1,1-二乙氧基乙烷(乙缩醛)

反应条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution containing chromene 4 (344 mg, 1.0 mmol), acetaldehyde diethylacetal (473 mg, 4.0 mmol), trifluoroacetic acid (1.5 mL, 19.4 mmol) and anhydrous pryidine (0.7 mL) was heated at 140° C. under N2. The reaction was monitored by TLC analysis. After 4 hours, the reaction mixture was cooled to room temperature, diluted with ehtyl acetate and washed several times with 10% aqueous NaHCO3 and brine. The organic layer was separated and dried over Na2SO4. The solvent was removed in vacuo and the crude product was purified by silica gel column chromatography eluting with ethyl acetate/hexane (2:3). Chromanone 7 (10,11-trans-dihydro-6,6,10,11-tetramethyl-4-propyl-2H,6H,12H-benzo[1,2-b:3,4-b':5,6-b"]-tripyran-2,12-dione) (110 mg, 30% yield) was obtained m.p. 176°-177° C. (Lit.5 130°-132° C.). 1H-NMR5 (CDCl3) δ 1.02 (3H, t, J=7.5 Hz, CH3); 1.21 (3H, d, J=6.8 Hz, CH3); 1.51 (3H, d, J=7.0 Hz, CH3); 1.55 (6H, 2s, 2 CH3); 1.63 (2H, sextet, J=7.0 Hz, CH2); 2.55 (1H, dq, J=6.9 Hz, J=11.0 Hz, H11); 2.88 (2H, t, J=7.6 Hz, CH2); 4.28 (1H, dq, J=6.3 Hz, J=11.0 Hz, H10); 5.60 (1H, d, J=9.9 Hz, H8); 6.04 (1H, s, H3); 6.65 (1H, d, J=11.8 Hz, H7); MS (CI): 369 (100, M+1). the reaction mixture was cooled to room temperature washed several times with 10% aqueous NaHCO3 and brine The organic layer was separated dried over Na2SO4 The solvent was removed in vacuo the crude product was purified by silica gel column chromatography eluting with ethyl acetate/hexane (2:3)

反应条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution containing chromene 4 (344 mg, 1.0 mmol), acetaldehyde diethylacetal (473 mg, 4.0 mmol), trifluoroacetic acid (1.5 mL, 19.4 mmol) and anhydrous pryidine (0.7 mL) was heated at 140° C. under N2. The reaction was monitored by TLC analysis. After 4 hours, the reaction mixture was cooled to room temperature, diluted with ehtyl acetate and washed several times with 10% aqueous NaHCO3 and brine. The organic layer was separated and dried over Na2SO4. The solvent was removed in vacuo and the crude product was purified by silica gel column chromatography eluting with ethyl acetate/hexane (2:3). Chromanone 7 (10,11-trans-dihydro-6,6,10,11-tetramethyl-4-propyl-2H,6H,12H-benzo[1,2-b:3,4-b':5,6-b"]-tripyran-2,12-dione) (110 mg, 30% yield) was obtained m.p. 176°~177° C. (Lit.5 130°~132° C.). 1H-NMR5 (CDCl3) δ 1.02 (3H, t, J=7.5 Hz, CH3); 1.21 (3H, d, J=6.8 Hz, CH3); 1.51 (3H, d, J=7.0 Hz, CH3); 1.55 (6H, 2s, 2 CH3); 1.63 (2H, sextet, J=7.0 Hz, CH2); 2.55 (1H, dq, J=6.9 Hz, J=11.0 Hz, H11); 2.88 (2H, t, J=7.6 Hz, CH2); 4.28 (1H, dq, J=6.3 Hz, J=11.0 Hz, H10); 5.60 (1H, d, J=9.9 Hz, H8); 6.04 (1H, s, H3); 6.65 (1H, d, J=11.8 Hz, H7); MS (CI): 369 (100, M+1). the reaction mixture was cooled to room temperature washed several times with 10% aqueous NaHCO3 and brine The organic layer was separated dried over Na2SO4 The solvent was removed in vacuo the crude product was purified by silica gel column chromatography eluting with ethyl acetate/hexane (2:3)

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Comparative experiment) A mixture of 250.2 g of metformin hydrochloride, 213.6 g of acetaldehyde diethyl acetal and 12.5 g of toluene-4-sulfonic acid monohydrate in 500 ml of isobutanol was heated under reflux for 40 hours. Some of the solvent was removed by distillation. The mixture was cooled to 10° C., and the white precipitate was separated off, giving 224.7 g (77.4%) of 4-amino-3,6-dihydro-2-dimethylamino-6-methyl-1,3,5-triazine hydrochloride. was heated under reflux for 40 hours Some of the solvent was removed by distillation the white precipitate was separated off

