Pendant Hydroxymethyl Research Articles

Tandem Amination/Oxetane Ring Opening toward Benzomorpholines.

Herein, a tandem approach that allows rapid access to the benzomorpholine scaffold is reported. This operationally simple method allows for valuable heterocycles to be isolated in moderate to high yields. The overall transformation consists of an initial C-N coupling, demonstrated using traditional Ullmann or Buchwald-Hartwig conditions, followed by an in situ oxetane ring opening. A range of functionality is tolerated on the aryl ring, and the cyclization exposes a pendant hydroxymethyl substituent, providing opportunities for further functionalization.

Tandem Suzuki Coupling/Intramolecular Oxetane Ring Opening to Form Polycyclic Ring Systems.

A tandem one-pot reaction featuring a cross-coupling followed by an intramolecular oxetane ring opening by mild nucleophiles is reported. The overall transformation comprises a carbon-carbon bond formation along with a carbon-heteroatom bond construction providing diverse multicyclic ring systems with a pendant hydroxymethyl handle for further elaboration. This approach constitutes a convergent method for rapid access to various scaffolds. Furthermore, a comparison of computed low-energy conformers is presented to rationalize instances in which cyclization was not observed.

Novel tris-buffer based Schiff base bearing long flexible alkoxy arm and its lanthanide complexes: Mesomorphism and photoluminescence

A new liquid crystalline salicylaldimine Schiff base having pendant hydroxymethyl (CH2OH) groups and a series of lanthanide(III) complexes of the type, [Ln(LH)3(NO3)3] {Ln = La, Pr, Sm, Gd, Tb; LH=(E)-2-((1, 3-dihydroxy-2-(hydroxyl methyl) propan- 2-ylimino)methyl)-5-(hexadecyloxy) phenol} have been synthesised. The compounds were characterised by FT-IR, 1H NMR, 13C NMR, UV–Vis, and FAB-mass spectroscopy. Thermal behaviour of these compounds was studied using polarising optical microscopy (POM) and differential scanning calorimetry. The phase confirmation and molecular organization in the mesophase was ascertained by variable temperature powder X-ray diffraction (XRD) study. The ligand and the complexes both showed highly viscous smecticA and columnar mesophase, respectively. A bilayer self organization of the ligand molecules with interdigitation of the alkyl chains in the mesophase is proposed. Molecular organizations of the complexes in the mesophase involve arrangement of all the aliphatic chain pointing in same direction leading to lamellar columnar phase. The ligand showed an intense blue emission at 452 nm while the gadolinium(III) complex exhibited an intense emission at 458 nm (λex = 310 nm). The samarium(III) complex is a bright orange light emitter over a wide range upon UV irradiation.

Dielectric spectroscopy of low-losses sugar lyophiles: III: The influence of moisture on the dielectric response of freeze-dried lactose

This paper presents the results of a dielectric spectroscopy study of freeze-dried lactose with a range of moisture contents. Dielectric properties were measured over a wide range of frequency (10 −1 to 10 6 Hz) and temperature (−120 °C to 120 °C). Four relaxation processes were analysed with respect to moisture content and corresponding relaxation mechanisms were suggested. Two processes ( γ and β) were observed in the sub- T g range of temperature and another two processes were observed near to and above the glass transition temperature, T g . The relatively high-frequency γ-process was ascribed to the mobility of pendant hydroxymethyl groups and exhibited only a weak dependence on moisture content. The most moisture sensitive process was the second sub- T g (Johari–Goldstein) β-process, whereby the relaxation time changed by 2 orders of magnitude as the moisture was increased by 7%. Also the third process ( α-relaxation, near T g ) was sensitive to moisture content and was in good agreement with DSC data measured for freeze-dried lactose. The fourth process was a proton percolation process at the micro-crystals formed at the surface of amorphous particles during heating at the temperatures higher than T g and shows the moisture dependence.

