Catalyzed and green process of malathion production

Abstract

To provide an improved method for the synthesis of malathion.SOLUTION: The presence of an acid facilitates the reaction between O,O-dimethyldithiophosphoric acid (O,O-DMDTPA) and maleate, resulting in products with excellent yield, shorter reaction time and fewer impurities.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a novel method for the synthesis of malathion using an acid as a catalyst. Due to the short reaction time and low levels of impurities, the synthesis method described herein has significantly less undesirable environmental impact than conventional methods. [Background technology]

[0002] Various methods for the production and / or purification of malathion are presented in the literature. Malathion (CAS number: 121-75-5) is an organophosphorus compound that inhibits cholinesterase activity in vivo. It is an acid-based insecticide. However, producing malathion efficiently and economically remains a challenge.

[0003] For example, formulations of malathion contain numerous impurities, some of which are formed during storage and some of which are formed during the manufacturing process. Many of these malathion impurities have been shown to be toxic.

[0004] O,O,S-trimethyldithiophosphate (MeOOSPS) and O,S,S-trimethylthiophosphate (MeOSSPO) can cause liver damage. Malathion is also liquid at room temperature (melting point: 2.9°C). ) and its physical properties, such as its difficulty in crystallization, make it difficult to remove impurities using conventional methods.

[0005] Therefore, there is a need for improved methods for preparing malathion. Summary of the Invention [Problem to be solved by the invention]

[0006] The present invention provides a novel approach for the production of malathion with good yields and significantly reduced impurities.

[0007] Malathion produced by the process of the present invention has low levels of harmful impurities and is storage stable as compared to other processes available in the literature for pharmaceutical use. [Means for solving the problem]

[0008] The process of the present invention generally comprises reacting O,O-dimethyldithiophosphoric acid (O,O-DMDTPA) in the presence of an acid. This involves reacting with diethyl maleate.

[0009] In an embodiment, the method of the present invention further comprises: (a) mixing O,O-dimethyldithiophosphoric acid (O,O-DMDTPA) with an acid prior to reacting O,O-DMDTPA with a maleate salt; (b) combining diethyl maleate to form a mixture; and (b) adding diethyl maleate to the mixture. include.

[0010] In an embodiment, the temperature of step (a) is controlled to about 5 to about 20° C. In an embodiment, the temperature of step (b) is controlled to about 10 to about 25° C. In an embodiment, the temperature is controlled to about 5 to about 20° C. After the addition of diethyl maleate is complete, the temperature is controlled between about 20° C. and about 50° C. In an embodiment, the temperature is controlled between about 35° C. and about 45° C. after the addition of diethyl maleate to the mixture is complete.

[0011] In embodiments, the acid is present in the mixture of step (a) in a range from about 0.1% to about 20% by weight. In embodiments, the acid is present in the mixture of step (a) in a range from about 1% to about 10% by weight.

[0012] In an embodiment, the acid comprises hydrochloric acid. In an embodiment, the acid comprises from about 20% by weight to about 37% by weight. In an embodiment, the acid consists essentially of saturated hydrochloric acid.

[0013] In an embodiment, the molar ratio between O,O-DMDTPA and diethyl maleate ranges from about 1:1.2 to about 1:1. In an embodiment, the molar ratio ranges from about 1:1.1 to about 1:1.02. In the example, diethyl maleate begins to react with O,O-DMDTPA when added to the mixture.

[0014] In an embodiment, the reaction between diethyl maleate and O,O-DMDTPA is allowed to continue for less than about 10 hours. In an embodiment, the reaction is allowed to continue for a period of less than about 8 hours.

[0015] In an embodiment, the method of the present invention further comprises, after step (b), a step (c) of forming a fluorinated compound as a result of step (b). The method further comprises the step of isolating the malathion by washing the entire mixture with an aqueous solution. In an embodiment, step (c) comprises removing the by-products by Wiped-Film Stills (WFS).

[0016] In an embodiment, the isolated malathion comprises less than about 0.55% O,O-DMDTPA by weight. Containing impurities In an embodiment, the isolated malathion contains less than about 0.35% by weight of an impurity consisting of O,O-DMDTPA.

[0017] In embodiments, the yield of malathion is greater than about 90%. In embodiments, the yield of malathion reaches greater than about 90% in a period of less than about 7 hours. Effect of the Invention

[0018] The present invention relates to an improved manufacturing process for preparing malathion. Compared to conventional processes, the process described herein achieves high yield production of malathion in a shorter time. Furthermore, the stability of malathion is improved due to the reduced amount of impurities. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] The following description sets forth specific components of the reaction or reaction conditions, but is not intended to limit the scope of the invention to such specific references or examples. Those skilled in the art will appreciate that various modifications may be made to the amounts of reactants, the temperature and length of the reaction, etc., based on practical and economic considerations.

