PROCESS FOR THE PREPARATION OF N-PHOSPHONOMETHYLGLYCINE

Abstract: A process for the preparation of N-phosphonomethylglycine is disclosed which comprises preparing an N-alkyl-N-phosphonomethylglycine or its ester represented by formula (I), wherein R is an alkyl group represented by formula (Ia) and R<1>, R<2> and R<3> are indenpendently selected from the group consisting of hydrogen and alkyl having one to about four carbon atoms, and R<4>, R<5> and R<6> are independently selected from substituted and unsubstituted alkyl groups having from one to about six carbon atoms wherein any substitution on the alkyl group has electron withdrawing properties, and hydrogen, provided that R<4>, R<5> and R<6> cannot all be hydrogen; and thereafter treating the N-alkyl-N-phosphonomethylglycine with an acid, other than a hydrohalic acid, having a pKa value below about +3 in the presence of an organic acid to provide N-phosphonomethylglycine.

Description: - l - PROCESS FOR THE PREPARATION OF N-PHOSPHONOMETHYLGLYCINE BACKGROUND OF THE INVENTION This invention relates to a process for the preparation of N-phosphonomethylglycine or its esters, and more particularly to the preparation of N-phosphonomethylglycine from N-substituted glycine derivatives. N-Phosphonomethylglycine, known by its common name of glyphosate, is widely used around the world as a broad- spectrum herbicide to control the growth of many plant species. Generally, it is used in an aqueous solution as one of its salts for application to plants to control the growth of woody plants, aquatic species, grasses, and the like. It is known to be generally non-toxic to humans and other mammals, and environmentally safe. Millions of liters of the formulated product are sold each year for such purposes. It is known that N-benzyl-N-phosphonomethylglycine (or its esters) undergoes hydrohalic acid debenzylation to yield benzyl halide and N-phosphonomethylglycine or its esters (see for example British Patent No 1 436 843) . A large excess of very concentrated (eg 48%) hydrohalic acid is required, however, amounting to many moles of acid for each mole of starting compound. This renders the processing and isolation of the desired glycine derivative difficult, mainly because of the problem of removing this large amount of hydrohalic acid after the reaction. Attempts to improve the process by the use of starting compounds having other substituents than benzyl on the nitrogen atom, eg to use N-alkyl-N-phosphonomethylglycines, have been attended with the same processing disadvantage (see for example US Patent No 3 927 080) . The literature contains no suggestions as to the use of acids other than the hydrohalic acids to remove the alkyl group from N-alkyl- *-ι _ — <£ — N-phosphonomethylglycine to produce the desired end product. Now, there is provided an easy procedure to dealkylate a wide variety of N-alkyl-N-phosphonomethylglycines to provide N-phosphonomethylglycine in high yields at an economical cost. SUMMARY OF THE INVENTION These and other advantages are achieved by a process for the preparation of N-phosphonomethylglycine which comprises: preparing an N-alkyl-N-phosphonomethylglycine or its ester represented by the formula wherein R is an alkyl group represented by the formula R 4 I R 6 - C - _• and R 1 , R 2 and R 3 are independently selected from the group consisting of hydrogen and alkyl having one to about four carbon atoms, and R 4 , R 5 and R 6 are independently selected from substituted and unsubstituted alkyl groups having from one to about six carbon atoms wherein any substitution on the alkyl group has electron withdrawing properties, and hydrogen, provided that R 4 , R 5 and R 6 cannot all be hydrogen; and thereafter treating the N-alkyl-N-phosphonomethylglycine with an acid, other than a hydrohalic acid, having a p B value below about +3 in the presence of an organic acid to provide N- phosphonomethylglycine. DETAILED DESCRIPTION OF THE INVENTION We have found that, apart from known processes using hydrohalic acids, certain N-alkyl-N-phosphonomethylglycine and their esters, in which