CA1081238A - Preparation of o,o-diethyl phthalimido-n-phosphorothioate - Google Patents

Abstract

ABSTRACT

A process for preparing an O,O-dialkyl phthalimido-phosphonothioate which comprises reacting a phthalic anhy-dride with an O,O-dialkyl phosphoramidothioate in presence of a tertiary amine as catalyst. The products are known to be useful as pesticides, particularly for control of fungi attacking plants.

Description

1081'h38 PREPARATION OF O,O-DIALKYL
PHTHALIMIDO-N-PHOSPHOROTHIOATE

rThis invention is for an improved method for pre- ;~
paring O,O-dial]cyl phthalimido-N-phosphorothioate (hereinater alternatively referred to as Compound~, corresponding to the general formula ~ 5<0R

"'' wherein each R is independently an alkyl group having from 1 to 4 carbon atoms.

The Compound, methods for its preparation, and teachings of its utility as a pesticide and as an active toxi-cant in compositions for the control of insect, mite, helminth, plant, fungal and bacterial organisms are described in British Patent Specification No. 1,034,493 and United States Patent Specifications Nos. 3,336,188; 3,450,713; 3,803,167; and 3,853,909. The method taught by the first two or the above United States patents basically entails the reaction of an N-alkali metal phthalimide with O,O-diethyl phosphoro-chloridothioate in the presence of an inert amido reaction medium such as, for example, N-methyl-2-pyrrolidone, dimethyl-ormamide, hexamethylphosphoramide, N-acetyl-morpholine, or dimethylacetamide.
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United S-tates Paten~ No. 3,803,167 teaches another method of preparing the Compound wherein O,O-diethyl phos-phorochloridothioate is reacted with N-alkali metal phthali-mide .in the presence o~ an aromatic tertiary amine catalyst, such as pyridine, alpha-picoline, dimethylaniline, triphenyl-amine, pyrazine, or quinoline, and a tertiary alcohol as solvent or reaction medium. Aliphatic tertiary amines were not found to be useful as catalysts in the process of United States Patent No. 3,803,167.
United States Patent No. 3,853,909 teaches preparing the Compound by reacting O,O-diethyl phosphorochloridothioate with N-alkali metal phthalimide in the presence o~ a catalytic amount of 1,4-diazabicyclo(2,2,2)octane and an inert tertiary `
alcohol as a solvent or reaction medium.
:; .': ' United States Patent No. 3,399,213 teaches several methods of prepari.ng the Compound. In one method, O,O~
-diethyl phosphoramidothioate is reacted with phthalic anhy~
20 dride in the presence of dimethylformamide reaction medium and .-sodium hydride under a nitrogen atmosphere.

The above-described processas effectively produce the Compound. However, the process of the present invention is desirable in that it utilizes readily available starting materials while producing the Compound, at least when optimum conditions are chosen, in good yields. The present process is particularly advantageous over the process described in United States Patent No. 3,399,213 because the sodium

3~ hydride, which is hazardous, difficul.t to handle, and non--recoverable is replaced by a tertiary amine catalyst which is recoverable, easily handled, and less hazardous than sodium hydride.

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;: ~ ~ . ' , ~ - : . ' In accordallce with the present invention, the Compound can be procluced by a method which comprises reacting a ph-thalic anhydrlde with the formula RO \ S

RO
in the presence of an effective catalytic amount of at least one amine, said amine being a tertiary am ne of the formula NR3 or a cyclic amine of the formula (CH2)n N -R where n is

4, 5 or 6, each R in the above formulae belng independently an alkyl group llaving from 1 to 4 carbon atoms, thereby to produce a dialkyl phthalimido-N-phosphorothioate.
The phthalic anhydride may be substituted such that it carries a substituent in the cyclic dicarboximido radical as described in British Patent Specification No. 1,034,4g3; .
however it is preferred that the phthalic anhydride is unsub-stituted and it is furthermore preferred that the alkyl groups of the O,O-dialkyl phosphoramidothioate are ethyl groups, as this compound has the best activity in the control of fungi and similar applications' Additionally, although the method :.
of the present invention may be effected by using as the catalyst a cyclic amine as defined above, it is preferred that the cyclic amine is N-ethylpiperidine.
.
It is generally preferred to carry out the reaction of the method of this invention without the use of a solvent although the reaction can be run in the presence of an alkane or lower haloalkane solvent (i.e. a haloalkane having up to 4 or 6 carbon atoms) or reaction medium. :

An essential feature of the present process is the utilization of the amine catalysts, preferably the tertiary 18,505 F .

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83L~ 8 am.ine o~ ormulcl ~R3 as above defined. The absence of this component will drastically reduce the yield of the desired Compound.

The alkyl group o group R may be straight or branched chain all~yl. Examples of suitable tertiary amine catalysts for use herein are triethylamine, trimethylamine, and tributylamine. The most preferred catalyst is triethylamine.
The catalyst may be N~ethylpyrrolidine or hexamethylene imine.

