Benzodiazapines and Related Substances

The huge clinical success of drugs in this class has spawned an enormous list of congeners. Synthetic activity has, however, now slowed to the point that a separate chapter dealing with these heterocycles is no longer warranted. 

El fazepam (80) not only is a tranquilizer, but also stimulates feeding in satiated animals. One of several syntheses involves reaction of benzophenone derivative with a glycine equivalent masked as an oxazolidine-2,5-dione (79).  

A water-soluble phosphine derivative of diazepam allows for more convenient parenteral tranquilizer therapy and avoids some complications due to blood pressure lowering caused by the propylene glycol medium otherwise required for administration. Fosazepam (82) is prepared from benzodiazepine by sodium hydride-mediated alkylation with chioromethyldimethyl phosphine 

Lormetazepam (84) is readily synthesized by Polonovski rearrangement of benzodiazepine oxide derivative by heating with acetic anhydride followed by saponification of the resulting rearranged ester.The mechanism of this rearrangement to 

Quazepam (88) has a highly fluorinated sidechain so as to make this tranquilizer resistant to dealkylation. It also incorporates a lipid-solubilizing 2-thione moiety. The synthesis begins with bi aryl ketone derivative by ] -al kylation with 2,2,2-trifluoroethyltriclate to give 86. 

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