An gano Etonitat da agonist na opioid agonist benzimidazole a ƙarshen 1950 ta ƙungiyar masu binciken Swiss da ke aiki a kamfanin harhada magunguna CIBA (yanzu Novartis).Ɗaya daga cikin mahadi na farko da ƙungiyar Swiss ta yi nazari shine 1- (beta-diethylaminoethyl) -2-benzyl benzimidazole, wanda aka gano yana da 10% na aikin analgesic na morphine a cikin kwayoyin halitta na rodent.Wannan binciken ya ƙarfafa ƙungiyar don fara cikakken nazari na 2-benzyl benzimidazole da kuma kafa dangantakar aiki-tsari don wannan sabon iyali na masu kashe ciwo.An haɓaka hanyoyin haɗin kai guda biyu don shirya waɗannan mahadi.

Hanya ta farko ta ƙunshi ƙaddamar da o-phenylenediamine tare da phenylacetonitrile don samar da 2-benzylbenzimidazole.Sannan ana alkylated benzimidazole tare da 1-chloro-2-dialkyl aminoethane da ake so don samar da samfur na ƙarshe.Wannan hanya ta musamman ita ce mafi amfani don shirya benzimidazole ba tare da maye gurbinsu akan zoben benzene ba

Mafi yawan haɗin kai [4] wanda ƙungiyar Swiss ta fara ya ƙunshi alkylation na 2, 4-dinitrochlorobenzene tare da 1-amino-2-diethylaminoethane don samar da N- (β-diethylaminoethyl) -2, 4-dinitroaniline [aka: N' - (2, 4-dinitrophenyl) -n, n-diethyl-ethane-1, 2-diamine.Abubuwan da ke maye gurbin 2-nitro akan mahadi na 2, 4-dinitroaniline sannan ana zaɓin rage su zuwa daidaitattun amines na farko ta amfani da ammonium sulfide azaman wakili mai ragewa.Ammonium sulfide na iya samar da iskar hydrogen sulfide a cikin wurin ta hanyar ƙara ammonium hydroxide mai taƙaddama da daidaita shi da maganin.Matsakaicin da aka kafa ta hanyar zaɓaɓɓen raguwa na 2-nitro-substituent 2- (β-diethylaminoethyl aminoethyl) -5-nitroaniline, wanda sannan ya amsa tare da iminoethyl ether hydrochloride na 4-ethoxy phenylacetonitrile (aka: p-ethoxy benzyl cyanide).Imnoether, 2- (4-ethoxy phenyl) -acetyliminoate ethyl ester hydrochloride, an shirya shi azaman iskar gas ta hanyar narkar da benzyl cyanide mai maye gurbin 4 a cikin cakuda ethanol mai anhydrous da chloroform, sannan saturating maganin tare da hydrogen chloride anhydrous.Halin da ke tsakanin 2- (beta-dialkyl aminoalkyl amine) -5-nitroaniline da hydrochloride na iminoethyl ether yana haifar da samuwar etonitrazine.Hanyar ya dace musamman don shirye-shiryen 4-, 5-, 6- da 7-nitrobenzimidazole.Zaɓin maye gurbin iminoethers na phenylacetic acid zai iya samar da mahadi tare da madogara da yawa a rukunin benzene 2.

Yawancin analogues an san su, kawai sauran sanannen fili da aka samu daga farkon binciken a cikin 1950s shine clonitacetone, wanda ya fi etonissini rauni (kimanin sau 3 morphine).Kwanan nan, tun a ƙarshen 2018, yawancin analogues masu zanen kaya sun fara bayyana a kasuwannin da ba bisa ka'ida ba a duniya, tare da fitattun mahadi sune metronidazole, isonidazole da ettazine, amma wasu suna ci gaba da bayyana.