An improved process for the synthesis of halogenated alkenone ethers compounds

Abstract

The present invention relates to a process for the preparation of Halogenated Alkenone Ethers of Formula (1) from a compound of Formula (2) using an iodide- based catalyst which enables superior process performance in terms of throughput, yield, and product purity when compared to the prior art, in addition to making the process more environmentally friendly by enabling the use of environmentally benign, inexpensive inorganic bases - in lieu of environmentally damaging organic bases, as were used in the prior art.

Description

[0001] TITLE: AN IMPROVED PROCESS FOR THE SYNTHESIS OF

[0002] HALOGENATED ALKENONE ETHERS COMPOUNDS

[0003] FIELD OF INVENTION:

[0004] Current invention relates to a process for the synthesis of halogenated alkenone ethers in economic, safe, efficient manner using an iodide-based catalyst. The process also follows the green chemistry approach.

[0005] BACKGROUND OF INVENTION:

[0006] Halogenated alkenone ethers are useful for preparation of several pesticides such as the insecticide Sulfoxaflor as described in US20080207910A1, and the insecticide Flonicamid as described in US5708175A.

[0007] Of particular interest are 4-alkoxy-l,l,l-trifluoro-3-buten-2-ones, which are used as building blocks for the pesticides mentioned above. An example of such a molecule is 4-ethoxy-l,l,l-trifluoro-3-buten-2-ones (ETFBO).

[0008] Processes for the synthesis of halogenated alkenone ethers (such as ETFBO) have been described in the prior art.

[0009] The route of synthesis predominantly followed involves reaction of an acid halide with an alkyl vinyl ether in the presence of a base - as shown below in Scheme 1.

[0010] Compound (6)

[0011] Scheme 1: Synthesis of halogenated alkenone ethers — following acyl halide approach

[0012] The synthesis of halogenated alkenone ethers from acid chlorides has been reported in WO2011003856, WO2011003854 and several more.

[0013] However, in the case of 4-alkoxy-l,l,l-trifluoro-3-buten-2-ones, this approach invites cryogenic process temperatures (~ -30°C) and involve the generation and handling of trifluoroacetyl chloride (boiling point = -27°C). This material is a gas at standard temperature and pressure conditions and is highly corrosive. Thus, to handle this material at industrial scale, pressure -rated and acid resistant equipment is required, making this process capital intensive and inherently hazardous due to necessity of handling corrosive gases.

[0014] Alternatively, the synthesis of halogenated alkenone ethers from Trifluoroacetic Anhydride, which is a liquid at standard temperature and pressure conditions, (boiling point = 40°C) has also been reported in W02003066558, WO2010118078 and more. However, this approach has an inherent disadvantage that Trifluoroacetic Anhydride is more expensive than Trifluoroacetic acid or Trifluoroacetyl Chloride, and that the process generates one equivalent of Trifluoroacetic Acid as a byproduct, which represents a significant cost. Hence, for this approach to be economically viable, recovery and purification of the byproduct trifluoroacetic acid is required, followed by regeneration of Trifluoroacetic Anhydride from the byproduct Trifluoroacetic Acid. Due to the number of additional operations involved like byproduct acid recovery and anhydride regeneration, this approach also suffers from a high capital cost and high operating cost.

[0015] Another less reported approach for the synthesis of halogenated alkenone ethers is synthesizing them from carboxylic acids. A ‘mixed anhydride’ intermediate is formed by reacting a carboxylic acid with a sulfonyl chloride.

[0016] In the case of 4-alkoxy-l,l,l-trifluoro-3-buten-2-ones, the starting material is trifluoroacetic acid (boiling point = 72.4°C), is a liquid at standard temperature and pressure conditions, making it much easier to handle. The synthetic approach is shown in Scheme 2.

[0017] Scheme 2: Synthesis 4-Alkoxy-l,l,l-trifuoro-buten-2-ones through carboxylic acid via ‘mixed anhydride’ approach

[0018] This approach does not involve any gaseous reactants, hence, can be conducted in simple glass-lined equipment at scale - substantially reducing the capital cost of the facility required for large scale manufacture. Examples of this synthesis approach have been described in CN105237376 and WO2016071243.

[0019] The reported processes use of nitrogen heterocycle bases, such as Pyridine. As per the synthesis, a minimum of two molar equivalents of base are required for the conversion of a single equivalent of carboxylic acid. During the reaction, the nitrogen heterocycle bases are converted to water soluble salts, which are then lost during the work-up process as organic effluent. Additionally, the process is slow and requires a substantial amount of time to reach a level of conversion that is necessary for commercial applications.

[0020] Furthermore, direct replacement of these nitrogen heterocycle bases in the reported processes with more environmentally benign and inexpensive inorganic bases results in substantial deterioration of process performance that is reduced yield and throughput.

