HRP940885A2 - Process for the preparation of n-phosphonomethyglycine - Google Patents

Description

Field of invention

This invention is a new process for obtaining N-phosphonomethylglycine.

The basis of the invention

N-phosphonomethylglycine and certain salts are particularly effective as post-emergence herbicides. The commercial herbicide is sold as a formulation containing the isopropylamine salt of N-phosphonomethylglycine.

N-phosphonomethylglycine can be made using a number of processes. One such procedure, as described in U.S. Pat. Patent 3,160,632 deals with the reaction of N-phosphonomethylglycine (glycine-methylenephosphonic acid) with mercury chloride in water at reflux temperature, and the subsequent separation of the reaction products. Other procedures are phosphonomethylation of glycine and the reaction of ethyl glycinate with formaldehyde. The latter procedure is described in U.S. Patent No. 3,868,407, 4,197,254 and 4,199,354.

Related earlier science is in the U.S. Patent 3,923,877 which suggests the reaction of 1,3,5-tricyanomethylhexahydro-1,3,5-triazine with excess disubstituted phosphite to form (RO)2P(O)CH2NHCH2CN (R is hydrocarbyl or substituted hydrocarbyl) which is hydrolyzed to give gets N-phosphonomethylglycine.

Because of the commercial importance of N-phosphonomethylglycine and certain salts as herbicides, improved procedures for the preparation of these compounds are valuable.

Brief description of the invention

This invention relates to a process for the preparation of N-phosphonomethylglycine, which includes:

(1) reaction of 1,3,5-tricyanomethylhexahydro-1,3,5-triazine with some acyl halide, preferably acyl chloride, so that N-cyanomethyl-N-halomethylamide acyl halide is formed;

(2) reaction of the amide with the phosphite to form N-acyl-methyl-N'cyanomethylphosphonate; and

(3) hydrolysis of this phosphonate to yield N-(phosphono-methyl)-glycine.

Detailed description of the invention

The process of this invention can be illustrated by the following reaction scheme:

[image]

where R is an aliphatic or aromatic group as defined hereinbelow, preferably C1-4 alkyl, most preferably methyl or ethyl and X is chlorine, bromine or iodo, preferably chlorine.

[image]

where R and X are defined as above and R1 and R2 are both aromatic groups or both aliphatic groups, preferably R1 and R2 are C1-C6 alkyl, more preferably C1-4 alkyl or R3 is an alkali metal (M) preferably sodium or potassium.

[image]

where R, R1 and R2 are as defined above and H+ is such a strong acid as hydrochloric, hydrobromic, hydroiodic, nitric, sulfuric, phosphonic or chloroacetic acid and OH- is such a strong base as sodium hydroxide or potassium -hydroxide, preferably in an aqueous, aqueous-alcoholic or alcoholic solution. The hydrolysis is preferably carried out in the presence of a strong acid.

In the above reaction scheme, the group R is not directly involved in the reaction phase (a) between 1,3,5-tricyanomethylhexahydro-1,3,5-triazine and acyl chloride. The groups R, R1 or R2 are not directly involved in the reaction phase (b) between N-cyanomethyl-N-chloro-methylamide of the reaction product in addition to phases (a) and phosphite. The groups R, R1 and R2 are separated in reaction step (c) when the phosphonate reaction product from reaction step (b) is subjected to hydrolysis. Therefore, the natural group R, R 1 and R 2 are not critical, although the group that will interfere with the reaction phase (a) and (b) should be avoided.

The group "C1-4 alkyl" includes methyl, ethyl, n-propyl, isopropyl n-butyl, isobutyl, sec-butyl and tert-butyl. The group "C1-4 alkyl includes the same radicals as C1-4 alkyl plus 6 pentyl and 16 hexyl.

The term "aliphatic group" is used in a broad sense to denote a large class of organic groups characterized by being derived from (1) series of acyclic (open chain structure) paraffinic, olefinic and acetylenic hydrocarbons and their derivatives or (2) alicyclic compounds. An aliphatic group can have from 1 to 10 carbon atoms.

The term "aromatic group" is used in a broad sense to distinguish it from an aliphatic group and includes a group derived from (1) compounds having 6 to 20 carbon atoms and characterized by the presence of at least one benzene ring, including monocyclic, bicyclic, and polycyclic hydrocarbons and their derivatives and (2) heterocyclic compounds having 5 to 19 carbon atoms which are similar in structure and which are characterized by having an unsaturated ring structure containing at least one atom different from carbon such as nitrogen, sulfur and oxygen and derivatives of these heterocyclic compounds.

