Ammonia → HCID 13922820, compound

Participants

Reaction Steps

6-Methoxy-2-sulfamoylbenzo[b]thiophene, a novel compound and a key intermediate for many of the other novel compounds of this invention, is obtained by reacting bromoacetaldehyde diethyl acetal in the presence of a base with at least a molar equivalent of m-methoxybenzenethiol in a suitable inert solvent, preferably acetone, at a temperature extending to reflux. After reaction is essentially complete the 1-[(2,2-diethoxy)ethylthio]-3-methoxybenzene obtained is collected and suitably extracted, washed and dried. The dried product is then slowly added to at least a molar equivalent of the catalyst boron trifluoride.etherate in an inert solvent such as chloroform at a temperature extending to reflux until reaction is essentially completed. Preferably the reaction is conducted under an inert atmosphere such as nitrogen. A mixture of 6-methoxybenzo[b]thiophene and 4-methoxybenzo[b]thiophene in an approximate ratio of 10:1 is obtained upon evaporation of the solvent. The mixture is treated with at least a molar equivalent of n-butyl lithium in an inert solvent such as tetrahydrofuran at a reduced temperature, preferably below -10° C., most suitably at -70° C. Sulfur dioxide gas is then passed over the solution at a rate such that the reaction mixture does not exceed a temperature of -10° C. After the reaction is complete, the solvents are removed and the product reacted with at least one molar equivalent of N-chlorosuccinimide at reduced temperature, generally 0° C. or less. The mixture of 4- and 6-methoxybenzo[b]thiophene-2-sulfonyl chlorides that is produced is treated with concentrated aqueous ammonia. The resulting mixture of 4- and 6-methoxy-2-sulfamoylbenzo[b]thiophenes is then collected and the isomers are separated by fractional crystallization. Each is further purified by reprecipitation from aqeuous base by treatment with acid and/or recrystallization from an appropriate solvent.

Provenance & Evidence