Meta effect

The APHA with a fluorine atom at the 3-position of the aryl exhibits a class-II/class-I HDAC selectivity of 176, whereas substitution at the 2-or 4-position gives respectively much lower selectivity ranging from 34 to a value less than 2. It is interesting to note that this meta-effect is much less pronounced when the substituent is a chloro atom and the effect is completely lost when a bromo-atom is introduced (data not shown). 

It should be added that no experimental evidence exists providing a molecular explanation for the requirements and role of the aromatic hydroxyl(s). Descriptively, it is clear that a hydroxyl "meta" to an aminoethyl fragment is important, but almost nothing is known about the cause of this "meta effect". Only the recent demonstration that this effect is chirally modulated 1 ) suggests that factors extrinsic to the drug (i.e., specific drug-receptor interactions), rather than purely intrinsic factors (e.q., 0-N distance or drug dipoles), may be responsible. 

Consistent with this mechanism, the addition of two meta-methoxy groups facilitates the reaction, on which was successfully tested a series of amino adds (Scheme 13.8) [33]. One of the main drawback of this group is the need for short-wavelength irradiation, which his frequently incompatible with features on the substrate. The true nature of the mechanism (e.g., homolysis versus heterolysis) has been discussed over the years, using among other arguments the meta effect [34—37]. 

Zimmerman, H.E. (1995) The meta effect in organic photochemistry mechanistic and exploratory organic photochemistry. Journal of the American Chemical Society, 117, 8988-8991. 

Wang, P Hu, H. and Wang, Y. (2007) Application of the excited state meta effect in photolabile protecting group design. Organic Letters, 9, 2831-2833. 

Fleming, S. A. Jensen, A. W. Substituent Effects on the Photocleavage of Benzyl-Sulfur Bonds. Observation of the Meta Effect. /. Org. Chem. [CD-ROM] 1996, 61, 7044. 

A meta effect has been proposed by Zimmerman and Sandel in which there is excess electron density at this position (as well as a smaller amount in the ortho... 

It was observed that an antf-homometa chloro group is selectively cleaved over that of an anri-homopara chloro group in the following bicyclic anisyl compound [74]. The meta effect in photochemistry was first demonstrated by Zimmerman... 

Photochemical generation of free radicals from ketones 20 Ester photolysis and the meta effect 21 Induced decomposition of radical initiators 21 Molecule-induced homolysis 22... 

Thus, one can state that an inductive effect of the substituents is distributed uniformly throughout the whole macrobicyclic system, and, unlike the well-studied substitution in aromatic systems, there is no pronounced ortho, para, and meta effects of the substituents in clathrochelates. A key role in the transfer of electromeric interactions in a clathrochelate molecule is played by the encapsulated central metal ion, rather than a a, r-bond system. Therefore, the electron interactions in the clathrochelate molecule are distributed isotropically rather than alternately [69]. 

Figure 3 shows the 70 eV EI-MS of the isomeric hydroxyanilines. Unlike the methoxy anilines, for which ortho, para and meta effects are quite pronounced, the EI-MS of these three positional isomers are very similar. The most abundant ion in the EI-MS of the hydroxyanilines is the molecular ion of m/z 109 whereas, by far the most prominent fragment ion is that of m/z 80, viz. [M — CO — H]+. A substantial contribution of the keto tautomer is suggested for the CO loss process38,42,43, as represented in Scheme 7 for the ortho isomer, and this tautomer may account for the weak positional effects. 

Photocleavage of benzyl-S bonds appears to proceed neither by an electron transfer pathway nor with participation of an exciplex. A meta effect seems to operate in these reactions as evidenced by the influence of 3-methoxy and of 3-cyano substituents on the efficiency of the cleavage process. Photolysis of 1,2-bis(phenoxymethyl)-, l,2-bis(phenylthiomethyl)-, and l,2-bis(phenylseleno-methyl)benzene induces a two-photon process to give o-quinonedimethane, which in the presence of dienophiles undergoes a cycloaddition reaction, and 4,8,10-trithiadibenzo[cd,ij]azulene 8-oxides gives the corresponding aldehydes and ketones together with 4,8,9-trithiacyclopenta[def]phenanthrene. The two... 

The enhanced photoreactivity of meta- vs. para-substituted benzenoids has been rationalised in terms of selective transmission of electron withdrawal or donation. A new example of the meta effect has been reported for the excited... 

Zimmerman, H. E., The meta Effect in Organic Photochemistry Mechanistic and Exploratory Organic Photochemistry, J. Am. Chem. Soc. 1995, 117, 8988 8991. 

In contrast to this proposal, in the Zimmerman mechanism the competition that controls the yield of radical pairs and ion pairs occurs between hom and kll. In other words, both homolytic and heterolytic cleavage occur from Si and the partitioning between these two pathways is controlled by the electron distribution of the excited state of the benzylic chromophore and, in particular, by substituents on the aromatic ring. Thus, the meta effect operates by, for instance, a... 

One may ask why these trends have not been recognized earlier, although such data have been available [32, 34,36]. Since the extent of the destabilizing effect in meta-substituted benzyl-type radicals is relatively small (cf. Table 3), such effects may have been masked by polar effects (cf. the two-parameter Hammett treatment in Fig. 14) in the kinetic scales (e.g., m-CN ac= —0.12 vs. opol = +0.56). In the case of the spectroscopic ax scale, due to the complexity of the EPR spectra for the meta-substituted benzyl radicals 13, which cover only a range of +0.20 G, the accuracy in the coupling constants may have been too low (+0.02 G) to expose the small, but systematic meta effect [36, 37, 55]. These shortcomings are less pronounced in the AD scale, for which polar effects are absent and the total range in the meta substituents covers + 14 G with an accuracy of 0.3 G. 

The mirror-image example " is found in Equation 1.11, where there is expulsion of an acetate anion. Here, metaelectron donors accelerate the reaction, and the dimethoxy-benzyl derivative shown was one of the best in exhibiting the meta effect. 

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