[0021] Hence, the currently known processes face one or all the following drawbacks -

[0022] • Require high capital costs and operating costs

[0023] • Necessitate the handling and storage of corrosive gases - making the production inherently unsafe

[0024] • Require substantial usage of organic bases that are expensive, costly to recover, and significantly add to the overall pollution load of the process

[0025] Therefore, there was a need to provide a process for the synthesis of halogenated alkenone ethers that is economic, safe, efficient manner. This is achieved through the introduction of an iodide-based catalyst into the process. The process also follows the green chemistry approach. Accordingly, the invention provides a process that enables the replacement of nitrogen heterocycle bases with cheaper and less polluting inorganic bases, while also increasing the rate of reaction substantially, without adversely affecting the process yield.

[0026] SUMMARY OF THE INVENTION:

[0027] In its primary aspect the invention provides a process for the synthesis of halogenated alkenone ether compounds of Formula (1), comprising;

[0028] Compound (1) in which, R1= C1-C4 alkyl a) preparing a reaction mixture having a water immiscible solvent, a base, a compound of Formula (2), an alkyl vinyl ether compound of Formula (6) and an iodide-based catalyst of Formula (4);

[0029] M+I Compound (4)

[0030] Compound (6)

[0031] Compound (2) in which M = Na, K, or in which, R1is Cl -C4 in which R2is selected (C4H9)N alkyl from -H, Na, K b) and adding a sulfonyl chloride compound of Formula (3) to said reaction mixture, to form the compound of Formula (1). o i i

[0032] O— s— Cl

[0033] Compound (3) in which R3is selected from C1-C4 alkyl, alkaryl, aryl

[0034] Various aspects of the present invention herein will be better appreciated and understood when considered in conjunction with the following description and the accompanying drawings.

[0035] BRIEF DESCRIPTION OF THE DRAWINGS:

[0036] The embodiments herein will be better understood from the following detailed description with reference to the drawings, in which the Figures illustrates:

[0037] FIGURE 1 refers to the gas chromatograph for the experiment 0;

[0038] FIGURE 2 refers to the gas chromatograph for the experiment 1A; FIGURE 3 refers to the gas chromatograph for the experiment IB;

[0039] FIGURE 4 refers to the gas chromatograph for the experiment 1C;

[0040] FIGURE 5 refers to the gas chromatograph for the experiment 2 A;

[0041] FIGURE 6 refers to the gas chromatograph for the experiment 2B;

[0042] FIGURE 7 refers to the gas chromatograph for the experiment 2C;

[0043] FIGURE 8 refers to the gas chromatograph for the experiment 2D;

[0044] FIGURE 9 refers to the gas chromatograph for the experiment 3 A;

[0045] FIGURE 10 refers to the gas chromatograph for the experiment 3B;

[0046] FIGURE 11 refers to the gas chromatograph for the experiment 3C;

[0047] FIGURE 12 refers to the gas chromatograph for the experiment 3D;

[0048] FIGURE 13 refers to the gas chromatograph for the experiment 4A;

[0049] FIGURE 14 refers to the gas chromatograph for the experiment 4B;

[0050] FIGURE 15 refers to the gas chromatograph for the experiment 5 A;

[0051] FIGURE 16 refers to the gas chromatograph for the experiment 5B;

[0052] FIGURE 17 refers to the gas chromatograph for the experiment 6A; and

[0053] FIGURE 18 refers to the gas chromatograph for the experiment 6B.

[0054] DETAILED DESCRIPTION:

[0055] As mentioned, in its primary aspect the invention provides a process for the synthesis of halogenated alkenone ether compounds of Formula (1), comprising;

[0056] Compound (1) in which, R1= C1-C4 alkyl c) preparing a reaction mixture having a water immiscible solvent, a base, a compound of Formula (2), an alkyl vinyl ether compound of Formula (6) and an iodide-based catalyst of Formula (4); M+I Compound (4)

[0057] Compound (6)

[0058] Compound (2) in which M = Na, K, or in which, R1is Cl -C4 in which R2is selected (C4H9)N alkyl from -H, Na, K d) and adding a sulfonyl chloride compound of Formula (3) to said reaction mixture, to form the compound of Formula (1).

[0059] Compound (3) in which R3is selected from C1-C4 alkyl, alkaryl, aryl

[0060] The present invention follows the route of synthesis shown below in Scheme 3.

[0061] Scheme 3: Synthesis 4-Alkoxy-l,l,l-trifuoro-buten-2-ones using an iodide-based catalyst The obtained compound of Formula (1) product is washed with water and given acid base treatment followed by concentration under vacuum to remove the solvent.

[0062] The water immiscible solvent is selected from aromatic hydrocarbons; ethereal solvents and halogenated hydrocarbons. Said aromatic hydrocarbons may be selected from the toluene, xylene and mixtures thereof; ethereal solvents may be selected from the diethyl ether, diiosopropyl ether, dibutyl ether cyclopentyl methyl ether, and mixtures thereof and halogenated hydrocarbons may be selected from methylene dichloride, ethylene dichloride, chloroform and mixtures thereof. In the preferred embodiment, the water immiscible solvent is methylene dichloride or ethylene dichloride.

