JPH0258276B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing N-phosphonomethylglycine.

N-phosphonomethylglycine and certain salts thereof are effective as post-emergent herbicides. Herbicides are sold commercially in formulations containing the isopropylamine salt of N-phosphonomethylglycine.

N-phosphonomethylglycine is produced by various methods. One method is US Patent No. 3160632.
N-phosphinomethylglycine (glycine methylene phosphonic acid)
is reacted with mercuric chloride in water at reflux temperature and the reaction product is then separated. Other methods are the phosphonomethylation of glycine and the reaction of ethyl glycinate with formaldehyde and diethyl phosphite. The latter method is described in U.S. Patent No.
Described in No. 3799758. Additionally, there are a series of patents relating to the preparation of N-phosphonomethylglycine, such as US Pat. No. 3,868,407, US Pat. No. 4,197,254 and US Pat.

As a prior document close to the present invention, US Patent No.
No. 3923877, in which 1,3,5-tricyanomethylhexahydro _- 1,3,5-triazine is reacted with excess disubstituted phosphite to form (RO) _2P (O) _CH2NHCH2CN ( R is hydrocarbyl or substituted hydrocarbyl), which is hydrolyzed to give N-phosphonomethylglycine.

Because of the commercial importance of N-phosphonomethylglycine and its salts as herbicides, improved methods for producing these compounds would also be of value.

The present invention relates to a method for preparing N-phosphonomethylglycine, which comprises the following steps.

(1) 1,3,5-tricyanomethylhexahydro 1,3,5-triazine is reacted with an acyl halide, preferably an acycluride to form the acyl halide N-cyanomethyl-N-halomethylamide; (2 ) This amide is reacted with a phosphite to give N-
Forming acylaminomethyl-N-cyanomethylphosphonate; (3) Hydrolyzing this phosphonate to yield N-(phosphonomethyl)-glycine.

The method of the present invention is shown by the following reaction formula; wherein R is an aliphatic or aromatic group as defined below, preferably _C1 - _C4 alkyl, most preferably methyl or ethyl and X is chlorine, bromine or iodine, preferably chlorine. .

where R and X are as defined above,
R ¹ and R ² are both aromatic groups or both aliphatic groups,
Preferably R ¹ and R ² are C _1-6 alkyl, more preferably C _1-4 alkyl and R ³ is an aliphatic group,
Preferably ^R3 is _C1-6 alkyl, more preferably
C _1-4 alkyl or R ³ is an alkali metal (M), preferably sodium or potassium.

where R, R ¹ and R ² are as defined above, H ⁺ is a strong acid such as hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid and chloroacetic acid, preferably Hydrochloric acid or hydrobromic acid, OH ^- is a strong base such as sodium hydroxide or sodium hydroxide, preferably its aqueous, hydroalcoholic or alcoholic solution. Preferably, hydrolysis is carried out in the presence of strong acids.

In the above formula, the group R is in reaction (a), i.e.
1,3,5-tricyanomethylhexahydro-
It is not directly involved in the reaction between 1,3,5-triazine and acyl chloride. The groups R, R ¹ , R ² are
It is not directly involved in reaction (b), that is, the reaction between the product N-cyanomethyl-N-chloromethylamide of reaction (a) and phosphite. The groups R, R ¹ , R ² are
Reaction (c), i.e., the phosphonate which is the product of reaction (b), is eliminated when it is hydrolyzed. Therefore,
The properties of the groups R, R ¹ and R ² are not particularly required as long as they do not inhibit the progress of reactions (a) and (b).

Groups _C1-4 alkyl include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, and the like.
In addition to the above, the C _1-6 alkyl group also includes 6 types of pentyl and 16 types of hexyl.

The term aliphatic group is used in a broad sense and includes (1) open ring structures of paraffins, olefins, acetylenic hydrocarbons, and (2) aliphatic cyclic compounds.
Aliphatic groups have 1 to 10 carbon atoms.

Aromatic groups are used to distinguish them from aliphatic groups, and include (1) hydrocarbons (including bicyclic or polycyclic rings) having 6 to 20 carbon atoms and at least one benzene ring, and derivatives thereof; , and (2) heterocyclic cyclic compounds having 5 to 12 carbon atoms, having a similar structure and having an unsaturated ring structure containing at least one atom other than carbon, such as nitrogen, sulfur, or oxygen; These are derivatives.

