Carbocation inductive effects

We can imagine the transition state for alkene protonation to be a structure in which one of the alkene carbon atoms has almost completely rehybridized from sp2 to sp- and in which the remaining alkene carbon bears much of the positive charge (Figure 6.16). This transition state is stabilized by hyperconjuga-lion and inductive effects in the same way as the product carbocation. The more alkyl groups that are present, the greater the extent of stabilization and the faster the transition state forms. 

For S vl attack, considerable charge separation has taken place in the T.S. (cf. p. 81), and the ion pair intermediate to which it gives rise is therefore often taken as a model for it. As the above halide series is traversed, there is increasing stabilisation of the carbocation moiety of the ion pair, i.e. increasing rate of formation of the T.S. This increasing stabilisation arises from the operation of both an inductive effect,... 

Alkyl groups are said to have a positive inductive effect. This means they are electron-donating and can push electrons onto the positively charged carbon atom, thus stabilising the carbocation. It follows that tertiary carbocatlons, with their three alkyl groups, are the most stable species and that primary carbocatlons, with just one alkyl group, are the least stable species. This suggests that tertiary haloalkanes are most likely to react with a nucleophile via an Sj. 1 mechanism. 

The carbocations that are formed to generate these two products are shown on the left. You will recall that alkyl groups can exert a positive inductive effect (see p. 59), i.e. they can push electrons towards the positively charged carbon atom in the carbocation and so stabilise it. Therefore carbocation A will be more stable than carbocation B because it has two alkyl groups directly attached to the positively charged carbon atom, whereas there is only one alkyl group in carbocation B. 

Through resonance, halogen tends to stabilise the carbocation and the effect is more pronounced at ortho- and para- positions. The inductive effect is stronger than resonance and causes net electron withdrawal and thus causes net deactivation. The resonance effect tends to oppose the Inductive effect for the attack at ortho- and para-positions and hence makes the deactivation less for ortho- and para-attack. Reactivity Is thus controlled by the stronger Inductive effect and orientation Is controlled by resonance effect. 

Experimental evidence concerning the relative rates for SnI reactions of halides is listed in Table 6.7. The differences in reactivity reflect stmctural features that stabilize the intermediate carbocation. Carbocations are stabilized by the electron-donating effect of alkyl groups, which help to disperse the positive charge. We have noted that alkyl groups have a modest electron-donating effect (see Section 4.3.3). In carbocations, this is not a simple inductive effect, but results from overlap of the a C-H (or C-C) bond into the vacant p orbital of the carbocation. This leads to a favourable delocalization of the positive charge. 

The vinyl halide product is then able to react with a further mole of HX, and the halide atom already present influences the orientation of addition in this step. The second halide adds to the carbon that already carries a halide. In the case of the second addition of HX to RC CH, we can see that we are now considering the relative stabilities of tertiary and primary carbocations. The halide s inductive effect actually destabilizes the tertiary carbocation. Nevertheless, this is outweighed by a favourable stabilization from the halide by overlap of lone pair electrons, helping to disperse the positive charge. 

The presence of fluorine strongly destabihzes a carbocation centered on the jS carbon because only the inductive effect takes place. " The effect on solvolysis or protonation reaction of double bonds can be very important. The destabilization of carbenium and alkoxycarbenium ions plays an importantrole in the design of enzyme inhibitors (cf Chapter 7) and in the hydrolytic metabolism of active molecules (cf. Chapter 3). 

Substituent effects Carbocations are formed in the S l reactions. The more stable the carbocation, the faster it is formed. Thus, the rate depends on carbocation stability, since alkyl groups are known to stabilize carbocations through inductive effects and hyperconjugation (see Section 5.2.1). The reactivities of SnI reachons decrease in the order of 3° carbocation > 2° carbocation > 1° carbocation > methyl cation. Primary carbocation and methyl cation are so unstable that primary alkyl halide and methyl halide do not undergo SnI reachons. This is the opposite of Sn2 reactivity. 

Fluoroalkylamines react with nitrous acid to produce the corresponding unstable fluoroahphatic diazomum ions Placement of the tnfluoromethyl group at a carbon position a, (i, or y to a diazomum ion was used to probe the inductive effect on the chemistry of the transient carbocation resulting from dediazomation [7] If the fluoroalkyl group is bound to the same carbon as the amino group, conversion to the more stable diazo compound occurs For example, 4-diazo-l,l,l,2,2-pentafluoro-3-pentafluoroethyl-3-tnfluoromethylbutane is obtained from the reaction of the poly-fluoroalkylamine salt with sodium nitrite [8, 9] (equation 8)... 

The effect of monofluorination on alkene or aromatic reactivity toward electrophiles is more difficult to predict Although a-fluonne stabilizes a carbocation relative to hydrogen, its opposing inductive effect makes olefins and aromatics more electron deficient. Fluorine therefore is activating only for electrophilic reactions with very late transition states where its resonance stabilization is maximized The faster rate of addition of trifluoroacetic acid and sulfuric acid to 2-fluoropropene vs propene is an example [775,116], but cases of such enhanced fluoroalkene reactivity in solution are quite rare [127] By contrast, there are many examples where the ortho-para-dueeting fluorine substituent is also activating in electrophilic aromatic substitutions [128]... 

These data show a decrease in the extent of /J-silyl stabilization with successive methyl substitution. The methyl (and phenyl) substituents stabilize the carbocation by polarization and inductive effects, resulting in a delocalization of positive charge away from the carbocation, and therefore a reduction in hyperconjugative interaction with the fi-substituent bond. 

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