Enantioseparation of protonated primary arylalkylamines and amino acids containing an aromatic moiety on a pyridino-crown ether based new chiral stationary phase

This paper reports the preparation and testing of a new pyridino-18-crown-6 ether based chiral stationary phase (CSP). The chiral crown ether was covalently bound to silica gel. Circular dichroism (CD) spectroscopy was used for probing the complex formation of the chiral crown ether with the enantiomers of protonated primary arylalkylamines. The (S,S)-dimethylpyridino-18-crown-6 ether selector having a terminal double bond was first transformed to a triethoxysilyl derivative by regioselective hydrosilylation, and then heated with spherical HPLC quality silica gel to obtain the CSP. The discriminating power of the HPLC column filled with the above CSP was tested by using the hydrogenperchlorate salts of racemic α-(1-naphthyl)ethylamine (1-NEA), α-(2-naphthyl)ethylamine (2-NEA) and the hydrochloride salts of aromatic α-amino acids and α-amino acids containing different aromatic side-chain protecting groups.     

Synthesis and Complexation Properties of Pyrimidine-Derived Crown Ether Ligands

Five new proton-ionizable macrocyclic ligands containing a pyrimidone-subcyclic unit, 6–10 , were prepared from the previously prepared pyrimidinocrown ethers 1–5 (see Figure 1 and Scheme 1). One of the new proton-ionizable crown ethers is chiral. The proton-ionizable pyrimidonocrown ethers were prepared in high yields by treating the appropriate methoxy-substituted pyrimidinocrown with 5 M sodium hydroxide in a 50% alcohol-water mixture. Complexation properties of four of the pyrimidine-derived macrocycles were studied by various nmr techniques. Pyrimidono-18-crown-6 (9) forms a strong complex with benzylammonium perchlorate and also forms a complex with benzylamine. (S, S)-Dimethyl-substituted pyrimidino- and pyrimidono-18-crown-6 ligands 4 and 9 form stronger complexes with the (R)-form of α-(1-naphthyl)ethylammonium perchlorate than with the (S)-form. (S, S)-Dimethyl-substituted pyrimidono-18-crown-6 ( 9 ) also forms a stronger complex with (R)-α-(1-naphthyl)ethylamine than with the (S)-form. The crystal structure for compound 7 is reported.     

Structural characterization of the crystalline diastereomeric complexes of enantiopure dimethylacridino-18-crown-6 ether and the enantiomers of 1-(1-naphthyl)ethylamine hydrogen perchlorate

This paper describes the X-ray crystal structure of the diastereomeric complexes formed by enantiopure dimethyl-substituted acridino-18-crown-6 ether (R,R)-1 and the enantiomers of 1-(1-naphthyl)ethylammonium perchlorate. We found that the heterochiral complex (R,R)-1–(S)-1-NEA is more stable than the homochiral one (R,R)-1–(R)-1-NEA. In the case of the heterochiral complex, the X-ray studies revealed a strong intermolecular π–π interaction between the naphthyl unit and the acridine moiety. However, in the case of the homochiral complex, π–π interaction was not found. We suggest that the existence or absence of the π–π interaction and the difference in steric repulsions in the diastereomers is responsible for the enantiomeric discrimination.     

Counterion Effects on the Columnar Mesophases of Triphenylene‐Substituted [18]Crown‐6 Ethers: Is Flatter Better?

The twisted lateral tetraalkyloxy ortho‐terphenyl units in dibenzo[18]crown‐6 ethers 1 a – f were readily converted into the flat tetraalkyloxytriphenylene systems 2 a – f by oxidative cyclization with FeCl₃ in nitromethane. Reactions of the latter with potassium salts gave complexes KX ?2 , which displayed mesomorphic properties. The aromatization increased both the clearing and melting points; the mesophase stabilities, however, were mainly influenced by the respective anions upon complexation with various potassium salts. In contrast, the alkyl chain lengths played only a secondary role. Among the potassium complexes of triphenylene‐substituted crown ethers KX ?2 , only those with the soft anions I^? and SCN^? displayed mesophases with expanded phase temperature ranges of 93 °C and 132 °C (for KX ?2 e ), respectively, as compared to the corresponding o‐terphenyl‐substituted crown ether complexes KI ?1 e (ΔT=51 °C) and KSCN ?1 e (plastic crystal phase). Anions such as Br^?, Cl^?, and F^? decreased the mesophase stability, and PF₆^? led to complete loss of the mesomorphic properties of KPF₆ ?2 although not for KPF₆ ?1 . For crown ether complexes KX ?2 (X=F, Cl, Br, I, BF₄, and SCN), columnar rectangular mesophases of different symmetries (c2 mm, p2 mg, and p2 gg) were detected. In contrast to findings for the twisted o‐terphenyl crown ether complexes KX ?1 , the complexation of the flat triphenylene crown ethers 2 with KX resulted in the formation of organogels. Characterization of the organogel of KI ?2 e in CH₂Cl₂ revealed a network of fibers.     