[0063] In another aspect of the invention, the iodide-based catalyst of Formula (4) in the process is preferably selected from sodium iodide, potassium iodide, quaternary ammonium-iodide salts and mixtures thereof. More preferably, the catalyst of Formula (4) is sodium iodide, tetra-n-butylammonium iodide or both of them can also be used.

[0064] Preferably, the iodide-based catalyst of Formula (4) is 0.5 mol% to 2.5 mol% with respect to the loading of compound of Formula (2).

[0065] The iodide-based catalyst of Formula (4) employed in the present invention greatly enhance the rate of reaction, product purity, and yield as can be seen in the Table 1 below.

[0066] Table 1. Comparison of prior art process (EXP 0 - based on \\()2016071243, without catalyst) with present invention (using iodide -based catalysts) with Trifluoroacetic Acid (TFA) as a compound 2

[0067] In the various embodiments of the invention, the base is selected from nitrogen heterocycles bases and inorganic carbonate bases. More suitably, the nitrogen heterocycles bases may be selected from pyridine, isomers of picoline, methylpyridine, isomers of lutidine, dimethylpyridine; and inorganic carbonate bases are selected from sodium carbonate, potassium carbonate, calcium carbonate, and mixtures thereof.

[0068] In the preferred embodiment of the invention, the base is potassium carbonate or pyridine.

[0069] In another embodiment of the invention, around 100.0 mol% to 220.0 mol% base with respect to the loading of compound of Formula (2) is employed in the process. It is important to note that the usage of such inorganic bases is also a novel attribute of the present invention, associated with the introduction of the catalyst of Formula (4). Direct replacement of Pyridine in the prior art process (without catalyst) with inorganic carbonate bases results in substantially deteriorated process performance (reaction rate, yield), whereas the catalyst increases the rate of reaction to lower the reaction time and substantially improves the yield and purity as can be seen in Table 2 below.

[0070] Table 2. Comparison of prior art process (EXP 6A - based on \\()2016071243, without catalyst) with present invention (using iodide -based catalysts) with Trifluoroacetic Acid (TFA) as a compound 2 and Na2CC (sodium carbonate) as base

[0071] In yet another embodiment of the invention, the compound of Formula (2) in the process is selected from a carboxylic acid compound and alkali metal carboxylate salt compound. In one preferred embodiment, the compound of Formula (2) is carboxylic acid compound and the base is pyridine. In another preferred embodiment, the compound of Formula (2) is alkali metal carboxylate salt compound and base is selected from sodium carbonate, potassium carbonate and pyridine.

[0072] It is important to note that the usage of alkali metal carboxylate salts in place of the free carboxylic acid is a novel attribute of the present invention, associated with the introduction of the catalyst of Formula (4). Direct replacement of the carboxylic acid with the alkali metal carboxylate salts in the prior art process (without catalyst) results in substantially deteriorated process performance (reaction rate, yield) whereas the catalyst increases the rate of reaction to lower the reaction time and substantially improves the yield and purity as can be seen in Table 3 below.

[0073] Table 3. Comparison of prior art process (EXP 2A, 3A - based on

[0074] \\()2016071243, without catalyst) with present invention (using iodide-based catalysts) with Sodium 2,2,2-Trifluoroacetate (TFA-Na Salt) and Potassium 2,2,2-Trifluoroacetate (TFA-K Salt) as a compound 2 — with organic and inorganic bases

[0075] In yet another embodiment of the invention, the compound of Formula (6) in the process is ethyl vinyl ether or n-Butyl vinyl ether.

[0076] In another embodiment, the sulfonyl chloride compound of Formula (3) in the process is selected from the methanesulfonyl chloride, benzenesulfonyl chloride, and p-toluenesulfonyl chloride.

[0077] The process of the present invention is compatible with sulfonyl chlorides of all the above categories, and also exhibits superior process performance compared to prior art as can be seen in Table 4 below.

[0078] Table 4. Comparison of prior art process (EXP 2A, 3A - based on WO2016071243, without catalyst) with present invention (using iodide-based catalysts) with Sodium 2,2,2-Trifluoroacetate (TFA-Na Salt) and Potassium 2,2,2-Trifluoroacetate (TFA-K Salt) as a compound 2 — with organic and inorganic bases In yet another embodiment, the process is carried out at a reaction temperature within the range of 15 to 40°C. More preferably the process is carried out at a reaction temperature within the range of 25 to 30°C.

[0079] As stated, the obtained compound of Formula (1) is washed with water and given acid base treatment followed by concentration under vacuum to remove the solvent. In this work-up procedure, preferably the acid in acid base treatment is dilute aqueous acid selected from hydrochloric acid, sulfuric acid and a combination thereof; and the base in acid base treatment is dilute aqueous alkali selected from aqueous solutions of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, calcium carbonate, and combinations thereof.

[0080] The compounds of Formula (2), Formula (3), Formula (4), Formula (6) used in the above process are obtained commercially.

