Para production

Substituting T = 298 K and the gas constant gives a ratio of about 81. Thus, we expect there will be 80 times as much para product as ortho product, assuming that the kinetic product is obtained. 

Table 10.9, the amount of ortho product is often comparable to the amount of para product. 

Electrophilic nitration of a substituted benzene may lead to ortho, meta or para products, depending on the substituent. According to the Hammond Postulate, the kinetic product will be that which follows from the most stable intermediate benzenium ion, i.e. 

The substitution reaction of toluene with Br2 can, in principle, lead to the formation of three isomeric bromotoluene products. In practice, however, only o- and jp-bromotoluene are formed in substantial amounts. The meta isomer is not formed. Draw the structures of the three possible carbocation intermediates (Problem 15.48), and explain why ortho and para products predominate over meta. 

Next ask yourself, "What is an immediate precursor of p-bromotoluene " Perhaps toluene is an immediate precursor because the methyl group would direct bromination to the ortho and para positions. Alternatively, bromobenzene might be an immediate precursor because we could carry out a Friedel-Cralts methylation and obtain a mixture of ortho and para products. Both answers are satisfactory, although both would also lead unavoidably to a product mixture that would have to be separated. 

Experiments with 14C-labelled substrates also demonstrated conclusively the intramolecularity of the rearrangement. The generally accepted scheme involves the formation of the dienone LXXXV which can lose a hydrogen atom if R = H, to form the ortho product or if R H further rearrangement to LXXXVI occurs with subsequent formation of the para product, viz. 

Early kinetic work127 showed that the formation of both ortho and para products was a first-order process and that the rates of reaction were insensitive to added acid or base and to change of solvent. The activation parameters were of the same order of magnitude for both reactions and the suggestion was made that both had a similar rate-determining step. Schmid et a/.128 showed that the formation of a dienone intermediate in the para rearrangement was also reversible since the radioactivity from allyl 2,6-dimethyl-4-allyl-y-14C phenyl ether LXXXVII became uniformly distributed in the y carbon atoms of the O- and C-allyl groups... 

Simultaneous inter- and intramolecular reaction have been suggested on the basis153 of the varying yields of the ortho and para isomers and also of the acetyl-ated product of added diphenyl ether as the dilution was changed 5-fold in the reaction of meta-tolyl acetate in the presence of diphenyl ether. In particular it was noted that as the dilution increased the amounts of acetylated diphenyl ether and the para product both decreased whilst that of the ortho product rose very slightly. 

This result together with the preferred formation of para-products suggests that the attacking species is electrophilic and that consecutively are involved formation of a charge transfer complex, addition of Br" ", and elimination of H" ". This picture is supported by Raman studies (ref. 24) of the system Br2-benzene-NaX. 

When the ortho-para directing group is one with an unshared pair (this of course applies to most of them), there is another effect that increases the amount of para product at the expense of the ortho. A comparison of the intermediates involved (p. 683) shows that C is a canonical form with an ortho-quinoid structure, while D has a para-quinoid structure. Since we know that para-quinones are more stable than the ortho isomers, it seems reasonable to assume that D is more stable than C, and therefore contributes more to the hybrid and increases its stability compared to the ortho intermediate. 

The mechanism as we have pictured it can lead only to an ortho product. However, a small amount of para product has been obtained in some cases. A mechanism in which there is a dissociation of the ArC—N bond (similar to the ion-pair mechanism of the Stevens rearrangement, p. 1419) has been invoked to explain the para products that are observed. 

Although mixtures are often obtained, usually one predominates, the one indicated above. This regioselectivity, in which the ortho or para product is favored over... 

The problem with this synthesis is that essentially only para product (2) is formed in the initial Fricdel-Crafts reaction. A solution is to block the para position with a chlorine atom which can be removed by hydrogenolysis. This tetralone (1) is now a commercial product. 

For example, in the case of aromatic substitution reactions the RME for production of para product is given by... 

