Patent GB-884206-A (GB)
Title: 4-alkoxymetanilamides and compositions containing them
IPC: C23F11/04
Filed: 1958-04-02
Abstract: Alkoxymetanilamides of the general formula <FORM:0884206/IV (b)/1> wherein R1 is an alkyl group having from 2 to 4 carbon atoms, and R2 and R3 represent hydrogen atoms or alkyl groups having from 1 to 3 carbon atoms, may be prepared using 4-halo-3-nitrobenzenesulphonic acid as starting material.  In an example, the potassium salt of 4-chloro-3-nitrobenzenesulphonic acid is dried in vacuo and then reacted at 100 DEG C. with a mixture of phosphorus pentachloride and phosphorus oxychloride to give 4-chloro-3-nitrobenzenesulphonyl chloride.  This sulphonyl chloride is reacted with concentrated ammonium hydroxide to give 4-chloro-3-nitrobenzenesulphonamide.  The latter is dissolved in n-propyl alcohol and, while maintaining a temperature of about 70 DEG C., a solution of sodium hydroxide in n-propyl alcohol is added; and, from the reaction mixture, 3-nitro-4-propoxybenzenesulphonamide is separated.  Finally, the nitro compound is hydrogenated in the presence of Raney nickel to yield 4-propoxymetanilamide.  If, a concentrated aqueous solution of methylamine or dimethylamine is used instead of the ammonium hydroxide in the second step of the above process, there is obtained 4 - chloro - 3 - nitro - N1 - methyl - benzenesulphonamide or 4-chloro-3-nitro-N1,N1-dimethyl-benzenesulphonamide respectively. Similarly, alcohols other than n-propyl alcohol can be employed in step 3.  The alkoxymetanilamides form salts with both acids and bases.  Salts of hydrochloric, sulphuric, acetic, citric and p-toluenesulphonic acids are mentioned.  Salts of sodium, potassium, lithium, calcium, triethylamine, ethylenediamine, morpholine and piperidine are also referred to. The alkoxymetanilamides may be used as local anaesthetics, fungicides (Group VI) and corrosion inhibitors (Group II).ALSO:Corrosion of iron and mild steel by aqueous sulphuric acid is inhibited by adding 5 to 10% of 4-propoxymetanilamide to the acid. For the preparation of the inhibitor-(see Group IV (b)).ALSO:Compositions suitable for use as local anaesthetics in the form of sterile solutions for injection, sprays, ointments, lotions and dusting powders, contain as active ingredient an alkoxymetanilamide of the general formula <FORM:0884206/VI/1> or a salt thereof, wherein R1 is an alkyl group having from 2 to 4 carbon atoms, and R2 and R3 are hydrogen atoms or alkyl groups having from 1 to 3 carbon atoms.  A sterile solution for injection may be prepared by mixing the active compound (0.5 to 1.5%) with polyethylene glycol (15 to 20%) and water (or isotonic saline), and heating the mixture at 120 DEG  C. in an autoclave.  Sympathomimetric agents such as beta-phenylethylamine, tyramine, synephrine, phenylephrine, levarterenol, epinephrine, phenyl propanolamine and ephedrine, may be included in the solution to be sterilized; also anti-bacterial agents such as methylparaben and benzoic acid, and anti-oxidants such as sodium bisulphite, may be added.  A specified ointment comprises 0.75% of 4-butoxymetanilamide hydrochloride, admixed at a temperature of 60 DEG  C. with petrolatum, and 0.2% of sodium propionate as fungicidal agent.  To obtain a lotion, the active anaesthetic compound may be emulsified with calamine, with the aid of a mixture of polyethylene glycol and the monostearate of glycol.  Suitable inert carriers, when the anaesthetic compound is required in the form of dusting powder, are talc, zinc oxide, zinc stearate, boric acid, starch, chalk, insoluble salts of bismuth and lycopodium.  The compounds of the invention are also useful as fungicides, e.g. an aqueous composition containing 0.5% of propoxymetanilamide may be sprayed on tomato plants to control Early Blight.  For the preparation of the compounds see Group IV (b).