Process for the preparation of methylenebisphosphonic acids

Details Process for the preparation of methylenebisphosphonic acids Process for the preparation of methylenebisphosphonic acids

1992-04-30

1993-08-17

Ramsuer, Robert W.

Organic compounds -- part of the class 532-570 series

Organic compounds

Phosphorus acids or salts thereof

C07F 938

Patent

active

052370941

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND OF THE INVENTION

The present invention concerns a novel process for the preparation of methylenebisphosphonic acids of the formula I ##STR3## wherein Q.sup.1 and Q.sup.2 are independently hydrogen or halogen, by hydrolyzing the corresponding methylenebisphosphonic acid tetraester of the formula ##STR4## wherein R has the meaning of a straight or branched alkyl group containing 1 to 4 carbon atoms, and Q.sup.1 and Q.sup.2 have the same meaning as above.
Prior known processes for the preparation of bisphosphonic acids by hydrolyzing the corresponding tetraesters have been based on the use of strong acids, such as halogen acids. Thus tetraesters, e.g. the isopropyl tetraester, have been boiled for several hours with concentrated hydrochloric acid (c.f. BE-patent 672205, example VI (B)). In the publication Houben-Weyl, Methoden der Organischen Chemie, XII, 1, 352-356, the hydrolysis of tetraesters with half-concentrated hydrochloric acid under elevated pressure and at 130.degree.-145.degree. C. is described. A disadvantage with these known processes is the impurity of the products obtained and the numerous purification steps needed to remove byproducts and excess acid. In addition, the processes are connected with substantial corrosion problems. From the EP-patent application 0200980 is known a process according to which methylenebisphosphonic acids have been prepared by hydrolysing tetraesters with plain water, by boiling at reflux temperature of the reaction mixture. In this case the above mentioned problems of impurities and corrosion are largely overcome, but another problem is the very long reaction time, which may be as long as 16 hours, which is disadvantageous, i.a. from the viewpoint of production economics.


SUMMARY OF THE INVENTION

Now a process has been invented for the preparation of the above mentioned methylenebisphosphonic acids and their salts according to the formula I, with a good yield and in a very pure form, whereby the corrosion problems caused by the use of a strong acid are avoided. By means of the process according to the invention it has also been possible to shorten the reaction time even up to one quarter or more as compared to the process known from the EP-patent application 0200980.
The process according to the invention is thus characterized in that the hydrolysis is performed in an aqueous solution of the tetraester and hydrochloric acid, which solution contains from 1.0 to 5% by weight of HCl, based on the whole mixture. Below the said limit the hydrolysis proceeds too slowly from a practical viewpoint and above the said limit no substantial rate increase is achieved in relation to the amount of chloride ions added to the mixture.


BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph of the yield of hydrolysis (mole percent free acid) versus reaction time in hours, of three hydrolysis mixtures of this invention compared to plain water according to the prior art.


DETAILED DESCRIPTION

The hydrolysis is advantageously performed by boiling the aqueous solution of the tetraester and hydrochloric acid at reflux temperature. Thus the reaction mixture contains an excess Of water with regard to the stochiometric amount of water necessary for the complete hydrolysis of the tetraester. This excess of water is not critical and thus a multiple excess with regard to the stochiometric amount may be used. A practical volumetric amount of aqueous hydrochloric acid solution from the viewpoint of carrying out the hydrolysis is approximately 6 to 7 times the weight of the tetraester, whereby, on the one hand, a sufficient degree of dissolution of the tetraester in the aqueous medium is obtained, but at the same time the difficulties caused by the increase in volume in the subsequent hydrolysis stage are avoided.
According to one advantageous embodiment the amount of hydrochloric acid in the mixture is approximately 2.5 to 5% by weight, whereby an optimal result from the viewpoint of byproduct formation and reaction time is achieved.
The free tetraacid obtained as a result of the

REFERENCES:
patent: 4621077 (1986-11-01), Rosini et al.
Houben-Weyl, Methoden der Organischen Chemie, XII, 1, 352-356 (1963).
Morrison & Boyd, Organic Chemistry, 5th Ed., p. 875, (1959).

Affiliated with

Also associated with

Rating

Process for the preparation of methylenebisphosphonic acids does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Process for the preparation of methylenebisphosphonic acids, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the preparation of methylenebisphosphonic acids will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2245440