Basicity substitution effects

The effect of pH is rarely of use for pK measurement it is more often of use in identifying the site of protonation/deprotonation when several basic or acidic sites are present. Knowing the incremental substitutent effects Z of amino and ammonium groups on benzene ring shifts in aniline and in the anilinium ion (40), one can decide which of the nitrogen atoms is protonated in procaine hydrochloride (problem 24). 

The effects of the nucleophile on aromatic substitution which are pertinent to our main theme of relative reactivity of azine rings and of ring-positions are brought together here. The influence of a nucleophile on relative positional reactivity can arise from its characteristics alone or from its interaction with the ring or with ring-substituents. The effect of different nucleophiles on the rates of reaction of a single substrate has been discussed in terms of polarizability, basicity, alpha effect (lone-pair on the atom adjacent to the nucleophilic atom), and solvation in several reviews and papers. ... 

From a variety of basic substituted pyridazinones investigated in Germany [176], ridazolol (59) (CAS 83395-21-5) has been selected for further evaluation as a cardioselective y9-blocker, since in vivo studies (anaesthetized dogs) had revealed that (59) is characterized by a high degree of cardioselectivity. The haemodynamic effects of ridazolol have been studied [177,178], Doses of 20-80 mg of ridazolol have been reported to cause dose-related decrease in exercise-induced tachycardia (for 8 h) and in systolic blood pressure (for 4h)[179],... 

As shown above, one of the drawbacks of HALS is that they can be basic. Substitution on the N of the HALS has an influence on the basicity (see Table 17.2). However, this substitution might also have an influence on its activity as stabilizer. Several studies on the influence of V-substitution of HALS on the UV stability of PP were done. Gugumus [115] showed that N substitution of LMW-HALS-1 only had a marginal effect on the UV stability of PP (see Table 17.3). 

Cohen and Jones (36) have shown that ortho substitution of two tert-butyl groups causes a large increase in the basicity of basic phenoxide ions. However, this effect becomes smaller with decreasing pK of the phenol and essentially disappears for phenols of pK < 7. This evidence indicates that the importance of solvation, and presumbly the number of solvating water molecules, decreases sharply for weakly basic substituted phenoxide ions. 

The basicity-decreasing effect of nitro substitution in the 3-position is almost entirely the result of its inductive effect, whereas that of nitro substitution in the 4-position is attributable to both inductive and resonance effects. In the case of para substitution (as well as ortho substitution), delocalization of the lone pair on the amino nitrogen involves not only the carbons of the aromatic ring but also oxygen atoms of the nitro group. 

In conclusion, descriptions of substitution effects not only require knowledge of more kinetic parameters, but also may lead to added mathematical difficulties, even for just the prediction of basic characteristics of the chemical system, such as the concentrations of functional groups. 

An additional benefit of using a Lewis acid cocatalyst in the carbocyanation reaction is that it enables the use of compounds with less reactive C(sp )-CN bonds. Aliphatic nitriles that bear no P-hydrogens, such as (substituted) acetonitrile [52], benzyl [53], and allyl cyanides [54], can be used successfully. Moreover, P-hydrogen-containing aliphatic nitriles also effectively furnish the carbo-cyanated product when the substrate has a suitable Lewis basic moiety at the y-position, as in 79 (Scheme 6.17) [55]. Intramolecular coordination of the Lewis basic group effectively suppresses undesired P-hydrogen elimination from intermediate 80. 

A series of bis-basic substituted aromatic compounds having direct antiviral and Interferon-inducing effectiveness has been described.6,42 The bisalkamine esters of fluorenone, fluorenol and fluorene had diminishing antiviral potency, respectively. Bis( -dibutylaminopropyl)-9-oxo-fluorene-2,7-dlcarboxylate dihydrochloride prolonged the survival of mice... 

The relative basicities of aromatic hydrocarbons, as represented by the equilibrium constants for their protonation in mixtures of hydrogen fluoride and boron trifluoride, have been measured. The effects of substituents upon these basicities resemble their effects upon the rates of electrophilic substitutions a linear relationship exists between the logarithms of the relative basicities and the logarithms of the relative rate constants for various substitutions, such as chlorination and... 

Sandstrom et al. (65) evaluated the Kj value for 4,5-dimethyl-A-4-thiazoline-2-thione (46) in water (Scheme 19) K-j= 10. A-4-Thiazoline-2-thiones are less basic in the first excited state (61) than in the ground state, so application of Forster s cycle suggests that the thione form is even more favored in the first excited state. Huckel molecular orbital (HMO) calculations suggest that electronic effects due to substitution in... 

The same situation is observed in the series of alkyl-substituted derivatives. Electron-donating alkyl substituents induce an activating effect on the basicity and the nucleophilicity of the nitrogen lone pair that can be counterbalanced by a deactivating and decelerating effect resulting from the steric interaction of ortho substituents. This aspect of the reactivity of thiazole derivatives has been well investigated (198, 215, 446, 452-456) and is discussed in Chapter HI. 

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