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Synthesis of 7‐hydroxythioridazine and 7‐hydroxysulforidazine
Author(s) -
Singh Shyam K.,
Patrick Kennedy S.
Publication year - 1992
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570290455
Subject(s) - chemistry , alkylation , xanthate , ether cleavage , ether , isopropyl , yield (engineering) , sodium hydroxide , medicinal chemistry , thiol , hydride , sodium hydride , zinc , metal , organic chemistry , catalysis , materials science , metallurgy
The thioridazine metabolites 7‐hydroxythioridazine (2a) and 7‐hydroxysulforidazine (2b) were synthesized. Commercial 4‐chloro‐3‐nitrophenylmethylsulfone was converted to the corresponding 4‐thiol through an intermediate xanthate ester. Subsequent zinc metal reduction provided the 3‐amino thiolate. This salt was condensed with chloroquinone to yield 7‐hydroxy‐2‐methylsulfonylphenothiazine which was then protected as the isopropyl ether. N ‐Alkylation with 2‐(2‐chloroethyl)‐1‐methylpiperidine using sodium hydroxide, then ether cleavage, afforded 2b . The N ‐alkylation followed by reduction with diisobutylaluminum hydride and deblocking yielded 2a . These reference standards will assist in an exploration of the potential role of meta‐bolically formed 2a and 2b in the neuroleptic response to thioridazine.