Electrophilic aromatic substitution para-addition

The effect of monofluorination on alkene or aromatic reactivity toward electrophiles is more difficult to predict Although a-fluonne stabilizes a carbocation relative to hydrogen, its opposing inductive effect makes olefins and aromatics more electron deficient. Fluorine therefore is activating only for electrophilic reactions with very late transition states where its resonance stabilization is maximized The faster rate of addition of trifluoroacetic acid and sulfuric acid to 2-fluoropropene vs propene is an example [775,116], but cases of such enhanced fluoroalkene reactivity in solution are quite rare [127] By contrast, there are many examples where the ortho-para-dueeting fluorine substituent is also activating in electrophilic aromatic substitutions [128]... 

Two of three nitrofluorobenzene isomers react with methoxide, but the third is unreactive. Obtain energies of methoxide anion (at left), ortho, meta and para-nitrofluorobenzene, and the corresponding ortho, meta and para-methoxide anion adducts (so-called Meisenheimer complexes). Calculate the energy of methoxide addition to each of the three substrates. Which substrate is probably unreactive What is the apparent directing effect of a nitro group Does a nitro group have the same effect on nucleophilic aromatic substitution that it has on electrophilic aromatic substitution (see Chapter 13, Problem 4) Examine the structures and electrostatic potential maps of the Meisenheimer complexes. Use resonance arguments to rationalize what you observe. 

Polymers such as polyetherketones and polyethersulfones can be prepared by electrophilic aromatic substitution using aromatic acid chlorides and aromatic sulfonyl chlorides, respectively [Eq. (25)]. However, due to ortho-substitution in addition to the desired para-substitution, it is difficult for these Friedel-Crafts acylations to compete with nucleophilic aromatic substitution of activated aromatic halides which are usually used for their synthesis. 

TriCTAs and TeCTAs were prepared by stepwise addition of sulfuryl chloride over 4 h at 60°C. The degree of chlorination was found to be three to four (only tri- and tetrachlorinated thianthrenes were observed as reaction products) when all of the parent compound was consumed. One TriCTA and one TeCTA were obtained as main products. In addition, two other TriCTAs, four TeCTAs, and some PeCTAs were observed in minor concentrations. Because of the ortho- and para-directing properties of sulfur in electrophilic aromatic substitution reactions, 237-TriCTA and 2378-TeCTA, the thio analogue of 2378-TeCDD, were obtained as the main products. Mass spectrometry and H NMR were used in the structure verification. 

At the low-temperature (0°) addition, rate-control is being observed. The o- and p-xylenes are formed faster. At the high-temperature (80°) addition, equilibrium-control is shown m-xylene is the most stable product. The methyl group of toluene activates the ring for electrophilic aromatic substitution and directs substituents to the ortho and para positions. Just as the methyl group favors alkylation at the ortho and para positions, it also favors dealkylation - via electrophilic attack by a proton - at these same positions. This means that while the ortho and para isomers are formed more rapidly, they are also dealkylated more rapidly as shown ... 

Functionalized benzenes preferentially induced ortho-para substitution with electron-donating groups and meta substitution with electron-withdrawing groups (see above). Additionally, the order of reactivity found with aromatics was similar to that of electrophilic aromatic substitution. These observations implicated an electrophihc metalation of the arene as the key step. Hence, Fujiwara et al. [4b] believed that a solvated arylpalladium species is formed from a homogeneous solution of an arene and a palladium(ll) salt in a polar solvent via an electrophilic aromatic substitution reaction (Figure 9.2). The alkene then coordinates to the unstable arylpalladium species, followed by an insertion into the aryl-palladium bond. The arylethyl-palladium intermediate then rapidly undergoes )8-hydride elimination to form the alkenylated arene and a palladium hydride species, which then presumably decomposes into an acid and free palladium metal. Later on, the formation of the arylpalladium species proposed in this mechanism was confirmed by the isolation of diphenyltripalladium(ll) complexes obtained by the C-H activation reaction of benzene with palladium acetate dialkylsulfide systems [19]. 

The fluorination of other activated aromatic compounds, such as anisole and phenol, undergo monofluorination mainly in the ortho and para positions, whereas the fluorination of deactivated aromatics, such as nitrobenzene, trifluoromethylbenzene and benzoic acid, give predominantly the corresponding meta fluoro-derivatives which is consistent with a typical electrophilic substitution process. Also, fluoro-, chloro- and bromo-benzenes are deactivated with respect to benzene itself but are fluorinated preferentially in the ortho and para positions [139]. At higher temperatures, polychlorobenzenes undergo substitution and addition of fluorine to give chlorofluorocyclohexanes [136]. 

Pyrones, which are the ring-oxygen equivalents of pyridones, are simply a- and y-hydroxy-pyrylium salts from which an 0-proton has been removed. There is little to recommend that 2- and 4-pyrones be viewed as aromatic they are perhaps best seen as cyclic unsaturated lactones and cyclic p-oxy-a,P-unsaturated-ketones, respectively, for example 2-pyrones are hydrolysed by alkali, just like simpler esters (lactones). It is instructive that, whereas the pyrones are converted into pyridones by reaction with amines or ammonia, the reverse is not the case - pyridones are not transformed into pyrones by water or hydroxide. Some electrophilic C-substitutions are known for pyrones and benzopyrenes, the oxygen guiding the electrophile ortho or para, however there is a tendency for electrophihe addition to the C-C double bond of the heterocyclic ring, again reflecting their non-aromatic nature. Easy Diels-Alder additions to 2-pyrones are further evidence for diene, rather than aromatic, character. 

An interesting case of a cathodic substitution is the EuCh-mediated reduction of oxygen that reacts with aliphatic CH bonds. The selectivity of 1-H 2-H 3-H being 1 6 19 was attributed to a radical intermediate, while in the aromatic substitution the preferred ortho- and para-substitution points to an electrophilic oxygen species [96]. In the FeCls-mediated oxygenation of n-hexane in a fuel cell, the addition of a- and /3-cyclodextrins improved the selectivity toward oxygenation of the terminal CHs-groups due to inclusion of the -hexane in the cyclodextrin cavity [97]. 

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