H5EPTPACH2OH: Synthesis, Relaxometric Characterization and 1H NMR Spectroscopic Studies on the Solution Dynamics of Its LnIII Complexes

AbstractThe synthesis and characterization of a new metal chelator, 4‐(S)‐hydroxymethyl‐3,6,10‐tri(carboxymethyl)‐3,6,10‐triazadodecanedioic acid (H5EPTPACH2OH), is reported. Protonation constants for the ligand H5EPTPACH2OH and for the previously reported H5EPTPAC16 have been determined by potentiometry, which reveals that both ligands display slightly higher protonation constants relative to that of the ligand DTPA5–. The stability constant for the [Gd(EPTPACH2OH)(H2O)]2– complex has also been determined by potentiometry. The obtained value (log KGdL = 16.7) is two orders of magnitude lower than that for the [Gd(EPTPA)(H2O)]2– complex, which indicates the destabilizing effect of the pendant hydroxymethyl group at the EPTPA backbone. The microscopic protonation scheme has been deduced from the pH dependence of the 1H NMR spectra of both H5EPTPACH2OH and H5EPTPAC16 ligands. The first two protonations occur exclusively at the backbone nitrogen atoms – the first protonation occurs preferentially at the more basic central nitrogen atom. The second proton distributes preferentially between the two terminal nitrogen atoms with the favoring of the trimethylene nitrogen atom over the ethylene nitrogen atom. The LnIII complexes of the ligand H5EPTPACH2OH have been prepared and their solution dynamics studied by 1H NMR spectroscopy. Two sets of resonances of very different intensities from two isomeric complexes have been observed. Relaxometric investigations (17O NMR and 1H NMRD) demonstrate that the [Gd(EPTPACH2OH)(H2O)]2– complex displays an accelerated water‐exchange rate (kex = 87.6 × 106 s–1) that is close to the theoretically derived optimal value. However, the kinetic stability of this complex in phosphate‐buffered solutions towards Zn2+ transmetallation is quite low, but higher than that of the corresponding methyl derivative.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Dielectric spectroscopy of low-loss sugar lyophiles: II. Relaxation mechanisms in freeze-dried lactose and lactose monohydrate

This article presents an analysis of the dielectric relaxation mechanisms of the disaccharide lactose, in both the freeze-dried state and the crystalline monohydrate. Complex dielectric permittivity spectra for both forms of lactose were measured over wide ranges of frequency (0.1Hz to 1MHz) and temperature (−120°C to +100°C). The crystalline monohydrate displays a sharp peak in the temperature domain which was ascribed to the percolation of migrating protons over the surfaces of the crystals. The freeze-dried material displayed three relaxation processes. The first (γ) and second (β) processes were observed at low temperature and present as very broad relaxations with low dielectric strength. The relaxation times for both processes showed Arrhenius temperature-dependencies, with activation energies of 52kJ/mol and 72kJ/mol, respectively. The mechanisms of dielectric relaxation were ascribed to the motion of the pendant hydroxymethyl group and the relative motion of the pair of saccharide rings, respectively. Analysis and discussion of the third relaxation process is beyond of the scope of this article.

Synthesis of new analogues of salacinol containing a pendant hydroxymethyl group as potential glycosidase inhibitors

The synthesis of new analogues of the naturally occurring glycosidase inhibitor, salacinol, and its ammonium analogue, ghavamiol is described. These analogues contain an additional hydroxymethyl group at C-1, which was intended to form additional polar contacts within the active site of glycosidase enzymes. The target zwitterionic compounds were synthesized by means of nucleophilic attack at the least hindered carbon atom of 2,4- O-benzylidene- l (or d)-erythritol 1,3-cyclic sulfate by 2,5-anhydro-1,3:4,6-di- O-benzylidene-2,5-dideoxy-5-thio (or 1,5-imino)- l-iditol.