Reaction (a) is preferably carried out at a temperature of 0-150°C, more preferably 40-110°C and most preferably 75-85°C. This reaction can be carried out under atmospheric pressure, slightly increased pressure or high pressure, but is preferably carried out under atmospheric pressure. Also, the reaction is
Preferably it is carried out in a solvent for the acyl halide such as ethylene chloride, methylene chloride, tetrahydrofuran and the like.

Three moles of acyl halide are required to react with one mole of 1,3,5-trisylanomethylhexahydro-1,3,5-triazine. Excess acyl halide is used to ensure complete reaction with triazine. The large excess of acyl halide serves as a solvent in this reaction. By removing the solvent and excess acyl halide, the acyl halide N-cyanomethyl-N-
Chloromethylamide is obtained in high yield. However, this amide decomposes rapidly either thermally or by hydrolysis and, if isolated, must be stored in an inert atmosphere.

Most preferably, the solvent used in reaction (a) is also used in reaction (b) without using excess acyl halide. In this way, there is no need to remove the solvent at the end of reaction (a), and it can be used as is in reaction (b).

In reaction (b), it is most preferable to use equimolar amounts of the acyl halide N-cyanomethyl-N-halomethylamide and the phosphite. A less preferred method is therefore to use an excess of up to 2 molar, and even less preferred, an excess of up to 10 molar.

This reaction is exothermic and ranges from about 0-150°C, preferably 40-100°C, most preferably 75-150°C.
Performed at 85°C.

Although no solvent is required for the reaction, inert solvents, preferably those having a boiling point in the range from 40 to 100°C, may be used. Examples of these solvents include ethylene chloride, methylene chloride, tetrahydrofuran, and the like. If you use an inert solvent,
The heat of reaction can be dissipated. Most preferred is to use the same solvent used in reaction (a).

The solvent used in this reaction is removed after reaction (c). Therefore, a solvent that can be removed by evaporation is preferred.

Alkali metal phosphite with the formula (wherein R ¹ and R ² are as previously defined and R ³ is an alkali metal) is reacted with N-cyanomethyl-N-halomethylamide under an inert atmosphere such as nitrogen. Alkali metal phosphites are disubstituted phosphites having the formula (where R ¹ and R ² are as defined above).

This reaction is carried out in an inert atmosphere such as nitrogen.

Alkali metal phosphite with the formula (where R ¹ , R ² , M are as defined above) also has the following structure due to tautomerism.

(wherein R ¹ and R ² are as previously defined and M is an alkali metal) In reaction (c), 1 mole of the phosphonate reaction product in reaction (b) is hydrolyzed with 5 moles of water. Hydrolysis is carried out in the presence of strong acids or strong hydrochloric acid as described above. Preferably, the hydrolysis is carried out in the presence of an acid catalyst, preferably an inorganic acid, most preferably hydrochloric acid or chlorobromic acid. This hydrolysis yields the desired N-phosphonomethylglycine. Preferably, at least 2 moles of acid are used. More preferably, a large excess of 2 molar or more is used. Preferred hydrochloric acid or chlorobromic acid is used in the form of a concentrated liquid or an aqueous solution.

This final reaction is carried out at a temperature in the range of about 0-200°C, preferably about 50-125°C, most preferably about 100-125°C.

It can also be carried out under atmospheric pressure, slightly increased pressure or high pressure. Preferably, hydrolysis is carried out under atmospheric pressure.

Solid N-phosphonomethylglycine reacts (c)
can be obtained in the usual way. Alcohol (methanol), chloride (methyl chloride), acid (acetic acid),
Volatile liquid products such as water and excess acid are removed by conventional stripping techniques. The desired N-phosphonomethylglycine can be obtained in high purity by decomposing it into water, adjusting the pH to 1 to 2, precipitating crystals, and filtering.

Examples of the present invention are shown below.

