LiAlH4 Research Articles

Ring Expansion Reactions via C-N Bond Cleavage in the Synthesis of Medium-sized Cycles and Macrocycles

The literature review discusses and systematizes synthetic approaches to medium-sized cycles and macrocycles based on ring expansion reactions of bi- or polycyclic systems via C-N bond cleavage. Ring expansion reactions of bicyclic ammonium salts proceed via thermal decomposition or the action of strong bases. Bi- or polycyclic systems containing a common amine group can be reduced with strong reducing reagents, e.g. lithium aluminum hydride. Ammonium derivatives are much more prone to nucleophilic attack and quite often are used as starting materials for the synthesis of medium-sized cycles. Bicyclic systems containing a common aminal or amidine group are used for the synthesis of medium-sized rings and macrocycles via cleavage of the endocyclic C-N bond. Various methods of their activation and reduction are discussed in the review.

Synthesis of N-Alkyl-1,3-dihydro-2,1-benzisoxazoles.

We describe a practical method for the synthesis of various substituted N-alkyl-1,3-dihydro-2,1-benzisoxazoles and their 2,1-benzisoxazolone precursors starting from readily available methyl 2-nitrobenzoates. The method entails partial nitro reduction with hydrazine and rhodium on carbon to give the hydroxylamines, followed by base-mediated cyclization to give the corresponding benzisoxazol-3(1H)-ones. Subsequent alkylation is conducted under basic conditions and is followed by reduction to the target 1,3-dihydrobenzisoxazoles, achieved with lithium aluminum hydride in the presence of trimethylsilyl chloride.

Rapid Synthesis of anti-1,3-Diamino-4-phenylbutan-2-ol Building Blocks via a Three-Component Oxyhomologation and a Two-Component Reducing System.

N1-substituted derivatives of anti-(2R,3S)-1,3-diamino-4-phenylbutan-2-ol are important building blocks for the synthesis of therapeutically important molecules. We describe a simple protocol that allows transformation of N,N-dibenzyl-L-phenylalaninal into such compounds in only two steps. The first step is a fully stereoselective three-component MAC (Masked Acyl Cyanide) oxyhomologation reaction implicating different amines to give a panel of ten N,N-dibenzyl-O-tert-butyldimethylsilyl-protected anti-(2S,3S)-allophenylnorstatin amides. The second step is a carbonyl-activated hydride deprotection/reduction protocol using trimethylsilyl chloride and lithium aluminium hydride; the one-pot two-component system is more efficient than the alternative approach of isolating the deprotected amide intermediate before reduction.

Core‐Fluorinated BODIPYs – a New Family of Highly Efficient Luminophores

AbstractA modular synthesis of novel series of 1,7‐difluorinated BODIPYs has been elaborated. First, the acid‐catalyzed condensation of ethyl 3‐aryl‐4‐fluoro‐1H‐pyrrole‐2‐carboxylates with aromatic aldehydes gives the corresponding dipyrromethane‐1,9‐dicarboxylates. The latter are subjected to the exhaustive reduction with lithium aluminum hydride to transform the ester moieties into methyl groups. The subsequent oxidation of the resulting 1,9‐dimethylated dipyrromethanes followed by the boron difluoride complexation afforded a family of novel core‐fluorinated BODIPYs in up to 74 % yield. Photophysical properties of the resulting BODIPYs were tuned by varying of the starting fluoropyrroles and aromatic aldehydes and were studied by UV‐visible and fluorescence spectroscopy. As a result, the fluorescence quantum yields of the obtained compounds reached up to 99 %. In addition, their ability to generate singlet oxygen and electrochemical properties were also evaluated. As a result, a new promising family of fluorophores with a good combination of the fluorescence and photosensitizing properties was obtained. It was found that conversion of ester groups into methyl ones at the 3,5‐positions of the BODIPY core is a crucial step toward fluorescence enhancement. In addition, DFT calculations were performed to elucidate a relationship between electronic structure, geometry and photophysical properties of these BODIPYs.

