Pushing boundaries—selective cooling crystallization as tool for selectivity compensation and product purification using a recyclable Pd/Xantphos catalyst in the methoxycarbonylation of methyl 10-undecenoate

The homogeneously catalyzed methoxycarbonylation of methyl 10-undecenoate allows for the synthesis of dimethyl 1,12-dodecandioate as an interesting bio-based drop-in alternative for 1,12-dodecandioic acid as polymer building block. Although the benchmark catalyst system of Pd/1,2-bis((di-tert-butylphosphino)methyl)benzene and methane sulfonic acid is very active and selective, long-term stability over a potential catalyst recycling is limited. In this work, modifications of this catalyst system in terms of protonation of the ligand and its replenishment during recycling are first investigated, proving that the reaction system is tolerant against minor changes. Finally, the commercially available ligand Xantphos, featuring higher stability but comes with a rather low l:b selectivity of 70:30, is applied. However, through the application of cooling crystallization, 58 g product (52% isolated yield) with an overall purity of 94% is obtained from the crude reaction solution without further treatment and a ∑TON of 4000 after ten reaction runs, while catalyst loss into the product is low. Practical Applications: Selective syntheses on the basis of renewable resources are a powerful tool for the production of value products in terms of green chemistry. Thereby, homogeneous transition metal catalysts are beneficial regarding selectivity. However, their separation and recycling are challenging due to their limited stability. The combination of a stable, commercially available catalyst with a selective purification method allows for isolation and purification from a crude reaction mixture without the need for any auxiliary or further purification steps. In this work, cooling crystallization is applied for subsequent purification of the linear diester dimethyl 1,12-dodecandioate. Thereby, a lower selectivity from the methoxycarbonylation reaction using the stable Xantphos ligand is compensated and combined with recycling of the homogeneous catalyst. Thus, the development of an integrated process covering a stable catalyst system in the reaction, and high selectivity in the purification is the key toward an efficient homogeneous catalyst recycling

Selective synthesis of primary amines by kinetic-based optimization of the ruthenium-Xantphos catalysed amination of alcohols with ammonia

The selective synthesis of primary amines directly from several alcohols and ammonia using a homogeneous catalyst based on HRuCl(CO)(PPh3)3 and Xantphos is presented. The key to success was the detailed understanding of all mutually influencing parameters such as temperature, ammonia excess, and substrate concentration. These studies were supported by the determination of the kinetics, which allowed the reaction order to be calculated as 0.7. Furthermore, the kinetic model derived from the mechanism was confirmed. After measuring reaction profiles for all influencing parameters, optimized conditions were obtained, which finally allowed the amination of aliphatic, cyclic, as well as primary and secondary alcohols with selectivities to the desired primary amine exceeding 90 % at quantitative alcohol conversion with only minimal formation of the undesired secondary amines. Furthermore, the catalytic activity of the commercially available and robust Xantphos system was drastically improved, corresponding to a turnover frequency (TOF)>60 h−1 after 30 minutes and a turnover number (TON) of 120

Catalytic synthesis of methyl 9,10‐dihydroxystearate from technical feedstocks in continuous flow via epoxidation and hydrolysis

