Meta substituents

When the phenyIhydra2one bears a meta-substituent, two isomeric indoles are possible ortho-substituents also frequentiy introduce compHcations. 

Reactions that occur with the development of an electron deficiency, such as aromatic electrophilic substitutions, are best correlated by substituent constants based on a more appropriate defining reaction than the ionization of benzoic acids. Brown and Okamoto adopted the rates of solvolysis of substituted phenyldimeth-ylcarbinyl chlorides (r-cumyl chlorides) in 90% aqueous acetone at 25°C to define electrophilic substituent constants symbolized o-. Their procedure was to establish a conventional Hammett plot of log (.k/k°) against (t for 16 /wcra-substituted r-cumyl chlorides, because meta substituents cannot undergo significant direct resonance interaction with the reaction site. The resulting p value of —4.54 was then used in a modified Hammett equation. 

The formation of the ortho regioisomer can be enhanced if electrostatic attraction between the carbonium ion and the meta substituent on the A ring can be accommodated. ... 

Calculated from meta substituent constants only. 

The method involves the following steps (1) Select a number of (especially) meta substituents whose a parameters can be considered invariant to use as a basis for the determination of the reaction constant p, (2) evaluate p, and (3) evaluate the a parameters for the remaining substituents according to Eq. (13). 

Nucleophilic aromatic substitution occurs only if the aromatic ring has an electron-withdrawing substituent in a position ortho or para to the leaving group. The more such substituents there are, the faster the reaction. As shown in Figure 16.18, only ortho and para electron-withdrawing substituents stabilize the anion intermediate through resonance a meta substituent offers no such resonance stabilization. Thus, p-ch oronitrobenzene and o-chloronitrobenzene react with hydroxide ion at 130 °C to yield substitution products, but m-chloronitrobenzene is inert to OH-. 

The special substituent constants for + R para-substituents are denoted by a, and those for — R para-substituents are denoted by a+ 54. They are based respectively on the reaction series discussed above. Selected values are given in Table 1. Characteristic a or a+ values are sometimes distinguished for meta-substituents also, but only for a minority of substituents which show very marked + R or — R effects do these differ significantly from ordinary a values. The range of applicability of the Hammett equation is greatly extended by means of a and cr+, notably to nucleophilic (by a ) and to electrophilic (by cr+) aromatic substitution. 

The effect of meta substituents has been studied much less, but it has been reported that here too, electron-withdrawing groups increase the rate See Nurgatin, V.V. Shamin, G.P. Ginzburg, B.M. J. Org. Chem., USSR, 1983, 19, 343. 

According to earlier considerations, the effects of m-substituents have been considered generally to be of the sigma zero type. Swain and Lupton have questioned this conclusion. We have proceeded in the following manner to obtain evidence on the issue. From all the known data, 11 sets of meta substituent reaction series data were found which meet the minimum substituent criterion for basis sets. These reactions are listed in Table XI, with the pT .Pr. ... 

Cardanol, a main component obtained by thermal treatment of cashew nut shell liquid (CNSL), is a phenol derivative having mainly the meta substituent of a C15 unsaturated hydrocarbon chain with one to three double bonds as the major. Since CNSL is nearly one-third of the total nut weight, a great amount of CNSL is obtained as byproducts from mechanical processes for the edible use of the cashew kernel. Only a small part of cardanol obtained in the production of cashew kernel is used in industrial fields, though it has various potential industrial utilizations such as resins, friction-lining materials, and surface coatings. Therefore, development of new applications for cardanol is very attractive. 

Some attempts have also been made to vary the para- or meta-substituents on the phenyl ring of the SlMes ligand, however none of the resulting NHC-Ru complexes showed better RCM activity than the original Grubbs 1114 when tested with standard substrates 1 and 7 [37 0]. 

Vemula, P.K., Mallia, V.A., Bizati, K. and John, G. (2007) Cholesterol Phenoxy Hexanoate Mesogens Effect of meta Substituents on Their Liquid Crystalline Behavior and in Situ Metal Nanoparticle Smtesis. Chemistry of Materials, 19, 5203-5206. 

Figure 5. Effect of side chain substituents on polymer crystallinity. Polymers with two para substituents (second row) are more crystalline than polymers with mixed para and meta substituents.

There also seems to be an unexpected effect of meta substituents. Lichtin and Glazer have suggested, since purely radical structures can not involve meta substituents, that combined radical and dipole structures are important 20... 

No similar meta substituent effect exists for ions since resonance between a singlet and triplet (diradical) state is prohibited. The dipolar ion theory would suggest that suitably disubstituted radicals should be especially stable, particularly in polar solvents, because of structures like III. 

