Dimethoxybenzaldehyde Preparation

While reaction solvents are not necessary for the process of this invention, suitable solvents may be employed if desired. If solvents are used it is necessary to select solvents which per se are not alkylated, i.e.,those which are inert to the alkylation effects of the dialkyl sulfate. Suitable such non-alkylatable solvents are diethyl ether, dioxane, acetone methyl ethyl ketone, ethyl acetate, butyl acetate, tetrahydrofu-ran, and the like. When the desired compound is recovered by pouring the reaction mixture into water after the completion of the reaction, solvents such as dioxane, acetone and methyl ethyl ketone miscible with water are preferably used. For instance, acetone is preferred. Agitation causes the reaction to proceed rapidly. The reaction time can be varied over a wide range depending upon conditions such as reaction temperature and agitation. For example, the reaction time can vary from several tens of minutes to several days. When the reaction is completed, which 

50 g of 2-hydroxy-5-methoxybenzaldehyde, 68 g of potassium carbonate and 50 g of dimethyl sulfate were refluxed in 250 mL. of acetone for about 3 hours under stirring. After the reaction, the reaction mixture was filtered and the acetone was distilled off from the filtrate and then the residue was poured into 300 mL. of water. The precipitated crystals were collected by filtration and dried whereby 45 g of 2,5-dimethoxybenzaldehyde having a melting point of 48° C were obtained (yield 82.5%). 

On standing, the mixture of 2-hydroxy-5-methoxybenzaldehyde, potassium carbonate and dimethyl sulfate as in Example 1 at room temperatures the reaction was completed in 7 days. This was confirmed by gas chromatography. By treating the reaction mixture as described in Example 1, 44.5 g of 2,5-dimethoxybenzaldehyde having a melting point of 47° C were obtained (yield 81.5%). 

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 

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Reflux 6.9 g triphenylphosphine and 6.6 g lauryl bromide (or equimolar amount of homolog) in 40 ml xylene for 60 hours. Remove solvent and wash residue with 5X20 ml ether (by decanting) to get 11 g lauryl triphenylphosphonium bromide (I). To a stirred suspension of 5.6 g (0.011M)(I) in 50 ml ether add 0.01M butyllithium solution (see Organic Reactions 8,258(1954) for preparation). Stir Vz hour at room temperature and slowly add 1.66 g 3,5-dimethoxybenzaldehyde (preparation given elsewhere here) in 10 ml ether over Vi hour. After 15 hours, filter, wash filtrate with water and dry, evaporate in vacuum. Dilute residue with pentane, filter and remove solvent. Dissolve the residual oil in 25 ml ethyl acetate and hydrogenate over O.lg Adams catalyst at one atmosphere and room temperature for 2 hours. Filter and evaporate in vacuum to get the 5-alkylresorcinol dimethyl ether which can be reciystallized from pentane and demethylated as described elsewhere here. 

As an allergen for testing purposes, synthetic 3-pentadecylcatechol is more useful than natural poison ivy extracts (of which it is one component). A stable crystalline solid, it is efficiently prepared in pure form from readily available starting materials. Outline a reasonable synthesis of this compound from 2,3-dimethoxybenzaldehyde and any necessary organic or inorganic reagents. 

Synthesis of Peptides by Hydrogenation of Dehydropeptides. In addition to the interest in dehydropeptides in their own right, these compounds are also used to prepare non-proteinogenic peptides by simple reduction. For example, the electrochemical reduction of dehydropeptides derived from 2,3-dimethoxybenzaldehyde has been described. ... 

An alternative focus based on known antitumor activity of adriamycin-type systems stimulated the synthesis of the aza-anthraquinones 599 and 600 (Scheme 177) (84CC897). Thus, synergistic chloro-oxazoline directed metalation of 597 with methyllithium followed by treatment with 2,5-dimethoxybenzaldehyde and acid-promoted cyclization provided the lactone 598. Radical bromination and base-induced hydrolysis gave an intermediate keto acid which, upon Friedel-Crafts cyclization with methanesulfonic acid, led to the aza-anthraquinone 599 in modest yield. The azanaphthacene dione 600 was prepared by an analogous series of reactions starting with 597. 

An alternative procedure49 for effecting the conversion of acid chlorides into aldehydes is chemical reduction with bis(triphenylphosphine)copper(i) tetrahy-droborate (see also Section 5.7.4, p. 594). The procedure is illustrated by the synthesis of 3,4-dimethoxybenzaldehyde which is isolated as the 2,4-dinitro-phenylhydrazine derivative50 (cognate preparation in Expt 6.120). 

