LiAlH4 Research Articles

Chemical Synthesis of Rare Natural Bile Acids: 11α-Hydroxy Derivatives of Lithocholic and Chenodeoxycholic Acids.

A method for the preparation of 11α-hydroxy derivatives of lithocholic and chenodeoxycholic acids, recently discovered to be natural bile acids, is described. The principal reactions involved were (1) elimination of the 12α-mesyloxy group of the methyl esters of 3α-acetate-12α-mesylate and 3α,7α-diacetate-12α-mesylate derivatives of deoxycholic acid and cholic acid with potassium acetate/hexamethylphosphoramide; (2) simultaneous reduction/hydrolysis of the resulting △11 -3α-acetoxy and △11 -3α,7α-diacetoxy methyl esters with lithium aluminum hydride; (3) stereoselective 11α-hydroxylation of the △11 -3α,24-diol and △11 -3α,7α,24-triol intermediates with B2 H6 /tetrahydrofuran (THF); and (4) selective oxidation at C-24 of the resulting 3α,11α,24-triol and 3α,7α,11α,24-tetrol to the corresponding C-24 carboxylic acids with NaClO2 catalyzed by 2,2,6,6-tetramethylpiperidine 1-oxyl free radical (TEMPO) and NaClO. In summary, 3α,11α-dihydroxy-5β-cholan-24-oic acid and 3α,7α,11α-trihydroxy-5β-cholan-24-oic acid have been synthesized and their nuclear magnetic resonance (NMR) spectra characterized. These compounds are now available as reference standards to be used in biliary bile acid analysis.

Self-condensation of N-substituted (4H-thieno[3,2-b]-pyrrol-5-yl)methanols into bis(thienopyrrolyl)methanes

N-Substituted (4H-thieno[3,2-b]pyrrol-5-yl)methanols were obtained by alkylation of methyl 4H-thieno[3,2-b]pyrrole-5-carboxylate followed by reduction with LiAlH4. These compounds on contact with Amberlyst 15 (H-form) in CH2Cl2 undergo self-condensation to produce bis(4H-thieno[3,2-b]-pyrrol-5-yl)methanes.

Characterisation of paraffin-based hybrid rocket fuels loaded with nano-additives

ABSTRACTIn this work, a new composition based on Paraffin wax and HTPB fuel, loaded with nanoparticles has been proposed for hybrid propulsion system. Lithium aluminium hydride (LiAlH4) and Magnesium hydride (MgH2) nanoparticles have been used as additives. A detailed rheological, thermal and ballistic characterisation has been carried out. The Magnesium hydride doped hybrid fuel exhibits lower viscosity as compared to the Lithium aluminium hydride doped one, leading to comparatively enhanced entrainment-aided combustion. LiAlH4 doped hybrid fuels also exhibit solid-like behaviour and thus greater stability in the solid phase in contrast to the MgH2 doped fuel. LiAlH4 doped fuel is thermally more stable and produces relatively greater residual-mass. The loading of nanoparticles significantly improves the fuel regression performance during ballistic firing. This can be attributed to the release of nascent hydrogen and metal nanoparticles during dehydrogenation of metal hydrides. Regression rate enhancement in the range of 350%–475% is observed in comparison to the conventional HTPB hybrid fuels. A power law governing regression rate has been proposed for the tested hybrid fuels.

Reaction of 11 C-benzoyl chlorides with metalloid reagents: 11 C-labeling of benzyl alcohols, benzaldehydes, and phenyl ketones from [11 C]CO.

In this article, we describe the carbon-11 (11 C, t1/2 =20.4minutes) labeling of benzyl alcohols, benzaldehydes, and ketones using an efficient 2-step synthesis in which 11 C-carbon monoxide is used in an initial palladium-mediated reaction to produce 11 C-benzoyl chloride as a key intermediate. In the second step, the obtained 11 C-benzoyl chloride is further treated with a metalloid reagent to furnish the final 11 C-labeled product. Benzyl alcohols were obtained in moderated to high non-isolated radiochemical yields (RCY, 35%-90%) with lithium aluminum hydride or lithium aluminum deuteride as metalloid reagent. Changing the metalloid reagent to either tributyltin hydride or sodium borohydride, allowed for the reliable syntheses of 11 C-benzaldehydes in RCYs ranging from 58% to 95%. Finally, sodium tetraphenylborate were utilized to obtain 11 C-phenyl ketones in high RCYs (77%-95%). The developed method provides a new and efficient route to 3 different classes of compounds starting from aryl iodides or aryl bromides.

