JPS5920680B2 - Method for producing phosphorothioate or phenyl phosphorothioate - Google Patents

Description

Detailed Description of the Invention Phosphorochloride thioate and phenylphosphonochloride thioate and an alkali metal salt of a hydroxyl-substituted carbocyclic or heterocyclic aromatic compound are used as a liquid reaction solvent and a catalyst (1 ) a quaternary ammonium or phosphonium salt and (2) a sterically unhindered nucleophilic tertiary organic amine to produce phosphorothioate and phenylphosphonothioate.

By using this catalyst system, high purity products can be obtained in short reaction times and in good yields. This invention relates to an improved process for making phosphorothioates and phenylphosphonothioates.

O-pyridyl phosphates and phosphorothioates are described in US Pat. No. 3,244,586.

These compounds are particularly useful as insecticides and fungicides. These are shown by formula (1), where R
represents halopyridyl, Z represents oxygen or sulfur, and each R independently represents lower alkoxy, amino or lower amino group. Although the above patents disclose several methods of preparing these compounds, the preferred method is to prepare a phosphorochloridate or phosphorochloridethionate of formula ( It consists of reacting a halopyridinol containing a tertiary amine with an alkali metal or amine salt.

The disclosed method is carried out in an inert organic solvent under anhydrous conditions. In each of the disclosed processes, alkali metal salts or quaternary amine hydrochlorides are formed as reaction by-products and must be removed by filtration. The present invention is based on the following formula (where R is an alkyl group, R2 is an alkoxy or phenyl group, and R is nitro, cyano, halo, alkyl,
6-membered carbocyclic or heterocyclic 6-membered aromatic ring containing 0 to 3 substituents selected from alkoxy, alkylthio and alkylsulfinyl groups, but not containing more than 1 nitro, alkylthio or alkylsulfinyl group A method for producing a phosphorothioate or phenylphosphonothioate corresponding to a compound in which the alkyl and alkoxy groups each contain from 1 to 4 carbon atoms, wherein R and R are as defined above. ) and a salt corresponding to the following formula R-0M or MO-C6H4-S-C6H4-0M (wherein R is the same as above and M is an alkali metal). As a liquid reaction solvent and catalyst (1) a quaternary ammonium or phosphonium salt having at least 10 carbon atoms and having a solubility of at least 1% by weight in the reaction solvent; and (2) nucleophilicity without steric hindrance. Provided is a production method characterized in that the reaction is carried out in the presence of a tertiary organic amine.

The main products are those in which R is of the following formula: where n is 0, 1, 2, or 3, and but R does not contain more than one nitro, alkylthio or alkylsulfinyl group).

All examples of alkyl and alkoxy groups have 1 to 4 carbon atoms (ie methyl, ethyl, propyl and butyl groups). Using this catalyst system, phosphorothioate and phenylphosphonothioate can be obtained with high purity and high yield at an industrially satisfactory reaction rate.

By using our catalyst compositions, the well-known reaction steps described above can therefore be improved. Conventionally, only amines were used as catalysts to increase the reaction rate.

However, the product yields obtained were generally lower than in accordance with the present invention, and significant amounts of by-products were present which had to be removed. This required an expensive and difficult purification process. The quaternary salt mentioned above is used only to catalyze the reaction and the product is obtained in completely pure form.

However, if the catalyst concentration is low, the reaction rate is too low for industrial use. Higher catalyst concentrations increase the reaction rate, but make it more difficult to remove the catalyst from the product. Therefore, the combination of the above-mentioned quaternary ammonium salts with certain tertiary amines accelerates the reaction rate at least as well as the use of amines alone, and produces fewer by-products while increasing product yields. It was surprising to find that this increased.

Essentially any of the quaternary ammonium and phosphonium salts known per se may be used in the present invention.

