engleski

Synthesis and evaluation of chiral stationary phases containing N-(1-arylpropyl)-3, 5-dinitrobenzamide selector

Based on our prior work in Laboratory for Stereoselective Catalysis and Biocatalysis at Ruđer Bošković Institute in the field of chiral recognition of Pirkle-type chiral stationary phases (CSPs) we designed and prepared the new sort of CSPs. To improve the chiral discrimination performance these new Pirkle-type CSPs have lack of some of non-stereoselective adsorption sites. An N-(1-arylpropyl)-3, 5-dinitrobenzamide unit possesses all the characteristics of a good selector – it is rigid and contains a strong -accepting 3, 5-dinitrobenzoyl (DNB), and a strong -donating aromatic group (Ar). Aromatic groups include 1-naphthalenyl, 4-methylphenyl, 3, 5-dimethylphenyl, 2-methylphenyl, 2, 4, 6-trimethyphenyl, 4-methylnaphthalen-1-yl, phenyl and 9-phenantryl. Enantiomerically pure allyl-arylamines emerge as a key intermediate in synthesis of aimed selectors. The preparation of selector starts with commercially available aldehydes which in easygoing Knoevenagel reaction with ethyl hydrogen malonate produces corresponding esters. Acrylic esters are easily reduced to allyl alcohols which are converted to trichloroacetimidates in the DBU catalyzed reaction with trichloroacetonitrile. The thermal Overman rearrangement of allyl trichloroacetimidates results in 2, 2, 2-trichloro-N-(1-arylallyl)acetamides which are hydrolyzed to racemic amines. Amine resolutions were accomplished using Candida antarctica lipase B in various organic solvents and with different acyl donors resulting with amines in a moderate to excellent enantiomeric excess. In reaction of prepared amines with 3, 5-dinitrobenzoyl chloride the targeted selectors were produced. In cases where enzymatic resolution did not result in satisfying ee, racemic amines were derivatised with 3, 5-dinitrobenzoyl chloride and enantiomers of obtained DNB-amides resolved using semi-preparative chiral liquid chromatography. A method for binding the chiral selector to silica gel was selected in such a manner that additional polar groups are not introduced in the structure of CSP. CSPs prepared in this way were further end-capped to minimize the number of polar silanol groups.

chiral stationaray phases; Pirkle-type

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