Metal Hydride Reduction Research Articles

Photochemical [2+2] Cycloaddition of Alkynyl Boronates.

A photochemical [2+2] cycloaddition of alkynyl boronates and maleimides is reported. The developed protocol provided 35-70 % yield of maleimide-derived cyclobutenyl boronates and demonstrated wide compatibility with various functional groups. The synthetic utility of the prepared building blocks was demonstrated for a range of transformations, including Suzuki cross-coupling, catalytic or metal-hydride reduction, oxidation, and cycloaddition reactions. With aryl-substituted alkynyl boronates, the products of double [2+2] cycloaddition were obtained predominantly. Using the developed protocol, a cyclobutene-derived analogue of Thalidomide was prepared in one step. Mechanistic studies supported the participation of the triplet-excited state maleimides and ground state alkynyl boronates in the key step of the process.

Reduction Performance and Mechanism of Liquid Terminated-Carboxyl Fluoroelastomers Using Unitary or Binary Metal Hydride Reduction Systems

Reduction Performance and Mechanism of Liquid Terminated-Carboxyl Fluoroelastomers Using Unitary or Binary Metal Hydride Reduction Systems

Enhanced thermal conductivity in Si3N4 ceramics prepared by using ZrH2 as an oxygen getter

This work reports the two-step sintering method and thermal conductivity of Si3N4 doped with 1.5 wt% MgO and varied contents of ZrH2 in the range of 0-5 wt%. The metal hydride reduction reaction in the first step sintering allows the in situ generations of ZrO2 and the elimination of native SiO2. A smaller amount of liquid phase with reduced oxygen content was produced during the second step sintering as a result of the replacement of ZrO2 by ZrH2. With the aid of ZrH2 as an oxygen getter, the native oxygen in those ZrH2-doped samples was removed via a route of SiO2 →ZrO2 →SiO(g). Consequently, the densified Si3N4 ceramics with larger volume percent of elongated purified β-Si3N4 grains and less glassy phase were obtained. Ultimately, the optimal thermal conductivity of 116.4 W m−1 K−1 was achieved after sintered at 1900 °C for 12 h by using 3 wt% ZrH2 and 1.5 wt% MgO as additives.

Improved thermal conductivity of β‐Si3N4 ceramics by lowering SiO2/Y2O3 ratio using YH2 as sintering additive

AbstractA two‐step sintering process was conducted to produce β‐Si3N4 ceramics with high thermal conductivity. During the first step, native SiO2 was eliminated, and Y2O3 was in situ generated by a metal hydride reduction process, resulting in a high Y2O3/SiO2 ratio. The substitution YH2 for Y2O3 endow Si3N4 ceramics with an increase of 29% in thermal conductivity from 95.3 to 123 W m−1 K−1 after sintered at 1900°C for 12 hours despite an inferior sinterability. This was primarily attributed to the purified enlarged grains, devitrified grain boundary phase, and reduced lattice oxygen content in the YH2‐MgO‐doped material.

Effect of in-situ formed Y2O3 by metal hydride reduction reaction on thermal conductivity of β-Si3N4 ceramics

The effect of YH2 on densification, microstructure, and thermal conductivity of Si3N4 ceramics were investigated by adjusting the amount of YH2 in the range of 0–4 wt% using a two-step sintering method. Native SiO2 was eliminated, and Y2O3 was in situ formed by a metal hydride reduction reaction, resulting in various Y2O3/SiO2 ratios. Full densification of YH2-doped samples could be achieved after sintering at 1900 °C for 4 h. The Y2O3/SiO2 ratio had a significant influence on the composition of crystalline secondary phases. Besides, the increased Y2O3/SiO2 ratio is conducive not only to the grain growth but also to the reduction of activity of SiO2 in the liquid phase, resulting in enlarged purified grains, reduced volume fraction of intergranular phases and increased Si3N4-Si3N4 contiguity. Ultimately, the thermal conductivity increased by 29 % from 95.3 to 123.0 W m−1 K−1 after sintering at 1900 ℃ for 12 h by the substitution of Y2O3 with YH2.

