WO1990006929A1 - Process for the preparation of n-phosphonomethylglycine - Google Patents
Process for the preparation of n-phosphonomethylglycine Download PDFInfo
- Publication number
- WO1990006929A1 WO1990006929A1 PCT/US1989/005711 US8905711W WO9006929A1 WO 1990006929 A1 WO1990006929 A1 WO 1990006929A1 US 8905711 W US8905711 W US 8905711W WO 9006929 A1 WO9006929 A1 WO 9006929A1
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- WO
- WIPO (PCT)
- Prior art keywords
- acid
- phosphonomethylglycine
- alkyl
- hydrogen
- group
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 26
- XDDAORKBJWWYJS-UHFFFAOYSA-N glyphosate Chemical compound OC(=O)CNCP(O)(O)=O XDDAORKBJWWYJS-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 24
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 16
- 150000002148 esters Chemical class 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
- 150000007524 organic acids Chemical class 0.000 claims abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 6
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 3
- 238000006467 substitution reaction Methods 0.000 claims abstract description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 30
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 16
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 150000003973 alkyl amines Chemical class 0.000 claims description 3
- 238000010931 ester hydrolysis Methods 0.000 claims description 3
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 2
- 239000004471 Glycine Substances 0.000 claims description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims 1
- YIWJBYZZVNVZBX-UHFFFAOYSA-N 2-[tert-butyl(phosphonomethyl)amino]acetic acid Chemical compound OC(=O)CN(C(C)(C)C)CP(O)(O)=O YIWJBYZZVNVZBX-UHFFFAOYSA-N 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 6
- 238000006900 dealkylation reaction Methods 0.000 description 6
- 150000002332 glycine derivatives Chemical class 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000020335 dealkylation Effects 0.000 description 5
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 4
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- TXHAHOVNFDVCCC-UHFFFAOYSA-N 2-(tert-butylazaniumyl)acetate Chemical compound CC(C)(C)NCC(O)=O TXHAHOVNFDVCCC-UHFFFAOYSA-N 0.000 description 1
- KOJRWLCMBRYCBJ-UHFFFAOYSA-N 2-[benzyl(phosphonomethyl)amino]acetic acid Chemical compound OC(=O)CN(CP(O)(O)=O)CC1=CC=CC=C1 KOJRWLCMBRYCBJ-UHFFFAOYSA-N 0.000 description 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 1
- 239000005562 Glyphosate Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108010049175 N-substituted Glycines Proteins 0.000 description 1
- 241000209504 Poaceae Species 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- -1 benzyl halide Chemical class 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229960001701 chloroform Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000006264 debenzylation reaction Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229940097068 glyphosate Drugs 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- DLDIDQIZPBIVNQ-UHFFFAOYSA-N hydron;2-methylpropan-2-amine;chloride Chemical compound Cl.CC(C)(C)N DLDIDQIZPBIVNQ-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
- C07F9/3813—N-Phosphonomethylglycine; Salts or complexes thereof
Definitions
- 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.
- N-benzyl-N-phosphonomethylglycine 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.
- N-phosphonomethylglycine to produce the desired end product.
- N-phosphonomethylglycine which comprises: preparing an N-alkyl-N-phosphonomethylglycine or its ester represented by the formula
- R is an alkyl group represented by the formula
- 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.
- the acid used is selected from the group that consists of sulfuric acid, p-toluene sulfonic acid, methylsulfonic acid (subgroup A) and trichloroacetic
- the acids of subgroup A are preferred, and sulfuric acid i especially preferred.
- an adequate molar proportion is less than about 10%, based on the moles of
- alkyl substituted glycine derivative used in the process.
- 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.
- 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
- 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 ⁇ 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.
- 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.
- 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.
- 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.
- * fe-butanol is obtained as a by-product.
- corresponding products are obtained when other glycine derivative are used.
- 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.
- 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%.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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, R2 and R3¿ are indenpendently selected from the group consisting of hydrogen and alkyl having one to about four carbon atoms, and R?4, R5 and R6¿ 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, R5 and R6¿ 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.
