PL247337B1 - New quaternary bisammonium salts with alkyl-1,ω-bis(trimethyl(carboxymethyl)ammonium) cation and 2-methyl-4-chlorophenoxyacetate anions, method of obtaining them and use as plant protection agents - Google Patents

Abstract

The subject of the application is new bis-quaternary ammonium salts with an alkyl-1,X-bis(trimethyl(carboxymethyl)ammonium) cation and 4-chloro-2-methylphenoxyacetate anions of the general formula 1, the method and preparation thereof and the use thereof as plant protection agents.

Description

Description of the invention

The subject of the invention are quaternary bisammonium salts with an alkyl-1,ω-bis(trimethyl(carboxymethyl)ammonium) cation and 2-methyl-4-dichlorophenoxyacetate anions, a method for obtaining them and their use as plant protection agents.

Bisammonium salts are a new type of organic compounds classified as quaternary ammonium salts, which are organic compounds with an ionic structure, having a positive charge on the nitrogen atom in their structure. In bisammonium salts, two cations are connected to each other by means of a linker, which can be a long or short non-polar alkyl chain substituted with various functional groups. These compounds are mainly used as surfactants, because they show high surface activity and low critical micellization concentration. Thanks to this, they are superior to conventional cationic surfactants and are an excellent alternative to them. Quaternary ammonium salts, in which there is an ester bond between the alkyl chain and the quaternary nitrogen atom, are called esterquats. Bissamonium salts classified as esterquads are also known in the literature (A.R. Tehrani-Bagha, H. Oskarsson, C.G. van Ginkel, K. Holmberg, J Colloid Interface Sci. 2007, 312, 444-452). It has been noted that bissamonium salts with an ester bond are characterized by much better biodegradability, which makes them more environmentally friendly compared to bissamonium salts containing only simple alkyl chains attached to nitrogen atoms.

N,N,N-trimethylglycine is known as glycine betaine and constitutes approximately 27% of molasses, a by-product of the confectionery industry. As a natural compound, it is readily available, biodegradable and non-toxic. As a result, betaine is currently used as an additive to creams and ointments, medicated cleansers, aftershaves and deodorants. Field studies indicate that betaine can increase fruit and vegetable yields by more than 20% if applied during the mid-flowering phase of plants. (M. Niemczak, Ł. Sobiech, M. Grzanka, J. Agric. Food Chem. 2020, 68 (47), 13661-13671). The use of betaine for the synthesis of bisammonium salts of esterquats containing biologically active anions as herbicides is not known. Only betaine alkyl esters with one ester bond and a herbicide anion have been described in the literature. (M. Niemczak, Ł. Sobiech, M. Grzanka, J Agric. Food Chem. 2020, 68 (47), 13661-13671; A. Nawrocki, R. Olszewski, J. Pernak, T. Praczyk, M. Niemczak, K. Czerniak, EP 3092898A1; J. Pernak, M. Niemczak, K. Czerniak, T. Praczyk, PL 230034; J. Pernak, I. Kędzia, M. Niemczak, PL 230764; J. Pernak, M. Niemczak, I. Kędzia, Z. Bartoszewska, K. Marcinkowska, T. Praczyk, PL 231021). It should be noted, however, that none of the indicated literature reports indicate that it is possible to obtain bisammonium betaine derivatives.

