Related to Benzhydrol

Many of the more debilitating symptoms of allergic states such as rashes, rhinitis, and runny eyes, are thought to be due to hist- 

Since there was some evidence that these compounds owe their action to interference with the action of histamine, this class has earned the soubriquet antihistamines. This class of drugs is further characterized by a spectrum of side effects which occur to a greater or lesser degree in various members. These include antispasmodic action, sedative action, analgesia, and antiemetic effects. The side effects of some of these agents are sufficiently pronounced so that the compounds are prescribed for that effect proper. Antihistamines, for example, are used as the sedative-hypnotic component in some over-the-counter sleeping pills. 

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 . 

Several analogs bearing different substituents on the aromatic rings are accessible by essentially the same route. The. ippropriate benzhydrol (4) is first prepared by reaction of an 

Inclusion of a second nitrogen atom in the side chain seemingly increases the spasmolytic effect of the benzhydrol derivatives. Alkylation of the benzdryl chloride (9) with the sodium 

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