Reaction phase (a) is preferably carried out at a temperature between 0°C to about 150°C, more preferably between 40°C to about 110°C and most preferably between 75°C to about 85°C. This reaction vessel can be operated at atmospheric, sub-atmospheric or super-atmospheric pressure, preferably at atmospheric pressure. It is preferable that the reaction is carried out in a solvent for acylhalogens, such as ethylene dichloride, methylene chloride, tetrahydrofuran or telulol.

Three moles of acyl halides are required to react with one mole of 1,3,5-tricyanomethylhexahydro-1,3,5-triazine. An excess of acyl halide can be used to ensure complete reaction with the triazine. A large excess of acyl halide can serve as a solvent in this reaction phase. The solvent or any excess acyl halide can be removed to isolate the N-cyanomethyl-N-chloromethylamide acyl halide in high yields. However, this amide rapidly degrades thermally and by hydrolysis and should be kept in an internal atmosphere if isolated.

Most preferably, no excess acyl halide is used and the solvent used in reaction step (a) is also used as a solvent in reaction step (b). Thus, the solvent does not have to be separated after the completion of phase (a) and is used in the reaction phase (b).

In the reaction phase (b), approximately equal molar amounts of N-cyanomethyl-N-halomethylamide acyl halide and phosphine react most preferably. Less preferably, up to 2 molar excess and least preferably up to 10 molar excess can be used.

The reaction is exothermic and can be carried out at a temperature between 0 to 150°C, preferably between 40°C to about 100°C, most preferably between 75°C to about 85°C.

No solvent is required for the reaction, however, any internal solvent can be used, preferably a solvent having a boiling point between 40°C to about 100°C. Examples of such solvents are ethylene chloride, methylene chloride, tetrahydrofuran and toluene. Using an internal solvent helps dissipate the heat of reaction. The most preferred solvent is the one used in reaction step (a). Any solvent used in this reaction step will be separated after completion of reaction step (c), so one that can be separated by evaporation is preferred.

Alkali metal phosphites having the formula:

[image]

wherein R 1 and R 2 are as defined and R 3 is an alkali metal they react with N-cyanomethyl-N-halomethylamide under such an internal atmosphere as nitrogen. An alkali metal phosphite can be made by reacting an alkali metal alkoxide, an alkali metal hydride, or an alkali metal with an equal molar amount of a disubstituted phosphite of the formula:

[image]

in which R1 and R2 are as defined. This reaction is carried out in such an internal atmosphere as nitrogen.

Alkali metal phosphites of the formula

[image]

in which R1 and R2 and M are as defined, due to tautomerism have the following complementary structural formula

[image]

where R1 and R2 are as defined and M is an alkali metal.

In reaction phase (c), a mole of phosphonate reaction product from reaction phase (b) is hydrolyzed with 5 moles of water. Hydrolysis is carried out in the presence of a strong acid or base as defined above. Acid-catalyzed hydrolysis is preferred, preferably with some non-aronic acid and most preferably with hydrochloric or hydrobromic acid. Hydrolysis gives the desired N-phosphonomethylglycine. Preferably, at least 2 moles of acid are used. Most preferably, a large excess above 2 moles is used. Hydrochloric or hydrobromic acid can preferably be used in concentrated or aqueous form.

The last reaction phase is carried out at a temperature between 0 to about 200°C, preferably between 50°C to about 125°C, and most preferably between 100°C to about 125°C.

Atmospheric, sub-atmospheric or super-atmospheric pressures can be used. Atmospheric pressure is preferably used during hydrolysis.

Solid N-phosphonomethylglycine can be regenerated by conventional techniques in reaction step (c). Volatile liquid products such as alcohols (methanol), chlorides (methyl chloride), acids (acetic acid), water, and excess acid can be separated using standard separation techniques. The desired N-phosphonomethylglycine is regenerated in high purity by dissolving it in water. Adjusting the pH of the solution to between 1 and 2 by allowing it to crystallize from the solution and separating it by filtration.

The process of the present invention can be better understood by reference to the following specific examples.

Example 1

Preparation of N-cyanomethyl-N-chloromethylacetamide

[image]

17 grams (g) (0.0835 mole) of 1,3,5-tricyanomethylhexahydro-1,3,5-triazine is suspended in a round bottom flask with 150 milliliters (nl) of 1,2-dichloroacetone. 40 ml (0.563 mol) of acetyl chloride was added at once and the reaction mixture was refluxed for 3 hours, then it was evaporated under reduced pressure so that 26.9 g (79.85%) of N-cyanomethyl-N-chloromethylacetamide were obtained. The structure was confirmed by the usual analytical methods (infrared, proton nuclear magnetic resonance and mass spectroscopy).