反应条件: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 900 g (7.4 mol) of acetaldehyde diethyl acetal (purity according to GC: 97%) and 0.85 g (0.75 ml, 6 mmol, 0.25 mol %) of boron trifluoride etherate were placed in a 2 l two-necked round flask fitted with a magnetic stirrer, a thermometer and a dropping funnel. 220 g (2.5 mol) of ethyl (1-propenyl) ether were added dropwise within about 30 minutes while cooling occasionally with ice at a temperature of about 35° C., but a maximum of 40° C. After completion of the addition the mixture was stirred at room temperature for a further 30 minutes. Then, 4 g of solid, powdered sodium carbonate were added thereto and the mixture was stirred at room temperature for 2.5 hours. Then the mixture was suction filtered and the excess acetaldehyde diethyl acetal was distilled off on a Raschig column, (30×2.5 cm) at 100 mbar. About 1 l of acetaldehyde diethyl acetal (content according to GC. 91%) was recovered in this manner at a boiling point of 40-43° C. The residue was then fractionated on the same column at a pressure of 12-13 mbar. This gave 344.5 g (66.2% yield) of 1,1,3-triethoxy-2-methyl-butane as a water-clear liquid with a boiling point of 81-84° C. and a content of 98.2% according to GC. fitted with a magnetic stirrer a maximum of 40° C After completion of the addition the mixture the mixture was stirred at room temperature for 2.5 hours filtered the excess acetaldehyde diethyl acetal was distilled off on a Raschig column, (30×2.5 cm) at 100 mbar About 1 l of acetaldehyde diethyl acetal (content according to GC. 91%) was recovered in this manner at a boiling point of 40-43° C

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1-(1,4-Dioxa-spiro[4.5]dec-8-yl)-1-(4-methyl-cyclohexyl)-3-(5-methyl-thiazol-2-yl)-urea was prepared in an similar manner to example 2 according to general procedures (A) and (B) using 1,4-dioxaspiro[4.5]decan-8-one, 4-methylcyclohexylamine and 2-amino-5-methylthiazole. The acetale was then hydrolysed in the following way:

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 236 g of acetaldehyde diethyl acetal (abbreviation: acetal) and 1 g of aluminum chloride are added in 500 ml of four necked bottle under protection of nitrogen, the solution is freezed to −10° C., and kept at −10° C.˜−5° C., a mixture of 118 g of acetaldehyde diethyl acetal and 86 g (0.945 mol) of ethyl-(1-propenyl)-ether is slowly dropped, and continue to stir it for 10 min after finishing dropping, and the end of reaction is detected by GC. A saturated NaHCO3 solution is added in the reaction to neutralize it to pH=7, and to layer, the oil layer is dried by anhydrous sodium sulfate after being washed by water, and heated to 50° C.; most of acetaldehyde diethyl acetal is recycled, to obtain 169.6 g of 1,1,3-triethoxy-2-methyl-butane by vacuum distillation, and its content is 97.2%, and its yield is 88%. is freezed to −10° C. kept at −10° C.˜−5° C. is slowly dropped the end of reaction to layer, the oil layer is dried by anhydrous sodium sulfate after being washed by water

