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Comparative study on the preparation of C (3)‐hydroxy‐1,3‐dihydro‐2 H ‐1,4‐benzodiazepin‐2‐ones
Author(s) -
Kovač T.,
Oklobdžija M.,
Šunjić V.,
Kajfež F.
Publication year - 1979
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.5570160732
Subject(s) - chemistry , sodium methoxide , trifluoroacetic acid , halogenation , acetic acid , hydrolysis , methanol , methylene , yield (engineering) , catalysis , solvent , aqueous solution , iodine , chloroform , carbon tetrachloride , acetyl chloride , chloride , oxidizing agent , organic chemistry , materials science , metallurgy
C (3)‐Hydroxy‐1,4‐benzodiazepin‐2‐ones 1–3 have been prepared in high yields using a new, two step approach. In the first step, the 3‐deoxy‐precursors 4–6 were acetylated at C (3) using the redox‐system lead tetraacetate and iodine, or potassium iodide, in acetic acid. The intermediary acetates 9–11 were quantitatively hydrolyzed into 1–3 in non‐aqueous conditions, i.e. in a methanol‐methylene chloride solvent mixture in the presence of sodium methoxide. Another route to the title compounds has been improved as follows. The yields of C (3)‐bromination of compounds 4–6 has been significantly augmented in relation to the known methods using the strong trifluoroacetic acid in very dilute carbon tetrachloride solutions as a catalyst for NBS mediated bromination. The intermediary C (3)‐bromo derivatives have been acetoxylated in situ , and compounds 9–11 have been isolated in over 80% yield. These compounds were solvolyzed into 1–3 as described above. The third part of this paper describes the search for feasible reaction conditions in the synthesis of 3 according to a known method (Scheme 1.); optimization of the yields in all steps was performed.