Main Group Metal Complexes of Si, Ge and Al with an Unsymmetrical N,N’‐substituted Diamide Ligand

Unsymmetrically N,N’‐substituted metal amides of silicon, germanium and aluminium were synthesized starting from N‐ethyl‐2‐(n‐propylaminomethyl)­phenyl­amine (1, Et,nPr‐ampaH2). Reaction of the dilithium compound of 1 with SiCl4 gave spirocyclic Si(Et,nPr‐ampa)2 (2) and Cl2Si(Et,nPr‐ampa) (3). Reduction of 3 with potassium resulted in the formation of the corresponding cyclotetrasilane [Si(Et,nPr‐ampa)]4 (4), whereas the reaction of 3 with lithium triethylborohydride gave the dihydro silane H2Si(Et,nPr‐ampa) (5). The corresponding germanium(IV) compounds Ge(Et,nPr‐ampa)2 (6) and Cl2Ge(Et,nPr‐ampa) (7) were synthesized starting from GeCl4, amine 1 and NEt3 using appropriate stoichiometric ratios. Reaction of Ge[N(SiMe3)2]2 with amine 1 provided the germylene [Ge(Et,nPr‐ampa)]2 (8). The aluminium dichloro compound Cl2Al(Et,nPr‐ampaH) (9) was obtained either by reaction of the dichlorogermine 7 with lithium aluminium hydride or by reaction of the dilithium salt of 1 with AlCl3. Reaction of trimethylaluminium with amine 1 provided the amido‐amine (CH3)2Al(Et,nPr‐ampaH) (10) which was converted into the diamide CH3Al(Et,nPr‐ampa) (11) by methane elimination.

Effect of the accelerated aging process on the thermal decomposition of LiAlH4-based composite solid propellants

In the present work, a study was carried out on the effect of the accelerated aging process on the thermal decomposition of two composite solid propellants based on ammonium perchlorate (AP) and hydroxy‑terminated polybutadiene (HTPB). The first one (CP1) was enriched with aluminum (Al) powders, while the second (CP2) contained a mixture of aluminum and lithium alanate (LiAlH4) as a high-energy fuel additive. The thermal properties of the investigated propellant samples were determined using differential scanning calorimetry (DSC) and thermogravimetry (TG) techniques. The obtained results clearly demonstrated the effect of the aging process on the thermal degradation of the aged samples compared to the unaged ones, by shifting the temperature peaks of their main decomposition step to lower temperatures with a decrease in their DSC heat release. In addition, the residual unburnt propellant was increased, particularly for the complex metal hydride-based propellant. Kinetic modeling of the main thermal degradation phase, applying two advanced isoconversional methods, revealed a significant decrease in activation energy for the aged samples. Furthermore, the three-dimensional diffusion model involved during the investigated decomposition phase of the unaged samples was changed to a random nucleation model after 60 days of aging time.

Role of the in situ formed LiAl(NH)2 and LiNH2 in significantly improving the hydrogen storage properties of the Mg(NH2)2-2LiH systems with Li3AlH6 addition

The Mg(NH2)2-2LiH system has attracted considerable interest due to its high hydrogen capacity and low theoretical dehydrogenation enthalpy. However, its practical application is limited by sluggish kinetics due to the slow mass transfer rate and the stable N-H bond. In response to these problems, this study introduced Li3AlH6 into the Mg(NH2)2-2LiH system, leveraging the mutual destabilization effects between lithium alanates and metal amides to attenuate the stability of the N-H bond in Mg(NH2)2. The results show that the Mg(NH2)2-2LiH-0.1Li3AlH6 composite can reversibly desorb/absorb hydrogen up to 4.33 wt% at 140 °C with an initial dehydrogenation temperature of 90 °C. This represents a significant improvement over the pristine sample's capacity of 1.23 wt% under the same conditions. Phase structure analyses reveal that the in situ formed LiAl(NH)2 and LiNH2 particles during ball milling play a crucial role in decreasing the energy required for cleaving the N-H bond, transferring mass, and initiating nucleation. Dehydrogenation curves suggest that the dehydrogenation process follows the Avrami-Erofe'ev equation, signifying that the process is controlled by both nucleation and diffusion processes. A pronounced correlation exists between dehydrogenation kinetic energy barriers and nucleation energy barriers of the dehydrogenation products. This finding implies that future reductions in operating temperature and enhancements of the dehydrogenation rate in the Mg(NH2)2-2LiH system can be achieved by decreasing the nucleation energy barriers of the dehydrogenation products.

