In-Pharma focus: Clariant's chemistry.
opportunity to review new developments at the CPhI Expo in Madrid,
Spain, making announcements on new investments in facilities in
Europe and the US as well as new business models and technology, as
In-PharmaTechnologist presents the first of a two part report.
Clariant are in an ideal position to take advantage of opportunities in the pharmaceutical outsourcing industry, which is increasingly seeing both innovator and generic sectors growing faster than the industry as a whole.
According to Norbert Dieterich, Head of the Pharmaceutical Fine Chemicals Business, the opportunities for outsourcing are there for companies that are able to understand and deliver customers unmet need.
"The fine chemicals business for pharmaceuticals has never been and will never be about the hardware you have on the ground. It is the offering that enables the commercialisation process that just happens to involve chemistry," he said.
Clariant announced its latest developments in the field of Organometallic Chemistry, a field that has becoming increasingly prominent in the pharmaceutical industry to develop new compounds more cost effectively.
The company has recently developed sulphonated hydroxybiphenyl phosphane ligands that yield highly polar ligand/catalyst systems. These systems show very high catalytic activities at low concentrations.
They allow work with a broad range of solvents, and by the specific property of their being present as an anion during the reaction, the removal of the catalyst/ligand system from the final product is achieved easily. The process has added benefit of not requiring expensive, bulky bases.
C,N couplings are currently a hot topic in organic synthesis because of their ability to be used in producing a broad range of substituted amines, which hold a great deal of interest for pharmaceutical applications.
Several catalytic systems have been developed in recent years by different groups for use in C,N couplings, often characterised by high loadings of expensive catalysts - a technological solution that is not ideal for commercial scale manufacture.
Other persistent problems included the need for expensive tertiary alcoholate bases, inflexibility of solvents utilised and, most importantly, the difficulties of removing catalyst and metal traces from the final product since these amines are often very efficient in binding catalysts such as palladium.
"One of the most interesting aspects of the organometallic reaction is the high level of value that it adds to the resulting products. We find these factors to be particularly relevant in the important areas of carbon-carbon and carbon-nitrogen bond formation in the functionalisation of molecules," said Dr Andreas Meudt, Head of R&D Operations for Clariant's Phamraceutical Fine Chemicals business in Germany.
"Our work in organometallic chemistry is significant because of the breakthrough is significant because of the breakthroughs that it offers the world of chemistry in general. But it offers new options and productivity increases for the pharmaceutical industry because it develops solutions that work at the commercial or multi-ton scale," he added.
Clariant has also developed new methods for coupling aliphatic boronic acid with aryl halides. Couplings of this type have suffered from limitations that made them impractical for commercial scale synthesis.
Clariant's new methodology requires only traces of palladium along with innovative ligands derived from oxaphosphorinchloride. The reaction takes place in a single step, offering the pharmaceutical industry an economical way for making highly complex substituted alkyl- and vinylarenes.
In speaking of further chemical developments, Clariant have put the emphasis on placing phosgenation technology as an important pharmaceutical technology of the future.
As a technology, phosgenation is finding increasing applications in pharmaceutical synthesis offering access to unusual and adaptable building blocks up to the hundred-ton scale with excellent economics.
Dr. Ralf Pfirmann, global business director for the Pharmaceutical Fine Chemicals Business of Clariant, told In-PharmaTechnologist.com: "Phosgene is a versatile reagent used in many well-known applications, including the synthesis of complex heterocycles, peptides and protecting groups."
Using triphosgene chemistry, Clariant has been to industrialise a short and efficient synthesis route to oxacarbazepine. The technology can be used in penultimate or ultimate steps of API synthesis delivering high product purity thus avoiding expensive purification.
