An Efficient Synthetic Route to Ethyl 2-Aryl-4-hydroxy-1,3(2H,4H)- dioxoisoquinoline-4-carboxylates¹

ChemInform Abstract: Facile Synthesis of 4‐Alkoxycarbonylisoquinoline‐1,3‐diones and 5‐Alkoxycarbonyl‐2‐benzazepine‐1,3‐diones via a Mild Alkaline Cyclization.

“…4-Substituted isoquinoline-1,3-dione framework may serve as the backbone for the production of several series of biologically active compounds, mainly in the field of diabetes (aldose reductase inhibitors) [1], inflammation [2] (cycloxygenase [3] and lipoxygenase [4] inhibitors), herbicides, and plant growth regulators [5]. Our current research program is devoted to the evaluation of 2hydroxyisoquinoline-1,3-diones as potential HIV-1 integrase and/or ribonuclease H inhibitors.…”

“…Two routes were possible (Scheme 1). The first one consists in synthesizing the 4-unsubstituted isoquinoline-1,3-dione by reaction of a primary amine with homophthalic anhydride, acid or diester (Scheme 1; route a) [1,3,5]. Then functionalization at position 4 is usually performed by reacting the isoquinoline-1,3-dione with a cyanoformate [1], a chloroformate [5], an acylchloride [3], or a sulfonylchloride [3] in presence of a base (pyridine, LiN(SiMe 3 ) 2 , NaH or DBU) [1,3,5].…”

“…The first one consists in synthesizing the 4-unsubstituted isoquinoline-1,3-dione by reaction of a primary amine with homophthalic anhydride, acid or diester (Scheme 1; route a) [1,3,5]. Then functionalization at position 4 is usually performed by reacting the isoquinoline-1,3-dione with a cyanoformate [1], a chloroformate [5], an acylchloride [3], or a sulfonylchloride [3] in presence of a base (pyridine, LiN(SiMe 3 ) 2 , NaH or DBU) [1,3,5]. In our hands, the reaction of 2-benzyloxyisoquinoline-1,3-dione with methyl chloroformate in presence of a base (LDA or NaH) allowed us to isolate the desired product only in poor yields, because of a low reactivity and a degradation of the quinoline ring.…”

Efficient synthesis of some 3-substuited-1(2H)-isoquinolones

“…These include the Gabriel-Coleman synthesis [17], ring enlargement of phthalimides [18], condensation of amines with homophthalic anhydrides [19], reaction of 2-methoxycarbonylstyrene oxide with ammonia or methylamine [20], and reaction of coumarin and isocoumarin derivatives [21] with ammonia and amines. The latter method has been used in the synthesis of (±)-licoricidine [22], narciclasine [23], (+)-deoxypancratistatin [24], and the benzophenanthridine alkaloid nitidine [25].…”

Efficient synthesis of some 3-arylisoquinolin-1(2H)-ones

“…These include the Gabriel-Coleman synthesis [18], ring enlargement of phthalimides [19], condensation of amines with homophthalic anhydrides [20], reaction of 2-methoxycarbonylstyrene oxide with ammonia or methylamine [21], and reaction of coumarin and isocoumarin derivatives [22] with ammonia and amines. The latter method has been used in the synthesis of (±)-licoricidine [23], narciclasine [24], (+)-deoxypancretistatin [25], and the benzophenanthridine alkaloid nitidine [26].…”