(Chief Bee)
08-09-02 04:40
No 343449
      Precursor: 2,4-Dihydroxy-3-methyl-benzaldehyde
(Rated as: excellent)

Patent US3975309

2,4-dihydroxy-3-methyl-benzaldehyde was first prepared by E T Jones et. al. by the condensation of 2,6-dihydroxytoluene with zinc cyanide and excess HCl (J. Chem. Soc. 1691 (1932)).

It may be produced by placing 496g of 2-methyl-resorcinol, 712 g of N-methyl-formanilide and 300 ml of benzene in a 3-necked five liter flask fitted with an agitator, reflux condenser, dropping funnel and thermometer. After a homogeneous solution is obtained by agitation at room temperature, 808g of phosphorus oxychloride are added over a period of 2 hours, maintaining the reaction temperature at 25-30C. After the addition is completed, agitation is continued for about 4 hours at 25-30C with occasional cooling. During the reaction, 600ml of benzene are added to the reaction mixture.

The reaction mixture is cooled in an isopropanol-dry ice bath. 100 ml of ice water are added in one portion to the reaction mixture, followed by the addition with agitation of 2000 ml of a 50% aqueous sodium acetate solution over a period of 50 minutes (exothermic) allowing the reaction temperature to rise to a maximum of 65C. The reaction mixture is cooled to 20C and 1000 ml of a 50% aqueous acetate solution (precooled to 25C) are added under agitation in one portion. 800 ml of ethyl acetate (solvent) are added. The mixture is agitated for about 5 minutes and permitted to separate into an aqueous part and an organic layer, which is washed with 200 ml of water. The solvent (ethyl acetate) is removed by distillation under vacuum from a steam bath. The crude reaction product is cooled to 20C and the formed crystals are filtered on a Buchner funnel. The crystals are recrystallized from a solution of 1000 ml of water and 600 ml of methanol. This first crop weighed 310g, with a mp of 158-160C (GLC: 100%)

To the mother liquor are added 300 ml of benzene and 100 ml of ether. The reaction mixture separates into two layers. The organic layer is washed three times with 200 ml portions of water and neutralized with a 10% aqueous solution of sodium bicarbonate. The solvent is removed by distillation from a steam bath under an ejector vacuum. The formed crystals are collected on a Buchner funnel and recrystallized from a solution of 200 ml of benzene and 100 ml of hexane. This second crop weighed 150g, with a mp of 156-158C (GLC: 100%)

The combined two crops from above are placed in a 3 liter 3-necked flask with an agitator and 1500 ml of water are added. The product is steam distilled for approximately 1 hour. The steam distillation is necessary to remove traces of contaminants which give an off-odor to the product. From 426 g of the product, 420g of 2,4-dihydroxy-3-methyl-benzaldehyde having a melting point of 151.5-152.5C result after distillation.