Over 100 years of vitamin E: An overview from synthesis and formulation to application in animal nutrition.

The groundbreaking discovery of vitamin E by Evans and Bishop in 1922 was an important milestone in vitamin research, inspiring further investigation into its crucial role in both human and animal nutrition. Supplementing vitamin E has been proved to enhance multiple key physiological systems such as the reproductive, circulatory, nervous and muscular systems. As the main antioxidant in the blood and on a cellular level, vitamin E maintains the integrity of both cellular and vascular membranes and thus modulates the immune system. This overview showcases important and innovative routes for synthesizing vitamin E on a commercial scale, provides cutting-edge insights into formulation concepts for successful product form development and emphasizes the importance and future of vitamin E in healthy and sustainable animal nutrition.

A Decade of Successful Collaborations in Nutritional Compound Process Research and Development.

Collaborations between academia and industry are vital for modern industrial research and development projects, combining the best of both worlds to develop sustainable chemical processes. Herein we summarize a number of successful cooperations between DSM Nutritional Products and Swiss academic institutions that have been carried out over approximately the past decade. A wide variety of reactions and processes have been investigated with experts located in Switzerland. New synthetic routes, chemical transformations and reactor concepts have been developed to produce industrially relevant compounds. Additionally the scope of known catalytic systems has been probed and new catalysts showing improved selectivity have been designed, synthesized and tested. We describe how the research was supported by DSM, the parallel in-house investigations and also how the projects were continued and further developed.

From Sugars to Nutritional Products - Active Ingredients.

A modern trend to carbon dioxide neutral production processes is based on renewable raw materials derived from sugars. Herein, an overview on modern approaches to fine chemicals for the nutritional industry is presented. In comparison to the traditional fossil-fuel-based processes the development of sustainable alternative transformations is necessary to enable the full potential of the new sustainable feedstocks.

Organophotocatalytic Aerobic Oxygenation of Phenols in a Visible-Light Continuous-Flow Photoreactor.

A mild photocatalytic phenol oxygenation enabled by a continuous-flow photoreactor using visible light and pressurized air is described herein. Products for wide-ranging applications, including the synthesis of vitamins, were obtained in high yields by precisely controlling principal process parameters. The reactor design permits low organophotocatalyst loadings to generate singlet oxygen. It is anticipated that the efficient aerobic phenol oxygenation to benzoquinones and p-quinols contributes to sustainable synthesis.

The impact of (E/Z)-isomerization and aggregation on the color of rhodoxanthin formulations for food and beverages.

Rhodoxanthin is a scarcely explored carotenoid with an extraordinarily large chromophore and high potential to function as red pigment. We report broad ranges of color shades accessible with rhodoxanthin across an unprecedented wide range of (E/Z)-ratios by thermal (E/Z)-isomerization, lyotropic aggregation, and two different formulation techniques, covering shares of the (all-E)-configured isomer of 19-91%. At (E/Z)-ratios of 75 and 23%, rhodoxanthin (E/Z)-isomer mixtures in acetone revealed color hues (CIE-h°) ranging from 20-44° to 36-54°. Lyotropic aggregation of rhodoxanthin (E/Z)-isomer mixtures in acetone/water yielded red (CIE-h° = 29°) to purple (-7°) and red-orange (44°) to pink (9°) color hues at (all-E)-proportions of 73 and 20%, respectively. Red and purple color hues were produced by micronization using solvent-based emulsification (CIE-h° = 33-37°) and high-performance wet-milling (-6°). The presented technological strategies for formulating nature-identical rhodoxanthin into water-dispersible forms showed its potential as promising pigment for imparting red, pink, and purple color to foods and beverages.

Kinetic and Thermodynamic Study of the Thermally Induced (E/Z)-Isomerization of the retro-Carotenoid Rhodoxanthin.

