N2_n-
octyl-(S)-phenylalaninamide and W-n-dodecyl-(S)-phenylalaninamide were synthesized by reductive alkylation from the corresponding (S)-phenylalaninamide and n-octanal and n-dodecanal, respectively, Both ligands coordinate to copper(II) as amidates, giving rise to two trans-bis(phenylalaninamidato)copper(II) complexes CuLzH_ 2 (1) and (2), respectively. The crystal structures of both complexes (1) and (2) were determined by X-ray crystallography. The striking feature is that in bis[W-alkyl-(S)-phenylalaninamidato]copper(II) complexes both alkyl groups are on the axial positions and on the same side of the coordination plane. The hydrocarbon chains produce a bilayer structure with polar and apolar alternating rones. The knowledge of the crystal structures of these complexes, which are used successfully as chiral selectors in HPLC (reversed phase), provides very useful information on the stereochemical features of the enantioselective selector and on the adsorption mode on a reversed phase CIS chromatographic column, In a general project aimed at studying the mechanism of chiral discrimination by copper(II) complexes in HPLC (reversed phase)l, we synthesized a wide series of chiral selectors which proved to be very efficient in the enantiomeric recognition of modified and unmodified amino acids, In particular, copper(II) complexes of amino acid amides and diamino-diamido-type ligands, added to the eluent, performed very efficient separations of D,L-dansyl-amino acids z ,3 and of unmodified amino acids 4 and were successfully applied to the analysis of D-amino acids in foods, serum and biological samples,5,6 The mechanism of chiral discrimination was shown to proceed via ligand exchange in HPLC 4 The knowledge of the crystal structures of these selectors 7 ,S, in addition to the studies of the equilibria in solution 9 ,1O, helped to rationalize chromatographic data and to support the mechanism suggested, Now, we have modified (S)-phenylalaninamide by introducing long hydrocarbon chains (R = CSH17 for (1) and R =C12HZ5 for (2Β» on the amino group in order to increase the lipophilicity of the copper(II) complexes to be adsorbed on the stationary phase of CIS columns, producing dynamically modified chiral columns. The main species formed in solution with both ligands from pH 7.5 on are of the type CuLzH_z, as reported below, in agreement with what previously observed with (S)-Phe-NHz and (S)-MePhe-NHz.9 Indeed, these selectors are able to perform enantiomeric separation of amino acids, amino acid amides, hydroxy acids and dipeptides. ll The elution order is different from that previously observed with the copper(II) 1233 complexes of (S)-phenylalaninamide (Phe-NH2) and NLmethyl-(S)-phenylalaninamide (MePhe-NH2)4 and, therefore, the mechanism of chiral discrimination involved must be different.
(1): R =C gIll?
(2):R=C 1 h
These particular structures may lead to "self-assembling" systems spontaneously arising owing to noncovalent forces among the component molecules. 12 With this in mind, we set out to prepare crystals to see how the long hydrocarbon chains would assemble and thus obtaining reasonable clues about the adsorption mode of the chiral selector on the column stationary phase and on the discriminating interactions with the enantiomers.
EXPERIMENTAL
(S)-phenylalaninamide was obtained from Sigma Chemical Co. (St. Louis, MO, U.S.A.). N-octanal and n-dodecanal were obtained from Merck (Darmstadt, Germany). Pd/C (10%) was purchased from Sigma.
Cu(OAchβ’H20 (RPE), methanol (RCS-grade) and ethyl ether (RCS-grade) were purchased from Carlo Erba (Milan, Italy). Melting points were recorded on an Electrothermal apparatus and were uncorrected. IH-NMR and 13C-NMR spectra were recorded on a Bruker AC 100 spectrometer. Infrared spectra were recorded on a Perkin Elmer Mod. 298 spectrophotometer. Mass spectra were recorded on a Finnigan MAT SSQ 710 spectrometer using electron impact ionization (70 eV, EI). Elemental analyses were performed on a Carlo Erba Mod. 1106 elemental analyzer. Optical rotations were measured on an Autopol III Rudolph Research polarimeter with a path length of 1 dm. UV-Vis spectra were recorded on a Kontron Uvikon 860 spectrophotometer. CD spectra were recorded on a Jasco 500A spectropolarimeter.
N2_n-oclyl-(S)-phenylalaninamide hydrochloride: to (S)-Phe-NH2 (8.2 g, 0.05 mol) dissolved in MeOH (200 mL) Pd/C (10%) (20% wlw, 1.64 g) and n-octanal (7.27 mL, 0.05 mol) were added under nitrogen. Hydrogenation was performed at 40Β°C for 12 h, the catalyst filtered and the solution evaporated to dryness. The crude product was treated with HClIMeOH, washed with ethyl ether (100 mL) to remove the residual aldehyde, then washed with a diluted alkali solution to remove the unreacted (S)-Phe-NH2. The product was recrystallized as the hydrochloride from MeOHlEt20. Yield: 70%; m.p. 212Β°C dec.; [a]n 25 =