As indicated above, the formation of the desired .
Compound will take place via the method defined above when a solvent is not employed and, therefore, a solvent should not be considered to be a critical feature in the present process.
15 However, when employing a solvent, the preferred solvents for : -use in the present invention are those which have a low di-electric constant. In particular, lower cyclic and non-cyclic alkane and lower haloalkane solvents such as cyclohexane, hexane, decane, and dichloroethane are preferred. The most 20 preferred solvent is hexane. The terms "lower cyclic and ~:.
non-cyclic alkane" and "lower haloalkane" as used herein refers to such compounds having from 5 to 12 carbon atoms.
The term "halo" as emplo~ed herein refers to the substitution of one or more atoms of bromo, chloro, or fluoro.
The amount of amine catalyst employed in the present method is an amount at which the amine will function effect-ively as a catalyst~ In the practice of the present invention, the molar ratio of the phthalic anhydride to diethyl phos-phoramidothio~lte is preferably between 1 and 4 and most pre-ferably between 2 and 3. The ratio of the moles of amine catalyst to the combined moles of the reactants is preferably between 0.5 and 2, and most preferably between 0.5 and 0.75.

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` ~338~238 It is believed that the tertiary amine behaves in the manner of a catalyst but further reacts with products of the reaction such that it is removed from an active part in the reaction. Accordin~31y in the preferred mode of operating the method of this invention a sufficient quantity o catalyst is added to provide sufficient amine to effect complete reaction and remove all or substantially all the acidic by-products.

10The reaction is generally carried out at a tempera-ture in the range of 20 to 85C. The preferred temperature range at atmospheric pressure is from 45 to 65C. The reaction is preferably carried out at an ambient pressure but it can also be operated under elevated or reduced pressures.
When operating within the preferred conditions of temperature, pressure, and reactant and catalyst ratios, reaction times of from 1-6 hours are sufficient for practical completion.
The rate of addition and/or order of addition of the reactants, i.e. the phthalic anhydride and O,O-diethyl phos- i~
phoramidothioate or the ~ike, and the amine catalyst are not critical to the present process.
Upon completion of the reaction in the more pre- -ferred aspects of the invention, the desired product of the method can be separated by treating the hot reaction mixture with an e.qual amount o hot water or acetone and stirring several minutes. The desired Compound can be filtered from the organic layer after the layer is cooled. The product can be further purified, if desired, hy solvent recrvstallization followed by drying. However, the speci~ic mode of product `
separation is not critical and other conventional separatory procedures can be employed. An additional advantage o~
this invention is that the teritary amine catalyst 18,505-F
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-is recycla~le ~n~ can be recovered ~rom the aqueous mothex liquor such as, ~or example, by treating the mother liquor with sodium hydroxide.

In order that the present invention may be more fully understood, the following examples are given primarlly by way o~ illustration and should not be construed as limitations upon the overall scope of the present invention.
~nalysis of product was by gas-liquid chromatography (GLC) and hi~h pressure liquid chromatography (HPLC), using internal standards.

Example 1 A mixture of 92.5 g (0.625 mole) phthalic anhydride and 42.3 g (0.25 mole) O,O-diethyl phosphoramidothioate in light petroleum (b.p. 60-80C) was stirred in a pressure bomb and then treated with 38 g ~0.644 mole) of anhydrous trimethylamine. The temperature of the reaction medium was raised to 55C over 20 minutes and maintained thereat for 2-l/2 hours. The bomb was open~d and the system was treated with 200 ml of warm water and stirred for several rninutes.
The hot organic layer was cooled overnight to 0-5C. A
solid was filtered and dried therefrom to give the Product Compound; which was analyzed at 88~ purity b~ GLC. The ~5 yield of Compound was calculated to be 20~ from the O,O-diethyl phosphoramidothioate.

Example 2 A mixture of the 74.06 y (0.5 mole) phthalic anhy-dride, 33.84 ~ (0.2 mole) O,O-diethyl phosphoramidothioate and 50.60 g (0.5 mole) triethylamine was heated at 55~C for 3.5 hours. Eighty three mls of water were added to the stirred mixture and the system was stirred for lO minutes and then cooled to 25C over a one hour period. The solid was filtered, washed with 150 ml water to give the Product 18,505-F
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Compound, ~naly%ed at 98% purity by GLC. The yield was calculated to be 76% from the phosphoramidothioate.

Example 3 A mixture of 103.7 g (0.7 mole) phthalic anhydride, 47.3 g (0.28 mole) O,O-diethyl phosphoramidothioate and 129.5 g (0.7 mole) tributylamine was stirred and heated at 55C for 3 hours. One hundred and thirty three mls o~ water were added to the mixture and the resulting solution was cooled. No solid precipitated, but the solution was shown by GLC analysis to contain the Compound in 20~ yield from the O,O-diethyl phosphoramidothioate.

