08-13-02 07:12
No 345054
      3,4,5-TMB from p-Cresol
(Rated as: excellent)

Efficient and Convenient Synthesis of 3,4,5-Trimethoxybenzaldehyde From p-Cresol
Ya-Fei Ji, Zhi-Min Zong, Xian-Yong Wei
Synthetic Communications Vol.32, No.18, pp. 28092814 (2002) (../rhodium/chemistry /345tmb.p-cresol.html)

With p-cresol as starting material, 3,4,5-trimethoxybenzaldehyde was synthesized in an overall yield of 67.4% via bromination, hydrolysis, methoxylation and methylation.


3-Necked round-bottomed flask equipped with a condenser attached to a calcium chloride drying tower,a mechanical stirrer,a thermometer,and a dropping funnel was charged with a solution of 43.2 g (0.40 mol)of p-cresol in 200 mL of o-dichlorobenzene. The solution was cooled to 10 C and treated during 1 h with a solution of 130.0 g (0.81 mol) of bromine in 100 mL of o-dichloro-benzene at such a state that the temperature was kept below 40 C. The mixture was stirred, heated at 160C and simultaneously dropped with another solution of 130.0 g (0.81 mol) of bromine in 100 mL of o-dichloro-benzene during 3 h. This deep red mixture was sequentially stirred for 30 min. After being cooled to room temperature and 145 mL of water being added,the mixture was heated to 120C and kept at the temperature for 4 h. After being cooled to 5C, the mixture was separated into upper organic layer, middle aqueous layer and lower solid layer. The solid product was collected by filtration and washed with water up to neutrality. It was dried in vacuo at 50C to give 91.4 g (81.6%)of the off-white solid m.p.180182C (lit.179 182 C).


About 142.0 g (0.740.79 mol) of freshly prepared 2830 wt %sodium methoxide, 8 mL of DMF, 4 g of cuprous chloride and 56.0 g (0.20 mol) of 3,4-Dibromo-4-hydroxybenzaldehyde were added into a 500 mL magnetically stirred stainless steel autoclave. After the air was replaced with N2, the autoclave was heated to 120C and kept at the temperature for 3 h. After being cooled to room temperature, the reaction mixture was taken out from the autoclave and transferred into a round-bottomed flask. Solvents were evaporated from the flask in vacuo below 60C, and the residue was treated with 200 mL of water. The mixture was stirred and heated to 90C for dissolution, then cooled to 0C for crystallization. After NaBr dissolved in the stock was removed by filtration, yellow green sodium phenolate 8 was obtained. The filter cake was dissolved in 300 mL of water, added with 1.5 g of active carbon,and then heated to 95C for 30 min. After hot-filtration for removing the filter residue (catalyst included), the filtrated stock was cooled to 40C, and was treated by slowly dropping 50.0 g (0.40 mol) of dimethylsulfate and 30 wt% 112 g (0.84 mol) of NaOH aqueous solution during 2 h. The pH value should be carefully controlled within 8.59.3. Stirring was continued at 50C for 30 min and then at 0C for 30 min, and the product was collected by filtration. It was washed with water up to neutrality and dried in vacuo at 45C to give 32.4 g (82.6%) of 3,4,5-trimethoxybenzaldehyde as colorless crystals, m.p. 7475C (lit. 7375C).
(Chief Bee)
10-04-03 13:21
No 462610

Similar to the above procedure...

Indian Journal of Chemistry 32B, 872-873 (1993)

Bromine (122.7g, 766 mmol) was added gradually at 25C in 1 hr to p-cresol (19.6 g, 181 mmol) in 60 ml anhydrous chlorobenzene. The temperature of the reactants was raised and the mixture stirred under reflux for 4 hr. Chlorobenzene was distilled in vacuo and the residue poured in cold methanol (200 ml) containing 1N HCl (100 ml). The precipitate was filtered, washed with water, dried and crystallized from dichloromethane-hexane furnishing fine crystals of the title product in 55% yield, mp 179-181C (lit. mp 180-82C).
(Chief Bee)
06-21-04 05:22
No 514596
      Many routes to 3,4,5-Trimethoxybenzaldehyde
(Rated as: excellent)

Synthesis of 3,4,5-Trimethoxybenzaldehyde
P.S. Manchand, P.S. Belica, and H.S. Wong
Synth. Commun. 20(17), 2659-2666 (1990) (../rhodium/chemistry /345-tmba.html)

The copper(I)-catalyzed exchange of bromine by methoxide in 5-bromovanillin and in 3,5-dibromo-4-hydroxybenzaldehyde provides an efficient method for preparing 3,5-dimethoxy-4-hydroxybenzaldehyde, from which 3,4,5-trimethoxybenzaldehyde is obtained by methylation with dimethylsulfate.

An Efficient Synthesis of 3,4,5-Trimethoxybenzaldehyde from Vanillin
D.V. Rao & F.A. Stuber
Synthesis 308 (1983) (../rhodium/chemistry /345-tmba.vanillin.html)

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