Benzhydryl-cation

Substituent effects on rates (Nishida, 1967) and equilibria (Mindl and Vecera, 1972) of the heterolytic formation of benzhydryl cations, analogous to those obtained in the bromination of 1,1-diphenylethylenes, can be analysed in terms of selectivity relationships (50) and (51). Here ak is... 

The hydrolysis of diphenhydramine and analogues (11.24, Fig. 11.2) has been studied extensively [46 - 48], These compounds are essentially inert toward base-catalyzed hydrolysis, but do undergo proton-catalyzed hydrolysis, the mechanism of which is shown in Fig. 11.2. The reaction begins with protonation of the ether O-atom and continues with the irreversible heterolytic cleavage of the C-0 bond to produce the benzhydryl cation. This reaction is greatly facilitated by the weakening effect of the benzhydryl moiety on the adjacent C-0 bond. The benzhydryl cation itself is stabilized by resonance, which also explains why the reaction is facilitated. The last step is the for-... 

The intramolecular 4 + 3-, 3 + 3-, 4 + 2-, and 3 + 2-cycloaddition reactions of cyclic and acyclic allylic cations have been reviewed, together with methods for their generation by thermal and photochemical routes.109 The synthetic uses of cycloaddition reactions of oxyallyl cations, generated from polybromo and some other substrates, have also been summarized seven-membered rings result from 4 + 3-cycloadditions of these with dienes.110 The use of heteroatom-stabilized allylic cations in 4 + 3-cycloaddition reactions is also the subject of a new experimental study.111 The one-bond nucleophilicities (N values) of some monomethyl- and dimethyl-substituted buta-1,3-dienes have been estimated from the kinetics of their reactions with benzhydryl cations to form allylic species.112 Calculations on allyl cations have been used in a comparison of empirical force field and ab initio calculational methods.113... 

There are other instances, however, where unusually large extents of elimination are encountered which cannot be explained in this way. An example is provided by a study of the nucleophilic and elimination reactions of the dipentamethyl benzhydryl cation 69.247 Comparisons of pA"R values (from extrapolations based on the HR acidity function) with those of the unmethylated and partially methylated benzhydryl cations shown below, indicate that methylation cumulatively stabilizes the cation relative to the alcohol (possibly in part because the latter is destabilized by steric congestion). 

As has been discussed elsewhere, Fig. 7 demonstrates the basis for using reactions with azide ion as a clock for determining values of log kH2o in the range pATR = -5 to —15. However, the discussion above cautions against too narrow an interpretation of this figure. The correlations apply to benzhydryl cations and trityl cations and, as we have seen, other families of cations can lead to less ideal dependences of kn2o and, presumably, kAz on p/fR. 

Choride ion is considerably less reactive than the azide ion. Thus, although values of kc 1/ kn2o have been quite widely available from mass law effects of chloride ion on the solvolysis of aralkyl halides, normally the reaction of the chloride ion cannot be assumed to be diffusion controlled and the value of kn2o cannot be inferred, except for relatively unstable carbocations (p. 72). Mayr and coworkers251 have measured rate constants for reaction of chloride ion with benzhydryl cations in 80% aqueous acetonitrile and their values of logk are plotted together with a value for the trityl cation19 in Fig. 7. There is some scatter in the points, possibly because of some steric hindrance to reaction of the trityl cations. However, it can be seen that chloride ion is more... 

Compared with chloride, the bromide ion is more reactive by rather less than a factor of 10 with respect to the benzhydryl cations and by less than a factor of 2 for the trityl cation. Fluoride and acetate ions are a little less reactive than chloride ion toward the trityl cation (less than a factor of 10) but their equilibrium affinities for the ion are more than 106-fold greater.19,219... 

Mayr initially defined a set of electrophilic parameters for the benzhydryl cations using a reference nucleophile, which was chosen as 2-methyl-1-pentene.268,269 Values of E were then defined as log k/k0, where k0 refers to a reference electrophile (E= 0), which was taken as the 4,4 -dimethoxybenzhydryl cation. Plots of log k against E for other alkenes are thus analogous to the plots of logk against p fR in Fig. 7 except that the correlation is referenced to kinetic rather than equilibrium measurements. However, they differ from plots based on the Swain-Scott or Ritchie relationships in which log k is normally plotted against a nucleophilic parameter, that is, n or N+, rather than E. 

In practice, rate constants for only a limited range of benzhydryl cations could be measured for 2-methyl-1-pentene itself. However, it became apparent that if reaction of the cation occurred at a methylene group (=CH2) plots of... 

Fig. 8 Plots of log k versus E for the reaction tt-nucleophiles with benzhydryl cations.

In the most recent correlation analysis based on Equation (33) a basis set of 23 benzhydryl cations and 39 Jt-nucleophiles, for which extensive measurements are available, were selected to provide a set of reference parameters which would not require further modification as data was acquired for new... 

Just as N for a nucleophile can be determined from a plot of log k against E for a series of electrophiles, in principle, the value of E for an electrophile can be determined from the intercept (at E + N = 0) of a plot of log (k/s) versus N for a series of nucleophiles (or indeed, if need be, from the measurement for a single nucleophile). In this way E values have been determined for many electrophiles other than benzhydryl cations, including metal-coordinated cations,186 BF3-coordinated aldehydes,274 tropylium ions, and many benzylic-and heteroatom-substituted carbocations. In the low reactivity range... 