The sequence of the homogeneously Ru-catalyzed epoxidation of methyl oleate and acid-catalyzed hydrolysis of the corresponding epoxide methyl 9,10-epoxy stearate is successfully transferred from batch into flow mode, allowing for the continuous production of methyl 9,10-dihydroxystearate. Thereby, methyl oleate is first converted up to 97% within 14 min at excellent selectivity in the epoxidation using aqueous hydrogen peroxide as the sole oxidant. In the subsequent hydrolysis, a residence time of 10 min is sufficient for quantitative conversion of the epoxide. The desired, pure vicinal diol is isolated upon crystallization from the crude reaction mixture in an integrated process starting from technical grade (91.5%) substrate. The isolated yield is increased upon the addition of water as a green antisolvent from 75% up to 97%. Finally, the concept is transferred to methyl oleate of even lower purity (76%), still obtaining an isolated yield of 66% of the vicinal diol. Thus, the integration of sequential epoxidation and hydrolysis into continuous flow and subsequent crystallization allows for high conversion and selectivities within a total residence time of 27 min, corresponding to a space–time yield of 190 g h−1 L−1 in the epoxidation and 164 g h−1 L−1 in the hydrolysis, respectively. Practical applications: The modular flow setup enables the targeted functionalization toward the epoxide intermediate or the vicinal diol. Both offer versatile applications for the production of polymers, surfactants, or toward further conversion as in oxidative cleavage starting from methyl oleate. The application of flow chemistry offers advantages for the safe handling of hydrogen peroxide even at high temperatures. With fats and oils being natural substances, oleochemicals such as fatty acid methyl esters are typically available in technical purity so that efficient strategies for the isolation of pure products are of need. Crystallization of the product is promising, as additional organic solvents are not required. Thus, using the difference in melting point and solubility behavior of the desired product compared to other compounds is a promising method for the applicability of renewable resource-based substrate mixtures

Synthesis of biobased amines via Pd-catalysed telomerisation of the renewable β-myrcene in a water/ethanol multiphase system: catalyst recycling enabled by a self-separating product phase

We developed an aqueous multiphase system for the synthesis of biobased alkyl amines via palladium-catalysed telomerisation based on the terpene β-myrcene. Ethanol was employed as a harmless co-solvent. With this “green” switchable multiphase solvent system, the recycling of the expensive homogeneous catalyst was successfully enabled by self-separating products at room temperature. The total turnover number (TON) was increased to almost 12 000 over 9 runs, with high selectivities towards the desired amine telomer products between 80 and 93% in each run. Furthermore, various amine nucleophiles were successfully used allowing to produce a wide variety of long-chain unsymmetrical alkyl amines with potential applications as, for instance, surfactant precursors or lubricants. In each case, the products self-separated after reaction from the aqueous multiphase system containing the homogeneous palladium catalyst allowing straightforward isolation by simple decantation. Finally, we proved the successful use of spirits (vodka) as solvents in this sustainable amine synthesis

From tandem to catalysis – organic solvent nanofiltration for catalyst separation in the homogeneously W-catalyzed oxidative cleavage of renewable methyl 9,10-dihydroxystearate

Feasibility of oxidative cleavage of methyl oleate in a homogeneous reaction, facilitating the subsequent recovery of the catalyst from a single phase, is a challenge. Using the high molecular catalyst phosphotungstic acid (2880 Da) as an affordable catalyst offers potential for membrane separation. To gain insight into side-reactions, the intermediate methyl 9,10-dihydroxystearate was first applied as a model substrate. Thus, the stability of the intermediate methyl 9,10-epoxystearate and the vicinal diol was significantly improved under reaction conditions. Oxidative cleavage of the vicinal diol as a stable intermediate is very promising reaching an overall selectivity of 90% and a selectivity towards the cleavage carboxylic acids of 80%, considering dilution and acidity as the most important parameters. Retention of the catalyst via organic solvent nanofiltration was investigated and we retained 94% of the catalyst in the monophasic system as the first step towards a process concept for a product purification or catalyst recycling strategy

Rhodium-catalysed reductive amination for the synthesis of tertiary amines

A procedure for the synthesis of tertiary amines via reductive amination of aldehydes with molecular hydrogen as a reducing agent using homogeneous rhodium catalysis is presented. Using an amine to aldehyde ratio of 4/1 enabled the synthesis of tertiary amines from nine different aldehydes and nine different secondary amines with selectivities up to 99% and turnover frequencies (TOF) up to 7200 h−1. The reaction showed a high tolerance against alcohol and ester functions allowing the formation of multifunctional molecules. In addition, secondary amines can also be produced by this synthesis. For all compounds, activities were determined by hydrogen gas-uptake. In order to increase the sustainability and efficiency of the procedure, a dosing strategy has been successfully developed. Using the determined reaction indicators enabled the stoichiometric use of aldehydes and amines without significant loss of selectivity

