Synthesis and analgesic activity of some substituted 1-benzofurans and 1-benzothiophenes

2-Benzoyl- and 2-(pyridylcarbonyl)-1-benzofuran-3-amines were prepared from 2-hydroxybenzonitrile and corresponding bromoethanone derivatives. 2-Benzo yl- and 2-(pyridylcarbonyl)-1-benzothiophene-3-amines were prepared analogo usly from 2-sulfanylbenzonitrile. 2-Benzoyl-1-benzofuran-3-amine treated wi th acetic anhydride or ethyl chloroformate provided the corresponding N-ace tyl or N-ethoxycarbonyl derivatives. These N-activated compounds were alkyl ated with ethyl bromoacetate to provide ethyl N-acetyl-N-(2-benzoyl-1-benzo furan-3-yl)glycinate and ethyl N-(2-benzoyl-1-benzofuran-3-yl)-N-ethoxycarb onylglycinate, respectively. Their mild hydrolysis gave the corresponding g lycine derivatives. Methylation of ethyl N-(2-benzoyl)-1-benzofuran-3-yl)ca rbamate gave the corresponding N-methyl carbamate, which was hydrolyzed to N-methyl-(2-benzoyl-1-benzofuran-3-yl)amine. 2-Benzoyl-7-methoxy-1-benzofur an-3-amine and 2-(4-methoxybenzoyl-1-benzofuran-3-amine were demethylated w ith boron tribromide to the corresponding hydroxy derivatives; their O-alky lation with ethyl bromoacetate than gave ethyl [(3-amino 2-benzoyl-1-benzof uran-7-yl)oxy]acetate and ethyl {4-[(3-amino-1-benzofuran-2-yl)carbonyl] ph enoxy}acetate, respectively. The mild hydrolysis of these esters provided c orresponding acids. Similarly, alkylation of the hydroxy derivatives with ( dimethylamino)propyl chloride gave corresponding (dimethylamino)propoxy der ivatives. 2-Hydroxybenzonitrile treated with 2-bromo-1-(2-, 3-, or 4-pyridy l)ethan-1-one provided the respective 2-(pyridylcarbonyl)-1-benzofuran-3-am ine. Similar 2-(pyridylcarbonyl)-1-benzothiophene-3-amines were prepared an alogously from 2-sulfanylbenzonitrile. 2-Benzoyl-3-(bromomethyl)-1-benzofur an treated with dimethylamine, 1-methylpiperazine, and sodium 1-methylpiper idine-4-thiolate gave the corresponding alkylation products. Several compou nds were found to exhibit considerable analgesic activity.