JPH0311087A - 2-acylamino-4-(hydroxyalkylphosphinyl)butyric acid salt and production thereof - Google Patents

Abstract

NEW MATERIAL:The compound of formula I [R<1> is lower (halo)alkyl; R<2> is lower (halo)alkyl or (substituted) phenyl; M is ammonium ion, alkali metal ion or alkaline-earth metal ion]. EXAMPLE:2-Acetylamino-4-(hydroxymethyiphosphinyl)butyric acid 2-sodium salt. USE:A herbicide. PREPARATION:The objective compound can be produced by reacting a 2- acylamino-4-(alkoxyalkylphosphinyl)butyric acid derivative of formula II [R<3> is H, lower (halo)alkyl or (substituted) phenyl; R<4> is H or lower (halo)alkyl] with a base (e.g. sodium hydroxide).

Description

DETAILED DESCRIPTION OF THE INVENTION (a) Industrial application field The present invention relates to N-acylated forms of 2-amino-4-(hydroxymethylphosphinyl)butyric acid, etc., which are known as active ingredients of herbicides. The present invention relates to 2-acylamino-4-(hydroxyalkylphosphinyl)butyrate and a method for producing the same.

Among 2-acylamino-4-(hydroxyalkylphosphinyl)butyric acids, 2-acetylamino-4-(hydroquinemethylphosphinyl)butyric acid was disclosed in Japanese Patent Publication No. 61-253.
Publication No. 58, Special Publication No. 62-47520, Special Publication No. 6
As described in Japanese Patent Publication No. 3-8760 and Japanese Patent Application Laid-Open No. 62-253389, optically active L- It can be optically resolved to 2-amino-4-(hydroxymethylphosphinyl)butyric acid.

This optically active L-2-amino-4-(hydroxymethylphosphinyl)butyric acid is a herbicide with 2-amino-4-(hydroxymethylphosphinyl)butyric acid.
It is known to be the active form of 4-(hydroxymethylphosphinyl)butyric acid.

(b) Problems to be Solved by the Prior Art and the Invention In general, acylation of amino acids is carried out by reacting raw amino acids with an acylating agent such as acetic anhydride.

However, in order to obtain 2-acylamino-4-(hydroxyalkylphosphinyl)butyric acid, 2-amino-4-(
When acylating the amino group of hydroxyalkylphosphinyl)butyric acid, it is necessary to use water as a solvent because the raw material 2-amino-4-(hydroxyalkylphosphinyl)butyric acid is very poorly soluble in organic solvents. Therefore, this method requires the use of a large amount of acylating agent and cannot be said to be an industrially useful method.

On the other hand, in Japanese Patent Application No. 62-129498, the present inventors reported a method for producing 2-acylamino-4-(alkoxymethylphosphinyl)butyric acid.

The alkoxy group of this 2-acylamino-4-(alkoxymethylphosphinyl)butyric acid is selectively hydrolyzed to give 2
There is no known method for obtaining -acylamino-4-(hydroxymethylphosphinyl)butyric acid.

Plutin, Chemical, Society, Of, Japan (B
ull, Chem, Soc, Jpn, ), Volume 61,
3699 true, 1988, 2-acetamido-4-
There is a description of hydrolyzing (ethoxymethylphosphinyl)butyric acid amide with hydrochloric acid, but only 2-amine 4-(hydroxymethylphosphinyl)butyric acid is obtained, and the method selectively hydrolyzes only the ethoxyphosphoryl group. is not known.

(c) Means for solving the problem The present inventors selectively hydrolyzed the alkoxy group of 2-acylamino-4-(alkoxyalkylphosphinyl)butyric acid to As a result of various studies on methods for obtaining alkylphosphinyl)butyric acid, we found that by hydrolysis under basic conditions,
The present inventors have discovered that 2-acylamino-4-(hydroxyalkylphosphinyl)butyrate can be obtained in high yield and purity and have completed the present invention.

