2,2,5,5-tetramethylimidazolidin-4-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 14.2 Grams (0.1 mole) of 2,2,5,5-tetramethylimidazolidin-4-one prepared as in example 2 was dissolved in 100 milliliters of 1 Normal sodium hydroxide solution (0.1 mole) in a 250 milliliter flask. The flask containing the mixture was placed in an ice bath and maintained at or below 10° C. with stirring while chlorine gas was bubbled in until the pH reached 7.0. The product 1-chloro-2,2,5,5-tetramethylimidazolidin-4-one which precipitated as a white solid was recovered by suction filtration and was purified by recrystallization from an ether/hexane mixture. The product yield was 17.7 grams or 95% of that theoretically expected. The product had a melting point range of 157.0°-157.5° C. Analysis of the product by proton NMR and IR spectroscopy yielded the following results: 1H NMR (CDCl3) δ=1.32 (S,6H), δ=1.46 (S,6H), δ=7.57 (Broad,1H); IR (KBr) 1670, 1720, 3160 cm-1. The flask containing the mixture was placed in an ice bath maintained at or below 10° C. was bubbled in until the pH The product 1-chloro-2,2,5,5-tetramethylimidazolidin-4-one which precipitated as a white solid was recovered by suction filtration was purified by recrystallization from an ether/hexane mixture a melting point range of 157.0°-157.5° C Analysis of the product by proton NMR and IR spectroscopy yielded the following results

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.4 Grams (0.045 mole) of 2,2,5,5-tetramethylimidazolidin-4-one prepared as in example 2 was dissolved in 55 milliliters of 1 Normal sodium hydroxide solution (0.055 mole) in a 250 milliliter flask. While maintaining the reaction mixture at a temperature of 5°-10° C. by use of an ice bath and stirring, 4.0 grams (0.025 mole) of liquid bromine was added dropwise. The reaction mixture was stirred at ice bath temperature for an additional 1 hour and then for 1-2 hours at cold water bath conditions (10°-20° C.). Following cooling the mixture below 10° C. again, 50 milliliters of 1 Normal sodium hydroxide solution (0.05 mole) was added, and chlorine gas was bubbled in while stirring at 5°-10° C. until the pH reached 6-7. The 1-bromo-3-chloro-2,2,5,5-tetramethylimidazolidin-4-one product precipitated as a white solid. The product was recovered by suction filtration and purified by recrystallization from hexane. The product yield was 11.2 grams or 97% of that theoretically expected. Elemental analysis of the product gave the following results: (calculated/found) % carbon 32.88/32.68, % hydrogen 4.70/4.74, % nitrogen 10.96/10.83, % bromine 31.31/33.37, % chlorine 13.89/12.67. The rather high and low found values as compared to the theoretical values for bromine and chlorine, respectively, indicate that the product was contaminated with a small amount of 1,3-dibromo-2,2,5,5-tetramethylimidazolidin-4-one. The product was found to have a solubility in water ranging from 0.102 grams in 100 milliliters of water at 3° C. to 0.193 grams in 100 milliliters of water at 37° C. The product had a melting point of 88° C.±2° C. Analysis of the product by proton NMR and infrared spectroscopy yielded the following results: 1H NMR (CCl4) δ=1.34 (S,6H), δ =1.50 (S,6H); IR (KBr) 1700, 2950 cm-1. While maintaining the reaction mixture at a temperature of 5°-10° C. by use of an ice bath The reaction mixture was stirred at ice bath temperature for an additional 1 hour Following cooling the mixture below 10° C. again chlorine gas was bubbled in while stirring at 5°-10° C. until the pH The 1-bromo-3-chloro-2,2,5,5-tetramethylimidazolidin-4-one product precipitated as a white solid The product was recovered by suction filtration purified by recrystallization from hexane Elemental analysis of the product gave the following results at 37° C yielded the following results

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: If, instead of 7,14-diaza-15-oxo-dispiro[5.1.5.2]pentadecane, 2,2,5,5-tetramethyl-4-oxo-imidazolidine is used, and this alkylated with benzyl chloride as described in Example 1, then 3-benzyl-2,2,5,5-tetramethyl-4-oxo-imidazolidine (VII), M.P. 210°C, is obtained.