[0081] The completion of the reaction may be monitored by any one of chromatographic techniques such as gas chromatography (GC), high pressure liquid chromatography (HPLC), ultra-pressure liquid chromatography (UPLC), thin layer chromatography (TLC) and alike.

[0082] The process of the present invention provides the compound of Formula (1) in yield, purity, and throughput superior to comparable processes in the prior art.

[0083] The foregoing description of the specific embodiments will so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and / or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope

[0084] Examples:

[0085] The following examples are given for the purposes of illustration and should not be construed to limit the scope of the present invention.

[0086] Experiment 0

[0087] To a suitable vessel, Ethyl Vinyl Ether (3.2g, 44 mmol) and Pyridine (7.0g, 88 mmol) were dissolved in Methylene Dichloride (26.0g) at 10°C. To this solution, was added Trifluoroacetic Acid (4.6g, 40 mmol) and more Methylene Dichloride (5.0g) at the same temperature range. The resulting mixture was stirred for 30 minutes at 10°C, after which, Methanesulfonyl Chloride (5.0g, 44 mmol) was added slowly while maintaining the temperature between 10-15°C - which took approximately 90 minutes. The resulting suspension was warmed to 25-30°C and then stirred till reaction completion. The reaction was completed after approximately 1,080 minutes (18 hours). After completion, the reaction mass was washed with water (10.0g ), dilute phosphoric acid (10.0g) , and phosphate buffer solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0088] Product Purity = 94.07% (area%, by GC)

[0089] Yield = 86.0% (isolated)

[0090] Observed Reaction Time = 1080 minutes (18 hours)

[0091] Refer Figure 1 for the chromatogram in which SI = ETFBO [Compound 1], RM02 = Ethyl Vinyl Ether

[0092] Experiment 1A

[0093] To a suitable vessel, Methylene Dichloride (31.1g), Sodium Iodide (0.15 g, 1 mmol) as a catalyst, and Pyridine (7.0g, 88 mmol) were added. The reaction mass was cooled to a temperature of 15-20°C. At this temperature range, Trifluoroacetic Acid (4.6g, 40 mmol) was added over approximately 60 minutes, followed by Ethyl Vinyl Ether (3.2g, 44 mmol) - after which the reaction mass was stirred for 30 minutes. Methanesulfonyl Chloride (5.0g, 44 mmol) was added to the reaction mass over 90 minutes while maintaining the temperature between 15-25°C. After completion of addition, the reaction mass was warmed to 25-30°C under stirring. The reaction was completed within 120 minutes (2 hours) after warming. The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0094] Product Purity = 96.92% (area%, by GC)

[0095] Yield = 92.4% (isolated)

[0096] Observed Reaction Time = 120 minutes (2 hours)

[0097] Refer Figure 2 for the chromatogram in which SI = ETFBO [Compound 1]

[0098] Experiment IB

[0099] To a suitable vessel, Methylene Dichloride (31.1g), Potassium Iodide (0.17 g, 1 mmol) as a catalyst, and Pyridine (7.0g, 88 mmol) were added. The reaction mass was cooled to a temperature of 15-20°C. At this temperature range, Trifluoroacetic Acid (4.6g, 40 mmol) was added over approximately 60 minutes, followed by Ethyl Vinyl Ether (3.2g, 44 mmol) - after which the reaction mass was stirred for 30 minutes. Methanesulfonyl Chloride (5.0g, 44 mmol) was added to the reaction mass over 90 minutes while maintaining the temperature between 15-25°C. After completion of addition, the reaction mass was warmed to 25-30°C under stirring. The reaction was completed within 120 minutes (2 hours) after warming. The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0100] Product Purity = 96.48% (area%, by GC)

[0101] Yield = 93.0% (isolated)

[0102] Observed Reaction Time = 120 minutes (2 hours) Refer Figure 3 for the chromatogram in which SI = ETFBO [Compound 1], RM02 = Ethyl Vinyl Ether) [Compound 6]

[0103] Experiment 1C

[0104] To a suitable vessel, Methylene Dichloride (31.1g), tetra-n-butylammonium Iodide (0.37 g, 1 mmol) as a catalyst, and Pyridine (7.0g, 88 mmol) were added. The reaction mass was cooled to a temperature of 15-20°C. At this temperature range, Trifluoroacetic Acid (4.6g, 40 mmol) was added over approximately 60 minutes, followed by Ethyl Vinyl Ether (3.2g, 44 mmol) - after which the reaction mass was stirred for 30 minutes. Methanesulfonyl Chloride (5.0g, 44 mmol) was added to the reaction mass over 90 minutes while maintaining the temperature between 15-25°C. After completion of addition, the reaction mass was warmed to 25-30°C under stirring. The reaction was completed within 180 minutes (3 hours) after warming. The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0105] Product Purity = 98.25% (area%, by GC)

[0106] Yield = 92.8% (isolated)

[0107] Observed Reaction Time = 180 minutes (3 hours)

[0108] Refer Figure 4 for the chromatogram in which SI = ETFBO [Compound 1]

