Hydrogenation Of Methyl Acetoacetate Research Articles

Stereoselective synthesis of optical isomers of ethyl 4-chloro-3-hydroxybutyrate in a microfluidic chip reactor

Ethyl (R)-4-chloro-3-hydroxybutyrate ((R)-CHBE) is a versatile fine chemistry intermediate. It is used as a precursor in the synthesis of several pharmacologically valuable products, including L-carnitine. It is usually produced by means of stereoselective biotechnology methods in enzymatic reactions. An alternative preparation strategy towards ethyl (R)-4-chloro-3-hydroxybutyrate is based on the asymmetric hydrogenation of ethyl 4-chloro-acetoacetate (ECAA) to the optically pure product ((R)-CHBE) over ((S)-Ru-BINAP) catalytic complex. The reaction conditions were optimised first using (R)-Ru-BINAP yielding the (S)-CHBE isomer. All reactions were performed under continuous regime in a microfluidic chip reactor. Three different solvent phases were employed. The methanol/water phase, the ethanol/water phase, and the [N8,222][Tf2N]/methanol/water phase. The attained conversions were total in all cases already at 408 K. The parameter of enantioselectivity ee was 99.4% towards the (S)-CHBE for the system in which (R)-Ru-BINAP was accommodated in [N8,222][Tf2N]/methanol/water phase. In the case of methanol/water experiment the ee parameter reached 92.5%. For ethanol/water ee was 91.8%. The (R)-CHBE isomer over (S)-Ru-BINAP was obtained with ee = 99.3% in the [N8,222][Tf2N]/methanol/water phase at 408 K. For the reactions leading to (S)-CHBE apparent activation energies were evaluated. They were similar for MeOH/water and EtOH/water (110.5 and 110.7 kJ.mol−1). The apparent activation energies corresponding with the [N8,222][Tf2N]/MeOH/water system were much higher (of about 90 kJ.mol−1) reaching the level of 200 kJ.mol−1. The impact of the molecular structure of the main reactant was negligible as appeared from the comparison with hydrogenation of methylacetoacetate (MAA, ~ 200 kJ.mol−1). The effect of the presence of the [N8,222][Tf2N] ionic liquid on the sum of the activation energy dominated. The effectiveness of the enantioselective synthesis was additionally assessed by nuclear magnetic resonance employing the method of enantioselective complexation of the chiral compound with a chiral solvating agent.

Adsorption of Methyl Acetoacetate at Ni{111}: Experiment and Theory

The hydrogenation of methyl acetoacetate (MAA) over modified Ni catalysts is one of the most important and best studied reactions in heterogeneous enantioselective catalysis. Yet, very little molecular-level information is available on the adsorption complex of the reactant. Here, we report on a combined experimental and theoretical study of MAA adsorption on Ni{111}. XPS shows that the chemisorbed layer is stable up to 250 K; above 250 K, decomposition sets in. In ultra-high-vacuum conditions, multilayers grow below 150 K. DFT modeling predicts a deprotonated enol species with bidentate coordination on the flat Ni{111} surface. The presence of adatoms on the surface leads to stronger MAA adsorption in comparison with the flat surface, whereby the stabilization energy is high enough for MAA to drive the formation of adatom defects at Ni{111}, assuming the adatoms come from steps. Comparison of experimental XPS and NEXAFS data with theoretical modeling, however, identifies the bidentate deprotonated enol o...

Enantio-differentiating hydrogenation of methyl acetoacetate over tartaric acid modified Ni catalyst at atmospheric pressure of hydrogen assisted by hydrogen transfer reaction

The enantio-differentiating hydrogenation of methyl acetoacetate was carried out under the atmospheric pressure of hydrogen (gauge pressure: 0 MPa) assisted by hydrogen transfer from 2-propanol. It was revealed that the tartaric acid-NaBr-modified supported nickel catalyst, especially Ni/CeO2, produced a higher enantioselectivity than the modified Raney nickel catalyst under the atmospheric pressure of hydrogen. Catalyst preparation and hydrogenation conditions for the hydrogenation over the modified Ni/CeO2 were studied. The Ni/CeO2 prepared by calcination at 773 K and reduction at 773 K gave the best result. The enantioselectivity of 64 % (22 % conversion) was attained under the atmospheric pressure of hydrogen at 323 K assisted the by hydrogen transfer from the solvent.

