PL237060B1 - [(3-Alkanoylmethylamino)propyl)dimethylammonium acetates and method of their preparation - Google Patents

Abstract

The subject of the application are [(3-alkanoylmethylamino)propyl]dimethylammonium acetates, of the general formula 1, in which R is a straight or branched, saturated or unsaturated hydrocarbon chain containing from 7 to 19 carbon atoms, preferably from 9 to 17 carbon atoms, which is used in household chemical products and cosmetic and pharmaceutical formulations. The invention also relates to a process for the preparation of [(3-alkanoylmethylamino)propyl] dimethylammonium acetates of the general formula 1, wherein R is a straight or branched, saturated or unsaturated, preferably saturated hydrocarbon chain containing from 7 to 19 carbon atoms, preferably from 9 to 17 atoms. carbon, characterized by the fact that in the first stage, N-[3-(dimethylamino )propyl]-N-methylalkylamide. In the second step, N-[3-(dimethylamino)propyl]-N-methylalkylamide is quaternized with sodium chloroacetate in a low-molecular-weight alcohol environment to obtain [(3-alkanoylmethylamino)propyl]dimethylammonium acetate, and the obtained crude product is purified by crystallization.

Description

Description of the invention

The present invention relates to novel [(3-alkanoylmethylamino) propyl] dimethylammonium acetates and a process for their preparation.

[(3-alkanoylmethylamino) propyl] dimethylammonium acetates are compounds belonging to the group of amphoteric surfactants containing hydrophilic groups constituting a zwitterion that can be used in household chemicals, cosmetic and pharmaceutical formulations.

From US7425527 [(3-alkanoylacetylamino) propyl] dimethylammonium acetates, N, N-dimethyltrimethylenediamine derivatives containing an amphoteric hydrophilic moiety are known. The reaction for the synthesis of [(3-alkanoylacetylamino) propyl] dimethylammonium acetates (quaternization of N-acetyl-N- [3- (dimethylamino) propyl] alkylamides with sodium chloroacetate) was carried out in the environment of boiling acetonitrile for 24 hours. oxygen-based bleach promoters in household chemicals.

From the patent description No. PL202821 there are known di-amidoamines, derivatives of long-chain aliphatic amines. They are obtained by reacting 3,3'- (alkylimino) dimethyl dipropionate with N, N-dimethyl-1,3-propanediamine under nitrogen atmosphere at 110-130 ° C. These compounds are characterized by poor or difficult solubility in water and show activity at interfaces. They can be intermediates for the production of surfactants, as well as components of cosmetic formulations and household chemicals.

AU 200630354 describes a method of producing [(3-alkanoylamino) propyl] dimethylammonium acetates, which consists in quaternizing N- [3- (dimethylamino) propyl] - N-alkylamides with sodium chloroacetate in an aqueous medium in the presence of a basic agent (preferably hydroxide) sodium at pH maintained around 7.5) at 98 ° C for 5 hours. According to the patent, these compounds could be used as components of fungicides for plant protection.

Known from the publication of J. Surfactant. Detergent., 2012, 15, 657 (D. Fen et al., "Synthesis and Surface Activities of Amidobetaine Surfactants with Ultra-long Unsaturated Hydrophobic Chains") method of obtaining amidobetaine surfactants (with an amide group in the linker) is based on the reaction Sodium chloroacetate N- [3- (dimethylamino) propyl] -N-alkylamides in ethanol: water (5: 1, w) with a 25% excess of sodium chloroacetate. The reaction is carried out at 79 ° C for 12 hours under reflux. The obtained product was purified by evaporation of the solvents and column chromatography using silica gel as the stationary phase and dry ethanol as the eluent.

The following are not known from the literature on the subject: [(3-alkanoylmethylamino) propyl] dimethylammonium acetates of the general formula I, which are the subject of the invention.

The invention relates to [(3-alkanoylmethylamino) propyl] dimethylammonium acetates of the general formula I, in which R is a straight or branched chain, a saturated or unsaturated hydrocarbon chain containing from 7 to 19 carbon atoms, preferably from 9 to 15 carbon atoms.