The hitherto scarcely investigated retro-carotenoid rhodoxanthin possesses high potential for coloration in the food and beverage industry using technofunctional formulations prepared thereof. Hence, we studied (E/Z)-isomerization pathways of rhodoxanthin, including seven (E/Z)-isomers comprising (Z)-configured double bonds at unusual exocyclic and inner polyene chain positions. A mathematical approach was developed to deduce kinetic and thermodynamic parameters of six parallel equilibrium reactions interconnecting (all-E)-rhodoxanthin with mono-, di-, and tri-(Z)-isomers using multiresponse modeling. At 40-70 °C in ethyl acetate, reaction rate constants regarding the rotation from (all-E)- to (6Z)-rhodoxanthin were 11-14 times higher than those of the common (E/Z)-isomerization reaction at C-13,14 of the non-retro-structured carotenoid canthaxanthin. Moreover, the equilibrium reaction between (all-E)- and (6Z)-rhodoxanthin was strongly product favored as indicated by negative Gibbs energies (-1.6 to -2.2 kJ mol-1), which is unusual for carotenoids within the studied temperatures. Overall, this study provides novel insights into structure-related dependencies of (E/Z)-isomerization reaction kinetics and thermodynamics of polyenes.

Catalyst Repurposing Sequential Catalysis by Harnessing Regenerated Prolinamide Organocatalysts as Transfer Hydrogenation Ligands.

A catalyst repurposing strategy based on a sequential aldol addition and transfer hydrogenation giving access to enantiomerically enriched α-hydroxy-γ-butyrolactones is described. The combination of a stereoselective, organocatalytic step, followed by an efficient catalytic aldehyde reduction induces an ensuing lactonization to provide enantioenriched butyrolactones from readily available starting materials. By capitalizing from the capacity of prolineamides to act as both an organocatalyst and a transfer hydrogenation ligand, catalyst repurposing allowed the development of an operationally simple, economic, and efficient sequential catalysis approach.

Validation and extension of the gas-phase superacidity scale.

RATIONALE: In recent years it has become increasingly evident that the previously reported experimental gas-phase acidity (GA) values of several strong acids differ markedly from the corresponding high-level computational values. In this work, the superacidic part of the current gas-phase acidity scale was validated and extended. METHODS: For that, the strongly acidic section of the gas-phase acidity scale was remeasured using the equilibrium Fourier transform ion cyclotron resonance (FTICR-MS) method, adding new compounds and introducing methodological changes. In particular, a novel approach for anchoring the scale was used - the results were anchored to the computational (W1BD) GA values of trifluoromethanesulfonic acid and bis(fluorosulfonyl)imide (291.3 and 286.2 kcal mol-1 , respectively). RESULTS: The newly measured section consists of 20 gas-phase superacids and its consistency standard deviation is 0.2 kcal mol-1 , indicating good consistency. In contrast to the previously reported experimental gas-phase acidities for a number of important superacids, the current results are consistent with high-level theoretical GA values. Structure-acidity relationships based on the current results as well as available MeCN and DCE acidity data were described and explained. CONCLUSIONS: The introduced methodological innovations were found to be adequate and strong evidence is presented in support of the current GA values of the strong acids.

Sonochemical preparation of alumina-spheres loaded with Pd nanoparticles for 2-butyne-1,4-diol semi-hydrogenation in a continuous flow microwave reactor.

A novel protocol for microwave-assisted alkyne semi-hydrogenation under heterogeneous catalysis in a continuous flow reactor is reported herein. This challenging task has been accomplished using a multifaceted strategy which includes the ultrasound-assisted preparation of Pd nanoparticles (average Ø 3.0 ± 0.5 nm) that were synthesized on the µ-metric pores of sintered alumina spheres (Ø 0.8 mm) and a continuous flow reaction under H2 (flow rate 7.5 mL min-1) in a microwave reactor (counter-pressure 4.5 bar). The semi-hydrogenation of 2-butyne-1,4-diol in ethanol was chosen as a model reaction for the purposes of optimization. The high catalyst efficiency of the process, in spite of the low Pd loading (Pd content 111.15 mg kg-1 from ICP-MS), is due to the pivotal role of ultrasound in generating a regular distribution of Pd nanoparticles across the entire support surface. Ultrasound promotes the nucleation, rather than the growth, of crystalline Pd nanoparticles and does so within a particularly narrow Gaussian size distribution. High conversion (>90.5%) and selectivity to (Z)-2-butene-1,4-diol (95.20%) have been achieved at an alkyne solution flow rate of 10 mL min-1. The lead-free, alumina-stabilized Pd catalyst was fully characterized by TEM, HR-TEM, EDX, IR, XRPD and AAS. Highly dispersed Pd nanoparticles have proven themselves to be stable under the reaction conditions employed. The application of the method is subject to the dielectric properties of substrates and solvents, and is therefore hardly applicable to apolar alkynes. Considering the small volume of the reaction chamber, microwave-assisted flow hydrogenation has proven itself to be a safe procedure and one that is suitable for further scaling up to industrial application.

