N-ethenylformamide

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 20 g of N-vinylpyrrolidone and 2 g of N-vinylformamide were polymerized in 120 ml of water, to which 1 ml of NH4OH solution was added, at 80° C. under a blanket of argon. Initiator α,α'-azoisobutyronitrile 110 mg, polymerization time 24 h. 145 ml of concentrated hydrochloric acid were added to the resulting aqueous copolymer solution, and the mixture was refluxed (110° C.) for 7 h. The mixture was subsequently worked up as described in A using a strongly basic ion exchanger. 160 g of aqueous solution of an N-vinylamine/N-vinylpyrrolidone copolymer with an N-vinylamine content of 5.7% by weight were then obtained. The solids content of the polymer solution was 9.53%, the pH was 10.1, and the reduced viscosity of the polymer was determined as 1.61 dl/g (measured on a 1% strength solution in H2O at 25° C.). was added, at 80° C. under a blanket of argon

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a dry 500 mL three-necked round-bottomed flask equipped with magnetic stirring bar and dropping funnel were placed 11.67 g (0.164 mol) of N-vinylformamide and 200 mL of anhydrous THF. The mixture was cooled to 15° C. in an ice bath under nitrogen and a total of 18.8 g (0.167 mol) of t-BuOK was added in three portions with constant stirring over 45 minutes. 1-Bromobutane, 24.5 g (0.179 mol) was then added to the reaction mixture dropwise over 30 minutes. When addition was complete, the reaction was allowed to warm to ambient temperature and stirred overnight. After potassium bromide salt was removed, the reaction mixture was concentrated under reduced pressure and diluted with 200 mL of water. The organic layer was extracted three times with diethyl ether. The combined organic layers were washed twice with water and dried over anhydrous magnesium sulfate. The resulting product was recovered after concentration in vacuum and purification by chromatography on silica (diethyl ether/petroleum ether (v/v=3:7). yield: 11.7 g (56%). IR (NaCl, v: cm−1): 1693 (—NHC(═O)H); 1630 (C═C). 1H-NMR (CDCl3, δ: ppm): 8.31, 8.14 (2s, 1H, —C(═O)H); 7.25–7.16, 6.61–6.52 (m, 1H, H2C═CH—); 4.62–4.45 (m, 1H, HaHbC═CH—); 4.43–(s, 1H, HaHbC═CH—); 3.60–3.45 (t, 2H, —NCH2CH2—); 1.61–1.54 (m, 2H, —CH2CH2CH2—); 1.40–1.32 (m, 2H, —CH2CH2CH3); 0.99–0.94 (t, 3H, —NCH2CH2CH2CH3). Into a dry 500 mL three-necked round-bottomed flask equipped with magnetic stirring bar When addition to warm to ambient temperature stirred overnight After potassium bromide salt was removed the reaction mixture was concentrated under reduced pressure diluted with 200 mL of water The organic layer was extracted three times with diethyl ether The combined organic layers were washed twice with water dried over anhydrous magnesium sulfate The resulting product was recovered after concentration in vacuum and purification by chromatography on silica (diethyl ether/petroleum ether (v/v=3:7)

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

Procedure: To a 1000 mL three-neck round bottom flask equipped with a cold water condenser and stirrer was added 215 grams (2.5 moles) of methyl acrylate, 195 grams (2.75 moles) of N-vinylformamide, and 0.1 gram of benzoquinone. The mixture was stirred at ambient temperature for two minutes and 1.5 grams of sodium methoxide was added in one portion. The mixture was stirred for approximately 2 hours at ambient temperature and allowed to stand overnight. The reaction mixture was distilled under vacuum and 361 grams of product (92% yield) boiling at 75° C. (0.8 mm Hg) was collected for analysis. 1H NMR analysis confirmed the identity of the 3-(N-vinylformamido) adduct. To a 1000 mL three-neck round bottom flask equipped with a cold water condenser and stirrer The mixture was stirred for approximately 2 hours at ambient temperature to stand overnight