The essence of the solution according to the invention is also the method of producing [(3-alkanoylmethylamino) propyl] dimethylammonium acetates of the general formula I, in which R is a straight or branched, saturated or unsaturated hydrocarbon chain containing 7-19 carbon atoms, it consists in a two-stage process in which the first step of the synthesis is the preparation of N- [3- (dimethylamino) propyl] -N-methylalkylamides by reacting N, N, N'-trimethyl-1,3-propanediamine with fatty acid chloride in a mixture of tetrahydrofuran and triethylamine (1: 1, in). The reaction is carried out by adding the fatty acid chloride dropwise to a solution of N, N, N'-trimethyl-1,3-propanediamine in a mixture of tetrahydrofuran and triethylamine with vigorous stirring for 15-60 minutes, preferably 30 minutes. The resulting suspension is then vigorously stirred for another 2-12 hours, preferably 4-6 hours. After this time, the precipitate of by-product (triethylamine hydrochloride) is removed from the reaction mixture by filtration, and the solvents are then evaporated under reduced pressure on a rotary evaporator. N- [3- (dimethylamino) propyIo] -N-methylalkylamides are obtained in the form of a liquid (when acid chlorides with chains containing 8 to 16 carbon atoms are used) or a solid (when acid chlorides with chains containing more than 16 carbon atoms are used) coal). In the second step, N- [3- (dimethylamino) propyl] -N-methylalkylamides and sodium chloroacetate (1.25 fold excess over N- [3- (dimethylamino) propyl] -N

PL 237 060 B1

-methylalkylamide) is introduced into the reaction vessel designed to carry out the reaction under elevated pressure, methanol is added and the reaction is carried out at a temperature of 75-100 ° C, preferably 85-95 ° C, for 6-72 hours, preferably 24-48 hours. During this process, there may be ethanol or its mixtures with water in a ratio of 5: 1 (v: v) to 20: 1 (κν). After cooling to room temperature, the byproduct (sodium chloride) and unreacted sodium chloroacetate deposited on the reaction mixture are removed, and the solvent is then evaporated off under reduced pressure using a rotary evaporator. The product obtained is subsequently dissolved in anhydrous ethanol, filtered again, and the filtrate is evaporated on a rotary evaporator until constant weight is obtained. The obtained crude product is purified by crystallization from an organic solvent, preferably anhydrous ethanol, a mixture of methanol and ethyl acetate, methanol and diethyl ether or methanol and acetonitrile at a temperature below 5 ° C, preferably around -20 ° C.

[(3-Alkanoylmethylamino) propyl] dimethylammonium acetates according to the invention potentially exhibit a number of interesting performance properties, the most important of which are interfacial surface activity, the ability to modify (increase) the viscosity of aqueous solutions, and pH-sensitivity. For this reason, they can be used as active ingredients of washing, washing, wetting agents, especially those intended for contact with the skin, as well as viscosity modifiers in various types of household chemicals, cosmetics and pharmaceuticals. Due to the pH-responsiveness (the possibility of changing properties under the influence of the transition from cationic to anionic form or vice versa at certain pH values), they can be the so-called intelligent carriers of biologically active substances.

The main advantage of the process according to the invention is the simple production of surface-active compounds using commonly available raw materials and a wide range of potential applications due to the presence of a pH-sensitive hydrophilic moiety.

The subject of the invention is illustrated by the preparation of [(3-tetradecanoylmethylamino) propyl] dimethylammonium acetate, [(3-octanoylmethylamino) propyl] dimethylammonium acetate, [(3-octadecanoylmethylamino) propyl] dimethylammonium acetate and [(3-methylamino) propylammonium] -methylammonium acetate and [(3-methylammonium) propylammonium] acetate. and in the Reaction Schemes of which Reaction Scheme 1 shows the reaction for the formation of N- [3- (dimethylamino) propyl] -N-methylalkylamide, and the reaction Scheme 2 for the preparation of [(3-alkanoylmethylamino) propyl] dimethylammonium acetate.

P r z k ł a d 1

In the first step, to obtain N- [3- (dimethylamino) propyl] -N-methyltetradecylamide, 10.00 g (0.0861 mol) of N, N, N'-trimethyl-1,3-propanediamine in 200 cm ³ of tetrahydrofuran: triethylamine (1: 1, r: r) is then added dropwise 21.24 g (0.0861 mol) of tetradecanoyl chloride over 30 minutes while vigorously stirring the contents of the flask. Stirring is then continued for 6 h and the precipitate of triethylamine hydrochloride is removed by filtration under reduced pressure. After evaporation of the solvents under reduced pressure, 27.94 g (99.4% by weight) are obtained.

