Para substituents, activation

As might be expected from a consideration of electronic effects, an amino substituent activates pyrazines, quinoxalines and phenazines to electrophilic attack, usually at positions ortho and para to the amino group thus, bromination of 2-aminopyrazine with bromine in acetic acid yields 2-amino-3,5-dibromopyrazine (Scheme 29). 

Electron-rich substituents activate positions ortho and para to themselves. Thus, electrophilic chlorination of 1- and 2-hydroxydibenzofurans... 

The Hammett equation is the best-known example of a linear free-energy relationship (LFER), that is, an equation which implies a linear relationship between free energies of reaction or activation for two related processes48. It describes the influence of polar meta-or para-substituents on reactivity for side-chain reactions of benzene derivatives. 

An example of a reaction series in which large deviations are shown by — R para-substituents is provided by the rate constants for the solvolysis of substituted t-cumyl chlorides, ArCMe2Cl54. This reaction follows an SN1 mechanism, with intermediate formation of the cation ArCMe2 +. A —R para-substituent such as OMe may stabilize the activated complex, which resembles the carbocation-chloride ion pair, through delocalization involving structure 21. Such delocalization will clearly be more pronounced than in the species involved in the ionization of p-methoxybenzoic acid, which has a reaction center of feeble + R type (22). The effective a value for p-OMe in the solvolysis of t-cumyl chloride is thus — 0.78, compared with the value of — 0.27 based on the ionization of benzoic acids. 

Fig. 12 Correlation between the calculated activation energy of the Bergman cyclization and the product of natural charges at the terminal acetylenic atoms of benzannelated enediynes. Only para substituents obey the correlation. Adapted from reference49.

Sterically compact ortho substituents such as Me, OH, anti-OMe, F, Cl, and CN destabilize the ground and transition states to a similar degree. As a result, changes in the activation energy are minor. The net effect of these substituents on the cyclization rate is similar to that of the para substituents, and the corresponding computational data fit well into the correlation in Fig. 12.49... 

A comparison of the activity levels of 7V-acetoxy-/V-butoxybenzamides 26, Ar-acetoxy-A -benzyloxybenzamides 27 and A-benzoyloxy-A-benzyloxybenzam-ides 28 with common para substituents showed increasing mutagenicity with size or hydrophobicity. Activities increased with increasing aromatic substitution. 

In a time course study on the conversion of ( )-l-phenylethanol 13 (X=H), formation of acetophenone was observed to a maximum of around 20% during the conversion of (S)- to (R)- alcohol which occurred over 24 h to give (R)-13 in 96 % yield, 99% e.e. The effect of ring substitution on the efficiency of the dera-cemization was notable. While para substituents (Cl, OMe, Me) gave good results, ortho derivatives could not be deracemized and the biocatalyst showed little activity towards meta substituted compounds. On addition of allyl alcohol, improvements in e.e. were obtained, particularly for the conversion of l-(m-methylphenyl)ethanol (from 21 to 94% e.e.). However these improvements did appear to be at the expense of yield (89% diminished to 55%). The authors sug-... 

A few nuclear-substituted variants of ( )-propoxyphene (XLV, Ar = Ph) have been reported. Para substituents (Cl, F, Me and OMe) in the 1-phenyl group reduce the activity of the acetoxy ester analogue of propoxyphene while o-F and... 

Although electron-donating substituents activate the ring towards electrophilic attack, they are both ortho and para directing, and an electrophilic... 

For the aromatic carboxylic acids, substituents on the aromatic ring may also influence the acidity of the acid. Benzoic acid, for example, has = 4.3 x 10 . The placements of various activating groups on the ring decrease the value of the equilibrium constant, and deactivating groups increase the value of the equilibrium constant. Table 12-2 illustrates the influence of a number of para-substituents upon the acidity of benzoic acid. 

The treatment of the 2-methyl- 1-propenylbismuthonium salt with KOf-Bu in the presence of excess styrene gives alkylidenecyclopropanes in good yield (Scheme 7). The para substituent effect on the relative reactivity is very small, indicating that a free alkylidene carbene is generated as the active species. In this case, the alkylidene carbene is trapped by the styrene in solution. 

Two para-substituents, phenyl and cyano depress and retard the rate of cyclization significantly (Table 11.2)." p-Phenyl and p-cyano are both radical stabilizing substituents. These conjugative substituents reduce the spin density on the carbon ortho to the nitrene nitrogen. The reduced spin density at carbons ortho to the nitrogen lowers the rate at which the 1,3-biradical cychzes. The effect with p-cyano and p-biphenyl singlet phenylnitrene is quite dramatic. The lifetimes of these singlet nitrenes at ambient temperature are 8 and 15 ns, respectively, and the activation barriers to cychzation are 7.2 and 6.8 kcal/mol, respectively. 

Probtom 11.24 Write resonance structures to account for activation in addition-elimination aromatic nucleophilic substitution from delocalization of the charge of the intermediate carbanion by the following para substituent groups (a) —NOj, (b) —CN, (c) —N=0, (d) CH==0. -4... 

I-Ph, or LNiIH-0-NiIUL) have been proposed as the active oxidant (92). In the reaction, E olefins are more reactive than the corresponding Z isomers, and a strong correlation was observed between the electron-donating effect of the para substituents in styrene and the initial reaction rate (91). Isotope labeling studies have shown that the epoxide oxygen is derived from PhIO. 

Eq. 54 indicates that the larger the van der Waals volume, the more favorable are the ortho substituents to the excitatory activity on the nerve cords within substituents tested here. The electron-withdrawing effect of the ortho substituents deteriorates the activity. The activity varies parabolically with the value, the optimum of which is around = 0. Eq. 55 and 56 show that the optimum van der Waals volume exists at about 4.9 and 2.2 for meta and para substituents, respectively. The hydro-phobicity of substituents is not favorable to the activity at the para position. 

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