Patent GB-735136-A (GB)
Title: Improvements in or relating to n-(5-nitro-2-furyl)-alkylidene-3-amino-2-oxazolidones
IPC: C07D405/12
Filed: 1953-02-27
Abstract: The invention comprises compounds of the formula <FORM:0735136/IV (b)/1> where R is hydrogen or alkyl and R1-R4 are hydrogen, alkyl, hydroxyalkyl or haloalkyl (of 1-4 carbon atoms).  These are prepared (a) by condensing 5-nitrofurfural or a derivative thereof such as the diacetate (R=H) or a 5-nitrofuryl ketone (R=alkyl) with the appropriate 3-amino-2-oxazolidone; (b) as in (a), using a condensation product of the aminooxazolidone with an aldehyde or ketone which is easily split off, e.g. the N-benzylidene derivative; (c) by ring closure of a compound of the formula <FORM:0735136/IV (b)/2> where X is alkoxy or NH2; (d) from the corresponding 2-imino-oxazolidines by hydrolysis.  The amino-oxazolidones used for method (a) are made as in Specification 735,169, and can be prepared in situ.  In the examples, (1) the reaction product of b  - hydroxyethylhydrazine and diethyl carbonate is condensed with 5-nitrofurfural or its diacetate to give N-(5 - nitrofurfurylidene) - 3 - amino - 2 - oxazolidone; (2) 5-nitrofurfural 2-(b -hydroxyethyl)-semicarbazone is ring-closed with thionyl chloride to N-(5-nitrofurfurylidene)-3-amino-2-imino-oxazolidine hydrochloride and the latter hydrolysed to the 2-oxazolidone; (3) N-(5-nitrofurfurylidene) - N1 - carbethoxy - N1 - (b -hydroxyethyl)-hydrazine is ring-closed with alkali to the product of (1); (4) 3-nitro-2-oxazolidone is electrolytically reduced and the product condensed with 5-nitrofurfural to give the oxazolidone of (1); (5) the following are made by the method of (1): N-(5-nitrofurfurylidene) - 3 - amino - 5 - methyl - 2 - oxazolidone from 1 - hydrazino - 2 - propanol; N - (5-nitrofurfurylidene) - 3 - amino - 4 - methyl - 2-oxazolidone from 2-hydrazino-1-propanol; N-(5 - nitrofurfurylidene) - 3 - amino - 5 - n - butyl-2 - oxazolidone from 1 - hydrazino - 2 - hexanol; N - (5 - nitrofurfurylidene) - 3 - amino - 4 - n-butyl - 2 - oxazolidone from 2 - hydrazino - 1-hexanol; N - (5 - nitrofurfurylidene) - 3 - amino-5 - ethyl - 2 - oxazolidone from 1 - hydrazino-2 - butanol; N - (5 - nitrofurfurylidene) - 3-amino - 5 - methylol - 2 - oxazolidone from the reaction product of 1-chloropropan-2 : 3-diol and hydrazine; N-(5-nitrofurfurylidene)-3-amino - 4 : 5 - dimethyl - 2 - oxazolidone from 3 - hydrazino - 2 - butanol; (6) the last-named product is also obtained from 4 : 4-dimethyl-3-nitro-2-oxazolidone by the method of (4); (7) N - (5 - nitrofurfurylidene) - 3 - amino - 5-chloromethyl-2-oxazolidone is prepared either from 5-nitrofurfural and 3-amino-5-chloromethyl-2-oxazolidone or by treating the corresponding 5-methylol compound with thionyl chloride; (8) methyl 5-nitro-2-furyl ketone is condensed with 3-amino-2-oxazolidone to give N - [a  - (5 - nitro - 2 - furyl) - ethylidene] - 3-amino-2-oxazolidone.  Hydrazines.-1 - Hydrazino - 2 - propanol and 1 - hydrazino - 2 - hexanol are made by reacting hydrazine hydrate with propylene chlorhydrin and 1-bromo-2-hexanol respectively. Glycerol a -monochlorhydrin may be reacted similarly. 2-Hydrazino-1-propanol and 2-hydrazino-1-hexanol are made by lithium aluminium hydride reduction of ethyl a -hydrazinopropionate and ethyl a -hydrazinocaproate respectively.  1-Hydrazino-2-butanol and 3-hydrazino-2-butanol are prepared from hydrazine hydrate and 1 : 2- or 2 : 3-epoxybutane respectively.  N-(5-nitro-furfurylidene)-N1 - carbethoxy - N1 - (b  - hydroxyethyl)-hydrazine is made by condensing 5-nitrofurfural with b -hydroxyethylhydrazine and reacting the product with ethyl chloroformate.  4 : 4 - Dimethyl - 3 - nitro - 2 - oxazolidone is prepared by the nitration of 4 : 4-dimethyl-2-oxazolidone.ALSO:Anti-bacterial compositions for oral administration contain as active ingredient a compound of the formula <FORM:0735136/VI/1> where R is hydrogen or alkyl and R1-R4 are hydrogen, alkyl, hydroxyalkyl or haloalkyl (of 1-4 carbon atoms). The compounds can be made up into tablets by granulating with starch paste, drying and adding dry starch, or into lozenges by granulating with sugar syrup and adding powdered sugar, dry starch and a flavouring.