Synthèse d'isocarbostyriles et de chloro‐1‐isoquinoléines

Abstract

A partir d'acides cinnamiques substitués on a préparé les styrylisocyanates correspondants qui, par cyclisation thermique, ont fourni des isocarbostyriles que l'action de l'oxychlorure de phosphore transforme en chloro‐1‐isoquinoléines. Ce procédé de synthèse s'est montré supérieur aux méthodes connues.

ChemInform Abstract: Synthesis of 3,4‐Dihydro‐1(2H)‐isoquinolinones.

“…Thus, reaction of the acid chloride of 8 with sodium azide gave the acyl azide, which was not isolated, but subjected to Curtius rearrangement to the corresponding isocyanate followed by ring closure in refluxing diphenyl ether/tributylamine. This gave the known 5-methyl isoquinolinone 9 [13,15] in 68% yield. The reaction was scaled up to 0.5 mole without any loss of yield.…”

“…The precipitated solids were collected by filtration, washed with two 250 mL portions of petroleum ether, and air dried to leave 60.3 g of a yellow solid, mp 178-184°. The solid was slurried in ~275 mL of methanol, the suspension boiled for 30 minutes, then filtered and dried to leave 47 g (59%) of pure 9 as a pale yellow solid, mp 185-187°(lit [13,15] mp 184-185°), with spectral data identical to that described before [15]. The methanol filtrate was concentrated to provide 15.8 g of additional impure product in two crops.…”

“…Because the above routes were poor yielding and generated a mixture of isomers, we decided to look for another approach to synthesize target compound 2, which we required in much larger quantities. A review of the literature revealed that such a route was available via thermal cyclization of an appropriately substituted styryl isocyanate precursor as described by Eloy and Deryckere [13]. Indeed they described application of this reaction toward the synthesis of isoquinolinone 9 in 62% yield from acid 8 on a 0.4 mole scale as shown in Scheme 2.…”

Synthesis of 4‐methylfuro[3′,2′:5,6]benzofuro[3,2‐c]pyridine

“…The aqueous solution was extracted with methylene chloride. Evaporation of the solvent gave a residue which was recrystallized from aqueous methanol to afford 0.114 g (57%) of compound 3 as colourless needles, mp 167-169'; nmr (deuteriochloroform): 6…”

“…Deryckere reaction [6,7] to afford compound 7 in 74% yield, which was transformed into the chloro derivative 8 by refluxing in phosphorus oxychloride. The target compound 3 was obtained from 8 by reduction with zinc and acetic acid in 57% yield.…”