Nucleophilic reaction inductive effects

He w as one of the founders of mechanistic organic chemistry and was responsible for developing the electronic theory of organic reactions, including ideas such as nucleophiles, electrophiles, inductive effects and resonance effects. With Cahn and Prolog he devised the priority rules for defining stereochemistry. 

The carbonyl group also possesses electrophilic properties at the carbon atom and nucleophilic properties at the oxygen atom. Nucleophilic attack of the carbonyl group is favored if this is attached to an aromatic ring (inductive effect) and there is also a methoxy or phenolic OH group present in the 4-position. Changing a neutral reaction medium by proton addition has the same effect. 

Oae and Khim measured the rates of hydrolysis of chlorophenyl phenyl sulfoxides and sulfones with hydroxide ion in aqueous DMSO at 158 °C. Both SOPh and S02Ph were found to activate the nucleophilic substitution from ortho- and para-positions, but the effect of SOjPh was considerably larger than that of SOPh. The results were interpreted in terms of 7t(pd) conjugation in the intermediate complexes. In a later paper it was shown that the introduction of a methyl group ortho to SOPh or S02Ph slightly retards the above and related reactions but this was attributed to the inductive effect of Me rather than steric inhibition of 7t(pd) conjugation (Section III.A.l). 

Peroxybenzoic acid readily oxidizes aryl and alkyl sulphoxides in acetone, methylene chloride or chloroform solutions, to the sulphone in high yield . The reaction is second order and acid catalysed as is the reaction with peracetic acid . The rate of oxidation is about five times faster than when peracetic acid is used. Other work considering the oxidation of sulphoxides with peracids gathered kinetic evidence and showed that the reaction was indeed second order and that the reaction involved nucleophilic attack by the sulphoxide sulphur atom on the peracid moiety. A further study by the same authors showed that with benzyl and phenyl alkyl sulphoxides the rate of reaction was very sensitive to the inductive effect of the alkyl group. Support for the nucleophilic attack by the sulphur atom on the peracid in acidic solution was forthcoming from other sources . ... 

Direct metalation at the /8-carbon of azoles can also occur, although it is a much less facile process than that for the adjacent a-carbon, because of the greater charge density at what is normally a nucleophilic center in enamine-type reactions. Thus in order for reaction to occur, it is usually necessary to either block the a-position or activate the /3-site. If both factors are accommodated than /8-metalation occurs readily, and thus 3,4-disubstituted-2(3//)-thiazolethiones undergo direct lithiation with lithium diisopropylamide (LDA) at the 5-position, which is activated by the inductive effect of the adjacent sulfur (Scheme 4) (80S800). 

The inductive effect is a priori unfavorable for an Sn2 substitution. Moreover, the strengthening of the C—bond disfavors its cleavage. Furthermore, the electronic as well as the steric repulsion phenomena inhibit the attack of the nucleophile. An important decreased rate is observed in the Sn2 reactions on carbons bearing a fluoroalkyl or CF3 group (Figure 1.13). 

In a preliminary step, adjacent ester groups undergo initial hydrolysis or alcoholysis, by the base, to the oxide anion. This step is reasonable for carboxylic esters, which are rapidly hydrolyzed under the conditions usually employed, but is rather more surprising for sulfonic esters, which are usually hydrolyzed only slowly by the nucleophilic attack on sulfur required for this reaction. With these disulfonic esters, the ease of hydrolysis has been explained by the inductive effect of the adjacent sulfonyloxy group.7... 

Unsaturated fluorinated compounds are fundamentally different from those of hydrocarbon chemistry. Whereas conventional alkenes are electron rich at the double bond, fluoroal-kenes suffer from a deficiency of electrons due to the negative inductive effect. Therefore, fluoroalkenes react smoothly in a very typical way with oxygen, sulfur, nitrogen and carbon nucleophiles.31 Usually, the reaction path of the addition or addition-elimination reaction goes through an intermediate carbanion. The reaction conditions decide whether the product is saturated or unsaturated and if vinylic or allylic substitution is required. Highly branched fluoroalkenes, obtained from the fluoride-initiated ionic oligomerization of tetrafluoroethene or hexafluoropropene, are different and more complex in their reactions and reactivities. 

Since tJtiis reaction is an equilibrium, the amount of cyanohydrin formed from any given carbonyl compound will depend on the relative stabilities of the carbonyl compound itself and the product. There can be many substituents X on a carbonyl compound R.CO.X, such as Cl, Me, NH2, Ph, OEt, H. Some have inductive effects, some conjugate with the carbonyl group. Some stabilise RCOX making it less reactive. Others activate it towards nucleophilic attack. Arrange the compounds RCOX, where X can be the substituents listed above, into an order of reactivity towards a nucleophile. 

A well understood case is that of quinoline reaction at position 2 is kinetically favored as compared with reaction at position 4, but the adduct from the latter is thermodynamically more stable. This situation, where the site of attack leading to the more stable adduct is the y position, is analogous with those regarding the formation of Meisenheimer adducts from benzene and pyridine derivatives and RCT nucleophiles. Presumably, with quinoline kinetic control favors the position that is more strongly influenced by the inductive effect of the heteroatom. The fact that position 2 of quinoline is the most reactive toward nucleophilic reagents is probably related to the lower 71-electron density at that position.123 However, the predominance of the C-4 adduct at equilibrium can be better justified by the atom localization energies for nucleophilic attachment at the different positions of quinoline. Moreover, both 7t-electron densities and atom localization energies indicate position 1 of isoquinoline to be the most favored one for nucleophilic addition. 

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