Ortho-para rule

Exceptions to the ortho para rule have been observed, so the prediction of the regiochemistry is still a stimulating challenge. 

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. 

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. 

Sometimes, the ortho-para rule doesn t work well, especially when two substituents on the diene have competing directing abilities. For example, a PhS substituent at Cldiene s more strongly directing than a MeO substituent at C2diene-By resonance arguments, the opposite should be the case, as MeO is a better resonance donor than PhS. 

There are 18 possible combinations of C-, Z- and X-substituted dienes and C-, Z- and X-substituted dienophiles. The ortho adduct is predicted (and found) to be the major product for eight of the nine possible combinations with 1-substituted dienes, and the para adduct predicted (and found) for eight of the nine possible combinations of 2-substituted dienes. The reactions of Z-substituted dienophiles with the 1-X-substituted diene 6.194 (see p. 303) and with the 1-Z-substituted diene 6.208 (see p. 304) illustrate two of these combinations, and here are examples of most of the rest which obey the ortho-para rule. 

The two exceptions to the ortho-para rule are the reactions between an X-substituted diene, with the X-substituent at C-l or C-2, and an X-substituted dienophile. The frontier orbitals in Fig. 6.32, taken from Fig. 6.25, 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. 

Experimental results and theoretical analyses have enabled rational predictions for the regiochemical preferences in Diels-Alder reactions. Known as the ortho, para rule, the strongest electron donating group on the diene ends up either ortho (1,2) or para (1,4) to the strongest electron-withdrawing group on the dienophile in the final cyclohexene product. For example, combination of isoprene (7) with methyl acrylate (8) yields mostly para product 9, while reaction of 8 with 1-methylbutadiene 11 furnishes ortho cyclohexene 12 as the major product. As shown in these cases, formation of mixtures is common under thermal conditions. ... 

The entrance of a third or fourth substituent can be predicted by Beilstein s rule. If a substituent Z- enters into a compound C H XY, both X and Y exert an influence, but the group with the predominant influence directs Z- to the position it will occupy. Since all meta-directing groups are deactivating, it follows that ortho—para activating groups predominate when one of them is present on the benzene ring. 

The ortho/para orientation rule of ground state chemistry appears to be followed in the photosubstitution reactions of nitrobenzene derivatives in liquid ammoniaa40) ... 

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). 

One may formulate in general terms a complementarity of rules for thermal and photochemical processes. However, such a generalization could possibly predict ortho-para orientation but not activation. First of all, careful experimental testing of the hypothesis seems required. We present a selection of very recent results. ... 

The regiochemistry is important. For example, does the reaction follow Markovnikov s rule or is the reaction anti-Markovnikov Or is the substituent a meta-director or ortho-para-director You learned rules such as this for a reason make sure you continually apply them. 

In all discussions of the application of the rule we make reference to the principal products of the reaction substitution occurs for the most part in accordance with the rule, or with the exceptions, and small amounts of other materials arc usually formed as by-products. In the mononitration of toluene, for example, about 96 per cent of the product is a mixture of o- and p-nitro-toluene, and about 4 per cent is the m-compound. Under the influence of ortho-para orienting groups, substitution occurs in the two positions without much preference for either one, but it appears to be the case that, when nitro groups are introduced, low temperatures favor the formation of p-coinpounds. The effect... 

The halobenzenes are exceptions to the general rules. Halogens are deactivating groups, yet they are ortho, para-directors. We can explain this unusual combination of properties by considering that... 

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