The Development of Organic Synthesis

If the solution to the waste problem in the fine chemicals industry is so obvious - replacement of classical stoichiometric reagents with cleaner, catalytic alternatives - why was it not applied in the past We suggest that there are several reasons for this. First, because of the smaller quantities compared with bulk chemicals, the need for waste reduction in fine chemicals was not widely appreciated. 

Organic synthesis followed a different line of evolution. A landmark was Perkin s serendipitous synthesis of mauveine (aniline purple) in 1856 [26] which marked the advent of the synthetic dyestuffs industry, based on coal tar as the raw material. The present day fine chemicals and pharmaceutical industries evolved largely as spin-offs of this activity. Coincidentally, Perkin was trying to synthesise the anti-malarial drug, quinine, by oxidation of a coal tar-based raw material, allyl toluidine, using stoichiometric amounts of potassium dichromate. Fine chemicals and pharmaceuticals have remained primarily the domain of 

A third reason, which partly explains the reluctance, is the pressure of time. Fine chemicals generally have a much shorter lifecycle than bulk chemicals and, especially in pharmaceuticals, time to markef is crucial. An advantage of many time-honored classical technologies is that they are well-tried and broadly applicable and, hence, can be implemented rather quickly. In contrast, the development of a cleaner, catalytic alternative could be more time consuming. Consequently, environmentally (and economically) inferior technologies are often used to meet market deadlines. Moreover, in pharmaceuticals, subsequent process changes are difficult to realise owing to problems associated with FDA approval. 

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Gilbert Stork (1921-1 was born on Mew Year s eve in Brussels, Belgium. He received his secondary education in France, his undergraduate degree atthe University of Florida, and his Ph.D. with Samuel McElvain atthe University of Wisconsin in 1945. Following s period on the faculty at Harvard University, he has been professor of chemistry at Columbia University since 1953. A world leader in the development of organic synthesis. Stork has devised many useful new synthetic procedures and has accomplished the laboratory synthesis of many complex molecules. 

It would be difficult to overestimate the role that the polyether antibiotics have played in the development of organic synthesis, particularly in the area of acyclic stereocontrol. These molecules have inspired many spectacular achievements in organic synthesis, achievements that have dramatically expanded the power and scope of the science. In fact, it would not be inaccurate to attribute much of our understanding about the factors controlling acyclic stereoselectivity for such fundamental processes as hydroboration,5 epox-... 

The next milestone in the development of organic synthesis was the preparation of the first synthetic dye, mauveine (aniline purple) by Perkin in 1856 Perkin, 1856, 1862). This is generally regarded as the first industrial organic synthesis. It is also a remarkable example of serendipity. Perkin s goal was the synthesis of the antimalarial drug quinine by oxidation of N-allyl toluidine (Fig. 2.4). 

The detection of olefination of carbonyl compounds with phosphoranes by Wittig in 1952 stimulated the development of organic synthesis in a high degree,... 

Further breakthroughs in the area of synthetic chemistry emerged with the development of organic synthesis on solid phase.223-226 As a consequence, the past decade has witnessed dramatic improvements in the area of solid phase-supported oligosaccharide synthesis.202,227-230 Polymer-supported synthesis is a very attractive techniques as it allows for rapid synthesis of oligosaccharide sequences without the... 

The development of organic synthesis by catalytic methods is also very much appealing to the use of zeolites. The potential of these solids as far as selectivity is concern should encourage the investigation of new reactions and new routes to known compounds through the use of the large body of porous structures. 

Since 1828 when urea was first synthesized in the lab from cyanic acid and ammonia the development of organic synthesis has seen remarkable innovations and discoveries. Using modem state of the art techniques allows almost any molecule that can exist under normal conditions (and many of those which cannot) to be synthesized. But this near-omnipotence comes with a price. Complex organic molecules often have multiple reactive pathways available under a variety of reaction conditions. In order to develop synthetic transformations that select one specific reactive pathway, chemists have often resorted to supplemental modifications of their starting materials to block non-... 

The ultimate goal is to apparently develop a more reactive, more selective, and more versatile catalyst. We believe that the realization of such an objective would be a tremendous beneht for the development of organic synthesis including green chemistry. 

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