Example 2

Preparation of 0,0-dimethyl-N-cyanomethyl-N-acetylaminomethylphosphone

[image]

The amide compound made in Example 1 (26.9 g, 0.3 mol) is diluted with 75 ml of dichloromethane. Trimethylphosphite (25.5 g, 0.206 mol) was added and the mixture was stirred at room temperature overnight, refluxed for 0.5 h and evaporated under reduced pressure to give 43.9 g (79.32%) of the desired product. The structure was confirmed using infrared (ir), proton nuclear magnetic resonance (nmr) and mass spectroscopy (ms).

Example 3

Preparation of N-phosphonomethylglycine

[image]

The phosphonate reaction product from Example 2 (19.5 g, 0.09 mol) is combined with 100 ml (1.21 mol) of concentrated hydrochloric acid, refluxed for 3 hours and evaporated under reduced pressure. After dissolving the residues in 30 ml of water, the pH is adjusted to 10 with 50% sodium hydroxide, the mixture is evaporated under reduced pressure. The product is redissolved in 30 ml of water and the pH is adjusted to 1 with concentrated hydrochloric acid. The mixture is kept in the refrigerator overnight and the next morning, 5.4 g (98.3% purity by weight) of the desired product (35.49% yield) is isolated by filtration. The structure was confirmed by IR spectroscopy, nmr and liquid chromatography (1c).

Example 4

Preparation of N-phosphonomethylglycine

50 ml. 1,2-dichlorooctene is heated at reflux in a 50 ml round-bottomed flask. Acetyl chloride (5.5 ml, 0.077 mol) and 3.4 g (0.0167 mol) of 1,3,5-tricyanomethylhexahydro-1,3,5-triazine are added simultaneously over 10 minutes while maintaining an excess of acetyl halide in the reaction vessel. The mixture is refluxed for 0.5 hours after the addition is complete and then evaporated under reduced pressure.

5 ml of toluene and 6.6 ml (0.05 mol) of trimethylphosphite are added to the residue and this mixture is refluxed for 15 minutes, stirred at room temperature for 2 hours and evaporated under reduced pressure. 30 ml of concentrated (0.36 mol) hydrochloric acid is added to the residue and the mixture is refluxed for 3 hours and separated under reduced pressure so that 11.3 g of solids containing 47.9% by weight are obtained. of the desired N-phosphonomethylglycine as determined by 1c. The structure was confirmed by C13 and proton nmr. The total yield of N-phosphonomethylglycine was 64%.

Example 5

Preparation of 0.0-dimethyl N-cyanoethyl-N-carboethoxyaminomethylphosphonate

[image]

Ethyl chloroformate (8 ml., 0.083 mol) was dissolved in 8 ml of methylene chloride and 3.4 g of 1,3,5-tricyanomethylhexahydro-1,3,5-triazine (0.0167 mol) were combined in a 50 ml round bottom flask equipped with with mixer and reflux condenser. The mixture is refluxed for 1 hour and evaporated under reduced pressure. The residue is dissolved in 5 ml of methylene chloride. Trimethylphosphite (5 ml, 0.042 mol) dissolved in 15 ml of methylene chloride was added. The reaction mixture is stirred for 1 hour. 50 ml of water is added to the cooled mixture. The mixture is extracted three times with 50 ml of methylene chloride. The organic parts are combined and dried with magnesium sulfate and evaporated under vacuum so that 6.9 g of the desired product is obtained, which is a 50 percent yield. The structure was confirmed by ir, nmr and ms.

Example 6

Preparation of N-phosphonomethylglycine

The phosphonate reaction product from Example 5 (4.9 g, 0.02 mol) is combined with 20 ml (0.24 mol) of concentrated hydrochloric acid, refluxed for 3 hours and evaporated under reduced pressure. After dissolving the residues in 30 ml of water, the pH is adjusted to 10 with 50% sodium hydroxide and the mixture is evaporated under reduced pressure. The product is re-dissolved in about 5 ml of water. The structure was confirmed by nmr and liquid chromatography (1c).

