Process for preparing thiophosphoryl chloride and acephate

Abstract

The present invention discloses an improved process for the preparation of acephate and its intermediates. More specifically, the present invention relates to a process for preparing thiophosphoryl chloride, which is useful in the commercial production of pesticides and pharmaceutically active compounds.

Description

[Technical Field]

[0001] The present invention relates to an improved process for the preparation of acephate and its intermediates. More specifically, the present invention relates to a process for preparing thiophosphoryl chloride, which is useful in the commercial production of pesticides and pharmaceutically active compounds. [Background technology]

[0002] Phosphoramidothioates are known for their excellent insecticidal activity against a variety of insects in a variety of environments. Acephate, a systemic insecticide, is one of the widely used phosphoramidothioates for controlling a wide range of chewing and sap-sucking insects, such as aphids, thrips, lepidopteran larvae, sawflies, leafminers, leafhoppers, and cutworms, in fruit (including citrus fruits), vines, hops, olives, cotton, soybeans, peanuts, macadamia nuts, beets, brassicas, celery, beans, potatoes, rice, tobacco, ornamentals, forestry, and other crops.

[0003] Thiophosporyl chloride is a useful starting material for the synthesis of organophosphorus compounds in the agrochemical industry.

[0004] German Patent No. 1145589 discloses that thiophosphoryl chloride can be obtained, either alone or together with a halogen, by treating phosphorus trichloride and sulfur with aluminum or its alloys in the liquid phase at atmospheric pressure. Similar processes using metal halides as catalysts are disclosed in the patent literature (U.S. Pat. Nos. 2715561, 2850354, and 2850354).

[0005] U.S. Patent No. 5,464,600 discloses a process for preparing thiophosphoryl chloride by reacting phosphorus trichloride with sulfur in the presence of a tertiary amine catalyst. The improvement in this process is the use of a tertiary amine (aromatic or aliphatic) as the catalyst. The tertiary amine is selected from the group consisting of 5-ethyl-2-methylpyridine, 2-methylpyridine, 2,4-dimethylpyridine, 2,6-dimethylpyridine, 2,4,6-trimethylpyridine, tri-n-propylamine, tri-n-butylamine, tris-[2-(2-methoxyethoxy)ethyl]amine, and 1,8-diazabicyclo[5.4.0]undec-7-ene. As described in the examples, the reaction mixture was cooked for 9 hours (via 5-ethyl-2-methylpyridine), or 14 hours (via 2,6-lutidine), or 3 hours 44 minutes (via tributylamine), or 19 hours 17 minutes (via N,N-dimethylaniline), or 15 hours 6 minutes (via 1,8-diazabicyclo[5.4.0.]undec-7-ene (DBU)).

[0006] U.S. Patent No. 6,251,350 discloses a process for preparing thiophosphoryl chloride by reacting phosphorus trichloride with sulfur in the presence of a catalytic amount of a tertiary amine and substantially in the presence of a catalytic amount of a nitrogen oxide free radical. The nitroso free radical is 2,2,6,6-tetramethyl-1-piperidinyloxy ("TEMPO"). Example 1 of this patent discloses a reaction carried out in the presence of a tertiary amine and TEMPO for about 2 hours and 8 minutes to produce thiophosphoryl chloride.

[0007] Activated carbon, commonly used as a solid-phase catalyst, has been observed to promote the thiolation reaction and result in quantitative conversion. However, this catalytic method is associated with numerous problems during use and commercial production. During product isolation by distillation, the catalyst is carried over, resulting in poor product appearance, such as blackening of the product. Other practical issues that can be immediately cited include foaming problems in the reactor pot / heel and flooding of the column with solid catalyst, resulting in catalyst depletion. This drawback, followed by efficient recycling, removal, and disposal of this highly corrosive, two-phase, highly viscous slurry mass of the heel and retained catalyst, is often a major effluent concern and safety hazard for disposal. Therefore, this process is not industrially viable and is not suitable for scale-up.

[0008] Therefore, there is a need to develop a simple, cost-effective, rapid and commercially viable process for the commercial-scale preparation of thiophosphoryl chloride, which is used as an intermediate for preparing organophosphorus compounds in the agrochemical industry. The present invention therefore provides an industrially viable and cost-effective process for the large-scale preparation of acephate and its intermediate thiophosphoryl chloride. Summary of the Invention

[0009] In one aspect, the present invention provides a commercial and rapid process for the preparation of thiophosphoryl chloride.

[0010] In another aspect, the present invention provides a continuous process for preparing thiophosphoryl chloride in high yield and purity.

[0011] In another aspect, the present invention provides a simple and time-saving commercial process for preparing acephate using thiophosphoryl chloride prepared according to the present invention.

