Inductive stabilization

The first generalization is illustrated by the behavior of the 2- and 4-vs. the 3-derivatives of pyridine, the second by the reactivity of 4- vs. 2-substituted pyridines, the third by the relation of 4- vs. 2-derivatives of pyrimidine, and the fourth by the appreciable reactivity of 3-substituted pyridines or 5-substituted pyrimidines compared to that of their benzene analogs. Various combinations of azine-nitrogens in other poly-azines supply further examples. Theoretical aspects of (1), (2) and (3) are discussed in Section II, B, 2. The effect involved in (4) is believed to be more the result of the inductive stabilization of an adjacent negative chaise in the transition state (cf. 251) than of the electron deficiency created in the ground state (cf. 252). The quantitative relation between inductive stabihzation and resonance stabilization is not precisely defined by available data. However, a... 

CT-bond or field effect, is considered herein to arise primarily from inductive stabilization of the resonating negative charge in the transition state. 

Figure 6.11 A comparison of inductive stabilization for methyl, primary, secondary, and tertiary carbocations. The more alkyl groups there are bonded to the positively charged carbon, the more electron density shifts toward the charge, making the charged carbon less electron-poor (blue in electrostatic potential maps).

For the deprotonation of less acidic precursors, which do not lead to mesomerically stabilized anions, butyllithium/TMEDA in THF or diethyl ether, or the more reactive, but more expensive,. seobutyllithium under these conditions usually are the most promising bases. Het-eroatomic substitution on the allylic substrate, which docs not contribute to the mesomeric or inductive stabilization often facilitates lithiation dramatically 58. In lithiations, in contrast to most other metalations, the kinetic acidity, caused by complexing heteroatom substituents, may override the thermodynamic acidity, which is estimated from the stabilization of the competing anions. These directed lithiations59 should be performed in the least polar solvent possible, e.g.. diethyl ether, toluene, or even hexane. 

Methyl ketones are degraded to the next lower carboxylic acid by reaction with hypochlorite or hypobromite ions. The initial step in these reactions involves base-catalyzed halogenation. The a-haloketones are more reactive than their precursors, and rapid halogenation to the trihalo compound results. Trihalomethyl ketones are susceptible to alkaline cleavage because of the inductive stabilization provided by the halogen atoms. 

Quantitative assessment of the electrophilic character of various types of phosphenium ions has been attempted using computational studies on hydride and halide exchange reactions, and the results attribute to 1,3,2-diazaphospholenium ions a lower electrophilicity (and thus higher stability) than other types of phosphenium ions [20, 66], The gain in stability due to aromatic -delocalization is predicted to be somewhat larger than inductive stabilization resulting from exhaustive A-alkylation of the parent diaminophosphenium ion, [P(NH2)2]+. 

Therefore deprotonation is a method used most often for the preparation of resonance and inductively stabilized carbanions. 

Branched iV-chlorohydroxamic esters exhibit much lower carbonyl frequencies in their IR spectra. Series of Ai-(phenylethyloxy)amides (Table 2, entries 1-7) and Af-butoxy-amides (Table 2, entries 12-16) show a clear movement to lower carbonyl stretch frequencies with branching alpha to the carbonyl, in accord with greater inductive stabilization of the polar resonance form III of the carbonyl (Figure la). Neopentyl (entry 17) is a special case. While the group should contribute much more inductive stabilization than ethyl, its carbonyl stretch frequency is higher. Similar changes have been noted in the IR spectra of branched ketones and have been ascribed to a degree of steric hindrance to solvation and therefore destabilization of the polar resonance form Dl". ... 

The relatively easy decarboxylation of a- (682) and y-carboxylic acids is a result of inductive stabilization of intermediate ylides of type (683) (cf. Section 3.2.1.8.2). By carrying out the decarboxylation in the presence of aldehydes or ketones, products of type (684) are formed (Hammick Reaction). 

A situation in which the pyridine nitrogen is not strictly the reaction site, but where the inductive stabilization of negative charge by the azonium site is the key role leading to reactivity is that of pyridine ylide formation, by deprotonation of the 2- and 6-positions of 3-substituted 1-methylpyridinium ions in D20 buffer solution catalyzed by OD. A reasonable correlation is produced using ox (p = 8.9) for the reactivity of... 

Many carbanionic nucleophiles that would be considered too hard to react as Michael donors can be made into effective reagents for conjugate addition reactions by appending resonance or inductively stabilizing groups to soften their intrinsic Lewis basicity. Such stabilized anionic Michael donors include enolates, alkylthio-substituted carbanions, ylides and nitro-substituted carbanions. 

In the absence of hyperconjugative and internal participation, there is essentially no silicon /1-effect. The inductive effect of the Me3Si group is essentially zero. This agrees with the calculations of Ibrahim and lorgensen39, which predict no inductive stabilization for secondary systems. 

The observed enhanced acidity of H4 and H5 of the 1,2,3-triazole 1-oxides 456 may be explained by inductive stabilization of the anion negative charge by the adjacent positive nitrogen atoms as discussed in Section 1.4.3. The relative acidity of H4 and H5 conforms to that predicted in Section 1.4.3.1 as reflected by the relative H/D exchange rate of H4 and... 

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