CS199378B1 - Method of producing allantoins - 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 invention relates to a process for producing allantoin. Allantoin is used as a cell regenerating agent in medicine and cosmetics.

The following methods are known for the synthesis of allantoin:

1) Oxidation of uric acid with lead oxide, hydrogen peroxide, or permanganates (Org. Synth. 13-1 / 1933 // and oxidation of glycoluril with hydrogen peroxide / J.Pract. Chem. 113, 92/1926/5 US Patent 2 802 011 / 1956 //.

2) Reaction of moaaxolic acid or alloxanoic acid and urea at elevated temperature.

3) Reaction of glyoxylic acid or glyoxylic acid-containing effluents with urea in the presence of inorganic acids or organic sulfoacids (DOS 1 939 924 (1971)).

4) Reaction of glyoxylic acid esters or glyoxylic acetal esters with urea in an acidic medium (U.S. Pat. No. 2,158,090 (1937)).

The processes mentioned in sub-1 and sub-2 have the drawback that expensive and technically unrecoverable compounds have to be used as starting products. The method of sub-3 requires either the use of pure 10 to 30% glyoxylic acid solutions, which is

199379 implementing an industrial scale rather expensive, or - the use of waste liquors containing the glyoxylic acid, this has involved costly purification operations and operations alo ^u now running for zkoncontrov ^ck, b ^y ee dos ^Ah lo ^p ro ^drug ADR ^KE tosmeticto ^uses Stopnete purity.

The method mentioned sub 4 / is envisaged for the manufacture of acetals of glyoxylic acid using alkali metal alcoholates and Jato honourest ^{t p} u ^p from the new DSO sn ^{b y} t ^{y e} z striking and tedious.

It is an object of the present invention to provide a process for the production of allantoin without the drawbacks of the known processes starting from new, inexpensive and technically accessible raw materials - and is feasible in a single container process, without intermediate isolation and without intermediate concentration and purification operations.

The c ^s l doséihne that the invention is glyoxal. from ^p raoov ^{a r at} 40 * 60 ° C at the catalytic action of soluble cobalt salts and ester of nitrous acid, nitrates, then adding ammonium salt of a strong - inorganic acids, then ee is cooled, filtered and the filtrate thus obtained is reacted with urea. Instead of combining nitric acid with β nitric acid, they can be used with equal success - nitrogen oxides or nitrogen oxides mixed with air.

Glyoxal may be used jeto technical solution of glyoxal, glyoxal or a polymer such as ^{2, 3-dichloro-l,} 4-dioxane. Jevýhodné ^p OUZ ^s vat 1 mol ^g l ^y oxalate 3.1 ~ ^ ⁰ to 6 ·. 10 ^"4 mol ⁱⁿ water-soluble" salt of the cobalt-Jato ^For example the nitrate koba3.tu, ^s wound with cobalt, cobalt acetate or cobalt chloride.

^Nitrous acid being used ^and zejmtaa in the form of SOH. Use 4E0 ^- 3 to 8 only.

• Ю ^"3 mole dusí.tanu, ^eg Ikla ^d eodnéto nitrite per 1 mol of ^g l ^y oxalate. Výhotaé edložit ^instance sodium nitrite, add 2/5 of the total amount of the solution of glyoxal and glyoxal 3.5 residue dissolved in nitric acid / 1 mole per 1 mole of glyoxal and / added dropwise. In this way, the maximum concentration of the catalyst is achieved. Nitrogen oxides, such as nitrogen dioxide or nitric oxide in admixture with air, are further used as oxidizing agents, with nitrogen dioxide being preferred. Here, 1 mole of nitrogen dioxide is used per mole of glyoxal.

Ammonium salts of strong inorganic acids are, for example, ammonium sulfate, ammonium nitrate, ammonium chloride or ammonium phosphate in amounts of 0.04 to 0 * 2 mol per 1 mol of glyoxal. The solution, which after the oxidation is completed after filtration of 2-6 moles of urea per ^{1 y l} mo ^Gly oxalate and heated ^and the 5- to ¹ 0 40 hours and ^from 90 ° C preferably ^60-80 ° C. P ^{s s} cooled to 30 ° ^C in ^{azide y} SR 'allantota and filtered with suction. Yields corresponding to about 40% of theory are obtained.

