Mark Edgar

Inorganic nanostructures from lyotropic liquid crystal phases

Lyotropic liquid crystalline phases are exploited as templates for the synthesis of inorganic nanostructures. In this approach the aggregates of non-ionic amphiphiles in water function as confining media, i.e. the polymerisation of a water-soluble precursor takes place in their aqueous domains. This approach to nanostructure design has considerable advantages over previous routes towards mesoporous ceramic oxides. (i) The nanostructure of the solid can be predicted a priori, (ii) this approach allows the use of non-ionic surfactants as templates and (iii) the progress of the formation can be monitored by various analytical techniques. The approach is tolerant to the introduction of metals into the silica framework, as is demonstrated using aluminium silicate as a representative example. The synthesis and a new way of monitoring the temporal evolution of the inorganic nanostructure using deuterium NMR spectroscopy are described. The results show that the lyotropic liquid crystal phase acts as a template. Further, a novel approach to studying sorption properties allows a comparison with other meso- and microporous materials.

Synthesis of fluorinated fused benzofurans and benzothiophenes: Smiles-type rearrangement and cyclisation of perfluoro(het)aryl ethers and sulfides

Lithium-bromine exchange in 2-bromophenyl perfluoroaryl ethers or sulfides affords fused fluorinated benzofurans or benzothiophenes respectively by S(N)Ar substitution of the adjacent fluorine in the perfluoroaryl substituent. The structures of the new compounds were confirmed by NMR spectroscopy and single crystal X-ray diffraction analysis. In the case of 2-bromophenyl tetrafluoropyrid-4-yl ether, lithiation promoted a Smiles-type rearrangement which led to formation of 4-(2-hydroxyphenyl)tetrafluoropyridine, for which the structure was confirmed by X-ray crystallography.

A Novel Bifunctional Allyldisilane as a Triple Allylation Reagent in the Stereoselective Synthesis of Trisubstituted Tetrahydrofurans

Three for the price of two: A bifunctional allyldisilane undergoes a two-step triple allylation sequence with pairs of aldehydes to give all-cis trisubstituted tetrahydrofurans in excellent enantio- and diastereoselectivity (see scheme). The first allylation step, which sets up the key stereogenic centres, is catalysed by a chiral Lewis base.

Stereoselective synthesis of the indolizinoindole ring system

We report a novel, facile and stereoselective approach to the indolizino[8,7-b]indole ring system from a readily available, non-racemic chiral template.

The effect of particle size on the dehydration/rehydration behaviour of lactose

Ethanolic suspensions of spray dried and micronized alpha lactose monohydrate (L(alpha)xH(2)O) with average particle size between 3 and 200 microm, have been prepared and their dehydration behaviour was investigated by (13)C CP-MASNMR spectroscopy. Sub-micron lactose suspension prepared by a novel high pressure homogenisation method has been compared with the standard ethanolic suspensions of (L(alpha).H(2)O prepared by reflux or static room temperature methods. In all cases, suspensions were shown to contain the stable anhydrous form of lactose ((L(alpha)(S)). Several approaches were employed to remove ethanol from these suspensions and the resulting dry lactose powders were then analysed by FT-IR, PXRD and SEM to evaluate the effect of drying procedure on type and distribution of lactose polymorphs and particle size. For samples with mean particle size greater than 1 microm, the stable anhydrous polymorphic form of lactose was retained on removal of the ethanol, although differences in the morphology and particle size of the crystals were apparent depending on method of suspension formation. Sub-micron (L(alpha)(S), while stable in dry conditions, has been shown to be less stable to atmospheric water vapour than (L(alpha)(S) with particle size between 3 and 200 microm.

Physical methods and techniques: NMR spectroscopy

NMR spectroscopy continues to evolve, with publications in 2011 providing an eclectic collection of applications, advances and incremental improvements. Publications highlights include: DNP in liquids and solids, decoupling effects at high spinning speed in solid-state, results from the 80 kHz spinning-speed 1 mm MAS rotor, enhanced diffusion methods, results from the new 1.0 GHz magnet, an intent to create a 1.3 GHz magnet, results from the 2.6 GHz pulsed-magnet, a cryogen-free MRI, and the use of multiple receivers to acquire multiple experiments within the same pulse sequence. I am indebted to the great and the good whose work has been reported here, all credit is theirs; errors, omissions and blame are all mine.