Guidance for working with lithium aluminum hydride

Guidance for working with lithium aluminum hydride

Improving the desorption properties of LiAlH4 by the addition of Ni0.6Zn0.4O

Lithium alanate (LiAlH4) is one of the most preferred materials for solid-state hydrogen storage materials owing to its relatively high hydrogen capacity (10.5 wt%). However, its high decomposition temperature and sluggish desorption kinetic restrict its potential application as a hydrogen storage medium for on-board hydrogen-powered applications. To overcome these problems, the impacts of Ni0.6Zn0.4O synthesized via a solid-state method on the desorption properties of LiAlH4 have been examined in this study. It was found that after the introduction of 10 wt% of Ni0.6Zn0.4O to LiAlH4, hydrogen started to release at 124 °C and 170 °C for the first two stages, respectively. Isothermal desorption kinetics also revealed that faster desorption kinetics can be observed at 90 °C for 120 min LiAlH4+10 wt% of Ni0.6Zn0.4O can desorb 3.1 wt% of H2, whereas undoped LiAlH4 can release approximately less than 0.5 wt% of H2 in the same time frame. According to the Kissinger method, the apparent activation energies for the first two steps of the LiAlH4+10 wt% of Ni0.6Zn0.4O composites have been found to be 73 kJ/mol and 85 kJ/mol, respectively, 32 kJ/mol and 40 kJ/mol less than milled LiAlH4. The in-situ formation of NiO and Zn or Zn-containing compounds during the heating process might contribute to the kinetic improvement of LiAlH4.

Reduction of Triple Bond in [B12H11NCR]− Anions by Lithium Aluminum Hydride: A Novel Approach to the Synthesis of N-Monoalkylammonio-Substituted closo-Dodecaborates

By reacting nitrilium derivative of the closo-dodecaborate anion, Bu4N[B12H11N≡CR] (where R = Me, Et, nPr, iPr, p-tolyl), with lithium aluminum hydride (LiAlH4), N-alkylammonium derivatives of the closo-dodecaborate anion, and Bu4N[B12H11NH2CH2R], were obtained. The reduction reaction procedure was optimized, achieving yields close to quantitative (90–95%). The structure of the compound Bu4N[B12H11NH2CH2CH3] was determined using X-ray structural analysis. It was found that substituting lithium aluminum hydride (LiAlH4) with sodium borohydride (NaBH4) leads to the same products but only upon heating, while the reaction with LiAlH4 proceeds at room temperature.

MEDT Study, hemisynthesis via regioselective ring opening of α-Himachalene-Epoxides, ADME survey and docking studies designed to target coronavirus and HIV-1

The ring-opening reaction of the two diepoxides, α-himachalenes 6 and 7, with aluminum lithium hydride (LiAlH4) in ether produced the title compounds C15H24O2 sesquiterpene alcohol. Both experimentally and conceptually, the regio- and stereospecificity of this ring opening reaction were investigated using the Molecular Electron Density Theory (MEDT). The Parr functions and the energy study correctly predicted the best interaction to be between the C13 carbon and the hydride, as evidenced by the attained regio- and stereo-specificity revealed through the experimental research. Moreover, the alcohol 8 is obtained from a kinetic and thermodynamic control while the alcohol 9 is obtained only by a kinetic control, in the maximum conformity with the findings of the experiments. In addition, the performed docking calculations to examine the coronavirus and HIV-1 activities of the products 1–9 revealed that alcohol 9 has a higher affinity against coronavirus while β-himachalene 1 against the HIV-1.

Highly Diastereoselective Preparation of Tertiary Alkyl Thiocyanates en Route to Thiols by Stereoinvertive Nucleophilic Substitution at Nonclassical Carbocations.

An effective InBr3-catalyzed nucleophilic thiocyanation of cyclopropyl alcohols has been developed. The reaction takes place at the quaternary carbon stereocenter of the cyclopropyl carbinol with a complete inversion of configuration, offering a novel pathway for the creation of complex tertiary alkyl thiocyanates with high diastereopurity. These substitution reactions proceed under mild reaction conditions and tolerate several functional groups. Additionally, thiocyanates were converted to thiols using lithium aluminum hydride.

