PL212807B1 - Imidazolic ionic liquids with nitroimidazolic anion and method of production of imidazolic ionic liquids with nitroimidazolic anion - Google Patents

Description

The present invention relates to imidazolium ionic liquids with a nitroimidazole anion and a method for the preparation of imidazolium ionic liquids with a nitroimidazole anion.

In heterocyclic amines, also called azoles, the nitrogen atoms are part of the ring. These compounds have retained their common names. A typical representative of the 5 membered azole ring is imidazole.

Nitroimidazoles are compounds known for many years, mainly due to their enormous therapeutic potential. Depending on the location of the nitro substituent in the ring, their therapeutic potential changes - derivatives with a substituent in position 2 show the strongest activity. One of the leading chemotherapeutic agents to fight anaerobic bacteria is metronidazole (systematic name 2-methyl-5-nitro-1H-imidazole-1). -ethanol). It is one of the 2-methyl-5-nitroimidazole derivatives.

The presence of more than two nitro groups causes a drastic increase in the explosiveness of the compound. Nitric imidazole derivatives are also used as explosives. No ion pairs containing a cation and an anion as an azole have been described in the literature so far. These vapors with melting points below 373 K constitute a new group of chemical compounds known as ionic liquids.

Currently, ionic liquids are defined as salts with a melting point below 373 K. Most often, these salts are characterized by a wide range of fluidity, sometimes exceeding 400 degrees (the range between the melting point and boiling point, or rather decomposition). Low vapor pressure and high thermal and chemical stability meant that ionic liquids were defined as green solvents. They are successfully tested as effective replacements for the popularly used molecular solvents. Since in some cases they exhibit catalytic activity, they can be used as catalysts and solvents simultaneously.

The invention relates to imidazolium nitroimidazoleates of the general formula I wherein R ¹ , R ³ represent a straight chain alkyl substituent containing from 1 to 18 carbon atoms, or an alkoxymethyl substituent (-CH2OR) containing from 2 to 18 carbon atoms or an alkylthiomethyl substituent (-CH2SR) containing from 2 to 18 carbon atoms, R ² is a proton or a straight chain alkyl substituent having 1 to 4 carbon atoms, R ⁴ is a proton or a methyl group, and R ⁵ is a nitro group.

The preparation of imidazolium nitroimidazolates of the general formula 1 consists in the imidazole halides of the general formula 2 in which R ¹ , R ³ are a straight chain alkyl substituent containing from 1 to 18 carbon atoms or an alkoxymethyl substituent (-CH 2 OR) containing 2 to 18 carbon atoms or an alkylthiomethyl substituent (-CH2SR) containing 2 to 18 carbon atoms, R ² is a proton or a straight chain alkyl substituent having 1 to 4 carbon atoms, Y is bromine or chlorine or iodine, is exchanged in a molar ratio 1: (0.8-1.5) at a temperature of 273 K to boiling in an alcoholic medium (methanol or ethanol or propanol or butanol) with an organic salt of the general formula 3, in which R ⁴ is a proton or a methyl group, R ³ is a nitro group, M is a lithium or potassium or sodium or ammonium cation, and after removing the inorganic salt, the alcohol is evaporated, then 5 - 25 cm ^{3 of} anhydrous acetone are added, and then the product is dried. the vacuum ark.

Another method of preparation consists in subjecting the imidazolium halides of the general formula II to metathesis, in a molar ratio of 1: (0.8-1.5) at a temperature of 273 to 373 K in water, with an organic salt of the general formula 3, then 20 - 200% of the original volume of hydrophobic organic solvent is added to the post-reaction mixture, and then the organic layer is rinsed with distilled water until the disappearance of halide ions in the effluent, the presence of which is monitored with silver nitrate solution, and it is dried after evaporating off the solvent.

Another method of preparation consists in subjecting the imidazolium halides of the general formula 2 to metathesis with an organic salt of the general formula 3 in a molar ratio of 1: (0.8-1.5) at a temperature of 273 K to the boiling point at d. chloroform or chloroform-acetone, or chloroform-methanol, or chloroform-ethanol, or dichloromethane or dichloromethane-acetone or dichloromethane-methanol or dichloromethane-ethanol environment, then the solvent is removed from the reaction mixture, and 5 - 25 cm is added to the residue. ³

Anhydrous acetone is then removed, then the precipitate is removed and the evaporation residue is dried in a vacuum oven.

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

- organic compounds with ionic structure not described in the literature were obtained;

- the synthesized compounds contain an imidazolium cation and a nitroimidazolium anion;

the compounds obtained belong to the imidazolium ionic liquids;

- isolated imidazolium ionic liquids, depending on the size of the cation, can be hydrophilic and hydrophobic;

- the ionic nature of the synthesized imidazolium ionic liquids causes that the compounds do not evaporate at moderate temperatures.

