

The carboxylates of indium and thallium are obtained by dissolving the oxides in acid. Acetate and trifluoroacetate salts are used extensively as reagents in organic synthesis. Certain other thallium compounds have been used also. The trifluoroacetate, T1(02CCF3)3, will directly thallate aromatic compounds to give arylthal-lium species, for example, C6H5T1(02CCF3)2 (cf. aromatic mercuration, Section 15-15) and oxidize arenes to biaryls. 

Thallationr-carbonylaiion of aromatics. ort/io-Thallation of benzoic acids, ben-zylic and (3-phenethyl alcohols, and benzamides followed by Pd(ID-catalyzed carbonyl-ation provides a route to aromatic carbonyl compounds such as phthalides, anhydrides, and imides. 

Although thallium(III) acetate fails to react with aromatic compounds under mild conditions, thallium (III) trifluoroacetate will effect rapid electrophilic thallation of a wide range of aromatic substances (40, 168, 169, 170, 203) according to the general reaction [Eq. (11)]. These reactions are very rapid and are usually completed in a few minutes at room temperature for activated aromatic nuclei, to give stable colorless solids that generally crystallize from solution. The orientation of thallation in such reactions may be influenced by temperature [Eq. (13)], or by the substituents on the aromatic nucleus. 

Now, these arylthallium compounds are useful, not in themselves, but as intermediates in the synthesis of a variety of other aromatic compounds. Thallium can be replaced by other atoms or groups which cannot themselves be introduced directly into the aromatic ring - or at least not with the same regiospecificity. In this way one can prepare phenols (ArOH, Sec. 24.5) and aryl iodides (Sec. 25.3). Direct iodination of most aromatic rings does not work very well, but the process of thallation followed by treatment with iodide ion gives aryl iodides in high yields. 

Aromatic iodides (3,287). The definitive paper on the synthesis of aromatic iodides by the reaction of arylthallium ditrifluoroacetates with potassium iodide has been published.1 Four procedures have been developed. 1) Thallation is carried out as usual and then an aqueous solution of potassium iodide is added directly. 2) The intermediate arylthallium ditrifluoroacetate is isolated and then treated with potassium iodide. 3) For acid-sensitive substrates solid TTFA in acetonitrile is used for thallation. 4) These methods are unsuccessful with highly reactive compounds such as naphthalene and diphenyl. In such cases molecular iodine is used as the electrophilic reagent and TTFA is used as oxidant for the hydrogen iodide formed in the reaction. 

Thallinm(ni) °, particnlarly as its triflnoroacetate salt , has been successfully used for the synthesis of phenols. This method can be carried out in a single step and is subject to isomer orientation control" . The aromatic compound to be hydroxylated is first thallated with thallium trifluoroacetate (TTFA)" and, by treatment with lead tetraacetate followed by triphenylphosphine and then dilute NaOH, it is converted to the corresponding phenol (equation 57). Table 1 shows some examples of these transformations . ... 

Reaction of electron-rich aromatic compounds with TTFA leads to intermolecular oxidative coupling to form the corresponding biaryls without aromatic thallation. The reaction proceeds through one-electron transfer from aromatic compounds to Tl(III) to give an aromatic radical cation which leads to biaryls (Schemes 9.52 and 9.53 [52]). Intramolecular aryl coupling also occurs (Schemes 9.54 [53] and 9.55 [54]) and, further, when the carboxylic acid moiety is present, intramolecular as well as intermolecular lactonization occurs (Schemes 9.56 [55] and 9.57 [56]). 

Thallium carboxylates, particularly the acetate and trifluoroacetate, which can be obtained by dissolution of the oxide in the acid, are extensively used in organic chemistry.14 Both Tl metal and Tl1 salts such as the acetylaceton-ate also have specific uses. One example is the use of thallium(m) acetate in controlled bromination of organic substances such as anisole. The trifluoroacetate will directly thallate (cf. aromatic mercuration, Section 18-9) aromatic compounds to give aryl thallium ditrifluoroacetates, e.g., C6H5Tl(OOCCF3)2. It also acts as an oxidant, inter alia converting para-substituted phenols into p-quinones. 

Consider thallation, an electrophilic substitution of an aromatic compound by a trivalent thallium compound, depicted below for benzene and T1(02CCF3)3 ... 

Thallium compounds are very poisonous, and must be handled with extreme care. Although substituent groups affect the reactivity of the aromatic substrate as expected for electrophilic substitution, orientation is unusual in a number of ways, and it is here that much of the usefulness of thallation lies. Thallation is almost exclusively para to —R, -Cl, and OCH3, and this is attributed to the bulk of the electrophile, thallium trifluoroacetate, which seeks out the uncrowded para position. 

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