The Solvent‐free Lithium Alanate {Li[t‐Bu2AlH2]}n: A New Product Obtained from a Long‐Known Reaction

AbstractWe report the isolation and characterization of an unknown reaction product from the reaction of AlBr3 with three equivalents of t‐BuLi. The polymeric and solvent‐free lithium alanate {Li[t‐Bu2AlH2]}n was characterized by X‐ray structure analysis, NMR and IR spectroscopy. The title compound was found to be a suitable starting material for the synthesis of [t‐Bu2AlH]3 by reacting it with readily available [t‐Bu2AlBr]2.

A tetradentate ligand enables iron-catalyzed asymmetric hydrogenation of ketones in a CO- or isocyanide-free fashion.

We herein reported the design and synthesis of a ferrocene-based tetradentate ligand that is featured with modular synthesis and rigid skeleton. Its iron(II) complex facilitates asymmetric hydrogenation of ketones without the participation of extra strong-field ligand such as CO and isocyanide. Hydride donor LAH converted non-reactive Fe(II) species to reactive Fe(II) hydride species. With this catalyst, various chiral alcohols including the intermediate for montelukast could be prepared with satisfactory yields and enantioinduction.

Zn2TiO4 synthesized via solid-state method and its effects on dehydrogenation properties of LiAlH4

Lithium alanate (LiAlH4) has high gravimetric capacity but its practical application is still severely constrained by poor reversibility and sluggish kinetics. In this study, the dehydrogenation behaviour of LiAlH4 was modified with the inclusion of Zn2TiO4. The initial temperature for the dehydrogenation of LiAlH4 was downshifted to 111 °C (first dehydrogenation) and 151 °C (second dehydrogenation) with the inclusion of 10 wt% Zn2TiO4. The as-milled LiAlH4 released only 0.1 wt% H2 while the LiAlH4–10 wt% Zn2TiO4 sample released 3.6 wt% H2 in 60 min at 90 °C which is 36 times faster than undoped LiAlH4. The dehydrogenation activation energies for the first two dehydrogenation process was also reduced by 24.1 and 21.0% than as-milled LiAlH4. The X-ray diffraction analysis revealed that the Zn2TiO4 reacts with LiAlH4 and the formed Al–Ti and Ti–Zn during the dehydrogenation leading to the superior dehydrogenation behaviour of LiAlH4.

Hydride‐Enhanced Plating and Stripping of Aluminum from Triflate‐based Organic Electrolytes**

AbstractIn the quest for developing rechargeable aluminum (Al) batteries, reversible Al plating in the absence of active‐halide components is considered an immense challenge. For this reason, the choice of electrolyte has been primarily limited to the highly corrosive chloroaluminate systems based on aluminum trichloride (AlCl3). In this work, we demonstrate reversible room‐temperature Al plating from an active‐halide‐free (AHF) organic electrolyte based on aluminum trifluoromethanesulfonate (Al(OTF)3) and lithium aluminum hydride (LiAlH4) in tetrahydrofuran (THF), as well as its AlCl3 counterpart. From insights obtained by Density Functional Theory (DFT) and Fourier‐Transform Infrared (FTIR) spectroscopy, ionic speciation in the electrolyte is explored, and mechanisms for the underlying electrochemical processes in the trifluoromethanesulfonate (OTF−)‐based electrolytes are proposed. Al plating and stripping were confirmed by optical microscopy, scanning electron microscopy (SEM) and X‐ray diffraction (XRD). Characterizing the Al deposits from either the OTF−‐ or the chloride (Cl−)‐based electrolytes via depth‐profile X‐ray Photoelectron Spectroscopy (XPS) analyses, we find that these deposits consist of metallic Al, aluminum oxide (Al2O3), and either aluminum trifluoride (AlF3) or aluminum chloride (AlxCly) contaminants arising from a reaction with the electrolyte components which occurs during the plating process.

Synthesis and Properties of the Novel High-Performance Hydroxyl-Terminated Liquid Fluoroelastomer.

