Solid-phase synthesis of isoquinolinones using Bischler–Napieralski cyclization

One‐Pot Synthesis of 3‐Substituted Isoquinolin‐1‐(2H)‐ones and Fused Isoquinolin‐1‐(2H)‐ones by SRN1 Reactions in DMSO

“…The photostimulated reactions of several acyclic enolates of aromatic (acetophenone, 1-(benzo[d] [1,3]dioxol-5-yl)ethanone, 1-and 2-naphthyl methyl ketones, and 2-, 3-, and 4-acetylpyridine), aliphatic (1-adamantyl methyl ketone), and cyclic ketones (1-and 2-indanone, α-and β-tetralone, and 1-benzosuberone) with substrate 1 in DMSO afford 3-substituted isoquinolinones and fused isoquinolinones in very good yields (42-91 %) by the S RN 1 mechanism.…”

“…DMSO was distilled under vacuum and stored under molecular sieves (4 Å). Acetophenone, 1-and 2-naphthyl methyl ketones, 1-(benzo[d] [1,3]dioxol-5-yl)ethanone, 1-adamantyl methyl ketone, 2-, 3-, and 4-acetypyridine, α-and β-tetralone, 1-and 2-indanone, and 1-benzosuberone were commercially available and distilled under reduced pressure. o-Iodobenzamide (1) was prepared from 2-iodobenzoic acid according to the literature procedure.…”

“…The photostimulated reaction of o-iodobenzamide (1) with the enolate of acetophenone (2) affords the 3-phenylisoquinolin-1-(2H)-one (3) in 91 % yield [Equation (6)]. This reaction does not occur in the dark and is partially inhibited by p-dinitrobenzene (p-DNB), a known radical anion scavenger (Table 1, Experiments 1-3).…”

“…A related nucleophile, the enolate of 1-(benzo[d] [1,3]dioxol-6-yl)ethanone (4), gives the ring closure product 5 in similar yields under irradiation with 1 [Equation (8) 3-(Naphthalen-1-yl)isoquinolin-1-(2H)-one (7a) is obtained by a photostimulated reaction of 1 with the enolate of 1-naphthyl methyl ketone (6a) in 83 % yield in DMSO. In the photostimulated reaction of 1 with 2-naphthyl methyl ketone (6b), 3-(naphthalen-2-yl)isoquinolin-1-(2H)-one (7b) is obtained in 68 % yield together with the reduced product benzamide in 7 % yield [Equation (9) and Table 1, Experiments 5 and 6].…”

“…It is well known that their structures are incorporated in several alkaloids and other pharmacologically important compounds such as thalifoline, [1] dorianine, [2] narciclasine, [3] pancratistatin, and lycoricidine. [4] Substituted isoquinolinones exhibiting antidepressant, [5] anti-inflammatory, [6] anti-ulcer, [7] analgesic, [5] hypolipidemic, [8] and antihypertensive [9] characteristics have also been described.…”