Diphenylmethane, bromination

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 . 

When the aldehyde is heated on the water-bath with 25 per cent, hydrochloric acid, it yields a triphenylmethane derivative, nonamethoxy-triphenylmethane, a body consisting of snow-white crystals, melting at 184 5°. The action of concentrated nitric acid upon the solution in glacial acetic acid of this triphenylmethane derivative gives rise to 1, 2, 5-trimethoxy-4-nitrobenzene (melting at 130°). With bromine, nonamethoxytriphenylmethane combines, with separation of a molecule of trimethoxy bromobenzene, into a tribromo additive compound of hexamethoxy diphenylmethane, a deep violet-blue body. The 1, 2, 5-tri-methoxy-4-bromobenzene (melting at 54 5°) may be obtained more readily from asaronic acid. 

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. 

Low susceptibility to Florida reef fishes due to secondary metabolites (Paul and Hay 1986). Specimens of Carrie Bow Cay, Belize, produce a brominated diphenylmethane derivative (avrainvilleol), which significantly deters feeding by reef fishes (Hay et al. 1990)... 

These complex molecules can be easily synthesized with some key steps. For instance (Fig. 23.15) diphenhydramine can start with the reaction of diphenylmethane and bromine to give the bromide, followed by reaction... 

Kennedy and Stock reported the first use of Oxone for many common oxidation reactions such as formation of benzoic acid from toluene and of benzaldehyde, of ben-zophenone from diphenylmethane, of fratw-cyclohexanediol from cyclohexene, of acetone from 2-propanol, of hydroquinone from phenol, of s-caprolactone from cyclohexanone, of pyrocatechol from salicylaldehyde, of p-dinitrosobenzene from p-phenylenediamine, of phenylacetic acid from 2-phenethylamine, of dodecylsulfonic acid from dodecyl mercaptan, of diphenyl sulfone from diphenyl sulfide, of triphenylphosphine oxide from triphenylphosphine, of iodoxy benzene from iodobenzene, of benzyl chloride from toluene using NaCl and Oxone and bromination of 2-octene using KBr and Oxone126. Thus, they... 

Sun, H. H., Paul, V. J., and Fenical, W., Avrainvilleol, a brominated diphenylmethane derivative with feeding deterrent properties from the tropical green alga Avrainvillea longicaulis, Phytochemistry, 22, 743, 1983. 

The reaction can be operated as a two-phase system in this case the process can be employed at the reflux temperature of the solvent. It should be noted that in some cases, no solvent need be used296 and this is especially efficacious where mono-brominated products are the target. An example of the system s versatility in solvent-free mode can be seen in Table 3.7. Here we see that at a molar ratio of 1 1.1 1 (hydrogen peroxide/hydrogen bromide/2-nitrotoluene) over 90% selectivity to the benzyl bromide is observed at a conversion of 76%. However, increasing the oxidant ratio to 3 3.2 1 (hydrogen peroxide/hydrogen bromide/2-nitrotoluene), a selectivity of 98% to the benzal bromide is afforded. Diphenylmethane can be fully converted to oxidized products with 96% selectivity to the benzophenone compound.297... 

Twenty grams (0.12 mole) of diphenylmethane is heated to 150-160° while 7 ml. (22 g., 0.14 mole) of bromine is added slowly, (/food.) The product is distilled under vacuum, and diphenylmethyl bromide boiling at 183°/23 mm. is obtained in 86% yield. 

Arylazo-methoxy-diphenylmethanes have been isolated as stable yellow crystals by reaction of benzophenone arylhydrazones with bromine, followed by methanolysis of the resulting... 

Bromodiphenylmethane may be prepared by the direet bromination of diphenylmethane which is then condensed with tropine, through the Williamson ether synthesis (making use of sodium alkoxide derivative of tropine), to yield the benztropine base. This is dissolved in an appropriate solvent and precipitated by treating it with an equimolar quantity of methanesulphonie aeid. 

A related system for the bromination of alkenes and alkynes using NaOCl, sodium bromide and a phase transfer agent such as tetra-butylammonium hydrogen sulfate has been reported [28]. In this reaction a third, red coloured phase formed between the aqueous and organic layers, which consisted mainly of tetrabutylammonium tribromide. This brominating system converted cyclohexene to 1,2-dibromocyclohexane (40%) and l-bromo-2-chlorocyclohexane (46%), 1-octyne to 1-bromo-l-octene (88%) and diphenylmethane to benzophenone (65%). 

For each of the following compounds, draw the structure and indicate where radical halogenation is most likely to occur upon heating in the presence of Br2. Then rank the compounds in approximate descending order of reactivity under bromination conditions, (a) Ethylbenzene (b) 1,2-diphenylethane (c) 1,3-diphenylpropane (d) diphenylmethane (e) (l-methylethyl)benzene. 

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