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: According to the present invention, a method for synthesizing 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde comprises the following steps: (1) adding acetaldehyde diethyl acetal (abbreviation: acetal) and ethyl-(1-propenyl)-ether under effects of a catalyst at a temperature of −10° C.˜0° C. to produce 1,1,3-triethoxy-2-methyl-butane; wherein the catalyst is ferric chloride or aluminum chloride; acetaldehyde diethyl acetal is prepared by the Chinese Patent No. ZL97115390.6 of Hoffmann-La Roche Ltd; (2) pyrolysis synthesizing 1,1,3-triethoxy-2-methyl-butane under catalytic effects of isoquinoline and p-Toluenesulfonic acid at a temperature of 180-200° C. to produce 1-methoxy-2-methyl-1,3-butadiene; but the catalyst used in the Chinese Patent ZL97115390.6 of Hoffmann-La Roche Ltd. is silicon-aluminum ball, to pyrolysis produce 1-methoxy-2-methyl-1,3-butadiene at high temperature, its conversion rate is only 41%, and its selectivity is 90%; (3) dissolving 1-methoxy-2-methyl-1,3-butadiene in anhydrous ethanol solvent for synthesis with a phase transfer catalyst and a chlorinating agent at a temperature of −5˜0° C. to generate 4,4-diethoxy-3-methyl-1-chloro-butene; wherein the phase transfer catalyst is cetyl-trimethyl ammonium bromide, the chlorinating agent is trichloroisocyanuric acid; (4) combining 4,4-diethoxy-3-methyl-1-chloro-butene with a triphenylphosphine salt at a temperature of 60˜65° C. to produce a phosphonic salt; and (5) condensing the phosphonic salt under effects of hydrogen peroxide at a temperature of 0˜5° C. in conjunction with sodium carbonate solution to generate 1,1,8,8-tetramethyl-2,7-dimethyl-2,4,6-octatriene at pH=8˜10; and then hydrolyzing under acidic conditions to synthesize 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: According to the present invention, a method for synthesizing 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde comprises the following steps: (1) adding acetaldehyde diethyl acetal (abbreviation: acetal) and ethyl-(1-propenyl)-ether under effects of a catalyst at a temperature of −10° C.˜0° C. to produce 1,1,3-triethoxy-2-methyl-butane; wherein the catalyst is ferric chloride or aluminum chloride; acetaldehyde diethyl acetal is prepared by the Chinese Patent No. ZL97115390.6 of Hoffmann-La Roche Ltd; (2) pyrolysis synthesizing 1,1,3-triethoxy-2-methyl-butane under catalytic effects of isoquinoline and p-Toluenesulfonic acid at a temperature of 180-200° C. to produce 1-methoxy-2-methyl-1,3-butadiene; but the catalyst used in the Chinese Patent ZL97115390.6 of Hoffmann-La Roche Ltd. is silicon-aluminum ball, to pyrolysis produce 1-methoxy-2-methyl-1,3-butadiene at high temperature, its conversion rate is only 41%, and its selectivity is 90%; (3) dissolving 1-methoxy-2-methyl-1,3-butadiene in anhydrous ethanol solvent for synthesis with a phase transfer catalyst and a chlorinating agent at a temperature of −5˜0° C. to generate 4,4-diethoxy-3-methyl-1-chloro-butene; wherein the phase transfer catalyst is cetyl-trimethyl ammonium bromide, the chlorinating agent is trichloroisocyanuric acid; (4) combining 4,4-diethoxy-3-methyl-1-chloro-butene with a triphenylphosphine salt at a temperature of 60˜65° C. to produce a phosphonic salt; and (5) condensing the phosphonic salt under effects of hydrogen peroxide at a temperature of 0˜5° C. in conjunction with sodium carbonate solution to generate 1,1,8,8-tetramethyl-2,7-dimethyl-2,4,6-octatriene at pH=8˜10; and then hydrolyzing under acidic conditions to synthesize 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: According to the present invention, a method for synthesizing 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde comprises the following steps: (1) adding acetaldehyde diethyl acetal (abbreviation: acetal) and ethyl-(1-propenyl)-ether under effects of a catalyst at a temperature of −10° C.˜0° C. to produce 1,1,3-triethoxy-2-methyl-butane; wherein the catalyst is ferric chloride or aluminum chloride; acetaldehyde diethyl acetal is prepared by the Chinese Patent No. ZL97115390.6 of Hoffmann-La Roche Ltd; (2) pyrolysis synthesizing 1,1,3-triethoxy-2-methyl-butane under catalytic effects of isoquinoline and p-Toluenesulfonic acid at a temperature of 180-200° C. to produce 1-methoxy-2-methyl-1,3-butadiene; but the catalyst used in the Chinese Patent ZL97115390.6 of Hoffmann-La Roche Ltd. is silicon-aluminum ball, to pyrolysis produce 1-methoxy-2-methyl-1,3-butadiene at high temperature, its conversion rate is only 41%, and its selectivity is 90%; (3) dissolving 1-methoxy-2-methyl-1,3-butadiene in anhydrous ethanol solvent for synthesis with a phase transfer catalyst and a chlorinating agent at a temperature of −5˜0° C. to generate 4,4-diethoxy-3-methyl-1-chloro-butene; wherein the phase transfer catalyst is cetyl-trimethyl ammonium bromide, the chlorinating agent is trichloroisocyanuric acid; (4) combining 4,4-diethoxy-3-methyl-1-chloro-butene with a triphenylphosphine salt at a temperature of 60˜65° C. to produce a phosphonic salt; and (5) condensing the phosphonic salt under effects of hydrogen peroxide at a temperature of 0˜5° C. in conjunction with sodium carbonate solution to generate 1,1,8,8-tetramethyl-2,7-dimethyl-2,4,6-octatriene at pH=8˜10; and then hydrolyzing under acidic conditions to synthesize 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde.