2,2′-Bis(methylene)biphenylidene-bridged bis(3-indenyl) dichloride complexes of Ti, Zr and Hf as catalyst precursors for ethylene polymerization

ansa metallocene complexes of Ti, Zr and Hf were synthesized, characterized and tested as catalysts for homogeneous ethylene polymerization. The ligand system comprises two indenyl moieties tethered at the 1,1′-positions via a 2,2′-dimethyl biphenylene bridge. The ligand precursor was obtained by the reduction of diphenic acid using lithium aluminum hydride (LiAlH4), followed by the reaction with phosphorus tribromide, and, finally, the reaction with indenyllithium. The corresponding group (IV) metal complexes were synthesized by deprotonation of the ligand precursors using n-BuLi followed by reactions of the corresponding metal tetrachloride. After activation with methylaluminoxane (MAO), the zirconium and hafnium complexes proved as highly active catalysts for ethylene polymerization. The zirconium complex 6 showed the best performance with 12,460 kg PE/mol cat. h. The titanium complex 5 showed no catalytic activity obviously because of decomposition reactions.

Excited state hyperpolarizability of LiAlH4 computed at the FSMRCCSD level and its use for mixed-frequency laser

The Constrained variation technique is used to obtain third-order energy response property in Fock space multi-reference coupled cluster singles and doubles (FSMRCCSD) formalism. Computational development is done to calculate first static hyperpolarizability of lithium aluminum hydride (LiAlH4) at its lowest excited state. It is observed that LiAlH4 is not optically active at its ground state. But, it is highly active in its excited state. Using this property of LiAlH4, a new technique is described to generate mixed-frequency laser which is a laser of the new kind, reported here for the first time. This also helps to generate a laser with shorter pulse duration compared to the laser pulse duration used as incident radiation. Third-order energy response properties of excited states of a closed-shell molecule in analytical FSMRCC approach are also reported here for the first time.

In Situ Synthesis of 3D Flower-Like Nanocrystalline Ni/C and its Effect on Hydrogen Storage Properties of LiAlH4.

Lithium alanate (LiAlH4 ) is of particular interest as one of the most promising candidates for solid-state hydrogen storage. Unfortunately, high dehydrogenation temperatures and relatively slow kinetics limit its practical applications. Herein, 3D flower-like nanocrystalline Ni/C, composed of highly dispersed Ni nanoparticles and interlaced carbon flakes, was synthesized in situ. The as-synthesized nanocrystalline Ni/C significantly decreased the dehydrogenation temperature and dramatically improved the dehydrogenation kinetics of LiAlH4 . It was found that the LiAlH4 sample with 10 wt % Ni/C (LiAlH4 -10 wt %Ni/C) began hydrogen desorption at approximately 48 °C, which is very close to ambient temperature. Approximately 6.3 wt % H2 was released from LiAlH4 -10 wt %Ni/C within 60 min at 140 °C, whereas pristine LiAlH4 only released 0.52 wt % H2 under identical conditions. More importantly, the dehydrogenated products can partially rehydrogenate at 300 °C under 4 MPa H2 . The synergetic effect of the flower-like carbon substrate and Ni active species contributes to the significantly reduced dehydrogenation temperatures and improved kinetics.

Chemoselective synthesis of isolated and fused fluorenones and their photophysical and antiviral properties

Highly functionalized fluorenones were synthesized by an intramolecular cyclization of 2''-halo-[1,1':3',1''-terphenyl]-4'-carbonitriles in the presence of n-butyllithium or lithium aluminium hydride. The precursor was synthesized by ring transformation of 2-oxo-6-aryl/heteroaryl-4-(sec.amino)-2H-pyran-3-carbonitriles or 2-oxobenzo[h]chromenes with o-bromo/chloro/fluoro-acetophenone under basic conditions in moderate yield. We performed the control experiment to understand the proposed mechanism and found that the presence of a secondary amine in the starting material directs the reactivity. The photophysical properties of 3-methoxy-7-(piperidin-1-yl)-5H-indeno[2,1-b]phenanthren-8(6H)-one was explored and solvent dependent emission was observed. These compounds were also tested against HIV-1 and low to moderate activity was observed.

