CS256289B1 - Purification method: 4-carboxybutyl / triphenylphosphonium bromide - Google Patents

Abstract

The method of purification of /4-carboxybutyl/triphenylphosphonium bromide of formula I //C6H5/3P/+/CH2CH2CH2CH2COOHj Br/-/ consists in dissolving the technical product containing 93 to 98% of the compound of formula 1 under boiling in ethanol or 2-propanol and after cooling to a temperature of 70 to 75 °C, ethyl acetate or isopropyl acetate in a 1 to 1.3-fold volume amount of alcohol is added dropwise to the solution with stirring, the suspension obtained is slowly cooled at a rate of 0.5 to 2 °C per minute to a temperature of 0 to +5 0 after 12 to 24 hours of standing, the separated crystalline portion is filtered off with suction, washed with ethyl acetate and after drying at a temperature of 90 to 110 °C and a pressure of 0.5 to 2 kPa, the product of general formula I is obtained.

Description

The invention relates to a method for cleaning / 4-carboxybutyl / triphenylphosphonium bromide of the formula I / 7c _{6h 5/5} ^{// +} p ^/ 2 CH ₂ CH ₂ CH ₂ Br ^and cooh7 ^/ / 1 /

The title compound of the formula I is used in the synthesis of natural macromolecules, in particular in the synthesis of prostaglandin and analogues thereof, where it is introduced into the molecule. Prostaglandins are biologically highly active substances affecting most vital functions (Prostaglandin Synthesis) Bindra J.S., Bindra R. / Academic Press, New York, 1977; Contact Alerck (1985), 26; Contact (Merck), 1984 (2), 50].

Methods for the preparation of phosphonium salts are well known (Methoden der organischen Chemie (Houben-Weyl), Volume E 1, p. 491, G. Thieme Verlag, Stuttgart, New York 1982, see also

4th volume XII / 1, p. 77 et seq. /. Up to now, phosphonium salts have been used in technical quality for synthesis or purified by crystallization from methyl cyanide (acetonitrile) (J. Am. Chem. Soc. 91: 5675 (1969)), US Pat. U.S. Patent Nos. 1,495,512, 4,075,804; trituration with acetone / US Pat. No. 4,095,650], toluene (cf. AO 228 058 or tetrahydrofuran J. Org. 55, 5504 (1968), or by reprecipitation from dichloromethane / ether (Synthesis 1977, 699> Chem. Ber, 109, 58 (1976), chloroform (ether) (Phosphorous 109 (1975)).

A disadvantage of the first method is the use of highly toxic acetonitrile. The second method uses solvents that are particularly hazardous in terms of hygiene and potential for abuse (particularly dangerous poison) and, in addition, the purity of the product is often 95 to 97% and yields are between 50 to 75%. The use of the phosphonium salt in the above purity often results in kon256 289

- 2 taminaci. target products with a small amount, mostly difficult to remove, of unwanted products. From the above data it is clear that the above-mentioned technical procedures are particularly inappropriate from the hygienic point of view and the possibility of abuse.

These known processes are followed in a positive manner by the process according to the invention, which substantially eliminates the above disadvantages. The process according to the invention is characterized in that the ternary (4-carboxybutyl) triphenylphosphonium bromide, d prepared according to AO 228 058, contains not more than 95 to 98% by weight. Dissolve hot in ethanol or 2-propanol. After spontaneously cooling the alcoholic solution to 70-75 ° C, ethyl acetate or isopropyl acetate in 1 to 1.3 times the volume of alcohol is slowly added with stirring. Thereafter, the suspension is cooled to 0 to +5 ° C per minute at a rate of 0.5 to 2 ° C and left at this temperature for 12 to 24 hours. The precipitated crystalline fraction is filtered off with suction, washed with the above-mentioned acetate and dried at a temperature of 90 to 110 [deg.] C. and a pressure of 0.5 to 2 kPa. This gives a product with a minimum content of 99.9% of the compound of the formula I in a yield of 88-92%.

The advantage of the process according to the invention is first of all simple for conducting, using hygienically harmless solvents and high product purity.

and

The method according to the invention is illustrated by several specific examples, which are not intended to limit the scope of the invention in any way.

Example

335 g of technical (4-carboxybutyl) triphenylphosphonium bromide, containing 97.2% of the compound of formula I, melting at 175 DEG-188 DEG C., was dissolved in hot in 447 ml of ethanol. The solution was then cooled to 70-75 ° C and 558 ml of ethyl acetate was added portionwise with stirring. Haze was already formed during the addition of ethyl acetate. Then the solution temperature was gradually lowered to room temperature and finally left at +2 to 5 ° C

256 289 at rest. The precipitated crystals were aspirated, washed with 2 x 500 ml ethyl acetate and dried in a vacuum oven at 100 ° C and 1 kPa. 301.5 g of product, m.p. 198 DEG-204 DEG C., containing 99.96% by weight of the title compound are obtained. (4-Carboxybutyl) triphenylphosphonium bromide, determined by alkalimetry.

Claims (1)

Method of purifying / 4-carboxybutyl / triphenylphosphonium bromide of formula I, pC ₆ H 5 / 5P ^{/ + /} CH ₂ CH ₂ CH2CH2C00Hj Br / '/ / 1 /, characterized in that the technical product containing not more than 93 to 98% by weight. the compounds of formula I are dissolved in boiling in ethanol or 2-propanol and, after cooling to 70 to 75 ° C, to the solution is added dropwise, with stirring, a quantity of ethyl acetate or isopropyl acetate of 1 to 1.3 times the volume of alcohol. 5 to 2 [deg.] C. per minute is cooled to 0 to +5 [deg.] C., after 12 to 24 hours standing, the precipitated crystalline fraction is filtered off with suction, washed with ethyl acetate and dried at 90 to 110 [deg.] C. and 0.5 to 2 kPa a product containing at least 99.9 wt. compounds of general interest