Synthesis and enantiomeric recognition studies of dialkyl-substituted 18-crown-6 ethers containing an acridine fluorophore unit

Selectivity of the reported dimethyl-substituted (R,R)-1, the diisobutyl-substituted (R,R)-2 acridino-18-crown-6 ethers and the newly synthesized acridino-crown ether (S,S)-3 containing the methyl groups one carbon-carbon bond further away from the acridine unit was studied towards the enantiomers of the hydrogen perchlorate salts of α-phenylethylamine, α-(1-naphthyl)ethylamine, phenylglycine methyl ester and phenylalanine methyl ester using fluorescence.     

Synthesis of novel functional poly[(R,S)-ß-hydroxybutyrate] containing phosphonoacetate end groups

Amorphous poly[(R,S)-ß-hydroxybutyrate], containing both phosphonoacetate and carboxylate functional end groups, was synthesized via anionic polymerization of racemic ß-butyro-lactone initiated by supramolecular complexes of potassium P,P-dimethylphosphonoacetate. The living homopolymers, with alkali metal counter ions complexed with a crown ether, were utilized for the synthesis of block copolymers via condensation reaction with alkylene dihalides. As a result of this approach, coupled block copolymers containing phosphonoacetate functional end groups were obtained.     

Enantiomerically pure chiral phenazino-crown ethers: synthesis,preliminary circular dichroism spectroscopic studies and complexes with the enantiomers of 1-arethyl ammonium salts

Enantiomerically pure chiral crown ethers containing the phenazine unit [(R,R)-2–(S,S)-8] were prepared by two types of cyclization reactions. Ligands (R,R)-2, (R,R)-3, (S,S)-4, (R,R)-5, (R,R)-6 and (R,R)-7 were prepared from phenazine-1,9-diol 9 and the appropriate ditosylates (S,S)-10–(S,S)-15 in weak basic conditions with complete inversion of configuration. Ligands (S,S)-2, (S,S)-7 and (S,S)-8, however, were prepared from 1,9-dichlorophenazine 19 and the appropriate diols (S,S)-16–(S,S)-18 in strong basic conditions with retention of configuration. Enantiomeric recognition of most of the chiral ligands with α-(1-naphthyl)ethylammonium perchlorate (NEA) and α-phenylethylammonium perchlorate (PEA) has been studied by CD spectroscopy.     

Enantiomeric recognition and separation of chiral organic ammonium salts by chiral pyridino-18-crown-6 ligands

Abstract

Optically pure allyloxy and dimethyl-substituted pyridino-18-crown-6 (8) was attached to silica gel by the following reactions. 4-Allyloxy-2,6-pyridinedimethyl ditosylate (23) was first prepared from chelidamic acid. Ditosylate 23 was treated with (S,S)-dimethyl-substituted tetraethylene glycol to form 8. Ligand 8 was treated with triethoxysilane using a platinum catalyst. The resulting chiral crown-substituted triethoxysilane 32 was reacted with silica gel in toluene at 90 C to attach the crown to silica gel. Preliminary results of the separation of [α-(1-naphthyl)ethyl]ammonium perchlorate into its (R) and (S) forms using the bound chiral crown with acetone/methanol (7/3) (v/v) as the eluant are reported. The preparation of chiral dimethyl(allyloxyphenyl)pyridino-18-crown-6 (9) that could be attached to silica gel on the side opposite to the pyridine ring is also reported.     

Synthese,Charakterisierung und Kristallstrukturen der Pseudohalogen‐Kronenether‐Komplexe [K([18]krone‐6)(X)(OPPh3)] (X = N3–, OCN– und SCN–)

