Patent GB-595703-A (GB)
Title: Improvements in or relating to the production of pyrazolone derivatives
Filed: 1945-05-23
Abstract: 1-Phenyl-2 : 3-dimethyl-4-methyleneamino-5-pyrazolone is manufactured by treating an aqueous solution of 1-phenyl-2 : 3-dimethyl-4-amino-5-pyrazolone with formic acid.  The product may be isolated as an oily monomer or preferably as a solid polymer which is formed on heating, or prolonged standing in the cold or on stirring with water and a water-immiscible solvent, e.g. benzene or toluene. In examples: (1) the reaction is effected in neutral aqueous solution in the cold, with or without stirring, and the oily monomer is separated; (2) alkali e.g. sodium carbonate, caustic soda or caustic potash, is added to the solution in which the reaction is effected, and the oil formed is taken up in benzene, the benzene solution is decanted and rapidly evaporated, and the residue isolated in the form of a salt, e.g. hydrochloride or sulphate; (3) in the process of (1), a large amount of benzene is added before or after the addition of the formaldehyde, the whole is stirred, the benzene evaporated and the polymer separated in powder form; if a smaller amount of benzene is used, a granular powder is obtained directly without evaporation of the solvent; (4) the process is effected with heating in the presence of a moderate amount of benzene, which is then evaporated, causing the polymer to separate in powder form; (5) the process of (4) is carried out in the cold with rapid stirring; (6) a solution of 1-phenyl-2 : 3-dimethyl-4-amino-5-pyrazolone hydrochloride and hydrochloric acid (obtained by hydrolysis of 1-phenyl-2 : 3-dimethyl-4-sulphamino-5-pyrazolone) is neutralized with sodium carbonate and treated as in (3) (using a large amount of benzene); (7) the solution neutralized as in (6) is made alkaline with caustic soda or other alkali and further treated as in (2), with the alternative of boiling the benzene or stirring it with water to obtain the polymine product; (8) the process of (6) is carried out with a smaller amount of benzene to produce the polymer in granular form.  1 - Phenyl - 2 : 3 - dimethyl - 4 - dimethylamino - 5 - pyrrazolone is manufactured by simultaneous or successive reduction and methylation of monomeric or polymeric 1-phenyl-2 : 3-dimethyl-4-methyleneamino-5-pyrazolone.  The single stage process may be effected by means of formaldehyde and a reducing agent, e.g. metal and an acid, formic acid or hydrogen in the presence of a hydrogenation catalyst, such as platinum, palladium or nickel.  For the two stage process, reduction may be effected, for example, with acid and a reducing metal, e.g. hydrochloric acid and zinc, with formic acid under heat, or with hydrogen in the presence of a metal hydrogenation catalyst, and the resulting 1-phenyl-2 : 3-dimethyl-4-monomethylamino-5-pyrazolone may be methylated with a methyl halide, dimethyl sulphate, or formaldehyde in the presence of a reducing agent.  In examples, simultaneous reduction and methylation are effected by means of formaldehyde under the following conditions: (9) in alcoholic solution in the presence of hydrogen and active nickel, by stirring at ordinary temperature and pressure or with the use of elevated temperature and superatmospheric pressure; (10) in the presence of zinc (or other metal, e.g. aluminium) and dilute hydrochloric acid (or other acid, e.g. sulphuric); (11) in the presence of aqueous formic acid at 85-95 DEG  C.  A sample has been furnished under Sect. 2 (5) of 1-phenyl-2 : 3-dimethyl-4-dimethylamino-5-pyrazolone prepared by reducing the methyleneamino compound with aqueous formic acid and treating the resulting solution of 1-phenyl-2 : 3-dimethyl-4-methylamino-5-pyrazolone formate with formaldehyde and formic acid.