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 ml. resin kettle, equipped with a mechanical stirrer, reflux condenser, thermometer in thermowell, and an addition funnel, was charged with 122.9 g. (0.8642 moles) of 2,2,5,5-tetramethylimidazolidin-4-one, 74.8 g. (0.8642 moles) of 37% formalin solution, and 200 ml. of water. This mixture was stirred without heating as 44.2 g. (0.8642 moles) of 90% formic acid was added over the course of 20 minutes, with the mixture warming up to 30° C. and becoming a solution in this time. resin kettle, equipped with a mechanical stirrer reflux condenser thermometer in thermowell, and an addition funnel, was charged with 122.9 g without heating as 44.2 g

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 14.2 Grams (0.1 mole) of 2,2,5,5-tetramethylimidazolidin-4-one prepared as in example 2 was dissolved in 100 milliliters of 1 Normal sodium hydroxide solution (0.1 mole) in a 250 milliliter flask. The flask containing the mixture was placed in an ice bath and maintained at or below 10° C. with stirring while chlorine gas was bubbled in until the pH reached 7.0. The product 1-chloro-2,2,5,5-tetramethylimidazolidin-4-one which precipitated as a white solid was recovered by suction filtration and was purified by recrystallization from an ether/hexane mixture. The product yield was 17.7 grams or 95% of that theoretically expected. The product had a melting point range of 157.0°-157.5° C. Analysis of the product by proton NMR and IR spectroscopy yielded the following results: 1H NMR (CDCl3) δ=1.32 (S,6H), δ=1.46 (S,6H), δ=7.57 (Broad,1H); IR (KBr) 1670, 1720, 3160 cm-1. The flask containing the mixture was placed in an ice bath maintained at or below 10° C. was bubbled in until the pH The product 1-chloro-2,2,5,5-tetramethylimidazolidin-4-one which precipitated as a white solid was recovered by suction filtration was purified by recrystallization from an ether/hexane mixture a melting point range of 157.0°-157.5° C Analysis of the product by proton NMR and IR spectroscopy yielded the following results

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.4 Grams (0.045 mole) of 2,2,5,5-tetramethylimidazolidin-4-one prepared as in example 2 was dissolved in 55 milliliters of 1 Normal sodium hydroxide solution (0.055 mole) in a 250 milliliter flask. While maintaining the reaction mixture at a temperature of 5°-10° C. by use of an ice bath and stirring, 4.0 grams (0.025 mole) of liquid bromine was added dropwise. The reaction mixture was stirred at ice bath temperature for an additional 1 hour and then for 1-2 hours at cold water bath conditions (10°-20° C.). Following cooling the mixture below 10° C. again, 50 milliliters of 1 Normal sodium hydroxide solution (0.05 mole) was added, and chlorine gas was bubbled in while stirring at 5°-10° C. until the pH reached 6-7. The 1-bromo-3-chloro-2,2,5,5-tetramethylimidazolidin-4-one product precipitated as a white solid. The product was recovered by suction filtration and purified by recrystallization from hexane. The product yield was 11.2 grams or 97% of that theoretically expected. Elemental analysis of the product gave the following results: (calculated/found) % carbon 32.88/32.68, % hydrogen 4.70/4.74, % nitrogen 10.96/10.83, % bromine 31.31/33.37, % chlorine 13.89/12.67. The rather high and low found values as compared to the theoretical values for bromine and chlorine, respectively, indicate that the product was contaminated with a small amount of 1,3-dibromo-2,2,5,5-tetramethylimidazolidin-4-one. The product was found to have a solubility in water ranging from 0.102 grams in 100 milliliters of water at 3° C. to 0.193 grams in 100 milliliters of water at 37° C. The product had a melting point of 88° C.±2° C. Analysis of the product by proton NMR and infrared spectroscopy yielded the following results: 1H NMR (CCl4) δ=1.34 (S,6H), δ =1.50 (S,6H); IR (KBr) 1700, 2950 cm-1. While maintaining the reaction mixture at a temperature of 5°-10° C. by use of an ice bath The reaction mixture was stirred at ice bath temperature for an additional 1 hour Following cooling the mixture below 10° C. again chlorine gas was bubbled in while stirring at 5°-10° C. until the pH The 1-bromo-3-chloro-2,2,5,5-tetramethylimidazolidin-4-one product precipitated as a white solid The product was recovered by suction filtration purified by recrystallization from hexane Elemental analysis of the product gave the following results at 37° C yielded the following results