Continuous production of amines directly from alkenes via cyclodextrin-mediated hydroaminomethylation using only water as the solvent

Aqueous hydroaminomethylation (HAM) is an atom economical route for the efficient production of amines in one reaction step, starting from basic chemicals like alkenes. Herein we present the first successful establishment of a continuous process for HAM in an aqueous multiphase system. The green mass transfer agents randomly methylated-β-cyclodextrins (CD) enabled the catalytic system consisting of rhodium/sulfoXantphos to achieve high yields of up to 70% with selectivities of up to 80% in several continuous experiments with a total run time of more than 220 h. The key here is that water and products have large polarity differences, but the reaction still proceeds effectively due to the addition of cyclodextrin, which made the application of solvents obsolete. The main achievements in this way were the investigation of the influence of the randomly methylated-β-cyclodextrin concentration on the reaction rate and the selectivity in batch studies and finding promising operating points in the first continuous experiments. In a final experiment, the separation temperature was investigated. It was shown that the catalyst loss in the product phase is enormously small at 0.003% h−1 of the initial mass (0.24% in total), which is the lowest ever reported value for the HAM on this scale. Within a run time of 78 hours, 2.87 kg of tertiary amine were produced using only 0.2 g (>14[thin space (1/6-em)]000[thin space (1/6-em)]:[thin space (1/6-em)]1) of transition metal, while the loss of rhodium per kg of product produced was mostly around 0.15 mg kg−1, suggesting possible economical applicability

Polymer-grade bio-monomers from oleochemicals by combining homogeneous catalysis and selective product crystallization in an integrated process

The homogeneously catalyzed methoxycarbonylation of bio-based methyl 10-undecenoate (C11-DME) produces linear 1,12-dimethyl dodecanedioate (l-C12-DME). Subsequent selective product crystallization from the reaction mixture with downstream filtration and washing allows for the generation of the bio-monomer in polymer grade quality (>99.9%). This effective purification enables its direct use, e.g., for bio-based polyamides, without further purification. It separates the expensive homogeneous catalyst dissolved in the liquid phase in its active state for efficient catalyst recycling. We present the complex interactions of process parameters regarding reaction and crystallization-based purification in an integrated catalyst recycling process. Furthermore, we demonstrate that purification of l-C12-DME with >99.9% purity over multiple consecutive recycling runs is possible. However, as the crystallization is highly sensitive towards changing concentrations of by-products and particularly unreacted substrates, this high purity is only achieved by maintaining a stable composition in the reaction mixture using a newly developed system for precise conversion control in the reaction step

Slug flow as tool for selectivity control in the homogeneously catalysed solvent-free epoxidation of methyl oleate

Catalytic oxidation of sustainable raw materials like unsaturated fats and oils, or fatty acids and their esters, lead to biobased, high-value products. Starting from technical grade methyl oleate, hydrogen peroxide as a green oxidant produces only water as by-product. A commercially available, cheap water-soluble tungsten catalyst is combined with Aliquat® 336 as a phase-transfer agent in solvent-free reaction conditions. In this study, we first report the transfer of this well-known batch system into continuous mode. The space–time yield is improved from 0.08 kg/L.h in batch to 1.29 kg/L.h in flow mode. The improved mass transfer and reduced back mixing of the biphasic liquid–liquid slug flow allows for selectivity control depending on physical parameters of slug flow namely volumetric phase ratio, volumetric flow rate, and slug length. Even though the product, methyl 9,10-epoxystearate is obtained at a maximum selectivity of only 58% in flow mode, higher space time yield combined with possible reactant recycling in flow mode offers a promising avenue of research. This work analyses the use of slug flow parameters as tools for controlling selectivity towards oxidation products of methyl oleate