Benzhydryl chlorides, solvolysis

It was of course not possible to introduce the deuterium atoms closer than three bonds away from the center of reaction , but the attenuation of the inductive effect with distance was not expected to affect the validity of the conclusions, especially considering the work of Streit-wieser and Klein (1964), who found that the isotope effect per deuterium in the solvolysis of benzhydryl chloride only decreased from 1 9% for deuterium in the ortho positions to l-5% for deuterium in the meta positions. 

Suggestive evidence for the protonation of diphenylcarbene was uncovered in 1963.10 Photolysis of diphenyldiazomethane in a methanolic solution of lithium azide produced benzhydryl methyl ether and benzhydryl azide in virtually the same ratio as that obtained by solvolysis of benzhydryl chloride. These results pointed to the diphenylcarbenium ion as an intermediate in the reaction of diphenylcarbene with methanol (Scheme 3). However, many researchers preferred to explain the O-H insertion reactions of diarylcarbenes in terms of electrophilic attack at oxygen (ylide mechanism),11 until the intervention of car-bocations was demonstrated by time-resolved spectroscopy (see Section III).12... 

The normal effect of NO2 on S l solvolysis of substrates such as benzhydryl chloride is to retard reaction. Thus in the ethanolysis of XQdLjCIIPhCI, logfc values (first-order rate coefficients, s 1) are as follows (50 °C) H, —3.05 m-N()2, —5.64 p-NCT. —5.99198. The p value for this reaction is about —3.7, so the logfc values for the m-NCT and p-NCT derivatives correspond fairly closely to the a values of 0.71 (or 0.73) and 0.78, respectively (Section III.B). This reaction is, of course, strongly accelerated by —R para-substituents through cross-conjugation in the carbocationic transition state (Section n.A). 

The amino group and its simple relatives, e.g. Me2N and PhNH, strongly accelerate the solvolysis of substrates such as benzhydryl chloride or tertiary cumyl chloride in solvents... 

Rate constants and products have been reported for solvolysis of benzhydryl chloride and /7-methoxybenzyl chloride in 2,2,2-trifluoroethanol (TFE)-water and-ethanol, along with additional kinetic data for solvolysis of r-butyl and other alkyl halides in 97% TFE and 97% hexafluoropropan-2-ol. The results are discussed in terms of solvent ionizing power Y and nucleophilicity N, and contributions from other solvation effects are considered. Comparisons with other 3 nI reactions show that the solvolyses of benzhydryl chloride in TFE mixtures are unexpectedly fast an additional solvation effect influences solvolysis leading to delocalized cations. 

Benzhydrylamines are better suited than benzylamines as acid-labile linkers for amines. The MBHA linker ( methylbenzhydrylamine ), which is usually used to prepare peptide amides (see Section 3.3), can also be used as a linker for amines (Entry 1, Table 3.21). Hydrogen fluoride is, however, required as the cleavage reagent. Easier to cleave are alkoxy-substituted benzhydrylamines (Entries 2-5, Table 3.21), which can be prepared from the corresponding benzhydryl chlorides [263] or by reductive alkylation [410] or solvolysis [411] of the Rink amide linker. In the case of benzhydrylamines linked to polystyrene as benzyl ethers, treatment with TFA can lead to the release of the linker into solution (acidolysis of the benzylic C-O bond, see Figure 3.18). 

Such cases are not uncommon, but full quantitative treatments are rare, since often relatively large amounts of Y must be added to obtain measurable effects. Complications may then arise from the effects of the added Y on the nature of the medium (see Chapters 2 and 3). These are particularly notable when Y and I are charged, as is often the case. Under those circumstances, maintenance of the constant ionic strength of the medium with a known non-participating ionic species is essential. The classic case of common ion depression in solvolysis of benzhydryl chloride is dealt with in Chapter 2. A more recent example of this kind of treatment with neutral reactants occurs in the elucidation of the mechanism of olefin metathesis [20], catalysed by the ruthenium methylidene 9, Scheme 9.6. With ca. 5% of 9, disappearance of diene 10 was clearly not first order. However, reactions run in the presence of large excesses of phosphine 11 were much slower and showed first-order kinetics. The plot of kQ K against 1/ [ 11 ] was linear, consistent with dissociation of 9 to yield an active catalytic species prior to engagement with the diene, with k t [11] 3 > fc2[diene]. Because first-order kinetics were observed under these conditions, determination of order with respect to the catalytic species (as well as the diene) was simplified, and an outline for the mechanism could be constructed (see also Chapter 12 for more detailed consideration of catalysed olefin metathesis). 