Example 4 A mixture of 222 g (1.5 moles) phthalic anhydride, 84.5 ~ (0.5 mole) O,O-diethyl phosphoramidothioate and 151 g (1.5 moles) triethylamine in 800 mls light petroleum (b.p. 60-80C) was stirred and heated at 67C for 5.75 hours. Two hundred and eighty mls of water were added to the vigourously stirred system. After several minutes, the mixture was allowed to stand, and the hot organic layer was separated and cooled to 0-5C to give the Product Compound as a colourless solid, m.p.~75-81C (97.5 purity by GLC). The yield was calculated to be 55% from the O,O-diethyl phos-phoramido~hioate. A further 4% yield of the Product Compound was obtained by filtering the cooled aqueous layer.
.
In a comparative run in which a tertiary amine catalyst was not utilized, a mixture of 148 g (1.0 mole) phthalic anhydride and 67.6 g ~0.4 mole) O,O-diethyl phos-phoramidothioate was stirred and heated at 55C for three hours. One hundred and ninet~ mls of water were added to the mixture. Analysis by GLC on the filtered solid indicated that no Product Compound was formed.
.

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L~ Z3~ -~8 Example 5 A mixture of 148 g (1.0 mole) phthalic anhydride, 67.6 g (0.4 mole) O,O-diethyl phosphoramidothioate and 113 g (1.0 mole) N-ethylpiperidine was heated at 55C for 3.5 hours. One hundred and ninety mls of water at 35C were added to the stirred mixture and the system was stirred for

5 minutes and then allowed to cool to ambient temperature.
The solid was filtered, washed with 25 ml water to give the Product Compound, analyzed at 94% purity by GLC. The yield was calculated to be 57% from the pho~phorami.dothioate.

Similar results may be obtained with N-ethyl-pyrrolidine or with hexamethylene imine, as the catalyst.

O,O-diethyl phosphoroamidothioate is a known compound and is available commercially. It may be prepared by methods known to those skilled in the art, such as by reacting a phosphorochloridate of the formula (C2H5O)2P~S)Cl with NH3, preferably in the presence of a hydrogen halide acceptor.
Other starting materials may be prepared by methods known to those skilled in the art.

The phosphoroc~loridate which is utilized to prepare O,O~diethyl phosphoroamidothioate may be prepared by reacting C13-P-S successively (in either order) or simultaneously with a compound of tha formula C2H5O-alkali metal as, for example, in the manner taught in United States Patent No. 3,399,213.
Phthalic anhydride is a well known compound and is available commercially.
Those who intend to practice this invention should note that phthalic anhydride is moderately toxic and a skin irritant and safety precautions should be employed when handling same. O,O-diethyl phthalimido-N-phosphorothioate exhibits a low degree of toxicity when compared with organo-18,505-F

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_9_ -phosphorus compounds in general. ~Iowever, it is a skin irritant and therefore should be handled with caution. O,O--diethyl phosphoramidothioate and tertiary amine catalysts should also be handled with caution.

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Claims (14)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A method of preparing a compound of the general formula:
which method comprises reacting a phthalic anhydride with the formula in the presence of an effective catalytic amount of at least one amine, said amine being a tertiary amine of the formula NR3 or a cyclic amine of the formula - R where n is 4, 5 or 6, each R in the above formulae being independently an alkyl group having from 1 to 4 carbon atoms, thereby to produce a dialkyl phthalimido-N-phosphorothioate.

2. A method as claimed in Claim 1, wherein the catalyst is N-ethylpiperidine.

3. A method as claimed in Claim 1 or Claim 2, wherein the phthalic anhydride is unsubstituted.

4. A method as claimed in Claim 1 wherein O,O--diethyl phosphoramidothioate is reacted with phthalic anhy-dride.

5. A method as claimed in Claim 4, wherein the tertiary amine is triethylamine.

6. A method as claimed in Claim 4 or Claim 5, wherein the reaction temperature ranges from 20° to 85°C.

7. A method as claimed in Claim 4 or 5, wherein the reaction temperature ranges from 45° to 65°C.

8. A method as claimed in Claim 5, wherein the ratio of the moles of triethylamine to the combined moles of O,O-diethyl phosphoramidothioate and phthalic anhydride is from 0.5 to 2.

9. A method as claimed in Claim 8, wherein the ratio of the moles of triethylamine to the combined moles of O,O-diethyl phosphoramidothioate and phthalic anhydride is from 0.5 to 0.75.

10. A method as claimed in Claim 4, wherein the mole ratio of phthalic anhydride to O,O-diethyl phosphoramido-thioate is from 1 to 4.

11. A method as claimed in Claim 10, wherein the mole ratio of phthalic anhydride to O,O-diethyl phosphoramido-thioate is from 2 to 3.

12. A method as claimed in Claim 4, wherein the reaction time is from 1 to 6 hours.

13. A method as claimed in Claim 4, wherein the reaction is run in the presence of a solvent selected from the group consisting of cyclohexane, decane and dichloro-ethane.

14. A method as claimed in Claim 4 or Claim 5, wherein the reaction is run in the presence of hexane.