[0012] In another aspect, the present invention provides a commercial process for preparing the intermediate thiophosphoryl chloride used in the preparation of acephate.

[0013] In another aspect, the present invention provides a continuous process for preparing acephate.

[0014] The aspects, advantageous features and preferred embodiments of the present invention summarized below, each alone or in combination, contribute to achieving this and other objects of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0015] The details set forth herein are merely by way of example and for purposes of illustrative discussion of various embodiments of the present invention, and are presented to provide what is believed to be the most useful and readily understood explanation of the principles and conceptual aspects of the present invention. In this regard, no attempt is made to show the details of the present invention in more detail than is necessary for a fundamental understanding of the invention, and the description will make clear to those skilled in the art how several forms of the present invention may be embodied in practice.

[0016] The present invention will now be described with reference to more detailed embodiments. However, the present invention may be embodied in different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.

[0017] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terms used herein in describing the present invention are for the purpose of describing particular embodiments only and are not intended to limit the present invention. When used in the description of the present invention and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. All publications, patent applications, patents, and other references mentioned herein are expressly incorporated by reference in their entirety.

[0018] Accordingly, co-pending Indian Patent Application No. 202021004454, entitled "A continuous flow process for preparation of Acephate and its intermediates," is hereby incorporated by reference in its entirety to the same extent as if such publication, patent, or patent application were specifically indicated to be incorporated by reference herein. The contents of this patent application and its publication are incorporated herein by reference.

[0019] Unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as modified in all instances by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and appended claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, there should be no attempt to limit the application of the doctrine of equivalents to the scope of the claims, and each numerical parameter should be construed in light of the number of significant digits and ordinary rounding approaches.

[0020] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values ​​set forth in the specific examples are reported as precisely as possible. However, any numerical value inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Every numerical range given throughout this specification includes every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly written herein.

[0021] Additional advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed.

[0022] Surprisingly, the improved process for preparing thiophosphoryl chloride as disclosed herein provides a scalable method that efficiently produces high quality product in reproducible yields, can safely handle large-scale production, and is lower cost.

[0023] The present invention provides an efficient, effective, and safe process for preparing the thiophosphoryl chlorides described herein.

[0024] In one aspect, the present invention provides a process for preparing thiophosphoryl chloride, comprising the reaction of phosphorus trichloride with sulfur in the presence of a catalytic amount of a base in thiophosphoryl chloride.

[0025] In one embodiment, the process involves the reaction of phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of a base, the reaction being carried out at a temperature in the range of 100-150°C.

[0026] In one embodiment, the process is well balanced, sufficient to ensure rapid conversion to the desired product and short heating times.

[0027] Surprisingly, it has been found that when the reaction is carried out in thiophosphoryl chloride in the presence of a base, the reaction time can be substantially and significantly reduced. Without wishing to be bound by theory, the inventors believe that the starting thiophosphoryl chloride acts as an autosolvent to bring together the reaction components, facilitating the reaction in the presence of a catalytic base and significantly reducing the reaction time.

[0028] The present invention therefore relates to a process for preparing thiophosphoryl chloride which comprises reacting phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of a base.

[0029] In one embodiment, the reaction of phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of a catalytic base is carried out in a time period of less than 60 minutes.

[0030] In one embodiment, the reaction is heated for 20 to 60 minutes to yield thiophosphoryl chloride.

[0031] In one embodiment, the reaction of phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of a base is carried out for 20 minutes.

[0032] In one embodiment, the reaction of phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of a base is carried out for 30 minutes.

[0033] In one embodiment, the reaction of phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of a base is carried out for 40 minutes.

[0034] In one embodiment, the reaction of phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of a base is carried out for 60 minutes.

[0035] In one embodiment, the catalyst is an alkylamine, preferably a trialkylamine.

[0036] In one embodiment, the catalyst is tributylamine.

[0037] In one embodiment, the catalyst is used in an amount ranging from 0.01 to 0.08 mole fraction relative to the initial charge of phosphorus trichloride.

[0038] In one embodiment, the molar ratio of phosphorus trichloride to sulfur is about 1:1.

[0039] In one embodiment, the reaction of phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of a base is carried out at a temperature in the range of 100-150°C.

[0040] In one embodiment, the reaction of phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of a base is carried out at a temperature in the range of 110-130°C.

[0041] In one embodiment, the reaction of phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of a base is carried out at atmospheric pressure.

[0042] In one embodiment, the phosphorus trichloride and sulfur are reacted in an equivalent ratio.

[0043] In one embodiment, the reaction of phosphorus trichloride with sulfur is carried out in the presence of catalytic amounts of base and thiophosphoryl chloride for a time period of less than 60 minutes to give the desired product.