[0020] As used herein, the articles "a" and "an" mean "one or more" or "at least one," unless otherwise indicated. That is, the reference to any element or component of the invention by the indefinite article "a" or "an" acknowledges the possibility that more than one element or component may be present. It is not something to be excluded.

[0021] As used herein, the term "about" refers to plus or minus 10% of the referenced numerical designation.

[0022] The method of the present invention comprises reacting O,O-dimethyldithiophosphoric acid (O,O-DMDTPA) with maleic acid in the presence of an acid. The process involves reacting the aldehyde with an acid, which acts as a catalyst, resulting in a shorter reaction time and improved yields, as well as fewer impurities. This efficient approach is also environmentally friendly with low production costs.

[0023] The initial mixing of the reactants may be controlled at a temperature, for example, of about 25° C. or less, about 20° C. or less, about 15° C. or less. It is possible.

[0024] After all reactants are mixed, the temperature can be raised to, for example, about 20 to about 50° C., about 35 to about 45° C., or about 35 to about 40° C. In embodiments, the total reaction time is generally less than about 15 hours, less than about 12 hours, less than about 10 hours, less than about 8 hours, less than about 7 hours, less than about 6 hours, or less than about 12 hours. or less than about 5 hours.

[0025] In an embodiment, the method includes combining O,O-dimethyldithiophosphoric acid (O,O-DMDTPA) with an acid to form a mixture; and adding diethyl maleate to the mixture.

[0026] The diethyl maleate can be added in portions to the mixture at controlled temperatures to minimize the formation of by-products without impairing the efficiency of the reaction. For example, the diethyl maleate can be added dropwise to the mixture at temperatures between 10-25°C, 15-20°C, or 1-20°C. The rate of addition and temperature are adjusted to allow the reaction to proceed without excessive accumulation of unreacted diethyl maleate.

[0027] After the addition of diethyl maleate, the reaction mixture can be warmed to a temperature of about 50, about 45, about 40, or about 35° C. The reaction can be continued for about 3 hours to about 12 hours, about 5 hours to about 12 hours, about 3 hours to about 10 hours, about 4 hours to about 6 hours, about 5 hours to about 10 hours, about 6 hours to about 8 hours, The treatment lasts for approximately 6 to 7 hours.

[0028] In embodiments, the temperature can be increased in stages, for example, first to about 20°C or about 25°C and then maintained at about 40°C.

[0029] The amount of acid ranges from about 0.1% to about 20% by weight of the mixture in step (a). In some embodiments, the amount of acid in the mixture is from about 0.5% to about 10%, from about 1% to about 10%, from about 3% to about 10%, or from about 2% to about 20%. from about 5% to about 10%, from about 3% to about 8%, or from about 4% to about 8%.

[0030] The acid can be, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, acetic acid, trifluoroacetic acid, or any combination thereof. In an embodiment, the acid is hydrochloric acid having a concentration of about 20%, about 25%, about 30%, or about 35% by weight. In an embodiment, the acid is saturated hydrochloric acid. In an embodiment, the acid is hydrochloric acid gas, which is introduced into the mixture, for example, by bubbling. In an embodiment, the acid is essentially saturated hydrochloric acid. Prior to adding diethyl maleate, the mixture can be cooled, for example, to a temperature of about 10 to about 20° C., or about 10 to about 15° C.

[0031] To ensure complete reaction of O,O-DMDTPA, the molar ratio between O,O-DMDTPA and diethyl maleate can be controlled, for example, from about 1:1.2 to about 1:1. In embodiments, the molar ratio between O,O-DMDTPA and diethyl maleate is from about 1:1.1 to about 1:1.01, from about 1:1.05 to about 1:1.01. , or in the range of 1:1.03 to about 1:1.01.

[0032] Isolating the product may involve removing impurities and / or purifying malathion. For example, the malathion prepared by the above process may be washed with water or an aqueous solution to reduce the level of impurities. In an embodiment, the crude product is treated with a sulfur solution. In an embodiment, a pH of less than about 7 is used to eliminate the formation of a dimer impurity. A sulfur solution having a pH of about 6.0 to about 7.0 is effective. In the examples, malathion is crystallized from a suitable solvent such as methanol to improve purity.

[0033] The organic phase contains the malathion product. Additional organic solvent may be used if desired. The organic phase is MP-1-S (phosphonothioic acid, O,O-dimethyl ester). Distillation may be performed to remove impurities including esters, MOOOPS (phosphonothioic acid, O,O,O-trimethyl esters), ME (diethyl maleate), FE (diethyl fumarate), MOSSPO and MOOSPS (phosphonodithioic acid, O,O,S-trimethyl esters). In this case, wiped-film stills (WFS) are applied to remove impurities.

