Developing Catalysts and Catalytic Processes with Industrial Relevance

The catalysis group of Solvias has its roots in the Central Research Laboratories of Ciba-Geigy. Since the early eighties its research has been focused on three areas of catalytic technology: heterogeneous hydrogenation, coupling catalysis, and enantioselective hydrogenation. Today, these are still the catalytic methods with the greatest industrial potential. In this overview a short description will be given how these methods have been developed further since the spin-off of Solvias in 1999. It will be discussed which strategies were successful and what the most important results have been in the first decade of Solvias

Looking Back on 35 Years of Industrial Catalysis

This article is an account of my 35 years in the Basel Chemical Industry, starting in 1976 as a young research chemist in the Central Research Laboratories of Ciba-Geigy until my retirement as Chief Scientific Officer of Solvias in 2011. In the first section, important aspects of industrial research are commented from my personal point of view with particular emphasis on the importance of team work and the situation of catalysis in the (Swiss) fine chemicals industry. In the next sections, the three most important areas of catalytic research are described where my colleagues and I could not only solve specific Ciba-Geigy / Novartis / Solvias problems, but also developed industrially relevant, generally applicable catalytic methodologies and contributed to the understanding of these complex catalytic transformations: i) Catalytic C–C and C–N coupling catalysis where we developed highly efficient catalysts for the Heck, Suzuki, Buchwald-Hartwig reactions; ii) Hydrogenations using modified heterogeneous catalysts, especially the chemoselective reduction of functionalized nitro arenes and the enantioselective hydrogenation of substituted ketones using Pt catalysts modified with chinchona alkaloids where mechanistic studies led to a working understanding of this fascinating reaction; iii) Enantioselective homogeneous hydrogenation and chiral ligands. The process development for the production of (S)-metolachlor, an important herbicide via an iridium–Josiphos catalyzed C=N hydrogenation is described in some detail, followed by a brief description how the Solvias Ligand Portfolio was developed

The Spin-Off of Scientific Services of Novartis into a New, Independent Technology Company Offering Services to the Pharmaceutical, Chemical, and Nutrition Industry

Starting on October 1, 1999, the three sections 'Central Analytics', 'Physics', and 'Catalysis Synthesis Services' of the Scientific Services of Novartis will operate as an independent company. The new company will have about 180 employees and will offer services to customers in the pharmaceutical, chemical, and nutrition industry as well as to authorities and service firms active in these fields. The focus of activities for the new company is the chemical and physical characterization (analytics), optimization of products and processes, and the development and application of special synthetic methods, in particular by utilizing catalysis. Support is offered via single services, comprehensive service packages, or by taking over assignments for entire areas. The combination of a high scientific and technical standard built up on an ISO 9001 quality-management system, including cGMP and GLP, with an attractive working environment will be the basis for an innovative center of chemical and physical expertise

Enantioselective Catalysis for Agrochemicals: The Case History of the DUAL MAGNUM® Herbicide

The use of enantioselective catalytic methods for the technical preparation of chiral agrochemicals is illustrated by the case history of the herbicide (S)-merolachlor (trade name DUAL MAGNUM®). The key step for the technical synthesis of the enantiomerically enriched compound is the asymmetric hydrogenation of an imine intermediate, made possible by a new iridium-ferrocenyldiphosphine catalyst system. Important aspects of the development of the catalyst system as well as minimal prerequisites for the use of enantioselective catalysts for the production of agrochemicals are discussed

Catalysis at Ciba-Geigy

After an introduction describing the significance and a short history of catalysis at Ciba-Geigy, the present role of the Catalysis Section within the Central Research Services is outlined. Its main activities are preparative services for the synthetic chemists in the fields of hydrogenation and high-pressure reactions, the development of catalytic processes and a research program in the fields of enantioselective catalysis, the modification of heterogeneous catalytic systems, acid-base catalysis and catalytic C–C-bond forming reactions. Because catalysis is considered by Ciba-Geigy to be a key technology, the main goal of its R+D program in catalysis is to create and maintain a reliable scientific and technical foundation for the optimal application of catalytic reactions throughout the company. Some results are presented that illustrate the work described above and an outlook on the opportunities of catalytic technologies in the fine chemicals industry is given

Strategies for Accelerating the Development of Catalytic Enantioselective Reactions

The development of enantioselective catalytic processes for the manufacture of chiral intermediates is a very complex endeavor and can be very time consuming and expensive. In this contribution the major issues which might lead to long development times will be discussed and strategies to deal with these problems are described. The general part is illustrated with the approach Solvias has chosen for assisting and supporting the development of enantioselective homogeneous hydrogenation processes, at the moment the most important industrial application of asymmetric catalysis. Special emphasis is given to the application of high-throughput screening (HTS) using a Symyx HiP system and the description of the Solvias portfolio of chiral ligands which makes a broad variety of diphosphine ligands available for all phases of process development from the first screening experiments to the large-scale manufacturing phase. Four case histories serve to illustrate the generic description of the development process

The Chiral Switch of Metolachlor: The Development of a Large-Scale Enantioselective Catalytic Process

The development of an enantioselective catalytic process for the technical preparation of chiral agrochemicals is illustrated by the case history of the herbicide (S)-metolachlor (trade name Dual Magnum®). Four synthetic routes were investigated in some detail. The key step for the technical process of the enantiomerically enriched compound is the asymmetric hydrogenation of an imine intermediate made possible by a new iridium ferrocenyl diphosphine catalyst system. Using optimized conditions, the isolated imine can be hydrogenated at a hydrogen pressure of 80 bar and 50°C with a substrate-to-catalyst ratio of >1'000'000. Complete conversion is reached within 4 h with an enantioselectivity of 79% with an initial turnover frequency (tof) exceeding 1'800'000 h-1. This sets a new standard for the technical application of enantioselective catalysts. Important aspects and results for the different phases of the process development of the catalyst system as well as minimal prerequisites for the use of enantioselective catalysts for the production of agrochemicals are discussed