Suitable quaternary ammonium and phosphonium salts at 25°C
have a minimum solubility in the reaction solvent of at least about 1% by weight and usually have a total carbon content of at least about 10 carbons, preferably from about 12 to about 31 carbons. The above ammonium and phosphonium salts have the formula R1″R2″R3″R4
"QlAe, where R/-R4' is a hydrocarbyl group (e.g., alkyl, aryl,
alkaryl, aralkyl, cycloalkyl, etc.) and Q+ is a quaternized atom of nitrogen or phosphorus. Furthermore, R/ can be combined with R to form a 5- or 6-membered heterocyclic compound containing at least one quaternary nitrogen or phosphorus atom in the ring; It may also contain non-phosphorous nitrogen, oxygen or sulfur atoms.
Typically R1-R1 is a hydrocarbyl group having 1 to 12 carbon atoms. A- is an inert neutralizing anion and can be varied as desired. "Inert" means not participating in the reaction in the process of the invention. Chloride and bromide are the preferred anions, but other suitable anions include, for example, fluoride, iodide, bisulfate, perchlorate, nitrate, acetate, thonlate, benzoate, and the like. The following compounds are illustrative: for example tetra-n-butyl-, tetrahexyl-, tri-n-butylmethyl-, cetyltrimethyl-, trioctylmethyl- and tridecylmethylammonium chloride, proma-4-do, bisulfate. , tetraalkyl ammonium salts such as tonlates: e.g. tetrabenzylammonium chloride, benzyltrimethyl-, benzyltriethyl-, benzyltributyl- and phenethyltrimethyl ammonium chloride, bromide; aralkylammonium salts such as e.g. triphenylmethylammonium fluoride, chloride. Or arylammonium salts such as bromide, N,N,N-trimethylanilinium bromide, N,N-diethyl-N-methylanilinium bisulfate, trimethylnaphthyl gamma monium chloride, p-methylphenyltrimethylammonium chloride, or tonlate. :For example, N-
Methylpyridinium chloride or methyl sulfate, N-hexyl pyridinium iodide, (4-pyridyl)monotrimethylammonium chloride, 1-methyl-1-azabicyclo[2.2,1]heptane bromide, N,N-dibutylmorporinium chloride, N-ethylthiazolium chloride,
5- and 6-membered heterocyclic compounds containing at least one quaternary nitrogen atom in the ring, such as N-butylpyrrolium chloride: and corresponding phosphonium salts and other similar compounds. Ammonium salts are currently preferred over phosphonium salts due to cost and commercial availability.

The most preferred catalysts are benzyltrimethyl, benzyltriethyl, tetra-n-butyl and tri-n-butylmethyl ammonium salts. In the present invention, these quaternary ammonium and phosphonium salts are used in small but catalytic amounts. For example, about 0
．． Amounts of 1 to 20 mole % are suitable, although amounts of about 0.5 to 10 mole % are generally preferred. The amines used in the present invention are nucleophilic organic tertiary amines without steric hindrance.

The amine suitable for use is reacted with phosphorochloride thioate and phenylphosphonochloride thioate to form a 1:1 molar ratio of adducts as reaction intermediates. This addition product can be analyzed by a person skilled in the art using any of the conventional analytical methods (e.g. U absorption spectroscopy).
It can be identified using However, in most cases, an alternative method to determine whether a tertiary amine is effective as a cocatalyst is the screening method described below (S
cleaning) method can be used. The screening method consists of mixing equimolar amounts of tertiary amine and phosphorochloride thioate or phenylphosphonochloride thioate in diethyl ether at room temperature and observing whether an ether-insoluble salt is formed.
In essentially all cases, if the tertiary amine is a suitable catalyst for the given reaction, 1
An ether-insoluble salt forms within 5 minutes. In fact, even less effective amine catalysts form ether-insoluble salts almost immediately upon mixing. Examples of suitable tertiary amines include 1,4-diazabicyclo[2,2,2]octane; diazoles such as imidazole, pyrazole or their 1-alkyl derivatives; aliphatic trihydrocarbyl amines such as trimethylamine,
Ethyldimethylamine, butyldimethylamine, N,N
, N,N-tetramethylethylenediamine, etc.); aliphatic heterocyclic amines (such as 1-azabicyclo[2,2
,2]Octane, 1-methyl-2-imidazoline, 1-
methylpyrrolidone); mixed aliphatic monoaromatic amines (such as methylpyrrolidone);
For example, 4-(N,N-dimethylamino)pyridine, 4
-(N-pyrrolidino)pyridine, phenyldimethylamine, etc.); and other similar nucleophilic organic tertiary amines without steric hindrance. Tertiary amines are used in the present invention in small but catalytic amounts.

For example, amounts of about 0.25 to 20 mole percent, based on the reactants, are suitable, with about 0.5 to 10 mole percent being generally preferred. Examples of suitable combinations of quaternary ammonium salts and tertiary amines include benzyltriethyl phosphonium
Chloride and trimethylamine, benzyltriethylammonium bromide and trimethylamine, tetra-
n-Butylammonium bisulfate and 1-azabicyclo[2.2,2]octane, tri-n-butylmethylammonium bromide and 1-methylpyrrolidine, triphenylmethylphosphonium chloride and 4-(N
, N-dimethylamino)pyridine, tetra-n-butylphosphonium acetate and pyridine, 2,4-dichlorobenzyl trimethylgammamonium chloride and 3-
or 4-picoline, tridecylmethylammonium chloride and 4-(N,N-dimethylamino)pyridine, octadecyltrimethylammonium bromide and trimethylamine, benzyltriethylammonium chloride and 1-methylimidazole, benzyltriethylammonium chloride and 1,4-diazabicyclo [2,2,2]Octane (triethylenediamine)
etc.

