Substitution, electrophilic ortho-para ratio

It has been noted that the ortho para ratio for protodetritiation of p-[ H] toluene varies with acid medium, and although side reactions are present with both sulphuric acid and Lewis acids, they are usually absent in trifluoroacetic acid. See (a) Taylor, R. Electrophilic Aromatic Substitution. J. Wiley and Sons, New York, 1990, pp. 61-64 (b) Baker, R. Eabcm C. Taylor, R. J. Chem. Soc. 1961,4927. 

Silicon group introduction by DoM also provides opportunity for design of E+-induced ipsodesilylation and sterically determined reactions. In the former, the operation of a /3-cation effect induces rate enhancements in ipso-substitu-tion in systems which are unreactive (EWG) or para-reactive (EDG) toward typical electrophilic reagents (24). The presence of strong EDG overrides the /3-cation effect but the bulk of the silane increases the ortho/para ratio which enables development of substitution patterns and types which are not easily derived by classical electrophilic reaction means (25) [23],... 

Ortho/para ratio The ratio of electrophilic substitution at the ortho, as opposed to the para, position of a monosubstituted aromatic ring. 

We cannot, then, expect this approach to understanding chemical reactivity to explain everything. We should bear in mind its limitations, particularly when dealing with subjects like ortho/para ratios in aromatic electrophilic substitution, where steric effects are well known to be important. Likewise solvent effects (which usually make themselves felt in the entropy of activation term) are also well known to be part of the explanation of the principal of hard and soft acids and bases. Some mention of all these factors will be made again in the course of this book. Arguments based on the interaction of frontier orbitals are powerful, as we shall see, but they must not be taken so far that we forget these very important limitations. 

For the unsubstituted pyridinium cation, reaction at the 2- and at the 4-position is predicted according to the theory. Indeed, reaction of protonated pyridine with the tcrt-butyl radical at low conversions (<30%) afforded selectively the ortho- and para-substituted derivatives without any alkylation at the meta position [16], It turned out that the ortho-para ratio is highly solvent dependent. If the reaction is conducted in H2O, the para product is formed as the major compound (see 10, ortho. para — 23 77). The same reaction in benzene afforded mainly the ortho compound [ortho-.para = 11 29). The reversal of the selectivity can be explained by assuming a reversible initial radical addition, especially if the reaction is conducted in H2O [16]. Similar results were obtained for the reaction with the tetrahydrofuryl radical [16]. The alkylations are generally stopped at low conversions. Since the alkylated pyridinium cations are only slightly less electrophilic than the starting pyridinium cations, overalkylation competes at higher conversion. For example, ethylation of the pyridinium cation at 100% conversion afforded a mixture of mono-, double- and tri-ethylated pyridinium salts (—> 11a e) [17]. 

Exactly how the stabilized aromatic cation radical is converted into the nuclear chlorinated product, is not at present fully understood. As represented in eqn (135), nucleophilic substitution could arise from initial capture of the aromatic cation radical by chloride ion involving appropriate substituted cyclohexadienyl-type radicals ( ArHCl), in which case the substitution pattern (at least the ortho/para ratio of products) might be expected to resemble more those from typical homolytic aromatic substitution processes rather than those from electrophilic substitutions, as observed experimentally. At present, there is a scarcity of significant mechanistic information relating to nucleophilic capture of aromatic cation radicals, although in every reported case [vide infra) the position of substitution corresponds with that arising from comparable electrophilic processes. 

The literature on basic- and acid-catalyzed alkylation of phenol and of its derivatives is wide [1,2], since this class of reactions finds industrial application for the synthesis of several intermediates 2-methylphenol as a monomer for the synthesis of epoxy cresol novolac resin 2,5-dimethylphenol as an intermediate for the synthesis of antiseptics, dyes and antioxidants 2,6-dimethylphenol used for the manufacture of polyphenylenoxide resins, and 2,3,6-trimethylphenol as a starting material for the synthesis of vitamin E. The nature of the products obtained in phenol methylation is affected by the surface characteristics of the catalyst, since catalysts having acid features address the electrophilic substitution in the ortho and para positions with respect to the hydroxy group (steric effects in confined environments may however affect the ortho/para-C-alkylation ratio), while with basic catalysts the ortho positions become the... 

Nevertheless, the liquid-phase methylation displays the typical features of the aromatic substitution by an extremely reactive, unselective electrophile such as CTs", which, however, appears capable of discriminating between the aromatic substrates ( T/fca 2), and gives a predominantly ortho/para orientation, characterized by a para Vi meta ratio of 2.5 in the formation of the xylenes. 

A homobimetallic rhodium catalyst derived from a P,N-ligand was found to allow for intermolecular direct arylations of unfunctionalized arenes [24]. Interestingly, aryl iodides, bromides-and even chlorides-could be employed as electrophiles, and a variety of valuable functional groups was tolerated by the catalytic system (Scheme 9.12). The C—H bond functionalization of toluene yielded ortho-, meta- and para-substituted regioisomers in a ratio of 71 19 10. Based on this observation and a Hammett correlation, a mechanism proceeding through radical intermediates was suggested. 

Electrophilic Aromatic Substitution. Micellar SDS has been used as a reaction medium for the chlorination and bromlnatlon of alkyl phenyl ethers T gjj(j phenol by several halogenatlng agents (eq 1). Compared to reactions in H2O alone, theparar.ortho product ratio increased for pentyl, nonyl, and dodecyl phenyl ether, and decreased for anlsole. Enhanced ortho relative to para substitution was obtained with phenol. In each case the observed regios-electivity derived at least in part from alignment of the substrate at the micelle-H20 interface and resultant differential steiic shielding of the para and ortho positions by the micelle superstructure. 

Chlorination of benzene is an electrophilic substitution reaction in which CL serves as the electrophile. The reaction occurs in the presence of a Lewis acid catalyst such as FeCls. The products are a mixture of mono- and dichlorobenzenes. The ortho- and the para-dichlorobenzenes are more common than meta-dichlorobenzene. The ratio of the mono-chloro to dichloro products essentially depends on the benzene/chlorine ratio and the residence time. The ratio of the dichloro-isomers (0- to p- to m-dichlorobenzenes) mainly depends on the reaction temperature and residence time ... 

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