Cognate preparation. 3,4-Dimethoxybenzaldehyde 2.4-dudtrophenylhydror zone (use of bis(triphenylphosphine)copper(i) tetrahydroborate)50 3,4-Dimethoxybenzoyl chloride (1.14g, 5.7 mmol) in acetone (100 ml) is treated with triphenylphosphine (3.04 g, 11.6 mmol). To this solution at room temperature, bis(triphenylphosphine)copper(i) tetrahydroborate (3.47 g, 5.8 mmol) (Section 4.2.49, p. 449) is added and the reaction mixture stirred for 45 minutes. The white precipitate of triphenylphosphine copper chloride (4.9 g, 5.5 mmol) is removed by filtration and the filtrate evaporated to dryness. The residue is extracted with ether (the ether-insoluble residue is shown to be triphenylphosphine borane). The ether is removed, the residue... 

Bromo-3,4-dimethoxybenzaldehyde was purchased from the Aldrich Chemical Company, Inc. (Milwaukee) or readily prepared by bromination of veratraldehyde (Aldrich Chemical Company, Inc. or Tokyo Kasei).4... 

The disadvantage of the intermolecular dipolar cycloaddition strategy is nonstereoselectivity. A recent stereoselective synthesis of lasubine 1 (2) utilizes the intramolecular tt cyclization of an /V-acyliminium ion as a key step (Scheme 4) (16). The reaction of carbinol 38, prepared from 3,4-dimethoxybenzaldehyde (33) and allylmagnesium bromide, with glutarimide under Mitsunobu conditions... 

Dimethoxycinnamic add has been prepared by heating 2,3-dimethoxybenzaldehyde with acetic anhydride and sodium acetate at 200° 2 and by the condensation of 2,3-dimethoxybenzaldehyde and ethyl acetate with sodium, followed by hydrolysis.3 The present preparation represents an adaption of the Doebner reaction. 

Several syntheses are on record which avoid the preparation of 5-benzyloxyindole in these procedures, the indole ring is usually formed after provision is made for the introduction of the ethanamine side chain. The first of these (107, 108) was an adaptation of Ewins original trypt-amine synthesis. A subsequent route (109) started from ethyl a-cyano-2,5-dimethoxycinnamate (VIII), which was prepared by condensation of 2,5-dimethoxybenzaldehyde with ethyl cyanoacetate. When this was boiled with potassium cyanide solution, addition of the elements of hydrogen cyanide was accompanied by hydrolysis of the ester function and decarboxylation, to give 2,5-dimethoxyphenylsuccinonitrile (IX). 

Arctigenin (472), prepared from 3,4-dimethoxybenzaldehyde, was submitted to PhI(OCOCF3)2-promoted oxidation in trifluoroethanol (TFE) (room temp., 24 h) to afford spirodienone 473 and a mixture of two cyclooctadienes (474 and 475) in 13 and 14% yields, respectively. When the reaction was repeated in hexafluoroisopropanol for 3.5 h, a 1 1 mixture of stegaue 474 and isostegane 475 was obtained in 26% yield (Scheme 93). Acid-catalyzed rearrangement of 473 with HCIO4 in CHCI3 provided a quantitative... 

Dimethoxybenzaldehyde was prepared by Wittig as follows 210 When a mixture of resorcinol dimethyl ether (13.8 g, 0.1 mole) and phenyllithium (0.1 mole) in anhydrous ether (100 ml) is kept at room temperature for 60 h, the lithio derivative separates as large transparent crystals. Then A-methylformamide (13.5 g), dissolved in anhydrous ether (100 ml), is dropped in, which causes the mixture to boil. When the main reaction has ceased, the mixture is set aside for 0.5 h, then poured into an excess of dilute sulfuric acid. The ether layer is separated, dried, and freed from solvent. The residue is distilled at 13 mm until the vapor temperature reaches 130°. The residue in the distillation flask crystallizes from cyclohexane or much water in needles, m.p. 98-99°. The yield is 55%. 

For a wide variety of (13 0), (15 0), (17 0) and higher alkyl substituted phenolic lipids a universally applicable method of preparation has been reaction of an OH-protected phenolic aldehyde with an even carbon number n-alkylmagnesium halide, followed by reduction (or dehydration and reduction) and removal of the protective group. This technique has been used with 3-methoxybenzaldehyde, 3,5-dimethoxybenzaldehyde or their isomers and further substituted versions. 

The oxalylfulgides (129) have been prepared and studied. These photochromic yellow dyes undergo ring closure in the conventional manner. The quantum yields for the process and the solvent dependency results are shown below the struetures. " A double Stobbe condensation of 3,5-dimethoxybenzaldehyde with succinic anhydride affords the fulgide (130). This is photochemically reactive and undergoes cyclization to afford a pink cyclic form on irradiation at 366 nm. ... 

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