4-Ethoxy-3-methoxybenzaldehyde

Ethoxy-3-methoxybenzyl alcohol 6, 2-(2-methoxyphenoxy)ethanol 8 and 1,3-dihydroxy-2-(2-methoxyphenoxy)propane 13 were formed from the B-0-4 dimer 1 in intact cultures, but not identified in the in vitro system. They axe probably formed secondeirily by reduction of initial cleavage products formed by the enzyme. In fact, this fungus reduces 4-ethoxy-3-methoxybenzaldehyde 7 and 2-benzyloxyacetaldehyde to the corresponding alcohols, il-ethoxy-3-methoxybenzyl alcohol 6 and a compound similar to 8, 2-benzyloxyethanol, respectively (23). 

C10H12O2 1-(2-hydroxy-3-methylphenyl)-1-propanone 3338-15-6 504 61 44.327 2 19635 C10H12O3 4-ethoxy-3-methoxybenzaldehyde 120-25-2 522.10 46.012 2... 

Demethylation of methyl aryl ethers (5, 409). The cleavage of 4-ethoxy-3-methoxybenzaldehyde ethylene acetal to 4-ethoxy-3-hydroxybenzaldehyde with (CeH5)2PLi has now been published. ... 

Practical-grade 4-cthoxy-3-methoxybenzaldehyde (4-ethoxy-m-anisaldehyde) was obtained by the submitters from MC and B Manufacturing Chemists and by the checkers from Aldrich Chemical Company, Inc. This material was purified by distillation (b.p. 125-135°/0.1 mm.), followed by one recrystallization from cyclohexane (100 ml./lO g. crude solid). Colorless crystals, m.p. 60-62°, wrere obtained after filtration and vacuum drying. Purification of 20 g. of the commercial material gave about 15 g. of recrystallized product. 

A solution of 7.3 g of 3-ethoxy-5-hydroxy-4-methoxybenzaldehyde in 100 mL acetone was treated with 5 mL methyl iodide and 8.0 g finely powdered anhydrous K2CO, and held at reflux on a steam bath for 6 h. The solvent was removed under vacuum, and the residue was suspended in H20. After making this strongly basic, it was extracted with 3x50 mLCH,CL, the extracts were pooled, and the solvent removed under vacuum. The residual amber oil was distilled at 110-120 °C at 0.4 mm/Hg to yield 7.3 g of a white oil. This spontaneously set to white crystals of 3,4-dimethoxy-5-ethoxybenzaldehyde which had a mp of 49-49.5 °C. Anal. (CmHi (04) C,H. This same aldehyde can be obtained, but in a less satisfactory yield, by the ethylation of 3,4-dimethoxy-5-hydroxybenzaldehyde described under the preparation of metaproscaline (MP). 

The molecular structures of vanillin (4-hydroxy-3-methoxybenzaldehyde), isovanillin (3-hydroxy-4-methoxybenzaldehyde) and ethylvanillin(3-ethoxy-4-hydroxybenzaldehyde) were determined by Egawa et al. (2006) by means of gas electron diffraction. Among them, vanillin and ethylvanillin have a vanilla odour but isovanillin smells different. Vanillin and isovanillin have two stable con-formers and ethylvanillin has four. 

The upper organic layer is washed and is then distilled at 120° C. under a reduced pressure of 10 mm of mercury (1330 Pa), to give 3-ethoxy-4-methoxybenzaldehyde. 

By rcpeatingthe procedures described in Example 1 except thai 61 gofdiotliyl sulfate were used instead of 50 g of dimethyl sulfate, 53 g of 2-ethoxy-o-methoxybenzaldehyde having a melting point of 47° - 48 C were obtained (yield 97.5%). Anal. Found C, 66.58 H, 6.74. Calcd. ( 66.67 H, 6.67. Source Imai 1975... 

SYNTHESIS A solution of 83 g bourbonal (also called ethyl vanillin, or vanillal, or simply 3-ethoxy-4-hydroxybenzaldehyde) in 500 mL MeOH was treated with a solution of 31.5 g KOH pellets (85% material) dissolved in 250 mL H20. There was then added 71 g methyl iodide, and the mixture was held under reflux conditions for 3 h. All was added to 3 volumes of H20, and this was made basic with the addition of 25% NaOH. The aqueous phase was extracted with 5x200 mL CH2CI2. The pooling of these extracts and removal of the solvent under vacuum gave a residue of 85.5 g of the product 3-ethoxy-4-methoxybenzaldehyde, with a mp of 52-53 °C. 

A well stirred solution of 125.4 g 3-ethoxy-4-methoxybenzaldehyde in 445 mL acetic acid was treated with 158 g 40% peracetic acid (in acetic acid) at a rate at which, with ice cooling, the internal temperature did not exceed 27 °C. The addition required about 45 min. The reaction mixture was then quenched in some 3 L H20. There was the generation of some crystals which were removed by filtration. The mother liquor was saved. The solid material weighed, while still wet, 70 g and was crude formate ester. A small quantity was recrystallized from cyclohexane twice, to provide a reference sample of 3-ethoxy-4-methoxyphenyl formate with a mp of 63-64 °C. The bulk of this crude formate ester was dissolved in 200 mL concentrated HCI which gave a deep purple solution. This was quenched with water which precipitated a fluffy tan solid. 

A mixture of 27 g methyltriphenylphosphonium bromide in 150 mL anhydrous THF was placed under a He atmosphere, well stirred, and cooled to 0 °C with an external ice water bath. There was then slowly added 50 mL of 1.6 N butyllithium in hexane which resulted in the initial generation of solids that largely redissolved by the completion of the addition of the butyllithium and after allowing the mixture to return to room temperature. There was then added 11.7 g of 4-ethoxy-3-ethylthio-5-methoxybenzaldehyde without any solvent. There was the immediate formation of an unstirrable solid, which partially broke up into a gum that still wouldn t stir. This was moved about, as well as possible, with a glass rod, and then all was added to 400 mL H20. The two phases were separated and the lower, aqueous, phase extracted with 2x75 mL of petroleum ether. The organic fractions were combined and the solvents removed under vacuum to give the crude 4-ethoxy-3-ethylthio-5-methoxystyrene as a pale yellow fluid liquid. 

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