Exemplary embodiment

19937В

Example 1 ·

13.14 kg of a 40% glyoxal solution (d 1.270 g / cm ³ ) are mixed in a solution of 0.5 ^L concentrated sulfuric acid in 3 L water. Was added -1.8 g of cobalt nitrate ^{Co /} H0 ^{j /} 2 · 6 H ^g 0, ^{mane e 50-6 at 0} ° C - ^{under stirring,} with ^d a n ^{e pl} nitrite ⁱⁿ 20 ^g sodtoto and was slowly begins ^Rik apávet mixture ^{1 to} 6 ^alkyl sel oncentrovan ^{s i} n ^y «iusičné (d = 1 ^{40 g} / cm @ ³ /.

4.2 l of water and 30 g of sodium nitrite. Under cooling and stirring, dropwise so that the temperature ^h mo la 4 maintained between ^0-60 ° C (addition time ^of IKAP ^{s i o n} 4-6 throws). After 30 ^g minutovta Dore OVaV ^s it was added to 2.4 ^{g of} ammonium amonnéto and někoHk 'throw the chilled ^DI at ^6-10 ° C. After filtration, the filtrate was charged to 14.5 kg of urea and heated to 70 ° C with stirring for 10 hours. ^S After cooling to 30 ° C, the precipitated ^p allantota ROMs aspirated and cold water.

Yield 6.3 kg (44% of theory);

m.p. 233 DEG-235 DEG C. (from water).

Example 2

To 1.97 ^g of a 40% ^- solution of ^g l ^y oxalate (d "1.27 ^g / cm ³⁾ was mixed with 75 ml Roztoky sulfuric acid in 450-ml water. Add 0.27 g of cobalt nitrate and heat to 45-5 ° C. Then 1 mol of acidic acid per mole is introduced. ^g polyoxypropylene-in over 4 ^h c for throw ^{bath, and} so ^ ab ^y ee toploto able to maintain between 45 and 50 ° C. After 30 minutes to react it ^s is charged with 40 ^{0 g} ammonium sulphate and it ^é chilled ^DI A few minutes of ^the hour at 5-10 ° C. After filtration, the filtrate was charged with 2.2 kg of urea and heated to 70 ° C with stirring for 1 hour.

^P of cooling ^- 30 ° ^C. the suction vyloutoný ^{allantoin, p} rom ^y with cold water. P ^{s é} cooled ^as the mother liquor it to 5 ° C, still todatetoé vylotoí bit allantoin. Yield 900 g (42% of theory);

TT 234 ^{and 2} 35 ° ^C (from water ^y).

Example 3

O

1.97 kg.40 of glyoxal solution (d * 1.27 g / m @ 2) are mixed with a solution of 75 ml of concentrated sulfuric acid in 450 ml of water. Was added 0.27 g of cobalt nitrate ^{C (j} N0) 2 · ^{6H G0} and to rock at 45 ^and 5 ⁰ ° C. Potoms ZAV ^{Adi 1} mole to ^y went ^to her with ^no dusnatoho N0 per one mole of glyoxal and air in excess of 4 hours so that the temperature could be maintained between ^the EIT 45 and ^from 50 ° C. After 3 ⁰ t ^{i d} minutoto orea ^g s ^and Van ^Í - added 400 ^g ammonium sulphate ^eh OA chilled ^DI n ^several hodi.n at 5-1 ^{0C. F} iltraci After the ^filtrate is supplemented ^by 2.2 kg močovi.n ^y and heated as it was you interfere ^Star hodi.n 10 to 70 ° C.

^S After cooling to 30 ° ^{C, characterized} in Lou ^No Eny - allantoi.n aspirated and the variable ^y is cold water. Yield was increased somewhat by allantoin crystallizing upon cooling the mother liquor to 50 ° C.

Claims (6)

Process for the production of allantoin, characterized in that glyoxal is treated at 40 to 60 ° C under the simultaneous catalytic action of soluble cobalt salts and nitrous acid with nitric acid, then the ammonium salt of a strong inorganic acid is added, cooled, filtered and thus obtained the filtrate is reacted with urea · 2. A process according to claim 1, wherein per mole of glyoxal is used 3 · 10 * 5 to 6. ίο ** mole of water-soluble cobalt salt · 3. The process according to claim 1, wherein the nitrous acid is used in the form of its salts in amounts of 4-10 * 8 to 8-10 mol of nitrite per mole of flyoxal. Process according to Claims 1 to 3, characterized in that it uses 0.04 to 0.2 mol of ammonium salt per 1 mol of glyoxal. The process of claims 1 to 4, wherein 2 to 6 moles of urea per 1 mol of glyoxal are used and the solution is heated to 50 to 80 ° C for 5 to 10 hours. 6 · A method according to claim 1, characterized in that instead of nitrous acid and nitric acid or nitrogen oxide is used oxides of nitrogen mixed with air, in each case 1 mole per 1 mole of glyoxal · _л