[0044] In accordance with the present invention, a reaction scheme illustrating a method for synthesizing thiophosphoryl chloride is depicted below:

[0045] [ka]

[0046] In one embodiment, the catalyst is a base. The base is a trialkylamine.

[0047] In one embodiment, the base is tributylamine and is used in an amount ranging from 0.01 to 0.08 mole fraction relative to phosphorus trichloride.

[0048] In one embodiment, the desired product is PSCl3, which is obtained in high yield and purity.

[0049] According to the present invention, the product yield is stabilized at 93-95% after 5-7 times recycling of the residue.

[0050] Therefore, the product PSCl3 obtained according to the present invention has a purity of more than 95%.

[0051] The product PSCl3 obtained according to the present invention has a purity of at least 98%.

[0052] The product PSCl3 obtained according to the present invention has a purity of at least 99%.

[0053] In one embodiment, the process further comprises distilling off thiophosphoryl chloride (PSCl) from the reaction mixture to leave an undistilled residue, referred to as "HEEL," which is recycled in subsequent batches. Typically, the residue is an undistilled residue / fluid comprising thiophosphoryl chloride and catalyst.

[0054] In one embodiment, the process comprises distilling pure thiophosphoryl chloride from the reaction mixture to leave a distillation residue.

[0055] In one embodiment, the process further comprises recycling the distillation residue to a subsequent batch.

[0056] In one embodiment, the process is carried out for at least 20-50 cycles.

[0057] In one embodiment, the process is carried out for more than 50 cycles.

[0058] In one embodiment, the process is carried out for about 20-30 cycles.

[0059] In one embodiment, the process may be carried out in either a batch or semi-continuous mode of operation.

[0060] In one embodiment, the process further comprises continuously recycling the distillation residue to the reaction step of phosphorus trichloride with sulfur to produce thiophosphoryl chloride.

[0061] According to the present invention, the process is well suited to either batch or continuous operation, in which the distillation residue is continuously recycled to the primary reactor stage where sulfur reacts with phosphorus trichloride, and this recycling can be effectively continued for about 20-50 cycles or more.

[0062] Typically, phosphorus trichloride is treated with sulfur in a solvent containing thiophosphoryl chloride, which holds the catalyst, or in the undistilled residue HEEL in the distillation pot. After completion of the reaction, the mixture is subjected to distillation, thereby separating the product in high yield and purity.

[0063] Typically, the reaction mixture is distilled to recover two product streams: Distillate-1, which is recycled to the residue, and Distillate-2, which contains thiophosphoryl chloride. Distillate-1, obtained during distillation of the reaction product, which mainly contains thiophosphoryl chloride, accounts for approximately 95-98% and is used as a reaction moderator for the continuous production of acephate.

[0064] The system is well balanced and the boiling range of the four component reaction mixture is high enough to ensure rapid conversion and consequently short heating times.

[0065] Advantages of the process of the present invention: i) The entire process is a single-phase reaction. ii) No foaming is observed in the reaction product during the reaction or workup. iii) Low vapor temperature during thiophosphoryl chloride recovery. iv) Easy and safe commercial disposal of HEEL after sufficient recycling. v) The quality of the product is greater than 98% as a colorless liquid (free of foreign matter). vi) The product yield is high at 93-95% after 5-7 reuses of HEEL. vii) The catalyst retained in the HEEL is available for subsequent reuse batches; additional charging may be required only after 50 cycles. Catalyst depletion is evident by the increased heating time required to complete the reaction. viii) Semi-continuous production system with reversal between fresh charges of Phosphorus Trichloride; Sulfur and catalyst (if required) for HEEL under nitrogen blanket; Heat-up time (30-60 mins) and distillation of two streams (HEEL as product & Distillate-1 for recycle to Thiophosphoryl Chloride). ix) After sufficient reuse (greater than 50 times), it has been observed that the HEEL is easily removed into a drum for disposal. Finally, the HEEL may be treated with aqueous caustic solution and scrubbed of off-gas for disposal. x) The improvement involves the use of a high boiler reaction medium with a liquid phase basic amine as a catalyst, which results in high quality and high yield products, ease of operation, high throughput, industrial hygiene and safety, and easy removal and disposal of residues after sufficient recycling. xi) The use of co-catalysts such as TEMPO is avoided to avoid harmful free radical side reactions. xii) There is a significant decrease in reaction time to completion.

[0066] In another aspect, the present invention provides a process for producing the insecticide, acephate (N-(methoxy-methylsulfanylphosphoryl)acetamide) and its intermediates.

[0067] In one embodiment, the present invention provides a process for preparing acephate, comprising reacting phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of a base to obtain thiophosphoryl chloride.

