Process for the production of 3-amino-1-hydroxypropane-1,1-diphosphonic acid

A process for the preparation of 3-amino-1-hydroxypropane-1,1-diphosphonic acid having the formula: ##STR1## wherein R.sub.1 and R.sub.2 are selected from the group consisting of hydrogen and lower alkyl, consisting essentially of the steps of reacting a .beta.-alanine compound selected from the group consisting of .beta.-alanine and lower alkylated .beta.-alanine with a phosphonating reactant selected from the group consisting of: PA0 (1) a mixture of phosphorous acid and PCl.sub.5, and PA0 (2) a mixture of phosphorous acid, PCl.sub.3 and Cl.sub.2, hydrolyzing the reaction mixture, and recovering said 3-amino-1-hydroxypropane-1,1-diphosphonic acid.

BACKGROUND OF THE INVENTION 
The invention concerns an improved process for the preparation of 
3-amino-1-hydroxypropane-1,1-diphosphonic acid in which the amino group 
may be substituted by lower alkyl radicals. 
The preparation of 3-amino-1-hydroxypropane-1,1-diphosphonic acid by 
reaction of .beta.-alanine with a mixture of phosphorous trichloride and 
phosphorous acid in the presence or absence of an organic diluent is known 
from the German Patent Specification No. 21 30 794. However, yellow-red 
by-products in the form of amorphous phosphorus-oxygen compounds of 
unknown structure are formed in this reaction and their separation, 
particularly in the presence of chlorobenzene, is very costly. Another 
factor to be considered in the large scale preparations is the dangerously 
high flammability of these phosphorus compounds. 
It is also known that 3-amino-1-hydroxypropane-1,1-diphosphonic acid can be 
prepared by reacting .beta.-alanine with a mixture of phosphorous acid and 
POCl.sub.3, with subsequent hydrolysis of the reaction mixture, to avoid 
these disadvantages. Among other drawbacks, however, this process is 
unsatisfactory with respect to the yields. 
OBJECTS OF THE INVENTION 
An object of the present invention is the development of a process for the 
production of 3-amino-1-hydroxypropane-1,1-diphosphonic acid in good 
yields with greatly decreased formation of phosphorus-oxygen by-products. 
Another object of the present invention is the development of a process for 
the preparation of 3-amino-1-hydroxypropane-1,1-diphosphonic acid having 
the formula: 
##STR2## 
wherein R.sub.1 and R.sub.2 are selected from the group consisting of 
hydrogen and lower alkyl, consisting essentially of the steps of reacting 
a .beta.-alanine compound selected from the group consisting of 
.beta.-alanine and lower alkylated .beta.-alanine with a phosphonating 
reactant selected from the group consisting of: 
(1) a mixture of phosphorous acid and PCl.sub.5, and 
(2) a mixture of phosphorous acid, PCl.sub.3 and Cl.sub.2, 
hydrolyzing the reaction mixture, and recovering said 
3-amino-1-hydroxypropane-1,1-diphosphonic acid. 
These and other objects of the present invention will become more apparent 
as the description thereof proceeds. 
DESCRIPTION OF THE INVENTION 
It has now been found that the previously employed methods to produce 
3-amino-1-hydroxypropane-1,1-diphosphonic acid can be improved by the use 
of the process described below. The new process is characterized by the 
fact that .beta.-alanine, in which the amino groups may be substituted by 
lower alkyl radicals, is reacted with a mixture of phosphorous acid and 
PCl.sub.5 or with a mixture of phosphorous acid, PCl.sub.3 and chlorine, 
and the reaction mixture is then hydrolyzed. 
More particularly, the present invention relates to a process for the 
preparation of 3-amino-1-hydroxypropane-1,1-diphosphonic acid having the 
formula: 
##STR3## 
wherein R.sub.1 and R.sub.2 are selected from the group consisting of 
hydrogen and lower alkyl, consisting essentially of the steps of reacting 
a .beta.-alanine compound selected from the group consisting of 
.beta.-alanine and lower alkylated .beta.-alanine with a phosphonating 
reactant selected from the group consisting of: 
(1) a mixture of phosphorous acid and PCl.sub.5, and 
(2) a mixture of phosphorous acid, PCl.sub.3 and Cl.sub.2, 
hydrolyzing the reaction mixture, and recovering said 
3-amino-1-hydroxypropane-1,1-diphosphonic acid. 
The starting product is particularly .beta.-alanine. Other .beta.-alanines, 
which have their hydrogen atoms located on the amino group partially or 
completely replaced by lower alkyl radicals, such as methyl, ethyl or 
propyl, also may be used as starting products. 
It is advantageous to use a substantially stoichiometric to an excess of 
the phosphorous acid and PCl.sub.5, such as 1 to 1.5 mols of H.sub.3 
PO.sub.3 and 1 to 1.5 mols of PCl.sub.5 per mol of .beta.-alanine. As was 
further discovered, PCl.sub.5 also may be replaced by a mixture of 
PCl.sub.3 and Cl.sub.2. When the process is performed in the 
last-mentioned manner, it is advantageous to prepare first a mixture of 
.beta.-alanine, H.sub.3 PO.sub.3 and PCl.sub.3 at a molar ratio of 
substantially 1:1:1, and to then inject a corresponding amount of chlorine 
gas. 
If desired, diluents, preferably chlorinated hydrocarbons, such as 
chlorobenzene, tetrachloroethane, tetrachloroethylene, trichloroethylene 
or carbon tetrachloride may be used to carry out the reaction. The 
reaction generally is performed at temperatures between 80.degree. C. and 
130.degree. C., preferably at about 100.degree. C. Then the reaction 
mixture is hydrolyzed by the addition of water, using advantageously 
enough H.sub.2 O barely to dissolve the reaction product. The hydrolysis 
is advantageously carried out at elevated temperatures, such as from 
30.degree. C. to 100.degree. C. The desired product then crystallizes from 
the aqueous solution, after separation of the solvent, if present. The 
yield can be increased by the separation of the mother liquor and the 
addition of alcohol or acetone thereto. 
The 3-amino-1-hydroxypropane-1,1-diphosphonic acids obtained, which may be 
alkylated at the nitrogen atom, if desired, are good complexing agents for 
heavy metals and alkaline earth metals that are also active in amounts 
below the stoichiometric quantity. Consequently, they can be used in 
cleaning and water treatment compositions.