[0109] Experiment 2A

[0110] To a suitable vessel, Methylene Dichloride (31.1g) and Pyridine (5.9g, 74 mmol) were added. The reaction mass was cooled to a temperature of 15-20°C. At this temperature range, Sodium 2,2,2-Trifluoroacetate (4.6g, 34 mmol) was added to the reactor, followed by Ethyl Vinyl Ether (2.68g, 37 mmol) - after which the reaction mass was stirred for 30 minutes. Methanesulfonyl Chloride (4.26g, 37 mmol) was added to the reaction mass over 90 minutes while maintaining the temperature between 15-25°C. After completion of addition, the reaction mass was warmed to 25-30°C under stirring. The reaction was maintained for over 1200 minutes - but the reaction did not reach completion. The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0111] Product Purity = 86.17% (area%, by GC)

[0112] Yield = 49.4% (isolated)

[0113] Observed Reaction Time = > 1200 minutes (> 20 hours)

[0114] Refer Figure 5 for the chromatogram in which SI = ETFBO [Compound 1]

[0115] Experiment 2B

[0116] To a suitable vessel, Methylene Dichloride (31.1g), Sodium Iodide (0.13 g, 0.85 mmol) as a catalyst and Pyridine (5.9g, 74 mmol) were added. The reaction mass was cooled to a temperature of 15-20°C. At this temperature range, Sodium 2,2,2- Trifluoroacetate (4.6g, 34 mmol) was added to the reactor, followed by Ethyl Vinyl Ether (2.68g, 37 mmol) - after which the reaction mass was stirred for 30 minutes. Methanesulfonyl Chloride (4.26g, 37 mmol) was added to the reaction mass over 90 minutes while maintaining the temperature between 15-25°C. After completion of addition, the reaction mass was warmed to 25-30°C under stirring. The reaction was after 210 minutes (3.5 hours). The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0117] Product Purity = 96.08% (area%, by GC)

[0118] Yield = 90.3% (isolated)

[0119] Observed Reaction Time = 210 minutes (3.5 hours)

[0120] Refer Figure 6 for the chromatogram in which SI = ETFBO [Compound 1], RM02 = Ethyl Vinyl Ether [Compound 6]

[0121] Experiment 2C

[0122] To a suitable vessel, Methylene Dichloride (31.1g), Sodium Iodide (0.13 g, 0.85 mmol) as a catalyst and Sodium Carbonate (3.9g, 37 mmol) were added. The reaction mass was cooled to a temperature of 15-20°C. At this temperature range, Sodium 2,2,2-Trifluoroacetate (4.6g, 34 mmol) was added to the reactor, followed by Ethyl Vinyl Ether (2.68g, 37 mmol) - after which the reaction mass was stirred for 30 minutes. Methanesulfonyl Chloride (4.26g, 37 mmol) was added to the reaction mass over 90 minutes while maintaining the temperature between 15-25°C. After completion of addition, the reaction mass was warmed to 25-30°C under stirring. The reaction was after 210 minutes (3.5 hours). The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0123] Product Purity = 97.86% (area%, by GC)

[0124] Yield = 89.8% (isolated)

[0125] Observed Reaction Time = 240 minutes (4 hours)

[0126] Refer Figure 7 for the chromatogram in which SI = ETFBO [Compound 1]

[0127] Experiment 2D

[0128] To a suitable vessel, Methylene Dichloride (31.1g), Sodium Iodide (0.13 g, 0.85 mmol) as a catalyst and Potassium Carbonate (5.1g, 37 mmol) were added. The reaction mass was cooled to a temperature of 15-20°C. At this temperature range, Sodium 2,2,2-Trifluoroacetate (4.6g, 34 mmol) was added to the reactor, followed by Ethyl Vinyl Ether (2.68g, 37 mmol) - after which the reaction mass was stirred for 30 minutes. Methanesulfonyl Chloride (4.26g, 37 mmol) was added to the reaction mass over 90 minutes while maintaining the temperature between 15-25°C. After completion of addition, the reaction mass was warmed to 25-30°C under stirring. The reaction was after 210 minutes (3.5 hours). The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0129] Product Purity = 97.72% (area%, by GC)

[0130] Yield = 90.2% (isolated)

[0131] Observed Reaction Time = 210 minutes (3.5 hours)

[0132] Refer Figure 8 for the chromatogram in which SI = ETFBO [Compound 1] Experiment 3A

[0133] To a suitable vessel, Methylene Dichloride (31.1g) and Pyridine (5.2g, 66 mmol) were added. The reaction mass was cooled to a temperature of 15-20°C. At this temperature range, Potassium 2,2,2-Trifluoroacetate (4.6g, 30 mmol) was added to the reactor, followed by Ethyl Vinyl Ether (2.38g, 33 mmol) - after which the reaction mass was stirred for 30 minutes. Methanesulfonyl Chloride (3.79g, 33 mmol) was added to the reaction mass over 90 minutes while maintaining the temperature between 15-25°C. After completion of addition, the reaction mass was warmed to 25-30°C under stirring. The reaction was maintained for over 1200 minutes - but the reaction did not reach completion. The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0134] Product Purity = 94.03% (area%, by GC)