Optimization and sustainability assessment of a continuous flow Ru-catalyzed ester hydrogenation for an important precursor of a β2-adrenergic receptor agonist

The development of a continuous flow ruthenium-catalyzed ester reduction using hydrogen gas is described. The assessment of green metrics show the protocol is substantially more sustainable than commonly employed metal hydride reductions.

Hydrogenation towards Synthetic Sandalwood Odorants in Fragrance Industry

AbstractThe use of metal hydrides as historical reagents for selective carbonyl group reduction is often still a really highly convenient solution for laboratory‐scale transformations due to the lack of requirement for specific equipment. Nevertheless, based on safety, environmental, but also economical industrial constraints, metal hydride reductions were replaced by hydrosilylation, hydrogen transfer, and mostly hydrogenation reactions. Among many other advantages, the use of hydrogen as a reducing agent indeed represents the most sustainable solution for implementation of such chemical transformation on industrial scale. Whereas heterogeneous catalysts have been initially sparsely employed, the most recent developments towards the synthesis of highly active and efficient homogeneous catalysts have become an indisputable solution for selective hydrogenation of both ketones and aldehydes in sandalwood odorant production according to green chemistry principles.

Hydride Reduction of BaTiO3 - Oxyhydride Versus O Vacancy Formation.

We investigated the hydride reduction of tetragonal BaTiO3 using the metal hydrides CaH2, NaH, MgH2, NaBH4, and NaAlH4. The reactions employed molar BaTiO3/H ratios of up to 1.8 and temperatures near 600 °C. The air-stable reduced products were characterized by powder X-ray diffraction (PXRD), transmission electron microscopy, thermogravimetric analysis (TGA), and 1H magic angle spinning (MAS) NMR spectroscopy. PXRD showed the formation of cubic products—indicative of the formation of BaTiO3–xHx—except for NaH. Lattice parameters were in a range between 4.005 Å (for NaBH4-reduced samples) and 4.033 Å (for MgH2-reduced samples). With increasing H/BaTiO3 ratio, CaH2-, NaAlH4-, and MgH2-reduced samples were afforded as two-phase mixtures. TGA in air flow showed significant weight increases of up to 3.5% for reduced BaTiO3, suggesting that metal hydride reduction yielded oxyhydrides BaTiO3–xHx with x values larger than 0.5. 1H MAS NMR spectroscopy, however, revealed rather low concentrations of H and thus a simultaneous presence of O vacancies in reduced BaTiO3. It has to be concluded that hydride reduction of BaTiO3 yields complex disordered materials BaTiO3–xHy□(x–y) with x up to 0.6 and y in a range 0.04–0.25, rather than homogeneous solid solutions BaTiO3–xHx. Resonances of (hydridic) H substituting O in the cubic perovskite structure appear in the −2 to −60 ppm spectral region. The large range of negative chemical shifts and breadth of the signals signifies metallic conductivity and structural disorder in BaTiO3–xHy□(x–y). Sintering of BaTiO3–xHy□(x–y) in a gaseous H2 atmosphere resulted in more ordered materials, as indicated by considerably sharper 1H resonances.

Gas–Solid Reaction of Carbon Dioxide with Alanates

An empirical study of the gas–solid reaction of carbon dioxide (CO2) with alanates is presented. This investigation was triggered by reports of hazards related to the reaction of lithium aluminum hydride with carbon dioxide, together with the recent emergence of alanates as potential hydrogen storage materials. Furthermore, the reduction of CO2 by hydrides is an alternative to the conventional CO2 reduction employing hydrogen gas in combination with a catalyst. Experimentally this work was carried out by studying the decomposition of alanate samples in a carbon dioxide atmosphere with thermogravimetric and ex situ IR spectroscopic techniques. It is shown that alanates react with CO2 at atmospheric pressure in two distinct temperature regions, yielding methane, hydrogen gas, and metal oxides as the major products. The experimental findings allowed us to postulate a mechanism for the complex metal hydride reduction of CO2, involving alane as a highly reactive intermediate. It is suggested that nucleophilic attack of alane hydride ions onto the carbonyl carbon of CO2 leads to sequential formation of aluminum formate and methoxy species which get converted into methane and metal oxides as the final products.

