Industrial examples Ibuprofen

Solvated crystals are also common in the chemical and pharmaceutical industries. Figure 2-18 shows the room temperamre solubility curve of ibuprofen-lysinate as a function of water content in ethanol. As shown in the figure, the crossover point between anhydrous solid and monohydrate is < 5% water. At room temperamre, ibuprofen-lysinate remains anhydrous when the water content is below 5% and transforms into monohydrate when the water content is above 5%. In this example, solvate and anhydrous materials also have different crystal habits, as shown in Fig. 2-19. 

It is responsible for almost all heart drugs, drugs for the CNS, anti-ulcer drugs, analgesics and anti-histamines. Many pharmaceuticals are made simply from readily available bulk chemicals. For example, the non-steroid antiinflammatory agent, ibuprofen, is made from toluene and propylene, two of the seven basic building blocks of the petrochemical industry. Chemical synthesis is also used to modify materials made from other sources, and chemical methods of extraction are used in the downstream processing of products from other sources. 

Besides the more common reactions such as hydrogenation, isomerization, alkylation, and the Diels-Alder reaction. Sharpless epoxidation and dihydroxylation by asymmetrical catalysis are rapidly emerging as reactions with immense industrial potential. Table 9.7 lists some important syntheses based on asymmetric catalysis. These include processes for the pharmaceutical drugs (S)-naproxen, (S)-ibuprofen, (,S)-propranolol, L-dopa, and cilastatin, a fragrance chemical, L-menthol, and an insecticide (/ )-disparlure. Deltamethrin, an insecticide, is another very good example of industrial asymmetric synthesis. The total synthetic scheme is also given for each product. In general, the asymmetric step is the key step in the total synthesis, but this is not always so, as in the production of ibuprofen. Many of the processes listed in the table are in industrial production. 

A major consideration in any industrial synthesis is atom economy it is most efficient to use only reagents whose atoms appear in the final product. An example of the evolution of syntheses with increasingly improved atom economy is the synthesis of ibuprofen. 

The new synthetic route to ibuprofen is an important example of how ideas of green chemistry can influence for the better the industrial synthetic methods used, not only from the point of view of economic efficiency, but also by introducing more effective methods of science and technology. Improved methods of synthesis for hexan-l,6-dioic acid (adipic aid) and cis-butenediol acid (maleic anhydride) - important for the industrial synthesis of nylon and polyesters respectively - are two other examples of the impact of a greener synthetic approach to industrial chemistry. 

A particularly impressive green example (Real Life 3-1) of this effect is achieved in the Friedel-Crafts acetylation of (2-methylpropyl)benzene with acetic anhydride, in an industrial approach to an ibuprofen intermediate (Chapter Opening see also Exercise 16-10). Here, a porous zeolite catalyst (see Section 3-3) provides not only the acidic surface sites necessary for the reaction to proceed, but also an environment that enhances para selectivity. This process avoids the use of the corrosive acetyl chloride and AICI3 reagents and with it the formation of the toxic HCl by-product of the classical Friedel-Crafts acetylation. Instead, the by-product is acetic acid, itself a valuable commodity. 

Chirality plays a major role in the development of drugs. A chiral molecule is defined as nonsuperimposable on its mirror image. Two chiral molecules commonly called enantiomers are often compared to the right and left hands. The same type and number of atoms are in the two enantiomers but the spatial arrangement of atoms is different Usually one enantiomer is preferred over the other. In the pharmaceutical industry chiral molecules constitute a large portion of pharmaceutical sales. More than half the drugs approved worldwide are chiral. Examples include Lipitor and Zocor , as well as ibuprofen sold under the common brand names Motrin and Advil . 

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