[0135] Yield = 50.2% (isolated)

[0136] Observed Reaction Time = > 1200 minutes (> 20 hours)

[0137] Refer Figure 9 for the chromatogram in which SI = ETFBO [Compound 1], RM02 = Ethyl Vinyl Ether [Compound 6]

[0138] Experiment 3B

[0139] To a suitable vessel, Methylene Dichloride (31.1g), Sodium Iodide (0.11 g, 0.75 mmol) as a catalyst and Pyridine (5.2g, 66 mmol) were added. The reaction mass was cooled to a temperature of 15-20°C. At this temperature range, Potassium 2,2,2- Trifluoroacetate (4.6g, 30 mmol) was added to the reactor, followed by Ethyl Vinyl Ether (2.38g, 33 mmol) - after which the reaction mass was stirred for 30 minutes. Methanesulfonyl Chloride (3.79g, 33 mmol) was added to the reaction mass over 90 minutes while maintaining the temperature between 15-25°C. After completion of addition, the reaction mass was warmed to 25-30°C under stirring. The reaction was after 210 minutes (3.5 hours). The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0140] Product Purity = 97.47% (area%, by GC)

[0141] Yield = 90.2% (isolated)

[0142] Observed Reaction Time = 210 minutes (3.5 hours)

[0143] Refer Figure 10 for the chromatogram in which S 1 = ETFBO [Compound 1], RM02 = Ethyl Vinyl Ether [Compound 6]

[0144] Experiment 3C

[0145] To a suitable vessel, Methylene Dichloride (31.1g), Sodium Iodide (0.11 g, 0.75 mmol) as a catalyst and Sodium Carbonate (3.5g, 33 mmol) were added. The reaction mass was cooled to a temperature of 15-20°C. At this temperature range, Potassium 2,2,2-Trifluoroacetate (4.6g, 30 mmol) was added to the reactor, followed by Ethyl Vinyl Ether (2.38g, 33 mmol) - after which the reaction mass was stirred for 30 minutes. Methanesulfonyl Chloride (3.79g, 33 mmol) was added to the reaction mass over 90 minutes while maintaining the temperature between 15-25°C. After completion of addition, the reaction mass was warmed to 25-30°C under stirring. The reaction was after 240 minutes (4 hours). The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0146] Product Purity = 97.06% (area%, by GC)

[0147] Yield = 90.0% (isolated)

[0148] Observed Reaction Time = 240 minutes (4 hours)

[0149] Refer Figure 11 for the chromatogram in which S 1 = ETFBO [Compound 1]

[0150] Experiment 3D

[0151] To a suitable vessel, Methylene Dichloride (31.1g), Sodium Iodide (0.11 g, 0.75 mmol) as a catalyst and Potassium Carbonate (4.6g, 33 mmol) were added. The reaction mass was cooled to a temperature of 15-20°C. At this temperature range, Potassium 2,2,2-Trifluoroacetate (4.6g, 30 mmol) was added to the reactor, followed by Ethyl Vinyl Ether (2.38g, 33 mmol) - after which the reaction mass was stirred for 30 minutes. Methanesulfonyl Chloride (3.79g, 33 mmol) was added to the reaction mass over 90 minutes while maintaining the temperature between 15-25°C. After completion of addition, the reaction mass was warmed to 25-30°C under stirring. The reaction was after 210 minutes (3.5 hours). The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0152] Product Purity = 97.28% (area%, by GC)

[0153] Yield = 90.2% (isolated)

[0154] Observed Reaction Time = 210 minutes (3.5 hours)

[0155] Refer Figure 12 for the chromatogram in which S 1 = ETFBO [Compound 1], RM02 = Ethyl Vinyl Ether [Compound 6]

[0156] Experiment 4A

[0157] To a suitable vessel, Methylene Dichloride (31.1g) and Pyridine (5.9g, 74 mmol) were added. The reaction mass was cooled to a temperature of 15-20°C. At this temperature range, Sodium 2,2,2-Trifluoroacetate (4.6g, 34 mmol) was added to the reactor, followed by Ethyl Vinyl Ether (2.68g, 37 mmol) - after which the reaction mass was stirred for 30 minutes. p-Toluenesulfonyl Chloride (7.09g, 37 mmol) was added to the reaction mass over 90 minutes while maintaining the temperature between 15-25°C. After completion of addition, the reaction mass was warmed to 25-30°C under stirring. The reaction was maintained for over 1200 minutes - but the reaction did not reach completion. The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0158] Product Purity = 86.73% (area%, by GC)

[0159] Yield = 48.0% (isolated)

[0160] Observed Reaction Time = > 1200 minutes (> 20 hours) Refer Figure 13 for the chromatogram in which S 1 = ETFBO [Compound 1], RM02 = Ethyl Vinyl Ether [Compound 6]

