(2,5-dioxopyrrolidin-1-yl) prop-2-enoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 9 (1.5 g) was dissolved in water/methanol (1:1, 10 mL) to which triethylamine was added to obtain pH 10. N-acryloyloxy succinimide (2.0 g) was added and the mixture was stirred for 2 hr. After TLC analysis indicated the complete disappearance of starting material 9, the volatiles were removed from the reaction mixture. The residue was chromatographed on a silica gel column using 20% methanol in dichloromethane. The appropriate fractions were pooled and solvent was removed to give the derivative 10 as a white foam (1.1g). 1H NMR (D2O) : δ, 1.62-1.95, mm, 6H; 2.64-2.80, m, 2H; 3.05-3.14, m, 2H; 3.28-3.35, m, 1H; 3.68-3.72, dd, 1H; 4.11-4.15, m, 2H; 4.24-4.29, m, 1H; 4.38-4.41, m, 2H; 5.82-5.86,dd, 2H, acryloyl CH2; 6.26-6.36,m, 1H, acryloyl CH: 13C NMR (D2O): 176.92, 175.14, 168.12, 129.42, 78.76, 74.44, 71.47, 66.38, 66.41, 65.70, 60.72, 38.21, 30.11, 27.62, 24.49, 22.31. was added to obtain pH 10 the volatiles were removed from the reaction mixture The residue was chromatographed on a silica gel column solvent was removed

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 9 (1.5 g) was dissolved in water/methanol (1:1, 10 mL) to which triethylamine was added to obtain pH 10. N-acryloyloxy succinimide (2.0 g) was added and the mixture was stirred for 2 hr. After TLC analysis indicated the complete disappearance of starting material 9, the volatiles were removed from the reaction mixture. The residue was chromatographed on a silica gel column using 20% methanol in dichloromethane. The appropriate fractions were pooled and solvent was removed to give the derivative 10 as a white foam (1.1g). 1H NMR (D2O) : δ, 1.62-1.95, mm, 6H; 2.64-2.80, m, 2H; 3.05-3.14, m, 2H; 3.28-3.35, m, 1H; 3.68-3.72, dd, 1H; 4.11-4.15, m, 2H; 4.24-4.29, m, 1H; 4.38-4.41, m, 2H; 5.82-5.86,dd, 2H, acryloyl CH2; 6.26-6.36,m, 1H, acryloyl CH: 13C NMR (D2O): 176.92, 175.14, 168.12, 129.42, 78.76, 74.44, 71.47, 66.38, 66.41, 65.70, 60.72, 38.21, 30.11, 27.62, 24.49, 22.31. was added to obtain pH 10 the volatiles were removed from the reaction mixture The residue was chromatographed on a silica gel column solvent was removed

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 9 (1.5 g) was dissolved in water/methanol (1:1, 10 mL) to which triethylamine was added to obtain pH 10. N-acryloyloxy succinimide (2.0 g) was added and the mixture was stirred for 2 hr. After TLC analysis indicated the complete disappearance of starting material 9, the volatiles were removed from the reaction mixture. The residue was chromatographed on a silica gel column using 20% methanol in dichloromethane. The appropriate fractions were pooled and solvent was removed to give the derivative 10 as a white foam (1.1g). 1H NMR (D2O) : δ, 1.62-1.95, mm, 6H; 2.64-2.80, m, 2H; 3.05-3.14, m, 2H; 3.28-3.35, m, 1H; 3.68-3.72, dd, 1H; 4.11-4.15, m, 2H; 4.24-4.29, m, 1H; 4.38-4.41, m, 2H; 5.82-5.86,dd, 2H, acryloyl CH2; 6.26-6.36,m, 1H, acryloyl CH: 13C NMR (D2O): 176.92, 175.14, 168.12, 129.42, 78.76, 74.44, 71.47, 66.38, 66.41, 65.70, 60.72, 38.21, 30.11, 27.62, 24.49, 22.31. was added to obtain pH 10 the volatiles were removed from the reaction mixture The residue was chromatographed on a silica gel column solvent was removed