In the second step, to obtain [(3-tetradecanoylmethylamino) propyl] dimethylammonium acetate, 6.00 g (0.018 mol) of N- [3- (dimethylamino) propyl] -N- metylotetradecyloamidu, 2.62 g (0.0225 mole) of sodium chloroacetate and 60 cm ³ of methanol. The vessel is then sealed and heated for 48 hours at 85 ° C in an oil bath. After cooling to room temperature, the reaction mixture is filtered and the filtrate is evaporated under reduced pressure using a rotary evaporator. ^{100 cm 3 of} anhydrous ethanol are added to the obtained product, filtered again, and the resulting solution is evaporated under reduced pressure. The residue obtained is dissolved in the minimum amount of ethanol (about 75 cm ³ ) and allowed to crystallize in a freezer (temperature -20 ° C) for at least 24 hours. The product obtained is filtered off with suction, washed with cold ethanol and left to dry in a desiccator. The product is then dissolved in the minimum amount of methanol (about 15 cm ³ ), then diethyl ether (about 200 cm ³ ) is added in portions until a persistent turbidity appears and allowed to crystallize in a freezer (temperature -20 ° C) for at least 24 hours. The product obtained is filtered off with suction, washed with cold diethyl ether and left to dry in a desiccator under reduced pressure. 6.03 g (87.1% by weight) of the product are obtained in the form of a white solid.

Surface tensions for 0.1 and 0.01 wt.% solution in distilled water at 295 K are respectively 34.6 and 32.1 mN / m.

PL 237 060 B1

¹ H NMR spectrum of ethyl [(3-tetradekanoilometylamino) propyl] -dimethyl (solution in CDCl3), δ [ppm] (value of chemical shift relative to tetramethylsilane): 0.840.91 [t, 3H, -COCH2CH2 (CH2) ioCH3]; 1.22-1.34 [m, 20H, -COCH2CH2 (CH2) oCH3]; 1.57-1.60 [m, 2H, -COCH2CH2 (CH2) oCH3]; 1.99 [m, 2H, -N + CH2CH2CH2N-]; 2.28-2.31 [t, 2H, -COCH2CH2 (CH2) oCH3]; 3.02-3.05 [s, 3H, -N (CH3) -]; 3.34-3.45 [s, 6H; -N ⁺ (CH3) 2-]; 3.63-3.67 [m, 4H, -N + CH2CH2CH2N-]; 3.994.03 [s, 2H, -N + CH2COO-].

P r z k ł a d 2

In the first step, to obtain N- [3- (dimethylamino) propyl] -N-methyloctylamide, 10.00 g (0.0861 mol) of N, N, N'-trimethyl-1,3-propanediamine in 200 cm ^{3 of a} mixture of tetrahydrofuran: triethylamine (1: 1, w), and then 14.01 g (0.0861 mol) of octanoyl chloride are added dropwise over 15 minutes, while vigorously stirring the contents of the flask. Stirring is then continued for 4 h and the precipitate of triethylamine hydrochloride is removed by filtration under reduced pressure. After evaporating the solvents under reduced pressure, 20.47 g (98.1% by weight) are obtained.

In the second step, to obtain [(3-octanoylmethylamino) propyl] dimethylammonium acetate, 4.36 g (0.018 mol) of N- [3- (dimethylamino) propyl] -N- are introduced into a vessel to be reacted under elevated pressure. methyloctylamide, 2.62 g (0.0225 mol) sodium chloroacetate and 100 cm ³ of ethanol: water (5: 1, w). The vessel is then sealed and heated for 6 hours at 100 ° C in an oil bath. The procedure is then as in Example 1. The residue obtained after evaporating off anhydrous ethanol is dissolved in a minimum amount of ethanol (about 10 cm ³ ), then ethyl acetate (about 150 cm ³ ) is added in portions until a persistent turbidity appears and the crystallization is allowed to take place in the freezer (temperature -20 ° C) for at least 24 hours. The product obtained is filtered off with suction, washed with cold ethyl acetate and left to dry in a desiccator under reduced pressure. 3.76 g (69.6 wt%) of the product are obtained in the form of a white solid.

Surface tensions for 0.1 and 0.01 wt.% solution in distilled water at 295 K are respectively 28.4 and 42.8 mN / m.

1H NMR spectrum of [(3-Octanoylmethylamino) propyl] dimethylammonium acetate (CDCl3 solution), δ [ppm] (chemical shift value from tetramethylsilane standard): 0.860.92 [t, 3H, -COCH2CH2 (CH2) 4CH3]; 1.20-1.35 [m, 8H, -COCH2CH2 (CH2) 4CH3]; 1.55-1.61 [m, 2H, -COCH2CH2 (CH2) 4CH3]; 2.01 [m, 2H, -N + CH2CH2CH2N-]; 2.25-2.35 [t, 2H, -COCH2CH2 (CH2) 4CH3];

3.00-3.06 [s, 3H, -N (CH3) -]; 3.31-3.46 [s, 6H; -N ⁺ (CH3) 2-]; 3.60-3.64 [m, 4H, -N + CH2CH2CH2N-]; 3.984.02 [s, 2H, -N + CH2COO-].