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

Procedure: To a 1000 mL three-neck round bottom flask equipped with a cold water condenser and stirrer was added 215 grams (2.5 moles) of methyl acrylate, 195 grams (2.75 moles) of N-vinylformamide, and 0.1 gram of benzoquinone. The mixture was stirred at ambient temperature for two minutes and 1.5 grams of sodium methoxide was added in one portion. The mixture was stirred for approximately 2 hours at ambient temperature and allowed to stand overnight. The reaction mixture was distilled under vacuum and 361 grams of product (92% yield) boiling at 75° C. (0.8 mm Hg) was collected for analysis. 1H NMR analysis confirmed the identity of the 3-(N-vinylformamido) adduct. To a 1000 mL three-neck round bottom flask equipped with a cold water condenser and stirrer The mixture was stirred for approximately 2 hours at ambient temperature to stand overnight

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

Procedure: To a 1000 mL three-neck round bottom flask equipped with a cold water condenser and stirrer was added 215 grams (2.5 moles) of methyl acrylate, 195 grams (2.75 moles) of N-vinylformamide, and 0.1 gram of benzoquinone. The mixture was stirred at ambient temperature for two minutes and 1.5 grams of sodium methoxide was added in one portion. The mixture was stirred for approximately 2 hours at ambient temperature and allowed to stand overnight. The reaction mixture was distilled under vacuum and 361 grams of product (92% yield) boiling at 75° C. (0.8 mm Hg) was collected for analysis. 1H NMR analysis confirmed the identity of the 3-(N-vinylformamido) adduct. To a 1000 mL three-neck round bottom flask equipped with a cold water condenser and stirrer The mixture was stirred for approximately 2 hours at ambient temperature to stand overnight

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 1H-1,2,3-benzotriazole (3.46 g, 29.1 mmol) in toluene (38 mL) was added 4-bromoaniline (5.09 g, 29.1 mmol) in toluene (4.7 mL) and the reaction mixture was bubbled with Argon gas then cooled to 0° C. Butanal (2.88 mL, 32 mmol) in toluene (4.7 mL) was added dropwise and the resulting mixture was allowed to warm to room temperature and stirred for 16 h before being treated with ethenylformamide (2.03 mL, 29.1 mmol), 4-methylbenzenesulfonic acid monohydrate (55.3 mg, 0.29 mmol). The resulting mixture was stirred at 72° C. for 3 h then cooled to room temperature and diluted with AcOEt (50 mL). The organic phase was washed with a 1M NaOH aqueous solution (20 mL), water (50 mL) then brine (50 mL), dried over MgSO4 and concentrated in vacuovacuo. The residue was recrystallised from petroleum/Et2O (1:10, 3×30 mL) to give [(cis)-6-bromo-2-propyl-1,2,3,4-tetrahydro-4-quinolinyl]formamide (2.59 g, 29%) as a white solid. the reaction mixture was bubbled with Argon gas to warm to room temperature The resulting mixture was stirred at 72° C. for 3 h then cooled to room temperature The organic phase was washed with a 1M NaOH aqueous solution (20 mL), water (50 mL) brine (50 mL), dried over MgSO4 concentrated in vacuovacuo The residue was recrystallised from petroleum/Et2O (1:10, 3×30 mL)

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

Procedure: 2,6-difluorobenzoyl chloride (35.4 ml, 50 g, 284 mmol) was added dropwise with stirring to a solution of N-vinylformamide (18 ml, 18.3 g, 258 mmol), 4-dimethylaminopyridine (3.1 g, 25.8 mmol), and triethylamine (53.8 ml, 39 g, 387 mmol) in dichloromethane (200 ml). The temperature was kept at ca 20° C. with an ice/water bath. After the addition the mixture was stirred two hours at room temperature then shaken between tBuOMe and water. The organic phase was washed with half saturated brine, dried with Na2SO4 and evaporated to give 47 g (87% crude) of 2,6-difluoro-N-formyl-N-vinyl-benzamide, which contained ca 60% of 2,6-difluoro-N-vinyl-benzamide, which is the product of the next step, in which the formyl group has already been cleaved. The temperature was kept at ca 20° C. with an ice/water bath After the addition the mixture The organic phase was washed with half saturated brine dried with Na2SO4 evaporated

