Acetic acid, 3,4-dimethoxyphenyl

Acetic acid, cyano-, ethyl ester 55, 58, 60 Acetic acid, 3,4 dimethoxyphenyl, 55, 45, 46... 

Dimethoxyphenyl acetic acid (homoveratric acid) [93-40-3] M 196.2, m 97-99 , pK 4.33. Crystd from water or benzene/ligroin. 

Tetramethoxyisoflavone (5) was the target of the cyclisation reaction of 3,4-dimethoxy-phenol (7) with formyl-(3,4-dimethoxyphenyl)acetic acid (2) in the presence of polyphosphoric acid. 

The A-substituted derivatives of 4-oxo-4//-pyrido[l,2-n]pyrimidine-3-carboxamides and -3-acetamides and l,6-dimethyl-4-oxo-1,6,7,8-tetrahy-dro-4//-pyrido[l,2-n]pyrimidine-3-carboxamide were prepared by treatment of the appropriate 3-carboxylic acids and acetic acid, first with an alkyl chloroformate in the presence ofNEt3 in CHCI3 below — 10°C, then with an amine (98ACH515). A-Phenethyl and A-[2-(3,4-dimethoxyphenyl)ethyl] derivatives of 6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetamide were obtained in the reaction of 6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l,2-n]pyrimidine-3-acetic acid and phenethylamines in boiling xylene under a H2O separator. Hydrazides of 4-oxo-4//- and 4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetic acid were prepared from the appropriate ester with H2NNH2 H2O in EtOH. Heating 4-oxo-4//- and 6-methyl-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetic hydrazides in EtOH in the presence of excess Raney Ni afforded fhe appropriafe 4-oxo-6,7,8,9-fefrahydro-4//-pyrido[l,2-n]pyrimidine-3-acefa-mide. In the case of the 4-oxo-4// derivative, in addition to N-N bond... 

A solution of 20.7 g (0.1 mmol) of (46 ,56 )-5-amino-2.2-dimethyl-4-phenyl-l,3-dioxane and 19.4 g (0.1 mol) of 3,4-dimethoxyphenyl-2-propanone in 70 mL of CH3OH is warmed to 60 "C and 9 mL of acetic acid is added. After 15 min the mixture is cooled with an ice bath. The precipitated product is filtered off, stirred with 1 L of water for 1 h to dissolve inorganic salts, and again collected by filtration. Drying over NaOH and recrystallization from CH3OH gives the product yield 33.6 g (82%) mp 127 128°C [a] 2 + 85.7 (c = 1, CHC1,). 

The heating of [2-(3,4-dimethoxyphenyl)ethylamino]methylenemal-onates (1386) in 24% aqueous hydrochloric acid gave tetrahydroisoquino-line-l-acetic acid hydrochlorides (1387) in good yields (56JOC336 761JC784). 

Dimethoxyphenyl-nitropropene. A solution of 10 g of 2,5 dimethoxybenzaldehyde, 4 g of ammonium acetate, and 6.8 g of nitroethane (or an equimolar amount of analog) in 50 ml of glacial acetic acid is heated on a boiling water bath for three hours, then the solvent is evaporated. The remaining residue is suspended in water and extracted with chloroform. Evaporation of the chloroform will leave the title compound. Crystallization from ethanol purifies. Yield 11 g, mp 73-75°. 

An important extension of this method has made it possible to synthesize polycyclic benzofurans under the influence of various demethylating and dehydrating media.335 For such ring closures, pyridine hydrochloride is especially suitable thus coumestan has been synthesized from 4-hydroxy-3-(2-methoxyphenyl)coumarin.8 4,7-Di hydroxy-3-(2,4-dimethoxyphenyl)coumarin gives coumestol with aniline hydrochloride 336 other polymethoxycoumestans have been obtained with pyridine hydrochloride or with HBr (or HI) and acetic acid.337-339... 

C,H] in 20 mL anhydrous MeOH, there was added a solution of sodium methoxide in MeOH (generated from 0.5 g metallic sodium in 20 mL anhydrous MeOH). After a few min there was added 10 mL acetic acid (no solids formed) followed by the slow addition of 50 mL of H20. A cream-colored solid was produced, which was removed by filtration and washed well with H20. After air drying the product, l-(4-bromo-2,5-dimethoxyphenyl)-l-methoxy-2-nitroethane, weighed 2.0 g. An analytical sample from MeOH was off-white in... 