An Improved Preparation of (R)-3-Aminobutanol, a Key Intermediate for the Synthesis of Dolutegravir Sodium

Background: Dolutegravir sodium is a HIV-1 integrase strand transfer inhibitor (INSTI) and in combination with other anti-retroviral agents, is recommended for the treatment of HIV-1 infection. Moreover, it is a second generation HIV integrase inhibitor designed to deliver potent antiviral activity. Originally, collaboration between Shionogi and Glaxo Smith Kline (GSK) led to dolutegravir sodium which is marketed under the trade name Tivicay®. Its synthesis involves the reaction of (R)-3-aminobutanol (1) with 3-benzyloxy-4-oxo-1-(2-oxoethyl)-1,4-dihydropyridine- 2,5-dicarboxylic acid 2-methyl ester. Later, the (R)-3-aminobutanol became a key intermediate for the synthesis of Dolutegravir sodium. Methods: In our method the (R)-3-aminobutanol is synthesized in a three/four-step synthetic protocol using 4-Hydroxy 2-butanone as starting material, initial formation of oxime with hydroxyl amine, followed by replacement of developed lithium aluminum hydride (LAH) for reduction of oxime using Raney ‘Ni’, which provided the enantiomeric mixture of 3-aminobutanol in about 85-90 % yield, which is more significant compared to earlier approach (yield: 70 %). Further the mixture was resolved with D-(-)-tartaic acid to obtain the R-isomer as an ester. The ester is then hydrolyzed with potassium carbonate in methanol to give pure (R)-3-amino butanol in 90 % yield and chiral purity was found to be 99.89 % by HPLC. Results: The present method is highly economical and eliminates the use of expensive catalysts. Moreover, the reaction conditions adopted in this process are mild and suitable for industrial applications and is further supported by our study with a large scale (up to 30 Kg) and the yields obtained are quite good. It is our claim that the present methodology is extremely useful for preparation of (R)-3-aminobutanol on commercial scale. Conclusion: We have developed a simple and efficient method for the synthesis of (R)-3- aminobutanol in industrial scale from 4-hydroxy-2-butanone. The process also involves the use of Raney Ni as an eco friendly reagent for the conversion of oxime to amine which is superior to reported LAH approach. Further, the process also uses an inexpensive D-(-)-tartaric acid as a chiral reagent. The developed method involves very cheap reagents, experimental procedures are highly convenient and the yields are impressive. Keywords: Dolutegravir sodium, (R)-3-aminobutanol, D-tartaric acid, resolution, Raney ‘Ni’, 4-hydroxy-2-butanone, chiral reagent.

Catalytic Reduction of Alkyl and Aryl Bromides Using Propan‐2‐ol

AbstractMilstein's complex, (PNN)RuHCl(CO), catalyzes the efficient reduction of aryl and alkyl halides under relatively mild conditions by using propan‐2‐ol and a base. Sterically hindered tertiary and neopentyl substrates are reduced efficiently, as well as more functionalized aryl and alkyl bromides. The reduction process is proposed to occur by radical abstraction/hydrodehalogenation steps at ruthenium. Our research represents a safer and more sustainable alternative to typical silane, lithium aluminium hydride, and tin‐based conditions for these reductions.

Catalytic Reduction of Alkyl and Aryl Bromides Using Propan-2-ol.

Milstein's complex, (PNN)RuHCl(CO), catalyzes the efficient reduction of aryl and alkyl halides under relatively mild conditions by using propan-2-ol and a base. Sterically hindered tertiary and neopentyl substrates are reduced efficiently, as well as more functionalized aryl and alkyl bromides. The reduction process is proposed to occur by radical abstraction/hydrodehalogenation steps at ruthenium. Our research represents a safer and more sustainable alternative to typical silane, lithium aluminium hydride, and tin-based conditions for these reductions.

Ir-catalyzed Hydrogenolysis Reaction of Silyl Triflates and Halides with H2

Synthesis of hydrosilanes by the hydrogenolysis reaction with H2 instead of reducing with strong hydride reagents such as lithium aluminum hydride was achieved. An iridium complex catalyst successfully converted silyl triflates and halides with H2 to the corresponding hydrosilanes in the presence of an amine under mild reaction conditions.