Example 1 Production of N-cyanomethyl-N-chloromethylacetamide 17 g (0.0835 mol) of 1,3,5-tricyanomethylhexahydro-1,3,5-triazine
Mix with 150 ml of 1,2-dichloroethane in a round bottom flask to form a slurry. 40ml (0.563mol)
of acetyl chloride at once and reflux for 3 hours. Stripped under vacuum, 26.9g (79.85
%) of N-cyanomethyl-N-chloromethylacetamide is obtained. The structure was determined using conventional analytical methods (infrared,
Confirmed by NMR, mass spectrometry).

Example 2 Preparation of O-O-dimethyl-N-cyanomethyl-N-acetylaminomethylphosphite 26.9g (0.2g) of the amide compound produced in Example 1
mol) was diluted in 75 ml of dichloromethane.
Add 25.5 g (0.206 mol) of trimethyl phosphite and stir overnight at room temperature. Reflux for 0.5 hours,
Stripping under reduced pressure yields 34.9 g (79.32%) of the desired product. The structure was confirmed by infrared, MNR, and mass spectrometry.

Example 3 Production of N-phosphonomethylglycine 19.5 g of phosphonate reaction product of Example 2
(0.09 mol) is mixed with 100 ml (1.21 mol) of concentrated hydrochloric acid, refluxed for 3 hours and then stripped under reduced pressure. Dissolve the residue in 30 ml of water and adjust the PH to 10 with 50% sodium hydroxide. Strip under vacuum. The product was further dissolved in 30 ml of water,
Adjust the pH to 1 with concentrated hydrochloric acid. Cool overnight;
Next morning, 5.4 g of desired product (98.3% purity by weight)
I got it. (Yield 35.49%). The structure is infrared, NMR,
Confirmed by liquid chromatography.

Example 4 Production of N-phosphonomethylglycine 50 ml of 1,2-dichloroethane was placed in a round bottom flask and heated to reflux. 5.5 ml (0.077 mol) acetyl chloride and 3.4 g (0.0167 mol) 1,3,5-tricyanomethylhexahydro-
Add the 1,3,5-triazine simultaneously over 10 minutes, keeping the acetyl halide in excess in the vessel. The mixture is refluxed for 0.5 h and stripped under reduced pressure.

To the residue, add 5 ml of toluene and 6.6 ml (0.05 mol)
of trimethylphosphite and reflux for 15 minutes. Stir at room temperature for 2 hours and strip under reduced pressure.

Add 30 ml (0.36 mol) of concentrated hydrochloric acid to the residue, reflux for 3 hours, and strip under reduced pressure. 11.3 g of a solid containing 47.9% by weight of the desired N-phosphonomethylglycine are obtained (confirmed by liquid chromatography).
The structure was confirmed by ^C13 and proton NMR. N
-The overall yield of phosphonomethylglycine was 64%.

Example 5 Preparation of O,O-dimethyl-N-cyanoethyl-N-carboethoxyaminoethyl phosphite Add 8 ml of methylene chloride to 8 ml of methylene chloride in a 50 ml round bottom flask equipped with a stirrer and reflux condenser.
(0.083 mol) of ethyl chloroformate and 3.4 g (0.0167 mol) of 1,3,5-
Charge tricyanomethylhexahydro-1,3,5-triazine. The mixture is refluxed for 1 hour and stripped under reduced pressure. Dissolve the residue in 5 ml of methylene chloride. Add 5 ml (0.042 mol) of trimethyl phosphite dissolved in 15 ml of methylene chloride. This is refluxed for 1 hour, and after cooling, 50 ml of water is added. Extract the mixture three times with 50 ml of methylene chloride. The combined organic portions are dried over magnesium sulfate and stripped under reduced pressure to yield 6.9 g of the desired product. Yield is 50
%. The structure was confirmed by infrared, NMR, and mass spectrometry.

Example 6 Preparation of N-phosphonomethylglycine 4.9 g of the phosphonate reaction product of Example 5
(0.02 mol) is combined with 20 ml (0.24 mol) of concentrated hydrochloric acid and refluxed for 3 hours. Then strip under reduced pressure. After dissolving the residue in 30ml of water,
Adjust the PH to 10 with 50% NaOH and strip the mixture under vacuum. The product is redissolved in 5 ml of water. The structure was confirmed by NMR and liquid chromatography.