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

Procedure: To a 1000 mL three-neck round bottom flask equipped with a cold water condenser and stirrer was added 215 grams (2.5 moles) of methyl acrylate, 195 grams (2.75 moles) of N-vinylformamide, and 0.1 gram of benzoquinone. The mixture was stirred at ambient temperature for two minutes and 1.5 grams sodium methoxide was added in one portion. The mixture was stirred for approximately 2 hours at ambient temperature and allowed to stand overnight. The reaction mixture was distilled under vacuum and 361 grams of product (92% yield) boiling at 75° C. (0.8 mm Hg) was collected for analysis. 1H NMR analysis confirmed the identity of the 3-N-vinylformamido adduct. To a 1000 mL three-neck round bottom flask equipped with a cold water condenser and stirrer The mixture was stirred for approximately 2 hours at ambient temperature to stand overnight

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 20 g of N-vinylpyrrolidone and 2 g of N-vinylformamide were polymerized in 120 ml of water, to which 1 ml of NH4OH solution was added, at 80° C. under a blanket of argon. Initiator α,α'-azoisobutyronitrile 110 mg, polymerization time 24 h. 145 ml of concentrated hydrochloric acid were added to the resulting aqueous copolymer solution, and the mixture was refluxed (110° C.) for 7 h. The mixture was subsequently worked up as described in A using a strongly basic ion exchanger. 160 g of aqueous solution of an N-vinylamine/N-vinylpyrrolidone copolymer with an N-vinylamine content of 5.7% by weight were then obtained. The solids content of the polymer solution was 9.53%, the pH was 10.1, and the reduced viscosity of the polymer was determined as 1.61 dl/g (measured on a 1% strength solution in H2O at 25° C.). was added, at 80° C. under a blanket of argon

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a dry 500 mL three-necked round-bottomed flask equipped with magnetic stirring bar and dropping funnel were placed 11.67 g (0.164 mol) of N-vinylformamide and 200 mL of anhydrous THF. The mixture was cooled to 15° C. in an ice bath under nitrogen and a total of 18.8 g (0.167 mol) of t-BuOK was added in three portions with constant stirring over 45 minutes. 1-Bromobutane, 24.5 g (0.179 mol) was then added to the reaction mixture dropwise over 30 minutes. When addition was complete, the reaction was allowed to warm to ambient temperature and stirred overnight. After potassium bromide salt was removed, the reaction mixture was concentrated under reduced pressure and diluted with 200 mL of water. The organic layer was extracted three times with diethyl ether. The combined organic layers were washed twice with water and dried over anhydrous magnesium sulfate. The resulting product was recovered after concentration in vacuum and purification by chromatography on silica (diethyl ether/petroleum ether (v/v=3:7). yield: 11.7 g (56%). IR (NaCl, v: cm−1): 1693 (—NHC(═O)H); 1630 (C═C). 1H-NMR (CDCl3, δ: ppm): 8.31, 8.14 (2s, 1H, —C(═O)H); 7.25–7.16, 6.61–6.52 (m, 1H, H2C═CH—); 4.62–4.45 (m, 1H, HaHbC═CH—); 4.43–(s, 1H, HaHbC═CH—); 3.60–3.45 (t, 2H, —NCH2CH2—); 1.61–1.54 (m, 2H, —CH2CH2CH2—); 1.40–1.32 (m, 2H, —CH2CH2CH3); 0.99–0.94 (t, 3H, —NCH2CH2CH2CH3). Into a dry 500 mL three-necked round-bottomed flask equipped with magnetic stirring bar When addition to warm to ambient temperature stirred overnight After potassium bromide salt was removed the reaction mixture was concentrated under reduced pressure diluted with 200 mL of water The organic layer was extracted three times with diethyl ether The combined organic layers were washed twice with water dried over anhydrous magnesium sulfate The resulting product was recovered after concentration in vacuum and purification by chromatography on silica (diethyl ether/petroleum ether (v/v=3:7)