[0068] In one embodiment, the present invention provides a process for preparing acephate, comprising: 1) preparing thiophosphoryl chloride by reacting phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of a catalytic amount of base; 2) preparing O-methyl phosphorodichloridothioate (monoester) using thiophosphoryl chloride from step (1); 3) preparing O,O-dimethyl phosphorochloridothioate (diester) using the monoester of step (2); 4) preparing O,O-dimethylphosphoramidothioate (DMPAT) using the diester of step (3); and 5) Preparing acephate using DMPAT from step (4).

[0069] The process described in step 4) involves treating DMPAT with a catalytic alkyl sulfate, such as dimethyl sulfate, to form methamidophos, which is subjected to an acetylation reaction using acetic anhydride to form N-(methoxy-methylsulfanylphosphoryl)acetamide.

[0070] Thus, in one embodiment, the process for preparing acephate comprises the reaction of phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of tributylamine catalyst to give thiophosphoryl chloride in high yield and purity.

[0071] In one embodiment, the reaction of phosphorus trichloride with sulfur in thiophosphoryl chloride is carried out at a temperature in the range of 100-150°C.

[0072] In one embodiment, the process for preparing acephate is characterized by the reaction of phosphorus trichloride in thiophosphoryl chloride with sulfur in the presence of tributylamine catalyst at a temperature in the range of 120-150°C for less than about 60 minutes to obtain thiophosphoryl chloride in high yield and purity.

[0073] In accordance with the present invention, a reaction scheme illustrating a method for synthesizing acephate is depicted as follows:

[0074] [ka]

[0075] In one aspect, the present invention provides a process for preparing acephate, comprising: a) preparing thiophosphoryl chloride; b) Conversion of thiophosphoryl chloride to acephate.

[0076] In one embodiment, step a) comprises treating phosphorus trichloride, thiophosphoryl chloride, and sulfur in the presence of a tributylamine catalyst to obtain thiophosphoryl chloride.

[0077] In one embodiment, the process further comprises distilling pure thiophosphoryl chloride from the reaction mixture to leave a distillation residue.

[0078] In one embodiment, the process further comprises recycling the distillation residue to a subsequent reaction step with phosphorus trichloride and sulfur to produce thiophosphoryl chloride.

[0079] In one embodiment, the converting in step b) comprises at least one step selected from the following: (i) treatment of thiophosphoryl chloride with methanol to give O-methyl phosphorodichloridothioate; (ii) treating O-methyl phosphorodichloridothioate with methanol to give O,O-dimethyl phosphorochloridothioate; or (iii) Treatment of O,O-dimethyl phosphorochloridothioate with base to give O,O-dimethyl phosphoramidothioate.

[0080] In one embodiment, the process further comprises acetylating O,O-dimethylphosphoramidothioate in the presence of acetic anhydride to obtain acephate.

[0081] In one embodiment, the process for preparing acephate comprises: a) reacting phosphorus trichloride with thiophosphoryl chloride and sulfur in the presence of a tributylamine catalyst to obtain thiophosphoryl chloride; and b) Preparing acephate using thiophosphoryl chloride prepared in step (a).

[0082] In one embodiment, the process for preparing acephate comprises: a) reacting phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of tributylamine catalyst to obtain thiophosphoryl chloride; and b) reacting thiophosphoryl chloride with methanol to prepare O-methyl phosphorodichlorodithioate (monoester); and c) Preparing acephate using O-methyl phosphorodichlorodithioate (monoester) prepared in step (b).

[0083] In one embodiment, thiophosphoryl chloride is reacted with methanol in continuous mode.

[0084] In one embodiment, thiophosphoryl chloride is reacted with methanol in batch mode.

[0085] In one embodiment, other alcohols, preferably lower alcohols, may also be used in place of methanol.

[0086] In one embodiment, the process for preparing acephate comprises: a) reacting phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of tributylamine catalyst to obtain thiophosphoryl chloride; and b) reacting thiophosphoryl chloride with methanol to prepare O-methyl phosphorodichlorodithioate (monoester); and c) reacting O-methyl phosphorodichlorodithioate (monoester) with methanol to prepare O,O-dimethyl phosphorochlorodithioate; and d) Preparing acephate using O,O-dimethyl phosphorochlorodithioate prepared in step (c).

[0087] In one embodiment, the step of reacting O-methyl phosphorodichlorodithioate (monoester) with methanol to prepare O,O-dimethyl phosphorochlorodithioate is carried out for 1 to 5 hours, preferably 2 to 3 hours.

[0088] In one embodiment, the process for preparing acephate comprises: a) reacting phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of tributylamine catalyst to obtain thiophosphoryl chloride; and b) reacting thiophosphoryl chloride with methanol to prepare O-methyl phosphorodichlorodithioate (monoester); and c) reacting O-methyl phosphorodichlorodithioate (monoester) with methanol to prepare O,O-dimethyl phosphorochlorodithioate (diester); d) reacting the diester with ammonium hydroxide and sodium hydroxide to produce DMPAT (O,O-dimethylphosphoramidothioate); and e) Preparing Acephate using the DMPAT produced in step (d).

