FI66836B - FOERFARANDE FOER FRAMSTAELLNING AV FAST SODIUM- ELLER POTASSIUM P-HYDROXIMANDELATMONOHYDRAT - Google Patents

Description

Γ- ANNOUNCEMENT

^ ** 1) utlAggningsskrift 668 36 C ί 1 ΐ'-ϋΐ J Cij ϋ.ιπί. ^ ty 13 12 1934

Patent ceddelat ^ ^ (51) K * Jt /v eng.a.3 c 07 C 59/50 SUOMI-FINLAND (21) r * ~ ** 4 ^ - ** mM ** 7815 ^ 5 (22) Hitolla » * —A-BlmlnpitH 16.05.78 'Fl' (23) Mm16.05.78 (41) Triht ΗΜμΜ - HMt offudlg \ ~ j yg wMOMrtW ».

Patent, och rtftaterttyralaan '' ΑμΝμ μΜ ock «L * rNfcM pMmi 31.08.84 (32) (33) (31) ry | 4« ** r «-» - »» f «rd priortut (71) Imperial Chemical Industries Limited , Imperial Chemical House, Hillbank, London SW1P 3JF, England-England (GB) (72) Robert Jeffrey Copeland, Macclesfield, Cheshire,

Philip Neil Edwards, Macclesfield, Cheshire, England-England (GB) (7 * 0 Oy Koi ster Ab (5 * 0 Method for the preparation of solid sodium or potassium p-hydroxymandelate monohydrate - Förfarande för framställning av fast sodium- or potassium- p-hydroximandelatmonohydrat

The invention relates to a process for the preparation of solid sodium or potassium p-hydroxymandelate monohydrate. p-hydroxymandelic acid of formula

HO ^ CHOH.COOH

many different synthetic routes have been proposed for its preparation. It can be prepared, for example, by reacting phenol with chloral and then hydrolyzing the trichloromethyl group to a carboxylic acid group (AT Patent No. 141,159; Chemical Abstracts 29 (1935) 4021); or by hydrolysis of p-hydroxybenzaldehyde cyanohydrin (Journal of the American Chemical Society 58 (1936) 1292); or by diazotization of p-aminomantelic acid (Il Farmaco, Edizione Scientlfica 10 (1955) 563); or by reacting the phenol with glyoxylic acid

TT

2,66836 (GB Patent Publication No. 1,377,243). Many of these preparation methods have used sodium hydroxide as a reagent, and thus sodium p-hydroxymandelate has been present in the solution.

It has now been found that alkali metal p-hydroxymandelate can be conveniently prepared as a solid in good yield and in pure form by reacting phenol with glyoxylic acid.

Sodium p-hydroxymandelate is a particularly valuable intermediate in the preparation of p-hydroxyphenylacetamide, which can be used for the preparation of the β-adrenergic blocker, atenolol, as described in the applicant's co-pending FI patent applications 781,544 and 781,546.

The process according to the invention for preparing solid sodium or potassium p-hydroxyrandelate monohydrate is characterized in that the phenol and glyoxylic acid are reacted in a manner known per se in the presence of sodium or potassium hydroxide, respectively, at a temperature of 20-60 ° C, the pH of the solution is adjusted to 5-6, the sodium or potassium salt is salted from the solution with a simple acid sodium or potassium salt and, if desired, the sodium or potassium p-hydroxymandelate monohydrate obtained is purified before drying by washing with saturated aqueous sodium or potassium chloride solution and then with acetone.

The phenol and glyoxylic acid are reacted with each other at 20 to 60 ° C, most preferably at 30 to 40 ° C, and preferably up to 50 to 100% by weight of excess phenol is used in the reaction.

The resulting sodium or potassium salt can be purified by washing with saturated sodium or potassium chloride solution, respectively, and then with acetone to remove excess phenol.

The reaction between phenol and glyoxylic acid does not produce organic by-products which form insoluble sodium or potassium salts and can thus be easily removed from the mother liquor.

The following examples illustrate the invention.

3,66836

Example 1

Phenol (368 g), ice water (400 g) and 68% by weight

A mixture of aqueous NaOH (160 ml) is added to a mixture of 50% by weight aqueous solution of glyoxylic acid (356 g), crushed ice (800 g) and 68% by weight aqueous NaOH (135 ml) under nitrogen, and the mixture is then heated to 30-35 ° C: in 18 hours. Concentrated hydrochloric acid (235 ml) is added to the mixture to adjust the pH to 6, then the mixture is stirred and heated at 75-80 ° C. Sodium chloride is added to the solution until it is almost saturated, the separated phenol is removed, and the aqueous solution is cooled in an ice bath and then filtered. The solid product is washed with saturated aqueous sodium chloride solution and then with acetone and dried at 80 ° C. 381 g of sodium p-hydroxymandelate monohydrate are thus obtained. Yield 76% based on the amount of glyoxylic acid used. The solid product also contains some sodium chloride, the amount of which was determined by AgNO 2 titration to be 45 g.

Example 2

To a stirred solution of phenol (368 g), aqueous glyoxylic acid (356 g), 50% by weight and water (1000 ml) maintained at 20 ° C under external cooling is slowly added aqueous NaOH (295 ml, 68% by weight). solution). After the addition is complete, the solution is heated at 35 ° C for 5 hours with stirring, then the mixture is acidified to pH 6 with concentrated hydrochloric acid (235 ml). Solid sodium chloride is added to the solution (the temperature of the solution rises to 70 ° C during the acid addition) until the solution is almost saturated, cooled to 20 ° C and filtered. The solid precipitate is washed with saturated aqueous sodium chloride solution and then acetone, and then dried at 60 ° C. This gives sodium p-hydroxymandelate monohydrate in 63% yield based on the amount of glyoxylic acid. It contains some sodium chloride as an impurity.

Example 3

A solution of potassium hydroxide (145.6 g) in water (120 ml) is added over 1 hour to a stirred mixture of phenol (184 g), water (700 ml) and 50% by weight aqueous glyoxylic acid (178 g), maintaining the temperature at 15 ° during the addition. C. The reaction temperature is then raised to 35 ° C, and the mixture is stirred at this temperature for 8 hours, after which the mixture is cooled. Concentrated hydrochloric acid is added until the pH is 6, followed by potassium chloride (300 g), and the mixture is stirred for 2 hours, then filtered. The solid residue is washed with saturated aqueous potassium chloride solution (200 ml) and acetone (250 ml), then dried. This gives solid potassium p-hydroxymandelate monohydrate (26 g) with solid potassium chloride as an impurity.

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