HU199488B - Process for producing alpha-hydroxyalkyl phosponic acids - Google Patents

Abstract

Mono-, di- and tri-phosphoric-acids of general formula (I) are prepd. from phosphorus-trichloride. - In the formula R1 is hydrogen, alkyl, aryl, aralkyl or amino-alkyl R2 is hydrogen, alkyl, aryl or -PO(OH)2, R3 is hydroxyl, amino or a gp. of formula (II), or if R2 is alkyl or aryl, a gp. of formula (III). R4 means hydrogen or alkyl, R5 is alkyl or aryl. - Mono-phosphonic-acids are prepd. by reacting 1 mole of a carbonyl cpd. with 1.0-1.3 mole phosphorus-trichloride at a temp. below 30 deg.C, resting the mixt. for 1-6 hours, adding 4-6 mole glacial-acetic-acid with stirring and cooling the mixt. and resting for 4-12 hours. The resulting two-phase system is sepd., the lower phase is poured into 20-30 mole ice-water, the water is subsequently evaporated and the resulting syrupy mono-phosphonic-acid is crystallised. The crystals are sepd. from the mother liquor in the known way, the prod. isopt. recrystallised. - Di-phosphonic-acids in which R1 is alkyl, R2 is PO(OH)2 and R3 is hydroxyl are prepd. by adding 2 mole phosphorus-trichloride to a mixt. of 3 mole glacial-acetic-acid and 3 mole water, heating the reaction mixt. to 120 deg.C and keeping it at this temp. for 1-3 hours. Subsequently the excess acetic-acid, water and the hydrochloric-acid liberated in the reaction are removed. The remaining syrupy di-phosphonic-acid is crystallised. There are three other methods for preparing di-phosphonic-acids starting from phosphorus-trihalogenides. - Tri-phosphonic acids are prepd. by adding ammonium-chloride followed by para-formaldehyde to the mixt. of phosphorus-trichloride and water at a temp. of at least 100 deg.C and crystallising the prod. between -10 and +24 deg.C. (Previously notified in week 8601)

Description

The present invention relates to an improved process for the preparation of? -Hydroxyalkylphosphonic acids of the formula I

C / I

(I) r ₂ oho oh - wherein R 1 is C 1-4 alkyl, phenyl or phenyl (C 1-3 alkyl), and R ₂ is hydrogen or C 1-4 alkyl.

The α-hydroxyalkylphosphonic acids of the formula I have excellent complexing properties, such as calcium, iron, zinc, and the like. They form strong complexes with ions, are accordingly effective water treatment agents and can be used as ion exchangers. In contact with metals in aqueous solution, they form an adsorption protective layer and thus exhibit corrosion inhibitory activity. In addition, the compounds of formula (I) may be used as starting materials for the preparation of a number of valuable chemical products or therapeutic agents.

The preparation of compounds of formula (I) and the mechanism of their reactions are described in detail in J.Am.Chem. Soc., 42, 2337 (1920). The authors have found that the carbonyl compounds of the formula R ₁ -CO-R ₂ are reacted with phosphorus trichloride to form a cyclic intermediate which, when treated with water, can be converted to the corresponding α-hydroxyalkylphosphonic acid. The cyclic intermediate is formed by an equilibrium reaction; in this regard, the desired α-hydroxyalkylphosphonic acid can only be obtained in sufficient yield if one of the starting reagents is used in large excess. However, when acetic anhydride or glacial acetic acid is added to the reaction mixture, the cyclic intermediate is further reacted, so that an appropriate yield can be obtained when the starting reagents are reacted in equimolar proportions or one of the reagents is used in small amounts.

According to the quotation, a-hydroxybenzylphosphonic acid can be obtained most favorably under the following conditions: 10 mol% excess of phosphorus trichloride is added to the benzaldehyde, the mixture is allowed to stand for a few hours at 20-40 ° C, followed by addition of 3 to 4 moles of glacial acetic acid per mole of benzaldehyde, held at 25 to 35 ° C for several hours, then 100 to 1 mole of starting benzaldehyde.