[0089] In one embodiment, to prepare acephate, DMPAT is subjected to an acetylation reaction.

[0090] In one embodiment, the process for preparing acephate comprises: a) reacting phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of tributylamine catalyst to obtain thiophosphoryl chloride; and b) reacting thiophosphoryl chloride with methanol to prepare O-methyl phosphorodichlorodithioate (monoester); and c) reacting O-methyl phosphorodichlorodithioate (monoester) with methanol to prepare O,O-dimethyl phosphorochlorodithioate (diester); d) reacting the diester with ammonium hydroxide and sodium hydroxide to produce DMPAT (O,O-dimethylphosphoramidothioate); and e) Preparation of acephate by isomerization of DMPAT with alkyl sulfate followed by acetylation reaction.

[0091] The reaction products obtained in the above steps may be isolated or separated from the reaction or carried on to the next step without further treatment by techniques known to those skilled in the art. Thus, the compounds described herein may be recovered from the reaction mixture and purified in a conventional manner.

[0092] The above-described process may proceed by isolating the product of each step, or may proceed as a continuous process without isolating the product of each step.

[0093] In one embodiment, the process for preparing acephate comprises treating phosphorus trichloride and sulfur in thiophosphoryl chloride in the presence of tributylamine catalyst to obtain thiophosphoryl chloride, which is further converted to acephate.

[0094] The process of the present invention provides thiophosphoryl chloride with a purity of at least 95%, preferably at least 99%.

[0095] In one embodiment, the present invention provides the conversion of a thiophosphoryl chloride described herein to an acephate described herein by the process steps described. In one embodiment, the conversion of a thiophosphoryl chloride to an acephate comprises the following steps: Step 1: Preparation of thiophosphoryl chloride. Step 2: Preparation of O-methyl phosphorodichloridothioate (monoester). Step 3: Preparation of O,O-dimethyl phosphorochloridothioate (diester). Step 4: Preparation of O,O-dimethylphosphoramidothioate (DMPAT); and Step 5: Preparation of acephate.

[0096] The sequence of steps outlined above can be integrated into an overall scheme for the production of acephate. Such an integrated process generally consists of the following steps under suitable reaction conditions as described herein: Step 1: The first step is the formation of thiophosphoryl chloride by treating thiophosphoryl chloride with phosphorus trichloride and sulfur in the presence of an alkylamine, such as tributylamine catalyst.

[0097] In one embodiment, the reaction is carried out at a temperature in the range of 100-150 degrees for about 60 minutes, preferably 30-40 minutes.

[0098] In one embodiment, alkylamines such as triethylamine, n-propylamine, tri-n-butylamine, diisopropylethylamine, and the like can also be used.

[0099] Step 2: In this step, O-methyl phosphorodichloridothioate is prepared by treating thiophosphoryl chloride with methanol at a low temperature of -10 to 0°C for about 1 to 5 hours.

[0100] Step 3: In this step, O-methyl phosphorodichloridothioate is treated with methanol in the presence of a base at a temperature of −10 to 0° C. for about 1 to 5 hours to give O,O-dimethyl phosphorochloridothioate (diester).

[0101] The base is selected from the group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, or mixtures thereof.

[0102] Step 4: In this step, the O,O-dimethyl phosphorochloridothioate (diester) obtained in step 3 is treated with ammonium hydroxide to obtain DMPAT. The reaction is preferably carried out at a temperature in the range of 20-30°C for 1-3 hours in the presence of a base, the base being selected from the group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, or a mixture thereof. The DMPAT thus obtained is isolated from the mixture by extraction with a suitable solvent such as methylene chloride.

[0103] Step 5: In this step, DMPAT is isomerized with an alkyl sulfate, such as dimethyl sulfate, to form methamidophos. The reaction is carried out in a suitable solvent, such as methylene dichloride, at a temperature ranging from 30 to 50°C for 2 to 5 hours. The reaction mixture containing methamidophos in the solvent is then used for its conversion to acephate by acetylation. The acetylation reaction is carried out using acetic anhydride and a suitable acid, such as sulfuric acid, to obtain the desired product, acephate, in high yield and purity. The acetylation is carried out at a temperature ranging from 30 to 50°C for 2 to 5 hours. The final product, acephate, thus obtained can be crystallized using a suitable solvent, such as ethyl acetate or methylene dichloride.

[0104] Advantageously, the process for preparing acephate comprises treating phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of tributylamine catalyst to obtain thiophosphoryl chloride in less than 60 minutes, which is further converted to acephate by the process described herein or conventional manner understood by one skilled in the art.

