Synthesis of a chiral macrocyclic dibenzodicyclohexanotetraamide-containing stationary phase for liquid chromatography

Allyloxy-substituted macrocyclic dibenzodicyclohexanotetraamide 2 was prepared by the following sequence. MonoBoc-protected chiral 1,2-cyclohexanediamine ( 3 ) was treated with isophthaloyl chloride followed by removal of the Boc group to form bisisophthalamide 5. Compound 5 was then treated with allyloxyphthaloyl chloride to form the macrocyclic tetraamide 2 in a 56% yield. Chiral selector 2 was converted to its ethoxydimethylsilane derivative and heated in a suspension of silica gel and toluene to form the chiral macrocycle-containing silica gel phase 1. This phase separated the enantiomers of (±)-α-methylbenzylamine and (±)-DL-α-aminobutyric acid methyl ester in a liquid chromatograph.     

Hydration of simple amides. FTIR spectra of HDO and theoretical studies

The hydration of formamide (F), N-methylformamide (NMF), N,N-dimethylformamide (DMF), acetamide (A), N-methylacetamide (NMA), and N,N-dimethylacetamide (DMA) has been studied in aqueous solutions by means of FTIR spectra of HDO isotopically diluted in H2O. The difference spectra procedure has been applied to remove the contribution of bulk water and thus to separate the spectra of solute-affected HDO. To facilitate the interpretation of obtained spectral results, DFT calculations of aqueous amide clusters were performed. Molecular dynamics (MD) simulation for the cis and trans forms of NMA was also carried out for the SPC model of water. Infrared spectra reveal that only two to three water molecules from the surrounding of the amides are statistically affected, from among ca. 30 molecules present in the first hydration sphere. The structural-energetic characteristic of these solute-affected water molecules differs only slightly from that in the bulk and corresponds to the clathrate-like hydrogen-bonded cage typical for hydrophobic hydration, with the possible exception of F. MD simulations confirm such organization of water molecules in the first hydration sphere of NMA and indicate a practical lack of orientation and energetic effects beyond this sphere. The geometry of hydrogen-bonded water molecules in the first hydration sphere is very similar to that in the bulk phase, but MD simulations have affirmed subtle differences recognized by the spectral method and enabled their understanding. The spectral data and simulations results are highly compatible. In the case of F, NMF, and A, there is a visible spectral effect of water interactions with N-H groups, which have destabilizing influence on the amides hydration shell. There is no spectral sign of such interaction for NMA as the solute. The energetic stability of water H-bonds in the amide hydration sphere and in the bulk fulfills the order: NMA > DMA > A > NMF > bulk > DMF > F. Microscopic parameters of water organization around the amides obtained from the spectra, which have been used in the hydration model based on volumetric data, confirm the more hydrophobic character of the first three amides in this sequence. The increased stability of the hydration sphere of NMA relative to DMA and of NMF relative to DMF seems to have its origin in different geometries, and so the stability, of water cages containing the amides.     

A new diaza‐18‐crown‐6 ligand containing two quinolin‐8‐ylmethyl side arms: Crystal structures and characterization of the ligand,the protonated ligand and its mononuclear barium(II) and dinuclear copper(II) complexes

A new 7,16‐bis(quinolin‐8‐ylmethyl)‐1,4,10,13‐tetraoxa‐7,16‐diazacyclooctadecane ligand, L, has been prepared and its crystal structure reported. In addition, the structure of the protonated ligand H₂L has been determined. H₂L is of interest because of interatomic interactions between the ligand and perchlorate ions. The mononuclear Ba(II) (Ba L ), and dinuclear Cu(II) (Cu₂L) complexes of L have been prepared and their crystal structures determined. Stability constants and other thermodynamic data valid in methanol at 23 or 25° for these and several other complexes of L have been obtained. Among the metal ions studied, L forms the most stable complex with Ba²⁺. In addition, L selectively binds Cu²⁺ over Ni²⁺ by about 3 orders of magnitude. Some of the complexes have been studied using nmr and uv‐vis spectroscopic techniques. Crystal data are given for L, space group, P2₁c, a = 8.8325(14) Å, b = 13.808(3) Å, c = 13.310(3) Å; β = 94.72(2)° Z=2, R = 0.0727; for H₂ L , space group, P2₁/c, a = 14.685(3) Å, b = 15.035(6) Å, c = 17.369(4) Å, β = 90.366(12)°, Z = 4, R = 0.0781; for Ba L , space group, Pbcn, a = 17.314(3) Å, b = 9.539(2) Å, c = 22.081(3) Å, Z = 4, R = 0.0354; and for Cu₂ L , space group, Cc, a = 19.762(2) Å, b = 14.413(2) Å, c = 14.935(2) Å, β = 98.753(12)°, Z = 4, R = 0.0564. Cu²⁺ forms a hydroxo‐bridged dinuclear complex with L while Ba²⁺ forms a mononuclear complex with L in which its two side arms are not involved in complexation.     

A simple crab-like cyclization procedure to prepare polyaza-crowns and cyclams with one or two unsubstituted macroring nitrogen atoms or with a hydroxy group

A simple and convenient method to prepare polyaza-crowns and cyclams containing one or two unsubstituted macroring nitrogen atoms or a hydroxy group is described. The process involves the reaction of a bis- chloroamide with a bis-secondary amine followed by reduction of the cyclic diamide. The bis-chloroamide resembles a crab with two reactive organochloride groups poised and ready to react, hence the term “crab-like” cyclization. Nine new polyaza-crowns and cyclams were prepared.     