Evaluating a sodium dispersion reagent for the Bouveault-Blanc reduction of esters.

A new sodium dispersion reagent has been evaluated for the reduction of esters. Na-D15, a sodium dispersion with sodium particle size of 5-15 μm, is a nonpyrophoric reagent that can be handled in air. In this study, a broad range of aliphatic ester substrates were reduced to primary alcohols by Na-D15/i-PrOH with good yields. The method compares favorably with modern metal hydride reductions and is much safer and efficient than the traditional Bouveault-Blanc reduction.

Some Recommended Procedures for Conversion of Carboxylic Acid and Its Derivatives to Aldehydes by Metal Hydride Reductions

Some recommended procedures for obtaining aldehydes from carboxylic acid itself and its derivatives, which have been developed in relatively recent years, are summarized. Such procedures should provide a new practical methodology to synthesize the desired aldehyde products in high yields. Key word : Metal Hydride, Reduction, Aldehyde, Carboxylic Acid

Spectrophotometric and thermodynamic studies of the charge transfer complexation of nitroimidazoles with chloranilic acid following metal hydride reduction

The spectrophotometric and thermodynamic properties of the charge-transfer (CT) complexation formed between reduced nitroimidazoles and chloranilic acid has been carried out. The possibility of room temperature reduction of metronidazole and tinidazole via hydride transfer using LiBH4 and NaBH4 was examined and the physicochemical properties of the resulting complex of the reduced nitroimidazoles with chloranilic acid were studied. The energy changes accompanying the formation of the CT band were studied over four temperature ranges of 30, 50, 60 and 80°C. The formation constants and molar absorptivities over these temperature ranges were obtained using the Benesi-Hildebrand plot. Other physicochemical parameters such as energy of transition, transition dipole, oscillator frequency and ionization energies and thermodynamic properties were estimated and related to the stability of the formed charge-transfer band. Reduction of nitroimidazoles with metal hydrides was completed at room temperature within 10 min with the formation of purple-coloured solution with chloranilic acid (CAA). The transition energies were of the order of 2.303 eV with ionization energy of 6.054 eV for the complexes. Variation existed in the oscillator frequency and transition dipole of the formed complexes with higher values obtained for MZ-CAA (metronidazole- chloranilic acid) complex. The Gibbs energy and entropy varied with the temperature and room temperature values favoured formation of stable complexes. The superiority of the metal hydride reduction was clearly evident from well defined physicochemical properties of the CT band and this is the first assessment of the utilization of the room temperature metal hydride reduction of nitroimidazoles. Key words: Nitroimidazoles, metal-hydride reduction, physico-chemical studies, thermodynamic studies.

Catalyst‐Controlled Diastereoselection in the Hydrogenation of Heterocycloalkyl Ketones

Abstractα‐Substituted chiral ketones that have small steric and electronic differences around the reaction sites are difficult substrates to reduce with high diastereoselectivity. Metal hydride reduction of 2‐(4‐benzoylmorpholinyl) phenyl ketone and 3‐(1‐tert‐butoxycarbonylpiperidinyl) phenyl ketone using sodium borohydride, zinc borohydride, and potassium tri‐sec‐butylborohydride as reducing agents affords the syn‐ and anti‐alcohols in a lower than 80:20 ratio. Hydrogenation of these ketones with a catalyst system of RuCl2(BIPHEP)(DMEN) and potassium tert‐butoxide in 2‐propanol results in the syn‐alcohols with ≥ 99:1 selectivity [BIPHEP=2,2′‐bis(diphenylphosphino)biphenyl, DMEN=N,N‐dimethylethylenediamine]. The marked difference in the diastereoselectivity suggests that the stereoselection in this hydrogenation is primarily regulated by the structure of the catalyst’s reaction field (“catalyst‐controlled diastereoselection”) but not the internal stereocontrol of the substrates. This chemistry is applied to the asymmetric hydrogenation through dynamic kinetic resolution with a RuCl2[(S)‐BINAP][(R)‐DMAPEN]/potassium tert‐butoxide catalyst [BINAP=2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl, DMAPEN=2‐dimethylamino‐1‐phenylethylamine]. A series of aryl heterocycloalkyl ketones has been converted to the alcohols in excellent diastereo‐ and enantioselectivities. The modes of catalyst‐controlled diastereoselection and enantioselection are interpreted by using transition‐state molecular models. (S,S)‐Reboxetine, a selective norepinephrine uptake inhibitor, was synthesized from one of product alcohols.

