Patent GB-594816-A (GB)
Title: Process for the production of substituted 3-amino-1-nitrobenzenes
Filed: 1941-12-18
Abstract: 3-Amino-1-nitrobenzenes substituted in the 4-position by an oxygen atom carrying a hydrocarbon radical having at least three carbon atoms, or their salts, are obtained by partially-reducing a 1.3-dinitrobenzene substituted as above in the 4-position and isolating the product from the mixed isomers obtained. Alternatively, 1 : 3-dinitrobenzenes substituted in the 4-position by a hydroxyl group may be used as starting materials and after the reduction replacing the substituent in the 4-position to furnish the requisite compound.  The hydrocarbon radical is optionally saturated and comprises an alkyl, alkenyl or alkyl or aralkenyl group and the benzene nucleus may contain also substituents, especially alkyl groups, in one or more of the positions 2, 5 and 6.  The solid product is isolated from the mixed isomers by treating the reaction mixture with an acid, especially hydrochloric or sulphuric acid, and separating the mixed salts by fractional solubilities in solvents such as water, or fractional crystallization.  Suitable starting-materials are the halogenobenzenes, preferably chlorobenzene, or phenol, which are nitrated to obtain 4 - chloro- or 4 - hydroxy - 1.3 - dinitro - benzene, when the halogen atom or the hydroxy group is replaced by the desired alkoxy, alkenoxy aralkoxy or aralkenoxy.  In examples: (1) a propanol solution of 4-chloro-1 : 3-dinitrobenzene is treated with sodium hydroxide and then sodium sulphide added.  The product is refluxed, extracted and acidified to produce the hydrochloride of 4-propoxy-3-nitro-1-amino-benzene; (2) as in example (1), but using 4-chloro-1 : 3-dinitrobenzene and butanol-1 as starting materials; (3) as in example (1) using 4-chloro-1 : 3-dinitrobenzene and allyl alcohol; (4) an alternative method of working up the reduction product of example (1); (5) an ethyl alcohol solution of 4-hydroxy-1 : 3-dinitrobenzene is reduced with sodium sulphide and acidified to give 4-hydroxy-3-amino-1-nitrobenzene, which is acetylated to 4-hydroxy-3-acetylamino-1-nitrobenzene and treated with allyl bromide to form 4-allyloxy-3-acetylamino1-nitrobenzene which is finally hydrolysed to the free amino compound.  A sample has been furnished under Sect. 2 (5) of 5 - methyl - 4 - n - propoxy - 3 - nitro - 1 - aminobenzene made by reducing 5 - methyl - 4 - n - propoxy-1 1 : 3-dinitrobenzene with sodium sulphide in n-propyl alcohol solution as in example (1) followed by acidification and purification by crystallization of its hydrochloride.ALSO:3-Amino-1-nitrobenzenes substituted in the 4-position by an oxygen atom carrying a hydrocarbon radical having at least three carbon atoms are powerful sweetening agents and may be used to sweeten foodstuffs luxuries and medicaments such as beverages, pudding powder, confectionery and pastry cook's products, preserves, jams or medicines.  The compounds may be mixed or coated with white edible substances such as lactose saccharose, dextrose or starch.  Such mixtures can be formed into tablets, pastilles or dragees.  Some of the compounds are active as local anaesthetics and are stated to be particularly suitable for use in the eye.  Specified compounds whose preparation is described include 4-propoxy-3-amino - 1 - nitrobenzene, 4 - butoxy - 3 - amino - 1 - nitrobenzene, 4 - allyloxy - 3 - amino - 1 - nitro - benzene, 4 - allyloxy - 3 - acetylamino - 1 - nitro - benzene and 5-methyl-4-n-propoxy-3-amino-1-nitrobenzene.