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.4 Grams (0.045 mole) of 2,2,5,5-tetramethylimidazolidin-4-one prepared as in example 2 was dissolved in 55 milliliters of 1 Normal sodium hydroxide solution (0.055 mole) in a 250 milliliter flask. While maintaining the reaction mixture at a temperature of 5°-10° C. by use of an ice bath and stirring, 4.0 grams (0.025 mole) of liquid bromine was added dropwise. The reaction mixture was stirred at ice bath temperature for an additional 1 hour and then for 1-2 hours at cold water bath conditions (10°-20° C.). Following cooling the mixture below 10° C. again, 50 milliliters of 1 Normal sodium hydroxide solution (0.05 mole) was added, and chlorine gas was bubbled in while stirring at 5°-10° C. until the pH reached 6-7. The 1-bromo-3-chloro-2,2,5,5-tetramethylimidazolidin-4-one product precipitated as a white solid. The product was recovered by suction filtration and purified by recrystallization from hexane. The product yield was 11.2 grams or 97% of that theoretically expected. Elemental analysis of the product gave the following results: (calculated/found) % carbon 32.88/32.68, % hydrogen 4.70/4.74, % nitrogen 10.96/10.83, % bromine 31.31/33.37, % chlorine 13.89/12.67. The rather high and low found values as compared to the theoretical values for bromine and chlorine, respectively, indicate that the product was contaminated with a small amount of 1,3-dibromo-2,2,5,5-tetramethylimidazolidin-4-one. The product was found to have a solubility in water ranging from 0.102 grams in 100 milliliters of water at 3° C. to 0.193 grams in 100 milliliters of water at 37° C. The product had a melting point of 88° C.±2° C. Analysis of the product by proton NMR and infrared spectroscopy yielded the following results: 1H NMR (CCl4) δ=1.34 (S,6H), δ =1.50 (S,6H); IR (KBr) 1700, 2950 cm-1. While maintaining the reaction mixture at a temperature of 5°-10° C. by use of an ice bath The reaction mixture was stirred at ice bath temperature for an additional 1 hour Following cooling the mixture below 10° C. again chlorine gas was bubbled in while stirring at 5°-10° C. until the pH The 1-bromo-3-chloro-2,2,5,5-tetramethylimidazolidin-4-one product precipitated as a white solid The product was recovered by suction filtration purified by recrystallization from hexane Elemental analysis of the product gave the following results at 37° C yielded the following results

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,2,5,5-Tetramethylimidazolidin-4-one (20.00 g, 140.6 mmol), prepared as described in U.S. Pat. No. 5,126,057 (Worely et al., Jun. 30, 1992), was dissolved in N,N-dimethylformamide (300 ml). To the stirring room temperature solution was added sodium hydride (60%, 5.06 g, 126.5 mmol), in 8 portions over 30 minutes. After an additional one hour of stirring at room temperature, [2-[2-(2-methoxyethoxy)ethoxy]ethoxy]p-toluenesulfonate (40.15 g, 126.1 mmol) was slowly added to the basic solution over a 20 minute period. The reaction mixture was stirred for an additional 18 hours at room temperature. The reaction mixture was concentrated under high vacuum. The solid material was dissolved in dichloromethane and the solution was filtered to remove any solid material. The organic layer was concentrated in vacuo, and crude material was purified by silica gel column chromatography (0 to 10% methanol in dichloromethane) to give 15.51 g (38%) of the title compound. 1H NMR (D2O, 400 MHz) δ 3.70-3.46 (m, 12H), 3.64-3.59 (m, 2H), 3.46 (t, J=6.2 Hz, 2H), 3.26 (s, 3H), 1.31 (s, 6H), 13C NMR (D2O, 100 MHz) δ 179.48, 76.22, 70.99, 69.59, 69.56, 69.39, 67.71, 58.90, 58.00, 39.70, 27.28, 25.67; LRMS (ESI/APCI) m/z 289 [M+H]+. The reaction mixture was stirred for an additional 18 hours at room temperature The reaction mixture was concentrated under high vacuum The solid material was dissolved in dichloromethane the solution was filtered to remove any solid material The organic layer was concentrated in vacuo, and crude material was purified by silica gel column chromatography (0 to 10% methanol in dichloromethane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,2,5,5-Tetramethylimidazolidin-4-one (3.54 g, 24.9 mmol), prepared as described in U.S. Pat. No. 5,126,057 (Worely et al., Jun. 30, 1992), was dissolved in N,N-dimethylformamide (150 ml). To the stirring room temperature solution was added sodium hydride (60%, 913 mg, 22.8 mmol), in 4 portions over 10 minutes. After an additional one hour of stirring at room temperature, the glycidol (1.4 ml, 21.1 mmol) was added to the reaction mixture. After the reaction mixture was stirred for 18 hours at room temperature, the mixture was concentrated in vacuo, and crude material is purified by silica gel column chromatography (0 to 20% methanol in dichloromethane) to give 250 mg (5%) the title compound. After the reaction mixture was stirred for 18 hours at room temperature the mixture was concentrated in vacuo, and crude material is purified by silica gel column chromatography (0 to 20% methanol in dichloromethane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: If, instead of 7,14-diaza-15-oxo-dispiro[5.1.5.2]pentadecane, 2,2,5,5-tetramethyl-4-oxo-imidazolidine is used, and this alkylated with benzyl chloride as described in Example 1, then 3-benzyl-2,2,5,5-tetramethyl-4-oxo-imidazolidine (VII), M.P. 210°C, is obtained.