This will probably be the most funky 2C-B precursor yet, but it's preparation is remarkably easy (that is if you have Ac2O and red P handy). Maybe it could serve to make an interesting (legal) pro-drug.
The preparation of 5-MeO-salicylaldehyde by the Reimer-Tiemann rxn of p-MeO-phenol has been covered before. The method submitted by Karel gives 75% yield.
From Biochem.Prep. vol. III, p 79-83 (1953) :
Condensation of 5-methoxysalicylaldehyde with hippuric acid.
The product of this condensation, described below, is a mixture of 2-phenyl-4(2'-acetoxy-5'-methoxybenzal)-5-oxazolone (II) and 2-keto-3-benzamido-6-methoxycoumarin (III).
In a 1L roundbottomed flask fitted with a ground-glass condensor, protected from moisture with a CaCl2 tube, there are placed 31 gr. (0.204 mol) of distilled 5-methoxysalicylaldehyde, 40 gr. (0.22 mol) of hippuric acid, 16.5 gr. (0.2 mol) of finely powdered sodium acetate, and 85 ml. of acetic anhydride. The mixture is heated on the steam bath for 45 minutes. All reactants dissolve during the first ten minutes of heating to give a clear, deep-yellow solution. The reaction mixture is allowed to stand overnight at room temperature. The yellow solid which has separated is broken up with a glass rod, and 300 ml of water is slowly added. The slow hydrolysis of the acetic anhydride is allowed to proceed at room temperature for at least 6 hours, and preferably overnight, with occasional trituration of the solid with a glass rod flattened at the end. The product is filtered on a 9 cm. Büchner funnel and washed on the funnel with 100 ml. of water. The still moist, sticky product is transferred to a beaker and thoroughly triturated with 75 ml. of ice-cold ethanol. It is filtered and washed on the filter with two 50 ml. portions of ether. After being dried in air, the light-yellow crystalline powder weighs 31.6-34.5 gr.
Nitrogen analysis (found: N, 4.34-4.51%) indicates that the product is a mixture of about equal parts of the azlactone (II, C19H15O5N requires: N, 4.15%) and the coumarin compound (III, C17H13O4N requires: N,4.75%). It is suitable as isolated for the preparation of the amino acid.
beta-2,5-dihydroxyphenyl-DL-alanine
In a 1L two-necked roundbottomed flask, fitted with a condenser and mercury seal stirrer, there are placed 40 gr. of the azlactone-coumarin mixture, 15 gr. of red phosphorous, 160 ml. of glacial acetic acid, and 125 ml. of hydriodic acid (sp. gr. 1.7). The reaction mixture is refluxed with stirring for 2 hours. The red phosphorous is filtered from the hot solution and washed with two 25 ml. portions of hot glacial acetic acid. The filtrate and washings are concentrated to dryness under reduced pressure (water pump) at 50-55°C in an atmosphere of nitrogen. Water (100 ml) is added to the residue, and the concentration to dryness is repeated. The dry residue is dissolved as completely as possible in 200 ml. of water and 200 ml. of ether. A small amount of material insoluble in either phase is removed by filtration. The aqueous phase is separated and extracted 3x with 100 ml. portions of ether to complete the removal of benzoic acid. The aqueous solution of the hydriodide of the amino acid is concentrated almost to dryness as above. The hydriodide is dissolved in approx. 200 ml. of hot water, and the hot solution is adjusted to pH 4-5 by the cautious addition of conc. NH4OH (about 40-50 ml are usually required). On cooling and standing in the cold for 2 or 3 days, 17.3-18.3 gr. of crude beta-2,5-dihydroxyphenyl-DL-alanine separate and are collected and washed with about 50 ml. of cold water
The amino acid is dissolved in boiling water containing a trace of NaHSO3, boiled briefly wih 1-2 gr. of activated carbon, and filtered. From the water-clear filtrate thereseparate on cooling 13.3-14.2 gr. of the pure amino acid hydrate. An additional 2-3 gr. is obtained when the filtrate from the first crop is concentrated to small volume in vacuum and allowed to stand in the cold.
The product gives correct analyses for nitrogen by the Kjeldahl procedure. The m.p. (245-250°C) is too variable to serve as a criterion for purity. The triacetyl derivative has an m.p. of 157-158°C
It gives the xanthoproteic and ninhydrin reactions, reduces AgNO3 slosly at pH 4-5 and instantaneously at alkaline reaction, and reduces phosphomolybdic acid in acid solution. In alkaline solution, the amino acid is unstable, the solution rapidly becoming black.
