HU176612B - Process for preparing allantoin - Google Patents

Abstract

The invention relates to a process for the preparation of allantoin in which glyoxal is treated at 40 to 60 DEG C under the catalytic action of cobalt salts and nitrous acid with nitric acid or of cobalt salts and in the presence of water and air [lacuna] oxides of nitrogen which form nitrous acid or nitric acid, then the ammonium salt of a strong mineral acid is added, the mixture is subsequently cooled and filtered, and the filtrate is reacted with urea. Allantoin is used as cell-regenerating agent in medicine and cosmetics.

Description

The present invention relates to a novel process for the preparation of allantoin by reacting glyoxylic acid with urea. Allantoin is used as a cell regenerating agent in medicine and cosmetics.

Several methods of synthesizing allantoin are known. For example, uric acid with lead oxide, hydrogen peroxide or permanganate [Org. Synth. 13, 1 (1933)] or glycoluril with hydrogen peroxide [7. park. Chem., 113, 92 (1926); No. 2,802,011 U.S. Pat. A disadvantage of these processes is that the starting materials are not available on an industrial scale. A further disadvantage of the process disclosed in the cited U.S. Patent is that the spacetime yield is poor due to the use of very dilute solutions. Accordingly, the energy requirement is high: 1.4 liters of water are required to evaporate 9.13 g of allantoin as described in Example 3.

Reaction of mesoxal or alloxanic acid with urea to allantoin is also known. The procedures are of only theoretical importance because the starting materials are not commercially available.

No. 1,939,924. Disclosure document in the Federal Republic of Germany and 7 725 095 According to the Japanese patent, glyoxylic acid or glyoxylic acid-containing alkalis are reacted with excess urea in the presence of mineral acids or organic sulfonic acids. The process uses as starting material either a 10 to 30% solution of pure glyoxylic acid, which is relatively expensive, or is based on waste liquors containing glyoxylic acid, which will result in costly purification and concentration as a purity for therapeutic or cosmetic purposes.

No. 2,158,090. U.S. Pat. No. 4,600,125 discloses glyoxylic acid esters or glyoxylic acid acetal esters with urea in an acidic medium. The process, as a stepwise synthesis, is expensive and cumbersome, and alkali metal alcoholates are required for the preparation of the acetal glyoxylic esters.

It is an object of the present invention to provide a process for the production of allantoin which is free from the disadvantages of known processes, starting from cheap and commercially available raw materials, and can be carried out in a single container process without the need for isolation, concentration or purification of intermediates.

The process of the present invention involves the oxidation of glyoxalized soluble cobalt salts and nitric acid together with nitric acid or soluble cobalt salts with nitric oxide or nitric oxide gas mixture, followed by addition of a strong mineral acid ammonium salt, filtration of the reaction mixture and filtration of the .

Glyoxal may be a technical grade glyoxal solution or polymerized glyoxal, or 2,3-dichloro-1,4-dioxane may also be used.

The water-soluble cobalt salt and nitric acid are added in catalytic amounts. One mole of glyoxal 3.10 ^-5 -6.10 ^"4 moles of a cobalt salt, preferably kobaltnitrátot, sulfate, acetate or chloride is used.

The most added salts of nitrous acid, namely one mole of glyoxal 4.10 -8.10 ^{-3 -3} mole quantities. Sodium nitrite is preferably used.

The oxidizing agent, i.e. nitric acid or nitric oxides, is reacted in equimolar amounts to glyoxal.

Preferably, two-fifths of the total amount of sodium nitrite used as the catalyst is added to the glyoxal solution, and the remaining three-fifths are dissolved in nitric acid and the solution is added dropwise to the glyoxal solution. In this way, the concentration of the catalyst can be kept constant.

Among the oxides of nitrogen, the oxidizing agent may be, for example, nitrogen monoxide or nitrogen dioxide. Preferably, a mixture of air and nitrogen dioxide is used, whereby one mole of nitrogen dioxide is counted per mole of glyoxal.

The ammonium salt of the strong mineral acid may be, for example, ammonium sulfate, nitrate, chloride or phosphate. 0.04-0.2 moles of ammonium salt are added per mole of glyoxal. 20

The oxidation is preferably carried out at a temperature of 40-60 ° C. After the oxidation has been completed the solution containing glyoxylic acid hydrate are now filtered and then reacted with urea so that urea per mole of glyoxal is added to 2 to 6 moles, and the reaction mixture is 25 5 to 10 40 to 90 hours at ⁹ ° C preferably 60-80 ° C. The reaction mixture is then cooled to 30 ° C and the precipitated allantoin is filtered off with suction. The yield of the process is about 40% based on the starting glyoxal.

