Ooops - forgot to mention the pat# - it's
Patent US4218567
There is also an absolutely hilarious synthesis of syringaldehyde from p-cresol in
two steps in that patent. The 1st one is simultaneous dibromination and oxidation of the methyl group to carbonyl. The 2nd is double methoxylation. Here:
1) 3,5-dibromo-4-hydroxybenzaldehyde A 2-l., 3-necked round-bottomed flask equipped with a condenser attached to a calcium sulfate drying tower, mechanical stirrer, thermometer, and dropping funnel was charged with a solution of 108.1 g. of p-cresol (99%) in 500 ml. of chlorobenzene (anhydrous). The solution was cooled to 10 C and treated during 30 minutes with a solution of 720 g. of bromine in 600 ml. of chlorobenzene at such a rate that the temperature was kept below 25 C. The mixture was stirred at room temperature for 30 minutes, heated under reflux for 4.5 hours, and then evaporated in vacuo (water aspirator) at 60 C to give a deep red oil which was dissolved in 1.0 l. of methanol. To the stirred, cooled (10 C) solution was added 500 ml. of 1 N hydrochloric acid at such a rate that the temperature was kept below 25 C. The mixture was left at 5 C overnight, diluted with 1.0 l. of cold (5 C) water and the product collected by filtration. The solid was washed with four 1-l. portions, a total of 4.0 l. of water, dissolved in 2.5 l. of warm (50 C) ethyl acetate, dried over magnesium sulfate, and evaporated to give 291 g. of an off-white solid. To the solid was added 600 ml. of methylene chloride and the heterogeneous mixture heated at reflux for 15 minutes, diluted with 600 ml. of hexane and left at 0 C overnight. The off-white solid was collected, washed with two 100 ml. portions, a total of 200 ml. of cold (5 C) hexane, and dried in vacuo at room temperature overnight to give 168.3 g. (60%) of 3,5-dibromo-4-hydroxybenzaldehyde as a colorless solid, mp 177 C-180 C. GLC analysis indicated a purity of 99.6%.
2) 3,5-dimethoxy-4-hydroxybenzaldehyde Into a 2-l., 3-necked, round-bottomed flask equipped with a mechanical stirrer, thermometer, and a condenser was added 700 ml. of methanol. 68.0 G. of clean sodium was then added in small pieces and under nitrogen. After the reaction was complete, the methanol was removed in vacuo at 45 C-50 C and to the residue was added 312 ml. of dimethylformamide and 156 ml. of methanol. 5.85 G. of cuprous chloride was added followed, after 5 minutes, by 165 g. of 3,5-dibromo-4-hydroxybenzaldehyde, an exotherm resulted (25 C to 50 C during 5 minutes). The mixture was heated under reflux for 4 hours, the solvents were evaporated in vacuo (0.1 torr) at 55 C, and the residue was treated with 440 ml. of 15% brine. The mixture was stirred at room temperature for 30 minutes, again cooled to 0 C, and filtered over 100 g. of celite. The filter cake was washed with three 250 ml. portions, a total of 750 ml. of cold (5 C) water (that is, until neutral) followed, after discarding the aqueous washings, by three 500 ml. portions, a total of 1.5 l. of hot (60 C) ethyl acetate. The ethyl acetate washings were added to a separatory funnel, excess water (about 10 ml.) was removed, and the ethyl acetate dried over magnesium sulfate and evaporated to give 95.0 g. (88.5%) of 3,5-dimethoxy-4-hydroxybenzaldehyde as a yellow solid, mp 107 C-109 C. GLC indicated a purity of 99.7%
Of course, PhCl ain't a particularly available solvt - so i wonder if CCl4 or TCE can bee substituted instead? Boiling points lower, but maybee longer rxn time will compensate for that.
Simple dibromination of cresol is also possible under milder conditions - compare:
3,5-dibromo-4-hydroxytoluene To a cooled (0 C) solution of 108 g. of p-cresol in 500 ml. of methanol was added 336 g. of bromine at such a rate that the internal temperature was kept below 10 C. The mixture was stirred at room temperature for 2 hours, and then evaporated in vacuo. The residue was dissolved in a mixture of toluene in hexane (1:1) and left at -20 C for 18 hours. The product was collected by filtration to give 252 g. of 3,5-dibromo-4-hydroxy-toluene, mp 46 C-47 C.
I wish there was a way to dibrominate benzaldehyde, but it's probably impossible, anyone knows anything on the issue?
Antoncho