And resonance effects

This led to the introduction of the concepts of inductive and resonance effects and to the establishment of the mechanism of electrophilic aromatic substitution. 

It should be emphasized that the concepts of inductive and resonance effect have not been derived from theory but have been introduced to "explain the experimental observations, to put them into a systematic framework of an ordering scheme. 

Let us illustrate this with the example of the bromination of monosubstituted benzene derivatives. Observations on the product distributions and relative reaction rates compared with unsubstituted benzene led chemists to conceive the notion of inductive and resonance effects that made it possible to explain" the experimental observations. On an even more quantitative basis, linear free energy relationships of the form of the Hammett equation allowed the estimation of relative rates. It has to be emphasized that inductive and resonance effects were conceived, not from theoretical calculations, but as constructs to order observations. The explanation" is built on analogy, not on any theoretical method. 

Clearly, the nex.t step will be to investigate the physicochemical effects, such as charge distribution and inductive and resonance effects, at the reaction center to obtain a deeper insight into the mechanisms of these biochemical reactions and the finer details of similar reactions. Here, it should be emphasized that biochemical reactions arc ruled and driven basically by the same effects as organic reactions. Figure 10.3-22 compares the Claisen condensation of acetic esters to acctoacctic esters with the analogous biochemical reaction in the human body. 

The quatemization reaction of the thiazole nitrogen has been used to evaluate the steric effect of substituents in heterocyclic compounds since thiazole and its alkyl derivatives are good models for such study. In fact, substituents in the 2- and 4-positions of the ring only interact through their steric effects (inductive and resonance effects were constant in the studied series). The thiazole ring is planar, and the geometries of the ground and transition states are identical. Finally, the 2- and 4-positions have been shown to be different (259. 260). 

The mix of inductive and resonance effects varies from one halogen to another but the net result is that fluorine chlorine bromine and iodine are weakly deactivating ortho para directing substituents... 

A tertiary carbonium ion is more stable than a secondary carbonium ion, which is in turn more stable than a primary carbonium ion. Therefore, the alkylation of ben2ene with isobutylene is much easier than is alkylation with ethylene. The reactivity of substituted aromatics for electrophilic substitution is affected by the inductive and resonance effects of a substituent. An electron-donating group, such as the hydroxyl and methyl groups, activates the alkylation and an electron-withdrawing group, such as chloride, deactivates it. 

In general, the dissection of substituertt effects need not be limited to resonance and polar components, vdiich are of special prominence in reactions of aromatic compounds.. ny type of substituent interaction with a reaction center could be characterized by a substituent constant characteristic of the particular type of interaction and a reaction parameter indicating the sensitivity of the reaction series to that particular type of interactioa For example, it has been suggested that electronegativity and polarizability can be treated as substituent effects separate from polar and resonance effects. This gives rise to the equation... 

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. 

If the two interaction mechanisms maintain the same relative importance throughout the reaction series, that is, if the ratio pj/pi is constant, Eq. (7-26) becomes identical in form with Eq. (7-24). This in fact appears to be the usual situation in Hammett correlations, PP- and the two interaction mechanisms are commonly discussed in terms of the inductive and resonance effects of electronic displacement. 

A further complication arises with Ingold s suggestion" that both the inductive and resonance effects are composed of initial state equilibrium displacements that reveal themselves in equilibrium properties like dipole moments and equilibrium constants and of time-dependent displacements produced during reaction by the approach of an attacking reagent, observed rate effects being resultants of both types of electronic effects. Hammett, however, claims that it is not necessary or possible to make this distinction. 

The reasonable extension of these ideas is to express o- as a sum of contributions from the inductive and resonance effects. Branch and Calvin suggested this, and much of the research on LFER of the past three decades has been concerned with... 

The general chemical reasonableness of the results in Table 7-7 is gratifying, but this does not constitute a demonstration that the separation of substituent effects into inductive effects and resonance effects is quantitatively possible, for these effects may interact so as to be nonadditive. Ritchie and Sager express reservations about the approach in general, and other authors " have criticized results based on Eqs. (7-33) and (7-34). 

Many other definitions of an ortho substituent constant have been made Shorter has reviewed these. Charton analyzed Oo in terms of Oi and CTr, i.e., = a(Ti -I- fpoR, finding that the distribution of inductive and resonance effects (the ratio a/b) varies widely with the substituent and, therefore, that no general Oo scale is possible. Charton also subjected to analysis according to Eq. (7-47),... 

In the acidic and alkaline hydrolysis rates of the same ester, the steric and resonance effects. re the same. 

