CS235338B2 - Method of n-phosphonomethylglycine preparation - Google Patents

Abstract

Process for preparing N-phosphonomethylglycine, in which the substituted one is reacted triazine with acyl chloride, N-alkoxycarbonylmethyl-N-chloramide formed to react with phosphite a, the phosphonet compound formed is hydrolyzed to N-phosphonomethylglycine.

Description

The present invention relates to a novel process for the preparation of N-phosphonomethylglycine.

N-phosphonomethylglycine and certain salts thereof are particularly effective post-emergence herbicides. The commercial herbicidal composition is marketed in the form of a composition comprising the isopropylemmonium salt of N-phosphonoraethylglyein.

N-phosphonomethylglycine can be prepared by a number of methods. One such method is described in U.S. Pat. No. 3,160,632: reacting N-phosphinomethylglycine (glycine methylenephosphonic acid) with mercuric chloride in water at reflux temperature, and then separating the reaction products. Another method is the phosphonomethylation of glycine and the reaction of ethyl glycine with formaldehyde and diethylphosphite. Another method is described in U.S. Pat. No. 3,799,758. In addition, there are a number of patents relating to a process for the preparation of N-phosphonomethylglycine, for example, U.S. Pat.

197,254 and 4,199,354.

U.S. Patent No. 3,923,877 describes the reaction of 1, 3,5-tri.kyanomethylhexahydro-1, 3,5-triazine with excess disubstituted phosphite ε to form the compound of formula (RO) ₂ P (O) NHCH ₂ CH ₂ CN where R R is an optionally substituted hydrocarbon group, whereupon said compound is hydrolyzed to form N-phosphonomethylglycine.

Due to the commercial importance of N-phosphonomethylglycine and certain salts thereof as herbicidally active compounds, improved processes for its preparation have continued to be addressed.

The invention therefore relates to a process for the preparation of N-phosphonomethylglycine comprising:

1. reacting 1,3,5-trialkoxycarbonylmethylhexahydro-1,3,5-triazine with acyl chloride;

2. reacting the resulting compound with phosphite

3. The resulting N-alkoxycarbonylmethyl-N-acylaminomethylphosphonate is hydrolyzed to form N- (phosphonethyl) glycine.

The following reaction schemes illustrate the process of the invention:

and)

N

δ *

wherein R is C 1 -C 4 alkyl and R is C 1 -C 6 alkyl, and wherein R and R ¹ are preferably methyl or ethyl.

(b)

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2 3 R and R are as defined above and wherein R and R each is alkyl of 1 to 6 carbon atoms, especially alkyl having 1 to 4 carbon atoms and R ⁴ represents an alkyl group having 1 to 6 carbon atoms and particularly alkylofou a C s-C group or a sodium or potassium ion.

C)

R «-CH ₂ 2 or

AB ³ h ₂ o

CH ₂ Pf q ^X OR 2 /

HN \

ch ₂ coh

CH, P.OH

I OH

Wherein R, R, R and R are as defined above and wherein H is a strong acid, for example hydrochloric, hydrobromic, nitric, sulfuric, phosphoric or chloroacetic acid, but preferably hydrochloric acid.

The reaction is preferably carried out in aqueous, aqueous-alcoholic or alcoholic solution. Hydrolysis may also be carried out in an alkaline medium, such as in the presence of a strong acid is preferred.

In the above reaction scheme, the groups R and R * are not directly included in reaction step a,) between 1,3,5-trialkoxycarbonymethylhexahydro-1,3,5-triazine and acyl chloride.

2

The groups R, R, R are not directly included in reaction step b) of the reaction product of the N-alkoxy-12-carbonylmethyl-N-chloromethylamide of step a) and phosphite. The groups R, R, R and R are removed in reaction step c) when the phosphonate reaction product of step b) is subjected

Hydrolysis. Therefore, the nature of the groups R, R, R and R is not critical, however groups which interfere with reactions according to equations a) and b) should be avoided.

C 1 -C 4 alkyl includes methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl. The C 1 -C 6 alkyl group includes the same groups as the C 1 -C 4 alkyl group, in addition to the 6 pentyl groups and the 16 hexyl groups.

Reaction step a) is preferably carried out at a temperature of 0 to about 150 ° C, preferably at a temperature of about 40 to about 110 ° C, and in particular at a temperature of about 75 to about 85 ° C. This reaction step may be carried out at atmospheric pressure or at or below atmospheric pressure, but is preferably carried out at atmospheric pressure. Preferably, the reaction is carried out in a solvent of aeyl chloride such as ethylene chloride, methylene chloride, tetrahydrofuran or toluene.