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-hydroxysuccinimide (NAS) (1.15 g, 10.0 mmol) and triethylamine (1.53 ml) in chloroform (15 ml), acryloyl chloride (0.99 g, 11.0 mmol), cooled at 0° C., was added dropwise, under mechanical stirring, over a period of 30-min. After an additional stirring of 20 min at 0° C., the solution was washed with ice-cold water (8 ml for 2 times), dried on Na2SO4 and then filtered. 2,5-Di-tert-butylhydroquinone (0.5 mg) (polymerization inhibitor) was added to the chloroform solution, which was concentrated to a volume of 3 ml, using a rotary evaporator and filtered. Ethyl acetate (3 ml) and n-hexane (2 ml) were slowly added while stirring to the chloroform solution, which was left at 0° C. for several hours. The precipitate, a colorless solid, was separated by filtration and washed with an ice-cold solution of ethyl acetate/n-hexane (4/1) and then washed only with n-hexane. was added dropwise, under mechanical stirring, over a period of 30-min the solution was washed with ice-cold water (8 ml for 2 times) dried on Na2SO4 filtered 2,5-Di-tert-butylhydroquinone (0.5 mg) (polymerization inhibitor) was added to the chloroform solution, which was concentrated to a volume of 3 ml a rotary evaporator filtered Ethyl acetate (3 ml) and n-hexane (2 ml) were slowly added while stirring to the chloroform solution, which was left at 0° C. for several hours The precipitate, a colorless solid, was separated by filtration washed with an ice-cold solution of ethyl acetate/n-hexane (4/1) washed only with n-hexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 400 ml of chloroform, 115 g of N-hydroxysuccinimide and 72 g of acrylic acid in a reaction vessel, 206 g of N,N-dicyclohexylcarbodiimide dissolved in 100 ml of chloroform was added dropwise over a period of 2 hours under cooling with ice water. Following a 2-hour stirring at room temperature, the precipitate was filtered off and the filtrate concentrated at low temperature for crystallization. The resulting crystals were filled to give 116 g of N-acryloyloxysuccinimide (mp=61°-62° C., yield=68%). The active ester content was determined by the method of Ronald L. Schnaar and Yuan Chuan Lee described in Biochemistry, p. 1535 (1975) as 5.2×10-3 eq./g. was added dropwise over a period of 2 hours Following a 2-hour the precipitate was filtered off the filtrate concentrated at low temperature for crystallization The resulting crystals were filled

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To NIPAM (10.06 g, 88.9 mmol) and N-acryloxysuccinimide (NAS) (380 mg, 2.2 mmol) under nitrogen was added inhibitor free THF (25 ml) and toluene (25 ml). Nitrogen was bubbled through the solution for 5 minutes. The stirred reaction mixture was heated at 50° C. and free radical initiator 1,1′-azobis(cyanocyclohexane) VAZO® 88 was added (30 mg, 0.12 mmol, 0.3% by wt). The reaction was heated to 71-73° C. over 15 minutes. The reaction was further heated at this temperature for 18 hours. After this time, the solution appeared more viscous. The reaction mixture was cooled to ambient and a TLC test indicated a small amount of monomer present. The polymer was precipitated by the addition of hexane (100 ml). The white polymer is filtered off and dried under vacuum (20 mbar) to yield p(NIPAM-NAS) copolymer. (10.01 g). Nitrogen was bubbled through the solution for 5 minutes The stirred reaction mixture The reaction was heated to 71-73° C. over 15 minutes The reaction was further heated at this temperature for 18 hours The reaction mixture was cooled to ambient and a TLC test The polymer was precipitated by the addition of hexane (100 ml) The white polymer is filtered off dried under vacuum (20 mbar)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To NIPAM (10.06 g, 88.9 mmol) and N-acryloxysuccinimide (NAS) (380 mg, 2.2 mmol) under nitrogen was added inhibitor free THF (25 ml) and toluene (25 ml). Nitrogen was bubbled through the solution for 5 minutes. The stirred reaction mixture was heated at 50° C. and free radical initiator 1,1′-azobis(cyanocyclohexane) VAZO® 88 was added (30 mg, 0.12 mmol, 0.3% by wt). The reaction was heated to 71-73° C. over 15 minutes. The reaction was further heated at this temperature for 18 hours. After this time, the solution appeared more viscous. The reaction mixture was cooled to ambient and a TLC test indicated a small amount of monomer present. The polymer was precipitated by the addition of hexane (100 ml). The white polymer is filtered off and dried under vacuum (20 mbar) to yield p(NIPAM-NAS) copolymer. (10.01 g). Nitrogen was bubbled through the solution for 5 minutes The stirred reaction mixture The reaction was heated to 71-73° C. over 15 minutes The reaction was further heated at this temperature for 18 hours The reaction mixture was cooled to ambient and a TLC test The polymer was precipitated by the addition of hexane (100 ml) The white polymer is filtered off dried under vacuum (20 mbar)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 9 (1.5 g) was dissolved in water/methanol (1:1, 10 mL) to which triethylamine was added to obtain pH 10. N-acryloyloxy succinimide (2.0 g) was added and the mixture was stirred for 2 hr. After TLC analysis indicated the complete disappearance of starting material 9, the volatiles were removed from the reaction mixture. The residue was chromatographed on a silica gel column using 20% methanol in dichloromethane. The appropriate fractions were pooled and solvent was removed to give the derivative 10 as a white foam (1.1g). 13N NMR (D2O): δ, 1.62-1.95, mm, 6H; 2.64-2.80, m, 2H; 3.05-3.14, m, 2H; 3.28-3.35, m, 1H; 3.68-3.72, dd, 1H 2H; 4.24-4.29, m, 1H; 4.38-4.41, m, 2H; 5.82-5.86,dd, 2H , acryloyl CH2; 6.26-6.36,m, 1H, acryloyl CH: 13C NMR (D2O): 176.92, 175.14, 168.12, 129.42, 78.76, 74.44, 71.47, 66.38, 66.41, 65.70, 60.72, 38.21, 30.11, 27.62, 24.49, 22.31. was added to obtain pH 10 the volatiles were removed from the reaction mixture The residue was chromatographed on a silica gel column solvent was removed

