3,4, 5-Trimethoxy benzaldehyde

Asaronealdehyde (2,4,5-trimethoxy-benzaldehyde) can be produced in the following way Methylate resorcinol. Product is 1,3-di-MeO-benzene. Do a Vilsmeyer aldehyde synthesis with POCI3/N-methylformanilide to obtain 2,4-di-MeO-benzaldehyde. Brominate and treat as described above to obtain asaronaldehyde. 

A solution of sodium methoxide (25% w, 115 ml, 532 mmol) in methanol (187 ml) was cooled to — 8 "C under nitrogen. A solution of 2,4,5-trimethoxy-benzaldehyde (25 g, 128 mmol) and methyl azidoacetate (59 g, 513 mmol) in a 1 2 mixture of methanol-THF (50 ml 4- 100ml) was added dropwisc to the sodium methoxide solution with stirring at — 8°C over a period of 45 min. The solution was stirred and kept below 5°C for 2 h. The mixture was then poured onto ice (1 kg) and stirred. The precipitate which resulted was collected by filtration, washed with water and dried over CaCl in a vacuum desiccator. The dried precipitate was dissolved in EtOAc (600 ml) and dried over Na2S04. 

The synthesis of 3-H-oxazol-2-ones was described by Nam et al. [69]. The substituted benzoin 89 was formed from the coupling of 3,4,5-trimethoxy-benzaldehyde 18 with 3-nitro-4-methoxybenzaldehyde, Scheme 22. Reaction with PMB-isocyanate and subsequent cyclization gave the protected oxazolone derivative 90. The PMB group was removed by reflux in TFA and reduction of the nitro-group was performed using Zn to give the combretoxazolone-aniline 91. 

Reaction of 2-acyl-l,2,3,4,ll,lla-6H-hexahydropyrazino[l,2-fr]isoqui-noline-l,4-diones with aromatic aldehydes in the presence of KOfBu in CH2CI2 afforded 2-unsubstituted-3-arylidene derivatives (09T2201). From a similar reaction of czs-6H,llaH-6-benzyloxymethyl-9-methyl-7,8,10-trimethoxy-2-pivaloyl-l, 2,3,4,11,11 a-6H-hexahydropyrazino[l, 2-b] isoquinoline-1,4-dione and 3-methyl-2,4,5-benzaldehyde 2-unsubsti-tuted-3-(3-methyl-2,4,5-trimethoxyphenyl)methylene and 2-pivaloyl-3,3-dihydroxy derivatives were isolated in 20% and 39% yields, respectively. 

Mono- and trimethoxyphenyl azolactone intermediates of Stepl were also prepared by the author by condensing the corresponding mono- or trimethoxy benzaldehyde with N-acetyl glycine and are described. 

Benzaldehyd 2,5-Dimethoxy-4-ethyl-E3, 24 (H - CHO) Benzocyclobutene 1,1,6-Trimethoxy-E17f, 976 [1-Br— 1-OR— benzene... 

Huai -Minltm-Wolff-Kishner rednction (1, 1197). Reduction of 3,4,5-trimethoxy-benzaldehyde ... 

The methylation of 5-hydroxyvanillin to 3,4,5-trimethoxy benzaldehyde is carried out by contacting the 5-hydroxyvanillin wit dimethyl sulfate in the presence of an alkali metal carbonate in ac organic medium. 

A different approach consists of a two-steps stereoselective synthesis of Combretastatin A-4, based on the Perkin condensation of 3,4,5-trimethoxy phenyl acetic acid and 3-hydroxy-4-methoxy benzaldehyde, followed by decarboxylation of the cirmamic acid intermediate using copper and quinoline [11] (Schema 4). 

For instance, p-cresol has been used as the starting material for manufacture ofp-anisaldehyde (a vital raw material for UV-B Sunscreen Chemicals and anti-hypertension drug, namely Dilitiazem), Synthetic Vanilin, 3,4,5-trimethoxy benzaldehyde (a starting material for Trimethoprim), perfumery products such as p-cresyl acetate, p-cresyl phenyl acetate, and a host of other products. 

It may be logical to assume that most of synthetic vanillin will be produced from p-cresol in future either in isolation or along with other important derivatives such as verataldehyde and 3,4,5-trimethoxy benzaldehyde. 

Para-hydroxy benzaldehyde is an important building block for a number of key organic compounds including p-anisic aldehyde, 3,4,5-trimethoxy benzaldehyde veratral-dehyde, bromoxylin and others. Important uses have been shown in Fig. 5.3. 

Para-anisic aldehyde and p-anisic alcohol are two important p-cresol derivatives which have provided critical feedstocks for some of the important bulk drugs. Trimethoprim made from 3,4,5-trimethoxybenzaldehyde is another example. p-Cresol has already replaced gallic acid as the preferred starting material for 3,4,5-trimethoxy benzaldehyde. As more R D work is undertaken, there will no doubt emerge more finished pharmaceutical items not only from p-cresol but also from o-cresol and m-cresol. Growth of meZo-cresol has indeed been remarkable after the process was commercialized for... 

In a cresols complex producing para-cresol and some of the downstream derivatives such as p-anisic aldehyde or other oxidation products such as 3,4,5-trimethoxy benzaldehyde, etc., important inorganic chemicals can be recovered and sold not only towards improvement of the eco-system but also for betterment of the bottom-line from sales of these by-products from the waste streams. 

Similarly use of cobalt acetate-manganese acetate as a catalyst for the oxidation processes of p-cresol to p-hydroxy benzaldehyde or 3,4,5-trimethoxy benzaldehyde will generate waste streams from which co-acetate and Mn-acetate are to be recovered and recycled. Use of other catalysts for other processes will similarly generate waste liquid streams containing unused surplus catalysts or as converted salts which need to be processed and make the liquid waste stream as much free from inorganic impurities as possible. Not only from ecologi-cal/environmental points of view, this is necessary but also commercially this will make the operations more viable and attractive. 

It is reliably learnt that one Japanese company is using Co-acetate-Mn-acetate in a predetermined ratio for oxidation of PCME to p-anisic aldehyde. Similarly these mixed acetate catalysts have been used for oxidation of p-cresol to 7 -hydroxy benzaldehyde at a high pressure (say 10 kg/cm ) and also 3,4,5-trimethoxy benzaldehyde manufacture for conversion of the methyl group to aldehyde as discussed in Chapter 5. Use of this catalyst system is an established fact for oxidation of p-xylene to ptuified terephthalic acid (PTA) or dimethyl terephthalate. 

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