Electron withdrawing substituent effect

An understanding of electron-donating and electron-withdrawing substituent effects is crucial to designing the synthesis of aromatic derivatives. For... 

Tributylstannyl ethers and dibutylstannylene acetals of a-D-glucopyranosides have been converted into 2,6-di-O-substituted derivatives in high yields with a wide range of electrophiles,74 107 151 152 but it should be noted that not all conditions result in selective reactions. 2,3,6-Tri-O-benzoyl derivatives can also be made in reasonable yields,74 153 constituting presumably another example of the electron-withdrawing substituent effect. 

Table 19 3 lists the ionization constants of some substituted benzoic acids The largest effects are observed when strongly electron withdrawing substituents are ortho to the carboxyl group An o nitro substituent for example increases the acidity of benzoic acid 100 fold Substituent effects are small at positions meta and para to the carboxyl group In those cases the values are clustered m the range 3 5-4 5... 

Hydrolysis reactions involving tetrahedral intermediates are subject to steric and electronic effects. Electron-withdrawing substituents faciUtate, but electron-donating and bulky substituents retard basic hydrolysis. Steric effects in acid-cataly2ed hydrolysis are similar to those in base-cataly2ed hydrolysis, but electronic effects are much less important in acid-cataly2ed reactions. Higher temperatures also accelerate the reaction. 

Table 36 summarizes the known annular tautomerism data for azoles. The tautomeric preferences of substituted pyrazoles and imidazoles can be rationalized in terms of the differential substituent effect on the acidity of the two NFI groups in the conjugate acid, e.g. in (138 EWS = electron-withdrawing substituent) the 2-NFI is more acidic than 1-NFI and hence for the neutral form the 3-substituted pyrazole is the more stable. 

Reactions of substituted cumyl benzoates in 50 50 trifluoroethanol-water show no effect of [NaN3] on the rate between 0 and 0.5 M. The product ratio, however, is highly dependent on the cumyl substituent. Electron-releasing substituents favor azide formation whereas electron-withdrawing substituents result in solvent capture. Formu-... 

Simple alkyl radicals such as methyl are considered to be nonnucleophilic. Methyl radicals are somewhat more reactive toward alkenes bearing electron-withdrawing substituents than towards those with electron-releasing substituents. However, much of this effect can be attributed to the stabilizing effect that these substiments have on the product radical. There is a strong correlation of reaction rate with the overall exothermicity of the reaction. Hydroxymethyl and 2-hydroxy-2-propyl radicals show nucleophilic character. The hydroxymethyl radical shows a slightly enhanced reactivity toward acrylonitrile and acrolein, but a sharply decreased reactivity toward ethyl vinyl ether. Table 12.9 gives some of the reactivity data. 

Similarly, carboxylic acid and ester groups tend to direct chlorination to the / and v positions, because attack at the a position is electronically disfavored. The polar effect is attributed to the fact that the chlorine atom is an electrophilic species, and the relatively electron-poor carbon atom adjacent to an electron-withdrawing group is avoided. The effect of an electron-withdrawing substituent is to decrease the electron density at the potential radical site. Because the chlorine atom is highly reactive, the reaction would be expected to have a very early transition state, and this electrostatic effect predominates over the stabilizing substituent effect on the intermediate. The substituent effect dominates the kinetic selectivity of the reaction, and the relative stability of the radical intermediate has relatively little influence. 

As to the electron-withdrawing substituents, the activating effect of a nitro group in the piperidino-dechlorination of 2-chloropyridine involves factors of 7.3 x 10 and 4.6 x 10 from the para and ortho positions, respectively. An ortho-cyano group was found to be... 

For the ordinary Diels-Alder reaction the dienophile preferentially is of the electron-poor type electron-withdrawing substituents have a rate enhancing effect. Ethylene and simple alkenes are less reactive. Substituent Z in 2 can be e.g. CHO, COR, COOH, COOR, CN, Ar, NO2, halogen, C=C. Good dienophiles are for example maleic anhydride, acrolein, acrylonitrile, dehydrobenzene, tetracya-noethylene (TCNE), acetylene dicarboxylic esters. The diene preferentially is of the electron-rich type thus it should not bear an electron-withdrawing substituent. 

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. 

They display the considerable trans-influence of hydride and aryl groups (the Pt-Cl bond lengths should be compared with the value of c. 2.31 A in PtCl4 ). The Pt-P bond lengths are more insensitive to the phosphine, but by synthesis of ds-Pt(PR3)(PR3)Cl2 [150] complexes, it has been possible to study the effect of electron-withdrawing substituents on the Pt-P bond, as well as on the trans-influence of the phosphine (Figure 3.94). 

The traditional means of assessment of the sensitivity of radical reactions to polar factors and establishing the electrophilicity or nucleophilieity of radicals is by way of a Hammett op correlation. Thus, the reactions of radicals with substituted styrene derivatives have been examined to demonstrate that simple alkyl radicals have nucleophilic character38,39 while haloalkyl radicals40 and oxygcn-ccntcrcd radicals " have electrophilic character (Tabic 1.4). It is anticipated that electron-withdrawing substituents (e.g. Cl, F, C02R, CN) will enhance overall reactivity towards nucleophilic radicals and reduce reactivity towards electrophilic radicals. Electron-donating substituents (alkyl) will have the opposite effect. 

---