A favorite strategem is to compare the reactivities of ortho- and para-substituted aromatic substrates, such as 13 and 14 the electronic (inductive and resonance) effects of the substituent should be about the same in the two cases, but only the o/-f/io-substituted compound can undergo intramolecular catalysis. 

A heteroatom (in ring A) will control the electron density at the position of ring closure by its inductive and resonance effects. If the substituent increases the electron density of the ring, then ring closure will be facilitated by the heteroatom. If the heteroatom decreases electron density, then the ring closure will be hindered. 

Taft, R. W., Jr. Separation of Polar, Steric, and Resonance Effects in Reactivity, in Steric Effects in Organic Chemistry (Newman, M. S. ed.), p. 556, New York, Wiley 1956... 

One further point inductive effects and resonance effects don t necessarily act in the same direction. Halogen, hydroxyl, alkoxyl, and amino substituents, for instance, have electron -withdrawing inductive effects because of the electronegativity of the -X, -O, or —N atom bonded to the aromatic ring but have resonance effects because of the lone-pair electrons on those same —X, -O, or —N atoms. When the two effects act in opposite directions, the stronger of the two dominates. 

Inductive and resonance effects account for the directing effects of substituents as well as for their activating or deactivating effects. Take alkyl groups, for instance, which have an electron-donating inductive effect and are ortho and para directors. The results of toluene nitration are shown in Figure 16.13. 

Meta-directing deactivators, such as —CHO, act through a combination of electron-withdrawing inductive and resonance effects that reinforce each other and are felt most strongly at the ortho and para positions. As a result, the ortho and para intermediates are less stable so reaction with an electrophile occurs at the meta position (Figure 16.16). 

Substituents may change the reactivity of a molecule through steric or electronic effects or both. The latter include electrostatic, inductive, and resonance effects. The exploration to learn whether an LFER can be established may be very helpful in assessing the contributions from these sources and may thus provide an informative probe of the mechanism, particularly as regards electronic effects. The following items illustrate some uses of LFER correlations or deviations from them ... 

B. The Separation of Inductive and Resonance Effects Substituent Constants from Spectroscopic Studies. 

These constitute the only category of substituted alkylsulfinyl and alkylsulfonyl groups for which there appears to be appreciable information. Compounds containing these groups have often been used in spectroscopic studies of inductive and resonance effects... 

SOMe the enhancement in the meta-position is almost as large as in the para-position. The authors go on to show the applicability of op (g) values to certain solution processes, particularly those in non-aqueous solvents, but including the dissociation of thiophenols in 48% ethanol, the results of Bordwell and Andersen80 to which reference has been made earlier (Section III.A.1). A separation of field/inductive and resonance effects is also essayed for the gas-phase acidities of the phenols, and SOMe and S02Me feature in the discussion. There is reference to a oR° value of + 0.07 for SOMe as an unpublished result of Adcock, Bromilow and Taft (cf. 0.00 from Ehrenson and coworkers65 and — 0.07 from Katritzky, Topsom and colleagues128.)... 

The variation of grating efficiency with wavelength shown in Fig. 2c is based on a simple model of diffraction which is valid for a > A. For finer rulings, polarisafion and resonance effects complicate the situation (Palmer 2000). In the simple case, the efficiency drops to 40% of the peak (blaze) value at the following wavelengths (Schroeder 2000). 

Taft, following Ingold," assumed that for the hydrolysis of carboxylic esters, steric, and resonance effects will be the same whether the hydrolysis is catalyzed by acid or base (see the discussion of ester-hydrolysis mechanisms. Reaction 10-10). Rate differences would therefore be caused only by the field effects of R and R in RCOOR. This is presumably a good system to use for this purpose because the transition state for acid-catalyzed hydrolysis (7) has a greater positive charge (and is hence destabilized by —I and stabilized by +1 substituents) than the starting ester. 

While the ortho ionization data are generally fitted with notably poorer precision than for the m- and p- positions, there appear to be characteristic trends indicative of predominant contributions from polar and resonance effects. Thus, for ionization from the ring position (pyridinium ions), p yX" > whereas for ionization from the side-chain position (anilinium ions and phenols),... 

Finally, in this account of multiparameter extensions of the Hammett equation, we comment briefly on the origins of the a, scale. This had its beginning around 1956 in the a scale of Roberts and Moreland for substituents X in the reactions of 4-X-bicyclo[2.2.2]octane-l derivatives. However, at that time few values of o were available. A more practical basis for a scale of inductive substituent constants lay in the o values for XCHj groups derived from Taft s analysis of the reactivities of aliphatic esters into polar, steric and resonance effects . For the few o values available it was shown that o for X was related to o for XCHj by the equation o = 0.45 <7. Thereafter the factor 0.45 was used to calculate c, values of X from o values of XCH2 . ... 

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