Preparation of macrocyclic di- and tetraamides containing unsubstituted macroring nitrogen atoms,tertiary amine sidearms and/or piperazine subcyclic units

Seven new macrocyclic di- and tetramides have been prepared by the cyclization reaction of various polyamines or, in one case, a dimercaptan with a bis(α-chloroamide) or diethyl malonate. Three of the resulting macrocyclic diamides were reduced with borane to form the corresponding polyaza-crown analogs. Macrocycles prepared include two tetraaza-12-crown-4, two tetraaza-13-crown-4, two tetraaza-14-crown-4, one dithiadiaza-14-crown-4, one tetraaza-15-crown-4 with a piperazine subcyclic group, one dibenzotetraaza-24-crown-8 and one octaaza-30-crown-8 with two piperazine subcyclic groups.     

Structure and thermodynamic aspects of macrobicyclic polyether-metal ion interactions

The crystals structure of a K⁺-diptychand-15C5-18C6 iodide complex has been determined from X-ray data. The complexed bicyclic molecule crystallizes in the triclinic space group witha = 9.995(4) Å,b = 10.097(4) Å,c = 13.725(6) Å, = 90.12(3)°, = 93.62(4)°, = 97.56(3)°. The structure was solved using heavy atom methods and refined toR = 0.032 for 3262 independent reflections. In the crystal structure, the K⁺ lies between the two crown ether rings, and is coordinated by the nine donor atoms of the ligand molecule. The complexation properties of the ligand with K⁺ and Na⁺ were studied by titration calorimetry in 90% (v/v) MeOH/H₂O solution. The studies indicate the formation of 1 : 1 ligand : metal ion complexes in both solid state and solution.This paper is dedicated to the memory of the late Dr C. J. Pedersen.     

One‐step syntheses of macrocyclic compounds: A short review

Macrocyclic ligands have been prepared by various one‐step cyclooligomerization processes. This short review covers one‐step cyclization reactions involving the formation of four to twenty or more new covalent bonds. The new macrocycles reviewed include cyclophanes, biscrown ethers, cryptands, macrolides, cage compounds, calixarenes, homocalixarenes, cucubiturils, and supercryptands all prepared by one‐step syntheses.     

Synthesis of chiral azamacrocycles using the bis(α-chloroacetamide)s derived from chiral 1,2-diphenylethylenediamine

Optically active diphenyl-substituted tetraaza-12-crown-4 diamide ( 10 ), tetraaza-15-crown-5 diamide ( 12 ), tetraaza-18-crown-6 diamide ( 11 ), and hexaaza-18-crown-6 diamide ( 9 ) ligands were prepared by treating the appropriate secondary diamines with the (R,R)- and (S,S)- forms of 1,2-bis(N-methyl-α-chloracetamido)-1,2-diphenylethane ( 20 ). Macrocyclic diamides 9 and 10 were reduced to form the optically active diphenyl-substituted hexaaza-18-crown-6 ( 13 ) and tetraaza-12-crown-4 ( 14 ), respectively. Reduction of macrocyclic diamide ligands 11 and 12 gave a complex mixture of products from which the desired tetraaza-15-crown-5 and 18-crown-6 compounds could not be isolated. Dichloride 20 was prepared by treating the chiral forms of 1,2- diphenylethylenediamine with chloroacetic anhydride or chloroacetyl chloride. The crystal structures for the (R,R)-form of dichloride 20 and the (S,S)-forms of macrocycles 10 and 11 are reported.     

Preparation of triazamacrocycles containing only secondary amine functions using both tosyl and boc protecting groups

1,8,15-Triazacycloheneicosane ( 1 ); 1,9,17-triazacyclotetracosane ( 2 ) and 1,10,19-triazacycloheptacosane ( 3 ) were prepared by treating the appropriate N,N-bis(ω-bromoalkyl)toluenesulfonamide 8–10 with the appropriate N,N′-ditosyl-α,ω-diaminoalkane 11–13 in dimethylformamide using sodium hydride as the base followed by phenol and 33% hydrobromic acid in acetic acid to remove the tosyl protecting groups. 2-Allyloxymethyl-4,11,18- triazaoxacycloheneicosane ( 4 ) was prepared in two ways. First, N,N′,N″-tritosylbis(hexamemylene)triamine ( 18 ) was treated with 2-allyloxymethyl-3-oxa-1,6-hexanediol ditosylate ( 23 ) and cesium carbonate in dimethylformamide followed by sodium amalgam to remove the tosyl protecting groups. The second preparation of 4 was done by treating the tri-BOC analog of 18 with 23 followed by hydrochloric acid in isopropyl alcohol to remove the BOC protecting groups. The overall yields of 4 using these two processes were very close.     

Thermal Removal of Boc-Protecting Groups During Preparation of Open-Chain Polyamines

Per-N-tosylated 3,8-diaza-1,10-decanediamine (9), 4,9-diaza-1,12-dodecanediamine (spermine) (10) and 3,6,9,14,17,20-hexaaza-1,22-docosanediamine (11) were prepared by treating mono-BOC-protected, per-N-tosylated 1,2-ethanediamine (5), 1,3-propanediamine (6) and triethylenetetraamine (7), respectively, with 1,4-dibromobutane and removing the BOC-protecting groups at 100–120 °C.