the N-alkyl substituent is 5 suitably chosen, can be dealkylated by treatment not only with a hydrohalic acid but with any acid whose pK a value i below +3. Preferably, the acid used is selected from the group that consists of sulfuric acid, p-toluene sulfonic acid, methylsulfonic acid (subgroup A) and trichloroacetic 10 acid, phosphoric acid and phosphorous acid (subgroup B) . The acids of subgroup A are preferred, and sulfuric acid i especially preferred. In the case of sulfuric acid, an adequate molar proportion is less than about 10%, based on the moles of 15 alkyl substituted glycine derivative used in the process. Of the other acids named, molar proportions of about 5% to about 50% can be used, the preferred range being 10% to 20 based on the moles of alkyl substituted glycine derivative used. 20 Any number of organic acids known to those skilled in the art can be used in the treatment of the N-alkyl-N- phosphonomethylglycine with the acid having a pK B value of less than about +3. It is only necessary that the organic acid is water soluble, and lower molecular weight organic 25 acids are preferred. Suitable organic acids include formi acid, acetic acid, propionic acid, butanoic acid, and the like, for use in the reaction medium. Acetic acid is preferred. The temperatures to be used in the present process ca 30 vary within wide ranges. Temperatures between about 20°C and about 100°C provide satisfactory results. Lower temperatures can be used, but the reaction is somewhat slo Temperatures above 100°c can be used, but as will occur to those skilled in the art, the reaction vessel may have to be pressurized at such higher temperatures. Temperatures between about 40°C and 100 β C are preferred. When sulfuric acid is used, dealkylation begins at a temperature of about 50°C, and becomes rapid at about 80°C, with copious evolution of the relevant alkene. In a preferred embodiment of the process of the invention the dealkylation is carried out in the presence of acetic acid as a solvent. This has been shown to impart economies to the process, since the target compound crystallizes directly from the acetic acid in the course of the dealkylation reaction. In another preferred embodiment, which can be combined with any of the embodiments described above, the process of the invention comprises preparing the alkyl derivative in a manner known per se. and thereafter dealkylating it according to the invention as set out above, without previous isolation, in a one-pot procedure. More specifically, in the preferred embodiment, the N-alkyl-N- phosphonomethylglycine or ester used is synthesized from ethyl chloroacetate and an appropriate alkylamine, followed by ester hydrolysis, followed by phosphonomethylation of the resulting N-alkyl glycine or ester, and that entire process is performed without isolation or purification of any intermediate. In the preferred embodiment N-t-butyl-N-phosphonomethylglycine may be prepared by phosphonomethylation of N-t-butylglycine which in turn may be the product of the coupling of t-butylamine and ethyl chloroacetate, followed by ester hydrolysis. When the most preferred glycine derivative, namely N-t- butyl-N-phosphonomethylglycine, is dealkylated in accordance with the invention, especially when acetic acid is used as a solvent, iso-butylene is evolved. If, however, there is a significant amount of water present in the reaction mixture, then in addition to iso-butylene , * fe-butanol is obtained as a by-product. As will occur to those skilled in the art, corresponding products are obtained when other glycine derivative are used. As previously stated, the dealkylation of N-t-butyl-N- phosphonomethylglycine proceeds more rapidly in acetic acid than it does in water; however, it is the hiσh yield of N- phosphonomethylglycine from the acetic acid medium, with minimal processing, that provides a major technical advantage in the process of the invention. A final product of purity exceeding 90% by weight is obtainable by the process of the invention in a routinely reproducible manner. Typical reaction times are 2 to 