Vernonia Oil: Conversion to a Mixture of Tertiary Amines Including N,N‐Dimethyl‐(12S,13R)‐epoxy‐cis‐9‐octadecenyl Amine

AbstractVernonia galamensis is a new potential industrial oilseed crop found in tropical Africa. It is the source of a naturally epoxidized oil called vernonia oil (VO) which is extracted from the seed of the plant. In this study VO was used as the starting material for the synthesis of a mixture of amines, with the major product amine being N,N‐dimethyl‐(12S,13R)‐epoxy‐cis‐9‐octadecenyl amine. VO was transesterified via a base catalyzed methanolysis using sodium methoxide to yield VO methyl esters (VOME). Aminolysis of the VOME with dimethylamine as reagent and solvent under reflux conditions afforded the tertiary amides, with N,N‐ dimethyl‐(12S,13R)‐epoxy‐cis‐9‐octadecenyl amide as the major product. The mixture was then subjected to metal hydride reduction with lithium aluminum hydride in diethylether under reflux conditions to obtain the desired amine mixture including N,N‐dimethyl‐(12S,13R)‐epoxy‐cis‐9‐octadecenyl amine. Electron impact mass spectrometry was used to characterize the mixture of amines. Additionally, proton NMR, 13C NMR, and FTIR were used for characterization of N,N‐dimethyl‐(12S,13R)‐epoxy‐cis‐9‐octadecenyl amine. To further confirm the conversion of VO to the amines, the quaternary ammonium salts were synthesized and characterized by matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry.

ChemInform Abstract: Directive Effect of the 2- and 3-Axial Hydroxy Groups that Appeared in the Complex Metal Hydride Reduction of Cyclohexanones.

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Synthesis of Sodium (+)‐(12S,13R)‐Epoxy‐cis‐9‐octadecenyl Sulfonate from Vernonia Oil

AbstractA water‐soluble, foaming epoxyalkene sulfonate, sodium (+)‐(12S,13R)‐epoxy‐cis‐9‐octadecenyl sulfonate, was synthesized from vernonia oil (VO) by a series of simple reactions that include transesterification, metal hydride reduction, tosylation, and SN2 reactions. Conversion of VO into vernonia oil methyl esters (VOME) using sodium methoxide was quantitative. Subsequent reduction of VOME with lithium aluminum hydride yielded (+)‐(12S,13R)‐epoxy‐cis‐9‐octadecenol (94%), along with minor amounts of hexadecenol, octadecenol, cis‐9‐octadecenol, and cis‐9,12‐octadecandienol. The (+)‐(12S,13R)‐epoxy‐cis‐9‐octadecenol, was tosylated with p‐toluenesulfonyl chloride to give (+)‐(12S,13R)‐epoxy‐cis‐9‐octadecenyl tosylate at 96% yield. Iodination of the tosylate with sodium iodide and subsequent SN2 reaction with sodium sulfite afforded (+)‐(12S,13R)‐epoxy‐cis‐9‐octadecenyl sulfonate (63% yield). This study demonstrates the ability to produce an epoxyalkenyl sulfonate, belonging to a class of anionic surfactants, from VO without destroying the epoxy functionality in the (+)‐(12S,13R)‐epoxy‐cis‐9‐octadecenyl moiety of VO. The critical micelle concentration of the synthesized sulfonate was also determined.