To assess the accuracy and precision of these other factors influencing relative reactivity. Recently, solvent effects were shown to produce important variations in the relative reactivity of very similar molecules. Thus the relative influence of m-methyl and m-t-butyl substituents on the rate of solvolysis of benzhydryl chloride depends on the solvent (Shiner and and Verbanic, 1957). Less remarkable but equally important variations in reactivity were detected among the p-alkylated benzhydryl chlorides (Shiner and Verbanic, 1957 Berliner and Chen, 1958). A full analysis of solvent influences (Clement et al., 1960) requires much detailed... 

Fig. 8 The plot of the log(/c//co) for the solvolysis of benzhydryl chlorides in 85% aqueous acetone (85A) at 0°C against the sum of the a values the reference correlation (p ) line was drawn for the plots ( ) for the symmetrically disubstituted (X = Y) series, and typical concave correlations for Y = p-MeO and Y = /7-NO2 series. Data taken from Fox and Kohnstam (1964) and Fujio et al. (unpublished).

Ionization is exothermic and favored at lower temperatures in systems such as trityl, alkoxycarbenium, and benzhydryl derivatives which generate stabilized carbenium ions due to their electron-donating substituents. The exothermicity of ionization of benzhydryl species with BCl3 in CH2CI2 decreases from AH = -62 kJ/mol for di(p-anisyl) to -22 kJ/ mol for less stabilized p-tolyl and phenyl derivatives, and to approximately -8 kJ/mol for unsubstituted benzhydryl chloride [193]. These values, based on the solvolysis rates, extrapolate to AH = -12 kJ/mol for cumyl chloride (HCl adduct of a-methylstyrene) and AH = 0 kJ/mol for 1-phenyl-ethyl chloride (styrene adduct) and ( -butyl chloride (isobutene adduct) [240]. The reported entropies of ionization do not vary significantly and... 

Kinetic studies also provide other evidence for the SnI mechanism. One technique used E NMR to follow the solvolysis of trifluoroacetyl esters. If this mechanism operates essentially as shown on p. 432, the rate should be the same for a given substrate under a given set of conditions, regardless of the identity of the nucleophile or its concentration. In one experiment that demonstrates this, benzhydryl chloride (Ph2CHCl) was treated in SO2 with the nucleophiles fluoride ion, pyridine, and triethylamine at several concentrations of each nucleophile. In each case the initial rate of the reaction was approximately the same when... 

A further possibility is bimolecular displacement of nitrogen from the benzhydryldiazonium ion. Again, this may reasonably be ruled out on the basis of the stability of the carbonium ion. Since benzhydryl chloride is known to solvolyse exclusively by an S l mechanism in ethanol, the benzhydryldiazonium ion with its superior leaving group should, a fortiori, do so. This conclusion is confirmed by Bethell and Callister s finding that in aqueous acetonitrile the reaction of DDM with dissociated toluenesulphonic acid leads to the same product distribution as the solvolysis of benzhydryl toluenesulphonate (p. 354). 

The ambiguity concerning the significance of the observed hydrocarbon products extends to the products of reaction with the solvent. In hydroxylic solvents there are several examples of well-established carbenoid reactions leading to alcohols or ethers as products (Kirmse, 1963,1964 Bethelle aZ., 1965). The photolysis of diphenyldiazomethane in the presence of lithium azide in methanol leads to the same proportions of benzhydryl azide and benzhydryl methyl ether as does the solvolysis of benzhydryl chloride under the same conditions (Kirmse, 1963). 

Effect of o-Deuteration in f ar -Alkyl Benzhydryl Chlorides on Solvolysis Rate... 

That the situation may be even more complex than it seems is suggested by some recent work of Pocker (98a) on the solvolysis of variously deuterated benzhydryl chlorides, also in 80% aqueous acetone.. Comparing the rates of solvolysis, racemization, and radio-chloride exchange, he concludes that solvolysis follows the prior formation of a rather loose ion-pair. Moreover, the isotope effect on solvolysis due to a-deuteration (k /ko = 1.15) is the same as that on the more rapid racemization, suggesting that the isotope effect in solvolysis can nearly be identified with that on an ionization pre-equilibrium. In addition, nuclear deuteration, according both to Pocker and to Klein... 