It is poured into 120 mol of water, the aqueous mixture is evaporated to dryness and the crude product obtained is recrystallized from dilute aqueous hydrochloric acid. The authors note that recrystallization of the crude product results in considerable losses due to the water solubility of α-hydroxybenzylphosphonic acid, and it is therefore advisable to isolate the product in the form of a salt. The aniline salt of a-hydroxybenzylphosphonic acid with aniline is reported to be obtained in a yield of 72%. According to our own experimental results, α-hydroxybenzylphosphonic acid, according to the procedure described in J. Am. Chem. Soc., 42, 2337 (1920),

Yield 40%.

The major disadvantage of the process described in J. Am. Chem. Soc., 42, 2337 (1920), from an industrial point of view, is that hydrolysis requires extremely large amounts of water (100-120 moles per mole of starting carbonyl compound), which is difficult and extremely difficult to remove. energy intensive operation. A further disadvantage is that there is no possibility of utilizing acetyl chloride as a by-product during the elution step, which is completely lost during hydrolysis and subsequent evaporation. Therefore, this known process is not economically viable enough.

It is an object of the present invention to provide a process for the preparation of compounds of formula (I) which enables the utilization of the by-product and thereby reduce the energy requirement of the bridge solution to the extent known in the art.

In our experiments, when one mole of the carbonyl compound of the formula R ₁ -CO-R _{2 is} reacted with 0.85-0.9 moles of phosphorus trichloride 30 and 4-6 moles of glacial acetic acid, the reaction is carried out in two phases. apart. The cyclic intermediate to be hydrolyzed contains the lower phase, whereas the upper phase consists essentially of acetyl chloride.

After separation of the two phases, acetyl chloride can be isolated by distillation from the upper phase in the form of a commercially available reagent in a yield of 80-90% of the phosphorus trichloride input. The lower phase can be completely hydrolysed with as much as 20-30 moles of water per mole of starting carbonyl compound. The hydrolysis is carried out at a temperature of up to 60 ° C during vacuum evaporation of the reaction mixture. The desired compounds of formula (I) are isolated from the remaining syrupy material in a known manner, optionally after salt formation. When R 1 is an aliphatic group, the compounds of formula I are obtained in excellent (almost quantitative) yield.

When the compounds of formula (I) wherein R1 is phenyl or phenylalkyl are prepared, the purification results in the losses mentioned in the above cited publication and are thus obtained in a yield of about 50%. However, the isolation of the products in the form of a salt can increase the yield to 70-75%.

The present invention therefore relates to a process for the preparation of a-hydroxyalkylphosphonic acids of formula (I) wherein R 1 and R ₂ have the meanings given above for the carbonyl compound of formula R ₁ -CO-R ₂ in which R 1 and R ₂ are as defined above - phosphorus trichloride is added at a temperature of up to 30 ° C, ice-2HU 199488 Β vinegar is added to the reaction mixture after standing for ⁶⁵ hours, and the resulting reaction mixture is kept at a temperature of 30 ° C and the resulting intermediate is hydrolyzed with water to isolate the compound of formula (I) obtained in a known manner and, if desired, purify in a known manner. According to the invention, based on the carbonyl compound of formula R, -CO-R ₂ from 0.85 to 0.9 mole of phosphorus trichloride, and 4-6 moles of glacial acetic acid used to one mole of, after the reaction, the mixture was phase separated into two phases were separated, the upper phase is drained to recover acetyl chloride and the lower phase is hydrolyzed with 20-30 mol of water per mole of carbonyl compound R ₁ -CO-R ₂ while simultaneously evaporating the water under reduced pressure at a temperature not exceeding 60 ° C.

The invention is further illustrated by the following non-limiting Examples.

Example 1

10.6 g of freshly distilled benzaldehyde are mixed with 12 g of phosphorus trichloride while cooling with water, so that the temperature of the mixture does not exceed 30 ° C. After standing at room temperature for 1.5 hours, glacial acetic acid (30 g) was added with vigorous stirring and cooling with ice-water. The reaction mixture was stirred at room temperature for 1.5 hours, then allowed to stand at room temperature for 5 hours. The phases of the reaction mixture separated into two phases are separated by suction. The upper layer was distilled off from a water bath to give 16.2 g (82% relative to phosphorus trichloride) of acetyl chloride; mp: 51-52 ° C. The lower dense syrupy reaction mixture was quenched with water jet vacuum and acetyl chloride and poured into 50 mL of ice water with vigorous stirring. The aqueous solution was concentrated on a rotary evaporator from a water bath at 60 ° C to constant weight. Water (20 ml) was added to the residue and evaporation was repeated. The resulting yellowish syrup was allowed to stand in a vacuum desiccator over an alkali and the resulting solid melt was recrystallized from a 2: 1 by volume mixture of benzene and acetic acid. Filtration afforded 6.7 g (41%) of snow-white, crystalline α-hydroxybenzylphosphonic acid, m.p. 165-167 ° C (m.p. 167-168 ° C).

