Benzhydryl halides

The reaction of sodium borohydride with benzhydryl halides under solvolytic conditions has been reinvestigated.132 Contrary to the literature, NaBHU was not found to be a convenient trap for benzhydryl carbocations. 

The O-alkylation of carboxylates is a useful alternative to the acid-catalyzed esterification of carboxylic acids with alcohols. Carboxylates are weak, hard nucleophiles which are alkylated quickly by carbocations and by highly reactive, carbocation-like electrophiles (e.g. trityl or some benzhydryl halides). Suitable procedures include treatment of carboxylic acids with alcohols under the conditions of the Mitsunobu reaction [122], or with diazoalkanes. With soft electrophiles, such as alkyl iodides, alkylation of carboxylic acid salts proceeds more slowly, but in polar aprotic solvents, such as DMF, or with non-coordinating cations acceptable rates can still be achieved. Alkylating agents with a high tendency to O-alkylate carboxylates include a-halo ketones [42], dimethyl sulfate [100,123], and benzyl halides (Scheme 6.31). 

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. 

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) ... 

Other compounds that have been studied are benzhydryl halides [132,133] and aiOt -dibromoxylenes [134]. Trifluoromethylbenzene, chlorodifluoromethylbenzene, and... 

Triebe EM, Borhani KJ, Hawley MD (1979) Electrochemistry of the carbon-halogen bond. 9-Fluorenyl and benzhydryl halides in dimethyUbimamide at platinum and vitreous carbon electrodes. J Am Chem Soc 101 4637 645... 

The photogenerations of benzhydrilium ions has been the subject of studies. For example, benzhydryl halides were subjected to photolysis and the chemistry was studied by femtosecond to millisecond transient absorption spectroscopy. " The results indicate that radical pairs are initially formed by homolysis of the carbon-halogen bond. 

The anion of DMSO undergoes a phenylation reaction with aryl halides under sunlight stimulation38. The presence of benzhydryl methyl sulfoxide (maximum yield 5%) in all runs, the sunlight activation, the order of reactivity of halobenzenes (I > Br > Cl), the inhibition of the reaction with oxygen, all hint at the SRN139-44 mechanism (Scheme 3). 

Bromoadamantane and 1-bromoadamantane are reduced to adamantane in yields of 84% and 79%, respectively, when treated with triethylsilane and catalytic amounts of aluminum chloride.186 Similar treatment of benzhydryl chloride and exo-2-bromonorbomane gives the related hydrocarbons in yields of 100% and 96%, respectively.186 In contrast, 2-bromo-l-phenylpropane gives only a 43% yield of 1-phenylpropane the remainder consists of Friedel-Crafts alkylation products.186 Some alkyl halides resist reduction by this method, even when forcing conditions are employed. These include p-nitrobenzyl bromide, 3-bromopropanenitrile, and 5-bromopentanenitrile.186... 

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. 

Polystyrene-bound benzhydryl- or trityl halides react much more rapidly with carboxylates than chloromethyl polystyrene, and the base used to form the carboxylate no longer plays a decisive role in these reactions (see Experimental Procedure 13.7). Support-bound phenyldiazomethanes have been used to prepare esters directly from carboxylic acids under mild reaction conditions. Unfortunately, the diazomethanes required are not easy to prepare, and have not yet found widespread application. 

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... 

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... 

Amino-1,2,4-thiadiazoles (16) are alkylated at the 4-position of the heterocyclic ring to produce salts of type (121) when heated with methyl iodide or reactive halides such as phenacyl bromide (77G1). The reaction is hindered when 3-substituents are present on the ring and when higher molecular weight alkyl, allyl or benzyl halides are used. By contrast, benzhydryl and trityl chlorides (which are harder electrophiles) alkylate (16) at the 5-amino function (presumably by an SN1 reaction) to produce products of type (122) as indicated in Scheme 53 (65AHC(5)119). 

Selective conversiou of allylic and benzylic alcohols into halides It was noted above that allylic or benzylic alcohols are not oxidized by the N-chlorosuccinimide-dimethyl sulfide reagent but instead are converted into chlorides. Corey et al. now report that this procedure can be used to form allylic and benzylic chlorides in high yield if the sulfoxonium intermediate corresponding to (3, above) is allowed to decompose in methylene chloride without addition of a tertiary amine. For example, the allylic or benzylic alcohol is treated with the complex of N-chlorosuccinimide-dimethyl sulfide as above in methylene chloride and then allowed to stand for 4 hr. at - 25°. In the case of benzhydroi [(CfcH5)2CHOH], benzhydryl chloride can be obtained in > 95% yield. 

Halides. Sodium borohydride reduces secondary and tertiary alkyl halides capable of forming relatively stable carbonium ions, for example benzhydryl... 

With primary halides, the first step is probably normally SN2, as commonly assumed, although the existing kinetic and stereochemical data do not establish this with certainty. Secondary halides are considerably less reactive and olefins are frequently found among the products, suggestive of greater importance for an SNl mechanism (260). A rather clear-cut example is seen in the exceptional reactivity of benzhydryl and 9-fluorenyl bromide with triethyl phosphite for which Smith and Burger (290) proposed prior formation of a carbonium ion ... 

With sodamide in liquid ammonia, dimeric halides (20b) were isolated in good yield. Experiments with optically active a-phenylethyl chloride indicated that the displacement reaction (20b) proceeds with Walden inversion. Clearly, the bimolecular displacement mechanism operates in the benzyl and benzhydryl series at low temperatures. 

In the case of triphenylsilane and trityl chloride, this reaction is first order in both reactants in benzene (233). The reaction rate for modified substrates indicates that with respect to R3CX, rate is a function of proclivity to ionize, trityl halides being more rapid than benzhydryl or allyl or tcr/-butyl halides. Indeed the latter required the presence of BBr3 as a catalyst. Within a given series. Cl > Br > I, phenylsilanes react more rapidly than alkyl silanes. A mechanism involving simultaneous nucleophilic attack of halide on silicon, and electrophilic attack on hydrogen by the carbonium ion is reasonable,... 

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