Synthesis of substituted linear furano[2,3-g][1]benzopyrones and [3,2-b]thianaphtenopyrones

Antiasthma agents. 1. 4-Oxo-4H-[1]benzothieno[3,2-b]pyran-2-carboxylic acid and 4-oxo-4H-[1]benzofuro[3,2-b]pyran-2-carboxylic acid

“…Ethyl 4-0x0-42/- [ 1 ] benzothieno [ 3,[2][3][4][5][6] pyian-2-carboxylate (5). To a stirred solution of 19.32 g (0.825 mol) of sodium in 2 1. of anhydrous ethanol was added 57.6 g (0.3 mol) of 3-hydroxy-2-benzothienyl methyl ketone4 and then, dropwise over the course of about 5 min, 120.3 g (0.825 mol) of diethyl oxalate.…”

“…4-Oxo-4//-[ 1 ] benzothieno [ 3,2-6] pyran-2-carboxylie Acid (2). A mixture of 44.1 g (0.162 mol) of ethyl 4-oxo-42Z-[ l]benzothieno- [3,[2][3][4][5][6]pyran-2-carboxylate (5) and 650 ml of a 1% sodium hydroxide solution (0.162 mol) was stirred for 30 min. The mixture was extracted with methylene chloride.…”

“…4-0x0-42/-[ 1 ] benzofuro [3,2-6 ] pyran-2-carboxylic Acid (3). A mixture of 1.26 g (0.0049 mol) of ethyl 4-oxo-42/-[ 1 jbenzofuro- [3,[2][3][4][5][6] pyran-2-carboxylate (7) and 20 ml of a 1% sodium hydroxide solution was stirred for 30 min.…”

“…( 6 Disodium cromoglycate (1) is a substance which has shown very promising antiasthmatic properties.1'2 We were inter-OH ested in investigating other compounds for this type of activity, particularly those compounds that possessed a fusedpyrone ring, similar to that found in the chromone ring of disodium cromoglycate. We chose for synthesis and for biological study 4-oxoAH-[ 1 [benzothieno [3,[2][3][4][5][6]pyran-2-carboxylic acid (2) and 4-oxoAH-[ 1 ] benzofuro [3,2-6] pyran-2carboxylic acid (3).…”

“…Chemistry. The only reference in the literature to the synthesis of 4-oxo-4//-[ 1 ] benzothieno [3,[2][3][4][5][6] pyrans is that of Mustafa3 who prepared 2-aryl derivatives by treatment of 3hydroxybenzothienyl-2-methyl ketone4 (4) with aromatic aldehydes followed by treatment of the resulting chalcone with selenium dioxide. We found that the desired 4-oxo AH-[ 1 ] benzothieno [3,[2][3][4][5][6] pyran-2-carboxylic acid (2) could be obtained readily in good yield from 3-hydroxybenzothienyl-2-methyl ketone4 (4) by treatment with diethyl oxalate in the presence of sodium ethoxide to give the corresponding ester 5 (obtained in 71% yield) which, upon hydrolysis, gave the desired acid 2.…”