In addition to their reactions with alkenes and carbanions as nucleophiles benzhydryl cations react with hydride donors.282 284 These hydride transfer reactions show the same linear dependence of log k upon E as the reactions with alkenes and the same constant relative selectivity, that is with slopes of plots close to 1.0, for structures ranging from cycloheptatriene to the... 

Fig. 10 Plot of E parameters against open circles, benzhydryl cations fdled circles, trityl cations squares, organometallic cations fdled triangles, tropylium ions open triangles, flavylium, xanthylium and other O-, S-, or N-conjugated cations.

McClelland has studied the reaction of four primary amines with benzhydryl and trityl cations.4,302 Rate constants for reactions of most of the benzhydryl cations were close to their values for diffusion control. However, he was able to measure diffusion free rate constants for substituted trityl cations. There was a further complication, consistent with earlier measurements by Berg and... 

The interpretation of reactivities here provides a particular challenge, because differences in solvation and bond energies contribute differently to reaction rates and equilibria. Analysis in terms of the Marcus equation, in which effects on reactivity arising from changes in intrinsic barrier and equilibrium constant can be separated, is an undoubted advantage. Only rather recently, however, have equilibrium constants, essential to a Marcus analysis, become available for reactions of halide ions with relatively stable carbocations, such as the trityl cation, the bis-trifluoromethyl quinone methide (49), and the rather less stable benzhydryl cations.19,219... 

Because systematic variations in selectivity with reactivity are commonly quite mild for reactions of carbocations with n-nucleophiles, and practically absent for 71-nucleophiles or hydride donors, many nucleophiles can be characterized by constant N and s values. These are valuable in correlating and predicting reactivities toward benzhydryl cations, a wide structural variety of other electrophiles and, to a good approximation, substrates reacting by an Sn2 mechanism. There are certainly failures in extending these relationships to too wide a variation of carbocation and nucleophile structures, but there is a sufficient framework of regular behavior for the influence of additional factors such as steric effects to be rationally examined as deviations from the norm. Thus comparisons between benzhydryl and trityl cations reveal quite different steric effects for reactions with hydroxylic solvents and alkenes, or even with different halide ions... 

Nevertheless, the acidity measurements based on the use of the benzhydryl cation indicator family87 show that the upper acidity limit of the HF-SbF5 system is reached with 10 mol% of SbF5. The weakest indicator available is protonated 4,4 -dimethoxy-benzhydryl cation (pA BH+ —23) and could not be further protonated, even in the most concentrated HF-SbF5 solutions. 

Dinitrobenzofuroxan (DNBF) is known as a superelectrophile due to its high reactivity both as an electrophile and in its pericyclic addition reactions. NMR studies show that reaction with 2-aminothiazole and its 4-methyl derivative yield anionic carbon-bonded adducts such as (11) by reaction at the 5-position, whereas the 4,5-dimethyl derivative reacts via the exocyclic amino group. Kinetic studies of the first two compounds, both in acetonitrile and in 70 30 (v/v) water-DMSO, have been used to assess their carbon nucleophilicities and place them on the Mayr nucleophilicity scale.55 In a related study, the nucleophilic reactivity, in acetonitrile, of a series of indoles with both DNBF and with benzhydryl cations have been compared and used to determine nucleophilicity parameters for the indoles.56... 

The kinetics of reaction of four indoles with a number of benzhydryl cations has allowed the determination of the nucleophilicity parameters N and S for these reactions.49 Kinetic data from the reaction of a number of indoles with 4,6-dinitroben-zofuroxan then allow determination of their N values. Correlation of these data with those for protonation at C(3) of 5-substituted indoles and 5-substituted 2-methylindoles... 

Equation 2.9 can also be interpreted as follows. Regardless of which nucleophile enters into an SN1 reaction with a given alkylating agent, the substitution product is produced with the same rate. Figure 2.12 illustrates this using as an example SN1 reactions of two different nucleophiles with P1l,CH—Cl. Both take place via the benzhydryl cation Ph2CH . In the first... 

Fig. 2.12. Rate and selectivity of SN1 reactions. Both reactions 1 and 2 take place via the benzhydryl cation. Both reactions (with pyridine and tri-ethylamine) take place with the same rate constant. The higher nucleophilicity of pyridine does not become noticeable until experiment 3, the "competition experiment" The pyridinium salt is by far the major product.

The situation is different in experiment 3 of Figure 2.12. There, both SN1 reactions are carried out as competitive reactions benzhydryl chloride heterolyzes (just as fast as before) in the presence of equal amounts of both amines. The benzhydryl cation is now intercepted faster by the more nucleophihc pyridine than by the less nucleophilic triethylamine. The major product will be determined by the relative rates of the reaction of each nucleophile with the benzhydryl cation. The major product in this case is the pyridinium salt. 

Allyl halides heterolyze just as easily as benzyl halides because they also produce a resonance-stabilized carbenium ion. Even faster heterolyses are possible when the charge of the resulting carbenium ion can be delocalized by more than one unsaturated substituent and can thereby be stabilized especially well. This explains the remarkably high SN1 reactivities of the benzhydryl halides (via the benzhydryl cation) and especially of the triphenylmethyl halides (via the trityl cation) ... 

Fig. 14.16. Regioselective pinacol rearrangement of an asymmetric glycol. As in the case depicted in Figure 14.15, the reaction proceeds exclusively via the benzhydryl cation.

Fig. 11.13. Regioselectivity of the pinacol rearrangement of an asymmetric glycol. The more stable carbenium ion is formed under product-development control. Thus, the benzhydryl cation B is formed here, while the tertiary alkyl cation D is not formed.

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