That is, the present invention provides general formula (I) 1 R'-P-CIl□C82C)I(NHCOR'') C
00M CI )M (wherein, R1 is a lower alkyl group, a halo lower alkyl group,
R2 represents a lower alkyl group, a halo-lower alkyl group, or an optionally substituted phenyl group, and M represents an ammonium ion, an alkali metal ion, or an alkaline earth metal ion. ) 2-acylamino-4-(hydroxyalkylphosphinyl)butyrate and -form (II) ρ R'4-CHzCHzCH (NHCORJ C0OR'
CII)OR" (wherein R3 is hydrogen, a lower alkyl group, a halo-lower alkyl group, an optionally substituted phenyl group, R4 is hydrogen,
Indicates a lower alkyl group and a halo-lower alkyl group. ) 2-acylamino-4-(alkoxyalkylphosphinyl)butyric acid derivative represented by general formula (1) %formula%) characterized by reacting a 2-acylamino-4-(alkoxyalkylphosphinyl)butyric acid derivative represented by This invention relates to a method for producing (hydroxyalkylphosphinyl)butyrate.

The lower alkyl groups R1, R2, R3 and R4 include methyl, ethyl, n-propyl, i-propyl, n
-butyl, i-butyl, L-butyl, n-pentyl, i
- Includes pentyl, neopentyl, etc.

Examples of the halo-lower alkyl group as R1, R2, R3 and R4 include halogenomethyl, halogenoethyl, halogenopropyl, halogenobutyl and the like.

Examples of the halogen of the halo-lower alkyl group include fluorine, chlorine, and bromine.

The optionally substituted phenyl groups that are R2 and R3 include phenyl, methyl-substituted phenyl, trimethyl-substituted phenyl, butyl-substituted phenyl, methoxy-substituted phenyl, cyano-substituted phenyl, fluorine-substituted phenyl, difluorine-substituted phenyl, fluorine- and chlorine-substituted phenyl. Examples include phenyl, chlorine-substituted phenyl, dichlorine-substituted phenyl, methyl- and chlorine-substituted phenyl, bromine-substituted phenyl, benzoyl-substituted phenyl, methyl-substituted phenylbutyl, naphthyl and benzyl.

In the above, R1 is preferably methyl, and R2 is preferably methyl or phenyl.

Bases include alkali metal compounds, alkaline earth metal compounds and ammonia.

Examples of the alkali metal compound include hydroxide, carbonate, chloride, alkali metal alcoholade, hydride, and the like.

Examples of the alkali metal hydroxide include lithium hydroxide, sodium hydroxide, potassium hydroxide, and the like.

Examples of alkali metal carbonates include lithium carbonate, sodium carbonate, potassium carbonate, and the like.

Examples of alkali metal chlorides include lithium chloride and sodium chloride.

Examples of the alkali metal alcoholade include lithium methoxide, sodium methoxide, potassium methoxide, lithium ethoxide, sodium ethoxide, potassium ethoxide, and potassium tert-butoxide.

Examples of alkali metal hydrides include lithium hydride and sodium hydride.

Further, examples of the alkaline earth metal compound include hydroxides, carbonates, chlorides, hydrides, and the like.

Examples of alkaline earth metal hydroxides include magnesium hydroxide, calcium hydroxide, barium hydroxide, and the like.

Examples of alkaline earth metal carbonates include magnesium carbonate, calcium carbonate, barium carbonate, magnesium hydrogen carbonate, calcium hydrogen carbonate, barium hydrogen carbonate, and the like.

Examples of alkaline earth metal chlorides include magnesium chloride, calcium chloride, barium chloride, and the like.

Examples of alkaline earth metal hydrides include calcium hydride.

Examples of ammonia include ammonia gas, liquid ammonium, and aqueous ammonia.

Among the above bases, bases such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium methoxide, and sodium ethoxide are preferred.

The present invention requires the use of a solvent.

The solvent is the base used in the reaction, 2-acylamino-4-(hydroxyalkylphosphinyl)butyrate of general formula (1) or 2-acylamino-4-(alkoxyalkylphosphinyl) of formula (II). Dissolve butyric acid derivative,
Any material may be used as long as it is inert to the reaction.