After reaction with one mole of 1,3,5-trialkoxycarbonylmethylhexahydro-1,3,5-triazine, three moles of aeyl chloride are required. An excess of aeyl chloride may be used to ensure complete reaction of the triazine. A large excess of aeyl chloride can be used as solvent for the reaction. The solvent or excess of aeyl chloride can be removed to isolate N-alkoxycarbonylmethyl-N-chloromethylamide in high yields. However, the amide is rapidly degraded by hydrolysis and is therefore to be kept in an inert atmosphere for isolation. Most preferably no excess of aeyl chloride is used.

In reaction step b), approximately the same molar amount of N-alkoxycarbonylmethyl-N-halomethylamide and phosphite are reacted most preferably. Less preferred is the use of a two molar excess, and most preferably up to 10 molar excess and most preferably up to 10 molar excess phosphite are used.

The reaction is exothermic and can be carried out at a temperature of about 0 to about 10 ° C, preferably at a temperature of about 40 to about 100 ° C, and especially at a temperature of about 75 to about 85 ° C.

35 3 38

No solvent is required for the reaction, but an inert solvent may be used, preferably a solvent having a boiling point of about 40 to about 100 ° C may be used. Examples of such suitable solvents are ethylene chloride, methylene chloride, tetrahydrofuran and toluene. The use of a solvent helps to dissipate the heat of reaction. Any solvent used in the reaction is removed after completion of reaction step c), so it is preferable to remove the solvent by evaporation,

The alkali metal phosphites have the general formula

OR2

R ³ O - r - OR 4 χ 2 4 wherein R and R are as defined above and R is an alkali metal; these phosphites are reacted with N-cyanomethyl-N-chloromethylamide in an inert atmosphere such as nitrogen. The alkali metal phosphite can be prepared by reacting an alkali metal alkoxide, an alkali metal hydride or an alkali metal alone with the same molar amount of the disubstituted phosphite of the general formula

OR2

Wherein R and R are as defined above. This reaction is carried out under an inert atmosphere, for example under nitrogen.

Alkali metal phosphites of general formula

OR2

Rb-P-OM

2 wherein R and R and M are as defined above may also have a structural formula

O θ / '

OR ¹

Where R and R are as defined above and

OR ² is an alkali metal ion.

In reaction step c), one mole of the phosphonate reaction product from reaction step b) is hydrolyzed with 5 moles of water. The hydrolysis is carried out in the presence of a strong acid or a strong base as mentioned above. Preferably, the hydrolysis is catalyzed by an acid, preferably an inorganic acid, and most preferably hydrochloric or hydrobromic acid. Hydrolysis yields the desired N-phosphomethylglycine. Preferably, at least two moles of acid are used. Most preferably, however, an excess of two molar excess of acid is used. The preferred hydrochloric or hydrobromic acid can be used in concentrated or aqueous form.

This reaction is carried out at a temperature of about 0 to about 200 ° C, preferably at a temperature of about 50 to about 125 ° C, and especially at a temperature of about 100 to about 125 ° C.

It can be operated at atmospheric pressure or at a pressure higher or lower than atmospheric pressure; preferably the hydrolysis is carried out at atmospheric pressure.

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Solid N-phosphonomethylglycine can be isolated by conventional methods in reaction step c). Volatile liquid products such as alcohols (methanol), chlorides (methylene chloride), acids (acetic acid), water with excess acid can be removed by conventional stripping methods. The desired N-phosphonomethylglycine is obtained in high purity by trituration in isopropyl alcohol and removal of the alcohol by filtration.

The process according to the invention is illustrated in more detail by the following examples.

He did

Preparation of N-ethoxycarbonylmethyl-N-chloromethylacetamide

About «

CHUCOCHoCH-t II of ^{2 23}

CHo-C-N

CH 3 Cl 2

Dissolve 1,3,5-triethoxycarbonylmethylhexahydro-1,3,5-triazine (5.76 g, 0.0167 mol) in 150 mL of 1,2-dichloroethane in a round bottom flask. Acetyl chloride (5.4 mL, 0.074 mol) was added dropwise. The reaction mixture was refluxed for 5 minutes, then stripped under reduced pressure to give N-ethoxycarbonylmethyl-N-chloromethylacetamide. Structure confirmed by proton nuclear magnetic resonance.