Preparation, Characterisation, and Crystal Structures of the Pseudohalogen Crown Ether Complexes [K([18]crown‐6)(X)(OPPh₃)] (X = N₃^–, OCN^– and SCN^–) The potassium crown ether complexes [K([18]Crown‐6)(X)(OPPh₃)] (with X = N₃^–, OCN^– and SCN^–) can be obtained by reaction of KX with 18‐crown‐6 (1, 4, 7, 10, 13, 16‐hexaoxacyclooctadecane and triphenylphosphane in THF exposed to UV light. All crown ether complexes were characterized by means of vibrational spectroscopy and X‐ray diffraction. They crystallize in the rhombic pointgroup R3m with three molecules in the unit cell: [K([18]crown‐6) (N₃)(OPPh₃)] ( 1 ): lattice constants at 293 K: a = b = 14.213(2) Å; c = 13.951(2) Å; R₁ = 0.0249. [K([18]crown‐6)(OCN)(OPPh₃)] ( 2 ): a = b = 14.239(2) Å; c = 13.8927(14) Å; R₁ = 0.0257. [K([18]crown‐6)(NCS)(OPPh₃)] ( 3 ): a = b = 14.339(2) Å; c = 14.266(2) Å; R₁ = 0.0264.     

Sodium and potassium benzeneazophosphonate complexes with crown ethers: Solid-state microwave synthesis, characterization and biological activity

The eco-friendly synthesis, spectroscopic (IR, MS, ¹H and ¹³C NMR) study and biological (cytostatic, antiviral) activity of sodium and potassium benzeneazophosphonate complexes, obtained by reaction in the solid state under microwave irradiation of the alkali salts of ethyl [α-(4-benzeneazoanilino)-N-benzyl]phosphonic acid and [α-(4-benzeneazoanilino)-N-4-methoxybenzyl]phosphonic acid with crown ethers containing 18-membered (dibenzo-18-crown-6 and bis(4′-di-tert-butylbenzo)-18-crown-6), 24-membered (dibenzo-24-crown-8) and 30-membered (dibenzo-30-crown-10) macrocyclic rings, have been described. The simple work-up solvent free reaction is an efficient green procedure for the formation of mononuclear crown ether complexes in which the sodium/potassium ion is bound to oxygen atoms of the macrocycle and the phosphonic acid oxygen. The free crown ethers, alkali benzeneazophosphonate salts and their complexes were evaluated for their cytostatic activity in vitro against murine leukemia L1210, murine mammary carcinoma FM3A and human T-lymphocyte CEM and MT-4 cell lines, as well as for their antiviral activity against a wide variety of DNA and RNA viruses. The investigated compounds showed no specific antiviral activity, whereas all the free crown ethers and their complexes demonstrated cytostatic activity, which was especially pronounced in the case of bis(4′-di-tert-butylbenzo)-18-crown-6 and its complexes.     

Thermal characteristics of solid-solid phase transitions in long-chain dialkyl ammonium salts

A series of symmetrical dialkyl ammonium salts, DC_nX, has been prepared and characterized with respect to temperature and enthalpy of solid-solid phase transitions, temperature of melting, thermal stability as well as the reversibility of the phase transitions. The number of carbon atoms, C_n, was varied between 8 and 18 and as anions X halides, nitrate, chlorate, perchlorate and hydrogen sulphate had been chosen. In dependence on chain length and anion type transition temperatures from 20 to 100 °C were observed. Mass specific solid-solid transition enthalpies reach values of 185 J g⁻¹, which makes this class of substances attractive for heat storage applications. The influence of anion type on the transition enthalpies is explained in terms of packing requirements, hydrogen bond network formation and contributions from hindered anion rotation.     

Cross-chiral examinations of molecular enantioselective recognition by fast atom bombardment mass spectrometry: Host–guest complexations between chiral crown ethers and chiral organic ammonium ions

Using fast atom bombardment (FAB) mass spectrometry (MS), cross-chiral relationships were confirmed for the first time for the diasteromeric host-guest complexations between the chiral crown ether host (1) and the chiral organic ammonium ion guest (2) on the basis of the relative peak intensities (RPI). Both host–guest combinations (R, R, R, R) – 1, (R) – 2 and (S, S, S, S) – 1, (S) – 2 obviously provided larger RPI values than the combination of both (R, R, R, R) – 1, (S) – 2 and (S, S, S, S) – 1, (R) – 2 by a factor of 1.6 as an averaged value: 1.87 (n = 4)/1.16 (n = 4) = 1.6. These results are consistent with the expected stabilities of the host-guest complexations by CPK model examinations. Successfully observed cross-chiral examinations strongly suggest a potentially useful FABMS/RPI methodology for rapidly searching newly designed and synthesized crown ether-like host compounds with a higher degree of enantioselectivity.     

