Method for preparation of N-phosphonomethylglycine

Disclosed is a method for the preparation of N-phosphonomethylglycine which comprises the steps of (1) reacting 1,3,5-tris(alkoxy- or aryloxy-substituted carbonylmethyl) hexahydro-s-triazine, with a substituted phosphorus compound having the formula PXYZ wherein X is a halogen, Y and Z are independently selected from the group consisting of halogen, alkoxy having from 1 to 10 carbon atoms, and aryloxy, in the presence of a protic acid and a low molecular weight carboxylic acid; (2) heating said reactants to a temperature ranging from about 10.degree. to about 25.degree. C. for a sufficient period of time to cause the formation of an N-phosphonomethylglycine ester,; and (3) hydrolyzing said phosphonomethylglycine ester to N-phosphonomethylglycine.

BACKGROUND OF THE INVENTION 
This invention relates to a novel method for the preparation of 
N-phosphonomethylglycine, a compound which is a known herbicide and plant 
growth regulator. 
Herbicides are widely used by farmers, commercial agricultural companies, 
and other industries in order to increase crop yields for such staple 
crops as corn, soybeans, rice, and the like, and to eliminate weed growth 
along highways, railroad rights-of-way, and other areas. Herbicides are 
effective in killing or controlling unwanted weeds which compete for soil 
nutrients with the crop plants, and by reason of the fact that they kill 
weeds, are responsible for improving the aesthetic appearance of highway 
and railroad rights-of-way. There are a number of different types of 
herbicides presently sold commercially, and these fall into two general 
categories. The categories are pre-emergence and post-emergence 
herbicides. The pre-emergence herbicides are incorporated into the soil 
prior to the emergence of the weed plants from the soil, and the 
post-emergence herbicides are applied to plant surfaces after emergence of 
the weeds or other unwanted plants from the soil. 
One of the earliest post-emergence herbicides used commercially was 2,4-D 
(2,4-dichlorophenoxyacetic acid). After a number of years of use of this 
and similar compounds such as 2,4,5-T (2,4,5-trichlorophenoxy acetic 
acid), it was found that certain decomposition products of these 
herbicides were long lasting and were not biodegradable. While there has 
been some dispute between governmental agencies and commercial interests 
regarding the effects of residual products of 2,4-D, 2,4,5-T and similar 
compounds, the agencies nevertheless restricted the use of these 
herbicides in the United States some years ago. Since that time, efforts 
have been made to develop herbicides which are biodegradable into harmless 
residues within a relatively short time after their application. 
One such compound, which has been found to be biodegradable, yet which is 
effective as a herbicide and plant growth regulator when employed at lower 
rates, is N-phosphonomethylglycine and various salts thereof. The 
N-phosphonomethylglycine and agriculturally effective salts have been 
approved for use by the U.S. Government, and, as a consequence, this 
herbicide has become extremely successful commercially. 
The N-phosphonomethylglycine and certain salts are the only effective and 
approved post-emergence herbicides in the field. The present commercial 
compound is the isopropylamine salt of N-phosphonomethylglycine and 
derivatives thereof. 
In field use it is normally applied in amounts of from 0.01 to about 20 
pounds per acre, preferably from 2 to 6 pounds per acre. 
The N-phosphonomethylglycines, and certain soluble salts thereof, can be 
made in a number of different ways. One such method, as described in U.S. 
Pat. No. 3,160,632 (Toy et al., Dec. 8, 1964) is to react 
N-phosphinomethylglycine (glycinemethylenephosphinic acid) with mercuric 
chloride in a water solvent at reflux temperature, and subsequently 
separating the reaction products. Another method is the reaction of ethyl 
glycinate with formaldehyde and diethylphosphite. The latter method is 
described in U.S. Pat. No. 3,799,758 (Franz, Mar. 26, 1974). In addition, 
there is a whole series of patents, relating to N-phosphonomethylglycines, 
their salts, and derivatives thereof, described as being useful herbicides 
and plant growth regulators. Such additional patents relating to the 
N-phosphonomethylglycines, methods of application, methods of preparation, 
salts, and derivatives, include U.S. Pat. No. 3,868,407, U.S. Pat. No. 
4,197,254, and U.S. Pat. No. 4,199,354, among others. 
Because of the importance of N-phosphonomethylglycine and certain salts as 
a herbicide, other methods of making the compounds are constantly being 
sought in order to provide improved or alternate methods of manufacture. 
SUMMARY OF THE INVENTION 
It has now been discovered that N-phosphonomethylglycine can be produced 
by: 
(1) reacting 1,3,5-tris(alkoxy- or aryloxycarbonylmethyl) 
hexahydro-s-triazine with a substituted phosphorus compound having the 
formula PXYZ wherein X is a halogen, Y and Z are each independently 
selected from the group consisting of halogen, alkoxy having from 1 to 10 
carbon atoms and aryloxy, in the presence of a relatively strong protic 
acid and a low molecular weight carboxylic acid having from 1 to 6 carbon 
atoms, and 
(2) hydrolyzing the intermediate ester of N-phosphonomethylglycine thus 
formed to convert said ester of N-phosphonomethylglycine to 
N-phosphonomethylglycine. 
Preferred starting compounds for use in the method of the invention include 
1,3,5-tris(ethoxycarbonylmethyl) hexahydro-s-triazine, and 
1,3,5-tris(propoxycarbonylmethyl) hexahydro-s-triazine. Other suitable 
compounds would include the aryloxy substituted carbonylmethyl 
hexahydro-s-triazines. 
Preferred substituted phosphorus compounds for use in the above process 
include phosphorus trichloride, phosphorus tribromide, ethyl 
dichlorophosphite, and diethyl chlorophosphite. 
Preferred relatively strong protic acids for use in the above process 
include hydrochloric acid, hydrobromic acid, hydriodic acid, sulfuric 
acid, and phosphoric acid, with the most preferred acid being hydrochloric 
acid. 
Suitable low molecular weight carboxylic acids include acetic acid, 
propanoic acid and butanoic acid. 
When phosphorus trichloride is the trivalent phosphorus compound used, the 
reaction products for the first step of the process are 
N-phosphonomethylglycine, C-ethyl ester hydrochloride, and a carboxylic 
acid chloride. N-Phosphonomethylglycine can then be produced by 
hydrolyzing the intermediate ester with a suitable hydrolyzing agent to 
yield N-phosphonomethylglycine. 
An optional feature of the method of the invention is that the 
N-phosphonomethylglycine compound produced as indicated above, can then be 
reacted with a suitable base to produce the soluble salts of the acid. 
Suitable bases for this purpose would include sodium hydroxide, potassium 
hydroxide, trimethylsulfonium hydroxide or the hydroxide or oxide of any 
agriculturally acceptable cation. 
In the process of the invention, phosphorus trichloride, hydrogen chloride, 
and acetic acid, are preferably used to react with the starting compound 
1,3,5-tris(alkoxy- or aryloxycarbonylmethyl) hexahydro-s-triazine. 
Alternatives to these compounds can be used, however. In the case of 
phosphorus trichloride, alternative compounds would be, for example, 
phosphorus tribromide, phosphorus dibromochloride, and ethyl 
dichlorophosphite. Instead of hydrogen chloride, suitable alternatives 
would be hydrogen bromide, hydriodic acid, sulfuric acid, and phosphoric 
acid. Instead of acetic acid, any low molecular weight carboxylic acid 
would be suitable, including propanoic and butanoic acid. 
The product of the above described reaction, the N-phosphonomethylglycine 
ester, is then hydrolyzed in aqueous acid, with subsequent alkaline 
work-up, or in aqueous base with subsequent acidic work-up to afford 
N-phosphonomethylglycine. 
The overall process, using the preferred ingredients, can be represented as 
follows: 
##STR1## 
The hexahydro-s-triazine and phosphorus trichloride are used in 
approximately stoichoimetric amounts and the hydrochloric acid and acetic 
acid in excess. The reaction is conducted at a temperature ranging from 
about 0.degree. to about 50.degree. C., preferably 10.degree. to 
25.degree. C., at atmospheric pressure, and for a time sufficient to bring 
the reaction to completion, which preferably ranges from about 3 to about 
18 hours.