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Comparative experiment: A mixture of 250.2 g of metformin hydrochloride, 213.6 g of acetaldehyde diethyl acetal and 12.5 g of toluene-4-sulfonic acid monohydrate in 500 ml of isobutanol was heated under reflux for 40 hours. Some of the solvent was removed by distillation. The mixture was cooled to 10° C., and the white precipitate was separated off, giving 224.7 g (77.4%) of 4-amino-3,6-dihydro-2-dimethylamino-6-methyl-1,3,5-triazine hydrochloride. was heated under reflux for 40 hours Some of the solvent was removed by distillation the white precipitate was separated off

反应条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution containing chromene 4 (344 mg, 1.0 mmol), acetaldehyde diethylacetal (473 mg, 4.0 mmol), trifluoroacetic acid (1.5 mL, 19.4 mmol) and anhydrous pryidine (0.7 mL) was heated at 140° C. under N2. The reaction was monitored by TLC analysis. After 4 hours, the reaction mixture was cooled to room temperature, diluted with ehtyl acetate and washed several times with 10% aqueous NaHCO3 and brine. The organic layer was separated and dried over Na2SO4. The solvent was removed in vacuo and the crude product was purified by silica gel column chromatography eluting with ethyl acetate/hexane (2:3). Chromanone 7 (10,11-trans-dihydro-6,6,10,11-tetramethyl-4-propyl-2H,6H,12H-benzo[1,2-b:3,4-b':5,6-b"]-tripyran-2,12-dione) (110 mg, 30% yield) was obtained m.p. 176°-177° C. (Lit.5 130°-132° C.). 1H-NMR5 (CDCl3) δ 1.02 (3H, t, J=7.5 Hz, CH3); 1.21 (3H, d, J=6.8 Hz, CH3); 1.51 (3H, d, J=7.0 Hz, CH3); 1.55 (6H, 2s, 2 CH3); 1.63 (2H, sextet, J=7.0 Hz, CH2); 2.55 (1H, dq, J=6.9 Hz, J=11.0 Hz, H11); 2.88 (2H, t, J=7.6 Hz, CH2); 4.28 (1H, dq, J=6.3 Hz, J=11.0 Hz, H10); 5.60 (1H, d, J=9.9 Hz, H8); 6.04 (1H, s, H3); 6.65 (1H, d, J=11.8 Hz, H7); MS (CI): 369 (100, M+1). the reaction mixture was cooled to room temperature washed several times with 10% aqueous NaHCO3 and brine The organic layer was separated dried over Na2SO4 The solvent was removed in vacuo the crude product was purified by silica gel column chromatography eluting with ethyl acetate/hexane (2:3)

反应条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution containing chromene 4 (344 mg, 1.0 mmol), acetaldehyde diethylacetal (473 mg, 4.0 mmol), trifluoroacetic acid (1.5 mL, 19.4 mmol) and anhydrous pryidine (0.7 mL) was heated at 140° C. under N2. The reaction was monitored by TLC analysis. After 4 hours, the reaction mixture was cooled to room temperature, diluted with ehtyl acetate and washed several times with 10% aqueous NaHCO3 and brine. The organic layer was separated and dried over Na2SO4. The solvent was removed in vacuo and the crude product was purified by silica gel column chromatography eluting with ethyl acetate/hexane (2:3). Chromanone 7 (10,11-trans-dihydro-6,6,10,11-tetramethyl-4-propyl-2H,6H,12H-benzo[1,2-b:3,4-b':5,6-b"]-tripyran-2,12-dione) (110 mg, 30% yield) was obtained m.p. 176°~177° C. (Lit.5 130°~132° C.). 1H-NMR5 (CDCl3) δ 1.02 (3H, t, J=7.5 Hz, CH3); 1.21 (3H, d, J=6.8 Hz, CH3); 1.51 (3H, d, J=7.0 Hz, CH3); 1.55 (6H, 2s, 2 CH3); 1.63 (2H, sextet, J=7.0 Hz, CH2); 2.55 (1H, dq, J=6.9 Hz, J=11.0 Hz, H11); 2.88 (2H, t, J=7.6 Hz, CH2); 4.28 (1H, dq, J=6.3 Hz, J=11.0 Hz, H10); 5.60 (1H, d, J=9.9 Hz, H8); 6.04 (1H, s, H3); 6.65 (1H, d, J=11.8 Hz, H7); MS (CI): 369 (100, M+1). the reaction mixture was cooled to room temperature washed several times with 10% aqueous NaHCO3 and brine The organic layer was separated dried over Na2SO4 The solvent was removed in vacuo the crude product was purified by silica gel column chromatography eluting with ethyl acetate/hexane (2:3)