Substituent chemical shifts (SCS) in NMR. Part 5. Mono- and di-fluoro SCS in rigid molecules

The complete assignment of the proton, carbon and fluorine NMR spectra of fluorocyclohexane (axial and equatorial conformers), 4-methyl-1,1-difluorocyclohexane, 4-tert-butyl-1,1-difluorocyclohexane, 3-methyl-1,1-difluorocyclohexane and 2,2-difluoronorbornane is reported and the proton substituent chemical shifts obtained. The fluorocyclohexane substituent chemical shifts (SCSs) are in close agreement with monofluoro SCS data obtained from steroids, the SCS of the 2ax- and 2eq-H being independent of the orientation of the fluorine. The SCS obtained from fluorocyclohexane are not applicable to the difluorocyclohexane systems and this non-additivity is shown to be general for CF2 and CF3 groups. The proton chemical shift calculation scheme previously given for hydrocarbons can now be extended to include fluoroalkanes using the data presented here. It is shown that the proton chemical shifts of a variety of fluoroalkanes can be well predicted on this scheme.

The in-situ solid-state NMR spectroscopy investigation of alcoholic lactose suspensions.

The polymorphic forms of lactose in alcoholic suspensions have been determined by (13)C CP-MAS NMR spectroscopy, employing hand-made glass inserts. Suspensions of alpha lactose monohydrate (Lalpha.H(2)O) with particle size between 2 and 200mum were prepared by 24h reflux or by storage for 28d in anhydrous ethanol without agitation. These suspensions were compared to an ethanolic sub-micron lactose suspension provided by a 3M Health Care (Loughborough). The (13)C CP-MAS NMR spectra indicated that Lalpha.H(2)O dehydrated to stable anhydrous alpha lactose polymorph (Lalpha(S)) whilst suspended in ethanol. In addition, strong ethanol (13)C resonances were observed for some samples, indicating a liquid-solid interaction between the ethanol and lactose surface. Replacement of ethanol with anhydrous methanol, n-butanol and 3-methylbutan-2-ol implied that the solvent mediated dehydration of Lalpha.H(2)O to Lalpha(S) occurs as a result of sterically controlled interactions.

Substituent chemical shifts in NMR spectroscopy. Part 6. A model for the calculation of proton chemical shifts in substituted alkanes

A development of a previous calculation of partial atomic charges (CHARGE3) is given which allows the prediction of the proton chemical shifts in a variety of substituted alkanes.This is accomplished by identifying the effects of substituents at the α, β, γ and the more distant protons. The hydrogen electronegativity is changed to a value close to the Pauling value, the γ(H.C.C.X) SCS (substituent chemical shift) is shown to be a function of the polarisability of X rather than the electronegativity and the problem of multi-substitution of electronegative substituents is overcome by an explicit correction for oxygen and fluorine substituents. These amendments allow the proton chemical shifts of CH4 –nXn and CH3CH3 –nXn(n= 1–3, X = H, NH2, OH, F, Cl, Br, I, SH) to be predicted generally to 0.1 ppm, apart from some of the Br and I compounds.The method has also been tested on a variety of cyclic alkanes, including substituted cyclohexanes and norbornanes, cis- and trans-decalin, bicyclo[2.2.2]octane, perhydrophenalene and anthracene and some tert-butylmethanes, providing a wide variety of steric interactions and strain energies, and also on fluoro and chloro substituted cyclohexanes and norbornanes.For these compounds the orientation dependence of the γ methyl SCS is considered both explicitly and as a result of steric effects. In contrast the effects of fluorine and chlorine SCSs at the γ(i.e. vicinal) proton are non-orientational.The long range effects of proton–proton interactions are shielding at the protons but the long range effects of C, F and Cl deshield the affected protons. For H, C and Cl an r–6 distance dependence was found but fluorine steric effects were better reproduced with an r–3 distance dependence. The calculations reproduced the observed proton chemical shifts of the compounds studied to 0.17 ppm. It was not necessary to invoke in these calculations either the magnetic anisotropy or the electric field effects of the fluorine and chlorine substituents, and the implication of these results on present theories of proton chemical shifts is discussed.

Analysis of triacetone triperoxide complexes with alkali metal ions by electrospray and extractive electrospray ionisation combined with ion mobility spectrometry and mass spectrometry.

The complexation of triacetone triperoxide (TATP) with a range of alkali metals has been studied by electrospray ionisation mass spectrometry to yield [M + Cat]+ ions for all of the alkali metals. The formation of [2TATP + Li + LiX]+ (X = Br, Cl) sandwich complexes was also observed. Collision cross-sections for the lithium-containing complexes of TATP were measured by travelling wave ion mobility spectrometry mass spectrometry and compared well with computationally determined structures. Extractive electrospray ionisation (EESI) using a lithium-doped electrospray is demonstrated for the detection of TATP vapours desorbed from a metal surface. The limit of detection for EESI was shown to be 20 ng using the [TATP + Li]+ ion.