Example 7

Preparation of 0,0-dimethyl-N-cyanomethyl-N-acetylaminomethylphosphonate

[image]

5.6 g (0.05 m) of potassium t-butoxide is suspended in a round-bottom flask with 25 ml of tetrahydrofuran (dried over molecular sieves) and the suspension is cooled in a water bath. Next, 6.44 ml (0.05 m) of diethylphosphite is added dropwise to the suspension over 5 minutes, under nitrogen. The mixture is cooled in an ice bath and 7.33 g (0.05 m) is added dropwise over 15 minutes.

N-cyanometh of N-chloromethylacetamide diluted with 50 ml of tetrahydrofuran. The mixture is allowed to warm to room temperature and stirred for 3 hours. The mixture is filtered over dicalite and the tetrahydrofuran is evaporated under reduced pressure to give 9.0 g of the desired product. The structure was confirmed by ir, nmr, ms, C-13 nmr.

Example 8

Obtaining phosphonomethylglycine

[image]

5.4 g (0.022 m) of the compound made in Example 7 was combined with 30 ml (0.363 m) of concentrated HCl, refluxed for 3 hours and then evaporated under reduced pressure to give the desired product as a semi-brown solid. The structure was confirmed using ir. C-13 nmr and 1c technique.

Example 9

Obtaining 0,0-dimethyl-N-cyanomethyl-N-aoethylaminomethylphosphonate

[image]

1.44 g (0.06 m) of sodium hydride is suspended with 25 ml of tetrahydrofuran (dried over molecular sieves) under dry nitrogen. 6.4 ml (0.05 ml) of dimethyl phosphate is added dropwise over 15 minutes. When all hydrogen gas has evolved, the mixture is cooled in an ice bath and 7.33 g (0.05 m) of N-cyanomethyl-N-chloromethylacetamide, diluted with 50 ml of dry tetrahydrofuran, is added dropwise over 15 minutes. The mixture is stirred overnight, filtered and evaporated under reduced pressure to give 11.5 g of the desired product as a yellow oil.

The structure was confirmed by ir, nmr, ms, C-13 nmr and gplc techniques.

The compound from Example 9 can be hydrolyzed to phosphonomethylglycine according to the teachings of Example 3.

Claims (15)

1. A process for obtaining N-phosphonomethylglycine, indicated by the fact that it comprises a) reaction of 1,3,5-triacinomethylhexahydro-1,3,5-triazine with acyl chloride of the formula [image] in which X is chlorine, bromine or iodine and R is an aliphatic or aromatic group to form an N-cyanomethyl-N-chloromethylamide acyl chloride having the structural formula [image] wherein X and R are as defined above; b) reaction of the amide formed in phase (a) with the phosphite of the formula [image] in which R1 and R2 are both aromatic groups or both aliphatic groups, and R3 is an aliphatic group or R3 is an alkali metal, so that a phosphonate compound of the formula is formed: [image] in which R1 and R2 are as defined and c) hydrolysis of the phosphonate formed in phase (b) so that N-phosphonomethylglycine is obtained. 2. Process according to claim 1, characterized in that R is C1-C4 alkyl and X is chlorine. 3. The method according to claim 1, characterized in that R is C1-C4 alkyl, R1 is C1-C6 alkyl, R2 is C1-C6 alkyl, R3 is C1-C6 alkyl sodium or potassium and X is chlorine. 4. The process according to claim 1, characterized in that R is C1-C2 alkyl, R1 is C1-C4 alkyl, R3 is C1-C4 alkyl, sodium or potassium and X is chlorine. 5. The process according to claim 1, characterized in that R is C1-C2 alkyl, R1 is C1-C2 alkyl, R3 is C1-C2 alkyl and X is chlorine. 6. Process according to claim 1, characterized in that R, R1, R2, R3 are methyl and X is chlorine. 7. The method according to claim 1, characterized in that phase (a) is performed at a temperature between about 0° to about 150°C. 8. Process according to claim 7, characterized in that phase (c) is carried out with an acid catalyst. 9. The method according to claim 8, characterized in that the acid catalyst is hydrochloric or hydrobromic acid. 10. Compound formula: [image] wherein C1-C4 alkyl or ethoxy and X is chlorobromo or iodo. 11. A compound according to claim 10, characterized in that R is methyl and X is chlorine. 12. A compound according to claim 10, characterized in that R is ethoxy and X is chlorine. 13. Compound formula; [image] wherein C1-C4 alkyl and R1 and R2 are both C1-C6 alkyl 14. Compound according to claim 13, characterized in that R is methyl, R1 is methyl and R2 is methyl. 15. A compound according to claim 13, characterized in that R is ethoxy, R1 is methyl and R2 is methyl.