PL223215B1 - 1-methylpiperidinium ionic liquids with the theophylline anion and a method for their preparation - Google Patents

Description

Description of the invention

The subject of the invention is 1-methylpiperidinium ionic liquids with theophylline anion and a method of their preparation for use as surfactants.

Theophylline (1,3-dimethylxanthine) is a purine alkaloid that occurs naturally, e.g. in cocoa beans (Theobroma cacao) and in tea leaves (Camellia sinensis). This compound has been used in the treatment of bronchial asthma and chronic obstructive bronchopulmonary disease, it stimulates the heart rate, increases blood pressure and has anti-inflammatory properties.

The use of ionic liquids - compounds consisting of an organic cation and an organic or inorganic anion with a melting point below 100 ° C - is determined by their properties. Ionic liquids often have high electrochemical and thermal conductivity, a wide temperature range in which they exist in the liquid state, a low vapor pressure, and the ability to dissolve many inorganic and organic compounds, or even some polymers. Ionic liquids can be designed mainly because the possible number of cation-anion combinations is 10 ¹⁸ . Ammonium ionic liquids are used as herbicides (world patent WO 2012/006313) multifunctional compounds (world patent WO 2007/044693), food detectors (Polish patent PL 211376), fungicidal compounds (Polish patent PL 208419) or cellulose solvents (patent applications P.392867 and P.392868) or dyes (patent application P.388038). The patent application P.399517 describes ionic liquids with theophylline anion for use as fungicides.

The present invention relates to 1-methylpiperidinium ionic liquids with theophyllinic anion of the general formula I, in which R is a straight-chain alkyl group containing from 1 to 20 carbon atoms, or a proton, or an aryl, or allyl, or vinyl, or chloroethyl or hydroxyethyl group, or benzyl, and the method of their preparation consists in reacting a theophylline salt of general formula II, in which M is lithium or sodium or potassium or silver, or NH ₄ , with a quaternary 1-methylpiperidinium halide of the general formula 3, in which X represents chlorine or bromine or iodine in a molar ratio of 1: 0.8-1.5 in organic solvent I, the whole is stirred at a temperature from 273 to 363K, preferably 298K, for at least 15 minutes, then the solution is separated from the precipitate formed, which is an inorganic salt, and then the organic solvent I is evaporated, and the residue is washed with anhydrous acetone to remove residual salt and excess unreacted of theophylline, the residue is then dried under reduced pressure at 303 to 343K, preferably 313K, for at least 15 minutes. The organic solvent I is a linear or branched alcohol, preferably methanol or ethanol.

Another method of obtaining 1-methylpiperidinium ionic liquids with theophylline anion of general formula 1 is that theophylline is neutralized with 1-methylpiperidinium quaternary hydroxide of general formula 4 in a ratio of 1: 0.8-1.5 in water or organic solvents I, at a temperature of 273 to 363K, preferably 298K, for at least 15 minutes, then excess unreacted theophylline is filtered off, the organic solvent I is evaporated off, and the product is dried under reduced pressure for at least 1 hour at a temperature of 303 to 353K, preferably 333K. The organic solvent I is a linear or branched alcohol, preferably methanol or ethanol.

A variation of the process for the preparation of 1-methylpiperidinium ionic liquids with the theophylline anion of general formula 1 is the reaction of the theophylline salt of general formula 2, in which M is lithium or sodium or potassium or silver, or NH4, with a quaternary 1- halide. methylpiperidinium salt of the general formula, where X is chlorine or bromine or iodine in a molar ratio of 1: 0.8-1.5, in water, at 273 to 363K, preferably 293K, for at least 15 minutes, then organic solvent II is added, then the organic phase is separated from the water phase, and the organic solvent II is evaporated on a vacuum evaporator, then the product is dried under reduced pressure for at least 1 hour at a temperature of 303 to 353K, preferably 323K. The organic solvent II is a solvent that is immiscible with water, preferably chloroform or dichloromethane or toluene or ethyl acetate.

