JPH01268695A - 2-alkoxycarbonylethylphosphinic acid and production thereof - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I (R is 1-8C alkyl). EXAMPLE:2-n-Butoxycarbonylethylphosphinic acid. USE:A precursor for producing a herbicide. PREPARATION:An acrylic acid ester (e.g., n-butyl acrylate) expressed by formula II is reacted with a hypophosphite (e.g., sodium hydrophosphite), preferably at a molar ratio of 1:1-1:10 in the presence of a radical initiator [e.g., methylethylketone peroxide or 1,1-bis(tert.butylperoxy)-3,3,5-trimethylcyclo- hexane]. Furthermore, the radical initiator is preferably used at an amount of 0.001-0.1mol based on 1mol acrylic acid ester.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a novel 2-alkoxycarbonylethylphosphinic acid and a method for producing the same.

Compounds according to the invention are useful as precursors for the manufacture of herbicides.

(Prior art) "Bialaphos", a type of herbicide, is a substance isolated from the culture solution of the actinomycete Streptomyces bigroscopicus, and it exhibits excellent herbicidal properties and is found in soil. Because it decomposes quickly, it is known as an extremely safe herbicide.

It has been found that the productivity of bialaphos is significantly improved when 3-(hydroxyphosphinyl)-2-oxobutyric acid is added to the culture solution of Streptomyces vigroscopicus and the culture is continued. (Unexamined Japanese Patent Publication No. 1983)
-219191 Publication), and at this time, by appropriately setting culture conditions, monophosphonotrigine, which is the herbicidal active ingredient of bialaphos, or L-2-amino-4-(hydroxymethylphosphinyl)butyric acid can also be produced. It has been found that this is possible (Japanese Unexamined Patent Publication No. 62-253389).

The 2-alkoxycarbonylethylphosphinic acid according to the invention is the 3-(hydroxyphosphinyl)-2-
It occupies an important position as an intermediate for the synthesis of oxobutyric acid, and therefore, the prior art related to the synthesis of this type of alkyl phosphine will be described below.

Several methods of reacting hypophosphorous acid, hypophosphites, or hypophosphite esters with olefins in order to synthesize alkyl phosphines are conventionally known as described below.

a) Reaction example using hypophosphorous acid: A method for synthesizing alkyl phosphinic acid or arylalkyl phosphinic acid by reacting hypophosphorous acid and alkyl ethylene or arylalkyl ethylene in the presence of a radical initiator (Japanese Unexamined Patent Application Publication No. 1983-1999) 8392 Publication), a method for synthesizing α-hydroxyphosphinic acid by reacting hypophosphorous acid and vinyl acetate (Japanese Unexamined Patent Publication No. 60-89491), and 2-carbamylethyl by reacting hypophosphorous anhydride with acrylamide. Method for synthesizing phosphinic acid ("Phospho")
Rusand 5ulfurj Volume 21 No. 187-18
8 p. 1984).

b) Example of reaction using hypophosphite: There is a method (Japanese Unexamined Patent Application Publication No. 58-219191) in which 3-dimethylpropylphosphinic acid is synthesized by reacting sodium hypophosphite with acrolein dimethylacecool.

C) Reaction side using hypophosphite ester Method for synthesizing methyl 2-methoxycarbonylethylphosphinate by reacting secondary methyl hypophosphite and methyl acrylate in the presence of a basic catalyst (r Phosphorus, Vol. 5) 9th
1-95, 1975).

(Problems to be Solved by the Invention and Objectives of the Invention) Production of bialaphos and monophosphonothricin, that is, L-2-amino-4-(hydroxymethylphosphinyl)butyric acid, which is considered to be its herbicidal active ingredient. 2-Alkoxycarbonylethylphosphinic acid useful for production is not known, as is clear from the above related prior art introduction.

In the above-mentioned prior art, as a related compound, the literature r
Phosphorus J Vol. 5 No. 91-95 (19
There is an ester form, namely methyl 2-methoxycarbonylethylphosphinate, disclosed in 1975), and although it is possible to derive this ester form into a free acid, the ester form is There are industrial problems in synthesizing it. That is, methyl hypophosphite, which is the starting material for this method, must be synthesized by a reaction between anhydrous hypophosphorous acid and methyl formate, resulting in high costs.Also, in the synthesis of phosphinic acid ester, two molecules are added to methyl hypophosphite. This is because the yield of the desired methyl 2-methoxycarbonylethylphosphinate decreases because methyl acrylate is accompanied by the addition of methyl bis(methoxycarbonylethyl)phosphinate.

Therefore, the basic object of the present invention is to provide 2-alkoxycarbonylethylphosphinic acids, whereby 3-
The object of the present invention is to facilitate the synthesis of (hydroxyphosphinyl)-2-oxobutyric acid and, in turn, to reduce the production cost of bialaphos and L-phosphonothricin.

