The Synthetic Study Of Pipothiazine

Pipothiazine,a representative drug of phenothiazines,was developed by Rhone-Poulenc Porer in France in 1970s,and is applied for the treatment of psychotic disorders.The types of psychotic disorders and the development of antipsychotic drugs were reviewed in this thesis.Here also introduced the different applications of Pipothiazine.For the sake of the synthesis of the target,two intermediates,N,N-dimethyl-10H-phenothiazine-2-sulfonamide (2)and 2-(piperidin-4-yl)ethanol(3)had to be prepared. After intensive investigation,2 was prepared from o-bromoaniline and o-nitrochlorobenzene via a 7-step sequence such as amonolysis,reduction and Ullmann reaction,while 3 was synthesized via a 4-step sequence from 1-benzylpiperidin-4-one including Wittig reaction, reduction and so on.After 2 was treated with 1-bromo-3-chloropropane to get compound 20,it was condensed with compound 3 and Pipothiazine(1)was eventually prepared.The structures of the target and some important intermediates were determined by ~1H NMR or MS spectra.During the amonolysis of the 4-chloro-3-nitrobenzene-1-sulfonyl chloride(12), inorganic bases proved to be better in water in higher yield without significant byproduct. The synthesis of phenothiazine 2 via Ullmann reaction between aryl bromide and arylamine was catalyzed by copper bronze in the presence of potassium carbonate and got a good result.