Etonitat le benzimidazole ea opioid e amanang le eona e ile ea sibolloa ho elella bofelong ba lilemo tsa bo-1950 ke sehlopha sa bafuputsi ba Switzerland ba sebetsang k'hamphaning ea meriana ea CIBA (eo hona joale e leng Novartis).E 'ngoe ea metsoako ea pele e ithutoang ke sehlopha sa Switzerland e ne e le 1-(beta-diethylaminoethyl) -2-benzyl benzimidazole, e fumanoeng e na le 10% ea ts'ebetso ea morphine ea analgesic ho rodent bioassometry.Se fumaneng sena se khothalelitse sehlopha ho qala boithuto bo hlophisitsoeng bo felletseng ba 2-benzyl benzimidazole le ho theha kamano ea sebopeho le ts'ebetso bakeng sa lelapa lena le lecha la lipilisi tsa bohloko.Ho ile ha etsoa mekhoa e 'meli e akaretsang ea ho kopanya metsoako ena.

Mokhoa oa pele o kenyelletsa condensation ea o-phenylenediamine le phenylacetonitrile ho theha 2-benzylbenzimidazole.Joale benzimidazole e entsoe alkylated le 1-chloro-2-dialkyl aminoethane e lakatsehang ho etsa sehlahisoa sa ho qetela.Mokhoa ona o bohlokoa haholo bakeng sa ho lokisa benzimidazole ntle le lintho tse ling tse ling tsa lesale la benzene

Tlhahiso e akaretsang ka ho fetisisa [4] e entsoeng ke sehlopha sa Switzerland pele e kenyelletsa alkylation ea 2, 4-dinitrochlorobenzene le 1-amino-2-diethylaminoethane ho theha N-(β-diethylaminoethyl) -2, 4-dinitroaniline [aka: N' - (2, 4-dinitrophenyl) -n, n-diethyl-ethane-1, 2-diamine].Li-substituents tsa 2-nitro ho 2, metsoako ea 4-dinitroaniline e ntan'o khethoa ka mokhoa o ikhethileng hore e be li-amine tse ka sehloohong tse tsamaisanang ka ho sebelisa ammonium sulfide e le ho fokotsa.Ammonium sulfide e ka etsa khase ea hydrogen sulfide in situ ka ho eketsa motsoako oa ammonium hydroxide le ho e tlatsa ka tharollo.Bohareng bo entsoeng ka ho fokotsa ho khethoa ha 2-nitro-substituent 2- (β-diethylaminoethyl aminoethyl) -5-nitroaniline, e ntan'o itšoara ka iminoethyl ether hydrochloride ea 4-ethoxy phenylacetonitrile (aka: p-ethoxy benzyl cyanide).Iminoether, 2-(4-ethoxy phenyl) -acetyliminoate ethyl ester hydrochloride, e lokiselitsoe e le khase ka ho qhibiliha 4-substituted benzyl cyanide ka motsoako oa anhydrous ethanol le chloroform, ebe o tlatsa tharollo ka anhydrous hydrogen chloride.Boitšoaro pakeng tsa 2-(beta-dialkyl aminoalkyl amine) -5-nitroaniline le hydrochloride ea iminoethyl ether e fella ka ho thehoa ha etonitrazine.Mokhoa ona o loketse ka ho khetheha bakeng sa ho lokisetsa 4-, 5-, 6- le 7-nitrobenzimidazole.Khetho ea li-iminoethers tse fetotsoeng tsa phenylacetic acid e ka fana ka metsoako e nang le likarolo tse ngata sebakeng sa benzene 2.

Li-analogue tse ngata lia tsebahala, motsoako o mong o hlokomelehang o nkiloeng thutong ea mantlha lilemong tsa bo-1950 ke clonitacetone, e fokolang haholo ho feta etonissini (makhetlo a ka bang 3 morphine).Haufinyane tjena, ho tloha ho elella bofelong ba 2018, li-analogues tse 'maloa tsa moqapi li qalile ho hlaha' marakeng o seng molaong ho pota lefatše, ka metsoako e tummeng ka ho fetisisa ke metronidazole, isonidazole le ettazine, empa tse ling li ntse li tsoela pele ho hlaha.