An alternative synthetic route to the neuroleptic compound Pipothiazine

Abstract

A simple and efficient synthesis of the neuroleptic compound Pipothiazine 1 is described, involving the reductive cyclation of (2-nitrophenyl)(phenyl)sulfanes 3 for the formation of the phenothiazine ring.

Synthesis and antifungal activity of some substituted phenothiazines and related compounds

“…MP: 195e198 C, yield 62%. The physical and spectroscopic data were consistent with those previously reported in the literature[22].5.1.1.2. 10-(3-Chloropropionyl)-10H-phenothiazine 4.…”

“…We have previously described the synthesis of compound 1, as starting material in the procedure to prepare the neuroleptic compound PIP [22].…”

“…The N-acyl derivatives 2 [22], 4 [22], 6 [23], 7 [24], and 8 (Chart 2) were synthesized using microwave irradiation (MW), with excellent yield and very short times of reaction, starting from the corresponding amines and using b-chloro propanoyl chloride (2, 4), a-chloro acetyl chloride (6,8) and acetyl chloride (7).…”

“…Compound 12 [27] was synthesized by a conventional procedure using acetyl chloride and carbazole (commercial) (Chart 4). The nitro compound 13, previously prepared by us [22], was reduced using Zn/CaCl 2 , affording compound 14. Treatment of this amine with a-chloro-acetyl chloride and MW, gave the N-acyl derivative 15, with good yield and very short time of reaction (Scheme 2).…”