Nucleophilic substitution of thiophene can also be enabled by the presence of electron withdrawing groups (e.g., -CHO <00SC1359>, -COMe <00T7573>, -NO2 <00JCS(P1)1811>) on carbon. The regioselectivity of the addition of amine nucleophiles onto 3,5-dibromothiophene-2-carboxaldehyde (54) has been studied and found to be independent of reaction conditions (para product 55 favored over ortho product 56) <00SL459>. 

A question of regioselectivity arises when both the diene and alkene are unsymmetrically substituted and two different orientations are possible. Thus a 1-substituted diene with a mono substituted dienophile may form an ortho and a meta adduct. The same dienophile with a 2-substituted diene can yield a meta and a para product. Actually it has been observed that 1 sustituted dienes preferentially form ortho adducts whereas with 2-substituted derivatives para adducts are formed. 

According to Scheme 11, the isomeric ortho para) product ratios are established during the collapse of the radical pair in (64) (most probably at the positions of AN+- with the highest electron density). Furthermore, the absence of a measurable kinetic isotope effect in the decay of the deuterated analogue (C6D5OCH.v) in Table 3 is predicted from Scheme 11 since the proton loss occurs in a subsequent, rapid step (65). The absence of a deuterium kinetic isotope effect also indicates that the presence of pyridine in the triad in (63) does not lead to the nitroanisoles by an alternative... 

The ambiphilic reactivity of aromatic cation radicals, as described in Schemes 12 and 13, is particularly subtle in the charge-transfer nitration of toluene and anisole, which afford uniformly high (>95%) yields of only isomeric nitrotoluenes and nitroanisoles, respectively, without the admixture of other types of aromatic byproducts. Accordingly, let us consider how the variations in the isomeric (ortho meta para) product distributions with... 

This means, for example, that in normal Diels-Alder reactions of 1-substituted dienes with 1-substituted ethenes, bond formation between C(4) of the diene and C(2) of the alkene, which leads to the ortho adduct, is favored over the other bond formation leading to the meta adduct. Formation of para products from 2-substituted dienes can be explained by a similar reasoning. 

The resonance structures 65 suggest that the pseudo-meta and pseudo-geminal positions are the preferred sites for substitution however, it has been observed (e.g. in the bromination and acetylation of 4-bromo[2.2]paracyclophane (67)) that there is predominant formation of pseudo-ortho and pseudo-para products 8 3b>8 5> (see Table 3) ... 

Photolysis of N-methylborazine with CH3OH (e = 100) yielded 67% ortho substituted product while the reaction with HN(CH3)2 yielded over 90% para product. These results are explained by sterically hindered attack of the CH3OH and HN(CH3)2 at the ortho site. A lower energy barrier is also postulated to explain the statistical distribution of products in the CH3OH + N-methylborazine reaction. 

Though not asked for, it might be useful to indicate that, because we have relatively bulky substituents in this example, the para product will be formed in preference to the ortho product. 

Prediction of the major product works well for m-directors, but what about o-p-directors Will the ortho or the para product be the major product ... 

Two positions are ortho and one is para, so the ortho product should be the major product (67 percent), and the para product should be the minor product (33 percent). Indeed, in the absence of steric factors, this prediction comes true. 

However, groups larger than an ethyl group tend to interfere with attack at the ortho position. For example, in the case of the halogenation of propylben-zene, the para product is the major product. 

Because of the large demand for p-xylene, another method is now being used by Amoco to increase the percentage of the para isomer in mixed xylenes. They are heated at 300°C with an acidic zeolite catalyst, which equilibrates the three xylenes to an o,m,p ratio of 10 72 18%. The para isomer is separated by fractional crystallization, whereas the o,m mixture is reisomerized with the catalyst to produce more para product. Theoretically, all the xylenes could be transformed into the desired para isomer. The zeolite catalyst has the following structure. 

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