Stereodivergent Quaternization of 2‐Alkyl‐2‐p‐tolylsulfinylacetonitriles: NMR Spectroscopic Evidence of Planar and Pyramidal Benzylic Carbanions

Enantiomerically enriched α,α‐disubstituted phenylacetonitriles have been readily prepared by stereoselective quaternization of 2‐alkyl‐2‐[2‐(p‐tolylsulfinyl)phenyl]acetonitriles with different alkylating electrophiles in the presence of bases. The use of potassium hexamethyldisilazane (KHMDS)/[18]crown‐6 ether and NHMDS with alkyl halides afforded S,S_S and R,S_S diastereoisomers, respectively, in high enantiomeric purities, thus providing stereodivergent processes for synthesizing both isomers. The dependence of the stereochemical course of the reactions on the experimental conditions (mainly on the counterion) has been rationalized by assuming a planar or pyramidal structure for the benzylic carbanions. This hypothesis has been supported by NMR spectroscopic studies, which permit one to assign a chelated pyramidal structure to the sodium benzylic carbanions and an almost planar naked carbanionic structure to the potassium benzylic carbanions generated in the presence of [18]crown‐6 ether.     

Preparation and temperature-dependent enantioselectivities of homochiral phenolic crown ethers having aryl chiral barriers: thermodynamic parameters for enantioselective complexation with chiral amines

Homochiral crown ether (S,S)-1 containing 1-naphthyl groups as chiral barriers together with the phenol moiety was prepared by using (S)-3 as a chiral subunit which was resolved in enantiomerically pure form by lipase-catalyzed enantioselective acylation of (±)-3. Homochiral phenolic crown ether (S,S)-2, containing phenyl groups as chiral barriers, was also prepared from (S)-5 which was derived from (S)-mandelic acid. The association constants for their complexes with chiral amines in CHCl₃ were determined at various temperatures by the UV–visible spectroscopic method demonstrating that the crown ethers (S,S)-1 and (S,S)-2 displayed the large Δ_R−SΔG values of 6.2 and 6.4 kJ mol⁻¹, respectively, towards the amine 21 at 15°C. Thermodynamic parameters for complex formation were also determined and a linear correlation between TΔ_R−SΔS and Δ_R−SΔH values was observed.     

A structural analysis of the complexes of (S,S)-dimethylpyridino-18-crown-6 with (R) and (S)-[α-(1-naphthyl)ethyl]ammonium perchlorate by NMR techniques and molecular modeling

Significant - interaction is found in the complexes of (S, S)-dimethylpyridino-18-crown-6 with (R)- and (S)-[-(1-naphthyl)ethyl]ammonium perchlorate. This finding is supported by the¹H NOESY NMR spectral technique, greater chemical shift changes of aromatic protons in both host and guest molecules upon complexation, and by molecular mechanics calculations. Because of the flexibility of the ligand, the tripod hydrogen bonding causes¹³C relaxation times of all periphery carbons to decrease without significant selectivity. Rotational energy barrier calculations of the methyl groups of the complexed ligand also show that the (S, S)-host-(R)-guest is the more stable complex.     

Stereoselectivity in Reactions of Metal Complexes. Part XV. Structure and stability of chiral cobalt(III) complexes with pentadentate ligands

The syntheses and characterization of four new linear pentadentate ligands and their Co^III complexes are described: N,N′-[(pyridine-2,6-diy)bis(methylene)]bis[sarcosine] (sarmp), N,N′-[(pyridine-2,6-diyl)bis(methylene)]bis[(R)- or (S)-proline] ((R,R)- or (S,S)-promp), N,N′-[(pyridine-2,6-diyl)bis(methylene)]bis[N-(methyl)-(R)- or (S)-alanine] ((R,R)- or (S,S)-malmp); 2,2′-[pyridine-2,6-diyl]bis[(S)- or rac-N-(acetic acid)pyrrolidine] ((S,S)- or rac-bapap). The complexes were characterized and, with but one exception, complex formation is stereospecific: Δ-exo-(R,R) (or Λ-exo-(S,S)) for promp and Λ-(R,R) (or Δ-(S,S)) for bapap. The exception is [Co((R,R)- or (S,S)-malmp)H₂O]ClO₄ for which two forms are obtained, to which Λ-endo-(R,R) (or Δ-endo-(S,S)) and, tentatively, Δ-unsymmetric-(R,R)- (or Λ-unsymmetric-(S,S)-) configurations are assigned. X-Ray crystal structures are presented for the complexes [Co(sarmp)H₂O]ClO₄, [Co((S,S)-promp)H₂O]ClO₄, [Co(rac-bapap)H₂O]ClO₄ and endo-[Co(rac-malmp)H₂O]ClO₄. Ligand acid dissociation and Co^II and Fe^II complex-formation constants are reported.     