[0161] Experiment 4B

[0162] To a suitable vessel, Methylene Dichloride (31.1g), Sodium Iodide (0.13 g, 0.85 mmol) as a catalyst and Pyridine Carbonate (5.9g, 74 mmol) were added. The reaction mass was cooled to a temperature of 15-20°C. At this temperature range, Sodium 2,2,2-Trifluoroacetate (4.6g, 34 mmol) was added to the reactor, followed by Ethyl Vinyl Ether (2.68g, 37 mmol) - after which the reaction mass was stirred for 30 minutes. p-Toluenesulfonyl Chloride (7.09g, 37 mmol) was added to the reaction mass over 90 minutes while maintaining the temperature between 15-25°C. After completion of addition, the reaction mass was warmed to 25-30°C under stirring. The reaction was after 120 minutes (2 hours). The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0163] Product Purity = 97.75% (area%, by GC)

[0164] Yield = 89.4% (isolated)

[0165] Observed Reaction Time = 120 minutes (2 hours)

[0166] Refer Figure 14 for the chromatogram in which SI = ETFBO [Compound 1]

[0167] Experiment 5A

[0168] To a suitable vessel, Methylene Dichloride (31.1g) and Pyridine (5.9g, 74 mmol) were added. The reaction mass was cooled to a temperature of 15-20°C. At this temperature range, Sodium 2,2,2-Trifluoroacetate (4.6g, 34 mmol) was added to the reactor, followed by Ethyl Vinyl Ether (2.68g, 37 mmol) - after which the reaction mass was stirred for 30 minutes. Benzenesulfonyl Chloride (6.57g, 37 mmol) was added to the reaction mass over 90 minutes while maintaining the temperature between 15-25°C. After completion of addition, the reaction mass was warmed to 25-30°C under stirring. The reaction was maintained for over 1200 minutes - but the reaction did not reach completion. The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0169] Product Purity = 89.34% (area%, by GC)

[0170] Yield = 48.2% (isolated)

[0171] Observed Reaction Time = > 1200 minutes (> 20 hours)

[0172] Refer Figure 15 for the chromatogram in which SI = ETFBO [Compound 1]

[0173] Experiment 5B

[0174] To a suitable vessel, Methylene Dichloride (31.1g), Sodium Iodide (0.13 g, 0.85 mmol) as a catalyst and Pyridine Carbonate (5.9g, 74 mmol) were added. The reaction mass was cooled to a temperature of 15-20°C. At this temperature range, Sodium 2,2,2-Trifluoroacetate (4.6g, 34 mmol) was added to the reactor, followed by Ethyl Vinyl Ether (2.68g, 37 mmol) - after which the reaction mass was stirred for 30 minutes. p-Toluenesulfonyl Chloride (7.09g, 37 mmol) was added to the reaction mass over 90 minutes while maintaining the temperature between 15-25°C. After completion of addition, the reaction mass was warmed to 25-30°C under stirring. The reaction was after 120 minutes (2 hours). The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0175] Product Purity = 97.21% (area%, by GC)

[0176] Yield = 88.70% (isolated)

[0177] Observed Reaction Time = 120 minutes (2 hours)

[0178] Refer Figure 16 for the chromatogram in which S 1 = ETFBO [Compound 1], RM02 = Ethyl Vinyl Ether [Compound 6]

[0179] Experiment 6A

[0180] To a suitable vessel, Ethyl Vinyl Ether (3.2g, 44 mmol) and Sodium Carbonate (7.0g, 88 mmol) were dissolved in Methylene Dichloride (26.0g) at 10°C. To this solution, was added Trifluoroacetic Acid (4.6g, 40 mmol) and more Methylene Dichloride (5.0g) at the same temperature range. The resulting mixture was stirred for 30 minutes at 10°C, after which, Methanesulfonyl Chloride (9.4g, 88 mmol) was added slowly while maintaining the temperature between 10-15°C - which took approximately 90 minutes. The resulting suspension was warmed to 25-30°C and then stirred till reaction completion. The reaction was maintained for over 1200 minutes - but the reaction did not reach completion. The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0181] Product Purity = 90.95% (area%, by GC)

[0182] Yield = 48.0% (isolated)

[0183] Observed Reaction Time = > 1200 minutes (20 hours)

[0184] Refer Figure 17 for the chromatogram in which S 1 = ETFBO [Compound 1], RM02 = Ethyl Vinyl Ether [Compound 6]

[0185] Experiment 6B

[0186] To a suitable vessel, Methylene Dichloride (31.1g), Sodium Iodide (0.15 g, 1 mmol) as a catalyst, and Sodium Carbonate (9.4g, 88 mmol) were added. The reaction mass was cooled to a temperature of 15-20°C. At this temperature range, Trifluoroacetic Acid (4.6g, 40 mmol) was added over approximately 60 minutes, followed by Ethyl Vinyl Ether (3.2g, 44 mmol) - after which the reaction mass was stirred for 30 minutes. Methanesulfonyl Chloride (5.0g, 44 mmol) was added to the reaction mass over 90 minutes while maintaining the temperature between 15-25°C. After completion of addition, the reaction mass was warmed to 25-30°C under stirring. The reaction was completed within 240 minutes (4 hours) after warming. The reaction mass was washed with water (10.0g), 0.5M hydrochloric acid (10.0g), and 5% sodium carbonate solution (10.0g). The washed organic layer was concentrated under vacuum - and the resulting crude product was analyzed.