If the product is isolated as the sodium salt by adding 10 mole% excess sodium hydroxide in the form of a 2N aqueous sodium hydroxide solution to the solid melt, ethanol is added to the resulting thick solution and the resulting mixture is crystallized. until the completion of drinking, it was stored in a refrigerator to give the crystalline sodium salt in 84% yield.

Example 2 Phenylacetaldehyde (g) was mixed with phosphorus trichloride (12 g), kept at room temperature for 2 hours, and glacial acetic acid (g) was added with stirring and allowed to stand at room temperature for 12 hours. The upper phase is separated; acetyl chloride is isolated from the upper phase by distillation in a yield of 84% relative to phosphorus trichloride. Hydrochloric acid and the remaining acetyl chloride were removed by suction from the lower phase and water (50 mL) was added to the lower phase. The mixture separates again into two phases. The phases were separated, the aqueous solution was evaporated and the resulting thick syrup was crystallized by standing over an alkali. 10.3 g (58.6%) of a-hydroxy-2-phenylethylphosphonic acid are obtained; Op .:

126-128 ° C.

Example 3

The procedure was as in Example 1, but using 4.4 g of acetaldehyde, 12 g of phosphorus trichloride, 30 g of glacial acetic acid and 50 ml of water. The resulting thick syrup was allowed to stand for 2 weeks.

Yield: 10.45 g (95.3%) of white crystalline α-hydroxyethylphosphonic acid; 76-78 ° C (liter. 74-78 ° C). As a by-product, acetyl chloride was isolated in 87% yield based on phosphorus trichloride.

Example 4

The procedure of Example 1 was followed, but using 7.2 g of butiraldehyde, 12 g of phosphorus trichloride, 30 g of glacial acetic acid and 50 ml of water.

13.4 g (99.2%) of a-hydroxybutylphosphonic acid are obtained in the form of white crystals; m.p. 153-155 ° C (literature: 154.4-155 ° C). As a by-product, acetyl chloride is isolated in a yield of 85% relative to phosphorus trichloride.

Example 5

The procedure of Example 1 was followed except that 5.8 g of acetone were used in 12 g of phosphorus trichloride, 30 ml of glacial acetic acid and 50 ml of water. After evaporation of the aqueous solution, the syrup was dried in a vacuum desiccator over an alkali and the resulting off-white crystalline material was recrystallized from acetic acid. 10.7 g (87.8%) of a-hydroxy-1-methylethylphosphonic acid are obtained; m.p. 167-169 ° C (literature: 167-169 ° C). The crystalline product contains two moles of crystalline water. As a by-product, acetyl chloride was isolated in a yield of 83% based on phosphorus trichloride.

Claims (1)

A process for the preparation of a-hydroxyalkylphosphonic acids of formula (I) R ₂ OH O OH - wherein R 1 is C 1 -C 4 alkyl, phenyl or phenyl (C 1 -C 3) alkyl, and R ₂ is hydrogen or C 1 -C 4 alkyl. -3HU 199488 Β means that phosphorus trichloride is added to a carbonyl compound of the formula R ₁ -CO-R ₂ in which R 1 and R ₂ are as defined above at a temperature not exceeding 30 ° C after standing for 1 to 3 hours. glacial acetic acid is added to the reaction mixture, the resulting reaction mixture is kept at a temperature of 30 ° C for up to 4 to 15 hours, and the resulting intermediate is hydrolyzed with water to isolate the compound of formula I in a known manner 0.85-0.9 moles of phosphorus trichloride and 4-6 moles of glacial acetic acid are used per mole of carbonyl compound R ₁ -CO-R ₂ , and the phases separated into two phases are separated after the reaction is completed. 5 from each other, the upper layer was removed recovering acetyl chloride, and the bottom phase per 1 mole of the carbonyl compound of formula R, -CO-R ₂ is hydrolyzed with water from 20 to 30 mol of water simultaneously, a reduced pressure W during distillation at a temperature not exceeding 60 ° C.