The invention relates to imidazolium nitroimidazoleates of the general formula I wherein R ¹ , R ³ are a straight chain alkyl substituent containing from 1 to 18 carbon atoms or an alkoxymethyl substituent (-CH2OR) containing from 2 to 18 carbon atoms or an alkylthiomethyl substituent (-CH2SR) containing from 2 to 18 carbon atoms, R ² is a proton or a straight chain alkyl substituent having 1 to 4 carbon atoms, R ⁴ is a proton or methyl group, R ⁵ is nitro.

The method of their preparation is illustrated by the following examples:

P r z k ł a d I

1-Butyl-3-methylimidazolium 4-nitroimidazoleate

In a 100 cm ³ bottom bottom flask equipped with a magnetic stirrer, 10 mmoles of 1-butyl-3-methylimidazolium iodide in 20 cm ^{3 of} methanol were added and 11.5 mm ^{3 of} sodium nitroimidazoleate in 10 cm 3 of methanol were added. The mixture was vigorously stirred for one hour at room temperature. The precipitate formed inorganic salt was then filtered off, and the filtrate's solvent was evaporated. ^{5 cm 3 of} anhydrous acetone were added to the residue. After mixing, the precipitate was removed, followed by the solvent. The residue was dried under reduced pressure.

The product, in the form of a yellow liquid, was obtained with a yield of 91%.

Compound purity was confirmed by elemental CHN analysis. The following values were found for the salt of the summarized formula C11H17N5O2 (M = 251.28): calculated C = 52.58; H = 6.82; N = 27.87, Found C = 52.16; H = 6.54; N = 27.56%.

P r z x l a d II

1-Methyl-3-pentylimidazolium 2-methyl-5-nitroimidazolate

10 mmol of 1-methyl-3-pentyloimidazoliowego in 20 cm ^{3 of} ethanol was added 15 mmol 2-methyl-5-nitroimidazolanu lithium in 10 cm ³ of ethanol. The mixture was vigorously stirred for an hour at reflux. After cooling to room temperature, the formed inorganic salt precipitate was filtered off, and the filtrate's solvent was evaporated. To the residue was added 10 cm ³ of acetone over 3A molecular sieves and the pellet was discarded. After acetone was evaporated, the residue was dried in a vacuum dryer at 353 K.

The product, in the form of a yellow liquid, was obtained with a yield of 98%.

The purity of 2-methyl-5-nitroimidazolane was confirmed by elemental CHN analysis. For the salt with the formula C13H21N5O2 (M = 279.34), the following values were obtained: calculated: C = 55.90; H = 7.58; N = 25.07; and measured: C = 55.74; H = 7.28; N = 24.83; expressed as a percentage.

P r z x l a d III

1-Methyl-3-pentyloxymethylimidazolium 4-nitroimidazoleate

0.01 mole of 1-methyl-3-pentyloksymetyloimidazoliowego dissolved in 20 cm ³ of chloroform was added 0.008 mol of 4-nitroimidazolanu ammonium in 10 cm ³ of methanol. The mixture was vigorously stirred for an hour at 313 K. The resulting inorganic salt precipitate was filtered off from the cool reaction mixture, and the solvent of the filtrate was evaporated. To the residue was added 20 cm ³ of acetone dehydrated with molecular sieves 3A was filtered off, and the remainder of the inorganic salt. After evaporating off the solvent, the residue was dried under reduced pressure at a temperature of 363 K.

The product, in the form of a yellow liquid, was obtained with a yield of 94%.

Compound purity was confirmed by elemental CHN analysis. For the salt of the summarized formula C13H21N5O3 (M = 295.34), the following calculated values were obtained: C = 52.87; H = 7.17;

N = 23.71; and experimental values: C = 52.49; H = 6.93; N = 23.49; they are expressed as a percentage.

PL 212 807 B1

P r x l a d IV

1-heptylthiomethyl-3-methylimidazolium 2-methyl-5-nitroimidazolate

0.01 Mole of 1-heptylthiomethyl-3-methylimidazolium bromide in 20 cm ^{3 of} dichloromethane and added potassium 2-methyl-5-nitroimidazoleate with a 20% excess dissolved in 10 cm ^{3 of} ethanol. The mixture was vigorously stirred for one hour at room temperature. The precipitate formed inorganic salt was then filtered off, and the filtrate's solvent was evaporated. To the residue was added 15 cm ^{3 of} anhydrous acetone and filtered remainder of potassium bromide. After evaporating off the solvent, the residue was dried under reduced pressure at 353 K.

The product in the form of a yellow liquid was obtained with a yield of 93%.

Compound purity was confirmed by elemental CHN analysis. For the salt with the formula C16H27N5O2S (M = 353.48) the calculated values: C = 54.37; H = 7.70; N = 19.81; and the values found C = 54.01; H = 7.38; N = 19.62; in%.