The use of bisammonium salts as plant protection agents has been described many times, including in patent PL 228522, where the synthesis of bisammonium salts with an alkyldiylbis(diethanolmethylammonium) cation and with an 4-chloro-2-methylphenoxyacetate and 3,6-dichloro-2-methyloxybenzoate anion and a method for their production was developed. Patent PL 236261 describes bisammonium ionic liquids with an alkyl-1,X-bis(decyldimethylammonium) cation, a method for their production and use as herbicides. Bisammonium ionic liquids di[2-(2,4-dichlorophenoxy)propionates] alkane-1,X-bis(decyldimethylammonium), a method for their preparation and use as herbicides were also developed in patent PL 228230. In 2018, a paper on the synthesis of dicationic herbicidal ionic liquids with a 2,4-dichlorophenoxyacetate anion was published (J. Niu et al., J. Agric. Food Chem. 2018, 66, 10362-10368), obtaining satisfactory results regarding herbicidal efficacy, however, the studies did not take into account the environmental fate of the synthesized compounds, and the cations used in their synthesis may be difficult to biodegrade and remain in the environment. (W. Wilms, M. Woźniak-Karczewska, A. Syguda, M. Niemczak, Ł. Ławniczak, J. Pernak, R.D. Rogers, Ł. Chrzanowski, J Agric. Food Chem. 2020, 68, 10456-10488) In the publication: M. Niemczak, R. Giszter, K. Czerniak, K. Marcinkowska, F. Walkiewicz, RSC Adv., 2015, 5, 15487-15493, bissamonium herbicide salts were described, however, in these compounds the linker between the positively charged nitrogen atoms was a straight alkyl chain or an alkyl chain with an ether bond, significantly differing in terms of physicochemical properties from the ester bond. Analyzing the state of the art, it should be noted that the use of bisammonium esterequats as plant protection agents has not attracted much interest in the scientific community so far. Only in patent application P.439594 salts with alkyl-1,ω-bis(dimethyldecyl(carboxymethyl)ammonium) cation and 3,6-dichloro-2-methoxyacetate anions were described, however, their production does not use glycine betaine, which is commonly found in the environment. Moreover, it has been proven many times that the presence of long alkyl chains in the cation hinders biodegradation due to high toxicity to bacteria. Moreover, the synthesis of the compounds that are the subject of the invention is cheap and simple. They are obtained as a result of the reaction of 1,X-dibromoalkanes with glycine betaine, which is a waste product generated during the production of sugar from sugar beets. During the synthesis, there are no side or competitive reactions, and this process does not burden the environment. Currently, there are no bisammonium quaternary salts known in the literature with an alkyl-1,ω-bis(trimethyl(carboxymethyl)ammonium) cation and 4-chloro-2-methylphenoxyacetate anions, nor any other salts with this cation that would exhibit herbicidal activity.

The essence of the invention is new quaternary bisammonium salts with an alkyl-1,X-bis(trimethyl(carboxymethyl)ammonium) cation and 4-chloro-2-methylphenoxyacetate anions of the general formula 1.

Examples of bisammonium quaternary salts with an alkyl-1,ω-bis(trimethyl(carboxymethyl)ammonium) cation and 4-chloro-2-methylphenoxyacetate anions include:

• Butyl-1,4-bis(trimethyl(carboxymethyl)ammonium di(4-chloro-2-methylphenoxyacetate) • Hexyl-1,6-bis(trimethyl(carboxymethyl)ammonium di(4-chloro-2-methylphenoxyacetate) • Octyl-1,8-bis(trimethyl(carboxymethyl)ammonium di(4-chloro-2-methylphenoxyacetate) • Decyl-1,10-bis(trimethyl(carboxymethyl)ammonium di(4-chloro-2-methylphenoxyacetate) • Dodecyl-1,12-bis(trimethyl(carboxymethyl)ammonium di(4-chloro-2-methylphenoxyacetate) The essence of the invention is also a method for the preparation of new quaternary bisammonium salts with an alkyl-1,X-bis(trimethyl(carboxymethyl)ammonium) cation and anions 4-chloro-2-methylphenoxyacetate bromides of general formula 1, in which method an alkyl-1,X-bis(trimethyl(carboxymethyl)ammonium bromide), of general formula 2, is subjected to an anion exchange reaction with a sodium or potassium salt of 4-chloro-2-methylphenoxyacetic acid in a molar ratio of the bisammonium bromide quaternary salt to the salt of 4-chloro-2-methylphenoxyacetic acid of 1:2, at a temperature of 20 to 50°C, preferably 40°C, in ethanol, in the presence of a buffer of neutral pH, and then the product is isolated.

Preferably, the resulting inorganic by-product is filtered off from the organic solvent, the solvent is evaporated from the filtrate and the reaction product is dried.

It is also advantageous when the resulting inorganic by-product is filtered off from the organic solvent, the solvent is evaporated from the filtrate, and further purification of the product is carried out by dissolving it in hot acetone or a mixture of ethyl acetate and ethanol in a 1:1 volume ratio, decanting the solution from the impurities, and then cooling it, filtering the product, washing it with ethyl acetate and drying it.

