02-12-02 13:34
No 268541
Organic Process Research & Development, Vol. 4, No. 6, 2000, pp. 534-543
ref & abstract were posted prior by foxy2 in Post 225604 (foxy2: "Re: 4-Methylaminorex Synth w/o CNBr", Novel Discourse). here are the recipes:
3,4-Dihydroxy Mandelic Acid
(Optimised Procedure). Catechol (5.00 g, 45.41 mmol) was dissolved in aqueous NaOH (3.21 g, 80.3 mmol in 55.0 mL of water) followed
by addition of Al2O3 (2.04 g, 20 mmol). After 5 min glyoxylic acid (7.10 g of 50% aqueous solution, 48.0 mmol) was added to the reaction mixture, and the mixture was heated
at 60 C for 24 h under vigorous stirring. The reaction mixture was then allowed to precipitate for 10 min. and filtered to remove Al2O3. The obtained filter cake was washed
with 1 M NaOH (20 mL). The basic washing water was combined with the water solution, and this was acidified to pH 3-4 with 6.0 mL of 37% HCl and extracted with ethyl
acetate to recover the unreacted catechol (1.2 g). The aqueous solution was further acidified to pH 1 by 2 mL of concentrated HCl and extracted with ethyl acetate to isolate
the mandelic acid derivative (5.1 g, 28.08 mmol). Conversion 77.5%, selectivity 90.5%.
Protocatechualdehyde
3,4-Dihydroxy mandelic acid (2 g, 10.86 mmol) was dissolved in 140 mL of ethyl acetate, and 11.11 g of CuCl2·2H2O was dissolved in 30 mL of
water. The two-phase system was vigorously stirred and heated at 60 C for 5 h under nitrogen atmosphere. The organic phase was separated, and the solvent was
removed. The HPLC analysis revealed a complete conversion of the mandelic acid derivative and the yield of protocatechualdehyde of 96%. The copper salt aqueous
solution/suspension was recycled by oxidising Cu(I) to Cu(II) by air after the removal of the organic phase; the results were substantially unchanged.
3,4-Dioxymethylene Mandelic Acid
Benzo[1,3]dioxole 15 (8.20 mmol) was added dropwise over a period of 30 min to a mixture of 8.41 mmol of glyoxylic acid, 14.59
mmol of sulphuric acid, and 11.34 mmol of water at 0-5 C. The reaction was run for 20 h at 0 C and then diluted with 20 mL of water. The 3,4-dioxymethylene mandelic
acid precipitated and was then filtered off. HPLC analysis revealed a yield of 86% with selectivity >95%.
Piperonal(Heliotropin)
(A) 3,4-Dioxymethylene mandelic acid (5 mmol), Na2S2O8 (6 mmol), and AgNO3 (0.05 mmol) in 30 mL of water and 30 mL of CH2Cl2 were refluxed for 5
h. The CH2Cl2 phase was removed and analysed by HPLC; a yield of 96% of piperonal(heliotropin) was obtained.
(B) 3,4-Dioxymethylene mandelic acid (5 mmol), CuCl2 (0.5 mmol), and 4.05 g of 37% HCl in 30 mL of water and 30 mL of toluene was heated at 80 C and bubbling O2
for 22 h. The organic phase was separated and analysed by HPLC; a yield of 98% of piperonal(heliotropin) was obtained. The aqueous solution is ready to be used for further oxidation.
(C) Protocatechualdehyde (13.1 g, 0.1 mol), NaOH (12 g), and tetrabutylammonium bromide (3.2 g) in 100 mL of water and 100 mL of CH2Cl2 were heated for 4 h at 80 C
in an autoclave. The aqueous phase was then separated and analysed by HPLC. The aqueous solution was acidified and extracted by ethyl acetate to recover the unreacted
protocatechualdehyde. The conversion was 58.6% and selectivity in piperonal(heliotropin) 64%.
the complete pdf is already on the way to rhodium ...
"Whatever there is to learn has to be learned the hard way."
Don Juan Matus
(Stranger)
02-12-02 16:01
No 268586
You should use adogen 464 instead tetrabutylammonium halide because the short-chained tetraalkyls are destroyed under basic conditions. If you use bromochloromethane or dibromomethane, you can bypass autoclave conditions.
60 degree centigrade is hot enough, reaction time 1-2 hours.