SYNTHESIS AND PROPERTIES OF 5-BROM- AND 5-CHLOROSUBSTITUTED trans-ACENAPHTHENE-1,2-DIOLS

We carried out transformations that describe the preparation of an unsubstituted trans-acenaphthene-1,2-diol using 5-bromo- and 5-chloro-substituted starting materials. Thus, by the reflux of trans-1,2,5-tribromacenaphthene and 1,2-dibromo-5-chlorocenaphthene in water we obtained the corresponding 1,2-diols, which are considered to be cis-isomers by melting points and NMR 1H-spectra. So hydrolysis of trans-1,2,5-tribromo- and 1,2-dibromo-5-chloroacenaphthenes leads to very moderate yields of 1,2-diols (25-26%) with undesired cis-stereoselectivity. By the reaction of 5-bromo- and 5-chlorocenaphthylenes with iodine and silver benzoate in benzene followed by hydrolysis, we obtained mixtures of cis- and trans-1,2-diols which were separated chromatographically and trans-isomers of 5-bromo- and 5-chloro-acenaphthene-1,2-diols were firstly isolated. The yield of trans-diols was low (10-15%), which led us to the search for a convenient method for preparation of trans-isomers. We found this method using the reduction reaction of 5-bromoacenaphthenequinone, replacing the explosive and non-selective reductant lithium aluminum hydride by a more selective and easy-to-handle sodium borohydride in isopropanol. Reduction of 5-bromocenaphthenequinone with sodium borohydride leads to a substantially pure trans-5-bromoacenaphthen-1,2-diol in a rather high yield (57% after re-crystallization).trans-5-Bromo- and 5-chloroacenaphthene-1,2-diols were analyzed by the complex of physical and chemical methods. It is shown that the trans-5-bromo- and 5-chloroacenaphthen-1,2-diols have essentially the same mass spectra with cis isomers, but substantially differ from them by melting points, IR and 1H NMR spectra. Melting points of trans-diols are generally lower than of cis-diols. In IR spectra cis-doils have two characteristic bands of O-H groups (due to association via intramolecular and intermolecular hydrogen bonds) whereas transisomers have only one broad band (only intermolecular hydrogen bonds are possible). In 1H NMR spectra significant differences in the region of the methyne protons at C1 and C2 are noticeable – their signals in the spectrum of the trans-diol are shifted to a weak field in comparison with the cis-isomer.

Preparation of Telechelic Hydroxyl Low Molecular Weight Fluoropolymers

Preparation of telechelic hydroxyl low molecular weight fluoropolymers by reduction reaction was presented. The telechelic carboxyl low molecular weight fluoropolymers were chosen as raw materials which were prepared by oxidative degradation method. The molecular weights of telechelic carboxyl low molecular weight fluoropolymers were about 3700. Then, using lithium aluminum hydride reacted with carboxyl groups to prepare the telechelic hydroxyl low molecular weight fluoropolymers. The effects of reaction temperatures, reaction times, contents of solvent and lithium aluminum hydride were investigated in detail. The structures, Mn and dynamic viscosity of low molecular weight fluoropolymers were analyzed by FTIR, 1H-NMR, GPC and viscometer respectively. Finally telechelic hydroxyl low molecular weight fluoropolymers were prepared. The conversion rate of that reduction reaction was about 95%. The product was a viscous fluid with a dynamic viscosity of 48Pa·s at 50°C.

The silanol content and in vitro cytolytic activity of flame-made silica

HypothesisThe surface chemistry of synthetic amorphous silicas is essential for their applicational performance and for understanding their interactions with biological matter. Synthesis of silica by flame spray pyrolysis (FSP) allows to control the content and type of hydroxyl groups which also affects the cytolytic activity. ExperimentsBy controlling the FSP process variables, silica nanoparticles with the same specific surface area but different surface chemistry and content of internal silanols are prepared by combustion of hexamethyldisiloxane sprays, as characterized by Raman and infrared spectroscopy, thermogravimetric analysis, and titration with lithium alanate. Cytolytic activity is assessed in terms of membrane damage in human blood monocytes in vitro. FindingsUnlike commercial fumed silica, FSP-made silicas contain a significant amount of internal silanol groups and a high surface hydroxyl density, up to ∼8OH/nm2, similar to silicas made by wet-chemistry. Increasing the residence time of particles at high temperature during their synthesis reduces the internal and surface hydroxyl content and increases the relative amount of isolated silanols. This suggests incomplete oxidation of the silica matrix especially in short and “cold” flames and indicates that the silica particle formation pathway involves Si(OH)4. The surface chemistry differences translate into lower cytolytic activity for “cold-” than “hot-flame” silicas.