Supramolecular Assembly of an Amphiphilic GdIII Chelate: Tuning the Reorientational Correlation Time and the Water Exchange Rate

We report the synthesis and characterization of the novel ligand H(5)EPTPA-C(16) ((hydroxymethylhexadecanoyl ester)ethylenepropylenetriaminepentaacetic acid). This ligand was designed to chelate the Gd(III) ion in a kinetically and thermodynamically stable way while ensuring an increased water exchange rate (kappa(ex)) on the Gd(III) complex owing to steric compression around the water-binding site. The attachment of a palmitic ester unit to the pendant hydroxymethyl group on the ethylenediamine bridge yields an amphiphilic conjugate that forms micelles with a long tumbling time (tau(R)) in aqueous solution. The critical micelle concentration (cmc = 0.34 mM) of the amphiphilic [Gd(eptpa-C(16))(H(2)O)](2-) chelate was determined by variable-concentration proton relaxivity measurements. A global analysis of the data obtained in variable-temperature and multiple-field (17)O NMR and (1)H NMRD measurements allowed for the determination of parameters governing relaxivity for [Gd(eptpa-C(16))(H(2)O)](2-); this is the first time that paramagnetic micelles with optimized water exchange have been investigated. The water exchange rate was found to be kappa(298)(ex) = 1.7 x 10(8) s(-1), very similar to that previously reported for the nitrobenzyl derivative [Gd(eptpa-bz-NO(2))(H(2)O)](2-) kappa(298)(ex) = 1.5 x 10(8) s(-1)). The rotational dynamics of the micelles were analysed by using the Lipari-Szabo approach. The micelles formed in aqueous solution show considerable flexibility, with a local rotational correlation time of tau(298)(l0) = 330 ps for the Gd(III) segments, which is much shorter than the global rotational correlation time of the supramolecular aggregates, tau(298)(g0) = 2100 ps. This internal flexibility of the micelles is responsible for the limited increase of the proton relaxivity observed on micelle formation (r(1) = 22.59 mM(-1) s(-1) for the micelles versus 9.11 mM(-1) s(-1) for the monomer chelate (20 MHz; 25 degrees C)).

A novel one-pot two-component synthesis of tricyclic pyrano[2,3- b]quinoxalines

A one-pot two-component synthesis of tricyclic pyrano[2,3- b]quinoxalines with a pendant hydroxymethyl fuction at the 2-position relevant to molybtopterin is described by the reaction of o-phenylenediamine and phenylhydrazone derivatives of sugars in good yields.

An Easy Access to γ‐Lactone‐Fused Cyclopentanoids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

An easy access to gamma-lactone-fused cyclopentanoids.

The tricyclic alpha-keto hemiacetals 3a,b and 8a-d obtained from ruthenium-catalyzed oxidation of tetrahalonorbornyl derivatives possessing a pendant hydroxymethyl group were cleaved using Pb(OAc)(4) or alkaline H(2)O(2) to give gamma-lactone-fused cyclopentane derivatives 5a,b and 9a-d. The alpha-keto hemiacetal 3b has also been elaborated to spiroepoxide derivative 25. The stable hydrate 4 formed from ruthenium-catalyzed oxidation of acrolein adduct 10 furnished an intramolecular hemiacetal 11 upon cleavage with Pb(OAc)(4). The alpha-halo ester moiety in 5a was transformed smoothly in a highly regio- and stereoselective manner to alpha-hydroxy esters through a lactone-assisted intermediate to furnish 18.

Construction of Supported Organometallics Using Cycloplatinated Arylamine Ligands

The preparation of ortho-chelating aminoaryl ligands ([C6H3(CH2NMe2)-2-R-4]-, abbreviated as C,N) containing a pendant hydroxymethyl group is described. These ligands have been cycloplatinated with cis-PtCl2(DMSO)2, yielding the corresponding C,N-platinum(II) complexes. The pendant hydroxymethyl substituent is a versatile group for attachment of the organometallic moiety to macromolecules, which has been demonstrated by attaching the C,N-platinum complexes to a dendritic wedge and to C60.

Stereoselective synthesis of the pyrroloisoquinoline ring system

In this paper we report a facile and stereoselective approach to the pyrroloisoquinoline ring system through the application of N-acyliminium chemistry from readily available non-racemic chiral templates. The stereochemical outcome of the cyclisation reactions has been determined by NOE and X-ray crystallography. We also demonstrate the synthetic potential of our new approach through removal of the pendant hydroxymethyl auxiliary from a product of cyclisation.