[0105] The process scheme of the present invention advantageously increases the yield and purity of the final product.

[0106] The overall scheme for the production of acephate according to the present invention is rapid, simple, inexpensive, robust, fast, e.g., short cycle time, and commercially and industrially feasible.

[0107] The present invention will now be described in more detail with reference to the following examples, which should not be construed as limiting the scope of the disclosure in any way, as these examples and other equivalents will be apparent to those skilled in the art in light of this disclosure. Those skilled in the art will appreciate that the general synthetic routes above show general reactions for varying the starting materials as necessary. Specific reactions not provided are known to those skilled in the art, and suitable conditions for such reactions are well known to those skilled in the art and are considered to be within the general knowledge of those skilled in the art. [Example]

[0108] Example 1 Preparation of thiophosphoryl chloride according to the present invention Sulfur (2.53 moles, 81 g) and thiophosphoryl chloride (450 g) were added to a 1 L four-neck round-bottom flask equipped with an overhead stirrer, a reaction mass temperature sensor, and an oil bath with a temperature sensor; a vapor temperature condenser cooled to 0°C, a nitrogen blanket, an adapter and collection flask, and a 5-10% caustic scrubber to quench the off-gassing. Tributylamine (5 g) was then added to the flask. The reaction mixture was gradually heated to reflux with continuous stirring. Phosphoryl trichloride (2.54 moles, 350 g) was added dropwise to the mixture. The reaction was monitored by the mass temperature sensor and gradually reached a constant temperature of 130°C. After reaching a stable mass temperature of 130°C, heating was continued for approximately 1 hour. After confirming that more than 95% of the phosphorus trichloride had been converted, the reaction mixture was subjected to atmospheric distillation. The first fraction of phosphoryl trichloride (Distillate-1, precursor fraction of the reaction mass: about 5%; 45-50 g) was collected, and then the main product stream of thiophosphoryl chloride (400-405 g) was collected as Distillate-2 with a purity of more than 98%. The residue remaining at the bottom of the reactor (Residue, 430 g) was used for subsequent recycle batches.

[0109] In subsequent recycle batches, Distillate-1 from the previous batch was mixed with the residue in the reaction flask as a solvent / reaction moderator, and sulfur and phosphorus trichloride were charged in the same manner as above to initiate the reaction. The reaction mass was heated at 130°C for 1 hour after addition and monitored by GC for reaction completion and distillation.

[0110] The details of the reaction experiments are given in Table 1 below.

[0111] [Table 1]

[0112] Table 2 shows the results of the reactions.

[0113] [Table 2]

[0114] Example 2 Thiophosphoryl chloride (430 g), tributylamine (9 g, 0.048 mol), and sulfur (90 g, 2.81 mol) were added to a 1-liter four-neck kettle equipped with an addition funnel, a TP, a reflux distributor, and a condenser, and the reaction mass was gradually heated to 120°C. Phosphorus chloride (350 g, 2.55 mol) was added at reflux and further heated at this temperature for 30 minutes. The progress of the reaction was monitored by GC chromatography. The reaction mass was then subjected to atmospheric distillation. Unreacted phosphorus chloride was distilled in a first fraction, and the product thiophosphoryl chloride was distilled in a second fraction at a temperature range of 120-125°C. The remaining residue (Heel residue) containing thiophosphoryl and tributylamine remaining in the mixture was used directly in the next recycling reaction as provided in Example 1. The distilled product was analyzed as thiophosphoryl chloride (429.5 g, 99.6%).

[0115] Example 3 Under the same procedure as described in Example 2, except that the product thiophosphoryl chloride is directly distilled by extending the heating time by 30 minutes, avoiding the first distillate, to give thiophosphoryl chloride (429.4 g, 99.5%).

[0116] Example 4 Thiophosphoryl chloride (6,330 kg) and tributylamine (300 kg) were added to the reactor, and the temperature of the reaction mass was gradually increased to 120°C. Molten sulfur (2,083 kg) and phosphorus chloride (8,495 kg) were added to the reactor at reflux conditions and further heated at this temperature for 40 minutes. The progress of the reaction was monitored by GC chromatography. The reaction mass was then subjected to atmospheric distillation. Unreacted phosphorus chloride was distilled in a first fraction, and the product thiophosphoryl chloride (10,469 kg, 99.7%) was recovered in a second fraction in the temperature range of 120-127°C. The remaining residue containing thiophosphoryl and tributylamine remaining in the reactor was retained for reuse in the batch reaction.

[0117] Example 5 A similar procedure to that described in Example 5 was carried out, except that the product thiophosphoryl chloride was distilled directly by extending the heating time to 90 minutes, avoiding the first distillate, to give thiophosphoryl chloride (10,470 kg, 99.5%).