This invention will be better understood by reference to the specific 
example which follows, which serves to illustrate the instant invention. 
EXAMPLE 1 
Preparation of N-Phosphonomethylglycine, Trisodium Salt 
To a three-necked, 50 milliliter (ml) round-bottom flask equipped with a 
magnetic stirrer, a nitrogen bubbler, a reflux condenser, and a 
thermometer, and a heating mantle was added 10 ml (175 mmole) of acetic 
acid, under a nitrogen atmosphere. Thereafter, 2.6 ml (30 mmole) of 
phosphorus trichloride was added in one portion to the flask. The solution 
was cooled in an ice bath and thereafter 2 grams (g) (54 mmole) of 
hydrochloric acid was added slowly. At the same time, 3.45 g (10 mmole) of 
1,3,5-tris(ethoxycarbonylmethyl)hexahydro-s-triazine was dissolved in 40 
ml of acetic acid and placed in a dropping funnel. The 
hexahydro-s-triazine solution was then added over 0.9 hours at 
6.degree.-12.degree. C. Hydrogen chloride addition was continued during 
the addition of the hexahydro-s-triazine and then stopped. A total of 6.5 
g (178 mmole) of hydrogen chloride was added. The reaction mixture was 
stirred for ca. one hour at 10.degree.-15.degree. C. and then for ca. 18 
hours at 20.degree. C. Thereafter, 5.0 ml of water was added dropwise at 
approximately 20.degree. C. over a 20 minute period to give a cloudy 
colorless solution. This solution was stirred at ambient temperature for 
2.5 hours, and concentrated in vacuo at 40.degree. C., yielding an opaque 
colorless oil. This oil (4.8 g) was then taken up in 5.0 ml of water, and 
basified to a pH of 12 with 10 molar sodium hydroxide. Then 5.0 ml more of 
10 molar sodium hydroxide was added. Thereafter the solution was heated to 
reflux and maintained at reflux for a period of approximately 6 hours. The 
reaction mixture was analyzed by .sup.13 C nuclear magnetic resonsance 
(nmr) spectroscopy and by high performance liquid chromatography (hplc) 
and found to contain the trisodium salt of N-phosphonomethylglycine in 41% 
yield. 
It will be recognized by those skilled in the art that variations in the 
quantities of reactants, temperatures used, mole ratios used, and time of 
reaction can be made in the method of the invention without departing from 
the spirit and scope of the appended claims.