SYNTHESIS A solution of 33.2 g of veratraldehyde in 15.0 g nitroethane was treated with 0.9 g of n-amylamine and placed in a dark place at room temperature. In a day or so, separated H20 was apparent and, after a couple of weeks, the mixture completely solidified. The addition of 50 mL EtOH and heating effected complete solution and, on cooling, this provided 1 -(3,4-dimethoxyphenyl)-2-nitropropene as yellow crystals, 29.0 g, with nip of 70-71 °C. The more conventional reaction scheme, 6 h heating of a solution of the aldehyde and nitroethane in acetic acid with ammonium acetate as catalyst, gave a much inferior yield of product (33.2 g gave... 

To a solution of 2.0 g N-(l-(2,5-dimethoxyphenyl)-2-propyl)phthalimide in 15 mL warm acetic acid which was being vigorously stirred, there was added a solution of 1.2 g iodine monochloride in 3 mL acetic acid. This was stirred for 2 h... 

SYNTHESIS A solution of 10.0 g 2,5-dimethoxybenzaldehyde in 50 mL glacial acetic acid was treated with 6.8 g of nitroethane and 4.0 g of anhydrous ammonium acetate. This mixture was heated on the steam bath for 3 h and then the reagent/ solvent was removed under vacuum. The residue was suspended in H20 and extracted with CHClj. Removal of the solvent from the pooled extracts yielded 11.2 g of an impure l-(2,5-dimethoxyphenyl)-2-nitropropene which, on recrystalliza-... 

However, the study of various direct iodinations and fluoridations that would have the N,N-dimethyl substitution on the amphetamine nitrogen atom, would require the 4-proteo- analogue, and this was made from the above nitrostyrene. A solution of the above nitrostyrene, 22.3 g 1 -(2,5-dimethoxyphenyl)-2-nitropropene in 100 mL acetic acid was added to a suspension of elemental iron in acetic acid (45 g in 250 mL) and worked up with water and base washing to give, after distillation at 92-106 °C at 0.35 mm/Hg, 13.8 g 2,5-dimethoxyphenylacetone as a pale yellow... 

SYNTHESIS To a solution of 68 g 2,4-dimethoxybenzaldehyde in 250 mL glacial acetic acid that had been warmed to 25 °C and well stirred, there was added, dropwise, 86 g of a 40% peracetic acid solution (in acetic acid). The reaction was exothermic, and the rate of addition was dictated by the need to maintain the internal temperature within a few degrees of 28 °C. External cooling was used as needed. The addition took 1 h, and when the reaction had clearly been completed (no further temperature rise) the entire reaction mixture was added to 3 volumes of H20. The excess acid was neutralized with solid K CO. (283 g were required). This was extracted with 3x100 mL EtjO, the extracts pooled, and stripped of solvent under vacuum to give 66 g of crude 2,4-dimethoxyphenyl formate. This was suspended... 

Dimethoxyphenyl)acetaldehyde Hydrochloric acid Acetic acid... 

The kinetics of the reaction of various silyl hydrides with tris(2,6-dimethoxyphenyl)methyl cation and some other stable carbocations in acetic acid have been systematically investigated by Carey and Wang-Hsu (92). The results were interpreted in terms of a four-center transition state involving a trigonal bipyramid at silicon with nucleophilic participation of the solvent. 

The synthesis of bufotenine itself followed closely upon the proof of its structure. Hoshino and Shimodaira reduced the ethyl ester of 5-ethoxy-indole-3-acetic acid by the Bouveault-Blanc procedure to the corresponding primary alcohol, which was treated with phosphorus tribromide and then dimethylamine, to give the ethyl ether of bufotenine, which was demethylated with aluminum chloride (130). In a later synthesis, 2,5-dimethoxybenzyl cyanide (XXIII) was alkylated by Eisleb s method with dimethylaminoethyl chloride in the presence of sodamide to give l-(2,5-dimethoxyphenyl)-3-dimethylaminopropyl cyanide (XXIV), which was then hydrogenated over Haney nickel to yield 2-(2,5-di-methoxyphenyl)-4-dimethylaminobutylamine (XXV R = Me). De-methylation of this with hydrobromic acid, followed by oxidation of the product (XXV R = H) with potassium ferricyanide yielded bufotenine (XIX) via the related quinone (109). 

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