Power of Substituents

Reaction with Aniline (PhNHa) Use of Protective Groups 

Protect AniUne for Acidic Electrophilic Aromatic Substitutions 

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Spin-density distributions obtained from the analysis of esr spectra can be taken to establish a scale for the radical-stabilizing power of substituents. 

Involvement of AModo species in electrophilic C-iodinations needs to be considered since a number of imidazoles are known to form such compounds in basic medium. Charge-transfer complexes, too, are quite well known. They seem to be of the n -type through the unshared electron pair at N-3. Equilibrium constants for their formation are known to increase regularly in line with electron-donating powers of substituents (or vice versa). Some KCT values at 20°C (L M are imidazole (200), 1-methylimidazole (333), 1,2-dimethylimidazole (1165), 4-phenylimidazole (152), and 4,5-diphenylimidazole (141) (83BSB923). The charge-transfer complexes formed between iodine and imidazole-2-thiones appear to involve the sulfur atoms (88JA2586). 

The electron donating/withdrawing power of substituents at the a-carbon of the monomer also influence the magnitude of and K2. This is well illustrated by the contrasting effects of change in size of alkyl group substituents on the rate of cationic and anionic polymerization. 

A first set of experiments, the study of the protonation of enolates obtained from benzaldehyde Schiff bases and Lithium Diisopropylamide, showed that the asymmetric induction was not significantly affected by the size of the R moiety of the amino acid (R = Me, Et, i-Pr, n-Bu, f-Bu, Ph ee = 44-56%). The two main factors improving the enantioselection were the Ar substituent of the Schiff base and the lithium amide used for the deprotonation. The following results (Table 1) indicate clearly that the enantioselectivity increases with the electron-donating power of substituents para to the Schiff base (eq 3), leading to 70% ee with the Schiff base of p-methoxybenzaldehyde derived from phenylglycine. ... 

The directing power of substituent groups has long intrigued the imagination of chemists. Correlations have been made between the... 

Monophenols are more slowly acting substrates as they have to be hydroxylated prior to then-oxidation to the corresponding o-quinones [7]. The commonest natural substrates for monophenol oxidase are probably tyrosine and p-coumaric acid or their derivatives. AU o-diphenol oxidases require the basic o-dihydroxyphenol structure for oxidase activity so that catechol is the simplest possible, but not necessarily the best, substrate 4-methyl catechol is usually the fastest [45]. The rate of oxidation of o-diphenols by PPO increases with increasing electron withdrawing power of substituents in the para position. o-Diphenol substitution (-CH3) at one of the positions adjacent to the -OH groups prevents oxidation. These positions should remain free for oxidation to take place [14]. 

The difficulty in overruling the directing power of substituents increases in the sequence alkyl, acyloxy, alkoxy, silyloxy. 

In order to calculate the similarity between fragments (substituents, spacers, or rings) that one wants to replace in the process of bioisosteric design, it is necessary to quantify somehow their properties and express them as a set of numerical values -descriptors. In the classical years of quantitative structure-activity relationship (QSAR), the properties of substituents were mostly characterized by experimentally derived parameters. Hammett sigma constants a (and several variations of this parameter) played a prominent role in characterizing the electron-donating or electron-accepting power of substituents 7], and the Hansch n parameter, defined... 

Guideline 2. Experimentally, we can rank the directing power of substituents into three... 

The same principles of resonance, steric considerations, and directing power of substituents apply to larger polycyclic systems, derived from naphthalene by additional benzofusion, such as anthracene and phenanthrene (Section 15-5). For example, the site of preferred electrophilic attack on phenanthrene is C9 (or CIO) because the dominant resonance contributor to the resulting cation retains two intact, delocalized benzene rings, whereas all the other forms require disruption of the aromaticity of either one or two of those rings. 

As for the reactivity (polymerizability), the situation is different from that of initiation. Indeed, the new free radical active center formed after monomer insertion in the polymeric chain is roughly identical to the last formed one. Thus, its formation does not entail an increase of stability. The negative variation of the free enthalpy is only due to the exothermic transformation of the monomer molecule into a monomeric unit. The stabilizing power of the substituent A carried by the double bond is exerted not only on the active center formed after addition but also on the monomer molecule. Logically, a progressive decrease of kp is observed with the increase of the stabilizing power of substituents A (see Table 8.5). 

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