Enantio-differentiating Hydrogenation Of Methyl Acetoacetate Research Articles

Enhanced Enantioselectivity Achieved at Low Hydrogen Pressure for the Asymmetric Hydrogenation of Methyl Acetoacetate over a Tartaric Acid NaBr-Modified Raney Nickel Catalyst: A Kinetic Study

Abstract To ensure high enantiopurity of the product, enantio-differentiating hydrogenation of methyl acetoacetate over a (R,R)-tartaric acid-modified Raney nickel catalyst is normally performed under elevated H2-pressure (∼10 MPa). In this study, higher enantioselectivity than previously reported for methyl acetoacetate was achieved (92% ee) under low H2-pressure of 0.42 MPa. Effects of reaction conditions on the enantioselectivity and hydrogenation rate were investigated using a low-pressure reaction system (<0.5 MPa of H2). It was found that impurities in the solvent greatly reduce the enantioselectivity of MAA. The low-pressure reaction system enabled a satisfactory kinetic approach. The reaction rate was well described by Langmuir-Hinshelwood formalism, verifying the previous assumption that the addition of adsorbed hydrogen to the substrate interacting with surface tartrate is a rate-determining step.

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.

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.

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.

Enantio-differentiating hydrogenation of methyl acetoacetate over modified Raney nickel catalysts prepared by two-step modifications

Two-step modifications of the Raney nickel were examined for the enantio-differentiating hydrogenation of methyl acetoacetate. Among the two-step modifications attempted in this study, the combination of ‘pre-modification with disodium tartrate and NaBr in water’ and ‘in-situ modification with tartaric acid’ resulted in the highest optical yield (84%). This modification process is a greener process than the conventional one carried out under weakly acidic conditions, because this process generated almost no Ni2+ ions. The pre-modification with the tartrate and NaBr preferentially eliminated Al3+ from the Raney nickel surface.

Studies of the effects of the modification conditions on the hydrogenation rate for the enantio-differentiating hydrogenation of methyl acetoacetate over a tartaric acid–NaBr-modified nickel catalyst

The effects of the modification conditions on the hydrogenation rate and the enantio-differentiating ability (e.d.a.) for the enantio-differentiating hydrogenation of methyl acetoacetate were studied over an (R, R)-tartaric acid–NaBr-in-situ-modified nickel catalyst. It was revealed that a tartaric acid modification increased the hydrogenation rate irrespective of the presence of the auxiliary modifier, NaBr. In the presence of the tartaric acid, NaBr would have two roles, i.e., Na+ activates the enantio-differentiating sites through the interaction with tartaric acid, and Br− deactivates both the enantio-differentiating sites and non-enantio-differentiating sites. The e.d.a. values and the hydrogenation rate would be determined by the combination of these effects of Na+ and Br−.

The Durability of the Enantio-Differentiating Ability of a Tartaric Acid–NaBr-Modified Reduced Nickel Catalyst Pre-Modified in Tetrahydrofuran

The enantio-differentiating hydrogenation of methyl acetoacetate was carried out over a (R,R)-tartaric acid–NaBr-modified reduced Ni catalyst. The reduced Ni was pre-modified in a tetrahydrofuran solution of tartaric acid and NaBr at atmospheric pressure or at a high hydrogen pressure. The enantio-differentiating ability of 70–90% was maintained during 40 runs over the reduced nickel catalyst pre-modified at 9 MPa hydrogen and 373 K. The results indicated that the durability of a high enantio-differentiating ability of an in-situ-modified catalyst would be attributed to the modification conditions at the high hydrogen pressure of 9 MPa and the high temperature of 373 K in the autoclave.

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.

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 tartaric acid-modified nickel catalysts: effects of preparation method of supported nickel on activity and selectivity of catalysts

Enantio-differentiating hydrogenation of methyl acetoacetate was carried out over supported nickel catalysts modified by (R,R)-tartaric acid and NaBr. The types of support and the preparation methods affected the enantiomeric excess of the obtained product, methyl (R)-3-hydroxybutyrate. Nickel supported on aluminum oxide gave the best enantio-selectivity. Silica-supported catalysts showed lower selectivities. In particular, precipitation deposition of nickel on silica forms nickel silicate, which was difficult to be reduced and constituted a lattice defect of nickel surface. Even reduced nickel surface could be contaminated by silicon in nickel silicate. This defect and the surface contamination may disrupt the arranged adsorption of tartaric acid and reduce the enantio-selectivity of the catalysts.