The following specific embodiments are illustrative of the practice of the 
invention without being limitative thereto. 
EXAMPLE 1 
A suspension of 1.5 mols of PCl.sub.5 in 500 ml of chlorobenzene was 
prepared and then mixed with 1.5 mols of H.sub.3 PO.sub.3. The exothermic 
reaction produced a clear solution with the formation of HCl. After 
cooling to room temperature, 1 mol of .beta.-alanine was added thereto. 
After stirring for 15 minutes, the mixture was heated to 100.degree. C. 
within one hour and kept at this temperature for three hours. The reaction 
mixture obtained after this time was hydrolyzed with 600 ml H.sub.2 O, 
leading to the complete solution of the practically solid product. After 
the separation of the chlorobenzene phase, pure 
3-amino-1-hydroxypropane-1,1-diphosphonic acid was obtained by 
crystallization from the cooled solution in a yield of 65.1%. The yield 
can be increased by mixing mother liquor with methanol. 
EXAMPLE 2 
A suspension of 0.345 mol of PCl.sub.5 in 120 ml of chlorobenzene was first 
mixed with 0.345 mol of H.sub.3 PO.sub.3 and, after cooling, with 0.23 mol 
of N,N-diethylaminopropionic acid. The mixture was stirred for ten minutes 
and then slowly heated to 100.degree. C., and the reaction mixture was 
then kept at this temperature for another three hours. Thereafter, the 
chlorobenzene phase was decanted, and the pasty reaction product was 
hydrolyzed with about 80 ml H.sub.2 O at 100.degree. C. 
The 3-(N,N-diethylamine)-1-hydroxypropane-1,1-diphosphonic acid was 
precipitated by adding the solution dropwise into an alcohol/acetone 
mixture (2/1). 
EXAMPLE 3 
A mixture of .beta.-alanine, H.sub.3 PO.sub.3 and PCl.sub.3 in a molar 
ratio of 1:1:1 in 500 ml of chlorobenzene, was prepared. Then chlorine gas 
was added at room temperature for two and a half hours. The reaction 
mixture was thereafter heated to 100.degree. C. and kept at this 
temperature for four hours. After cooling, the hydrolysis was performed at 
50.degree. C. with 400 ml of H.sub.2 O. The chlorobenzene phase was 
separated and the 3-amino-1-hydroxypropane-1,1-diphosphonic acid was 
crystallized by further cooling to 0.degree. to 10.degree. C. The yield 
was 72%. 
The preceding specific embodiments are illustrative of the practice of the 
invention. It is to be understood, however, that other expedients known to 
those skilled in the art or disclosed herein, may be employed without 
departing from the spirit of the invention or the scope of the appended 
claims.