Methanol, esters perchlorate

METHANESULFONYL CYANIDE, 57, 88 Methane, triphenyl-, 55, 11 Methanol, (4-methylphenylsulfonyl) esters, perchlorate, 57, 100... 

Hydrolysis of the acetate ester with alkali, e.g., sodium methoxide in methanol, affords the free alcohol, 16/3-methyl-1,4,9( 11 )-pregnatriene-17o, 21-diol-3,20-dione. To a suspension of 3 grams of 16/3-methyl-1,4,9(11)-pregnatriene-17o,21-diol-3,20-dione-21-acetate in 40 ml of acetone is added at 0°C with stirring 2 grams of N-chlorosuccinimide and then 7 ml of a perchloric acid solution prepared by dissolving 0.548 ml of 70% perchloric acid in 33 ml of water. The resulting reaction mixture is stirred at 0°C for about 4 hours 45 minutes. 

A general synthesis of a-hydroxy esters is based on 2-ethylthio-l,3-benzodithiole which serves as a methoxycarbonyl anion equivalent. Thus reaction of the lithium compound (216) with ketones followed by treatment with mercury perchlorate in methanol leads to the formation of a-hydroxy acid derivatives (217) (81SC209). 

Both routes actually use vanilly alcohol 34 (3-methoxy-4-hydroxybenzyl alcohol) as the starting material. Application of method (a) requires that 34 could be trimerized to C3-cyclotriguaiacylene, 5 (Table 1). However, as was said above, this reaction does not work, presumably because the phenolic group makes the molecule too reactive under the strong acidic conditions employed the allyl protected derivative 35 was thus used instead of 34 itself, and, on reaction with perchloric acid in methanol, gave the tris-allyl protected derivative 9 in 55% yield. Palladium catalysed cleavage of the allyl groups then led to the desired racemic triphenol 5. The latter could eventually be resolved by separation of its dia-stereoisomeric esters with co-camphanic acid [13]. 

The presence of the /3-hydroxypropionic ester unit in deacetylpicraline is established by oxidation with chromic acid in acetone, which yields an aldehyde base, picralinal, C21H22N2O4 the latter is readily deform yla ted by short treatment with methanolic potassium hydroxide, which affords picrinine in quantitative yield. Reduction of picralinal with sodium borohydride regenerates deacetylpicraline. Vigorous treatment of deacetylpicraline with sodium borohydride gives a noncrystalline indoline base, which exhibits the UV-absorption of an anilinium ion in concentrated perchloric acid hence, the Na-carbinol-amine ether function must have suffered reduction. Since acetylation of the noncrystalline base gives a product which exhibits acylaniline UV-absorption, picraline and its derivatives must contain an NaH group (53, 54). 

Melinonine B is formulated as C2oH2 N20+ on the basis of analyses of the chloride, iodide, and perchlorate the chloride, mp 311° (dec.), has [a]D —14.8° (methanol-water) (54). The alkaloid has one A-methyl group but no methoxyl or (7-methyl groups. Its UV-spectrum is that of a 2,3-disubstituted indole and its IR-spectrum exhibits both hydroxyl (3.05 /x) and N—H (3.20 /x) absorption. Acetylation of melinonine B gives a crystalline 0,A-diacetyl derivative which results from attack at the indolic Na, since the UV-spectrum of this derivative is that of an A-acylindole and its IR-spectrum has both ester and amide bands. 

Oxidative esterification. The H2O2-V2O5 reagent converts aromatic aldehydes to methyl esters in methanol (perchloric acid is also present). 

Fig. 11.8.1. Reversed phase separation of vitamin A alcohol and esters. Chromatographic conditions stationary phase, Zorbax C-8 (250 x 4.6 mm I.D.) mobile phase, 99.8% water-0.2% perchloric acid (60%), and 99.8% methanol-0.2% perchloric acid flow rate, 1.6 ml/min detection, UV at 254 nm. Peaks 1, vitamin A alcohol 2, impurity 3, vitamin A acetate 4, vitamin A palmitate. Reproduced from Dupont Analytical Systems with permission.

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