Purification may involve filtering off the inorganic residues, then cooling the mixture to a temperature of -20 to -4°C, filtering the product and drying it.

The essence of the invention is also the use of new quaternary bisammonium salts with an alkyl-1,X-bis(trimethyl(carboxymethyl)ammonium) cation and 4-chloro-2-methylphenoxyacetate anions of general formula 1 as plant protection agents, preferably in the form of a solution in distilled water in an amount corresponding to 400 g of active substance per 200 dm ³ of working liquid per 1 ha. Thanks to the use of the solution according to the invention, the following technical and economic effects were achieved:

• a simple and effective method for obtaining a new group of bisammonium quaternary salts with an alkyl-1,X-dioxybis(N,N,N-trimethyl-2-oxoethylammonium) cation and 4-chloro-2-methylphenoxyacetate anions was developed;

• the obtained salts, due to the presence of two ionic bonds, are characterized by immeasurably low volatility and do not pose a risk of atmospheric pollution;

• the synthesized compounds, thanks to two ester bonds in the cation, are susceptible to hydrolysis and biodegradation in the natural environment, without posing a risk of contamination;

• the developed synthesis methods do not generate additional pollutants that are difficult to manage;

• due to the instability of the cation in acidic and alkaline conditions, the compounds are obtained by an anion exchange reaction with strict control of the pH of the reaction mixture;

• anion exchange reactions should be carried out in an ethanol environment, because the use of methanol leads to transesterification of the bisammonium cation used, whereas in longer alcohols the reaction does not occur;

• in order to avoid undesirable hydrolysis reactions, the water content in the mixture should be controlled so that it does not exceed 2%;

• the developed synthesis methods run with yields reaching 99%, with 100% atom efficiency, and the obtained salts are characterized by high purity;

• the products demonstrate selective herbicide activity against dicotyledonous plants; these are new crop protection products.

The method of preparing the title quaternary bisammonium salts is illustrated by the following examples:

Example I

Method for producing butyl-1,4-bis(trimethyl(carboxymethyl)ammonium)di(4-chloro-2-methylphenoxyacetate)

In a 100 cm ³ round-bottomed flask were placed 6.53 g (0.0145 mol) of butyl-1,4-bis(trimethyl(carboxymethyl)ammonium chloride), 6.92 g (0.0290 mol) of 2-methyl-4-chlorophenoxyacetic acid potassium salt and 20 cm ³ of anhydrous ethanol.

To the reaction mixture was added 0.5 cm ³ of alcoholic solution of phosphate buffer with pH equal to 7. The ion exchange reaction was carried out under reflux condenser at 40°C for 5 min, constantly stirring the reagents. After this time, a precipitate of inorganic salt precipitated, which was filtered off, and then the solvent was evaporated from the filtrate under reduced pressure, obtaining 10 g of solid. The last stage of the synthesis was purification of the product by hot dissolution in a mixture of ethyl acetate and ethanol (volume 1:1), decantation of the solution from impurities, and then cooling to 4°C. The cooled mixture was filtered under reduced pressure, and the precipitate was washed with ethyl acetate. The solid residue was placed in a vacuum oven and dried to obtain 9.0 g of butyl 1,4-bis(trimethyl(carboxymethyl)ammonium di(4-chloro-2-methylphenoxyacetate) in a yield of 90%.

The structure of the compound was confirmed by performing proton and carbon nuclear magnetic resonance spectra:

1H NMR (400 MHz, DMSO-d6) δ [ppm] = 1.69-1.75 (m, 4H); 3.32 (p, 18H); 2.16 (p, 6H); 4.20-4.26 (m, 4H); 4.29 (s, 4H); 4.68 (s, 4H); 6.70 (d, J = 8.9 Hz, 2H); 7.07-7.11 (m, 2H); 7.15 (dd, J = 2.8; 0.7 Hz, 2H).

^{1 3} C NMR (100 MHz, DMSO-d6) δ [ppm = 16.0; 24.4; 52.9; 62.2; 65.1; 67.9; 112.8; 122.8; 125.9; 127.9; 129.5; 156.0; 165.2; 170.3.

