4-Chlorobenzhydryl chloride

O.OB mol (19 g) of 4-chlorobenzhydryl chloride and 0.16 mol (16g) of methylpiperazine were mixed in about 20 cc of dry benzene. The flask containing the reaction mixture was covered by a watch glass and set in a steam bath, and heating was continued for 6 hours. The contents of the flask were partitioned between ether and water and the ethereal layer was washed with water until the washings were neutral. The ethereal layer was extracted successively with 30-and 10-cc portionsof 3 N hydrochloric acid. On evaporation of the ether layer there remained a residue of 2.5 g. The aqueous extracts were united and basified with concentrated alkali. The oily base was taken into ether and dried over potassium carbonate. On evaporation of the ether, N-methvl-N -(4-chlorobenzhvdryl) piperazine was recovered in the form of a viscous oil in 75% yield. The N-methvl-N -(4-chlorobenzhvdryl) piperazine was dissolved in absolute alcohol and ethanolic hydrogen chloride added in excess. The dihydrochloride crystallized... 

Chlorobenzhydryl chloride Piperazine 1-carboxylic acid ethyl ester 4-tert-Butylbenzyl chloride... 

A solution of 28.2 g (0.2 mol) of 3-tropanol is prepared in 50 ml of xylol, and to this solution is added 23.8 g (0.1 mol) of 4-chlorobenzhydryl chloride. The resultant solution is heated for 7 h at 145°-155°C, following which the mixture is cooled and filtered. The clear filtrate thus obtained is washed with 50 ml of 5% aqueous potassium carbonate solution and then with three successive 25 ml portion of water. The xylol solution is then extracted with three successive 50 ml portions of 2 N hydrochloric acid. The xylol layer is discarded and the acid extracts are combined and rendered strongly basic by the addition of 22.5% aqueous potassium hydroxide, resulting in the formation of an oily base which separates and which is then extracted with... 

Hydroxyethyl)piperazine p-Chlorobenzhydryl chloride Diethylene glycol... 

A mixture of 1.5 mols of 1-(2 -hydroxyethyl)piperazine and 1 mol of p-chlorobenzhydryl chloride is heated at 150°C for 15 minutes. The substance is dissolved in water, basified by caustic soda and extracted with benzene. 

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. ... 

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... 

Lui et al. [8] prepared buclizine by reducing p-chlorophenyl phenyl ketone 1 with potassium borohydride to p-chlorobenzhydryl alcohol 2, which was converted into p-chlorobenzhydryl bromide 3. The latter compound 3 was prepared by reaction of p-chlorophenylmagnesium bromide 4 with benzaldehyde 5. p-ferf-Butylbenzyl chloride 6 was condensed directly with piperazine 7 to give p-ferf-butylbenzylpiperazine 8. Treatment of p-chlorobenzhydryl bromide 3 with p-ferf-butylbenzylpiperazine 8 in the presence of anhydrous sodium carbonate gave buclizine 9 hydrochloride. 

Cossement et al. [9] s)nithesized the enantiomers of l-(p-chlorobenzhy-diyl)-4-(p-methylphenyl)sulfonyl piperazine 3 and used it as an intermediate for fhe preparation of buclizine 6 and other histamines. The enantiomers of (+)- and (—)-l-(p-chlorobenzhydryl)-4-(p-foluene sulfo-nyl)piperazine 3 were prepared and converted by hydrolysis to the enantiomers of (+)- or (—)- of p-chlorobenzhydryl piperazine 4. Compound 3 was prepared by refluxing p-chlorobenzhydrylamine 1 with N-bis-2-chloroethyl-p-toluene sulfonamide 2 with ethyl diisopropylamine. Reaction of p-ferf-bufylbenzyl chloride 5 wifh p-chlorobenzhydryl piperazine 4 gives buclizine 6. 

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