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The synthesis of 5,10‐dihydro‐ and 2,3,5,10‐tetrahydrothiazolo‐[3,2‐ b ] [2,4]benzodiazepines, 1,2,3,4,7,12‐hexahydrobenzothiazolo‐[3,2‐ b ] [2,4] benzodiazepine, and 9,14‐dihydro‐6 H ‐[1]benzothiopyrano‐[4′,3′:4,5]thiazolo[3,2‐ b ] [2,4] benzodiazepine via 1,2,4,5‐Tetrahydro‐3 H ‐2,4‐benzodiazepine‐3‐thione
Author(s) -
Elslager Edward F.,
Worth Donald F.,
Haley Neil F.,
Perricone S. C.
Publication year - 1968
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.5570050504
Subject(s) - chemistry , medicinal chemistry , benzodiazepine , yield (engineering) , phthalazine , carbon disulfide , ethyl iodide , alkylation , organic chemistry , catalysis , stereochemistry , biochemistry , materials science , receptor , metallurgy
Catalytic reductive scission of phthalazine (II) utilizing a two‐stage palladium‐Raney nickel procedure afforded o ‐xylene‐α,α′‐diamine (III) in 97% yield. Treatment of III with carbon disulfide gave [ o ‐(aminomethyl)benzyl]dithiocarbamic acid (IV), which upon thermal cyclization furnished 1,2,4,5‐tetrahydro‐3 H ‐2,4‐benzodiazepine‐3‐thione (V). Reaction of V with 1,2‐dibromoethane, chloro‐2‐propanone, ethyl 2‐chloroacetoacetate, ethyl chloroacetate, and ethyl 2‐bromohexanoate gave 2,3,5,10‐tetrahydrothiazolo[3,2‐ b ][2,4]benzodiazepine (VII) and substituted 5,10‐dihydrothiazolo[3,2‐ b ][2,4]benzodiazepines (Villa and b, IX, and X), respectively. Condensation of V with 2‐chlorocyclohexanone and 3‐bromothiochroman‐4‐one afforded 1,2,3,4,7,12‐hexahydrobenzothiazolo[3,2‐ b ][2,4]benzodiazepine (XII) and 9,14‐dihydro‐6 H ‐[1]benzothiopyrano[4′,3′:4,5]thiazolo[3,2‐ b ][2,4]benzodiazepine(XIll). None of the compounds possessed appreciable biological activity.