APPLICATION OF TRANSITION METALS, COMPLEX IONS, COORDINATION COMPOUNDS.

Pharmaceutical Industries
The continued development of new medicines by the pharmaceutical industry is a critical endeavour to improve and maintain human health, and the associated benefits to society are obvious. In order to develop new drugs, pharmaceutical chemists must prepare large collections of diverse compounds in order to identify a promising hit, which is then taken on for further development in the production of further collections of compounds. Therefore, as one might imagine, the methods (chemical reactions) which are used to prepare these compounds must be very efficient, reliable, and general in nature. Although a huge number of chemical reactions are known, (a number that continues to grow on a daily basis), only a very small proportion of these reactions are suitable for use in the preparation of these compound libraries. This is because most reactions fail to meet one or more of a list of demanding criteria that are applied in the generation of compound libraries. For example, many reactions only work for a narrow, restricted range of cases, or they require the use of exotic reagents or inconvenient reaction conditions. This limiting factor provides a powerful obstacle to the efficient development of new medicines. The proposed research is aimed at developing a reaction that has been known for a long time, but is rarely used by medicinal chemists in the pharmaceutical industry. This reaction employs a transition-metal catalyst to promote the reaction between several reaction partners to generate cyclic molecules that feature prominently in drugs and drug-like molecules. Transition metals open up new opportunities for synthesis, because their means of bonding and their reaction mechanisms differ from those of the elements of the s and p blocks. In the last decade, the subject has mushroomed. Established reactions are seeing both technical improvements and increasing numbers of applications. New reactions are being developed. The practicality of the subject is demonstrated by the large number of publications coming from the process development laboratories of pharmaceutical companies. This volume considers the ways in which transition metals, as catalysts and reagents, can be used in organic synthesis. It concentrates on the bond-forming reactions that set transition metal chemistry apart from "classical" organic chemistry.

Organ catalysis has recently emerged as a field of research providing practical alternative or complementary technologies to the more traditional transition metal catalyzed systems. A key advantage of organ catalytic systems is that they provide clean, green and cheap solutions to some of the most difficult problems in organic synthesis. Generally, the organ catalyst can be recovered at the end of a reaction through aqueous workup or column chromatography. In this way, the organ catalyst can be recycled and used repeatedly in subsequent reactions leaving the desired organic product uncontaminated. This contrasts with transition metal catalysts where trace metallic residues often contaminate the final organic product.

This issue is of considerable importance in the pharmaceutical industry where there are strict limits on the level of impurity allowed in a product before it can be released onto the market. Transition metal catalysts and their associated ligands are also very expensive in comparison to most organ catalysts and this has limited their use in the pharmaceutical industry. Catalysis has become increasingly important for the pharmaceutical industry. Catalysis is a critical technology that enables economical and environmentally-sound manufacturing processes. The development of a viable catalytic process for industrial scales is a complex task that requires the collaboration of multiple disciplines. In this article, a number of selected, noteworthy industrial examples are discussed to showcase the catalytic technologies that have been successfully practiced on large scales for active pharmaceutical ingredient (API) synthesis, involving transition metal catalysis, bio catalysis and organ catalysis. In addition, several examples of potential and future catalytic transformations are included which can be utilized in pharmaceutical industry in large-scale operational settings.

The ability to prepare functionalized organic molecules rationally and predictably, whether individually or in libraries is central to organic synthesis, medicinal chemistry and the pharmaceutical industry. The aims of this work are to develop new and/or improved methods for the formation of carbon-nitrogen and carbon-oxygen bonds. Included in this work is the development of new strategies and techniques for the preparation of complex heterocyclic, which are the building blocks of medicinal chemistry and the pharmaceutical industry, via cross-coupling methodology. Further, information gained from this work will help to understand the mechanism of the processes that are being developed in order to increase the rate of improvement of the techniques that we are studying. The development of new methods for organic synthesis is the key to the development of the field of organic chemistry as a whole. These reactions are of critical importance to the pharmaceutical industry. Cross-coupling methods for carbon-heteroatom bond formation are regularly used by those in the pharmaceutical industry for the preparation of analogues with increased potency and reduced side effects. Moreover, the methods can be employed for the preparation of quantities of new substances for preclinical and clinical testing and for the actual manufacture of a pharmaceutical agent. The techniques that are being developed allow for these important functions to be carried out in a more rapid and efficient fashion than previously possible. Moreover, they allow for the preparation of new substances, which have previously been inaccessible. These new compounds have the possibilities of having physiological properties of great importance in medicinal chemistry and the pharmaceutical industry. Further these techniques are used by researchers in both academia and industry in a variety of areas of bioorganic and materials research including in the formation of new sensory materials. The crosscoupling methods we are developing for carbon-heteroatom bond formation are regularly used by those in the pharmaceutical industry for the preparation of analogues with increased potency and reduced side effects. Moreover, the methods can be employed for the preparation of quantities of new substances for preclinical and clinical testing and for the actual manufacture of a pharmaceutical agent.

The complex formation of cobalt(II)-, nickel(II) and copper(II) sulphate hydrates with 3,5-dimethyl-1-thiocarboxamidepyrazole (HL) was studied. The influence of the anions on the course of the reaction was also examined, using nickel(II) salts with various anions. Beside the NiSO47H2O the reaction has been carried out with Ni(OAc)2, Ni(CF3COO)2 and Ni(SCN)2. Compounds with the following composition were obtained: Co(L)3, Ni(L)2 and [Cu(SCN)L]2. The structure of the ligand and the Co(L) 3 complex was determined by single crystal X-ray analysis, while that of the Ni(L)2 was solved by analysis of powder diffraction X-ray data. The most probable structure of the copper(II) complex is proposed on the basis of the elemental analyses data, FT-IR spectrometry and magnetic measurement. The thermal decomposition of the complexes was investigated by thermogravimetry, DSC and coupled TG-MS measurements. In the case of the nickel(II) compound, a relatively stable intermediate was detected in the 550-650 K temperature range. The composition of the intermediate, Ni(SCN)(NCS), was determined by FT-IRspectrometry.