Author Topic: Novel synthesis of 3,4,5-Trimethoxybenzaldehyde  (Read 637 times)

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  • Guest
Novel synthesis of 3,4,5-Trimethoxybenzaldehyde
« on: September 26, 2002, 07:15:00 PM »

A solution of 39.6 g (0.2 mole) of 3,4,5-trimethoxybenzyl alcohol in 250 ml of methanol was stirred and cooled to 0°C. Bromine (54 ml) was added with stirring over a period of one hr keeping the temperature at 0°C. The stirred mixture was allowed to acquire room tempterature gradually and stirred further for 2 hr. A saturated solution of sodium thiosulfate (about 30 ml) was added to effect complete decomposition of excess bromine. 3,4,5-Trimethoxybenzaldehyde was filtered off and recrystallized from benzene to give 31 g (80%) as colourless needles, m.p. 73-74°C.

Reference: J. Chem. U.A.R., 11, No. 3, 401-404 (1968)


  • Guest
so how watched is 3,4,5 benzyl alcohol?
« Reply #1 on: September 27, 2002, 03:59:00 PM »
so how watched is 3,4,5 benzyl alcohol?

Who is that masked man?


  • Guest
Enough for you not wanting to buy it, if you live ...
« Reply #2 on: September 27, 2002, 04:19:00 PM »
Enough for you not wanting to buy it, if you live in the US that is.


  • Guest
Rosenmund Reduction of Acid Chlorides
« Reply #3 on: September 29, 2002, 08:32:00 AM »
3,4,5-trimethoxybenzaldehyde can be also prepared by Rosenmund reduction of 3,4,5-trimethoxybenzoyl chloride as described in Organic Syntheses, CV 6, 1007.


A pressure vessel (Note 1) is charged in order with 600mL of dry toluene (Note 2), 25g (0.30 mole) of anhydrous sodium acetate (Note 3), 3g of dry, 10% palladium-on-carbon catalyst (Note 4), 23g (0.10 mole) of 3,4,5-trimethoxybenzoyl chloride (Note 5), and 1mL of Quinoline S (Note 6). The pressure vessel is flushed with nitrogen, sealed, evacuated briefly, and pressured to 50 p.s.i. with hydrogen. The mixture is shaken with 50 p.s.i. of hydrogen for 1 hour at room temperature (Note 7), then heated at 35–40° C for 2 hours. Agitation is continued overnight while the reaction mixture cools to room temperature. The pressure on the vessel is released, the vessel is opened, and the mixture is filtered through 10g of Celite filter aid, and the insoluble material is washed with 25mL of toluene. The combined filtrates are washed successively with 25mL of 5% sodium carbonate solution and 25mL of water. The toluene solution is dried over 5g of anhydrous sodium sulfate and filtered. The filtrate is concentrated by distillation at reduced pressure using a water aspirator. The residue (Note 8) is distilled through a 10-cm. Vigreux column with warm water circulating through the condenser, to prevent crystallization of the distillate, yielding 12.5–16.2g (64–83%) of 3,4,5-trimethoxybenzaldehyde, b.p. 158–161° C (7–8 mm.), m.p. 74–75° C (Note 9) and (Note 10).


1.) Both glass-lined and stainless-steel autoclaves have been used successfully. The checkers used a 1.2-l., Hastelloy autoclave.

2.) Reagent grade toluene was heated at reflux to remove a small forerun, then allowed to cool.

3.) Anhydrous sodium acetate was dried in a vacuum oven at 115° C for 48 hours. The use of less than 3 moles of sodium acetate per mole of acid chloride results in a lower yield of product.

4.) A catalyst available from Engelhard Industries was used after being dried in a vacuum oven at 115° C for 48 hours.
Caution! Palladium-on-carbon is pyrophoric, and vacuum drying increases this hazard. Catalysts kept in the oven for longer periods of time were extremely pyrophoric.

5.) The acid chloride or the acid may be purchased from Aldrich Chemical Company, Inc. The acid chloride must be pure (99% minimum by GC analysis) whether purchased or prepared. Purification was effected by recrystallization from Skellysolve B.

6.) Quinoline S was prepared according to the procedure in Org. Synth., Coll. Vol. 3, 629 (1955).

7.) Repressuring with hydrogen is required during this period. The amount of repressuring required is dependent upon the free space of the pressure vessel. The submitters report lower yields if the pressure falls below 30 p.s.i. No further repressuring is made at the end of 1 hour.

8.) The crude aldehyde (prior to distillation) is sufficiently pure for most purposes. Isolation of the aldehyde may also be achieved via the bisulfite-addition compound.2

9.) The product shows a strong IR band (KBr) at 1690 cm.?1 (C=O). The 1H NMR spectrum (CCl4) has peaks at ä 3.84 (s, 3H), 3.87 (s, 6H), 7.03 (s, 2H), and 9.76 (s, 1H).

10.) The submitters state that the aldehyde is obtained in 78–84% yield when the reaction is conducted on a scale 5 times that described. The amount of catalyst and Quinoline S need not be increased proportionately. The pressure vessel is charged with 3L of dry toluene, 123g of anhydrous sodium acetate, 10g of dry, 10% palladium-on-carbon catalyst, 115g of 3,4,5-trimethoxybenzoyl chloride, and 4mL of Quinoline S.

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