Benzhydryl chloride

Diphenylmethyl chloride (benzhydryl chloride) [90-99-3] M 202.7, m 17.0°, b 167°/17mm, n 1.5960. Dried with Na2S04 and fractionally distd under reduced pressure. 

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. ... 

Reaction of benzhydryl chloride with JV-methylpiperazine fb) gives cyclizine (97) analogous reaction with p-chlorobenzhy-dryl chloride (5d) affords chlorocyclizine (98)... 

One-tenth mol (20 g) of benzhydryl chloride was mixed with 0.19 mol (19 g) of N-methyl-piperazine and about 10 cc of benzene and the whole was heated on the steam bath four hours. The contents of the flask was partitioned between ether and water, and the ethereal layer was washed with water until the washings were neutral. The base was then extracted from the ethereal layer by N hydrochloric acid and the extract, made acid to Congo red paper, was evaporated under vacuum, 29.5 g of the pure dihydrochloride of N-methyl-N -benzhydryl piperazine was recovered from the residue by recrystallization from 95% alcohol melting above 250°C with decomposition. 

Reaction scheme. Propose reaction steps consistent with the rate law for the hydrolysis of benzhydryl chloride relate a and /3 to the rate constants. 

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

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. 

CijHiiBr 776-74-9) see Diphenhydramine Diphenylpyraline Ebastine Manidipine benzhydryl chloride... 

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... 

Bowden and Thomas report that the effect of methyl groups on the conductivity of trityl chloride in sulfur dioxide is in the order p>o>m> none.1 1 The trityl chloride-stannic chloride complex and a whole series of trityl bromides are strong electrolytes in sulfur dioxide.160-152 Benzhydryl chloride, ra-chlorobenzhydryl chloride, and -dimethylbenzhydryl chloride do not conduct in sulfur dioxide. Earlier reports to the contrary may have been due to the use of impure compounds.162 Dimesitylmethyl chloride has also been reported to conduct in sulfur dioxide.163... 

The source of some of the difficulties encountered in trying to explain the effects of structural changes on ionization rates may be due to the different parts played by the solvent, as for example, the sulfur dioxide of the trityl chloride equilibrium experiments and the aqueous acetone of the benzhydryl chloride rate data. The solvent is bound to modify the effect of a substituent, and although the solvent is usually ignored in discussing substituent effects this is because of a scarcity of usable data and not because the importance of the solvent is not realized "... solvation energy and entropy are the most characteristic determinants of reactions in solution, and... for this class of reactions no norm exists which does not take primary account of solvation. 220 Precisely how best to take account of solvation is an unanswered problem that is the subject of much current research. 

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... 

This procedure illustrates a process which is general for 1,1-diphenyl substituted hydrocarbons. Diphenylmethane has been alkylated3 with benzyl chloride, benzhydryl chloride, a-phenyl-ethyl chloride, /3-phenylethyl chloride, isopropyl chloride, 2-ethylbutyl bromide, and re-octyl bromide in yields of 99, 96, 97, 88, 86, 96, and 99%, respectively. 

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. 

Benzhydryl chloride and bromide are both reduced at a more negative potential than that required for reduction of the benzhydryl radical. Reduction in dimeOiyl-... 

The adduct could also be synthesized from preformed benzophenone. Thus, 5.2 mmoles of benzophenone reacted in 25 ml. of DMSO (80% )-tert-butyl alcohol (20%) containing 5.7 mmoles of potassium tert-butoxide to give a 93% yield of the adduct in 15 minutes at 25°C. The DMSO-benzophenone adduct was also isolated by benzene extraction of the hydrolyzed and acidified oxidates of benzhydryl chloride, benzhydryl bromide, benzhydryl amine, diphenylacetonitrile, and 1,1-diphenylace-tone in DMSO (80% )-tert-butyl alcohol (20% ). 

Kinetic studies also provide other evidence for the SnI mechanism. If this mechanism operates essentially as shown on p. 298, 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 S02 with the nucleophiles fluoride ion, pyridine, and triethylamine at several concentrations of each nucleophile.23 In each case the initial rate of the reaction was approximately the same when corrections were made for the salt effect. The same type of behavior has been shown in a number of other cases, even when the reagents are as different in their nucleo-philicities (see p. 348) as H20 and OH. ... 

Benzene, (cHLORO-teri-BuTYL)-, 32, 90 2-chloro-1, 3-dinitro-, 32, 23 ETHYNYL-, 30, 72 HEXAMETHYL-, 35, 73 1,2,3-trimethyl-, 34, 56 Benzeneboronic ACID, 39, 4 Benzeneboronic anhydride 39, 3 Benzenediazonium chloride, 32, 84 Benzenesulfenyl chloride, 36, 101 Benzenesulfonyl chloride, 31, 83 9,10-o-Benzenoanthracene, 9,10-dihydro-, 39, 75 Benzhydrol, 33, 11 Benzhydryl chloride, 39, 74 Benzidine, 36, 21... 

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). 

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