Examples of the solvent include alcohols such as ethyl alcohol, methyl alcohol, isopropyl alcohol, and tertiary-butyl alcohol, tetrahydrofuran, dioxane, water, and mixed solvents thereof.

The amount of base used is 2-acylamino- of the form (I[)
4-(Alkoxyalkylphosphinyl)butyric acid derivative 1
range of 2 to 100 equivalents, preferably 2 to 5 equivalents
The equivalent range is good.

The reaction temperature ranges from O'C to 150°C, preferably 20°C.
The range is preferably from °C to 100 °C.

2-acylamino-4-(alkoxyalkylphosphinyl)butyrate of the form (N) can be recrystallized if necessary.

A mixed system of water and a water-soluble organic solvent is suitable as the solvent used for recrystallization.

Examples of water-soluble organic solvents include alcohols, ethers, carboxylic acids, and the like.

Examples of alcohol include ethanol, methanol, isopropyl alcohol, and the like.

Examples of the ether include tetrahydrofuran and dioxane.

Examples of carboxylic acids include acetic acid and propionic acid.

Among the water-soluble organic solvents, methanol and ethanol are preferred.

(d) Effects of the Invention The present invention allows 2-acylamino-4-(hydroxyalkylphosphinyl)butyrate of the form (1) to be easily obtained in high yield and purity, and is industrially extremely important. This is an advantageous method.

In addition, related metal compounds such as 2-acetamido-4-(hydroxymethylphosphinyl)butyric acid have poor crystallinity and are difficult to purify.
Acylamino-4-(hydroxyalkylphosphinyl)butyrate has good crystallinity and is easy to purify.

Furthermore, the mineral salt of 2-amino-4-(hydroxymethylphosphinyl)butyric acid can be obtained by hydrolyzing the 2-acylamino-4(hydroxymethylphosphinyl)butyrate of the form CI) with mineral acid. It can be easily obtained and derived from it to 2-amino-4-(hydroxymethylphosphinyl)butyric acid, which is an active ingredient of herbicides.

(E) Examples Hereinafter, the present invention will be explained in detail by giving Examples, but the present invention is not limited to these.

Example 1 0.25 g (1 mmol) of 2-acetylamino-4-(ethoxymethylphosphinyl)butyric acid was added to 511f! 2.5ml of 4% sodium hydroxide aqueous solution (2.5ml) dissolved in water.
, 5 mmol) and heated at 100°C for 1 hour.

After cooling to room temperature, a 5% aqueous hydrochloric acid solution was added to the reaction solution to neutralize it.

After distilling off the water, add ethanol and filter out the precipitated salt.
Ethanol was distilled off to obtain a solid.

This solid was recrystallized with a water-ethanol mixed solvent,
Obtained 0.36 g of colorless needle crystals (melting point 211-213
°C1 decomposition).

Weight loss after drying at 105°C for 3 hours is 30.62%
Met. The following analysis was performed on this product.

[Elemental analysis] C7H, JO5PNa Calculated values C=31.47χ, H, 4,53χ, N=5.
24χ, 0=29.95X.

P, 11.60χ, Na=17.21χ actual value C=
31.45Ll+=4.652. N=5.192,0
=29.27χ.

P=11.75χ, Na=17.69χ [I)l-
NMI? (020) Spectrum] δ (ppm) 1.
22 (3H, d, J = 13Hz), 1.6-2.0 (4
day, m) 2.01 (38, s), 4.78 (LH, bt
)(” C-NMR (020) spectrum] δ(ppm
) 15.54. 19.67, 24.60□ 2
B, 07. 28.32°32.45. 58.12.
58.89, 176.22, 181.15 From the above results, the obtained crystals are 2-acetylamino-4-(hydroxymethylphosphinyl)butyric acid disodium salt, and the crystals before drying are free from crystallization water. It was confirmed that it has.

Example 2 0.25 g (1 mmol) of 2-acetylamino-4-(nidoxymethylphosphinyl)butyric acid was added to 10 ml of methanol.
Dissolve 0.8 M sodium methylate in methanol N? 2.5m at night! ! , (2 mmol) was heated under reflux for 10 hours.