An additional object of the present invention is to provide a method for producing 2-alkoxycarbonylethylphosphinic acid, which can be implemented industrially in terms of reaction and cost.

(Means and effects for solving the problem and achieving the object) According to the present invention, the above problem can be solved by the formula % (in the formula, R means an alkyl group having 1 to 8 carbon atoms) 2-alkoxycarbonylethylphosphinic acid, shown in , achieves the above basic objective.

The compound represented by the general formula (1) is obtained by combining an acrylic acid ester represented by the general formula % (in the formula %) (in which R has the above-mentioned meaning) and a hypochlorite*#Ii salt as a radical initiator. can be prepared by reacting in the presence of a compound, thereby achieving the above-mentioned incidental object.

When carrying out the method of the invention, an alkali metal salt of hypophosphorous acid, such as a sodium salt, can be used as the hypophosphite. On the other hand, acrylic esters include alkyl esters such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, isoamyl,
-Ethylhexyl ester may be mentioned. The reaction conditions vary depending on the type of radical initiator and solvent employed, but - numerically, the temperature is about 50-150°C;
The reaction time is about 1-24 hours, preferably 2-5 hours. The molar ratio of hypophosphite and acrylic acid ester, which are reaction participants, is generally from about 1=1 to about 10:1. The amount of the radical initiator to be used is a catalytic amount which is sufficient, and numerically, it is about 0, θ01 to 0.1 mole per mole of acrylic ester.

As the radical initiator, those commonly used in this type of reaction can be used, such as ketone peroxides such as methyl ethyl ketone peroxide and cyclohexanone peroxide; 1-bis(butylperoxy)-3,3,5-1-limethylcyclohexane, 1,1-bis(butylperoxy)cyclohexane, 2,2-bis(butylperoxy)butane peroxyesters such as t-butyl hydroperoxide, hydroperoxides such as cumene hydroperoxide, dialkyl peroxides such as di-butyl peroxide, di-butyl cumyl peroxide, di-cumyl peroxide, etc. , diacyl peroxides such as acetyl peroxide, propionyl peroxide, benzoyl peroxide, peroxycarbonates such as di-iso-10-vinyl peroxycarbonate, di-2-ethylhexyl peroxycarbonate, and butyl peroxyacetate. , peroxyesters such as t-butyl peroxyin butyrate, and azobisisobutyronitrile.

As the reaction solvent, any inert solvent can be used, and there are no particular limitations, but alcoholic solvents such as methanol, ethanol, isopropyl alcohol, and t-butyl alcohol are advantageous from the viewpoint of cost and the like.

(Examples, etc.) Next, the present invention will be described in further detail with reference to Examples and Reference Examples.

Sodium hypophosphite hydrate 3.18g (30mmo
l) in methanol (30 ml), add acrylic acid n-
Add 1.28 g (10 mmol) of butyl and 100 ml of 2,2-bis(t-butylperoxy)butane,
This mixture was stirred in a sealed tube at 120°C for 2 hours. After cooling, the reaction mixture was concentrated under reduced pressure and methanol was distilled off. Add 30 ml of water to the residue and
The pH was adjusted to 9-10 with an aqueous NaOH solution, washed twice with 15 ml of ethyl ether, and then the pH of the aqueous layer was adjusted to 1.0 with concentrated hydrochloric acid. The solution was saturated with sodium chloride and extracted three times with ethyl ether 251. The ether extract layers were combined, washed twice with 10 ml of water, and then dried over anhydrous magnesium sulfate. Then,
By distilling off the solvent under reduced pressure, 1.57 g of the desired compound was obtained as a colorless wave. The yield was 81%, calculated based on the n-butyl acrylate used.

NMR (CDCl2) δ ppm: 0.94 (3H, t, J=7Hz, CH
3) 1.20- ], 70 (4H, Ill, -0-
CH2-CH-CH-CH3)2.06
(2H,m, P-CH2-)2.64
(2H, dL, J46Hz, J=8Hz.

P-CH2-C-CO-) 4.08 (2H,L, J=8H2,0
-CH2-)7.18 (1)1. d
, J=565)1z, P-H)11.22
(LH, s, P-OH) To a solution of 3.18 g (30 mmol) of sodium hypophosphite hydrate in methanol (30 ml), 1.28 g of loubutyl acrylate was added.
(10 mmol) and 100 μm of butyl peroxide
was added and the mixture was heated at 140°C in a sealed tube for 1.
The reaction mixture was stirred for 5 hours. The reaction mixture was then worked up as in Example 1, yielding the desired compound 1.
48g was obtained (yield near 6%).

