Optical Resolution of 2′-Methoxy-1,1′-binaphthyl-2-carboxylic Acid, and Application to Chiral Derivatizing Agent for HPLC Separation of Enantiomeric Alcohols and Amines

Abstract

Racemic 2′-methoxy-1,1′-binaphthyl-2-carboxylic acid was separated on a multi-gram scale into its antipodes via silica-gel column chromatography followed by alkaline hydrolysis of the diastereomeric esters prepared from (R)-1-phenylethanol or (−)-menthol. The molecular structure of (−)-menthyl (aS)-2′-methoxy-1,1′-binaphthyl-2-carboxylate was determined by single-crystal X-ray analysis. The (aS)-acid was converted to crystalline acid chloride, which was conveniently utilized as efficient chiral derivatizing agent for differentiation of enantiomeric alcohols and amines by high-performance liquid chromatography on silica gel. The elution behavior of a pair of diastereomeric esters or amides was explained by the steric interactions between the solutes and the silica-gel stationary phase on the basis of the X-ray analysis.

1‐Arylfluorenols: Convenient preparation via the ester‐mediated nucleophilic aromatic substitution protocol, facile racemization, and intrinsic chiral induction ability

“…A mixture of racemic fluorenol 1a (1.00 g, 3.87 mmol), acid chloride (S)-7 16 (1.62 g, 4.67 mmol) and dry pyridine 1-ARYLFLUORENOLS (13 ml) was stirred at room temperature for 20 hr. The mixture was poured into 1 M HCl and extracted with chloroform.…”

1-Arylfluorenols: Convenient preparation via the ester-mediated nucleophilic aromatic substitution protocol, facile racemization, and intrinsic chiral induction ability

“…A mixture of racemic fluorenol 1a (1.00 g, 3.87 mmol), acid chloride (S)-7 16 (1.62 g, 4.67 mmol) and dry pyridine To a cooled solution of the diastereomerically pure ester (+)-8 (205 mg, 0.360 mmol) in THF (3.0 ml) was added LiAlH 4 (27 mg, 0.711 mmol) portionwise at 0°C and the mixture was stirred for 1 hr and then allowed to warm to room temperature. After being stirred at this temperature for a further 3 hr, the mixture was cooled to 0°C and quenched by successive additions of ethanol (1.0 ml), water (1.0 ml) and 1 M HCl (5.0 ml).…”

“…Recently, we and other research groups have shown that 2Ј-methoxy-1,1Ј-binaphthyl-2-carboxylic acid is very useful as a chiral derivatizing agent for the discrimination of enantiomeric alcohols and amines by HPLC or 1 H NMR. 16,[22][23][24] Then we adopted the binaphthylcarboxylic acid as the resolving agent of 1-phenylfluorenol (1a) (Scheme 2). Treatment of racemic fluorenol 1a with 1.2 mol equiv.…”

Facile Enantiomer Analysis by Combination of N‐Dansyl Amino Acid as Diastereomerizer and Molecular‐Shape Recognitive RP‐HPLC Using Comb‐Shaped Polymer‐Immobilized Silica

“…Many diastereomerizing reagents for RPLC have been developed: e.g., o-phthaladehyde-N-acetyl-Lcystein, [1] (þ)-1-(9-fluorenyl)ethyl chloroformate, [2] (a2)-2 0 -methoxy-1,1 0binaphthyl-2-carboxylate, [3] (S)-(2)(2,3-naphthalene dicarboximidyl)-propionyl fluoride, [4 -6] and chiral monohalo-s-triazines, [7] 4-nitro-7-(3-aminopyrrolidin-1-yl)-2,1,3-benzoxadiazole, [8,9] (1R,2R)-N-[(2-iso-thiocyanato)cyclohexyl]-6methoxy-4-quinolinylamide), [10] and O-(4-nitro-benzyl)-tyrosine methyl ester [11] for racemic amines and/or amino acids. When this method is combined with reversed-phase liquid chromatography (RPLC), it yields very convenient and quick analysis of enantiomer mixtures, although not suitable for fractionating.…”