COMPARATIVE-STUDY ON THE PREPARATION OF C(3)-HYDROXY-1,3-DIHYDRO-2H-1,4-BENZODIAZEPIN-2-ONES

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. Copyright © 1979 Journal of Heterocyclic Chemistry