Ligand-Acceleration by a Chiral Modifier in the Enantioselective Hydrogenation of Methyl Acetoacetate on a Raney Nickel Catalyst: Effect of a Modifier Configuration

Abstract Reaction rate and enantioselectivity of asymmetric hydrogenation of methyl acetoacetate were studied over Raney nickel catalysts modified with (R,R)-tartaric acid, malic acid, or succinic acid to reveal the impacts of the modifier configuration. Catalysts comodified with two different acids were also examined to confirm the conclusions. From analysis of the enantiomer ratio of the hydrogenation product and initial reaction rate, tartaric acid (TA) was found to have dual functions as the modifier during the hydrogenation; effective suppression of the racemic catalysis on bare Ni surface and extensive enantiodifferentiating ligand acceleration by adsorbed TA. It was demonstrated that each adsorbed chiral modifier molecule independently takes part in the enantiospecific hydrogenation.

Theoretical interpretation of the role of the ionic liquid phase in the (R)-Ru-BINAP catalyzed hydrogenation of methylacetoacetate

Recently, the work focusing on the role of alkyl chain length in the N[R,222][Tf2N] ionic liquids and its reflection in the kinetic parameters of stereoselective hydrogenation of methylacetoacetate over (R)-[RuCl(binap)(p-cymene)]Cl complex was reported. Irregular trends in the principle parameter of enantioselectivity were observed. Here, a possible theoretical explanation of such irregular trends elucidated with the help of molecular simulations methods is presented. A stepwise approach is proposed for evaluating the energetically most stable conformers of a series of individual N[R,222][Tf2N] for the interpretation of selectivity-structure effects observed experimentally. Initially, Monte Carlo molecular mechanics was used followed by a semi-empirical PM3 method to elucidate also the characteristic thermodynamic functions of state and theoretical molecular spectra. The density functional theory was finally applied. The specific absolute entropy data revealed that due to the partition of the cation and anion twisted closer approach the ionic liquids N[8,222][Tf2N] and N[12,222][Tf2N] may stabilize the structures of the (R)-[RuCl(binap)(p-cymene)]Cl complex.

Enantio-differentiating hydrogenation of methyl acetoacetate over tartaric acid-NaBr-modified Raney nickel catalyst under a low hydrogen pressure

The enantio-differentiating hydrogenation of methyl acetoacetate was carried out over a (R,R)-tartaric acid-NaBr-modified Raney nickel catalyst under low hydrogen pressure. The rate of the supply of hydrogen on the catalyst surface would be an important factor for attaining high enantioselectivity, especially under low hydrogen pressure. A maximum enantioselectivity of 82% was attained under an initial hydrogen pressure of 0.2 MPa at 333 K with a high stirring rate.

ChemInform Abstract: The Enantioselective Hydrogenation of Methyl Acetoacetate Over Supported Nickel Catalysts. Part 1. The Modification Procedure.

ChemInform Abstract: The Enantioselective Hydrogenation of Methyl Acetoacetate Over Supported Nickel Catalysts. Part 1. The Modification Procedure.

ChemInform Abstract: Role of Catalyst Activation in the Enantioselective Hydrogenation of Methyl Acetoacetate Over Silica-Supported Nickel Catalysts

ChemInform Abstract: Role of Catalyst Activation in the Enantioselective Hydrogenation of Methyl Acetoacetate Over Silica-Supported Nickel Catalysts

Propionate Analogues of Zearalenone Bind to Hsp90

By replacement of an acetate with propionate through organic synthesis a range of zearalenone analogues were prepared. As key steps in the synthesis of the analogues we used the Noyori hydrogenation of methyl acetoacetate followed by Frater alkylation of the enantiomeric 3-hydroxybutyrates. This converted the second acetate to a propionate. Through the derived alkyne, chain extension led to 3-methylundec-10-en-2-ol derivatives. These were condensed with 2,4-dimethoxy-6-vinylbenzoic acid. Ring-closing metathesis of the obtained esters led to macrolactones, which were deproteced to give the zearalenone analogues. Several of the analogues showed cytotoxicity against the L929 mouse fibroblast cell line comparable to zearalenone (9 microM) itself. In the thermal-shift assay, two analogues 35 and ent-35 displayed stronger binding than the natural product geldanamycin to the chaperone Hsp90.