Example 1

13.14 kg of 40% glyoxal solution (d = 1.270 g / cm ³ ) are mixed with 0.5 liter of concentrated sulfuric acid in 3 liters of water. To the solution was added 1.8 g of cobalt (II) nitrate hexahydrate. The mixture is heated to 50-60 ° C and 20 g of sodium nitrite are added with stirring. A solution of 6 liters of concentrated nitric acid (d = 1.40 g / cm ³ ) and 30 g of sodium nitrite in 4.2 liters of water is then added dropwise to the reaction mixture under cooling and stirring, so that the reaction temperature is between 40 and 60 ° C. we can keep it. Time for instillation

4-6 hours. The mixture was allowed to stand for 30 minutes, 2.4 kg of ammonium sulfate was added and the mixture was cooled to 6-10 ° C for several hours. After filtration, the filtrate was mixed with 14.5 kg of urea, heated to 70 ° C with constant stirring and kept at this temperature for 10 hours. Allantoin precipitated from the reaction mixture cooled to 30 ° C is filtered off with suction and washed with cold water. 6.3 kg of 50 (44% of theory) of allantoin are obtained, m.p. 233-235 ° C (recrystallization from water).

Example 2 55

1.97 kg of a 40% solution of glyoxal (d = 1.27 g / cm ³ ) was mixed with a solution of 75 ml of concentrated sulfuric acid in 450 ml of water, 0.27 g of cobalt (II) nitrate hexahydrate was added and heat the solution to 45-50 ° C. Subsequently, 1 mole of nitrogen dioxide per liter of glyoxal was introduced with cooling for 4 hours so that the temperature was maintained at 45-50 ° C. After a 30 minute post-reaction, 400 g of ammonium sulfate was added and the mixture was cooled to below 5-10 ° C and maintained at this temperature for several hours. After filtration, 2.2 kg of urea were added to the filtrate and the reaction mixture was heated at 70 ° C for 10 hours with constant stirring. Allantoin precipitated from the solution cooled to 30 ° C is suctioned off and washed with cold water. After cooling the mother liquor to 5 ° C, an additional fraction can be obtained. 900 g (42% of theory) of allantoin are obtained, m.p. 234-235 ° C.

Example 3

1.97 kg of a 40% solution of glyoxal (d = 1.27 g / cm ³ ) is mixed with a solution of 75 ml of concentrated sulfuric acid in 450 ml of water, 0.27 g of cobalt (II) nitrate hexahydrate are added and the mixture is added. Heat to 45-50 ° C. After cooling, a mixture of nitrogen monoxide and air is introduced into the solution for 4 hours at such a rate that the temperature does not rise above 45-50 ° C. After a 30 min post-reaction, 400 g of ammonium sulfate was added to the reaction mixture, which was maintained at 5-10 ° C for several hours. The mixture was filtered, 2.2 kg of urea was added to the filtrate and the mixture was kept at 70 ° C for 10 hours with constant stirring. Allantoin precipitated from the solution cooled to 30 ° C is suctioned off and washed with cold water. The mother liquor was cooled to 5 ° C to isolate additional allantoin. Yield: 43%; mp 232-234 ° C.

Claims (1)

Process for the preparation of allantoin by reacting glyoxylic acid with urea, characterized in that the glyoxal is at 40-85 ° C, preferably 40-60 ° C. counting a) 1 mol of glyoxal 3.10 -6.10 ^-J ~ ⁴ mol of water-soluble cobalt salt, preferably cobalt nitrate and 4.10 -8.10 ~ ^{3 '3} moles of nitrous acid or a salt thereof in the presence of nitric acid, 1 mole Or bj calculated glyoxal 3.10 ^-5 -6.10 ^-4 mol of water-soluble cobalt salt, preferably cobalt nitrate in the presence of nitric oxide or oxidized glyoxylic gas mixture of nitric oxide-containing amiköris the oxidizing agent is employed in equimolar amounts, and then with a strong mineral acid amtnóniumsóját, preferably ammonium sulfate is added in an amount of 0.04-0.2 mole per mole of glyoxal, then the reaction mixture is filtered and the filtrate is reacted in a manner known per se at 50-80 ° C with 2-6 moles of urea per mole of glyoxal for 5-10 hours. .