3,4, 5-Trimethoxybenzaldehyd

Syringaldehyde is easily methylated or ethylated with the known procedures in high yields forming the highly-desirable 3,4,5-trimethoxybenzaldehyde or the 3,5-di-MeO-4-EtO-benzaldehyde (Escaline, 72, 40-60 mg, 8-12 hrs.). 

A group of arylalkylketones containing a basic substituent in the side chain shows CNS activities. Roletamide (190) is a hypnotic agent. It is prepared from 3,4,5-trimethoxybenzaldehyde (187) by addition of sodium acetylide (to give 188), followed by Jones oxidation of ethynylarylketone 189. Michael addition... 

The synthesis of the furan-imidazole derivatives, shown in Scheme 2, were also described by Wang et al. [34]. Reaction of 4-(dimethylamino)benzalde-hyde (20) with trimethylsilylcyanide (TMS)-CN in the presence of Znl2 produced the TMS cyanohydrin 21. Compound 21 was treated with LDA followed by the addition of 3,4,5-trimethoxybenzaldehyde to give the benzoin intermediate 22. Oxidation with CUSO4 in aqueous pyridine, followed by reaction with 3-furaldehyde in acetic acid, produced the substituted imidazole 23. 

Synthesis of the amino-triazole derivative (43) was performed in the authors laboratory by Pati et al. [52] (Scheme 7). Substituted benzyl bromide was reacted with triphenylphosphine to produce the phosphonium bromide starting material, 44. The Wittig reagent, obtained by treatment with sodium hydride, was reacted with 3,4,5-trimethoxybenzaldehyde 18 to generate the nitro-stilbene 45 in good yields. The alkyne 46 was obtained by bromination of the stilbene, followed by didehydrobromination. Compound 46 was then reacted under thermal conditions with benzyl azides... 

Mix 5.5 g 3,4,5-trimethoxybenzaldehyde (or analog), 2.5 g NH4 Acetate, 25 ml nitroethane (or equimolar amount nitromethane for the analog), 25 ml benzene and reflux about twenty hours water being removed with a Dean-Stark tube. Cool and wash with 2X25 ml water, 2X25 ml saturated NaHS03 and 2X25 ml water and dry and evaporate in vacuum the benzene to get (I). Reduce the nitropropene (or nitrostyrene) by any method such as follows To a stirred suspension of 3 g lithium aluminum hydride in 50 ml tetrahydrofuran, add 4.4 g (I) in 50 ml tetrahydrofuran and reflux one hour. Cool in ice bath and treat slowly with wet tetrahydrofuran... 

All of the other syntheses begin with 3,4,5-trimethoxybenzaldehyde. According to one of them, condensation of 3,4,5-trimethoxybenzaldehyde with 3-ethoxy- or 3-anilinopropionitrile... 

Trimethoprim has also been synthesized by condensing 3,4,5-trimethoxybenzaldehyde with malonic acid dinitrile in a Knoevenagel reaction, which forms the derivative (33.1.53), which is partially reduced to the enamine (33.1.54) by hydrogen using a palladium on carbon catalyst, which upon being reacted with guanidine is transformed into trimethoprim [52,53]. 

Trimethoxybenzaldehyde has been prepared by the classical Rosenmund3-5 reduction, from 5-hydroxyvanillin by methylation,6 and by oxidation of 3,4,5-trimethoxybenzyl alcohol.7... 

The reaction has been carried out on large- and small-scale batches (Note 10). This modification,8 as exemplified by 3,4,5-trimethoxybenzaldehyde, has been applied by the submitters to the preparation of other aldehydes9 such as 3,4-dimethyl-benzaldehyde10 (90% yield), 3-benzyloxy-4,5-dimethoxybenz-aldehyde11 (88% yield, with retention of the benzyl group), and 3-methoxy-4-nitrobenzaldehyde12 (62% yield, with retention of the nitro group). 

The conjugate addition of aryl dithiane anions to 2-butenolide has been examined as a route to ( )-podorhizol and ( )-isopodophyllotoxone (78JOC985). The dithiane of piperonal (802) was deprotonated and reacted with 2-butenolide to give the lactone anion which was trapped in turn with 3,4,5-trimethoxybenzaldehyde to afford a mixture of the threo and erythro aldol products (803). Desulfurization of the erythro dithiane with Raney nickel gave ( )-podorhizol (804 Scheme 188). 

SYNTHESIS To a solution of 45 g 3,4,5-trimethoxybenzaldehyde in 1.2 L IPA, there was added 125 g nitropropane and 67.5 g t-butylammonium acetate and the reaction mixture was held at reflux for 16 h. This was poured into 6 L H20, and extracted with 2x250 mL hexane. The pooled extracts were stripped of solvent under vacuum giving a residue that slowly set to a crystalline mass. On filtering,... 

SYNTHESIS A solution of 20 g 3,4,5-trimethoxybenzaldehyde, 40 mL nitromethane, and 20 mLcyclohexylamine in 200 mL of acetic acid was heated on the steam bath for 1 h. The reaction mixture was then diluted slowly and with good stirring, with 400 mL H,0, which allowed the formation of a heavy yellow crystalline mass. This was removed by filtration, washed with H20, and sucked as dry... 

The Wittig reaction of methylenetriphenylenephosphorane with ketones 117 gave 4-methyleneoxo-phosphorinane 118 in 66% yield <1996JA10168> (Equation 23). Reaction of the phenyl phosphonium bromide 73 with 3,4,5-trimethoxybenzaldehyde gave alkenes with greater trans selectivity <1998SL497>. 

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