Alkali metal phenates, pyridinates and pyrimidinates have the following formulas R-0-M+ and M+-0-QlI4-
S→? 810-M+ (wherein R is the same as above and M is an alkali metal such as Li, Na, K, etc., with sodium and potassium being more preferred and sodium being most preferred). .

0,0-Dialkyl phosphorochloride thioates and O-alkyl phenyl phosphonochloride thioates are likewise known compounds, which have the following formula: where R1 and R2 are each independently lower alkyl, in particular methyl or ethyl preferred).

A variety of phosphorothioates and phenylphosphonothioates can be made using various combinations of the reactants listed above.

Representative examples of suitable reactants and combinations thereof are shown in Tables 1 and 2. The reaction proceeds at a satisfactory rate at temperatures from about 0°C to about 100 meC, and at a preferred rate at temperatures from about 40 to about 60°C. There is no limit to the reaction pressure, and generally atmospheric pressure or higher pressure is used.
Under the above conditions, reaction times of up to 8 hours are typical, although 0.25 to 5 hours are sufficient to substantially complete the reaction. Suitable reaction solvents include hydrocarbon solvents (
Examples include benzene, toluene, xylene, cyclohexane, etc.), chlorinated hydrocarbon solvents (such as methylene chloride, chloroform, carbon tetrachloride, tetrachloroethylene, etc.).

Also, a two-layer mixture of water and an inert solvent that is immiscible with water (
(e.g. hydrocarbons or chlorinated hydrocarbons and water)
is also suitable. Methylene chloride or a mixture of methylene chloride and water is the preferred reaction solvent. The method is carried out under alkaline conditions.

This is easily accomplished by carrying out the process in the presence of caustic soda (NaOH) or other bases or using a suitable buffer system. Stir the reaction mixture (
(e.g., stirring), especially when carrying out the method in a bilayer reaction solvent (e.g., methylene chloride and water).

The following examples further illustrate the invention.

Example 1-4 In a mixture of methylene chloride and water, benzyltrimethylammonium chloride (3 mol%
) and one of the following amines (1-2 mol %) with 0,0-diethyl phosphorochloride thioate (9.5 g, 0.05 mol) and sodium 3,
5,6-trichloro-2-pyridinate (12.09,
0.05 mol (L) was reacted.

The product, 0,0-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate, was converted to a
Obtained with a yield of 0% or more.

The resulting product was recovered by separating the inorganic aqueous layer of the reaction mixture, washing the organic layer three times with water, and removing the solvent by fractional distillation of the organic layer. Examples 5-14 Using the catalyst combinations listed in Table 3, the products of Examples 1-4 could be made in excellent yields in substantially the same manner as Examples 1-4.

Example 15 0,0-dimethyl O-3,5,6-trichloro-2-
Preparation of Pyridyl Phosphorothioate In a three-loaf flask equipped with a stirrer, condenser and dropping load, add 30 d of methylene chloride, 74 d of water, 3 d of sodium chloride.
．． 39, sodium hydroxide 0.389, boric acid 0.79,
Benzyltriethylammonium chloride 0.13
9 (0.56 mmol), 1-methylimidazole 0.059 (0.56 mmol) and sodium 3
,5,6-trichloro-2-pyridinate (NaTCP
)12.5f! (56 mmol) was added.

The mixture was stirred and heated to 35°C, and 0,0-
Dimethyl phosphorochloride thioate 9.039 (5
6.3 mmol) was added over about 1 minute. This mixture was rebraxed (42° C.) for 1.5 hours. CH2Cl2
The layers were separated, washed with 100 g of water, and then the CH2Cl2 was removed on a rotary evaporator. When the product is cooled in an ice bath, 0,0-dimethyl 0-3,5,6
17.31 white crystals (yield 93.7%) of -trichloro-2-pyridyl phosphorothioate were obtained. In the same way, we conducted the following experiment. Example 160,0-
Preparation of diethyl 0-3,5,6-trichloro-2-pyridyl phosphorothioate In a three-loaf flask equipped with a stirrer, condenser and dropping load, methylene
30 grams of chloride, 74 ml of water 1) Sodium chloride 3.5
9. Sodium hydroxide 0.439, boric acid 0.78g, benzyltriethylammonium chloride 0.141
(0.6 mmol), 1-methylimidazole 0.0
4θ (0.45 mmol) and NaTCPl3.2
θ (60 mmol) was added.