P r z k ł a d V

1-heptyloxymethyl-3-propylthiomethylimidazolium 4-nitroimidazoleate

20 cm ^{3 of} chloroform was dissolved 0.012 mol of 4-nitroimidazolanu potassium was added 0.01 mol of 1-heptyloksymetylo-3-propyltiometyloimidazoliowego in 10 cm ³ of methanol. The mixture was vigorously stirred for an hour. The precipitate formed inorganic salt was then filtered off, and the filtrate's solvent was evaporated. To the residue was added 10 cm ³ of acetone containing no water and filtered off the remainder of the potassium chloride. After evaporating off the solvent, the residue was dried under reduced pressure at a temperature of 373 K.

The product in the form of a yellow liquid was obtained with a yield of 96%.

The purity of the nitroimidazoleate was confirmed by elemental CHN analysis. With the following calculated values for the salt of the formula C18H31N5O3S (M = 397.53): C = 54.38; H = 7.86; N = 17.62 and measured values C = 54.06; H = 7.58; N = 17.36 they are expressed as a percentage.

P r x l a d VI

1-Methyl-3-octylimidazolium 2-methyl-5-nitroimidazolate

In a bottom 100 cm ³ bottom flask equipped with a magnetic stirrer, 0.01 mol of 1-methyl-3-octylimidazolium bromide in 20 cm ^{3 of} acetone was introduced and 0.008 mol of sodium 2-methyl-5-nitroimidazole in 10 cm was added. ^{3 of} dichloromethane. The mixture was vigorously stirred for an hour at reflux. The resulting inorganic salt precipitate was then filtered off from the cool solution and the solvent was evaporated. To the residue was added 10 cm ³ of anhydrous acetone and odsą czono remainder sodium bromide. After evaporating off the solvent, the residue was dried under reduced pressure at a temperature of 353 K.

The product in the form of a yellow liquid was obtained with a yield of 96%.

Purity was determined acid-base by titration with 0.1M HCl against methyl orange. Getting a purity of 95%.

The purity of the nitroimidazoleate was confirmed by elemental CHN analysis. For the salt with the formula C15H25N5O2 (M = 307.39), the following values were obtained: calculated: C = 58.61; H = 8.20; N = 22.78 and measured C = 58.29; H = 8.02; N = 22.52 expressed as a percentage.

Claims (4)

CLAIMS 1. Imidazolium nitroimidazoleates of general formula I wherein R ¹ , R ³ represent a straight chain alkyl substituent containing from 1 to 18 carbon atoms or an alkoxymethyl substituent (-CH2OR) containing from 2 to 18 carbon atoms or an alkylthiomethyl substituent (-CH2SR) containing from 2 to 18 carbon atoms, R ² is a proton or a straight chain alkyl substituent having 1 to 4 carbon atoms, R ⁴ is a proton or methyl group, and R ³ is nitro. Process for the preparation of imidazolium nitroimidazolates according to claim 1, characterized in that the imidazole halides of the general formula 2, wherein R ¹ , R ³ represent a straight chain alkyl substituent containing from 1 to 18 carbon atoms or an alkoxymethyl substituent (-CH 2 OR) containing 2 to 18 carbon atoms or an alkylthiomethyl substituent (-CH2SR) containing 2 to 18 carbon atoms, R ² is a proton or a straight chain alkyl substituent having 1 to 4 carbon atoms, Y is bromine or chlorine or iodine, molar 1: (0.8-1.5) at a temperature of 273 K to boiling in an alcoholic medium, preferably in methanol or ethanol or propanol or butanol with an organic salt of the general formula 3, in which R ⁴ PL 212 807 B1 is a proton or a methyl group, R ³ is a nitro group, M is a lithium or potassium or sodium or ammonium cation, and after removing the inorganic salt, the alcohol is evaporated, then 5 - 25 cm ³ are added from anhydrous acetone and then the product is dried in a vacuum oven. Process for the preparation of imidazolium nitroimidazolates according to claim 1, characterized in that imidazolium halides of the general formula 2 are subjected to a metathesis reaction in a molar ratio of 1: (0.8-1.5) at a temperature of 273 to 373 K in water, with an organic salt of the general formula 3, 20-200% of the original volume of the hydrophobic organic solvent is added to the reaction mixture, then the organic layer is washed with distilled water until the disappearance of halide ions in the effluent, and after evaporation of the solvent, the whole is dried. Process for the preparation of imidazolium nitroimidazolates according to claim 1, characterized in that imidazolium halides of general formula 2 are metathesized with an organic salt of general formula 3 in a molar ratio of 1: (0.8-1.5) at a temperature of from 273 K to boil in chloroform or chloroform-acetone, or chloroform-methanol, or chloroform-ethanol, or dichloromethane or dichloromethane-acetone or dichloromethane-methanol or dichloromethane-ethanol, and then remove the solvent from the reaction mixture. the residue is added to 5-25 cm ^{3 of} anhydrous acetone, then the precipitate is removed and the evaporation residue is dried in a vacuum oven.