Functional liquid fluoroelastomers are in high demand in new energy fields. And these materials have potential applications in high-performance sealing materials and as electrode materials. In this study, a novel high-performance hydroxyl-terminated liquid fluoroelastomer (t-HTLF) with a high fluorine content, temperature resistance, and curing efficiency was synthesised from a terpolymer of vinylidene fluoride (VDF), tetrafluoroethylene (TFE), and hexafluoropylene (HFP). A carboxyl-terminated liquid fluoroelastomer (t-CTLF) with controllable molar mass and end-group content was first prepared from a poly(VDF-ter-TFE-ter-HFP) terpolymer using a unique oxidative degradation method. Subsequently, an efficient "one-step" reduction of the carboxyl groups (COOH) in t-CTLF into hydroxyl groups (OH) was achieved via the functional-group conversion method using lithium aluminium hydride (LiAlH4) as the reductant. Thus, t-HTLF with a controllable molar mass and end-group content and highly active end groups was synthesised. Owing to the efficient curing reaction between OH and isocyanate groups (NCO), the cured t-HTLF exhibits good surface properties, thermal properties, and chemical stability. The thermal decomposition temperature (Td) of the cured t-HTLF reaches 334 °C, and it exhibits hydrophobicity. The oxidative degradation, reduction, and curing reaction mechanisms were also determined. The effects of solvent dosage, reaction temperature, reaction time, and ratio of the reductant to the COOH content on the carboxyl conversion were also systematically investigated. An efficient reduction system comprising LiAlH4 can not only achieve an efficient conversion of the COOH groups in t-CTLF to OH groups but also the in situ hydrogenation and addition reactions of residual double bonds (C=C) groups in the chain, such that the thermal stability and terminal activity of the product are improved while maintaining a high fluorine content.

Synthesis and biological activity of 4-fluorophenylcyclohexyl(tetrahydropyranyl)methyl-substituted aryloxypropanolamines

By alkylation of 4-fluorophenylacetonitrile with dibrompеntane and 2.2-dichlor-diethylether the corresponding nitriles were obtained, with which reduction by lithium aluminium hydride [1-(4-fluorophenyl)cyclohexyl]- and [1-(4-fluorophenyl)tetrahydro-2 H -pyran-4-yl]methanamines were isolated. By the reaction of the latters with substituted in aromatic cycles aryloxymethyloxiranes new aryloxypropanolamines were been synthesized. Some of them by the action of formaline were transformed to the corresponding oxazolidines.

Metal‐Free Catalytic Reduction of Amides: Recent Progress

AbstractAmines are one of the most important functional groups in organic synthesis, particularly in scaffolds constituting the active ingredients of natural products, pharmaceutical molecules, and agrochemicals. Among various transformations to access amines, amide reduction has been considered as the most facile and efficient strategy, but it is also one of the most problematic, often requiring the use of highly reactive stoichiometric reductants, such as lithium aluminum hydride, as well as rare transition metal catalysts, or both, and harsh reaction conditions. This review covers recent advances in the catalytic reduction of amides to amines without the need for metal catalysts, thus overcoming such problems.

Lithium Aluminium Hydride and Metallic Iron: A Powerful Team in Alkene and Arene Hydrogenation Catalysis

AbstractAlkenes that normally do not react with LiAlH4 (3‐hexene, cyclohexene, 1‐Me‐cyclohexene), can be reduced to the corresponding alkanes by a mixture of LiAlH4 and Fe0 (the iron was activated by Metal‐Vapour‐Synthesis). This alkene‐to‐alkane conversion with a stoichiometric quantity of LiAlH4/Fe0 does not need quenching with water or acids, implying that both H's originate from LiAlH4. The LiAlH4/Fe0 combination is also a remarkably potent cooperative catalyst for hydrogenation of multi‐substituted alkenes and benzene or toluene. An induction period of circa two hours and the minimally required temperature of 120 °C, suggests that the actual catalyst is a combination of Fe0 and the decomposition product of LiAlH4 (LiH and Al0). A thermally pre‐activated LiAlH4/Fe0 catalyst did not need an induction time and is also active at room temperature and 1 bar H2. A combination of AliBu3 and Fe0 is an even more active hydrogenation catalyst. Without pre‐activation, tetra‐substituted alkenes like Me2C=CMe2 and toluene could be fully hydrogenated.