We have previously discussed the possibilities of racemization or inversion of the product RS of a solvolysis reaction. However, the formation of an ion pair followed by internal return can also affect the stereochemistry of the substrate molecule RX. Cases have been found where internal return racemizes an original optically active RX, an example being solvolysis in aqueous acetone of a-p-anisylethyl p-nitrobenzoate, while in other cases partial or complete retention is found, for example, solvolysis in aqueous acetone of p-chloro benzhydryl p-nitrobenzoate. the pathway RX R+X some cases where internal return involves racemization, it has been shown that such racemization is faster than solvolysis. For example, optically active p-chlorobenzhydryl chloride racemizes 30 times faster than it solvolyzes in acetic acid. ... 

A new Y solvolysis scale has been developed for benzylic species with extensive charge delocalization, based upon the solvolyses of some benzhydryl bromides and /-butyl(2-naphthyl)methyl bromides.39 Chlorides have negative salt effects on the ionization of benzhydryl bromide in 7-butyrolactone.40 The X-ray structure of the dimerization product of l,8-bis(dhnethylammonio)-4-naphthyl(phenyl)methyl carbocation has been determined it appears to be formed via a 4n + 2n-cycloaddition mechanism 41... 

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... 

A critical analysis of the log ks = st(Ef + Nf) equation has been published96 and new equations that provide more reliable E and Nf values have been suggested. The proposed Ef and Nf values are Ef = log rci/bohcs °c 1 -87 and Nf = 6.14 + log nx/any soivent/25°o where RC1 and BX are chlorides and benzhydryl substrates, respectively. A new equation, log /-aikyix/any solvent - 14 + N f where N = 3.90 + Yany solvent + logfc(X/Cl) is proposed for the solvolysis of /-butyl chloride and similar substrates. 

A very interesting paper80 reported studies of the reactions of several substituted benzhydryl carbenium ions, generated by laser flash photolysis, with halide ions in several solvents. This work provided the nucleophilicity N of chloride and bromide ions in several solvents. These data, along with the ionization rate constants and the solvolysis rate constants for the reactions of substituted benzyhdryl halides, was used to construct quantitative energy surfaces for the. S N 1 reactions of substituted benzhydryl halides in several solvents. 

Numerous solvolytic studies on diarylmethyl derivatives have been carried out under a variety of conditions. The analysis of substituent effects in the solvolysis of the monosubstituted chlorides [22] was reported earlier (Yukawa and Tsuno, 1959 Yukawa etal., 1966). The purpose of this analysis is to clarify the effect of a fixed substituent Y in one ring on the substituent effect of the variable substituents X on the second ring. Three extensive sets of kinetic data for the solvolysis of X, Y-disubstituted benzhydryl systems under fixed conditions have been reported one for the ethanolysis (Nishida, 1967), one for the chloride hydrolysis in 85% aqueous acetone at 0°C (Fox and Kohnstam, 1964) and one for the bromide hydrolysis (Mindl et al., 1972 Mindl and... 

Ruasse (1993) pointed out that substituent effects (Mindl and Vecera, 1971, 1972 Mindl, 1972) on the equilibria for forming benzhydryl cations, by analogy with those obtained in the solvolyses of chlorides (Nishida, 1967), can be analysed in terms of the selectivity-reactivity relationship (3). The values of the selectivity coefficient S = 0.34 (thermodynamic) and S = 0.52 (for the solvolysis), show elegantly that the transition-state shift is significant in this process. 

MeO , OH , or EtO and methyl fluoride, anisole, and 4-fluoroanisole on the gas-phase 5 2 reactions between dimethylmethylphosphonate and methylformate and HOO versus HO , MeO , or EtO in an attempt to discover the origin of the O -effect on the Sf 2 reaction of carbanions with 4-substituted benzyl chlorides in liquid ammonia " on the solvolysis reaction and the 2 reaction between phenoxide ions, and both neutral and negatively charged amines and 4-substituted benzyl chlorides in liquid ammonia on the ionization rates (the step) of the 5" 1 reactions of many substituted trityl halides and carboxylates in aqueous acetone and in aqueous and pure acetonitrile in the presence of piperidine on the ionization rates ( i) of the 5 reactions of various diarylmethyl chlorides in the presence of piperidine, pyridine, or PPh3 in several dipolar aprotic solvents on the solvolyses of X,Y-substituted benzhydryl acetates in various aqueous MeOH and EtOH solutions and on the dispersions observed in Grunwald-Winstein correlations of 5 solvolyses of substrates with substituents containing adjacent tt-electrons. ... 

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