4 hours. With cooling and filtration over 90% yields are obtainable. The following examples serve further to illustrate the invention: Example I N-t-Butyl-N-phosphonomethylglycine (100 g, 96% pure, 0.426 mol) was mixed with acetic acid (500 ml) and 97% sulfuric acid (4.0 g, 0.04 mol). On heating the mixture to 50°C in a round-bottomed flask fitted with a Liebig condenser, iso-butylene was detected downstream of the condenser. At 80°C large quantities of iso-butylene were evolved and the rate of evolution of this off-gas increased with temperature. After 3 hours at 100°C there was no N-t- butyl-N-phosphonomethylglycine detectable by HPLC in the reaction vessel, and large quantities of crystalline N- phosphonomethylyglycine were present. Cooling to ambient, filtering and drying gave N-phosphonomethylglycine (69.0 g, 95% pure, 91.2% yield). Analysis of the mother liquor showed a further 3.7 g of N-phosphonomethylglycine, giving a total chemical yield for this dealkylation of 96.3%. Example II N-t-Butyl-N-phosphonomethylglycine (100 g, 96% pure, 0.42 mol) was mixed with acetic acid (500 mis) and p_-toluene sulfonic acid (14.6 g, 0.085 mol). Heating at 100°C for 4 hours completed the reaction and the chemical yield of the dealkylation was 94%. Example III Ethyl chloroacetate (122.5 g 1.0 mole) was reacted with excess t-butylamine in trichloromethane and the ethyl glycinate separated from the t-butylamine hydrochloride. The ethyl glycinate was hydrolyzed with hydrochloric acid and the N-t-butyl-N-phosphonomethylglycine (167.6 g as determined by HPLC) was reacted with sulfuric acid (3.8 mis, 0.07 mol) at ambient temperature and the mixture was then heated at 100°C for 4 hours. Cooling to 20°C, filtering and drying gave N-phosphonomethylyglycine (118.5 g, 95.8% purity, 90.3% yield). The overall yield from ethyl chloroacetate was 67.2%. The invention is not limited by or to the details of the specific embodiments described, many of which can undergo wide variation without departing for from the scope of the invention.

Claims: WHAT IS CLAIMED IS: 1. A process for the preparation of N- phosphonomethylglycine which comprises: preparing an N-alkyl-N-phosphonomethylglycine or its ester represented by the formula wherein R is an alkyl group represented by the formula R 4 R 6 - C - R 5 and R 1 , R 2 and R 3 are independently selected from the group consisting of hydrogen and alkyl having one to about four carbon atoms, and R 4 , R 5 and R 6 are independently selected from substituted and unsubstituted alkyl groups having from one to about six carbon atoms wherein any substitution on the alkyl group has electron withdrawing properties, and hydrogen, provided that R 4 , R 5 and R° cannot all be hydrogen; and thereafter treating the N-alkyl-N-phosphonomethylglycine with an acid, other than a hydrohalic acid, having a pK a value below about +3 in the presence of an organic acid to provide N- phosphonomethylglycine. 2. The process of Claim 1 wherein R is isopropyl or t-butyl. 3. The process of Claim 1 wherein R is t-butyl. 4. The process of Claim 1 wherein the acid having a pK 8 value below about +3 is selected from the group consisting of E-toluene sulfonic acid, methyl sulfonic acid, sulfuric acid, trichloroacetic acid, phosphoric acid and phosphorous acid. 5. The process of Claim 4 wherein the acid in sulfuric acid. 6. The process of Claim 1 wherein the organic acid in acetic acid. 7. The process of Claim 1 wherein the N-alkyl- phosphonomethylglycine is synthesized by reacting ethyl chloroacetatic with an alkylamine, followed by ester hydrolysis, followed by phosphonomethylation of the resulting N-alkyl glycine. 8. The process of Claim 7 wherein the alkylamine in t-butylamine. 9. N-Phosphonomethylglycine produced by any of the processes in claims 1-8.

Inventors: GRAYSON DAVID, MCSWEENEY NIGEL, MORIARTY CIARA, RUSSELL NOEL, SHELLY DECLAN, TULLY LIAM, GRAYSON, DAVID, MCSWEENEY, NIGEL, MORIARTY, CIARA, RUSSELL, NOEL, SHELLY, DECLAN, TULLY, LIAM
Applicants: MONSANTO CO, MONSANTO COMPANY
Application year: 1989
Main classification: C07F9
IPC codes: C07F9