Aromatic substitution reactions, role

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. 

This rather discouraging picture arose mainly because of an overconcentration on homolytic aromatic arylation, the results of which had a distorting influence on the development of homolytic aromatic substitution reactions generally. It was recently realized that polar factors play a more important role in some homolytic aromatic substitutions than foreseeable on the basis of a transition state similar to the cr-complex... 

Fig. 5.55. Mechanistic aspects III of nucleophilic aromatic substitution reactions of aryldiazonium salts via radicals introduction of Nu = I through reaction of aryldiazonium salts with KI. In this (chain) reaction the radical I2 —apart from its role as chain-carrying radical—plays the important role of initiating radical. The scheme shows how this radical is regenerated the initial reaction by which it presumably forms remains to be provided, namely (1) Ar-N =N + I -> Ar- N=N + h ...

Fig. 5.45. Mechanism of the nucleophilic aromatic substitution reaction of Figure 5.44. The radical I2 plays the role of the chain-carrying radical and also the important role of the initiating radical in this chain reaction. The scheme shows how this radical is regenerated. It remains to be added how it is presumably formed initially (1) Ar—N+=N + I- ->...

For example, acetylation reactions of alcohols and carbohydrates have been performed in [Bmim]-derived ionic liquids.If the dicyanamide anion [N(CN)2] is incorporated into the liquid, mild acetylations of carbohydrates can be performed at room temperature, in good yields, without any added catalyst.In this example, it was shown that the RTIL was not only an effective solvent but also an active base catalyst. In a recent study, Welton and co-workers performed calculations on the gas phase basicity of the conjugate acids of possible anions from which to construct their liquid.Using these data, they were able to choose the optimum RTIL in which to conduct a nucleophilic aromatic substitution reaction of an activated aniline with an activated arylhalide. Given the enormous number of possible anions and cations from which to build up an ionic liquid, the role of computation in experimental design such as this will become increasingly important. 

There is, for example, no end-of-text chapter entitled Heterocyclic Compounds. Rather, heteroatoms are defined in Chapter 1 and nonaromatic heterocyclic compounds introduced in Chapter 3 heterocyclic aromatic compounds are included in Chapter 11, and their electrophilic and nucleophilic aromatic substitution reactions described in Chapters 12 and 23, respectively. Heterocyclic compounds appear in numerous ways throughout the text and the biological role of two classes of them—the purines and pyrimidines—features prominently in the discussion of nucleic acids in Chapter 27. 

Since their discovery during the 1860s, electrophilic aromatic substitution reactions played the dominant role for functionalizations of arenes, and were often the method of choice for the synthesis of substituted arenes. For example, Hermann Kolbe, a student of Friedrich Wohler, devised a synthesis for salicylic acid (7) [13, 14], which set the stage for the industrial preparation of acetylsalicylic acid (ASA, aspirin) (1) by Arthur Eichengriin and Felix Hoffmann at Bayer in 1897 (Scheme 1.2). 

Issues of regioselectivity in the Blanc chloromethylation and related Friedel-Crafts reactions have been studied extensively. As is common with a majority of electrophilic aromatic substitution reactions, substitution typically occurs ortho or para to electron-donating substituents, with issues of steric strain playing a role in the relative ratio of ortho and para products. The Blanc reaction is t3q)ically somewhat regioselective, favoring the para-isomer but accompanied by lesser amounts of the ortho product. ... 

N. Cheron, L. El Kaim, L. Grimaud, P. Fleurat-Lessard, Chem.-Eur. J. 2011, 17,14929-14934. Evidences for the key role of hydrogen bond in nucleophihc aromatic substitution reactions. 

The catalyst functions exactly as expected (compare the role of AICI3 here to the role that it plays in Section 19.2). The result here is the formation of a carbocation, which is an excellent electrophile and is capable of reacting with benzene in an electrophilic aromatic substitution reaction (Mechanism 19.6). 

An interesting method for the substitution of a hydrogen atom in rr-electron deficient heterocycles was reported some years ago, in the possibility of homolytic aromatic displacement (74AHC(16)123). The nucleophilic character of radicals and the important role of polar factors in this type of substitution are the essentials for a successful reaction with six-membered nitrogen heterocycles in general. No paper has yet been published describing homolytic substitution reactions of pteridines with nucleophilic radicals such as alkyl, carbamoyl, a-oxyalkyl and a-A-alkyl radicals or with amino radical cations. 

Hence the positional selectivity is different from that of the furan additions to 417 (Scheme 6.90). Assuming diradical intermediates for these reactions [9], the different types of products are not caused by the nature of the allene double bonds of 417 and 450 but by the properties of the allyl radical subunits in the six-membered rings of the intermediates. Also N-tert-butoxycarbonylpyrrole intercepted 450 in a [4 + 2]-cycloaddition and brought about 455 in 29% yield. Pyrrole itself and N-methylpyr-role furnished their substituted derivatives of type 456 in 69 and 79% yield [155, 171b]. Possibly, these processes are electrophilic aromatic substitutions with 450 acting as electrophile, as has been suggested for the conversion of 417 into 442 by pyrrole (Scheme 6.90). 

In the above examples, the nucleophilic role of the metal complex only comes after the formation of a suitable complex as a consequence of the electron-withdrawing effect of the metal. Perhaps the most impressive series of examples of nucleophilic behaviour of complexes is demonstrated by the p-diketone metal complexes. Such complexes undergo many reactions typical of the electrophilic substitution reactions of aromatic compounds. As a result of the lability of these complexes towards acids, care is required when selecting reaction conditions. Despite this restriction, a wide variety of reactions has been shown to occur with numerous p-diketone complexes, especially of chromium(III), cobalt(III) and rhodium(III), but also in certain cases with complexes of beryllium(II), copper(II), iron(III), aluminum(III) and europium(III). Most work has been carried out by Collman and his coworkers and the results have been reviewed.4-29 A brief summary of results is relevant here and the essential reaction is shown in equation (13). It has been clearly demonstrated that reaction does not involve any dissociation, by bromination of the chromium(III) complex in the presence of radioactive acetylacetone. Furthermore, reactions of optically active... 

In the preceding reactions, the arylation was regioselective with an outcome similar to electrophilic aromatic substitution. However, with simple benzene derivatives, mixtures of biaryl derivatives have been obtained (Scheme 10.53).85 The role of silver trifluoroacetate in these arylations was crucial and, as proposed by the authors, this silver salt could enhance the reactivity and reoxidize Pd species. 

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