Selective Hydrogenation of α,ß-Unsaturated Aldehydes and Ketones by Air-Stable Ruthenium NNS Complexes.

The selective hydrogenation of the carbonyl functionality of α,ß-unsaturated aldehydes and ketones is catalysed by ruthenium dichloride complexes bearing a tridentate NNS ligand as well as triphenylphosphine. The tridentate ligand backbone is flexible, as evidenced by the equilibrium observed in solution between the cis- and trans-isomers of the dichloride precatalysts, as well as crystal structures of several of these complexes. The complexes are activated by base in the presence of hydrogen and readily hydrogenate carbonyl functionalities under mild conditions. Despite the activation by base, side reactions are negligible, even for aldehyde substrates, because of the low amount of base. Thus, the corresponding allylic alcohols can be isolated in very good yields on a 10-25 mmol scale. Turnover numbers up to 200 000 were achieved.

Ultrasonically improved semi-hydrogenation of alkynes to (Z-)alkenes over novel lead-free Pd/Boehmite catalysts.

This paper reports the application of ultrasound in the semi-hydrogenation of alkynes over two novel Pd/Boehmite catalysts. The semi-hydrogenations of phenylacetylene, diphenylacetylene and 2-butyne-1,4-diol have either been investigated in an ultrasonic bath under atmospheric hydrogen pressure, or in an ultrasonic horn reactor under 0.1-0.5MPa hydrogen pressure. Alkyne hydrogenation was suppressed by sonication under atmospheric hydrogen pressure, but promoted by sonication under 0.1MPa of hydrogen pressure. Sonication increased selectivity towards the semi-hydrogenated products in both cases. Catalyst loading, hydrogen pressure, temperature and the presence of quinoline, all impacted on hydrogenation rate, activity and selectivity to semi-hydrogenated products. Palladium leaching from the catalyst was evaluated in ethanol and hexane both under plain stirring and sonication.

New trends in (heterogeneous) catalysis for the fine chemicals industry.

New catalytic methods and modern trends for the synthesis of fine chemicals, especially vitamins, carotenoids, flavoring and fragrance compounds are presented. In particular the application of heterogeneous catalysis in the formation and production on industrial scale of these classes of organic compounds will be highlighted and its use in the replacement of former stoichiometric processes.

Total synthesis of (R,R,R)-α-tocopherol through asymmetric Cu-catalyzed 1,4-addition.

By introducing a disposable activating substituent at C-3, the asymmetric 1,4-addition to a notoriously unreactive 2-substituted chromenone was achieved with high levels of (2R)-stereoselectivity in the presence of a chiral Cu(I)-phosphoramidite complex as a catalyst. This paved the way for an efficient and conceptually novel synthesis of (R,R,R)-α-tocopherol from readily available starting materials.

Thermal behavior of pinan-2-ol and linalool.

Linalool is an important intermediate for syntheses of isoprenoid fragrance compounds and vitamins A and E. One process option for its production is the thermal gas-phase isomerization of cis- and trans-pinan-2-ol. Investigations of this reaction were performed in a flow-type apparatus in a temperature range from 350-600 °C and a residence time range of 0.6-0.8 s. Rearrangement of the bicyclic alcohol led to linalool, plinols arising from consecutive reactions of linalool and other side products. Effects of residence time, temperature, surface-to-volume-ratio, carrier gas, and the presence of additives on yield and selectivity were studied. Furthermore, the effects of such parameters on ene-cyclization of linalool affording plinols were investigated. Results indicate that manipulation of the reaction in order to affect selectivity is difficult due to the large free path length to other molecules in the gas phase. However, conditions have been identified allowing one to increase the selectivity and the yield of linalool throughout pyrolysis of pinan-2-ol.

