Benzhydryl chlorides, alkylation with

Benzhydryl chloride, alkylation of sodium sodiophenylacetate with, 40, 39... 

Under comparable conditions the corresponding alkylations of phenylacetic acid with a-phenylethyl chloride and benzhydryl chloride have been effected to form o ,/3-diphenylbutyric acid and a ,/3,/3-triphenylpropionic acid in yields of 74% and 51%, respectively. ... 

Benzhydrylamine Derivatives Attachment of piperazine nitrogen directly to a benzhydryl carbon leads to a pair of compounds which show vasodilator activity, and which should be useful in disease states marked by impaired blood circulation. Reaction of piperonyl chloride (18) with a mixture of piperazine and piperazine dihydrochloride leads to the monoalkylation product (19). (It may be supposed that the mixture of free base and salt equilibrates to the monobasic salt, thus making the second amine less nucleophilic.) Alkylation of 19 by means of benzhydryl chloride then... 

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. 

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). 

This procedure illustrates a process which is general for 1,1-diphenyl substituted hydrocarbons. Diphenylmethane has been alkylated with benzyl chloride, benzhydryl chloride, a-phenyl-ethyl chloride, /3-phenylethyl chloride, isopropyl chloride, 2-ethylbutyl bromide, and n-octyl bromide in yields of 99, 96, 97, 88, 86, 96, and 99%, respectively. 

Shiner and Yerbanic also measured the isotope effect resultii from p-alkyl deuteration in several p-aJkylated benzhydryl chlorides on sol-voly in solvents of varying composition. In their results, summarized in Table XV, two trends are discemable (i) The effect decreases, rather than increases asin 8-effects, with branchii at the a-car-bon atom of the p-alkyl group (it) the effect decreases with increasing water content of aqueous acetone—as does the difference between the effects of methyl and ethyl deuteration. This is not a simple consequence of a change in gross dielectric constant, since in that respect 90% ethanol is the least polar solvent of all. 

Alkylation of 5-amino-1,2,4-thiadiazoles (17) with methyl iodide leads to N-4 derivatives of type (18) which undergo a Dimroth rearrangement to (110) on warming in ethanol when R = H (Scheme 26). When R = methyl, phenyl, or benzyl the reaction is severly hindered <84CHEC-I(6)463>. In contrast, benzhydryl and trityl chlorides (which are harder electrophiles) alkylate (17) at the 5-amino function to give compounds of type (109) (Scheme 26). 

Methylation of 3-amino-5-phenyl-l,2,4-thiadiazole (111) with trimethyloxonium tetrafluoro-borate produces the N-2 quaternary salt (112) which on basification undergoes a Dimroth rearrangement to give the 3-methylamino derivative (113) (Scheme 27) <82AHC(32)285>. By analogy with 5-amino-l,2,4-thiadiazole (17) (R = H), the 3-amino-1,2,4-thiadiazole (111) is alkylated by benzhydryl and trityl chlorides to give (114) (Scheme 27). 

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). 

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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