Etonitat ndi opioid agonist benzimidazole anapezeka kumapeto kwa zaka za m'ma 1950 ndi gulu la ofufuza a ku Switzerland omwe amagwira ntchito ku kampani yopanga mankhwala ya CIBA (tsopano Novartis).Chimodzi mwazinthu zoyamba zomwe gulu la Switzerland lidaphunzira ndi 1-(beta-diethylaminoethyl) -2-benzyl benzimidazole, yomwe idapezeka kuti ili ndi 10% yamankhwala a morphine mu rodent bioassometry.Kupeza kumeneku kunalimbikitsa gululo kuti liyambe kufufuza mozama za 2-benzyl benzimidazole ndi kukhazikitsa ubale wogwirizana ndi banja latsopanoli la opha ululu.Njira ziwiri zophatikizira zonse zidapangidwa kuti zikonzekere izi.

Njira yoyamba ikukhudza condensation wa o-phenylenediamine ndi phenylacetonitrile kupanga 2-benzylbenzimidazole.benzimidazole ndiye alkylated ndi 1-chloro-2-dialkyl aminoethane yofunidwa kuti apange chomaliza.Njira imeneyi ndiyothandiza kwambiri pokonza benzimidazole popanda zolowa m'malo mwa mphete ya benzene

Kaphatikizidwe kambiri [4] kopangidwa ndi gulu la Swiss koyamba kumakhudza alkylation ya 2, 4-dinitrochlorobenzene ndi 1-amino-2-diethylaminoethane kupanga N-(β-diethylaminoethyl) -2, 4-dinitroaniline [aka: N' - (2, 4-dinitrophenyl) -n, n-diethyl-ethane-1, 2-diamine].Ma 2-nitro substituents pa 2, 4-dinitroaniline mankhwala ndiye amachepetsedwa mwapadera kuti agwirizane ndi ma amine oyambirira pogwiritsa ntchito ammonium sulfide monga kuchepetsa wothandizira.Ammonium sulfide imatha kupanga mpweya wa hydrogen sulfide mu situ powonjezera madzi osungunuka a ammonium hydroxide ndikuwudzaza ndi yankho.Wapakatikati wopangidwa ndi kuchepetsedwa kosankhidwa kwa 2-nitro-substituent 2- (β-diethylaminoethyl aminoethyl) -5-nitroaniline, yomwe imakhudzidwa ndi iminoethyl ether hydrochloride ya 4-ethoxy phenylacetonitrile (aka: p-ethoxy benzyl cyanide).Iminoether, 2-(4-ethoxy phenyl) -acetyliminoate ethyl ester hydrochloride, imakonzedwa ngati mpweya mwa kusungunula 4-mmalo mwa benzyl cyanide mu osakaniza a anhydrous ethanol ndi chloroform, ndiyeno kudzaza yankho ndi anhydrous hydrogen chloride.Zomwe zimachitika pakati pa 2-(beta-dialkyl aminoalkyl amine) -5-nitroaniline ndi hydrochloride ya iminoethyl ether zimabweretsa kupanga etonitrazine.Njira makamaka yabwino yokonza 4-, 5-, 6- ndi 7-nitrobenzimidazole.Kusankhidwa kwa ma iminoethers osinthidwa a phenylacetic acid kumatha kubweretsa zinthu zambiri m'malo mwa benzene 2-site.

Ma analogue ambiri amadziwika, chinthu china chokha chodziwika bwino chochokera ku kafukufuku woyambirira m'zaka za m'ma 1950 ndi clonitacetone, yomwe ndi yofooka kwambiri kuposa etonissini (pafupifupi 3 times morphine).Posachedwapa, kuyambira chakumapeto kwa chaka cha 2018, ma analogue angapo opanga ayamba kuwonekera pamsika wosaloledwa padziko lonse lapansi, ndi mankhwala odziwika kwambiri omwe ndi metronidazole, isonidazole ndi ettazine, koma ena akupitiliza kuwonekera.