Example 2

Preparation of N, Ο-dimethyl-N-ethoxycarbonylmethyl-N-acetylaminomethylphosphonate

O o ch ₂ co ₃ ch ₃ ch ₃ -cn ch ₂ p- (och ₃ ) ₂ o

The amide of the compound prepared as described in Example 1 was diluted with 10-12 ml of toluene. Trimethyl phosphite (6.7 g, 0.0515 mol) was added and the mixture was refluxed for 15 minutes, then stripped under reduced pressure to give the desired product. The structure of the product was confirmed by proton nuclear magnetic resonance.

Example 3 ·

Preparation of N-phosphonomethylglycine

O

I _from CH ₂ -C-OH

HN ^x CH ₂ P- (oh ( ₂

O

The phosphonet reaction product, prepared as described in Example 2, was treated with 30 mL (0.36 mol) of concentrated hydrochloric acid, refluxed for three hours, and stripped under reduced pressure. The reaction product is triturated in 50 ml of isopropyl alcohol and filtered to give 5.6 g of the desired product. The structure of the product was confirmed by proton nuclear magnetic resonance, ¹ nuclear magnetic resonance and infrared spectroscopy and liquid chromatography.

Example

Preparation of O, O-diethyl-N-ethoxycarbonylmethyl-N-acetylaminomethylphosphonate

O

_Z O CH ₂ CH ₂ occhi CH ₃ CN-CH ₂ p- (OC ₂ H _{5) 2}

O

3.9 g (0.035 mol) of potassium tert-butoxide are suspended in a round-bottomed flask in 25 ml of tetrahydrofuran (dried by molecular sieve) and the suspension is cooled to a water lesion. 4.5 ml (0.035 mol) of < 31 ethylphosphite was added dropwise in a nitrogen atmosphere over 5 minutes. The mixture was cooled in an ice bath and 6.77 g (0.035 mol) of N-ethoxycarbonylmethyl-N-chloromethyl acetamide diluted with 25 ml of tetrahydrofuran was added dropwise over 15 minutes. The mixture was allowed to warm to ambient temperature, stirred for three hours and then filtered through dicalite and stripped. This gave 9.6 g of an amber oil. Structure confirmed by infrared analysis, nuclear magnetic resonance and ¹ X nuclear magnetic resonance.

Example 5

Preparation of N-phosphonomethylglycine _from CH ₂ -E-OH

HN ^x ch ₂ p - (oh) ₂

O

6.6 g (0.022 mol) of the compound obtained as described in Example 4 are mixed with 30 ml (0.363 mol) of concentrated hydrochloric acid and refluxed for three hours and then stripped to give 4.7 g. of the desired product as a brown semisolid. Structure confirmed by nuclear magnetic resonance, X nuclear magnetic resonance.

Claims (4)

OBJECT OF THE INVENTION What is claimed is: 1. A process for the preparation of N-phosphonomethylglycine comprising reacting 1,3,5-trialkoxycarbonylmethylhexahydro-1,3,5-triazine of formula (I) at 0 to 150 ° C; · ^? rocch ₂ - n ^ n - ch ₂ cor ch ₂ cor o wherein R is C 1 -C 4 alkyl, with an acyl chloride of formula O R1-C-Cl in the presence of a solvent for acyl chloride, wherein r 'is an alkyl group having 1 to 6 carbon atoms, the resulting N-alkoxycarbonylmethyl-N-chloromethylamide of formula O η 11 _z ch ₂ cor r'-cn ^ ^x CH ₂ Cl 35338 2 wherein R and R ¹ have the above meanings, is reacted at 0 to 150 ° C in the presence of a solvent with a phosphite of the formula OR ³ R ² O-R-OR 4 Where R @ 1 and R @ 2 are each C1 -C6 alkyl and R @ 1 is C1 -C6 alkyl or sodium or potassium and the phosphonate of the formula O 9 / _R CHnéoR 1_C N? ^CH 2 _{OR 2} £ ^p x OR ³ wherein R, R, R and R have the abovementioned meanings, are hydrolysed in the presence of hydrochloric acid at 0 to 200 ° C. 2. A process according to claim 1, wherein the starting compounds are reacted. 1 2 wherein R and R represents an alkyl group having 1-2 carbon atoms, R represents an alkyl group having 1 to 4 carbon atoms, R₁ represents an alkyl group having 1 to 4 carbon atoms and R @ ⁴ lower alkylene alkyl group having from 1 to 4 carbon atoms or sodium or potassium atoms. 3. The method according to claim 1, characterized by reacting the starting material wherein R, R ¹ ', R ^2, R @ b R @ ⁴ are each alkyl having 1-2 carbon atoms. 4. A process according to claim 1, wherein the starting compounds are reacted, Wherein R is ethyl, R, R and R are each methyl.