Stereoselective synthesis of tri- and tetrasubstituted tetrahydropyrans from syn- and anti-1-R-2-(4-bromophenyl)-5-methylhex-4-en-1-ols and some chemical transformations of the products

Tri- and tetrasubstituted tetrahydropyranes fused to one and two heterocycles with various functional groups (COOEt, Br, MeC=CH2) were synthesized in stereoselective fashion by reactions of syn- and anti-1-R-2-(4-bromophenyl)-5-methylhex-4-en-1-ols (R = Bu, PhCH2) with trifluoromethanesulfonic acid, aldehydes in the presence of boron trifluoride–diethyl ether complex (Prins reaction), and salicylaldehydes in the presence of trimethyl orthoformate and p-toluenesulfonic acid. The obtained compounds were brought into Suzuki coupling with thiofen-2-ylboronic acid, hydrolysis, and reduction of the ester group with lithium tetrahydridoaluminate. The resulting carboxylic acid was converted to carboxamide, and the alcohol was oxidized to aldehyde which was converted to oxime. The steric configuration of substituents remained unchanged in all chemical transformations.

Regeneration of LiAlH4 at sub-ambient temperatures studied by multinuclear NMR spectroscopy

Lithium aluminium hydride (LiAlH4) has long been identified as a viable hydrogen storage material, due to its high attainable theoretical gravimetric hydrogen capacity of 7.9 wt%. The main impediment to its viability for technical application is its limitation for regeneration. Recently, solvent-mediated regeneration has been achieved at room temperature using dimethyl-ether, Me2O, although the reaction pathway has not been determined. This in situ multinuclear NMR spectroscopy study (27Al and 7Li) has confirmed that the Me2O-mediated, direct synthesis of LiAlH4 occurs by a one-step process in which LiAlH4·xMe2O is formed, and does not involve Li3AlH6 or any other intermediates. Hydrogenation has been shown to occur below ambient temperatures (at 0 °C) for the first time, and the importance of solvate adducts formed during the process is demonstrated.

Synthesis of LiAlH4 Nanoparticles Leading to a Single Hydrogen Release Step upon Ti Coating

Lithium aluminum hydride (LiAlH4) is an interesting high capacity hydrogen storage material with fast hydrogen release kinetics when mechanically activated with additives. Herein, we report on a novel approach to produce nanoscale LiAlH4 via a bottom-up synthesis. Upon further coating of these nanoparticles with Ti, the composite nanomaterial was found to decompose at 120 °C in one single and extremely sharp exothermic event with instant hydrogen release. This finding implies a significant thermodynamic alteration of the hydrogen properties of LiAlH4 induced by the synergetic effects of the Ti catalytic coating and nanosizing effects. Ultimately, the decomposition path of LiAlH4 was changed to LiAlH4 → Al + LiH + 3/2H2.

Preliminary Kinetic Characterization of Lithium–Aluminum Based Hydrides for Airbreathing Propulsion

The aim of this research is to present a preliminary experimental investigation on the behavior of lithium–aluminum complex hydrides when exposed to gaseous nitrogen in the range of 20–350°C for airbreathing propulsion applications. This specific task is part of the long-term project devoted to the use of lithium–aluminum hydrides in airbreathing propulsion applications. It is known that a launch system based on the airbreathing technology, by using air as oxidizer, reduces the cost per kilogram of the launch; it is therefore much more profitable than common rocket engines (solid and liquid rockets). The effect of nitrogen gas on the thermal behavior and the kinetic parameters of lithium–aluminum hydride and trilithium–aluminum hydride has been investigated. Differential scanning calorimeter tests, performed using nitrogen gas, have shown the presence of a strong exothermic peak that, when using helium or argon gas, is barely noticeable. A nitridation reaction has been suggested to explain the increase of the sample mass after each differential scanning calorimeter test, which supports the experimental data. The activation energy and frequency factor for the samples of lithium–aluminum hydride and trilithium–aluminum hydride have been calculated using two simplified kinetic methods: the Ozawa method and the Kissinger method.

Isotopic effect on the non-isothermal dehydrogenation kinetics of lithium alanates

The isotopic effect on the dehydrogenation kinetics of lithium alanate has been studied. The desorption of hydrogen/deuterium of LiAlH4/LiAlD4 occurs in two steps below 300 °C. The deuterium desorption temperature of LiAlD4 was found to be marginally higher for both the steps as compared to hydrogen desorption of LiAlH4. The apparent activation energy of hydrogen/deuterium desorption was evaluated and found to be in the order of EaLiAlH4>EaLiAlD4. The higher desorption temperature of LiAlD4 has been explained on the basis the zero point energy per unit H/D atom of the alanates. The results indicate the normal isotopic effect of lithium alanate, which could be extended for the tritium.