6-Methoxyisoquinoline

Chemical Properties

Clear Oil

Uses

6-Methoxy Isoquinoline (cas# 52986-70-6) is a compound useful in organic synthesis.

Preparation

6-Methoxyisoquinoline synthesis: Using benzaldehyde as the starting material, m-methoxybenzaldehyde is obtained through nitration, reduction, diazotization, hydrolysis and methylation, and 3-methoxybenzaldehyde is obtained through condensation with nitromethane Shiff base and reduction of aluminum hydride -p-Phenylethylamine. The Pictet-Spengler reaction of 3-methoxyl-p-phenylethylamine and 40% aqueous formaldehyde produces 6-methoxyl-1,2,3,4-tetrahydroisoquinoline, and then obtains the target compound in dehydrogenation 6-Methoxyisoquinoline.

Synthesis Reference(s)

Journal of the American Chemical Society, 69, p. 1939, 1947 DOI: 10.1021/ja01200a028

Synthesis

General procedure for the synthesis of 6-methoxyisoquinoline from the compound (CAS:112435-06-0): the product obtained from step B (15) was dissolved in dichloromethane (200 mL) and the solution was cooled to 0 °C. Subsequently, titanium tetrachloride (86.0 g, 453 mmol) was slowly added and the reaction mixture was heated to reflux overnight. After the reaction was completed, the mixture was allowed to cool naturally to room temperature. Next, an aqueous solution (500 mL) of sodium hydroxide (73 g) was added and vigorously shaken for 10 minutes. The resulting titanium dioxide precipitate was removed by filtration and the filtrate was extracted with 3N hydrochloric acid. The pH of the aqueous phase was adjusted to 10 and the product in the aqueous phase was extracted with dichloromethane. The organic phases were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure to afford 5.32 g (45% yield) of the target product 16 (6-methoxyisoquinoline) with mass spectral data of m/z = 160 (M + H)+. The product did not require further purification and could be used directly in the subsequent reaction.

References

[1] Journal of Organic Chemistry, 1983, vol. 48, # 19, p. 3344 - 3346
[2] Patent: WO2007/14921, 2007, A1. Location in patent: Page/Page column 74-75