Thanks to the solution according to the invention, the following technical and economic effects were obtained:

- a new group of compounds classified as ionic liquids was obtained,

- the synthesized ionic liquids contain theophylline anion, it is the anion of the purine alkaloid,

PL 223 215 B1

- 1-methylpiperidinium theophyllinates have a low melting point,

- the obtained theophyllinates are non-volatile, thermally and chemically stable,

- the synthesized ionic liquids are soluble in water, alcohols, dichloromethane and acetone and are insoluble in hexane,

- the obtained compounds show surfactant activity,

- the compounds described can be used as washing and surface tension reducing agents.

The invention is 1-methylpiperidinium ionic liquids with theophyllinic anion of the general formula 1, and the method of their preparation is illustrated by the following examples.

P r z k ł a d I

1-dodecyl-1-methylpiperidinium theophylline

In a flask of 250 cm equipped with a mechanical stirrer was charged 0.045 mol of 1-dodecyl-1-metylopiperydyniowego dissolved in 50 cm _{3 of} ethanol and 0.045 mol of the lithium salt of theophylline dissolved in 50 ml of ethanol. The whole was intensively stirred for 12 hours at the temperature of 313K. The resulting inorganic salt was filtered off and the methanol was removed under reduced pressure. The mixture was then dried for 36 hours in an oven, vacuum _three cherry at a temperature of 328K. 50 ml of anhydrous acetone was added to the dried reaction mixture, and the precipitated inorganic salt, which was KCl, was filtered off, and the solvent of the filtrate was evaporated. Finally, the product was dried for 24 hours at the temperature of 333K under reduced pressure.

1-dodecyl-1-methylpiperidinium theophyllinate was obtained with a yield of 98%.

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

¹ H NMR (DMSO-d6) δ ppm = 0.86 (t, J = 5.9 Hz, 3H); 1.24 (m, 18H); 1.51-1.56 (m, 2H); 1.611.65 (m, 2H); 1.78 (m, 4H); 3.01 (s, 3H); 3.21 (s, 3H); 3.28-3.30 (m, 6H); 3.41 (s, 3H); 7.32 (s. 1H).

¹³ C NMR (DMSO-d6) δ ppm = 13.90; 19.28; 20.68; 20.96; 22.10; 25.87; 27.33; 28.56; 28.74; 28.86; 28.96; 29.03; 29.04; 29.76; 31.31; 46.81; 59.84; 62.44; 113.48; 145.41; 149.37; 151.68; 156.93.

Elemental CHN analysis for C25H45N5O2 (M = 447.66): calculated values: C = 67.08; H = 10.13; N = 15.64;

measured values C = 67.29; H = 10.27; N = 15.96.

P r z x l a d II

1-Benzyl-1-methylpiperidinium theophylline

To a IL beaker was added 0.01 moles of bromide _1-benzyl-1-3 metylopiperydyniowego dissolved it in 25 cm ³ of water. Then, with continuous stirring, is added 0.01 mole of the sodium salt of theophylline spread of dissolved in ₃ 30 cm of water. The reaction was carried out for 16 hours at the temperature of 300K. To the mixture was added a strait ₃ 55 cm of dichloromethane, shaken and allowed to phase separation. The organic phase was separated from the aqueous phase and evaporated on a rotary evaporator. The product was dried for 24 hours at the temperature of 313K under reduced pressure.

1-benzyl-1-methylpiperidinium theophyllinate was obtained with a yield of 99%.

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

¹ H NMR (DMSO) δ ppm = 1.47-1.49 (m, 2H); 1.59-1.62 (m, 2H); 1.63 (m, 4H); 2.94 (s, 3H); 3.32 (s, 3H); 3.31-3.35 (m, 4H); 3.39 (s, 3H); 4.61 (s. 2H); 7.30 (s. 1H); 7.50 (d, J = 8.9 Hz, 2H); 7.54 (t, J = 6.7 Hz, 1H); 7.56 (t, J = 7.3 Hz, 2H).

¹³ C NMR (DMSO-d6) δ ppm = 19.35; 20.77; 27.38; 29.83; 30.65; 45.88; 59.72; 66.41; 114.16; 127.69; 128.82; 130.14; 133,063; 145.94; 149.59; 151.76; 157.22.

Elemental CHN analysis for C ₂ o H ₂₁ N ₅ O 2 (M = 369.46) calculated values: C = 65.02, H = 7.37, N = 18.96;

measured values: C = 65.35; H = 7.38; N = 19.13.