Sodium hypophosphite hydrate 22.3g (210mm
Acrylic flln-fluf 8.97. g (70 mmol) and 1 g of azobisisobutyronitrile were added, and the mixture was reacted under reflux conditions for 7 hours. The reaction mixture was then worked up in the same manner as in Example 1, yielding 8.96 g of the desired compound (yield: 75.2%).

Sodium hypophosphite hydrate 3.18g (30mmo
1.0 g (10 mmol) of ethyl acrylate and 2,2-bis(L-
100 μm of butylperoxy)butane were added and the mixture was stirred for 2 hours at 120° C. in a sealed tube. The reaction mixture was then worked up in the same manner as in Example 1 to obtain 1 g of the desired compound (yield: 60%>).

NMR (CDCl2>δppm: 1.25 <3H,t, J=7Hz, CH3)2
．． 0 (2H, m, P-Ctb)2.60 (
2H, dt, J46Hz, J=8Hz.

P-CH2-CH-Co-) 4.10 (2H,q,JJ)lz,0-CF(2
-)7.20 (IH, d, J=568Hz, P-
H) 9.60 (IH,s, P-01-sodium hypophosphite hydrate 3.18 g <30 mmol) in methanol <30 ml), 1.11 g (f5 mmol) of 2-ethylhexyl acrylate and 2 , 50 μm of 2-bis-(L-butylperoxy)butane was added,
This mixture was stirred in a sealed tube at 1.20° C. for 2 hours. The reaction mixture was then worked up in the same manner as in Example 1, yielding 1.28 g of the desired compound as an oil (yield: 85%).

NMR (CDCl2>δppm: 0.83-0.91 <6t(,dt,, 2x
CHJl, 24-1.40 [9H,m, -0-C
F(2-CI-(C-2)3-]H1 2,06(2H,m, P-CH2-)2.64
<28. dt, J=16Hz,' J=8Hz
.

P-CHz-CHjL-) 4.05 (2H, d, J=8NZ,
0-CH2-)7.18 (IH,d,
J=564Hz, P-H) 10.86
(LH, s, P-OH)
3.69 g (20 mmol) of 2-ethylhexyl acrylate and 500 mg of azobisisobutyronitrile were added to a methanol (100 ml) solution of ol), and the mixture was reacted under reflux conditions for 5 hours. was post-treated in the same manner as in Example 1, and 3.25 g of the desired compound was obtained as an oil. Yield: 65
%).

Yoshi Sodium Ethylate 272B (0,004mol,
Oxalic acid di(
2-ethylhexyl) 691.7mg (0,002
2 mol, 1.1 equivalents) and 388 mg (0,002 m
ol) was added thereto, and the mixture was stirred at room temperature for 24 hours. Next, 10 ml of concentrated hydrochloric acid and 5 ml of water were added, and the mixture was heated under reflux for 8 hours. The reaction mixture was separated, the aqueous layer was concentrated under reduced pressure,
By purifying with WA-10 (CI type) 50ml, 285mg of the desired compound was obtained (yield:
85.7%).

NMR (D20) δpplIl: 1.52-1.82 (2H, m, P-CH2-)
2.70-2-82 <2)! , m, P-CH2
-CHL-)6.96 (IH, d, J=5
12Hz, P-H) Same as in Reference Example 1, except that 500 mg of 2-ethylhexyloxycarbonyl)ethylphosphinic acid was used instead of 2-(n-butoxycarbonyl)ethylphosphinic acid.
(289 mg of the desired compound was obtained by using 0,002 mole (yield: 287.0%).

(Effects of the Invention) The 2-alkoxycarbonylethylphosphinic acid according to the present invention facilitates the synthesis of 3-(hydroxyphosphinyl)=2-oxobutyric acid, and furthermore, it facilitates the synthesis of 3-(hydroxyphosphinyl)=2-oxobutyric acid, which in turn facilitates the synthesis of bialaphos and L-phosphonothricin, which have herbicidal activity. resulting in a reduction in production costs.

On the other hand, the method of the present invention makes it possible to easily synthesize 2-alkoxycarbonylethylphosphinic acid starting from raw materials that are easily and inexpensively available, and the yield is also good.

""1. i! −j−

Claims (2)

[Claims] (1) 2-alkoxycarbonylethylphosphinic acid represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (I) (In the formula, R means an alkyl group having 1 to 8 carbon atoms). (2) An acrylic ester represented by the general formula CH_2=CH-COOR(II) (in the formula, R means an alkyl group having 1 to 8 carbon atoms) and a hypophosphite are combined in the presence of a radical initiator. A method for producing 2-alkoxycarbonylethylphosphinic acid represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (I) (in the formula, R has the meaning described above).