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United States Patent 4,190,583
Bauer , et al. February 26, 1980
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Process for the preparation of 3,4-methylenedioxymandelic acid
The course of the reaction according to the invention is surprising, since it is known, from Gazz. Chim. Ital. 96 (4), 465 (1966), that the reaction of glyoxylic acid alkyl esters with alkyl-substituted aromatic compounds in a strongly acid medium indeed leads to mandelic acid derivatives, but with alkoxy-substituted aromatic compounds, such as veratrole, gives only diphenylacetic acid derivatives.
3,4-Methylenedioxymandelic acid is, inter alia, an important starting material for the preparation of the valuable aroma substance piperonal. Piperonal is prepared from 3,4-methylenedioxymandelic acid by oxidative decarboxylation (see Current Sci. (India) 27, 22 (1958)).
EXAMPLE 1
46 g (0.5 mol) of glyoxylic acid monohdrate, 61 g (0.5 mol) of 1,2-methylenedioxybenzene and 200 g (1.74 mols) of 85% strength phosphoric acid are brought together at 25.degree. C. and the mixture is stirred for 5 hours. The temperature thereby rises to 38.degree. C. In order to preserve the stirrability of the reaction mixture, 40 ml of water are added. After 5 hours, a further 160 ml of water are added, the mixture is further stirred for 10 minutes and the crystals obtained are filtered off. The crystals are dissolved in 650 ml of water and 100 ml of toluene at 85.degree. C. and the phases are separated. After washing the toluene phase several times with 20% strength sodium hydroxide solution and distilling off the solvent, 7.1 g of 1,2-methylenedioxybenzene are recovered. After cooling the aqueous phase to room temperature, 57.6 g of 3,4-methylenedioxymandelic acid crystallise out, and after concentrating the mother liquor a further 8.3 g of 3,4-methylenedioxymandelic acid crystallise out. The yield of 3,4-methylenedioxymandelic acid is 76.1% of theory, relative to 1,2-methylenedioxybenzene reacted. It can be increased further by working up the strongly acid filtrate of the reaction mixture. However, since the working up is very expensive, it is more advantageous to concentrate the acid filtrate and re-use it.
EXAMPLE 2
200 g of 90% strength sulphuric acid are added dropwise to a mixture of 148 g (1 mol) of 50% strength aqueous glyoxylic acid and 122 g (1 mol) of 1,2-methylenedioxybenzene at 5.degree. C. in the course of 40 minutes, whilst stirring. After stirring the mixture for a further 6 hours, 500 g of ice-water are added and the mixture is stirred for a further 10 minutes. The crystals which have precipitated are filtered off and worked up as in Example 1. 6.1 g of 1,2-methylenedioxybenzene are recovered from the toluene phase. 167.3 g of 3,4-methylenedioxymandelic acid, corresponding to a yield of 85.3% of theory, relative to 1,2-methylenedioxybenzene reacted, are obtained from the aqueous phase.
EXAMPLE 3
A mixture of 92 g (1 mol) of glyoxylic acid monohydrate and 122 g (1 mol) of methylenedioxybenzene is stirred at 80.degree. C. for 4 hours, 700 ml of water and 150 ml of toluene are then added and the phases are separated. After cooling the aqueous phase to room temperature, 44.7 g of 3,4-methylenedioxymandelic acid crystallise out, and after concentrating the aqueous phase a further 17.3 g of 3,4-methylenedioxymandelic acid crystallise out. After extracting the toluene phase by shaking with 100 ml of 20% strength sodium hydroxide solution and distilling off the toluene, 10.5 g of unreacted 1,2-methylenedioxybenzene are obtained. The yield of 3,4-methylenedioxymandelic acid is 34.6% of theory, relative to 1,2-methylenedioxybenzene reacted.
EXAMPLE 4
39 g (0.424 mol) of glyoxylic acid monohydrate are dissolved in 126 g of trifluoroacetic acid, and 51.7 g (0.424 mol) of 1,2-methylenedioxybenzene are added at 20.degree. C. The initially homogeneous mixture is stirred at 20.degree. C. for 3.5 hours. The crystals which have precipitated are then filtered off and worked up as described in Example 1. 10 g of bis-(3,4-methylenedioxyphenyl)-acetic acid are obtained from the toluene phase. 62.2 g of 3,4-methylenedioxymandelic acid are obtained from the aqueous phase. This corresponds to a yield of 75% of theory, relative to 1,2-methylenedioxybenzene employed. The yield can be increased by working up the strongly acid filtrate of the reaction mixture. However, it is more advantageous to concentrate the acid filtrate and re-use it.
If, instead of glyoxylic acid monohydrate, an equivalent amount of 50% strength aqueous glyoxylic acid is employed and the mixture is stirred for 6 hours instead of 3.5 hours, 8.58 g of bis-3,4-methylenedioxyphenylacetic acid are obtained from the toluene phase and 73.4 g of 3,4-methylenedioxymandelic acid, corresponding to a yield of 76.3% of theory, relative to 1,2-methylenedioxybenzene employed, are obtained from the aqueous phase.
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