Resonance effects protonation

The mobility of the proton in position 2 of a quaternized molecule and the kinetics of exchange with deuterium has been studied extensively (18-20) it is increased in a basic medium (21-23). The rate of exchange is close to that obtained with the base itself, and the protonated form is supposed to be the active intermediate (236, 664). The remarkable lability of 2-H has been ascribed to a number of factors, including a possible stabilizing resonance effect with contributions of both carbene and ylid structure. This latter may result from the interaction of a d orbital at the sulfur atom with the cr orbital out of the ring at C-2 (21). 

This is due to a resonance effect. Aniline is stabilized by sharing its nitrogen lone-pair electrons with the aromatic ring. In the anilinium ion, the resonance stabilization is dismpted by the proton bound to the lone pair. 

Substituent effects (substituent increments) tabulated in more detail in the literature demonstrate that C chemical shifts of individual carbon nuclei in alkenes and aromatic as well as heteroaromatic compounds can be predicted approximately by means of mesomeric effects (resonance effects). Thus, an electron donor substituent D [D = OC//j, SC//j, N(C//j)2] attached to a C=C double bond shields the (l-C atom and the -proton (+M effect, smaller shift), whereas the a-position is deshielded (larger shift) as a result of substituent electronegativity (-/ effect). 

In the El cb mechanism, the direction of elimination is governed by the kinetic acidity of the individual p protons, which, in turn, is determined by the polar and resonance effects of nearby substituents and by the degree of steric hindrance to approach of base to the proton. Alkyl substituents will tend to retard proton abstraction both electronically and sterically. Preferential proton abstraction from less substituted positions leads to the formation of the less substituted alkene. This regiochemistry is opposite to that of the El reaction. 

A combination of steric and electrostatic factors is presumably decisive with regard to the form of the acid most stable in sulfuric acid solution. The simple protonated form XX of benzoic acid is stabilized by resonance structures sterically prohibited in mesitoic acids. The ortho methyl groups of mesitoic acid would interfere with a coplanar dihydroxymethylene group. On the other hand, the inductive and resonance effects of the methyl groups help stabilize the acylium ion form of mesitoic acid as in the formulae XXI. In the case of 2,4,6-tribromobenzoic acid the steric effect and its abetting electronic effects are not sufficient, and this acid behaves like benzoic acid.17 >177... 

The reactivities of carbenes toward alkenes have been correlated with the inductive and resonance effects of the carbene substituents, log k — a Eat + fcEaR+ + c.m Analogous correlations cannot be obtained for the reaction rates of carbenes with alcohols, neither with the substituent parameters used by Moss,109 nor with related sets.110 In particular, the substituent parameters do not describe the strong, rate-enhancing effect of aryl groups. For a detailed analysis, see the discussion of proton affinities (Section V.A). 

Cephalosporins such as cefixime (5.40) and cefotaxime (5.41) undergo epimerization at C(7) under alkaline conditions without preliminary /3-lactam ring opening. The epimerization is believed to begin with the removal of the acidic H-atom at C(7). The acidity of this proton derives from the resonance effect of the neighboring carbonyl group (Fig. 5.13) enhanced by the presence of electron-withdrawing substituents at C(3 ) [113][114],... 

Primary and secondary nitroalkanes, and substrates containing terminal em-dinitroaliphatic functionality, have one or more acidic a-protons, a consequence of inductive and resonance effects imposed by the nitro group. As a result, such compounds can behave like carbanions and participate in a number of addition and condensation reactions which are typical of substrates like ketones, aldehydes, and /S-ketoesters. Such reactions are extremely useful for the synthesis of functionalized polynitroaliphatic compounds which find potential use as explosives, energetic oligomers and plasticizers. 

Conversely, we can reason that the formation of conjugate acids from bases will be favoured by electron-donating substituents and inhibited by electron-withdrawing groups. However, the feature of bases is that they have a lone pair of electrons that are able to coordinate with a proton. Sometimes, this lone pair may feed into the molecule via a resonance effect, and this can stabilize the free base and inhibit conjugate acid formation. With bases, therefore, we normally consider two approaches, either stabilization of the conjugate acid, which increases basicity, or stabilization of the free base, which decreases basicity. 

In these systems, the resonances of protons closer to the metal surface are more seriously broadened, whereas the effect is less pronounced for the protons that are farther away. (Adapted from Liu et al, 2001)... 

AC2O/S11CI4), and nitration [Cu(N03)2] of thienothiophenes 1 and 2. He recently also studied the effect of the a-substitution (with halogen, CH3, SCHj, CN, NO2, COCH3, and COOH groups) on the chemical shifts of protons. He observed a good correlation between the shifts, reactivity constants, F (the field effect), and R (the resonance effect). ... 

The DSP approach nicely answers the controversial question about which substituent parameters should be employed to correlate pKa data for 4-substituted pyridinium ions. Statistically, the best correlation is given by Eq. (9), which has values to measure the resonance contribution of a substituent, a result in keeping with chemical intuition. This correlation is statistically superior to a Hammett treatment, where both resonance and inductive effects of a group are combined into a single parameter, p or ap.53,54 Moreover, now it is possible to rationalize why a simple Hammett treatment using ap works so well. Equation (9) reveals that the protonation equilibrium is much more sensitive to an inductive effect (p, — 5.15) than to a resonance effect (p = 2.69). Hence, substituent parameters, such as erp, which are derived from a consideration of the dissociation constants for benzoic acids where resonance contributions are small serve as a useful approximation. The inductive effect is said to have a larger influence on pKa values for pyridinium ions than for benzoic acids because the distance between the substituent and the reactive site is shorter in the pyridine series.53... 

These place a positive charge on the oxygen atom of the unionized molecule, and so cause it to repel the proton. On analysis of the experimental values for Ka at 25°C it is found that the inductive effect of a nitro group increases Ka by a factor of about 45, and the resonance effect in the ortho and para positions gives another factor of about 22. The acid constant of a nitrophenoi can be found approximately by multiplying that for phenol, l.t X 10 10, by the factor 45 for every meta nitro group and 1000 for every ortho or para nitro group in the molecule. The comparison of the values calculated in this way with those found by experiment is shown in Table 8-1. ... 

Fluorination can, under certain circumstances, increase the CH acidity, but again the distance of fluorine from the acidic proton has a direct impact on this process. For conjugate anions that are nonplanar, a-fluorination always increases acidity since inductive effects predominate. However, for planar conjugate anions where resonance effects are important, a-fluorination can decrease acidity but not in a predictable manner (see Table 5). 

Acid-catalysed solvolysis of N-aryl phosphoramidates is characterised by the negative value of the reaction constant (p = -1.2).These inversed substituent effects illustrate two points discussed before. First, if the N-protonated form repre -sents the reactive intermediate in solvolysis of (2), much stronger dependence of the protonation preequilibrium on the effect of N-substitution is expected. Secondly, if the resonance effects are poorly transmitted to the P atom through the -NH- bridge, structural variation in the N-aryl substituent should have weak effect upon the ability of phosphorus to accept a nucleophile. 

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