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To NIPAM (10.06 g, 88.9 mmol) and N-acryloxysuccinimide (NAS) (380 mg, 2.2 mmol) under nitrogen was added inhibitor free THF (25 ml) and toluene (25 ml). Nitrogen was bubbled through the solution for 5 minutes. The stirred reaction mixture was heated at 50° C. and free radical initiator 1,1′-azobis(cyanocyclohexane) VAZO® 88 was added (30 mg, 0.12 mmol, 0.3% by wt). The reaction was heated to 71-73° C. over 15 minutes. The reaction was further heated at this temperature for 18 hours. After this time, the solution appeared more viscous. The reaction mixture was cooled to ambient and a TLC test indicated a small amount of monomer present. The polymer was precipitated by the addition of hexane (100 ml). The white polymer is filtered off and dried under vacuum (20 mbar) to yield p(NIPAM-NAS) copolymer. (10.01 g). Nitrogen was bubbled through the solution for 5 minutes The stirred reaction mixture The reaction was heated to 71-73° C. over 15 minutes The reaction was further heated at this temperature for 18 hours The reaction mixture was cooled to ambient and a TLC test The polymer was precipitated by the addition of hexane (100 ml) The white polymer is filtered off dried under vacuum (20 mbar)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 9 (1.5 g) was dissolved in water/methanol (1:1, 10 mL) to which triethylamine was added to obtain pH 10. N-acryloyloxy succinimide (2.0 g) was added and the mixture was stirred for 2 hr. After TLC analysis indicated the complete disappearance of starting material 9, the volatiles were removed from the reaction mixture. The residue was chromatographed on a silica gel column using 20% methanol in dichloromethane. The appropriate fractions were pooled and solvent was removed to give the derivative 10 as a white foam (1.1 g). 1H NMR (D2O): δ, 1.62-1.95, mm, 6H; 2.64-2.80, m, 2H; 3.05-3.14, m, 2H; 3.28-3.35, m, 1H; 3.68-3.72, dd, 1H; 4.11-4.15, m, 2H; 4.24-4.29, m, 1H; 4.38-4.41, m, 2H; 5.82-5.86,dd, 2H, acryloyl CH2; 6.26-6.36,m, 1H, acryloyl CH: 13C NMR (D2O): 176.92, 175.14, 168.12, 129.42, 78.76, 74.44, 71.47, 66.38, 66.41, 65.70, 60.72, 38.21, 30.11, 27.62, 24.49, 22.31. was added to obtain pH 10 the volatiles were removed from the reaction mixture The residue was chromatographed on a silica gel column solvent was removed