[0118] Example 6 In a 1-liter, four-necked kettle equipped with an addition funnel, reflux distributor, and condenser, thiophosphoryl chloride (430 g), tributylamine (9 g, 0.048 mol), and sulfur (90 g, 2.81 mol) were added, and the reaction mass was gradually heated to 120°C in 30 minutes. 350 g (2.55 mol) of phosphorus chloride was added at reflux and further heated at this temperature for 45 minutes. The progress of the reaction was monitored by GC chromatography. The reaction mass was then subjected to atmospheric distillation. Unreacted phosphorus chloride was distilled as the first fraction, and the product was distilled in the temperature range of 120-125°C to obtain thiophosphoryl chloride (429.5 g, 99.6%). The remaining residue containing thiophosphoryl and tributylamine was retained for recycle.

[0119] Example 7 Comparative Example 1: Synthesis of thiophosphoryl chloride Thiophosphoryl chloride (430 g) was added as a residue to a 1-liter, four-necked kettle equipped with an addition funnel, a TP, a reflux distributor, and a condenser. Activated carbon (10.5 g) and sulfur (90 g, 2.81 mol) were charged to the kettle, and the reaction mass was gradually heated to 120 °C. Phosphorus chloride (350 g, 2.55 mol) was added at reflux and further heated at this temperature for 60 minutes. The progress of the reaction was monitored by GC chromatography. The reaction mass was then subjected to atmospheric distillation. Unreacted phosphorus chloride was distilled as the first fraction, and the product was distilled as the second fraction in the temperature range of 120-125 °C to obtain thiophosphoryl chloride. Thiophosphoryl chloride was obtained as a black color. Foaming during the addition of PCl3 and distillation of the product were also observed.

[0120] Comparative Example 2: Synthesis of thiophosphoryl chloride To a 1-liter, four-necked kettle equipped with an addition funnel, a temperature regulator, a reflux distributor, and a condenser, 350 g (2.55 mol) of phosphorus chloride and sulfur (90 g, 2.81 mol) were added. The addition of tributylamine (9 g, 0.048 mol) produced a slight exotherm, and the reaction mass was gradually heated to 120°C in 90 minutes and further heated at this temperature for 240 minutes to complete the reaction. The progress of the reaction was monitored by GC chromatography. The reaction mass was subjected to atmospheric distillation. Unreacted phosphorus chloride was distilled as the first fraction, and the product thiophosphoryl chloride was distilled as the main fraction in the temperature range of 120-125°C to obtain thiophosphoryl chloride (429 g). The reaction time was significantly longer and therefore not commercially viable.

[0121] Example 8 Industrial process for preparing acephate according to the present invention: Step 1 - Preparation of Thiophoshporyl chloride: Thiophosphoryl chloride (6.33 × 10 3Kg) was added to the reactor. Tributylamine (0.3×10 3 Kg) was added to the reactor and the reaction mass was gradually heated to 120°C. Then, molten sulfur (2.083 x 10 3 Kg) was added to the reactor, and phosphorus chloride (8.495 x 10 3 Addition of 10.47×10 Kg of thiophosphoryl chloride was started at reflux condition. The mixture was heated at this temperature for 60 minutes. After completion of the reaction, the reaction mass was subjected to atmospheric distillation. Unreacted phosphorus chloride was distilled as the first fraction and thiophosphoryl chloride (10.47×10 3 The distillate-2 (99.7%) was recovered in the temperature range of 120-127°C and used for the preparation of o-methyldichlorothiophosphate by a continuous process in the next step. The remaining residue containing thiophosphoryl and tributylamine was used for the recycle batch.

[0122] Step 2 - Preparation of O-methyl dichlorothiophosphate: A continuous stirred tank reactor (CSTR) was charged with thiophosphoryl chloride (1.309 x 10) from step 1. 3 kg / h), and methanol (flow rate 1.129 x 10 3 Kg / hr) was added at a temperature of -5±3° C. while maintaining the residence time of the reaction at 3 hours. After completion, the reaction mass was quenched with chilled water and the product was isolated and stored for use in the next step to prepare O,O-dimethylchlorothiophosphate.

[0123] Step 3 - Preparation of O,O-dimethylchlorothiophosphate: Methanol (2.85 × 10 3 Kg) was added to the CSTR, and the O-methyldichlorothiophosphate (4.482 × 10 3 Kg) was added to the reactor at a temperature of -10°C. Sodium hydroxide solution (32% solution, 3.75 x 10 3 Kg) was added to the mixture by maintaining the temperature at -5±3° C. After completion, the reaction mass was diluted with water and the product was isolated and used in the next step to prepare O,O-dimethylphosphoramidothioate.