Example 7 Preparation of O,O-diethyl-N-cyanomethyl-N-acetylaminomethylphosphonate 5.6 g of potassium t-butoxide are mixed into a slurry in a round bottom flask with 25 ml of tetrahydrofuran (dried over molecular sieves) and the slurry is cooled in water. Then 6.44ml (0.05
mol) of diethyl phosphite was added dropwise to the slurry over 5 minutes under a stream of nitrogen, the mixture was cooled with an ice bath, and 7.33 g (0.05 mol) of N-cyanomethyl-N-chloromethylacetamide was added to 50 ml of tetrahydrofuran. Add dropwise to the dilution over 15 minutes. Warm this mixture to room temperature,
Stir for 3 hours. The mixture was filtered and tetrahydrofuran was stripped under reduced pressure to give the desired product.
Obtain 9.0g. The structure was confirmed by infrared, NMR, and mass spectrometry.

Example 8 Production of phosphonomethylglycine 5.4 g (0.022 mol) of the compound prepared in Example 7 were combined with 30 ml (0.363 mol) of concentrated HCl;
Reflux for 3 hours and then strip under reduced pressure.
10.8 g of brown semi-solid desired product were obtained. The structure was confirmed by infrared, NMR, C ¹³ NMR and liquid chromatography.

Example 9 Preparation of O,O-dimethyl-N-cyanomethyl-N-acetylaminomethylphosphonate 25 ml of 1.44 g (0.06 mol) sodium hydride
Slurry in tetrahydrofuran (dried over molecular sieves) under a stream of nitrogen. 6.4ml
(0.05 mol) of dimethyl phosphite is added dropwise over 15 minutes. When all the hydrogen gas was released, the mixture was cooled with ice, and 7.33 g (0.05 mol) of N-cyanomethyl-N-chloromethylacetamide was added to the
15 ml diluted with dry tetrahydrofuran
Add dropwise over minutes. The mixture is stirred overnight, filtered and stripped under reduced pressure to give 11.5 g of the desired product as a yellow oil. The structure was determined by infrared analysis, NMR,
Confirmed by C ¹³ NMR and GLPC.

The compound of Example 9 can be hydrolyzed by the method of Example 3 to obtain phosphonomethylglycine.

Claims (1)

[Claims] 1. A method for producing N-phosphonomethylglycine comprising the following reaction: (a) 1,3,5-tricyanomethylhexahydro-1,3,5-triazine and an acyl having the following formula: halide Here, X is chlorine, bromine, or iodine, R is an aliphatic or aromatic group, and is reacted to form N-cyanomethyl-N-halomethylamide of acyl halide having the following formula: where X and R are as defined above. (b) converting the amide produced in reaction (a) to a phosphite having the formula Here, R ¹ and R ² are both aromatic groups or both aliphatic groups, and R ³ is an aliphatic group or an alkali metal. Here, R ¹ and R ² are as defined above to obtain. (c) Hydrolyzing the phosphonate produced in reaction (b) to obtain N-phosphonomethylglycine. 2. The method of claim 1, wherein R is _C1-4 alkyl and X is chlorine. 3 R is C _1-4 alkyl, R ¹ is C _1-6 alkyl, R ²
2. The method of claim 1, wherein R3 is _C1-6 alkyl, ^R3 is _C1-6 alkyl, sodium or potassium, and X is chlorine. 4 R is C _1-12 alkyl, R ¹ is C _1-4 alkyl, R ²
The method of claim 1, wherein R3 is _C1-4 alkyl, ^R3 is _C1-4 alkyl, sodium or potassium and X is chlorine. 5 R is C _1-12 alkyl, R ¹ is C _1-2 alkyl, R ²
2. The method of claim 1, wherein R3 is _C1-2 alkyl, ^R3 is _C1-2 alkyl and X is chlorine. 6. The method of claim 1, wherein R, R ¹ , R ² and R ³ are methyl and X is chlorine. 7. The method of claim 1, wherein reaction (a) is carried out at a temperature between about 0 and 150°C. 8. The method of claim 7, wherein reaction (c) is carried out with an acid catalyst. 9. The method of claim 8, wherein the acid catalyst is hydrochloric acid or hydrobromic acid.