[0187] Product Purity = 96.48% (area%, by GC)

[0188] Yield = 92.4% (isolated)

[0189] Observed Reaction Time = 240 minutes (4 hours) Refer Figure 18 for the chromatogram in which S 1 = ETFBO [Compound 1], RM02 = Ethyl Vinyl Ether [Compound 6]

[0190] Below is the short summary of the experiments 0 to 6B:

[0191] Thus, the process efficiency is apparent from the above data. It proves that the process is economic, safe, efficient manner. It also follows the green chemistry approach as it enables the replacement of nitrogen heterocycle bases with cheaper and less polluting inorganic bases, while also increasing the rate of reaction substantially, without adversely affecting the process yield.

Claims

4AVe claim:

1. A process for the synthesis of halogenated alkenone ethers compounds of Formula (1), comprising;Compound (1) in which, R1= C1-C4 alkyl a) preparing a reaction mixture having a water immiscible solvent, a base, a compound of Formula (2), an alkyl vinyl ether compound of Formula (6) and an iodide-based catalyst of Formula (4);M+ICompound (4)Compound (6)Compound (2) in which M = Na, K, or in which, R1is Cl -C4 in which R2is selected (C4H9)N alkyl from -H, Na, K b) and adding a sulfonyl chloride compound of Formula (3) to said reaction mixture, to form the compound of Formula (1).Compound (3) in which R3is selected from C1-C4 alkyl, alkaryl, aryl2. The process as claimed in claim 1, wherein the water immiscible solvent is selected from aromatic hydrocarbons; ethereal solvents and halogenated hydrocarbons.

3. The process as claimed in claim 2, wherein said aromatic hydrocarbons are selected from the toluene, xylene and mixtures thereof; ethereal solvents are selected from the diethyl ether, diiosopropyl ether, dibutyl ether cyclopentyl methyl ether, andmixtures thereof and halogenated hydrocarbons are selected from methylene dichloride, ethylene dichloride, chloroform and mixtures thereof.

4. The process as claimed in claim 1, wherein the water immiscible solvent is methylene dichloride or ethylene dichloride.

5. The process as claimed in claim 1, wherein the base is selected from nitrogen heterocycles bases and inorganic carbonate bases.

6. The process as claimed in claim 5, wherein the nitrogen heterocycles bases are selected from pyridine, isomers of picoline, methylpyridine, isomers of lutidine, dimethylpyridine; and inorganic carbonate bases are selected from sodium carbonate, potassium carbonate, calcium carbonate, and mixtures thereof.

7. The process as claimed in claim 1, wherein the base is selected from potassium carbonate and pyridine.

8. The process as claimed in claim 1, wherein the base is 100.0 mol% to 220.0 mol% with respect to the loading of compound of Formula (2).

9. The process as claimed in claim 1 , wherein the iodide-based catalyst of Formula (4) is 0.5 mol% to 2.5 mol% with respect to the loading of compound of Formula (2).

10. The process as claimed in claim 1, wherein the iodide-based catalyst of Formula (4) is selected from sodium iodide, potassium iodide, quaternary ammonium- iodide salts and mixtures thereof.

11. The process as claimed in claim 1, wherein the catalyst of Formula (4) is sodium iodide, tetra-n-butylammonium iodide or both.

12. The process as claimed in claim 1, wherein the compound of Formula (2) is selected from a carboxylic acid compound and alkali metal carboxylate salt compound.

13. The process as claimed in claim 1, wherein the compound of Formula (2) is carboxylic acid compound and the base is pyridine.

14. The process as claimed in claim 1, wherein the compound of Formula (2) is alkali metal carboxylate salt compound and base is selected from sodium carbonate, potassium carbonate and pyridine.

15. The process as claimed in claim 1, wherein the compound of Formula (6) is ethyl vinyl ether or n-Butyl vinyl ether.

16. The process as claimed in claim 1, wherein the sulfonyl chloride compound of Formula (3) is methanesulfonyl chloride, benzenesulfonyl chloride, and p- toluenesulfonyl chloride.

17. The process as claimed in claim 1, wherein the process is carried out at a reaction temperature within the range of 15 to 40°C.

18. The process as claimed in claim 17, wherein the process is carried out at a reaction temperature within the range of 25 to 30°C.

19. The process as claimed in claim 1, wherein the obtained compound of Formula (1) is washed with water and given acid base treatment followed by concentration under vacuum to remove the solvent.

20. The process as claimed in claim 19, wherein the acid in acid base treatment is dilute aqueous acid selected from hydrochloric acid, sulfuric acid and a combination thereof; and the base in acid base treatment is dilute aqueous alkali selected from aqueous solutions of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, calcium carbonate, and combinations thereof.

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