IL33278A - 2-nitroimidazoles with antibacterial activity and their preparation - Google Patents

Description

WITH ANTIBACTERIAL ACTIVITY AND THEIR PREPARATION The invention is with a new class of imidazole tives of the formula wherein one of the radica a lower alkyl and the other is a The compounds of the invention are prepared by diazotizing the corresponding with an alkali metal nitrite in concentrated fluoboric The obtained diazo derivative is then again contacted with an alkali metal in an aqueous in the presence of copper powder as the Though the amount of the alkali metal nitrite is not strictly it is advisable in the first step of the to use an about equimolecular amount of it in respect of the starting while in the second stage an tional equimolecular quantity or preferably a large is to be The weight of the catalyst is also not but we have found that parts by weight in respect of the give the best The end products are then removed ding to usual for instance by acidifying the dium to a pH of about 2 and extracting the compound with a table Other analogous derivatives active as trichomonacides are but are quite different from for as to the substituents In in 700 only the preparation of methyl derivatives of is and refers to vhich are substituted solely at the position various radicals are present at the position but an example in which the substituent is a group is never the nitroimidazoles of the invention proved excellent as antibacterial and more particularly against Trichomonas In respect of the compounds and of other known such as azomycin and they display a remarkably higher activity and a lower The activity data as as the toxicity of some tatives of the class and of the two known cited comparatively reported hereinafter in table The symbol represents the oral dose in effective in the 50 of the treated animals the experimental infection from Trichomonas vaginalis in Also the toxicity is relevant to by oral route and expressed in Table 1 Compound of example 1 70 2 16 608 12 700 4 11 500 5 35 1500 6 17 azomycin 80 The following examples are given by way of illustration and are not to be considered as a limitation of this many variations of which are without depavting from the scope and spirit xamp e 1 i tro imidazole propionaldehyde diethyl A mixture of of diethyl 128 of ethanolamine and 400 of cyclohexanol are refluxed for five The cyclohexanol and the excess of ethanolamine are evaporated off and the dissolved in 450 of is once with of The layer is dried and the solvent removed with the aid of The residue is distilled collecting the fractions boiling at Yield of amino prop diethyl ydroxyethyl imidazole A solution of of de diethyl acetal in 7 of 1 hydrochloric acid is stirred three hours at The cooled solution is cautiously brought to with sodium then 23 of cyanamide are The mixture is warmed two hours at maintaining the pH at the above value with hydrochlor and extracted with chloroform in order to remove the The aqueous layer is separated and concentrated to and the residue is extracted several times with ethanol The combined alcoholic extracts are concentrated to The oily containing the hydrochloride of the desired is dissolved in 100 of water and into a boiling solution of of cric in 800 of Crystals are formed of im ida zole The correspond ng hydrochloride is again obtained by dissolvin the picrate in a boiling mixture of 500 of hydrochloric acid and 1000 of The aqueous phase is sep washed with and concentrated to The consisting 3 o hydrochloride is ized from methyl ethyl Yield roxyethyl of l dissolved in of of aqueous fluoboric acid are The mixture is cooled at then a solution of of sodium nitrite in 7 of water are slowly added during 20 while After ding 10 minutes at the liquid is poured into a mixture of of copper of sodium nitrite and 700 of under strong which is then protracted for After filtering the pi 1 is adjusted to with hydrochloric and the solution is extracted with ethyl ace organic extracts are washed with aqueous sodium dried over sulphate and the solvent distilled The of ydroxyethyl is ized from isopri yl Yield Analysis Calculated for Found E 2 e roxyethylain ino d acetal Prepared as described in Example item f om of diethyl acetal and of ethanolamine Yield 4 imidazole Prepared from of hyde diethyl acetal and of according to the method described under item of example Yield J A solution of 10 of imidazole hydrochloride in 22 of water and 44 5 of aqueous fluoboric acid is cooled at and additioned dropwise while with of sodium nitrite in 10 of The temperature is kept for 10 minutes Then the solution is a mixture of of copper of sodium nitrite and 1100 of under strong Stirring is continued for then the liquid is acidified to with hydrochloric then repeatedly extracted with ethyl The combined ethyl acetate extracts are washed with aqueous sodium dried over then the solvent is distilled The residue is Crystallized from ving of Analysis Calcul ed for 3 1 1ydroxyethy o y 1 1 Prepared substan according to the described in the previous diethyl acetal Prepared from 267 of aleraldehyde diethyl acetal and 1000 of ethanolam ropylimid hydrochloride Prepared from 62 of diethyl acetal and 37 of Yield Prepared from of midazole hydrochloride and 41 of sodium Yield Analysis Calculated J 3 3 Found E 4 imidazole Prepared substan to the method described in ple diethyl from 100 of diethyl acetal and 500 of ethanolamine Yield b roxyethyl opropyl imidaz hydrochlo ide Prepared from 37 oxye diethyl acetal and of Yield c oxyethyl ro Prepared from of roxyethyl hydrochloride and of sodium Yield is Calculated for Example 5 a hydrochloride To a solution of chloride in a yield by refluxing for one hour a of roxybutyr acid in ethanol with hydrogen in 4 of water and 200 of of sodium amalgam are added in about two keeping the temperature between and and the pH at the value of by adding dropwise hydrochloric The mixture is stirred two more hours to complete the then the mercury is separated and the pH brought to by cautious o at a temperature of Forty two of added and the resulting solution is heated for two hours at keeping the pH at about with chloric The solution is then evaporated to the residue is washed with and extracted with lic hydrogen The alcoholic solution is evaporated to dryness and the residue recrystall ized from isopropyl alcohol giving of imidazole p 7 Prepared according to the method described under item of Example from of hydrochloride and of sodium Yield Calculated for N 0 9 3 3 Found Exampl e yl imidazole a hydrochloride Prepared according to the method described in item of example from of chloride in a yield by refluxing for one hour a solution of inovaleric acid in tured with hydrogen and of The hydrochlo ide is obtained an oily which can be purified by dissolving it in of water and pouring into a boiling solution of of cric acid in 1300 of The precipitate is crystallized from giving of imidazole b Prepared according to the desc ibed under item of Example from 5 of thylimidazole hydrochloride and of sodium Yield Analysis Calculated C H 0 J Found insufficientOCRQuality

Claims (1)

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