P r z k ł a d 3

In the first step, to obtain N- [3- (dimethylamino) propyl] -N-methyloctadecylamide, 10.00 g (0.0861 mol) of N, N, N'-trimethyl-1,3-propanediamine in 200 cm ^{3 of a} mixture of tetrahydrofuran: triethylamine (1: 1, w), and then 28.50 g (0.0861 mol) of octadecnooyl chloride are added dropwise over 30 minutes while vigorously stirring the contents of the flask. Stirring is then continued for 2 h and the precipitate of triethylamine hydrochloride is removed by filtration under reduced pressure. After evaporating the solvents under reduced pressure, 35.10 g (99.5% by weight) are obtained.

In the second step, to obtain [(3-octadecanoylmethylamino) propyl] dimethylammonium acetate, 7.38 g (0.018 mol) of N- [3- (dimethylamino) propyl] -N- methyloctadecanoylamide, 2.62 g (0.0225 mol) sodium chloroacetate and 120 cm ³ of ethanol: water (20: 1, w). The vessel is then sealed and heated for 72 hours in an oil bath at 75 ° C. The procedure is then as in Example 1. The residue obtained is dissolved in a minimum amount of ethanol (about 100 cm ³ ) and left to crystallize in a freezer (temperature -20 ° C) for at least 24 hours. The product obtained is filtered off with suction, washed with cold ethanol and left to dry in a desiccator. The product is then dissolved in a minimum amount of ethanol (about 45 cm ³ ), then ethyl acetate (about 120 cm ³ ) is added portionwise until a persistent turbidity appears and allowed to crystallize in a freezer (temperature -20 ° C) for at least 24 hours. The product obtained is filtered off with suction, washed with cold ethyl acetate and left to dry in a desiccator under reduced pressure. The product obtained is filtered off with suction, washed with cold ethyl acetate and left to dry in a desiccator.

PL 237 060 B1 under reduced pressure. 7.40 g (87.9 wt%) of the product are obtained in the form of a white solid.

Surface tension for 0.01 wt.% the solution in distilled water at 295 K is 33,6 mN / m.

1H NMR spectrum of [(3-Octadecanoylmethylamino) propyl] dimethylammonium acetate (CDCl3 solution), δ [ppm] (chemical shift value from tetramethylsilane standard): 0.880.93 [t, 3H, -COCH2CH2 (CH2) 14CH3]; 1.25-1.36 [m, 28H, -COCH2CH2 (CH2) i4CH3]; 1.54-1.60 [m, 2H, -COCH2CH2 (CH2) 14CH3]; 1.99 [m, 2H, -N + CH2CH2CH2N-]; 2.24-2.35 [t, 2H, -COCH2CH2 (CH2) i4CH3]; 3.03-3.06 [s, 3H, -N (CH3) -]; 3.31-3.46 [s, 6H; -N + (CH3) 2-]; 3.63-3.66 [m, 4H, -N + CH2CH2CH2N-]; 4.004.05 [s, 2H, -N ⁺ CH2COO-].

P r z k ł a d 4

In the first step, to obtain N- [3- (dimethylamino) propyl] -N-methylicosylamide, 10.00 g (0.0861 mol) of N, N, N'-trimethyl-1,3-propanediamine in 200 cm ^{3 of a} mixture of tetrahydrofuran: triethylamine (1: 1, w), and then 28.50 g (0.0861 mol) of icosyl chloride are added dropwise over 60 minutes, while vigorously stirring the contents of the flask. Stirring is then continued for 12 h and the precipitate of triethylamine hydrochloride is removed by filtration under reduced pressure. After evaporating the solvents under reduced pressure, 35.24 g (99.9% by weight) are obtained.

In the second step, to obtain [(3-icosylmethylamino) propyl] dimethylammonium acetate, 7.38 g (0.018 mol) of N- [3- (dimethylamino) propyl] -N- are introduced into a vessel to be reacted under elevated pressure. methylicosylamide, 2.62 g (0.0225 mol) of sodium chloroacetate and 150 cm ^{3 of} ethanol. The vessel is then sealed and heated for 24 hours at 95 ° C in an oil bath. The procedure is then as in Example 1. The residue obtained is dissolved in a minimum amount of ethanol (about 100 cm ³ ) and allowed to crystallize in a freezer (temperature -20 ° C) for at least 24 hours. The product obtained is filtered off with suction, washed with cold ethanol and left to dry in a desiccator. The obtained residue after evaporation of the anhydrous ethanol is dissolved in the minimum amount of methanol (about 10 cm ³ ), then acetonitrile (about 150 cm ³ ) is added in portions until a permanent turbidity appears and the crystallization is allowed to take place in the refrigerator (temperature 2-4 ° C). for at least 24 hours. The product obtained is filtered off with suction, washed with cold acetonitrile and left to dry in a desiccator under reduced pressure. 8.96 g (90.9 wt%) of the product are obtained in the form of a white solid.

