Benzhydryl bromide

Ammonium thiocyanate Anisoyl chloride Benzhydryl bromide... 

The prototype of the antihistamines based on benzhydrol, diphenhydramine (3), is familiar to many today under the trade name Benadryl . Light-induced bromination of diphenylmethane affords benzhydryl bromide (2). This is then allowed to react with dimethylaminoethanol to give the desired ether. Although no mechanistic studies have been reported, it is not unlikely that I he bromine undergoes SNi solvolysis in the reaction medium the carbonitjm ion then simply picks up the alcohol. It might be noted in passing that the theophyline salt of 4 is familiar to many Iravelers as a motion sickness remedy under the trade name Oram amine . 

As described in U.S. Patent 2,421,714 (a) benzhydryl bromide is first prepared as follows 840 parts by weight of diphenylmethane is heated to 130°C with stirring. In the presence of a 200 watt electric light 6 inches from the flask, 880 parts of bromine is added slowly. Liberation of HBr occurs and addition requires 1 hour and 45 minutes. The temperature is maintained at 130°C for an additional 30 minutes. A fine stream of air is blown in to remove HBr and Brj while the reaction mixture cools. Benzene (180 parts) is added and the solution used immediately in (b) below. 

If pure benzhydryl bromide is desired the above reaction mixture is dissolved in ether, washed with water, sodium carbonate solution and finally with water. The ether is removed, benzene added and distilled off and the benzhydryl bromide distilled in vacuo. Yield 85%. 

Methyl4-piperidinol Benzhydryl bromide Hydrogen chloride... 

A mixture of 46 grams of Tmethyl-4-piperidinol (0.4 mol), 49.4 grams of benzhydryl bromide (0.2 mol) and 100 ml of xylene was refluxed for approximately 24 hours. The reaction mixture separated into two phases with the upper phase containing the desired... 

C 3H,20 91-01-0) see Adrafinil Modafinil benzhydroximic acid chloride (C7H C1N0 698-16-8) see Imolamine Oxacillin benzhydryl bromide... 

C28H24N2O4S 64324-01-2) see Latamoxef diphenylmethyl bromide see under benzhydryl bromide... 

Benzhydryl bromide (BHB) undergoes solvolysis in aqueous dioxane to produce benzyhydryl alcohol (BHA) and hydrogen bromide. 

Benzhydryl bromide, b326 / -Benzidine, bl40 2-Benzimidazolethiol, ml7... 

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% ). 

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... 

A long series on the kinetics and mechanism of the unimolecular heterolysis of commercial haloorganic compounds has continued in a study of the effect of bromide salts and lithium perchlorate on the ionization rate of benzhydryl bromide in y-butyrolactone and acetone.122 The verdazyl indicator method was applied. The nature of special and normal salt effects has also been discussed.123... 

Benzhydrazide, b72 Benzhydrol, d677 Benzhydrylamine, d678 Benzhydryl bromide, b274 Benzidine, b 36... 

The manufacture of a related compound is first described. 28.1 parts of p-chloro-benzhydryl bromide are heated to boiling, under reflux and with stirring, with 50 parts of ethylene chlorohydrin and 5.3 parts of calcined sodium carbonate. The reaction product is extracted with ether and the ethereal solution washed with water and dilute hydrochloric acid. The residue... 

A mixture of 46 g of l-methyl-4-piperidinol (0.4 mol), 49.4 g of benzhydryl bromide (0.2 mol) and 100 ml of xylene was refluxed for approximately 24 hours. The reaction mixture separated into two phases with the upper phase containing the desired ether compound dissolved in xylene. The lower phase consisted of the hydro bromide salt of the excess l-methyl-4-piperidinol. The upper phase was separated from the lower phase and the desired benzhydryl ether recovered in the crude state by distilling off the xylene under reduced pressure. The crude benzhydryl ether was a clear reddish oil. It was dissolved in 75 ml of 20% hydrochloric acid and the aqueous acid solution then washed three times with 50 ml portions each of ethyl ether. The aqueous acid solution was then decolorized with activated carbon and thereafter slowly admixed with 75 ml of 28% aqueous ammonia. The benzhydryl ether separated as an oily material and was removed from the aqueous mixture by extraction with three 50 ml portions of ethylether. On evaporation of the ethyl ether from the ethyl ether solution, the benzhydryl ether was recovered as a pale yellow oil. The benzhydryl ether was dissolved in 60 ml of isopropanol and the isopropanol solution acidified to a PH of 3 with dry hydrogen chloride-methanol solution. The acidic propanol solution was then diluted with ethyl ether until a faint turbidity was observed. In a short time, the crystalline hydrochloride salt of the benzhydryl ether separated from the propanol solution. The crystallized salt was recrystallized once from 75 ml of isopropanol with the aid of ethyl ether in order to further purify the material. 

For the rapid production of analogues, parallel synthesis techniques are often desirable. Morphy and coworkers have published two solid-supported syntheses of benzhydrylpiperazines and related compounds [44,45]. Both of these approaches utilize a displacement of the benzhydryl bromide by an amine (piperazine, e.g.) to build the molecules. However, these two routes are complementary, traceless linker approaches. In one, the piperazine is attached to the solid support while the molecule is built, allowing significant variation on other parts of the molecule. Cleavage is effected via quaterniza-... 

Alternatively, benzhydrylsulfanylacetic acid 14 was prepared from benzhydryl bromide 15 and thioglycolic acid, 13 in excellent yield (Scheme 3). Similarly, the reaction of benzhydryl chloride and thioglycolic acid, 13 also provided benzhydrylsulfanylacetic acid 14.28... 

Ammonium thiocyanate Anisoyl chloride Benzhydryl bromide (diphenyl methyl bromide) Benzoyl cnloride Benzyl bromide Benzyl chloride Benzyl chloroformate (benzyl chlorocarbonate) Butyl acid phosphate Chloracetyl chloride... 

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