Example II

Method for producing hexyl-1,6-bis(trimethyl(carboxymethyl)ammonium) di(4-chloro-2-methylphenoxyacetate)

26.7 g (0.0557 mol) of hexyl-1,6-dioxybis(trimethyl-2-oxoethylammonium) dibromide and 26.6 g (0.1114 mol) of 2-methyl-4-chlorophenoxyacetic acid potassium salt were added to a 500 cm ³ reaction vessel. Then 120 cm ³ of anhydrous ethanol was added. 2 cm ³ of MOPS buffer with pH 7 was added, and the reaction was carried out for 5 min at 50°C under reflux, with constant stirring until a precipitate precipitated. Then the temperature of the mixture was lowered to room temperature to reduce the solubility of the by-product, i.e. the inorganic salt. The precipitate obtained during the reaction was filtered off, after which the solvent was evaporated from the filtrate and 120 cm ³ of acetone was added. The resulting mixture was heated to boiling with constant stirring. The resulting solution was decanted from impurities by decantation and then placed at -20°C to lower the temperature of the system. In the next step, filtration under reduced pressure was used, obtaining the product in the form of a white solid. After washing the precipitate with ethyl acetate and drying, it was found that the reaction had occurred with a yield of 95%, giving 38 g of the product, which was hexyl-1,6-bis(trimethyl(carboxymethyl)ammonium) di(4-chloro-2-methylphenoxyacetate).

The identity of the product was confirmed by 1H and ¹³ C NMR spectra:

1H NMR (400 MHz, DMSO-d6) δ [ppm] = 1.33-1.41 (m, 4H); 1.58-1.68 (m, 4H); 3.35 (p, 18H); 4.20 (t, J = 6.5 Hz, 4H); 4.73 (s, 4H); 2.16 (p, 6H); 4.26 (s, 4H); 6.70 (d, J = 8.9 Hz, 2H); 7.07-7.11 (m, 2H); 7.15 (dd, J = 2.8; 0.7 Hz, 2H).

^{1 3} C NMR (100 MHz, DMSO-d6) δ [ppm] = 16.0; 24.7; 27.6; 52.9; 62.2; 65.5; 67.9; 112.8; 122.8; 125.9; 127.9; 129.5; 156.0; 164.9; 170.3.

Example III

Method for producing octyl-1,8-bis(trimethyl(carboxymethyl)ammonium) di(4-chloro-2-methylphenoxyacetate)

13.58 g (0.0268 mol) of octyl-1,8-dioxybis(trimethyl-2-oxoethylammonium dibromide), 11.94 g (0.0536 mol) of 2-methyl-4-chlorophenoxyacetic acid sodium salt, 45 cm ^{3 of} 98% ethanol and 1 cm ³ of an alcoholic phosphate buffer solution at pH 7 were introduced into a 250 cm ³ reactor. The reaction was carried out for 30 minutes at room temperature, with constant stirring using a magnetic stirrer. A precipitate of the crude product contaminated with sodium bromide precipitated from the reaction mixture. The precipitate was separated, and the solvent was evaporated from the filtrate. Then 50 cm ³ of acetone at 56°C was added to the residue. The whole was stirred for 20 minutes, then the inorganic salt precipitate was filtered off, and the filtrate was cooled to -20°C, as a result of which the product precipitated. Then, vacuum filtration was carried out, and then the precipitate was washed with ethyl acetate and dried. 19 g of the product was obtained in the form of a white solid, i.e. octyl-1,8-bis(trimethyl(carboxymethyl)ammonium) di(4-chloro-2-methylphenoxyacetate).

The reaction yield was 95%.

Based on the analysis of proton and carbon nuclear magnetic resonance spectra, the structure of the compound was confirmed:

1H NMR (400 MHz, DMSO-d _e ) δ [ppm]= 1.26-1.40 (m, 8H); 1.57-1.67 (m, 4H); 2.16 (p, 6H); 3.34 (p, 18H); 4.19 (t, J = 6.6 Hz, 4H); 4.26 (s, 4H); 4.71 (s, 4H); 6.70 (d, J = 8.9 Hz, 2H); 7.07-7.11 (m, 2H); 7.15 (dd, J = 2.8; 0.7 Hz, 2H).

