Regioselectivity para-selectivity

Our own earlier work on the chlorination of toluene had been subject to similar constraints. In this case, chlorination with ferf-butyl hypochlorite had proved to be advantageous. In the presence of silica gel as catalyst the yield of chlorotoluenes was quantitative but the regioselectivity was more or less statistical (ref. 8). However, the use of proton-exchanged zeolite X allowed the production of chlorotoluenes with a para-selectivity of more than 90 % (Fig. 4) (ref. 9). No HCl is generated in this process since the by-product is tert-butanol, and there is no inhibition of the catalyst. Indeed, the catalyst can be reused if necessary. 

Kinetic results on the chlorination of aniline by A-chloro-3-methyl-2,6-diphenylpiperi-din-4-one (3) suggest that the protonated reagent is reactive and that the initial site of attack is at the amino nitrogen. The effects of substituents in the aniline have been analysed but product studies were not reported. Zinc bromide supported on acid-activated montmorillonite K-10 or mesoporous silica (100 A) has been demonstrated to be a fast, selective catalyst for the regioselective para-bromination of activated and mildly deactivated aromatics in hydrocarbon solvents at 25 °C. For example, bromobenzene yields around 90% of dibromobenzenes with an ortholpara ratio of 0.12. 

Butadienes with alkyl substituents in the 2-position favor the formation of the so-called para-products (Figure 15.25, X = H) in their reactions with acceptor-substituted dienophiles. The so-called mefa-product is formed in smaller amounts. This regioselectivity increases if the dienophile carries two geminal acceptors (Figure 15.25, X = CN). 2-Phenyl-1,3-butadiene exhibits a higher para -selectivity in its reactions with every unsymmetrical dienophile than any 2-alkyl-1,3-butadiene does. This is even more true for 2-methoxy- 1,3-butadiene and 2-(trimethylsilyloxy)-l,3-butadiene. Equation 15.2, which describes the stabilization of the transition states of Diels-Alder reactions in terms of the frontier orbitals, also explains the para "/"meta "-orientation. The numerators of both fractions assume different values depending on the orientation, while the denominators are independent of the orientation. 

Regioselective chlorination. This N-chloroammonium salt (1) as well as N-chlo-ropiperidine, chlorinates aromatic compounds substituted with an electron-donating group with high para-selectivity. Benzene and toluene are attacked only slowly. 

Recently, several selective bromination reagents for reactive aromatic amines have been developed, for example, 2,4,4,6-tetrabromocyclohexa-2,5-dienone (35), iV-bromosuccinimide-dimethylformamide (36), and hexabro-mocyclopentadiene (37). Although molecular bromine is too reactive to perform selective bromination (mono- versus polybromination), the combined used of bromine and zeolites X and Y has been reported to be applicable to the selective bromination of halobenzenes and alkylbenzenes (38). This zeolite method, however, was not successful in the selective bromination of highly active aromatic compounds. Bromine preadsorbed on zeolite 5A (Ca type) was found to monobrominate aniline in carbon tetrachloride with excellent regioselectivity (91-93% para selectivity) in the presence of organic base, pyridine or 2,6-lutidine (Table XII) (39). The preadsorption of bromine on zeolite 5A is necessary for selective bromination, because the inverse procedure of adding bromine to aniline that had been adsorbed on zeolite beforehand caused a nonselective reaction. 

Kwok and Jayasuriya [20] performed regioselective mono-nitration of toluene with n-propyl nitrate in the liquid phase at ambient to reflux temperatures over H-ZSM-5 zeolites with different Si/Al ratios. It was found that high Si/Al ratios enhanced regioselectivity for p-NT. The best product distribution was achieved by use of H-ZSM-5 with a Si/Al ratio of 1000. The yield was 54 % with 95 % p-NT selectivity. Contrary to literature reports, solvents other than toluene led to sluggish reactions. Enhanced para selectivity with a p o ratio of up to 4.53 was reported by Zhang et al. [21] for the nitration of chlorobenzene with nitric acid over H-ZSM-5. Conversion was relatively low, however, reaching only 11.9% at a reaction temperature of 90 °C and a 1 1 reactant ratio (65% HNO3). 

Subsequent reports showed that a wide range of arene substrates could be borylated, with regioselectivity predominantly dictated by steric factors [77]. In the case of monosubstituted arenes, borylation generally occurs predominantly at the meta and para positions, with a near-statistical ratio while substitution at the ortho position is minor (Scheme 4). In the case of 1,3-disubstituted arenes, borylation occurs exclusively at 5-position. The selectivity was reversed in favor of the ortho position in the case of diethylbenzamide, presumably due to chelation [77]. 

The regioselectivity of chlorination and bromination of A,A-dialkylbenzamides in aqueous acetic acid is strongly influenced by the alkyl groups." Ortho and para orientation results fairly selectively from substrates with large alkyl substituents. For example, A(Al-diisopropylbenzamide gives o-, m- and jo-chloro derivatives in the proportion 47 11 42. 

Regioselectivity (selective formation of one regioisomer, for example ortho vs para substitution in aromatic rings)... 

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 meta, has been explained by molecular-orbital considerations.864 When X = N02, regioselectivity to give the ortho or "para product was very high at room temperature, and this method, combined with subsequent removal of the N02 (see 0-82) has been used to perform regio-selective Diels-Alder reactions.865... 

The solid acid catalyzed adamantylation of substituted benzene derivatives was studied with the aim to achieve high para regioselectivities. Of various acidic resins, zeolite HY, sulfated zirconia, perfluorolkanesulfonic acids, and phosphotungstic acid, Amberlyst XN-1010 was found to be the catalyst of choice to afford para-substituted alkylbenzenes with selectivities exceeding 70%.398 In further systematic studies with a Nafion-H-silica nanocomposite catalyst,399 and various... 

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