DE2658961C3 - Process for the preparation of 1-hydroxy-3-aminopropane-1,1-diphosphonic acids - Google Patents

Description

Ϊ /

V-CH ₂ -CH ₂ -C-OH
PO ₃ H ₂

where Ri and R ₂ denote a hydrogen atom or an alkyl radical with 1-4 carbon atoms, from J3-alanine or poly-jS-alanine or jS-alanine alkylated on nitrogen and phosphorous acid in the presence of a phosphorus halide, marked thereby

genid phosphorus oxychloride is used.

that as phosphorus halo

The subject of the application is a process for the production of l-hydroxy-S-aminopropane-l.l-diphosphonic acid or their derivatives alkylated on the nitrogen and salts thereof of the general formula:

R.

N-CH ₂ -CH ₂

PO ₃ H ₂
-C-OH
PO ₃ H ₂

where Ri and R ₂ denote a hydrogen atom or an alkyl radical having 1-4 carbon atoms, by reacting / ϊ-alanine or poly-j3-alanine or j3-alanine alkylated on the nitrogen with phosphorous acid and a phosphorus halide.

It is known from German patent specification 21 30 794 1-hydroxy-3-aminopropane-1,1-diphosphonic acid by reacting β -alanine or poly-j3-alanine with a mixture of phosphorous acid and phosphorus trochloride in the presence of or Establish absence of an organic diluent. ß-alanine, phosphorous acid and the diluent are heated in a boiling water bath and phosphorus trichloride is added dropwise. The disadvantage of this method is that when the phosphorus trichloride is added dropwise, a sticky reaction product is formed which is difficult to stir. In addition, yellow by-products occur, which are due to partial decomposition of the phosphorus trichloride at the boiling point. Working with an organic diluent in technical approaches is disadvantageous for reasons of price, and separating the diluent requires an additional work step!

It has now been found that the above Difficulties do not arise if one uses as phosphorus halide iPhosphoröxychlörid.

It is advantageous to work in such a way that J3-alanine, phosphorous satire and phosphorus oxychloride are combined with stirring at Zini 'uring temperature and the mixture is then ^{heated to an internal temperature of 10O 0} C or 3-alanine and phosphorous acid at 90-100 ⁰ C presented as a clear melt, the phosphorus oxychloride added dropwise and the mixture stirred briefly at an ^{internal temperature of 100 °} C. After dilution with water, the phosphonic acid precipitates in crystalline form.

You can also use j3-alanine and water at room temperature submit and the formation of the phosphorous

Add dropwise the corresponding amount of phosphorus trichloride to the acid. Then phosphorus oxychloride is added, heated to an internal temperature of 100 ° C and diluted with water. With this working method, the final aqueous solution must expediently be made up briefly.

be boiled, otherwise the phosphonic acid will be difficult to crystallize

In contrast to the previous process with phosphorus trichloride instead of phosphorus oxychloride a well-stirrable syrup is always obtained, which dissolves well in water. Yellow by-products do not occur.

example 1

89.1 g (1.0 mol) of 0-alanine and 164.0 g (2 mol) of phosphorous acid are initially charged as a clear melt at 90-10 ° C. with stirring Moles) phosphorus oxychloride. By exothermic reaction, the internal temperature rises to about 115 ° C and then falls under gentle reflux of POCl ₃ to about 85 ⁰ C.

The mixture is stirred for 20-30 minutes until Rückflußende, and to reach about 100 ⁰ C inside. It is then diluted with 198 g (11 mol) of water. When diluting, the internal temperature rises briefly to 165 ° C. and then quickly falls again under reflux of water.

On cooling to room temperature, the phosphonic acid separates out as pure white crystals. the The yield is 112.0 g (51.14% of theory).

Further phosphonic acid precipitates by concentrating the mother liquor and adding methanol.

Example 2

89.1 g (1.0 mol) of j9-alanine and 72 g (4.0 mol) of water are initially introduced as a suspension with stirring at room temperature. 274.7 g (2.0 mol) of phosphorus trichloride are then added dropwise in 20-30 minutes. The temperature is kept ^{below 35 ° C. by cooling.}

After the addition of the phosphorus trichloride, the internal temperature is increased to 90-100 ° C. Then drips 122.7 g (0.8 mol) of phosphorus oxychloride are added in 20-30 minutes and the mixture is then stirred for a further 10-15 Minutes at an internal temperature of 90-100 ° C. To crystallize the phosphonic acid, 180 ml (10.0 Mol) water to this and refluxed for 5 minutes.

After cooling and suction, 99.0 g (45.2% of theory) of phosphonic acid are obtained.

Example 3

222.3 g (1.45 mol) of phosphorus oxychloride are poured into a gas mixture of 89.1 g (1 mol) / 5-alariin and 221.4 g (2 ₍ 7 mol) phosphorous acid. It forms under for a few seconds HCU development of a thin, white foam and the internal lime value increases to 45 - 50 ° C due to the exothermic reaction.

Thereafter untef stirring heated indoor Are 95- 100 ⁰ C is reached, the mixture is stirred for 30 minutes

OC CQ Ω £ ^ υ jo ζ / ν

according to this temperature. Then one drips in 2-3 by concentrating the mother liquor and adding

Minutes 180 g (10 mol) of water, the methanol still discharging further phosphonic acid,

Internal temperature briefly rises to approx. 160 ° C. N-alkylated ß- alanines can be prepared in an analogous manner

Cool down, suck off the pure white crystals, convert,

Yield: 93.7 g (42.8% of theory), -3

Claims (1)

Claim: Process for the preparation of l-hydroxy-3-aminopropane-l, l-diphosphonic acid or their derivatives alkylated on the nitrogen and salts thereof of the general formula: R ₁ PO ₃ H ₂