^13C NMR (100 MHz, DMSO- _d6 ) δ [ppm]= 16.0; 25.2; 27.9; 28.6; 28.9; 52.9; 62.3; 65.7; 67.9; 112.8; 122.8; 125.9; 127.9; 129.5; 156.0; 165.1; 170.3.

Example IV

Method for the preparation of decyl-1,10-bis(trimethyl(carboxymethyl)ammonium)di(4-chloro-2-methylphenoxyacetate)

In a 100 cm ³ reaction vessel equipped with a magnetic stirrer, 6.91 g (0.0129 mol) of decyl-1,10-bis(trimethyl(carboxymethyl)ammonium dibromide) and 5.75 g (0.0258 mol) of sodium salt of 2-methyl-4-chlorophenoxyacetic acid were placed. 60 cm ³ of anhydrous ethanol and 0.5 cm ³ of MOPS buffer with pH 7 were added to the vessel. The reaction was carried out at 35°C for 7 minutes under a reflux condenser. The inorganic residue was filtered off and then the mixture was cooled to - 20°C. After filtration, the solvent was removed from the filtrate under reduced pressure. 8.5 g of the product was obtained as a white solid with a yield of 85%.

The structure of the product was confirmed by performing proton and carbon nuclear magnetic resonance spectra:

1H NMR (400 MHz, DMSO- _d6 ) δ [ppm]= 1.20-1.33 (m, 12H); 1.54-1.63 (m, 4H); 2.16 (p, 6H); 3.27 (p, 18H); 4.15 (t, J = 6.6 Hz, 4H); 4.26 (s, 4H); 4.61 (s, 4H); 6.70 (d, J = 8.9 Hz, 2H); 7.07-7.11 (m, 2H); 7.15 (dd, J = 2.8; 0.7 Hz, 2H).

^13C NMR (100 MHz, DMSO- _d6 ) δ [ppm] = 16.0; 25.2; 27.8; 28.6; 28.9; 52.9; 62.3; 65.7; 67.9; 112.8; 122.8; 125.9; 127.9; 129.5; 156.0; 165.1; 170.3.

Example V

Method for producing dodecyl-1,12-bis(trimethyl(carboxymethyl)ammonium) di(4-chloro-2-methylphenoxyacetate)

10.52 g (0.0187 mol) of dodecyl-1,12-bis(trimethyl(carboxymethyl)ammonium dibromide) and 8.93 g (0.0374 mol) of 2-methyl-4-chlorophenoxyacetic acid potassium salt were added to a 250 cm ³ flask. Then 100 cm ³ of anhydrous ethanol and 0.7 cm ³ of MOPS buffer, pH 7, were added. The reaction was carried out for 5 min at 40°C under reflux, with constant stirring using a magnetic stirrer. After the reaction was complete, when a precipitate of potassium bromide precipitated, it was separated by filtration. The solvent was evaporated from the obtained filtrate, which was the ethanol solution of the product, under reduced pressure. The reaction was found to be 95% efficient and 14.25 g of dodecyl-1,12-bis(trimethyl(carboxymethyl)ammonium di(4-chloro-2-methylphenoxyacetate) was obtained.

The structure of the product was confirmed by ¹ H and ¹³ C NMR spectra:

H NMR'(400 MHz, DMSO- _d6 ) δ [ppm]= 1.20-1.33 (m, 16H); 1.54-1.63 (m, 4H); 2.16 (p, 6H); 3.27 (p, 18H); 4.15 (t, J = 6.6 Hz, 4H); 4.26 (s, 4H); 4.60 (s, 4H); 6.70 (d, J = 8.9 Hz, 2H); 7.07-7.11 (m, 2H); 7.15 (dd, J = 2.8; 0.7 Hz, 2H).

^13C NMR (100 MHz, DMSO- _d6 ) δ [ppm]= 16.0; 25.2; 27.9; 28.6; 28.9; 52.9; 62.3; 65.7; 67.9; 112.8; 122.8; 125.9; 127.9; 129.5; 156.0; 165.1; 170.3.