Highly Effective Total Synthesis of Benzofuran Natural Product Egonol

Benzo[b]furan natural products isolated from the Styracaceae family such as Styrax japonicum, S. formosanus, S. obassia, S. macranthus and S. officinalis show variety of biological activities including insecticidal, fungicidal, antimicrobial, antisweet, antiproliferative, cytotoxic and antioxidant properties. Egonol, 5-(3-hydroxypropyl)-7-methoxy-2-(3,4-methylenedioxyphenyl)benzofuran, was first isolated in 1915 from the seed oil of Styrax japonicum and first synthesized by Kawai condensing an o-hydroxybenzaldehyde with an α-chlorophenylacetic acid and known to be an effective pyrethrum synergist. A number of total synthesis of egonol have been reported by using Sonogashira coupling, Lewis acid induced dehydrocyclization, dienylacetylene coupling with carbene complex, and palladium-catalyzed cross-coupling reaction. We report herein the most effective total synthesis of egonol (1, Figure 1) in 5 steps with 74% overall yield from vanillin by using Sonogashira coupling reaction. Vanillin (2) reacted with I2/Ag2SO4 in EtOH at room temperature to give iodovanillin 3 in 80% yield (Scheme 1). Sonogashira coupling of 3 with 3,4-methylenedioxyphenylacetylene (4), which was easily prepared from piperonal via Colvin rearrangement, by using Pd(PPh3)4/CuI/Et3N in DMF yielded benzofuran 5 in 95% yield through successive coupling and cyclization in one-step. Sonogashira coupling reactions were very sensitive to the haloaryl substituents as shown in Scheme 2. Bromovanillin 8 was not reactive with acetylene 4 in Sonogashira coupling reaction, and Wittig coupled bromide 9 and iodide 10 were also not reactive with 4 in coupling reaction, which indicated that the reaction sequences were very important in egonol synthesis and Sonogashira coupling should be done before Wittig reaction. Wittig reaction of 5 with (carbethoxymethylene)triphenylphosphorane produced carbethoxyethenylbenzofuran 6 in 99% yield, which was reduced to 7 in 99% yield by H2/PdC. Direct reduction of conjugated ester 6 to egonol 1 was performed by using LiAlH4 or LiBH4 as shown in Scheme 3. Partially reduced alcohol 11 with egonol and some other byproducts were formed in both cases and it was not easy to separate egonol from the alcohol 11 by column chromatography. Finally, reduction of ester 7 with DIBAL-H gave egonol (1) in 99% yield. Khan isolated a new egonol derivative, 5-(3-propanoyloxypropyl)-7-methoxy-2-(3,4-methylenedioxyphenyl)benzofuran (12), from Styrax obassia (Scheme 4). The newly found benzofuran 12 was easily prepared from our synthetic egonol 1 by esterification with propanoic acid using DCC in 99% yield and confirmed by NMR data with literature. In conclusion, the 5 steps reaction procedures including iodination, Sonogashira coupling, Wittig reaction, hydrogenation and metal hydride reduction produced egonol in

Synthesis of Proanthocyanidins. Part 1. The First Oxidative Formation of the Interflavanyl Bond in Procyanidins

A novel and efficient method for the oxidative condensation of tetra-O-methyl-3-oxocatechin 4 with tetra-O-methylcatechin is described. Treatment of a solution of 3 (2 equiv) and 4 (1 equiv) with silver tetrafluoroborate readily affords the phenolic per-O-methyl ethers of 3-oxocatechin(4-8)-catechin 18 and 19. Subsequent metal hydride reduction provides access to procyanidin B-3 analogues with the 3,4-cis diastereomers predominating.

2-Chloroquinazoline. Synthesis and reactivity of a versatile heterocyclic building block

Starting from 2,4-dichloroquinazoline, various methods for the selective removal of the 4-chloro substituent were tested, including catalytic hydrogenation, metal–halogen exchange, metal hydride reduction and reduction with tributyltin hydride—the latter both in a radical and in a Stille-type reaction. Amongst these, the most efficient method was found to be the Stille-type coupling. Furthermore, we have studied the reactivity of 2-chloroquinazoline and found it to act as a versatile building block for the direct introduction of the 2-quinazolinyl moiety.

New Pd-catalyzed selective reduction of carboxylic acids to aldehydes.

A catalyst generated in situ from palladium acetate and tricyclohexylphosphine efficiently catalyzes the reduction of carboxylic acids with sodium hypophosphite in the presence of pivalic anhydride to give aldehydes with high selectivity. The low cost and convenient handling of the reagents makes this process a valuable alternative to hydrogenations and metal hydride reductions.