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
R4 I
R6 - C -
_• and R1, R2 and R3 are independently selected from the group consisting of hydrogen and alkyl having one to about four carbon atoms, and R4, R5 and R6 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 R4, R5 and R6 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 pKa 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 pKB 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 100βC 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
1. A process for the preparation of N- phosphonomethylglycine which comprises: preparing an N-alkyl-N-phosphonomethylglycine or its ester represented by the formula
R6 - C -
R5 and R1, R2 and R3 are independently selected from the group consisting of hydrogen and alkyl having one to about four carbon atoms, and R4, R5 and R6 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 R4, R5 and R° 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.
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 pK8 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.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019900701832A KR910700255A (en) | 1988-12-22 | 1989-12-20 | Method for preparing N-phosphonomethylglycine |
| JP50196789A JPH04505154A (en) | 1989-12-20 | 1989-12-20 | Method for producing N-phosphonomethylglycine |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE883838A IE883838L (en) | 1988-12-22 | 1988-12-22 | N-phosphonomethylglycine |
| IE3838/88 | 1988-12-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1990006929A1 true WO1990006929A1 (en) | 1990-06-28 |
Family
ID=11039131
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1989/005711 WO1990006929A1 (en) | 1988-12-22 | 1989-12-20 | Process for the preparation of n-phosphonomethylglycine |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0449987A1 (en) |
| KR (1) | KR910700255A (en) |
| AU (1) | AU620489B2 (en) |
| CA (1) | CA2006270A1 (en) |
| IE (1) | IE883838L (en) |
| WO (1) | WO1990006929A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1062221A1 (en) * | 1998-02-12 | 2000-12-27 | Monsanto Company | Process for making glyphosate by oxidizing n-substituted glyphosates |
| EP1520857A1 (en) * | 1998-08-12 | 2005-04-06 | Monsanto Technology LLC | Process for the preparation of N-(phosphonomethyl) glycine by oxidizing N-substituted N-(phosphonomethyl) glycine |
| US7091376B2 (en) * | 1997-05-05 | 2006-08-15 | Monsanto Technology Llc | Method for preparing formylphosphonic acid |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3927080A (en) * | 1974-09-03 | 1975-12-16 | Monsanto Co | Process for producing N-phosphonomethyl glycine |
| US4650613A (en) * | 1984-12-28 | 1987-03-17 | Monsanto Company | Process for preparing N-phosphonomethylglycine and derivatives |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4851159A (en) * | 1988-05-02 | 1989-07-25 | Monsanto Company | Process for the preparation of N- phosphonomethylglycine |
-
1988
- 1988-12-22 IE IE883838A patent/IE883838L/en unknown
-
1989
- 1989-12-20 AU AU48418/90A patent/AU620489B2/en not_active Ceased
- 1989-12-20 EP EP19900902002 patent/EP0449987A1/en not_active Withdrawn
- 1989-12-20 WO PCT/US1989/005711 patent/WO1990006929A1/en not_active Application Discontinuation
- 1989-12-20 KR KR1019900701832A patent/KR910700255A/en not_active Application Discontinuation
- 1989-12-21 CA CA002006270A patent/CA2006270A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3927080A (en) * | 1974-09-03 | 1975-12-16 | Monsanto Co | Process for producing N-phosphonomethyl glycine |
| US4650613A (en) * | 1984-12-28 | 1987-03-17 | Monsanto Company | Process for preparing N-phosphonomethylglycine and derivatives |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7091376B2 (en) * | 1997-05-05 | 2006-08-15 | Monsanto Technology Llc | Method for preparing formylphosphonic acid |
| EP1062221A1 (en) * | 1998-02-12 | 2000-12-27 | Monsanto Company | Process for making glyphosate by oxidizing n-substituted glyphosates |
| EP1062221A4 (en) * | 1998-02-12 | 2001-10-17 | Monsanto Technology Llc | Process for making glyphosate by oxidizing n-substituted glyphosates |
| EP1520857A1 (en) * | 1998-08-12 | 2005-04-06 | Monsanto Technology LLC | Process for the preparation of N-(phosphonomethyl) glycine by oxidizing N-substituted N-(phosphonomethyl) glycine |
Also Published As
| Publication number | Publication date |
|---|---|
| AU4841890A (en) | 1990-07-10 |
| EP0449987A1 (en) | 1991-10-09 |
| CA2006270A1 (en) | 1990-06-22 |
| KR910700255A (en) | 1991-03-14 |
| AU620489B2 (en) | 1992-02-20 |
| IE883838L (en) | 1990-06-22 |
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