This mixture was heated to 35°C with stirring, and then
,0-diethylphosphorochloride thioate (DE
PCT) 11.39 (60 mmol) was added over 1 minute. The reaction mixture was then rebraxed for 3.9 hours with stirring. Separate the CH2Cl2 layer and add 10% water
Washed with 0ml. Next, CH2Cl2 was removed using a rotary evaporator. The product was cooled in an ice bath to give white crystals 19.419 (92.4% yield of product with 99.5% purity). In the same way, we conducted the following experiment.

Examples 17-22 The following experiments were conducted using substantially the same procedure.

In each example, the catalyst used is a mixture of benzyltriethylammonium chloride and 1-methylimidazole. The catalyst concentration in Examples 17-21 is 0.75 mol % based on the total amount of starting materials, and in the case of Example 22 it is 1.0 mol %.
It is. Furthermore, boric acid was added to Examples 17-19 (Example 1
5 and 16) were not added to Examples 20-22. The experimental results are shown in Table 6. Example 23 0,0-diethyl O-3,5,6-trichloro-2-
Production of pyridyl phosphorothioete (1) Sodium
3,5,6-trichloro-2-pyridinate (13.2
9.0.06 monomer dissolved in 30 ml of methylene chloride and 74 ml of water, (2) 1 mol% of triethylenediamine, (3) 1 mol% of benzyltriethylammonium chloride, and (4) PH buffer consisting of NaOH and sodium borate. To the stirred mixture of liquids was added dropwise 0,0-diethyl phosphorochloride thioate (11.3 g, 0.06 mol).

The reaction mixture was maintained at 42° C. for about 1.5 hours;
It was then cooled to room temperature and the organic layer was separated from the aqueous layer. The organic layer was washed once with about 30 ml of water and the organic solvent was removed under reduced pressure. The title compound was obtained in 97% yield. The purity was very good (approximately 99%). Examples 24-25 The following examples were carried out using essentially the same procedures, reactants and conditions as in Example 1, except for catalyst and reaction time.

The results are as follows. 6DEPCT''' means 0,0-diethyl phosphorochloride'' thioate.

The procedures and conditions for this series of experiments are substantially the same as those in Example 23.

However, the reaction time was 3-4 hours and no boric acid was added. Further, the catalyst concentration was reduced to 0.75 mol% for triethylenediamine and 0.75 mol% for benzyltriethylammonium chloride based on the total amount of starting materials.
The product yields of Examples 26 and 27 were 92.1 and 93.1%, respectively. Example 28 0,0-diethyl O-3,5,6-trichloro-2-
Preparation of Pyridyl Phosphorothioate In a three-loaf flask equipped with a stirrer, condenser and dropping load, add 30 ml of methylene chloride, 74 ml of water, and 3.0 ml of sodium chloride.
59, sodium hydroxide 0.439, boric acid 0.789,
Tetrabutylphosphonium chloride 0.189, 1
．． 4-Diazahicyclo[2,2,2]octane 0.07
9 and 3.29 (60 mmol) of NaTCPl.

The mixture was heated to 35°C with stirring and added 0,
0-Diethyl phosphorochloride thioate (DE
PCT) 11.3f! (60 mmol) was added over 1 minute. The initial H of the mixture was 13.2. The reaction mixture was then rebraxed for 1.5 hours with stirring. At that time, the amount of 0,0-diethyl phosphorochloride thioate remaining in the sample is 0.50t)
It was below. Ribraxed for an additional 2.4 hours. C
The H2Cl2 layer was separated and washed with 100ml of water. Next, CH2Cl2 was removed using a rotary evaporator. The product was cooled in an ice bath to give 19.79% of white crystals. The impurity in it was 0.075%. Example 29 0,0-diethyl O-3,5,6-trichloro-2-
Preparation of Pyridyl Phosphorothioate In a three-loaf flask equipped with a stirrer, condenser and dropping load, add 30 d of methylene chloride, 74 d of water, 3.
59, sodium hydroxide 0.439, boric acid 0.78fI
1 triphenylmethylphosphonium bromide 0.2
8 g (0.6 mmol), 1,4-diazahicyclo[2
,2,2]octane (0.45 mmol) and DEPCT (60 mmol).

The mixture was heated to 35°C with stirring and added 0,
0-Diethyl phosphorochloride thioate (DE
PCT) 11.39 (60 mmol) was added over 1 minute.