[0034] Malathion obtained by the present invention has much fewer impurities than conventional methods, in embodiments, the impurity of O,O-DMDTPA is about 0.65% or less, about 0.55% or less, about 0.5% or less, about 0.45% or less, about 0.4% or less, about 0.35% or less, about 0.3% or less, about 0.25% or less, about 0.15% or less, or about 0.1% or less by weight.

[0035] The methods of the present invention achieve much higher yields of malathion than conventional methods, in embodiments, the yield is about 80% or greater, about 85% or greater, about 90% or greater, or about 95% or greater.

[0036] Since diethyl maleate is insoluble in the aqueous phase, mixing of the reactants is necessary to facilitate the reaction. For example, mechanical shaking, stirring, or any type of agitation can be applied to facilitate mixing of the reactants. In an embodiment, an inert organic solvent can be added to the reaction mixture to facilitate mixing of the reactants. EXAMPLES

[0037] An environmentally friendly method for producing malathion [ka]

[0038] MP-1 (45.1 g) and concentrated hydrochloric acid (2.5 g) were weighed and added in sequence to a 0.5 L jacketed reactor. The temperature was adjusted to 10-15°C. Diethyl maleate (50.0 g) was added dropwise while maintaining the temperature at 15-20°C. After the addition, the reaction was controlled at 20°C for 1.0 hour under constant stirring. The temperature was then raised to 40°C and maintained for 7 hours.

[0039] Samples were taken and the conversion GC-FID (MP-1 ≦ 0.5 A %) was checked periodically. After it was judged that the extract could be obtained, the temperature was increased to 30°C and water was added (25.0 g). The organic phase was distilled on a water-filled paper to remove impurities such as MP-1-S, MOOOPS, ME, FE, MOSSPO, and MOOSPS. The yield of malathion was 87.2 g (98% wt).

[0040] Summary of the effects of hydrochloric acid on reactions [Table 1]

[0041] It will be understood by those skilled in the art that numerous and various modifications can be made without departing from the spirit of the present invention. Therefore, it should be understood that the various embodiments described herein are merely illustrative and are not intended to limit the scope of the present invention.

Claims

1. A method for producing malathion, comprising reacting O,O-dimethyldithiophosphoric acid (O,O-DMDTPA) with diethyl maleate in the presence of an acid.

2. The method according to claim 1, further comprising the steps of: a) mixing O,O-dimethyldithiophosphoric acid (O,O-DMDTPA) with an acid to form a mixture; and b) adding diethyl maleate to the mixture.

3. The process according to claim 2, wherein the temperature of step (a) is controlled at about 5 to about 20°C.

4. The method according to claim 2, wherein the temperature of the step (b) is controlled at about 10 to about 25° C. Manufacturing method.

5. The process of claim 2, wherein the temperature is controlled at about 20 to about 50° C. after the addition of diethyl maleate to the mixture is completed.

6. The process of claim 2, wherein the temperature is controlled at about 35 to about 45° C. after the addition of diethyl maleate is complete.

7. 2. The method of claim 1, wherein the acid is in the range of about 0.1% to about 20% by weight in the mixture of step (a).

8. 2. The process of claim 1, wherein the acid is present in the mixture of step (a) in a range of about 1% to about 10% by weight.

9. The process according to claim 1, wherein the acid is hydrochloric acid or sulfuric acid.

10. 2. The method of claim 1, wherein the acid is hydrochloric acid having a concentration of about 20% to about 37% by weight, or sulfuric acid having a concentration of about 70% to about 98% by weight.

11. 2. The process according to claim 1, characterized in that the acid is essentially saturated hydrochloric acid.

12. The process of claim 1, wherein the molar ratio of O,O-DMDTPA to diethyl maleate is from about 1:1.2 to about 1:

1.

13. 2. The process of claim 1, wherein the molar ratio between O,O-DMDTPA and diethyl maleate ranges from about 1:1.1 to about 1:1.

02.

14. The process according to claim 1, wherein the reaction between diethyl maleate and O,O-DMDTPA is initiated by contact of the two.

15. 10. The process of claim 1, wherein the reaction of diethyl maleate with O,O-DMDTPA continues for less than about 10 hours.

16. 10. The method of claim 1, wherein the reaction of diethyl maleate with O,O-DMDTPA continues for less than about 8 hours.

17. The process of claim 1, further comprising washing with water or an aqueous solution after the reaction.

18. The method of claim 1, further comprising removing by-products after the reaction by wiped film still (WFS).

19. 10. The method of claim 1, further comprising isolating the malathion, wherein the isolated malathion has less than about 0.55% by weight of impurities including O,O-DMTPA.

20. 10. The method of claim 1, further comprising isolating the malathion, wherein the isolated malathion has less than about 0.35% by weight of impurities including O,O-DMTPA.

21. 2. The process of claim 1, wherein the yield of malathion is about 90% or greater.

22. 2. The process of claim 1, wherein the yield of malathion reaches about 90% or more in a reaction time of less than about 7 hours.

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