Refernces
10.1021/ol9028622
The research presents a study on the isolation of primary adducts from Ugi four-component condensation (Ugi-4CC), which leads to the formation of isocoumarins. The researchers used 2-formylbenzoic acid, phenacylamine dimethyl acetal, and isocyanides as reactants and successfully isolated the primary adducts, which were stable enough for characterization. They also found that using anilines instead of amines yielded stable isocoumarins. The experiments involved stirring the reactants in methanol, followed by filtration to isolate the yellow solid product. The product's structure was confirmed through analytical and spectral data, as well as X-ray diffraction analysis. The study also explored the rearrangement of these primary adducts to form "normal" Ugi-4CC adducts upon treatment with acid and the deprotected Ugi-4CC adducts when exposed to higher concentrations of hydrochloric acid. The researchers highlighted the importance of controlling reaction conditions to ensure good yields and easy workup of the compounds, which were found to be stable in solid state but tended to rearrange in solution. The study provides a straightforward route to isocoumarins, a class of compounds with various biological activities.
10.1007/s10593-008-0140-3
The research aimed to efficiently synthesize a series of 3-arylisoquinolin-1(2H)-ones, which are nitrogen analogues of isocoumarins and are found in various bioactive natural products. These compounds have therapeutic value, exhibiting activities such as antidepressant, anti-inflammatory, and analgesic properties. The study focused on converting 3-substituted isocoumarins into their nitrogen analogues by refluxing with methanamide. The process was successful, yielding isoquinolin-1(2H)-ones in 76–85% yield and high purity. The chemicals used in this process included 3-substituted isocoumarins (1a-j) and methanamide, with the reaction progress monitored by TLC, and the products characterized by comparing their mp, IR, 1H NMR, and mass spectral data with those of the corresponding isocoumarins. The conclusion of the research was that a one-pot conversion of 3-substituted isocoumarins to the corresponding isoquinolones was achieved, demonstrating a synthetically feasible procedure for accessing these bioactive heterocycles.
10.1039/c3ra40969d
The study explores a CuI–K2CO3-PEG 400 catalytic system for the ultrasound-mediated coupling-cyclization of o-iodobenzoic acid with terminal alkynes to synthesize 3-substituted isocoumarins. This method is highlighted as a greener and more selective alternative to traditional approaches. The CuI acts as the catalyst, K2CO3 serves as the base, and PEG 400 functions both as a solvent and a ligand, facilitating the formation of isocoumarins with high regioselectivity. The process avoids the use of expensive or toxic palladium catalysts and harmful organic solvents, making it a more sustainable and practical option for producing isocoumarins, which have significant pharmacological interest.
