1. Field of the Invention
The present invention relates to a method for preparing an N-acylaminomethylphosphonic acid useful as an intermediate for synthesizing N-phosphonomethylglycine known as the herbicide glyphosate.
2. Description of Prior Art
Reaction between an N-methylolamide compound and a phosphorus trihalide to prepare an N-acylaminomethylphosphonic acid or aminomethylphosphonic acid has been known by itself and can roughly be classified into 1) a process in which the reaction proceeds without solvents; 2) a process in which the reaction proceeds in an organic solvent; and 3) a process in which the reaction proceeds in an organic acid.
However, the known processes have various defects as described below and are practically disadvantageous.
For example, 1) as for the process without solvents, a process is disclosed in Synthetic Communication, vol. 16, No. 7, p.733, in which process N-methylolbenzamide is added to a mixture of phosphorus trichloride and trimethylphosphite for reaction to obtain O,O'-dimethyl-N-phosphonomethylbenzamide in a yield of 79%, which then is hydrolyzed to prepare amiomethylphosphonic acid. This process is economically disadvantageous since it uses a large amount of trimethylphosphite, which is relatively expensive. Also, Sb. Vys. Sk. Chem.-Technol. Praze. Org. Chem. Technol., C28, p.115 discloses a process in which aminomethylphosphonic acid is prepared from N-methylolformamide and phosphorus trichloride in the absence of solvents. This process gives a very low yield as low as 29.5%, which is practically unacceptable.
U.S. Pat. Nos. 2,328,358 and 2,304,156 disclose processes in which various N-methylolamide compounds and phosphorus trihalides are reacted in the absence of solvents, and then brought into contact with excess of water to obtain amiomethylphosphonic acid. However, the examples therein use long reaction times ranging 1 to 4 days with low yields. As to the yield of the objective compounds, only the yield of the reaction using N-methylolstearylamide, 62%, was recited but nothing was described about the other reactions. Afterwards, referring to this U.S. patent, J. Pract. Chem., vol. 329, No. 1, p.19 pointed out that the yield of N-acylaminomethylphosphonic acid before the hydrolysis of the amide was 20% to 35%.
As described above, the reactions in the absence of solvents not only have various disadvantages that they generally must use relatively expensive raw materials in excessive amounts, the reaction times are long, yields are low, and so on, but also they suffer difficulty in control since they use phosphorus trihalides which makes them exothermic reactions. Thus, the solventless reactions are in no way practical.
2) As for the process in which reaction proceeds in an organic solvent, examples which use carbon tetrachloride, ethyl acetate, acetic acid or the like are described in U.S. Pat. Nos. 2,328,358 and 2,304,156 referred to above. Although accurate evaluation is impossible because no concrete yield values were shown in those U.S. patents, one skilled in the art might expect no great differences with respect to the long reaction time and low yield from those in the case of solventless reactions.
In U.S. Pat. No. 2,304,156, explanation is made to the effect that the reaction proceeds in two stages: first, an N-methylolamide compound is reacted with phosphorus trichloride in the absence of solvents or in an organic solvent to prepare dichlorophosphorus ester (RCONHCH.sub.2 OPCl.sub.2), which then is converted to aminomethylphosphonyl dichloride (RCONHCH.sub.2 POCl.sub.2) by a rearrangement reaction, and the latter compound is reacted with water to give rise to N-acylaminomethylphosphonic acid [RCONHCH.sub.2 PO(OH).sub.2 ]. However, none of these intermediates has been isolated from the reaction mixture and put to determination of the chemical structure. Among the aforementioned reactions, the rearrangement reaction from dichlorophosphorus ester to phosphonyl dichloride is said to take a long time as long as on the order of day.
Reportedly, the low reaction rate could be improved by elevating the reaction temperature, or by addition of a small amount of a weak acid such as acetic acid, propionic acid or acetic anhydride. However, the present inventors have found that the effect of increasing yield by these attempts is insufficient. For example, when N-methylolacetamide and phosphorus trichloride were reacted for 24 hours at room temperature and then the reaction mixture was brought in contact with a large amount of water, the yield of the resulting N-acetylaminomethylphosphonic acid was found to be 32%. When the reaction was continued for 3 hours with elevating the reaction temperature to 90.degree. C., the yield of N-acetylaminomethylphosphonic acid was 38% and it was only a slight improvement. When the reaction proceeded for 3 hours at 90.degree. C. after addition of acetic acid, the yield was 65% at a ratio of acetic acid to phosphorus trichloride being 1.5 times molar amount, and 63% at a ratio of acetic acid to phosphorus trichloride being even 10 times molar amount. Thus, improvements, if any, were insufficient. While the reasons why the yield is low are unclear, one possible reason may be that N-methylolamide is splitted to methylenediamide and formaldehyde in contact with phosphorus trichloride although the present inventors do not want to be bound thereto.
3) The processes in which the reaction proceeds in an organic acid, particularly the one which uses acetic acid, exhibit relatively higher yields among the known processes, and hence most of recently proposed processes relate to improvement of such processes.
For example, Synthesis, 1989, No. 4, p.547 discloses a process in which N-methylolbenzamide or 1,3,5-triacetylhexahydro-1,3,5-triazine is reacted with phosphorus trichloride in acetic acid to prepare N-acylaminomethylphosphonic acid, which is then hydrolyzed after acetic acid and acetyl chloride are distilled off from the reaction mixture to obtain aminomethylphosphonic acid. However, it is reported that sufficient results can be obtained only when aromatic starting compounds are used and that nitrilotrismethylphosphonic acid is a major product when aliphatic starting compounds are used.
European Patent 370,992 discloses a process in which after treating acetamide and paraformaldehyde in a nonaqueous system containing acetic acid, phosphorus trichloride is added thereto for reaction to prepare N-acetylaminomethylphosphonic acid, which is then hydrolyzed to obtain aminomethylphosphonic acid after distilling off the solvent and by-products from the reaction mixture. Polish Patent 117,780 discloses a process in which N-methylolbenzamide is reacted with phosphorus trichloride in acetic acid, the resulting N-benzoylaminomethylphosphonic acid is hydrolyzed to prepare aminomethylphosphonic acid.
These processes involving the reactions in acetic acid solvents exhibit relatively higher yields than the other known processes but on the other hand, acetyl halides are by-produced and hence additional efforts are needed in order to separate and collect them as well as acetic acid as the solvent, which leads to economical disadvantage.
USPTO Backgrounds
USPTO Backgrounds