PL 247337 Β1

Example use:

Studies of biological activity against weeds in greenhouse conditions.

The test plant was white mustard (Sinapis Alba L.). The plant seeds were sown in separate pots with a diameter of 12 cm filled with soil. The seeds were sown to a depth of about 1 cm, then covered with soil and watered. The plants were grown in a suitably prepared room with a humidity of 60% and a temperature of 25°C during the day and 22°C at night. The daily cycle was 18 hours of light and 6 hours of darkness. After germination and the production of cotyledons, thinning was carried out, leaving 5 plants in each pot. After the plants had developed the first 4 leaves, a selection was made as to which plants should be included in the test groups and the control group, and which ones should be removed from the study. The selection was made based on observations of the development of the plants, and the groups were created in such a way that the plants in all groups were at a similar level of development. Finally, 5 pots were selected for each test compound and the control group, each containing 5 plants.

The test groups that were created were then sprayed using a hand-held pressure sprayer, the nozzle of which was placed 40 cm from the plants. The spraying was performed after calibrating the sprayer for each application solution by spraying onto a catching bowl with a surface area identical to the surface of the pot. Each pot was sprayed separately. The application solutions were prepared by dissolving the tested compound in distilled water in an amount corresponding to 400 g of active substance per 200 dm ³ of working liquid per 1 ha. The potassium salt of 4-chloro-2-methylphenoxyacetic acid was used as the reference herbicide. After spraying, the plants were placed in a randomized manner in a room. After two weeks, the plants were cut at the soil surface and weighed. The masses of the plants after application of the herbicide salts were compared with the masses of the control objects. Based on these data, fresh mass reduction values were determined. Table 1 presents the effectiveness of selected compounds and the commercial herbicide.

Table 1

Efficacy of the tested compounds and the reference preparation on white mustard plants.

Test No. Name of the measure Fresh weight reduction (%) 1 butyl-1,4-bis(trimethyl(carboxymethyl)ammonium)di(2-methyl-4-chlorophenoxyacetate) 67% 2 di(2-methyl-4-chlorophenoxyacetate) dodecyl-1,12-bis(trimethyl(carboxymethyl)ammonium) 56% 3 2-methyl-4-chlorophenoxypotassium acetate 40%

The results of the conducted studies indicate better biological activity of the tested bisammonium salts compared to the potassium salt of the herbicide. After their application, a value of reduction in the fresh mass of plants was observed higher by at least 16% compared to the potassium salt.

Claims (6)

Patent Claims 1. New quaternary bisammonium salts with alkyl-1,X-bis(trimethyl(carboxymethyl)ammonium) cation and 4-chloro-2-methylphenoxyacetate anions of general formula 1. 2. A method for the preparation of bisammonium quaternary salts as described in claim 1, characterized in that alkyl-1,X-bis(trimethyl(carboxymethyl)ammonium bromide), of general formula 2, is subjected to an anion exchange reaction with sodium or potassium salt of 4-chloro-2-methylphenoxyacetic acid in a molar ratio of bisammonium bromide quaternary salt to 4-chloro-2-methylphenoxyacetic acid salt of 1:2, at a temperature of 20 to 50°C, preferably 40°C, in ethanol, in the presence of a buffer of neutral pH, and then the product is isolated. 3. The method according to claim 2, characterized in that the resulting inorganic by-product is filtered off from the organic solvent, the solvent is evaporated from the filtrate and the reaction product is dried. 4. The method according to claim 2, characterized in that the resulting inorganic by-product is filtered off from the organic solvent, the solvent is evaporated from the filtrate, and further purification of the product is carried out by dissolving it in hot acetone or a mixture of ethyl acetate and ethanol in a volume ratio of 1:1, decanting the solution from the impurities, and then cooling it, filtering the product, washing it with ethyl acetate and drying it. 5. The method according to claim 2, characterized in that the purification consists in filtering off the inorganic residues, then cooling the mixture to a temperature of -20 to -4°C, filtering the product and drying it. 6. Use of bisammonium quaternary salts described in claim 1 as plant protection products, preferably in the form of a solution in distilled water in an amount corresponding to 400 g of active substance per 200 dm ³ of application liquid per 1 ha.