The reaction mixture was then rebraxed for 3.9 hours with stirring. The CH2CI12 layer was separated and washed with 100 d of water. Next, CH2C in a rotary evaporator
Il2 was removed. The product was cooled in an ice bath to give white crystals 19.29. It contained 0.07% of impurities. Example 30 0,0-diethyl 0-3,5,6-trichloro-2-
Preparation of Pyridyl Phosphorothioate In a three-loaf flask equipped with a stirrer, condenser and dropping load, add 30 d of methylene, 30 d of chloride, 74 d of water, 3.1 d of sodium chloride.
59, sodium hydroxide 0.439, boric acid 0.78fI
1tetra-n-butylphosphonium chloride 0.1
8 g, 0.059 (0.45 mmol) of 1-methylimidazole, and 60 mmol of DEPCT.

The mixture was heated to 35°C with stirring and added 0,
0-Diethyl phosphorochloride thioate (DE
PCT) 11.39 (60 mmol) was added over 1 minute. The reaction mixture was then rebraxed for 3.9 hours with stirring. Separate the CH2Cl2 layer and add 100% water
Washed with 1 nt. Next, CH2C22 was removed using a rotary evaporator. The product was cooled in an ice bath, resulting in white crystals of 19.6f! (purity 99.4%) was obtained. Embodiments of the invention are as follows.

1. In the manufacturing method claimed in the claims, (1) and (
2), each of which is present in a proportion of 0.1 to 20 mol% relative to the reactant; The manufacturing method according to the claims, characterized in that (1) and (2) are each present in a proportion of 0.5 to 10 mol % based on the reactant.

3. A manufacturing method according to the claims and any one of (1) to (2) above, characterized in that the reaction is carried out at a temperature in the range of 0 to 100°C.

4. A manufacturing method according to any one of the claims and (1) to (2) above, characterized in that the reaction is carried out at a temperature in the range of 40 to 60°C.

5. A manufacturing method as claimed in the claims and any one of (1) to (4) above, characterized in that the liquid reaction solvent consists of a hydrocarbon solvent or a chlorinated hydrocarbon solvent.

6. 7. In the manufacturing method according to claims and any one of (1) to (4) above, the liquid reaction solvent comprises an inert and water-immiscible organic solvent and water. Production method 98. In the production method of 6 above, the organic solvent is methylene chloride. In the claims and any of the manufacturing methods (1) to (7) above, the quaternary ammonium or phosphonium salt is
A method characterized in that it contains from 2 to 31 carbon atoms.

9. In the claims and the manufacturing method according to any one of (1) to (8) above,
A production method characterized in that the quaternary ammonium salt is selected from bromide and tetra-n-butylammonium chloride.

10. In the claims and the manufacturing method in any one of (9) above, (2-1-azabicyclo[2,2,
2] Octane, trimethylamine, N-methylpyrrolidone, 4-(N,N-dimethylamino)pyridine, 4-picoline, quinuclidine, tributylamine, N,N-dimethylaniline, N-methylmorpholine, tetramethylethylenediamine, benzyldimethylamine , triphenylamine, 1,4-diasabicyclo[2,2,2]octane or 1-methylimidazole.

11. In the claims and any of the manufacturing methods (1) to (self) above, R is represented by the following formula (in the formula, n is o to 3, and X is cyano, halo, alkyl,
alkoxy, alkylthio or alkylsulfinyl, but in the case of nitro, alkylthio or alkylsulfinyl, X does not exceed 1, and the alkyl and alkoxy groups contain from 1 to 4 carbon atoms). A manufacturing method characterized by:

12. In the claims and any of the manufacturing methods described above (C-QVJ), R is 3,5,6-trichloro-2
- A method characterized in that it is pyridyl.

Claims (1)

[Claims] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R_1 is an alkyl group, R_2 is an alkoxy or phenyl group, and R is nitro, cyano, halo, A 6-membered carbocyclic or heterocyclic aromatic compound containing 0 to 3 substituents selected from alkyl, alkoxy, alkylthio and alkylsulfinyl groups, but not containing more than one nitro, alkylthio or alkylsulfinyl group; , the alkyl and alkoxy groups each containing 1 to 4 carbon atoms), the following formula ▲ mathematical formula, chemical formula, table, etc. ▼ (in the formula R_1 and R_2 is the same as above) and a chlorophosphorus compound corresponding to the following formula R-OM or M
O-C_6H_4-S-C_6H_4-OM (wherein R is the same as above and M is an alkali metal) as a liquid reaction solvent and a catalyst (1) containing at least 10 carbon atoms. and (2) a sterically unhindered nucleophilic tertiary organic amine. .