A comparative study of the dielectric relaxation behaviour of glucose, maltose, and their mixtures with water in the liquid and glassy states

The dielectric relaxation behaviour of glucose, maltose, and their mixtures with water up to a concentration of 12.0 and 23.0% w/w, respectively, were examined in the frequency range 10 2 to 10 5Hz. A primary relaation was observed at temperatures above the glass transition temperature, T g, and a secondary relaxation at sub- T g temperatures. The addition of water shifted the primary relaxations to lower temperatures. For the glucose mixtures, water increased the strength of the secondary relaxation and resulted in a merging of the primary and secondary relaxations. The increase in strength of the secondary relaxation was much more marked for the maltose-water mixtures and, in this case, the relaxations remained separate over the range of frequency and water contents studied. For the maltose-water mixtures, the dependence of the strength of the secondary relaxation on the water content was bilinear with a change in gradient at ∼ 10.0% w/w water. The sub- T g relaxations were thought to arise from motions of pendant hydroxymethyl groups attached to the hexose rings and from the reorientation of water molecules. The difference in the secondary relaxation behaviour of glucose and maltose indicates that structural factors, in addition to the presence of hydroxymethyl groups, are also important.

Metal-directed syntheses of dithiadiazacyclotetradecane macrocycles with pendant alcohol and nitro or carboxylate groups involving macrocycle ring expansion

Copper(II)-directed condensation of 4-hydroxymethyl-3,6-dithiaoctane-1,8-diamine with nitroethane or diethyl malonate and formaldehyde yielded (anti-6-methyl-6-nitro-1,11-dithia-4,8-diazacyclotetradecan-13-ol)copper(II) and (diethyl 13-hydroxy-1,11-dithia-4,8-diazacyclotetradecane-6,6-dicarboxylate)copper(II) respectively in good yields. The latter was readily converted by decarboxylation and hydrolysis in aqueous base to the copper(II) complex of anti-13-hydroxy-1,11-dithia-4,8-diazacyclotetradecane-6-carboxylic acid from which the free ligand can be obtained by zinc–acid reduction of the copper ion, whereas the former can be converted by zinc–acid reduction directly to the hydrochloride salt of the free anti-6-amino-6-methyl-1,11-dithia-4,8-diazacyclotetradecan-13-ol ligand. The condensations should yield a thirteen-membered macrocycle with a pendant hydroxymethyl group fused to a macrocyclic ring carbon, but the molecules undergo a Wagner–Meerwein or alternate carbon skeleton rearrangement to yield the fourteen-membered macrocycle with a pendant alcohol group. The pendant alcohol can act as an axial donor group, as illustrated in the crystal structure analyses of (anti-6-methyl-6-nitro-1,11-dithia-4,8-diazacyclotetradecan-13-ol)copper(II) and (anti-13-hydroxy-1,11-dithia-4,8-diazacyclotetradecane-6-carboxylato)copper(II) as perchlorate salts. The former complex crystallizes in the monoclinic P21/c space group, a= 8.703(2), b= 18.699(2), c= 13.293(2)A, β= 105.15(1)° and the latter in the monoclinic P21/n space group, a= 7.450(1), b= 15.325(2), c= 16.772(1)A, β= 98.38(1)°. In both complexes the alcohol is disposed anti to the nitro or carboxylate group. In the former, the copper ion lies in a distorted-octahedral environment of two sulfur donors (Cu–Sav 2.333 A), two nitrogen donors (Cu–Nav2.016 A), the pendant alcohol donor [Cu–O 2.365(3)A] and a perchlorate anion [Cu–O 2.544(3)A], whereas in the latter a dimer with each copper in a very distorted octahedral environment exists where each carboxylate bridges to the alternate copper ion [Cu–O 2.293(3)A] and the alcohol is weakly bound [Cu–O 2.520(3)A] in addition to the macrocycle heteroatoms (Cu–Nav 2.035, Cu–Sav 2.353 A).