Tranquilizers, synthesis

Preparation of spirooxaziridines from cyclic ketones poses no problems nor does oxaziridine synthesis from cyclic Schiff bases, which was preferably carried out with pyrro-lines to give, for example (245) (59JCS2102) and, in connection with tranquilizer synthesis, with heterocyclic seven-membered rings to give, for example, (246) (63JOC2459). 

A -dialkylchloroalkylamines, R2N(CH2)nCI. Formed by treating the alkanolamine with thionyl chloride. Of importance in the synthesis of pharmaceuticals, particularly tranquillizers, e.g. amidons. 

The alkaloid reserpiae [50-55-5] which is isolated from the roots of Kauwoljia serpentina T., contains a gaUate trimethyl ether moiety. Reserpiae is used as an antihypertensive and a tranquilizer. A vinylogue of reserpiae, rescinnamine [24815-24-5] is also an antihypersensitive (75). Methoxsalen [298-81-7] (8-methoxypsoralen 7JT-9-methoxy-furo [3,2- ] [l]benzopyran-7-one) (21), a furocoumatia that occurs ia plants, eg, l eguminosae and Umbelliferae is used ia the treatment of vitiligo, as a suntanning promoter, and as a sunburn protectant. It is also available by synthesis (76). 

The synthesis of the tranquilizer, spiropiperone (130) is completed by removal of the benzyl group by hydrogenolysis... 

Another CNS active agent in this structural class is the tranquilizer-antidepressant caroxazone (52). Its published synthesis begins by reductive aminatiwi of salicylaldehyde and glycinamide to give The synthesis is completed by reaction with phosgene and sodium bicarbonate. ... 

Synthesis of the CNS depressant/tranquil izer tioperidone (59) begins by alkylation of piperazine derivative with 4-chlorobutyronitrile to give Lithium aluminum hydride... 

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. 

Next the product is acylated with bromoacetyl chloride and the glycine equivalent is constructed in place by a Gabriel amine synthesis (phthalamide anion followed by hydrazine) subsequent to which cyclization to benzodiazepine occurs. The synthesis of the tranquilizer quazepam (88) is finished by thioamide conversion with phosphorus pentasulfide. ... 

A somewhat more complex example of the Fischer indole synthesis is provided by the tranquilizer, milipertine (8). It can be prepared by reaction of... 

Combining the nucleophilicity of the indole 3-position just illustrated and the well-known tendency of C-2 and C-4 vinyl pyridines to add nucleophiles, a convenient synthesis of the tranquilizer benzindopyrine (19) was devised.6 Reaction of N-benzylindole (17) with 4-vinylpyridine (18) in acetic acid produced 19 directly. 

A somewhat more complex example of the Fischer indole synthesis is provided by the tranquilizer. 

Benzodiazepine derivatives are a basic class of anxiolytics or tranquilizers—compounds for treating conditions of general anxiety, and their synthesis and properties as such will be considered separately. However, despite the fact that the principal clinical effect... 

Benzodiazepines are primarily used in medicine as tranquilizers. However, they also have been snccessfully used for epilepsy in controlling long-lasting convnlsions. The most widely nsed is diazepam (5.1.2) and chlordiazepoxide (5.1.22). The synthesis of these was described in Chapter 5. 

Only in the case of chlordiazepoxide can one speak in terms of goal-directed development here the intention was to find tranquillizing compounds in a new and patentable class of substances. In no case, however, was there a biochemical hypothesis concerning the illness or symptoms to be treated that would have led to the rational synthesis and development of appropriate pharmaceuticals. 

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