Nucleophilic aromatic substitution reaction characteristics

Displacements such as this show all the usual characteristics of electrophilic aromatic substitution (substituent effects, etc., see below), but they are normally of much less preparative significance than the examples we have already considered. In face of all the foregoing discussion of polar intermediates it is pertinent to point out that homolytic aromatic substitution reactions, i.e. by radicals, are also known (p. 331) as too is attack by nucleophiles (p. 167). 

We take up the aryl halides in a separate chapter because they differ so much from the alkyl halides in their preparation and properties. Aryl halides as a class are comparatively unreactive toward the nucleophilic substitution reactions so characteristic of the alkyl halides. The presence of certain other groups on the aromatic ring, however, greatly increases the reactivity of aryl halides in the absence of such groups, reaction can still be brought about by very basic reagents or high temperatures. We shall find that nucleophilic aromatic substitution can follow two very different paths the bimolecular displacement mechanism for activated aryl halides and the elimination-addition mechanismy which involves the remarkable intermediate called benzyne. 

Scheme 36, A and Turnover numbers up to approximately 500,000 were reported for the reaction of iodobenzene with methyl acrylate and an impressive nnmber (about 100,000) was also achieved with bromobenzene and 4-methoxy-bromobenzene. Characteristic featnres of these tridentate PCP catalysts are thermal stability and air stability. A competitive experiment, including 4-bromoiodobenzene, iodobenzene, 4-methyliodoben-zene, and 4-methoxy-iodobenzene with methyl acrylate provided a linear correlation with Hammet cr-valnes, which, however, exhibited a low p valne (1.39). It was concluded that nucleophilic aromatic substitution is not rate determining, bnt a snbsequent step with different electronic requirements, such as alkene insertion, may acconnt for this observation. Chlorobenzene could not be coupled with these catalyst. Very recently, Milstein s group reported new cyclopalladated, phosphine-free imine complexes as catalysts in the Heck arylation reaction (Scheme 36, The new dimeric imine complexes show... 

The high performance characteristics of polyetherimide polymers and our desire to prepare them by an economically attractive scheme led us to explore several synthetic approaches. The key reaction in all of these was the formation of the diaryl ether linkage by a nucleophilic aromatic displacement reaction on suitably substituted (and activated) phthalic derivatives. Chloride displacement proceeded relatively slowly and gave polymers having only modestly high molecular weights. Fluoride displacement was quite facile, but processes based on the fluoro-deriviatives were economically unattractive. The synthetic and economic accessibility of appropriate nitro-substituted phthalic... 

The effects of the nucleophile on aromatic substitution which are pertinent to our main theme of relative reactivity of azine rings and of ring-positions are brought together here. The influence of a nucleophile on relative positional reactivity can arise from its characteristics alone or from its interaction with the ring or with ring-substituents. The effect of different nucleophiles on the rates of reaction of a single substrate has been discussed in terms of polarizability, basicity, alpha effect (lone-pair on the atom adjacent to the nucleophilic atom), and solvation in several reviews and papers. ... 

The special substituent constants for + R para-substituents are denoted by a, and those for — R para-substituents are denoted by a+ 54. They are based respectively on the reaction series discussed above. Selected values are given in Table 1. Characteristic a or a+ values are sometimes distinguished for meta-substituents also, but only for a minority of substituents which show very marked + R or — R effects do these differ significantly from ordinary a values. The range of applicability of the Hammett equation is greatly extended by means of a and cr+, notably to nucleophilic (by a ) and to electrophilic (by cr+) aromatic substitution. 

Photoexcited aromatic compounds undergo substitution reactions with (non-excited) nucleophiles. The rules governing these reactions are characteristically different and often opposite to those prevailing in aromatic ground state chemistry 501a,b>, in contrast to the well known ortho/para activation in thermal aromatic substitutions, nitro groups activate the meta position in the photochemical substitution, as shown in (5.1) 502). 

The arene oxide valence tautomer of oxepins in principle should undergo nucleophilic substitution reactions (Sn2) which are characteristic of simple epoxides. In reality oxepin-benzene oxide (7) is resistant to attack by hard nucleophiles such as OH-, H20, NH2- and RNH2. Attempts to obtain quantitative data on the relative rates of attack of nucleophiles on (7) in aqueous solution hqye been thwarted by competition from the dominant aromatization reaction. 

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