Abstract:
The present invention relates to a process for producing piperonal, more specifically to a process for producing a high quality piperonal with high yield by using 1,2-methylenedioxybenzene as a starting material and without taking 3,4-methylenedioxymandelic acid which is an intermediate in the course of the reaction as a crystal.
Example 1
In a flat bottom separable flask having an inner volume of 7 liters, 500.0 g (4.09 mol) of 1,2-methylenedioxybenzene and 250 ml of 4-methyl-2-pentanone were charged under nitrogen atmosphere, and the mixture was cooled to -5 DEG C while stirring. Then, a mixture comprising 833.4 g (4.44 mol) of a 40% by weight aqueous glyoxylic acid solution and 857.8 g (8.40 mol) of 96% by weight sulfuric acid was gradually added dropwise, and then, the mixture was stirred at -5 DEG C for 21 hours.
Then, 3000 ml of 4-methyl-2-pentanone was added, and 1030.0 g(16.9 mol) of 28% by weight aqueous ammonia was gradually added to the mixture while maintaining the liquid temperature to -10 to 5 DEG C to effect neutralization. After the neutralization, the mixture was heated to 80 DEG C, and 3,4-methylenedioxymandelic acid was extracted in a 4-methyl-2-pentanone layer (an organic solvent layer). At this time, the reaction mixture was separated into two layers of an organic solvent layer and an aqueous layer.
Then, the aqueous layer was removed, and the organic solvent layer was concentrated (2200 ml of 4-methyl-2-pentanone was removed). After concentration, the reaction mixture in a slurry state was transferred to a round bottom separable flask with an inner volume of 20 liters, and cooled to 10 DEG C while stirring under nitrogen atmosphere. Thereafter, 1746.7 g (2.78 mol) of 10% by weight nitric acid was gradually added dropwise, and the temperature of the mixture was raised to 50 DEG C and the mixture was stirred at the temperature for one hour.
After completion of the reaction, the mixture was cooled to 25 DEG C, 140 ml (1.00 mol) of a 25% by weight aqueous sodium hydroxide solution was added to the mixture to make up the whole reaction mixture weak basic (pH=7.9). Subsequently, 4-methyl-2-pentanone layer (an organic solvent layer) and an aqueous layer were separated, and the organic solvent layer was analyzed by gas chromatography, then no 1,2-methylenedioxy-4-nitrobenzene which is a by-product was detected. Also, when it was analyzed by high performance liquid chromatography, a conversion of 1,2-methylenedioxybenzene was 97%, and a yield of piperonal was 78% (in terms of mole).
Example 2
In a flat bottom separable flask having an inner volume of 500 ml, 50.0 g (409.4 mmol) of 1,2-methylenedioxybenzene and 50 ml of acetic acid were charged under nitrogen atmosphere, and then, the mixture was cooled to 0 DEG C while stirring. Then, a mixture of 83.4 g (450.6 mmol) of a 40% by weight glyoxylic acid aqueous solution and 85.8 g (839.8 mmol) of 96% by weight sulfuric acid was gradually added dropwise, and then, the mixture was stirred at 5 DEG C for 21 hours.
Then, 200 ml of ethyl acetate was added to the mixture, and then, 102.0 g (1677 mmol) of 28% by weight aqueous ammonia was gradually added to the mixture while maintaining the liquid temperature to -10 to 5 DEG C to effect neutralization. After the neutralization, the mixture was heated to 60 DEG C, and the 3,4-methylenedioxymandelic acid was extracted in an ethyl acetate layer (an organic solvent layer). At this time, the reaction mixture was separated into two layers of an organic solvent layer and an aqueous layer.
Then, the aqueous layer was removed, and the organic solvent layer was concentrated (ethyl acetate was completely removed by distillation), 173 ml of water and 160 ml of toluene were newly added to the concentrate, and the mixture was cooled to 0 DEG C while stirring under nitrogen atmosphere. Then, 33.9 g (328.2 mmol) of 61% by weight nitric acid was gradually added dropwise, and the temperature of the mixture was raised to 40 DEG C, and the mixture was stirred at the temperature for one hour.
After completion of the reaction, the mixture was cooled to 0 DEG C, 80 ml (0.57 mol) of a 25% by weight aqueous sodium hydroxide solution was added to the mixture to make up the whole reaction mixture weak basic (pH=7.9). Subsequently, the toluene layer and the aqueous layer were separated, and the toluene layer was analyzed by gas chromatography, no 1,2-methylenedioxy-4-nitrobenzene which is a by-product was detected. Also, when it was analyzed by high performance liquid chromatography, a conversion of 1,2-methylenedioxybenzene was 97%, and a yield of the piperonal was 80% (in terms of mole).
Pat #: EP1253147
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