20.15 g of syringaldehyde, 100 ml of dry DMF (technical grade, fractionally distilled once under vacuum and stored over 3 A molecular sieves),
11.71 g of anhydrous K2CO3 (anhydrous photography grade, ground by mortar and pestle and dried for 1 hour at 300 C), 6.10 g of TBAB, and 22 ml of
dimethyl carbonate (technical grade, fractionally distilled once and stored over 3 A molecular sieves) were added to a 500 ml 3-neck round bottom
flask equipped with a condenser, pressure equalizing addition funnel, thermometer, and magnetic stirring. The addition funnel was charged with an
additional 22 ml of DMC. The apparatus was sealed from atmosphere by leading a hose adapter on the head of the condenser to a small beaker filled with
mineral oil. A latex balloon septum was fitted to the head of the addition funnel and the apparatus was gently purged for 10 seconds with a nitrogen
wine preserver, and then the septum was very quickly replaced with a stopper. Stirring was initiated and the reaction mixture was brought to a gentle
reflux between 120 – 130 C. The DMC within the addition funnel was added in several small portions in the first 3 hours of reflux. From the
initiation of reflux, the reaction was allowed to proceed for approximately 20 hours. A light brown/caramel reaction mixture was observed. The
reaction mixture, while still hot, was poured into 200 ml of room temperature water. The solution turned a clear orange-red and no precipitation was
observed. The mixture was allowed to cool to room temperature, accelerated by the use of a refrigerator. A milky precipitate was then observed, and so
another 600 ml of water was added, the total volume now being approximately 1000 ml. Precipitation was observed immediately and the beaker was placed
in a freezer for 1 hour. Large amounts of crystals were observed, which were vacuum filtered for approximately 5 minutes. The light beige colored
filtrate was discarded and the delicate mass of crystals, off-white and slightly beige in appearance, were dissolved in 100 ml of ethyl acetate and
transferred to a separatory funnel. The crude product was then washed with 2 x 50 ml of 5% w/w NaOH, 2 x 50 ml water, and 2 x 50 ml brine. At the
conclusion of the washings, approximately 80 ml of a yellow liquid was collected, dried over MgSO4, and evaporated under gentle vacuum to yield 15.39
g (71% yield) of a crude 3,4,5-trimethoxybenzaldehyde as a light beige solid.
24.20 g syringaldehyde, 120 ml DMF, 14.02 g K2CO3, 7.30 g TBAB, and 27 ml DMC was combined in the previously described apparatus. The addition
funnel was charged with an additional 27 ml of DMC. The apparatus was protected from atmosphere and purged as before. The mixture was heated, with
stirring, to a gentle reflux between 120 – 130 C. Additional DMC was added at the rate of one drop every 3-6 seconds once reflux was reached. Total
reflux time was 14 hours. The reaction mixture, still hot, was quenched with 200 ml room temperature water. The mixture was allowed to cool to room
temperature with aid of a refrigerator. Upon cooling, milky precipitate was noted. The mixture was then diluted with more water to the 1000 ml line,
and the precipitate appeared more defined and crystalline, as in the previous trial. The mixture was placed into a freezer for 1 hour and the large
volume of crystals was vacuum filtered for 5 minutes. The solids were dissolved in 100 ml of ethyl acetate and the workup was performed as before: 2 x
50 ml 5% w/w NaOH, 2 x 50 ml water, 2 x 50 ml brine. The yellow liquid was dried over MgSO4 and evaporated under gentle vacuum to yield 17.74 g (68%
yield) of a crude 3,4,5-trimethoxybenzaldehyde as a light beige solid.
The outputs of both trials were combined, total mass of 33.09 g after accounting for some minor losses, and a short path vacuum distillation
apparatus was set up. Because the product is a solid well above room temperature (lit. MP 73 C), it was a motherfucker to vacuum distill. The reaction
flask and vertical section of the short path apparatus, except for small viewing ports, were wrapped in aluminum foil and the flask was heated over an
oil bath with maximum stirring. The distillate rose up the vertical section of the still head but would repeatedly stall, and so the apparatus was
brought up to temperature with a 750-watt heat gun. (Use metal keck clips so they don't melt.) The 3,4,5-trimethoxybenzaldehyde distilled at
approximately 140 C, although it was hard to pinpoint an exact temperature due to the output of the heat gun. A small amount of dark brown/orange
liquid which did not solidify at room temperature was left behind in the reaction flask. Total mass of recovered product was 29.75 g (90% recovery) as
a snow-white amorphous mass which was stored in an air-tight container in a freezer, to protect against any potential degradation to
3,4,5-trimethoxybenzoic acid.
|
