Green Chemistry Blog

A collaboration between scientists at Frankfurt’s DECHEMA Research Institute and the Delft University of Technology has established a biocatalytic route to make bio-based antiseptics from carvacrol and thymol. Halogenation of monoterpenes yields interesting antimicrobial compounds, some with anti-tumour activity and other desirable medicinal properties. As more is discovered about enzymatic halogenation (and significant progress on this front is only recent) it becomes increasingly viable as a benign technology for the synthesis of these important molecules.

A chloroperoxidase enzyme was used to form hypochloride from sodium chloride and hydrogen peroxide, with later experiments exploring combined electrochemical enzymatic halogenation, producing the hydrogen peroxide in situ from oxygen. The hypochloride then reacts with carvacrol or thymol to produce their respective monochloro-derivatives. For example, an ortho-chlorothymol to para-chlorothymol molar ratio of 70:30 was achieved, with yields exceeding 80% under optimised conditions.

The greenness of this methodology is apparent upon comparison to the typical reaction conditions, as highlighted by Getrey et al. and found here. In contrast to the application of copper(II) chloride as a catalyst in the chlorination of phenol derivatives with oxygen and lithium chloride, this new enzymatic process operates at a lower temperature with less catalyst, and does not require an organic solvent.

By James Sherwood

Click below to read the full article. Free to access until 8th January.

Enzymatic halogenation of the phenolic monoterpenes thymol and carvacrol with chloroperoxidase, Laura Getrey, Thomas Krieg, Frank Hollmann, Jens Schrader and Dirk Holtmann, Green Chemistry, 2014, DOI: 10.1039/C3GC42269K

Olefin metathesis is a route to the formation of new C=C bonds, and is, thus, ubiquitous in organic chemistry. Reactions of this type include cross metathesis (CM) and ring-closing metathesis (RCP), among others, where Grubbs-type ruthenium (Ru) complexes bearing N-heterocyclic carbene (NHCs) ligands are commonly used commercial catalysts. Traditionally, chlorinated and aromatic solvents, e.g., DCM and toluene, are employed; their use, however, is accompanied by health and environmental concerns. Less hazardous reaction media, including water and ionic liquids (ILs), have been previously investigated, but special reaction conditions, or catalysts that are not readily available, are required for their success.

In this paper, the authors sought to evaluate the performance of several types of commercial metathesis catalysts in non-traditional solvents, viz., MeOH, i-PrOH, EtOAc, DMC, CPME, and 2-MeTHF. These solvents were chosen based on their adherence to “green” solvent selection criteria. A series of ten Ru-based catalysts with varied (NHC) ligand architecture was chosen for this study. The most effective solvent/catalyst combinations for ROP of dienes and CM of esters were first determined using model compounds. A number of substrates, having motifs prevalent in natural products, were subsequently tested in the best performing solvent, i.e., EtOAc. The results indicated that the catalyst systems, when used in ester solvents at 70 °C, produced similar yields and selectivites to analogous reactions in toluene and DCM. These results were obtained in air rather than under an inert gas. Moreover, the reactions were carried out in solvents that had not been degassed or distilled, as is typically the case. This presents a valuable alternative to the less sustainable conditions commonly used in industry and academia.

By Jenna Flogeras

To read the full article, please click the link below. The paper is free to access for 4 weeks!

In an attempt to provide green solvent selection guide for olefin metathesis, Tomasz Krzysztof Olszewski, Krzysztof Skowerski, Andrzej Tracz and Jacek Bialecki, Green Chem., 2013, DOI: 10.1039/C3GC41943F

Cross coupling reactions are immensely useful in the construction of organic molecules, a fact recognised with the award of the 2010 Nobel Prize in chemistry to Akira Suzuki, Richard Heck, and Ei-ichi Negishi. Now scientists in Beijing have discovered that adding common salts like sodium chloride, in a large excess, to Pd/C catalysed Suzuki-Miyaura reactions can more than double the achievable yield. This use of cheap and abundant materials would appear to be an excellent way to improve the productivity of the reaction without drastically increasing its burden on the environment.

It is known that Suzuki-Miyaura reactions can be conducted without any catalyst specifically being added to the reaction. Instead, the reaction is catalysed by trace amounts of palladium in the inorganic base. The authors of this present work report that the inorganic salts are not catalytic themselves, but enhance the activity of the true catalyst. The nature of this synergetic effect was deduced from infra-red and X-ray photoelectron spectroscopy studies, showing evidence of the auxiliary salt interacting with both the bromoarene reactant and the palladium catalyst. The polarisation of the reactive C-Br bond, and the increased electron density placed on the metal catalyst, is said to enhance the rate determining oxidative addition step of the reaction.

By James Sherwood

Click below to read the full article, free until December 1st:

Acceleration of Suzuki coupling reaction by abundant and non-toxic salt particles, Binbin Zhang, Jinliang Song, Huizhen Liu, Jinghua Shi, Jun Ma, Honglei Fan, Weitao Wang, Peng Zhang and Buxing Han, Green Chem., 2013, DOI: 10.1039/C3GC42088D