P r x l a d III

1-Allyl-1-methylpiperidinium theophyllinate

In a reactor equipped with a magnetic stirrer, 0.005 mol of 1-allyl-1-methylpiperidinium hydroxide was dissolved in methanol, and then 0.006 mol of theophylline was added with continuous stirring. The reaction was carried out for 1.5 hours at the temperature of 303K. At the end of the process, the precipitate formed, which was unreacted theophylline, was removed and the solvent was evaporated under

Under reduced pressure, the finished product was dried at 323K for 48 hours under reduced pressure. 1-allyl-1-methylpiperidinium theophyllinate was obtained with a yield of 96%.

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

¹ H NMR (DMSO) δ ppm = 1.50-1.54 (m, 2H); 1.60-1.64 (m, 2H); 1.76 (m, 2H); 3.00 (s, 3H); 3.25 (s, 3H); 3.28-3.34 (m, 4H); 3.41 (s, 3H); 4.00 (d, J = 6.0 Hz, 2H); 4.85-4.91 (m, 2H); 5.54 (m, 1H), 7.23 (s, 1H).

¹³ C NMR (DMSO-d6) δ ppm = 25.54; 27.38; 29.82; 30.81; 46.85; 62.38; 113.99; 115.53; 130.41; 146.14; 149.56; 151.39 157.82.

Elemental CHN analysis for C ₁₆ H _{2 5} N ₅ O ₂ (M = 319.40): calculated values: C = 60.17, H = 7.89, N = 21.93;

measured values: C = 60.01; H = 7.67; N = 21.71.

P r x l a d IV

1- (2-Hydroxyethyl) -1-methylpiperidinium theophylline ₃

A round bottom flask with a capacity of 100 cm, equipped with a magnetic stirrer intro ₃ wadzono 0.01 mole of 1- (2-hydroxyethyl) -1-metylopiperydyniowego dissolved in 15 cm ₃ of isopropanol and 0.01 mole of the lithium salt of theophylline dissolved in 15 cm of isopropanol . The whole was intensively stirred for 3 hours at the temperature of 298K. The resulting inorganic salt was filtered off and the isopropanol was removed under reduced pressure. Then the mixture was dried for 12 hours in a vacuum dryer at the temperature of 323K. ₃ cm of anhydrous acetone was added to the dried reaction mixture, and the precipitated inorganic salt, which was LiCl, was filtered off, and the solvent of the filtrate was evaporated. Finally, the product was dried for 48 hours at the temperature of 333K under reduced pressure.

1- (2-Hydroxyethyl) -1-methylpiperidinium theophylline was obtained with a yield of 97%. The structure of the compound was confirmed by proton and carbon nuclear magnetic resonance spectra:

¹ H NMR (DMSO) δ ppm = 1.49-1.53 (m, 2H); 1.59-1.63 (m, 2H); 1.78 (m, 2H); 1.96 (s. 1H); 2.97 (s, 3H); 3.21 (s, 3H); 3.29-3.33 (m, 4H); 3.39 (s, 3H); 3.78 (t, J = 8.7 Hz, 2H); 4.02 (m, 2H); 7.15 (s. 1H).

¹³ C NMR (DMSO-d6) δ ppm = 25.53; 27.39; 29.82; 30.80; 46.85; 55.54; 62.38; 69.94; 114.30; 146.81; 149.93; 151.22; 157.67.

Elemental CHN analysis for C15H25N5O3 (M = 323.39): calculated values: C = 55.71, H = 7.79, N = 21.66;

measured values: C = 55.49; H = 7.56; N = 21.78.

P r z k ł a d V

1-Hexyl-1-methylpiperidinium theophyllinate ₃

0.012 ₃ mol of 1-hexyl-1-methylpiperidinium bromide dissolved in 15 cm of water and 0.012 mol of ₃ potassium theophyllinate dissolved in 15 cm of water were introduced into a 100 cm flask equipped with a magnetic stirrer. The reaction mixture was vigorously stirred for 45 minutes at room temperature.

₃

Then 20 ml of chloroform was added, mixed intensively and the aqueous phase was removed. Or ₃ ganiczną phase was washed four times with distilled water (4 x 20 cm), then removed from the solvent and the residue was dried at 333K under reduced pressure.

1-hexyl-1-methylpiperidinium theophyllinate was obtained with a yield of 92%.

