Patent GB-727471-A (GB)
Title: Improvements in or relating to a process of recovering glucuronolactone
IPC: C07H19/01
Filed: 1951-10-01
Abstract: Crystalline glucuronolactone is obtained from aqueous mixtures containing glucuronosides (resulting from the oxidation of glucose derivatives) by treatment with ion-exchange resins whereby the acidic components (including glucuronosides) are separated from the non-acidic components, concentrating the solution of the former, hydrolysing the concentrated solution until the hydrolysis of glucuronoside is not more than 85 per cent complete, and recovering crystalline glucuronolactone.  The product may be further purified by solution in water, treatment with carbon, removal of the latter and evaporation in vacuo until crystals form; all these steps are carried out at 20-60 DEG  C., preferably below 40 DEG  C.; the mother liquor from the crystals may be recycled by adding it to a new solution of crude crystalline glucuronolactone.  The mother liquor from the first crystallization step may also be recycled by adding it to fresh concentrated glucuronoside solution and repeating the hydrolysis, concentration and crystallization procedures until the glucuronic acid content of the mother liquor decreases to 30 per cent glucuronic acid on a dry basis; the mother liquor can be treated separately with glacial acetic acid to obtain glucuronolactone. The starting material may be prepared by oxidizing a glucose derivative in which the aldehyde group is protected (e.g. methyl or ethyl glucoside), e.g. with oxygen and a platinum or palladium catalyst (Specification 679,776), with nitric acid in the presence of nitrous acid, a nitrite or nitrogen trioxide (Specification 670,929), or with liquid nitrogen dioxide (Specification 673,446). If the oxidation was carried out in alkaline solution or a buffered system containing inorganic salts the metal ions are first removed by treatment with a cation-exchange resin.  The metal-free solution obtained in either way is adsorbed on an anion-exchange resin and eluted with a base such as sodium hydroxide.  Further treatment with a cation-exchange resin converts the acidic components to the free acid state.  The concentration step is carried out until the solid content is 30-50 per cent.  The acid catalyst is then added, e.g. sulphuric acid to 0.3N-2.0N (preferably 0.3-0.7) or hydrochloric acid to 0.1N-0.5N.  The glucuronoside is hydrolysed by heating the resulting mixture, the aglucone being distilled off, for, e.g., 24 minutes at 129 DEG  C.  The times for other temperatures at varying acid concentrations are shown on a graph.  Heating is carried on until hydrolysis of the glucuronoside is 60-85 per cent complete.  The hydrolysate is cooled, filtered and concentrated in vacuo (without removal of the acid catalyst) at 30-60 DEG  C., preferably below 40 DEG  C., until the solids content of the hydrolysate exclusive of the mineral acid is about 80-85 per cent. For further purification the resulting crystals are dissolved in water, 1-5 per cent of decolorizing carbon is added and after removal of the latter the solution is evaporated under vacuo to 80-90 per cent solids content and cooled quickly to cause crystallization. Conversion of glucuronic acid to glucuronolactone occurs during the concentration.  For recycling, the crystals are washed with methanol, the wash diluted with water, methanol removed therefrom and the methanol-free liquid together with the mother liquor from the crystallization returned to the concentrated crude solution, further mineral acid being added if necessary.  Recycling is carried on until the concentration of free glucuronic acid reaches 40 per cent, when the residual liquor is concentrated in vacuo to 80-90 per cent solids content, heated to 90-100 DEG  C. for 10 minutes for lactonization and crystallized.  Examples are given of various ways of carrying out the invention.  The purification methods claimed in Specifications 670,929 and 673,446 are disclaimed.