Regioselectivity ortho/para

Why IS there such a marked difference between methyl and trifluoromethyl substituents m their influence on electrophilic aromatic substitution s Methyl is activating and ortho para directing trifluoromethyl is deactivating and meta directing The first point to remember is that the regioselectivity of substitution is set once the cyclohexadienyl cation intermediate is formed If we can explain why... 

The ortho-para rule is explained by FMO theory on the basis of the orbital coefficients of the atoms forming the cr-bonds. The regiochemistry is determined by the overlap of the orbitals that have larger coefficients (larger lobes in Scheme 1.15). The greater the difference between the orbital coefficients of the two end atoms of diene and two atoms of dienophile, which form the two cr-bonds, the more regioselective the cycloaddition. 

Lewis-acid-catalyzed cycloadditions of dienophiles, such as a,/l-unsaturated carbonyl compounds, with open-chain carbon-dienes, are generally highly ortho-para regioselective because the oxygen complexation increases the difference of LUMO coefficients of the alkene moiety. 

HPA amount/g Regioselectivity ortho/% meta/% para/% para/ortho Total yield of mononitrotoluene/%... 

All the substituents in 2,6-dibromoanisole are ortho, para-directing, and their effects are felt at different positions. The methoxy group, however, is a far more powerful activating substituent than bromine, so it controls the regioselectivity of nitration. 

Regioselectivity para > ortho para > ortho metd)... 

An example from a recent report on arylations with aryl and heteroaryl radicals is depicted in Scheme 38. Within this series of experiments, in which the substrate was used as solvent, remarkable regioselectivities were observed for some examples. The arylation of chlorobenzene with a 2-pyridinyl radical derived from bromide 103 gave a ratio of ortho para arylation products 104 and 105 of 13 1 [156, 157]. 

The regioselectivity in certain aromatic chlorinations by hypochlorite is also pH-depen-dent. The ortho/para ratio in phenol chlorination increased from 0.64 at pH = 4 to 4.3 at pH = 10794. Selective 4-chlorination of phthalic acid is obtained in aqueous sodium hypochlorite solution795. Iodination of phenols in aqueous systems is also pH-dependent and the ortho iodophenol yield grows at stronger basic media796,797. 

The two exceptions to the ortho-para rule are the reactions between an X-substituted diene and an X-substituted dienophile. The frontier orbitals in Fig. 6.27, taken from Fig. 6.22, indicate that the preferred combination, whichever pair of frontier orbitals and whichever diene, 1-substituted or 2-substituted, is taken, will lead to the meta adduct. Neither frontier orbital interaction is between orbitals close in energy (> 11 eV in all combinations), with the result that the reaction can be expected to be very slow, and is in practice exceedingly rare. One example is the combination of the (vinylogous) 2-X-substituted diene 6.158, derived from the benzcyclobutene by electrocyclic ring-opening, and ethyl vinyl ether 6.159. Although not usefully regioselective, the reaction does take place, assisted by the aromatisation of the diene, and the meta adduct is the major product. 

In fact, because most Diels-Alder reactions proceed by the reaction of nucleophilic dienes with electrophilic dienophiles, the following rule can be formulated as follows Diels-Alder reactions proceed to put the most electron donating substituent on the diene and the most electron withdrawing substituent on the dienophile either ortho or para to one another. This ortho-para rule misuses the terms ortho and para, which really apply only to benzene rings, but it allows one to remember the regioselectivity of these reactions fairly easily. 

V(Ce, X) populations are close to their values in the corresponding halobenzene however, there is a small electron transfer towards this basin for X = F, whereas the iodine atom undergoes an opposite effect. With respect to phenol, the regioselectivity of the electrophilic substitution is softened because as the OH and X = F, Cl, Br groups are both ortho-para directors, they contribute in opposite directions. As all the positional indices of CeHsI are positive, they are enhanced in the trans orf/io-iodophenol. The additive rule works satisfactorily for all positions as the largest discrepancy between estimated and calculated value does not exceed 0.002. 

Due to the industrial importance of the 2-nitrophenol, extensive research has been focused on enhancing the regioselectivity of the nitration of phenol . The regiochemistry of the nitration is dramatically increased, giving an ortho/para ratio of 13.3 with acetyl nitrate as the reagent, when dry sUica gel was used for the catalysis. In chloroform solvent, in the absence of silica gel, a normal ortho/para ratio of 1.8 was obtained . 

Phenols are monochlorinated regioselectively nsing sulfuryl chloride and amines (snch as di-iec-bntylamine) as the catalysts in nonpolar solvents (eqnation 82). In a typical experiment an ortho/para ratio of 22 was obtained with yields of abont 90% . 

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