[0124] Step 4 - Preparation of O,O-dimethyl phosphoramidothioate: The O,O-dimethylchlorothiophosphate obtained in step (3) (flow rate 1.058 × 10 3 Kg / hour) was added to the premix (flow rate 1.821 x 10 3 kg / hour; Premix 766 x 10 3 Kg / hour, 32% caustic soda and 1.055 x 10 3 Addition of aqueous ammonia solution (17%) at 175 Kg / hr was continued over a residence time of 1.5 hours. The progress of the reaction was monitored by GC chromatography. After completion, the reaction mass was extracted with dichloromethane to remove O,O-dimethylphosphoramidothioate (825 kg / hr) which was used in the next step.

[0125] Step 5 Preparation of acephate The O,O-dimethylphosphoramidothioate (4.54 × 10) obtained in step (4) above 3 Kg) was added to methylene dichloride (3.17 × 10 3 Two lots of dimethyl sulfate (0.546 × 10 3 The reaction mass was heated at 45-48°C for 4 hours to form O,S-dimethylphosphoramidothioate. The isomerized product was then transferred to another reactor for acetylation.

[0126] Then, acetic anhydride (3.103 × 10 3 Kg) and sulfuric acid (0.094 × 10 3 A pre-cooled mixture of acephate (4.826 × 10) was added to the reaction mixture over 1.5 hours at 35-45°C and heating was continued for 1 hour at the same temperature. The resulting mass was neutralized with liquid ammonia and the product was extracted with dichloromethane to give the desired product, acephate (4.826 × 10) 3 kg) was obtained as a white solid with a purity of 98%.

Claims

1. An improved process for preparing thiophosphoryl chloride, comprising reacting phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of a trialkylamine, A process wherein the reaction is carried out in a time period of less than 60 minutes and the process is recycled 5 to 7 times.

2. 10. The process of claim 1, wherein the thiophosphoryl chloride is an autosolvent for the reaction.

3. 2. The process of claim 1, wherein the trialkylamine is tributylamine.

4. 2. The process of claim 1, wherein the trialkylamine is used in an amount ranging from 0.01 to 0.08 mole fraction relative to phosphorus trichloride.

5. 2. The process of claim 1, wherein the molar ratio of phosphorus trichloride to sulfur is 1:

1.

6. 10. The process of claim 1, wherein the reaction is carried out at a temperature in the range of 100 to 150°C.

7. 10. The process of claim 1, wherein the reaction is carried out at atmospheric pressure.

8. 10. The process of claim 1 further comprising distilling pure thiophosphoryl chloride from the reaction mixture to leave a distillation residue.

9. 9. The process of claim 8, further comprising recycling the distillation residue to a subsequent reaction step with phosphorus trichloride and sulfur to produce thiophosphoryl chloride.

10. A process for preparing acephate, comprising reacting phosphorus trichloride with sulfur in thiophosphoryl chloride in the presence of a trialkylamine within a period of less than 60 minutes to obtain thiophosphoryl chloride.

11. 11. The process of claim 10, wherein the reaction of phosphorus trichloride with sulfur in thiophosphoryl chloride is carried out at a temperature in the range of 100 to 150°C.

12. 1. A process for preparing acephate, comprising: a) preparing thiophosphoryl chloride; b) converting thiophosphoryl chloride to acephate; Including, A process wherein step a) comprises treating phosphorus trichloride, thiophosphoryl chloride, and sulfur in the presence of a tributylamine catalyst to obtain thiophosphoryl chloride within a period of less than 60 minutes.

13. 13. The process of claim 12, further comprising distilling pure thiophosphoryl chloride from the reaction mixture to leave a distillation residue.

14. 14. The process of claim 13, further comprising recycling the distillation residue to a subsequent reaction step with phosphorus trichloride and sulfur to produce thiophosphoryl chloride.

15. The conversion in step b) is (i) treating thiophosphoryl chloride with methanol to give O-methyl phosphorodichloridothioate; (ii) treating O-methyl phosphorodichloridothioate with methanol to give O,O-dimethyl phosphorochloridothioate; or (iii) treating O,O-dimethyl phosphorochloridothioate with a base to obtain O,O-dimethyl phosphoramidothioate; 13. The process of claim 12, comprising at least one step selected from:

16. 16. The process of claim 15, further comprising acetylating O,O-dimethylphosphoramidothioate in the presence of acetic anhydride to obtain acephate.

17. 17. The process of any one of claims 12 to 16, wherein steps a) and b) proceed by isolating the products of each step, or proceed as a continuous process without isolating the products of each step.

18. 10. The process of any one of claims 1 to 9, wherein thiophosphoryl chloride is obtained with a purity of at least 95%.

19. 20. The process of claim 18, wherein the thiophosphoryl chloride is obtained in a purity of at least 99%.

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