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.

High durability of asymmetrically modified nickel catalysts prepared by in situ modification

The in situ modification of a reduced Ni catalyst at the first run showed a high durability for the repeated use with high optical yields in the enantio-differentiating hydrogenation of methyl acetoacetate. Reduced Ni from Ni oxide and fine Ni powder were the best materials in comparison with Raney Ni. For attaining high optical yields and high durability, in situ modification and a Ni surface suitable for the enantio-differentiating hydrogenation are necessary. One of the reasons for the low durability of the conventional pre-modified Ni with repeated use would be the desorption of tartaric acid from the catalyst surface during the hydrogenation reaction.

Highly Durable Enantio-Differentiating Nickel Catalyst for Repeated Use for the Hydrogenation of Methyl Acetoacetate

Abstract The enantio-differentiating hydrogenation of methyl acetoacetate was repeated 30 times over a fine Ni powder catalyst while modifiers (optically active tartaric acid and NaBr) were directly added to the reaction media only in the first run. Over 80% optical yields were attained for the repeated runs. The addition of sodium 2-ethylhexanoate increased the optical yields in the subsequent runs. The very simple and highly durable enantio-differentiating nickel catalyst for repeated use was developed by an in situ modification.

Application of an in situ modification of nickel catalysts to the enantio-differentiating hydrogenation of methyl acetoacetate

In situ modification (( R, R)-tartaric acid and NaBr were directly added to the reaction media) of fine Ni powder (FNiP) and reduced Ni catalysts was applied to the enantio-differentiating hydrogenation of methyl acetoacetate (MAA). The high optical yield of 89% was attained by the reduced Ni catalyst. This is the highest value reported so far for the hydrogenation of methyl acetoacetate using the in situ modification. The addition of a small amount of NaBr to the reaction media increased both the optical yield and hydrogenation rate, while the hydrogenation rate decreased with the addition of NaBr to the modification solution for the conventional modification method. NaBr added to the reaction media for the in situ modification would have both of the following roles: (i) Na + increased the optical yield and the hydrogenation rate; and (ii) Br − increased the optical yield and decreased the hydrogenation rate.

Enantio-differentiating hydrogenation of methyl acetoacetate over tartaric acid-NaBr-modified supported nickel catalyst prepared from nickel acetylacetonate

Supported nickel catalysts were prepared from nickel acetylacetonate, and then modified in a solution containing tartaric acid and sodium bromide. The enantio-differentiating hydrogenation of methyl acetoacetate was carried out over this catalyst. The effects of the preparation variables of the supported nickel catalysts on the optical yield and the effects of the conditions for the nickel surface modification on the optical yield were examined. The catalysts were also characterized by XRD and TEM. The maximal optical yield of 87% was attained when crystallized α-alumina (sumico rundum) was used as a support.

Enantio-differentiating hydrogenation of methyl acetoacetate over fine nickel powder with in situ modification

Enantio-differentiating hydrogenation of methyl acetoacetate (MAA) was carried out using fine nickel powder (FNiP) by adding tartaric acid (TA) and sodium salts to the reaction media (in situ modification) instead of using a conventionally modified nickel catalyst. This catalyst prepared by the in situ modification gave an optical yield up to 79%.

Enantio-differentiating Hydrogenation of Methyl Acetoacetate over Asymmetrically Modified Supported Nickel Catalyst Prepared from Nickel Acetylacetonate

Abstract Various supported nickel catalysts were prepared from nickel acetylacetonate in a solvent-free condition, and then these catalysts were modified in the solution containing tartaric acid and NaBr. Enantio-differentiating hydrogenation of methyl acetoacetate was carried out over the resulting tartaric acid-NaBr-modified supported Ni catalysts. Maximal optical yield 86% was attained when zeolite was used as a support.