1-Phenylethylamine, 3,5-dinitrobenzoyl

Nitrobenzoyl chloride and 3,5-dinitrobenzoyl chloride were each reacted with dl-1-phenylethylamine and 4-amino-l-benzylpiperidine using a phase-transfer reaction [23]. The amines were in the aqueous phase and the acid chlorides in the organic phase. By this means, a 2 x 2 library was created in one experimental run. 

P 9] DL-l-Phenylethylamine and 4-amino-l-benzylpiperidine were dissolved in 0.1 M NaOH aqueous solution [23]. 3-Nitrobenzoyl chloride and 3,5-dinitrobenzoyl chloride were used as ethyl acetate solutions. The concentration of all reactants was set to 0.01 M. Syringe pumps served for liquid feed. The flow rate was 50 plmin and room-temperature processing was applied. No further temperature control was exerted as the reaction is only mildly exothermic. After having passed the micro reactor, the phases were settled in test-tubes and the organic phase was withdrawn for analysis. 

Kagan and coworkers determined and studied in detail the crystal structure of a 1 1 molecular complex between (i )-methyl p-tolyl sulfoxide (10) and S)-N-(3,5-dinitrobenzoyl)-l-phenylethylamine (11). They suggested that amide 11, which had been used as a chiral solvating agent for sulfoxides, might find use as a resolving agent for these compounds. ... 

Measured by proton NMR spectroscopy with Eu(hfc)3 or (R)-(3,5-dinitrobenzoyl)l-phenylethylamine [27,28], All sulfoxides have (R) configuration,... 

Achiral lanthanide chelates can also be added to CSAs such as arylperfluoroalkyl-carbinols, the ethyl ester of 3,5-dinitrobenzoyl-L-leucine (25) , the 3,5-dinitrobenzoyl derivative of 1-phenylethylamine, Af-(l-(l-naphthyl)ethyl)trifluoroacetamide (26) and a series of l-(l-naphthyl)ethyl urea derivatives of amino acids (27) to enhance the enantiomeric discrimination. With sulfoxide or lactone substrates , the europium ion preferentially associates with the substrate in the bulk solution. Provided the enantiomers have different association constants with the CSA, the isomer that shows the weaker association with the CSA shows the larger lanthanide-induced shifts. Low concentrations of lanthanide relative to the substrate and CSA lead to enhancements of enantiomeric discrimination in the NMR spectrum. If the concentration of lanthanide is too high, binding of the substrate to the lanthanide strips the substrate from the chiral solvating agent and diminishes the chiral discrimination in the NMR spectrum. 

S)-l-Phenylethylamine was purchased from Aldrich Chemical Co., Inc. and used as received. The enantiomeric purity of (S)-l-phenylethylamine was determined as the dinitrobenzoyl derivative to be 95% ee using a chiral stationary phase HPLC column and a chiral stationary phase SEC column (see (Note 21)). The submitters used reverse phase CSP HPLC analysis for this purpose (Daicel CROWNPAK CR, aq. HCIO4 (pH 1.5), 0.8 mL/min, 25°C, 210 nm). 

Pirkle and Murray first reported the temperature-dependent elution order reversal in Pl-basic proline-derivatized CSPs in 1993. They used (/ 5)-A-(3,5-dinitrobenzoyl)-a-phenylethylamine as the solute to investigate the response of the chromatographic behavior by changing the temperature on the CSP. 

Researchers at the University of Tokyo prepared a small (2 X 2) library in a chip microreactor by reacting 3-nitroben-zoyl chloride and 3,5-dinitrobenzoyl chloride, each with dl-1-phenylethylamine and 4-amino-1-benzylpiperidine using a phase-transfer catalyst. GlaxoSmithKline (GSK) generated a 2 x 2 library for a domino reaction, which consisted of a Knoevenagel condensation that gave an intermediate that immediately underwent an intramolecular hetero-Diels-Alder reaction with inverse electron demand. GSK published the synthesis of a 3 x 7 library using... 

Distinct NMR resonances were first observed for the enantiomers of 2,2,2-trifluoro-l-phenylethanol in the presence of (/ )-phenylethylamine. With (/ )-2-naphthylethylamine the magnitude of the non-equivalence was increased. A systematic study of a series of aryl alcohols in the presence of amines showed a consistent correlation between the sense of non-equivalence and the absolute configuration of the alcohol. From the simple solvation models proposed, the reciprocality of the CSA approach is evident, i.e. if chiral A can be used to assay racemic B then chiral B can be used to assay racemic A. With this in mind 1 -(9-anthryl)-2,2,2-trifluoroethanol (15a) was developed as a CSA for chiral amines. It is also effective with alcohols, lactones, a-amino acid esters, a-hydroxy acid esters and sulphoxides and is the most widely used chiral solvating agent. Other more specific solvating agents have been developed. Kagan has developed A -(3,5-dinitrobenzoyl)-l-phenylethylamine,forexample, as a CSA specifically for the assay of chiral sulphoxides prepared from sulphides by a modified Sharpless oxidation (section 6.3.2). 

The compounds (Figure 50.13) Af-(3,5-dinitrobenzoyl)-l-phenylethylamine 39, A -(3,5-dinitrobenzoyl)-L-leucine ethyl ester(40), ° A -(3,5-dinitrobenzoyl)-4-amino-3-methyl-l,2,3,4-tetrahydrophenanthrene 41, and 1-(1-... 

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