Surface tension 0.01 wt.% the solution in distilled water at 295 K is 39,3 mN / m.

1H NMR spectrum of [(3-icosylmethylamino) propyl] dimethylammonium acetate (solution in CDCl3), δ [ppm] (chemical shift value from tetramethylsilane standard): 0.89-0.91 [t, 3H, -COCH2CH2 (CH2) 16CH3]; 1.24-1.33 [m, 32H, -COCH2CH2 (CH2) isCH3]; 1.55-1.61 [m, 2H,

-COCH2CH2 (CH2) 16CH3]; 1.98 [m, 2H, -N + CH2CH2CH2N-]; 2.25-2.37 [t, 2H, -COCH2CH2 (CH2) isCH3]; 3.01-3.04 [s, 3H, -N (CH3) -]; 3.30-3.44 [s, 6H; -N + (CH3) 2-]; 3.62-3.65 [m, 4H, -N + CH2CH2CH2N-]; 4.034.05 [s, 2H, -N ⁺ CH2COO-].

Claims (11)

Patent claims CLAIMS 1. [(3-alkanoylmethylamino) propyl] dimethylammonium acetates, of the general formula I, in which R is a straight or branched, saturated or unsaturated hydrocarbon chain containing from 7 to 19 carbon atoms, preferably from 9 to 17 carbon atoms. 2. A method for producing [(3-alkanoylmethylamino) propyl] dimethylammonium acetates of general formula I, wherein R is straight or branched, saturated or unsaturated, preferably saturated hydrocarbon chain containing from 7 to 19 carbon atoms, preferably from 9 to 17 carbon atoms characterized in that in the first step by reacting N, N, N'-trimethyl-1,3-propanediamine with a fatty acid chloride in an organic solvent in the presence of a basic hydrogen chloride scavenger, N- [3- (dimethylamino) is obtained propyl] -N-methylalkylamide in a second step quaternization of N- [3- PL 237 060 B1 - (dimethylamino) propyl] -N-methylalkylamide with sodium chloroacetate in a medium of low molecular alcohol to give [(3-alkanoylmethylamino) propyl] dimethylammonium acetate, and the obtained crude product is purified by crystallization. 3. The method according to p. The process of claim 2, characterized in that the first step of the reaction is carried out in a solvent mixture, preferably tetrahydrofuran / triethylamine. 4. The method according to p. The process according to claim 2, characterized in that the dropwise addition of the fatty acid chloride in the first reaction stage takes 15-60 minutes, preferably 30 minutes. 5. The method according to p. The process of claim 2, characterized in that stirring is continued for 2-12 h, preferably 4-6 h in the first reaction step after the dropwise addition of the fatty acid chloride is completed. 6. The method according to p. The process of claim 2, wherein triethylamine is used as the hydrogen chloride scavenger. 7. The method according to p. The process of claim 2, characterized in that the quatemization of N- [3- (dimethylamino) propyl] -N-methylalkylamide with sodium chloroacetate is carried out in a low molecular weight alcohol medium, preferably methanol, ethanol or an ethanol-water mixture. 8. The method according to p. The process of claim 2, characterized in that the quaternization of N- [3- (dimethylamino) propyl] -N-methylalkylamide with sodium chloroacetate is carried out for 6-72 h, preferably 24-48 h. 9. The method according to p. The process according to claim 2, characterized in that the quaternization of N- [3- (dimethylamino) propyl] -N-methylalkylamide with sodium chloroacetate is carried out at a temperature of 75-100 ° C, preferably 85-95 ° C. 10. The method according to p. The process of claim 2, characterized in that [(3-alkanoylmethylamino) propyl] dimethylammonium acetates are purified by crystallization from low molecular weight alcohol, preferably ethanol or a mixture of solvents: methanol and ethyl acetate, methanol and diethyl ether or methanol and acetonitrile. 11. The method according to p. The process of claim 2, wherein the crystallization of [(3-alkanoylmethylamino) propyl] dimethylammonium acetates is carried out at a temperature below 5 ° C, preferably around -20 ° C.