One hundred years of vitamins-a success story of the natural sciences.

The discovery of vitamins as essential factors in the diet was a scientific breakthrough that changed the world. Diseases such as scurvy, rickets, beriberi, and pellagra were recognized to be curable with an adequate diet. These diseases had been prevalent for thousands of years and had a dramatic impact on societies as well as on economic development. This Review highlights the key achievements in the development of industrial processes for the manufacture of eight of the 13 vitamins.

Large-scale production of bioactive ingredients as supplements for healthy human and animal nutrition.

In this review, synthetic strategies and the development of environmentally benign methods for the production of economically important vitamins, carotenoids, and nutraceuticals used as food and feed supplements are illustrated by selected examples. The application of efficient catalytic transformations in multi-step chemical syntheses of such natural products enables technically feasible and cost-effective processes. For the preparation of fat-soluble (isoprenoid) vitamins A and E and the water-soluble vitamin (+)-biotin, homogeneous metal catalysis, including enantioselective transformations, heterogeneous and enzymatic catalysis serve as key methodologies. In the area of carotenoids, general building concepts and coupling methods for the total synthesis of beta-carotene and astaxanthin are discussed. Biotechnological methods and isolation from natural sources are also employed successfully, as exemplified for the xanthophyll lutein and the antioxidant (-)-epigallocatechin gallate. Lastly, key steps of the chemical synthesis of the polyphenol resveratrol are highlighted.

Reusable task-specific ionic liquids for a clean ε-caprolactam synthesis under mild conditions.

Brønsted-acidic ionic liquids that bear a sulfonic acid group, known as Forbes acids, show a good catalytic activity for the Beckmann rearrangement, used to prepare ε-caprolactam, which is a precursor of Nylon 6. The activity essentially stems from the acidity of the sulfonic acid group. Although these task specific ionic liquids suffer from a high viscosity, this drawback can be circumvented at higher temperatures. A combination of the hydrogen sulfate anion and the sulfonic acid group of the cation is needed to obtain the rearrangement product rapidly under mild conditions. When using an excess of ionic liquid, we postulate that the internal pressure of the ionic medium, generated by the high viscosity and the high number of hydrogen-bonds, is strong enough to contribute to a decrease of the thermodynamic barrier. In accordance with the "Principles of Green Chemistry," we have developed a synthesis of ε-caprolactam that requires no additional chemicals except cyclohexanone oxime and the reusable TSIL.

Online ESI-MS analysis of reactions under high pressure.

A new approach for real-time mass spectrometric analysis and identification of intermediates in confined, pressurized vessels is presented. The high-pressure reaction media is depressurized, mixed with a solvent, and fed directly to the atmospheric pressure electrospray ionization source of a tandem mass spectrometer. The method was applied to track product evolution for the dehydration of hydroxenin monoacetate, a commercially, important vitamin A precursor, and for the hydrogenation of 5-norbornene-2-carbonitrile with Pd/CaCO(3) as catalyst. Faster access but comparable results as by conventional off-line methods were obtained in every case.

A practical approach for ambient-pressure hydrogenations using Pd on porous glass.

A Pd on porous glass catalyst system was used in the liquid-phase hydrogenation of terpenoid substrates with dihydrogen at room temperature and atmospheric pressure. A multitude of substances were hydrogenated selectively with yields of 90-100 %. In all experiments, only C--C, C--N, and N--N double bonds were hydrogenated. Studies revealed that carbonyl and aromatic double bonds are inert towards catalytic reduction with dihydrogen under the conditions employed. In some cases, hydrogenation was accompanied by isomerization, so that treatment of beta-pinene, for example, afforded isomeric alpha-pinene, which was subsequently hydrogenated to pinane.