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

¹ H NMR (DMSO) δ ppm = 0.85 (t, J = 4.8 Hz, 3H); 1.23-1.29 (m, 6H); 1.49-1.55 (m, 2H); 1.611.64 (m, 2H); 1.78 (m, 4H); 3.01 (s, 6H); 3.28 (t, J = 2.7 Hz, 2H); 3.29-3.34 (m, 4H); 3.40 (s, 4H); 7.16 (s. 1H).

¹³ C NMR (DMSO-d6) δ ppm = 13.80; 19.28; 20.70; 20.90; 21.90; 25.51; 27.32; 29.81; 30.70; 46.82; 59.83; 62.38; 114.78; 146.33; 149.72; 151.78; 157.39.

Elemental CHN analysis for C19H33N5O2 (M = 363.50): calculated values: C = 62.78 H = 9.15, N = 19.27;

measured values: C = 62.51, H = 9.32, N = 19.51.

Example VI - Application ₃

Theophyllinate 1.15 g of 1-dodecyl-1-metylopiperydyniowego dissolved in 250 cm ³ of distilled water. A clear solution was obtained, from which individual solutions were prepared by the method of sequential dilution. Measurements of the surface tension values were carried out using the drop shape method at 25 ° C, using the DSA100 drop shape analyzer by Kruss (Germany), at 25 ° C.

The surface activity of the aqueous solution of 1-dodecyl-1-methylpiperidinium theophyllinate is described by individual parameters: the critical concentration of micellisation within the range of 1.27x10 mol / dm and the surface tension at which the critical micellisation concentration of 28 mN / m was achieved.

Claims (6)

Patent claims 1.1-Methylpiperidinium ionic liquids with theophyllinic anion of general formula I, in which R is a straight-chain alkyl group containing from 1 to 20 carbon atoms, or a proton, or an aryl or allyl or vinyl or chloroethyl or hydroxyethyl group, or benzyl. Process for the preparation of 1-methylpiperidinium ionic liquids with theophylline anion according to claim 1, characterized in that the theophylline salt of general formula 2, in which M represents lithium or sodium or potassium or silver, or NH ₄ , is subjected to reaction with a quaternary 1-methylpiperidinium halide of the general formula 3, in which X is chlorine or bromine or iodine in a molar ratio of 1: 0.8-1.5 in an organic solvent I, the whole is stirred at a temperature from 273 to 363K, preferably 298K, for at least 15 minutes, after which the solution is separated from the precipitate formed, which is an inorganic salt, and then the organic solvent I is evaporated, and the residue is washed with anhydrous acetone to remove residual salt and excess unreacted theophylline, then the residue is dried under reduced pressure at a temperature of 303 to 343K, preferably 313K for at least 15 minutes. Process for the preparation of 1-methylpiperidinium ionic liquids with theophylline anion according to claim 1, characterized in that theophylline is neutralized with 1-methylpiperidinium quaternary hydroxide of general formula 4 in a ratio of 1: 0.8-1.5 in water or organic solvent I at a temperature of 273 to 363K, preferably 298K, for at least 15 minutes, then the excess of unreacted theophylline is filtered off, the solvent is evaporated and the product is dried under reduced pressure for at least 1 hour at a temperature of 303 to 353K, preferably 333K. 4. The method according to claims 2 and 3, characterized in that the organic solvent I is a linear or branched alcohol, preferably methanol or ethanol. Process for the preparation of 1-methylpiperidinium ionic liquids with theophylline anion according to claim 1, characterized in that the theophylline salt of general formula 2, in which M represents lithium or sodium or potassium or silver, or an NH ₄ group, is subjected to reaction with a quaternary 1-methyl-piperidinium halide of general formula 3, in which X is chlorine or bromine or iodine in a molar ratio of 1: 0.8-1.5, in water, at a temperature of 273 to 363K, preferably 293K, for at least 15 minutes, then the organic solvent II is added, then the organic phase is separated from the water phase, the organic solvent II is evaporated in a vacuum evaporator, the product is further dried under reduced pressure for at least 1 hour at a temperature of 303 to 353K, preferably 323K. 6. The method according to claim 5, characterized in that the organic solvent II is a solvent which is immiscible with water, preferably chloroform or dichloromethane or toluene or ethyl acetate.