Enantio-Differentiating Hydrogenation of Methyl acetoacetate over Asymmetrically Modified Reduced Nickel Catalysts: The Effects of the Coverage of the Modifiers on the Enantio-Differentiating Ability

In order to investigate the factors for attaining a high enantio-differentiating ability (e.d.a.) for the enantio-differentiating hydrogenation of methyl acetoacetate over a tartaric acid pre-modified reduced nickel catalyst, the relation between the coverage of the modifiers on a nickel surface and e.d.a. was investigated. A Ni773 or Ni1373 (the reduced nickel catalyst prepared from a nickel oxide which was calcined at 773 K or 1,373 K, respectively) was used for the preparation of a modified catalyst. It was revealed that the tartaric acid coverage of about 0.2, the appropriate surface for the enantio-differentiation, such as the conditioned surface of Ni1373, and the inhibition of the hydrogenation on non-enantio differentiating sites by Br−, were all important for attaining a high e.d.a. This would be interpreted that only when tartaric acid is adsorbed as an isolated molecule on the appropriate surface, the acid exerts its intrinsic e.d.a.

Effects of Sodium Acetate and Residual Aluminum on the Hydrogenation Rate, Optical Yield and Catalyst Durability for the Enantio-Differentiating Hydrogenation of Methyl Acetoacetate Over Tartaric Acid-Modified Raney Nickel Catalysts

The effects of Na acetate and residual aluminum on the hydrogenation rate, optical yield and catalyst durability for the enantio-differentiating hydrogenation of methyl acetoacetate were studied over tartaric acid-modified Raney nickel catalysts with the in situ modification. There was an optimal Na acetate amount at which the highest optical yield and high hydrogenation rate were achieved. The addition of Na acetate in the repeat use could improve the catalyst durability significantly. The amount of the residual aluminum in Raney nickel catalysts also played an important role in this catalyst system. The highest optical yield of 61.6% was achieved over the improved T-1 RNi catalyst. Compared with previous literatures, this is the best result for the enantio-differentiating hydrogenation of methyl acetoacetate over in situ modified Raney nickel catalysts.

The effect of chiral solvent and various kinds of chiral organic salts on the asymmetric hydrogenation of methyl acetoacetate over an improved tartaric acid modified Raney nickel catalyst

The influence of the chiral ionic liquid (CIL) on the asymmetric hydrogenation of methyl acetoacetate (MAA) over an improved tartaric acid-modified Raney nickel catalyst using it as reaction medium was investigated. At the same time, we also studied the effect of up to eight chiral ionic salts, and ionic liquids on this reaction using these ionic salts as co-catalyst. Although no obviously improved optical yields were gained, the possible cause has been given.

Kinetic Studies of Asymmetric Hydrogenation of Methylacetoacetate in Different Solvents

Kinetic Studies of Asymmetric Hydrogenation of Methylacetoacetate in Different Solvents

Studies of the effect of pivalic acid on the hydrogenation rate and the enantio-differentiating ability for the hydrogenation of 2-octanone over a tartaric acid-NaBr-modified nickel catalyst

The effects of the addition of pivalic acid to the reaction media on the hydrogenation rate and the enantio-differentiating ability (e.d.a.) for the hydrogenation of 2-octanone were studied over an (R,R)-tartaric acid-NaBr-in-situ-modified nickel catalyst. It was revealed that the modification with both tartaric acid and NaBr was necessary for increasing the e.d.a. by the addition of pivalic acid to the reaction media. The role of pivalic acid in the enantio-differentiating hydrogenation of 2-octanone was different from that of acetic acid in the hydrogenation of methyl acetoacetate.

