Lucia Liguori

Organocatalyzed Epoxidation of Alkenes in Continuous Flow using a Multi-Jet Oscillating Disk Reactor

Several epoxidation reactions and methods have been reported in the literature, and the majority of these are based on transition metal catalysis. Examples include the Mukaiyama epoxidation, 3] Sharpless epoxidation, and Jacobsen–Katsuki epoxidation. Even though such transition metal-catalyzed processes offer several advantages, a serious disadvantage exists if the epoxide is to be used in the preparation of pharmaceuticals, nutraceuticals, or other food and feed additives: the need for an extensive purification of the synthesized target product. Guidelines from The European Medicines Agency state that the oral permitted exposure to, for example, palladium and nickel in pharmaceutical ingredients should be <2.6 mgPd kg 1 day 1 and 20 mg Ni kg 1 day, 1 respectively. Developing protocols that meet these requirements can be a challenging task, but this can usually be solved by means of classical purification methods. These often involve several consecutive purification steps and/or a combination of several methods. A new, emerging technology known as organic solvent nanofiltration can also be applied, without the need of several repeating steps. However, processing in this manner increases costs and decreases throughput and yield. Competitive organic processes that do not require the use of any transition metals in order to operate exist, but from an industrial point of view these also suffer from a drawback, namely the need for long reactor residence times to reach suitable product yields. This of course limits the efficiency and throughput of the process. The epoxidation of alkenes via aerobic oxidation with an aldehyde as a co-reagent has been reported by Kaneda and collaborators, Lassila and collaborators, and Beak and Jarboe. The Shi epoxidation gives access to epoxides starting from various alkenes using a fructose-derived organocatalyst with Oxone as the terminal oxidant. Minisci and co-workers disclosed an organocatalyzed epoxidation (Scheme 1) in which olefins 1 are treated with acetaldehyde 2 under an oxygen atmosphere in the presence of N-hydroxyphthalimide (NHPI) 3 as catalyst, to obtain epoxides 4 in good to excellent yields. The Minisci epoxidation was demonstrated to operate superbly with a-olefins and cyclic olefins, producing the corresponding epoxides in excellent yields and selectivities, while internal acyclic olefins were proven to be unreactive. Even though the Minisci epoxidation can be said to be a green and economical process, it also suffers from a disadvantage from an industrial point of view: its low relative efficiency owing to long batch reactor residence times (24–48 h). To overcome this major drawback, we initialized a project for technology transfer, development, and optimization to realize an aerobic epoxidation catalyzed by NHPI (3) under continuous-flow conditions by means of a new technology: the multijet oscillating disk (MJOD) reactor. During recent years, we have in our laboratories at the University of Bergen and at Fluens Synthesis designed, manufactured, developed, and investigated an approach for flow organic synthesis that has resulted in this novel reactor platform. A detailed account of the MJOD reactor technology was recently disclosed by us, but a short description of the MJOD reactor technology follows here. A 3D drawing of the MJOD reactor that includes the input section, reactor body, output section, and oscillator section is shown in Figure 1. A process flowchart for the experiments disclosed herein is given in Figure 2. The right-hand side of Figure 1 shows a transparent top-down view of the input section, together with a small section of the reactor zone. The MJOD unit is placed in the center of the reactor tube. The outer shell of the reactor body forms a ring-shaped room that encapsulates the whole length of the reactor tube. This room is used for circulating a heating or cooling fluid. Due to the advantageous reactor net volume versus the heating/cooling surface ratio of the reactor tube, an exceptionally good heat transfer capacity is achieved. A variable-frequency and variable-amplitude oscillator is used for the vertical “piston movement” of the MJOD unit. An electric motor connected to a cam mechanism is used to power the up–down movement of the MJOD assembly. In addition, the cam assembly provides control of the amplitude by linear translation of the cam assembly to a predefined position (i.e. , the distance to the motor shaft). Frequencies in the range of f = 1–10 Hz and amplitudes in the range of A = 0.5–15 mm can be achieved by adjusting the motor speed and the cam assembly. Various types of feeding [a] Dr. R. Spaccini, Prof. Dr. H.-R. Bjørsvik Department of Chemistry University of Bergen All gaten 41, 5007 Bergen (Norway) Fax: (+ 47) 55 58 94 90 E-mail : hans.bjorsvik@kj.uib.no [b] Dr. L. Liguori, Prof. Dr. H.-R. Bjørsvik Fluens Synthesis Thormøhlensgate 55, 5008 Bergen (Norway) [c] Dr. R. Spaccini, Dr. C. Punta Dipartimento di Chimica, Materiali e Ingegneria Chimica, “Giulio Natta” Politecnico di Milano Via Mancinelli 7, 20131 Milano (Italy) Scheme 1. The Minisci epoxidation process.

Carboxylic acids from methyl aryl ketones by means of a new composite aerobic oxidation process

A new aerobic oxidation method for conversion of methyl aryl ketones to the corresponding benzoic acids is presented. The method is cheap and environmentally friendly, which also makes it suitable for large scale industrial use. The method affords a yield of >75% with an almost 100% selectivity. Experiments have shown that the process operates following two mechanistic pathways, namely by base-catalysed autoxidation and by single electron transfer processes.

New free-radical chain processes involving substitution of vinyl and aryl chlorides by alkanes, alkenes, esters and ethers

Abstract New free-radical substitutions of vinyl and aryl chlorides by alkanes, alkenes, ethers and esters are described. The free-radical chains are rationalized on the basis of the known kinetics of the elementary steps involved.

A NEW DIRECT HOMOLYTIC IODINATION REACTION OF ALKANES BY PERFLUOROALKYL IODIDES

A new method for the direct free-radical chain iodination of alkanes by perfluoroalkyl iodides is described.

Extraction, isolation, and purification of analytes from samples of marine origin--a multivariate task.

The development of a multivariate study for a quantitative analysis of six different polybrominated diphenyl ethers (PBDEs) in tissue of Atlantic Salmo salar L. is reported. An extraction, isolation, and purification process based on an accelerated solvent extraction system was designed, investigated, and optimized by means of statistical experimental design and multivariate data analysis and regression. An accompanying gas chromatography-mass spectrometry analytical method was developed for the identification and quantification of the analytes, BDE 28, BDE 47, BDE 99, BDE 100, BDE 153, and BDE 154. These PBDEs have been used in commercial blends that were used as flame-retardants for a variety of materials, including electronic devices, synthetic polymers and textiles. The present study revealed that an extracting solvent mixture composed of hexane and CH₂Cl₂ (10:90) provided excellent recoveries of all of the six PBDEs studied herein. A somewhat lower polarity in the extracting solvent, hexane and CH₂Cl₂ (40:60) decreased the analyte %-recoveries, which still remain acceptable and satisfactory. The study demonstrates the necessity to perform an intimately investigation of the extraction and purification process in order to achieve quantitative isolation of the analytes from the specific matrix.