A classical Hansch approach and an artificial neural networks approach were applied to a training set of 32 substituted phenylpiperazines characterized by their affinity for the 5-HTiA-R and the generic arAR [91]. The study was aimed at evaluating the structural requirements for the 5-HTiA/ai selectivity. Each chemical structure was described by six physicochemical parameters and three indicator variables. As electronic descriptors, the field and resonance constants of Swain and Lupton were used. Furthermore, the vdW volumes were employed as steric parameters. The hydrophobic effects exerted by the ortho- and meta-substituents were measured by using the Hansch 7t-ortho and n-meta constants [91]. The resulting models provided a significant correlation of electronic, steric and hydro-phobic parameters with the biological affinities. Moreover, it was inferred that the... 

The hydrolysis of substituted phenyl acetates has been studied in the presence of cyclodextrins (Van Etten et al, 1967a, b). No correlation was found between the rate constants for hydrolysis and a for the substituent group. Specificity was directed towards meta-substituents. m-t-Butylphenyl acetate hydrolyses 240 times faster in the presence of 0-01 M cyclohepta-amylose. Comparison of spectral shifts upon inclusion of p-t-butyl and m-t-butylphenol indicated that benzene rings of p-substituted phenols are included within the cavity of cyclodextrins [45], but that the benzene ring of the meta-isomer... 

In accord with the above scheme, variation of the meta-substituent altered the rate of acylation but not that of deacylation. The reaction of equation (27) is similar to reaction of a-chymotrypsin with phenolic esters. 

The roles of ortho and para substituents are similar for mite and egg a meta substituent is disadvantageous for mite toxicity to the egg is apparently unaffected by substitution at this position. 

In 1998, Yang and coworkers reported a series of (7 )-carvone derived ketones (63) containing a quaternary center at and various substituents at (Fig. 22) [119]. The ees of fran -stilbene oxide varied with different para and meta substituents when 63b was used as the catalyst. The major contribution for the observed ee difference is from the n-n electronic repulsion between the Cl atom of the catalyst and the phenyl group of the substrate. The substitution at also influences the epoxidation transition state via an electrostatic interaction between the polarized C -X bond and the phenyl ring on franx-stilbene (Table 6, entries 3-7, 10-14). In 2000, Solladie-Cavallo and coworkers reported a series of fluorinated carbocyclic ketones... 

The (m) fraction is in the range 0.6-0.7 for polymerization at high monomer concentration in the temperature range —25 to 25°C [Resconi et al., 2000]. Substituents on the phenyl groups of the 2-phenylindene ligands, especially meta substituents, slow down the conformational interconversion, and this increases the isotacticity of the polymerization. Both steric and electronic factors operate to affect the interconversion of conformers. Bis(2-phenylin-dene)zirconium dichloride/MAO yields polypropene with (mmmm) = 0.33 for polymerization of liquid propene at 20°C. 3,5-Di-f-butyl and 3,5-difluoromethyl substituents increase (mmmm) above 0.70 [Lin and Waymouth, 2002 Wilmes et al., 2002a,b]. 

Azetidinones (682) can be converted by treatment with trifluoroacetic acid into dihy-droquinol-4-ones should the iV-aryl group carry a meta-substituent mixtures of 5- or 7-substituted dihydroquinolones are obtained (76H(4)1649, 80JCS(P1)2105). Diketene, with hydroxylamines, gives 3-acetyl-6-hydroxy-l-oxypyrid-2-ones (683) (71YZ772, 72CPB1368). 

The transition states for the stepwise (fej, Fig. 2.3) and concerted (fecon) reactions of (4-MeO,X)-3-Y lie at distinct well-separated positions on the More O Ferrall diagram and show different sensitivities to changes in solvent polarity, meta substituents X at the aromatic ring, and the leaving group Y. For example, in 50 50 (v/v) water/trifluoroethanol (4-MeO,H)-3-Cl reacts with azide ion exclusively by a stepwise mechanism through the primary carbocation intermediate (4-MeO,H)-3" with a selectivity for reaction with azide ion and solvent of feaz/ s = 25 However, two-thirds of the azide ion substitution product obtained from the reaction of (4-MeO,H)-3-Cl in the less polar solvent 80 20 acetone/water forms by concerted bimolecular substitution and only one-third forms by trapping of the carbocation intermediate (4-MeO,H)-3 with a selectivity of k z/h = 8 The preferred... 

Very little substitution occurs in the sterically hindered position between meta substituents. 

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