Role of Acetic Acid Added to the Reaction Media for the Enantio-differentiating Hydrogenation of Methyl Acetoacetate Over a Tartaric Acid-modified Nickel Catalyst

The role of acetic acid added to the reaction media for the enantio-differentiating hydrogenation of methyl acetoacetate over a (R,R)-tartaric acid-in-situ-modified nickel catalyst was studied from the viewpoint of the hydrogenation rate during repeated runs. The hydrogenation of methyl acetoacetate on the “enantio-differentiating sites” of a tartaric acid-modified nickel catalyst was specifically accelerated by the acetic acid added to the reaction media to increase the enantio-differentiating ability of the catalyst. In order to increase the enantio-differentiating ability, the addition of acetic acid to the reaction media was required in each run during the repeated use of the catalyst.

Enantio-differentiating hydrogenation of methyl acetoacetate over reduced nickel catalysts pre-modified in methanol

The enantio-differentiating hydrogenation of methyl acetoacetate was carried out over a (R,R)-tartaric acid-NaBr-modified reduced Ni catalyst. Reduced Ni was pre-modified in a methanol solution of tartaric acid and NaBr. It was revealed that the pre-treatment of methanol by molecular sieves was essential for attaining the high enantio-differentiating ability of 80–90% and high durability during repeated uses of the recovered catalyst.

Study of the properties of nickel oxide and nickel as precursors for the tartaric acid-NaBr-modified nickel catalyst

Nickel oxide was prepared by the decomposition of nickel hydroxide and then the nickel oxide was reduced to form the nickel catalyst. The properties of the nickel oxide and the reduced nickel were studied in relation to the enantio-differentiating ability (e.d.a.) of a tartaric acid-NaBr-modified reduced nickel catalyst. The modified nickel catalyst prepared from nickel oxide with less non-stoichiometric oxygen produced a high e.d.a. for the hydrogenation of methyl acetoacetate. The high crystallinity of the nickel oxide and the resultant nickel would be required to attain a high e.d.a.

Asymmetrically modified bimetallic catalyst for the enantio-differentiating hydrogenation of methyl acetoacetate

The effects of addition of a second metal as promoter to (R,R)-tartaric acid-NaBr-modified Ni catalyst were investigated. The addition of Pd increased the enantioselectivity for the hydrogenation of methyl acetoacetate.

Enantio-differentiating hydrogenation of methyl acetoacetate over modified nickel catalysts: effects of nickel dispersion on the enantio-selectivity of catalysts

Enantio-differentiating hydrogenation of methyl acetoacetate was performed over the supported nickel catalysts modified by the solution of (R,R)-tartaric acid or (S)-malic acid and NaBr. The reduction temperature of supported nickel was the most important factor determining the enantio-selectivity of catalysts. The reduction temperature changed the nickel dispersion, by which the quantity and coverage of modifier adsorption were varied. The enantio-selectivity of modifiers both (R,R)-tartaric acid and (S) -malic acid were compared at various reduction temperatures. (R,R)-tartaric acid with two hydroxyl groups in a molecule showed an optimum coverage on the nickel surface that gave the maximum ee value. The maximum ee value was 72% at the reduction temperature of 973 K. In contrast, (S)-malic acid with one hydroxyl group in a molecule showed a monotonous decrease in ee and decreasing amounts of adsorbed modifier with increasing reduction temperatures.

Enantio-differentiating hydrogenation of methyl acetoacetate over asymmetrically modified reduced nickel catalysts The effects of the nickel sources on the enantio-differentiating ability

Abstract The enantio-differentiating hydrogenation of methyl acetoacetate was carried out over a tartaric acid–NaBr-modified reduced nickel catalyst. Nickel hydroxide and nickel carbonate were used as the precursors of the nickel oxide. They were calcined to nickel oxides, then reduced to nickel metal (reduced nickel catalyst). It was revealed that the calcination temperature of the precursors was an important variable for attaining the high enantio-differentiating ability (e.d.a.) of the catalyst. The nickel surface with the least lattice defects would be appropriate for attaining a high e.d.a.