Trennung und absolute Konfiguration der C(8)-epimeren (all-E)-Neochrome (Trollichrome) und -Dinochrome

Separation and Absolute Configuration of the C(8)-Epimeric (app-E)-Neochromes (Trollichromes) and -Dinochromes The C(8′)-epimers of (all-E)-neochrome were separated by HPLC and carefully characterized. The faster eluted isomer, m.p. 197.8–198.3°, is shown to have structure 3 ((3S,5R,6R,3′S,5′R,8′R)-5′,8′-epoxy-6,7-dodehydro-5,6,5′,8′-tetrahydro-β,β-carotene-3,5,3′-triol). To the other isomer, m.p. 195-195.5°, we assign structure 6 , ((3S,5R,6R,3′S,5′R,8′R)-5′,8′-epoxy-6,7-didehydro-5,6,5′,8′-tetrahydro-β,β-carotene-3,5,3′-triol). The already known epimeric dinochromes (= 3-O-acetylneochromes) can now be formulated as 4 and 5 , (‘epimer 1’ and its trimethylsilyl ether) and 7 and 8 , (‘epimer 2’ and its trimethylsilyl ether), respectively.     

Chiral Carbon Nanorings: Synthesis,Properties and Hierarchical Self-assembly of Chiral Ternary Complexes Featuring a Narcissistic Chiral Self-Recognition for Chiral Amines

We report the synthesis and chiroptical properties of novel chiral carbon nanorings S p-/Rp-[12]PCPP containing a planar chiral [2.2]PCP unit, and demonstrate that S p-/Rp-[12]PCPP can not only host crown ether 18-Crown-6 to form ring-in-ring complexes with a binding constant 3.35×10³ M⁻¹, but also accommodate the complexes of 18-Crown-6 and S/R-protonated amines to form homochiral S @Sp -/ R @Rp - and heterochiral S @Rp -/ R @Sp - ternary complexes, displaying significantly larger binding constants of up to 3.31×10⁵ M⁻¹ depending on the chiral guests. Importantly, homochiral S @Sp -/ R @Rp - ternary complexes exhibit an enhanced CD signal, while the heterochiral S @Rp -/ R @Sp - ones have a constant CD signal compared with the chiral carbon nanorings, respectively, which suggests that homochiral S @Sp -/ R @Rp - ternary complexes display a highly narcissistic chiral self-recognition for S/R-protonated chiral amines, respectively. Finally, the chiral ternary complexes can be further applied to determine the ee values of chiral guests. The findings highlight a new application of carbon nanorings in supramolecular sensors, beyond the common recognition of π-conjugated molecules.     

Polysalt complexes of poly(vinylbenzo-18-crown-6) and of poly(crown acrylate)s with polyanions

Macrocyclic polyether or crown ether ester derivatives of acrylic and methacrylic acid were synthesized and polymerized. The cation binding properties of the polymers determined by extraction of picrate salts were similar to those obtained for poly(crown ether)s derived from styrene. In the presence of a crown-complexable cation both polymers form insoluble polysalt complexes with sodium carboxymethylcellulose, potassium poly(styrene sulfonate), and potassium polyacrylate. The extent of precipitation depends on the type and concentration of cation as well as on the ratio polyanion to poly(crown ether). The precipitate appears to have an equal number of positive and negative charges. An insoluble hydrogen-bonded complex is formed in the absence of salt when poly(vinylbenzo-18-crown-6) and poly(acrylic acid) are mixed in 0.01M HCl. Organic solutes bound to the poly(crown ether)s, which occur in an aqueous mixture of poly(vinylbenzo-18-crown-6) and picrate anions, are precipitated with the poly(crown ether) when the polysalt complex is formed.     

Novel synthesis of polyphosphonates by the polyaddition of bis(epoxide) with diaryl phosphonates

The polyaddition of bisphenol A diglycidyl ether (BPGE) with bis(4‐chlorophenyl) phenylphosphonate was carried out using quaternary onium salts or crown ether complexes as catalysts. When the polyaddition was performed using tetrabutylammonium chloride, tetrabutylphosphonium chloride, or 18‐crown‐6/KCl in N‐ methyl‐2‐pyrrolidone at 110°C for 48 h, the corresponding polyphosphonate with moderated molecular weights was obtained in 88–96% yields. The structure of the resulting polyphosphonate was confirmed by IR and ¹H‐NMR spectra. The polyaddition of BPGE with various diaryl phosphonates also proceeded very smoothly to produce the corresponding polyphosphonates with moderate molecular weights. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 959–965, 1999