After cooling to room temperature, methanol was distilled off, and a 5% aqueous hydrochloric acid solution was added to the residue to neutralize it.

After distilling off the water, add ethanol and filter out the precipitated salt.
Ethanol was distilled off to obtain a solid.

This solid was recrystallized with a water-ethanol mixed solvent,
Obtained 0.36 g of colorless needle crystals (melting point 211-213
°C1 decomposition).

When dried at 105°C for 3 hours and analyzed, elemental analysis values, 'H-NMR (D20) spectrum and I3C
-NMR (020) spectrum almost matched that of 2-acetylamino-4-(hydroxymethylphosphinyl)butyric acid disodium salt of Example 1.

Example 3 0.28 g (1 mmol) of 2-acetylamino-4-(β-chloroethoxymethylphosphinyl)butyric acid was added to 5 m of water.
Dissolved in 4% sodium hydroxide aqueous solution 2.5nF!
(2.5 mmol) was added, and the reaction was carried out at 100°C for 1 hour.

After cooling to room temperature, 5% aqueous hydrochloric acid solution was added to neutralize.

After distilling off the water, add ethanol and filter out the precipitated salt.
Ethanol was distilled off to obtain a solid.

This solid was recrystallized with a water-ethanol mixed solvent,
Obtained 0.35 g of colorless needle crystals (melting point 211-213
°C1 decomposition).

Weight loss after drying at 105°C for 3 hours is 30.64%
Met. This crystal was analyzed.

[Elemental analysis] CrH+tNO5PNa calculated value C=3
1.47X, H=4.532. N=5.24X, 0
=29.95χ.

P=11.60X, Na=17.21! Actual value C
=31.46χ, I+, 4.64χ, N, 5.19X
, 0=29.28χ.

P=11.75χ, Na=17.682, 'H-
NMR (020) 7! , vector and “C-NMR (
020) The spectrum was consistent with that of 2-acetylamino-4-(hydroxymethylphosphinyl)butyric acid disodium salt of Example 1.

Example 4 In a 50 ml stainless steel autoclave equipped with an electromagnetic induction stirrer, 0.25 g (1 mmol) of 2-acetylamino-4-(ethoxymethylphosphinyl)butyric acid and 5 ml of water were placed.
After charging 15 ml of nl, l Q% aqueous ammonia and purging with nitrogen, the reaction was carried out at 80°C for 2 hours.

After cooling to room temperature, the reaction solution was concentrated under reduced pressure and recrystallized with a mixed solvent of ethanol and water to obtain 0.2°4 g of colorless needle-like crystals (melting point 172-174°C 1 decomposition). Analysis was performed after drying for an hour.

[Elemental analysis] C? H. Nff0. P calculation value C=
32.69L H=7.84χ, N=16.34%, 0
=31.10χ.

P=12.04χ Actual value C=32.58L H=7.92! , N=I6
．． 33X, 0=31.11χ.

P=12.06χ Also, 'H-NMR (020) spectrum and "C-
The NMR (020) spectrum almost matched that of 2-acetylamino-4-(hydroxymethylphosphinyl)butyric acid disodium salt of Example 1.

Claims (2)

[Claims] (1) General formula [I] ▲Mathematical formulas, chemical formulas, tables, etc.▼[I] (In the formula, R^1 is a lower alkyl group, halo-lower alkyl group, R^2 is a lower alkyl group, halo-lower alkyl group , an optionally substituted phenyl group, M represents an ammonium ion, an alkali metal ion, or an alkaline earth metal ion). (2) General formula [II] ▲Mathematical formulas, chemical formulas, tables, etc.▼[I] (In the formula, R^3 is hydrogen, a lower alkyl group, a halo-lower alkyl group, an optionally substituted phenyl group, R ^4 represents hydrogen, a lower alkyl group, or a halo-lower alkyl group.) General formula [characterized by reacting a 2-acylamino-4-(alkoxyalkylphosphinyl)butyric acid derivative represented by the following with a base] I 〕 ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ Method for producing 2-acylamino-4-(hydroxyalkylphosphinyl) butyrate represented by [ I 〕.