Ibuprofen, green synthesis

Table 12.3. Materials involved in the green synthesis of ibuprofen...

Why is the process of manufacturing ibuprofen an excellent example of green synthesis ... 

The modern industrial-scale synthesis of ibuprofen has very high atom efficiency, and it has been modified from the original synthesis to be both more environmentally friendly and more cost effective. The original method involved six synthetic steps but used stoichiometric (as opposed to catalytic) quantities of reagents, had lower atom efficiency, and produced undesirable quantities of waste. The modern alternative, on the other hand, requires just three steps, each of which is catalytic in nature. The first step employs a recyclable catalyst (hydrogen fluoride, HF) and produces almost no waste. The second and third steps each achieve 100% atom efficiency (wow ). This process truly represents an idetd benchmark for excellence in green synthesis on the industrial scale. 

The original synthesis of the pain reliever ibuprofen required six reactions that together sent 23 H atoms, 7 C atoms, 8 O atoms, and 1 Cl, 1 Na, and 1 N atoms into waste products. A new green synthesis using the same starting materials requires only three steps and creates waste products containing only 4 H atoms, 2 C atoms, and 2 O atoms. 

Devise a synthesis of 5-Ibuprofen that, in terms of the principles of green chemistry, compares favourably with the commercial route outlined in Chapter 2. 

Lastly, Cann featured Colin Baird s Environmental Chemistry as an example of a text that has green chemistry integrated throughout every chapter. In addition, the preface is an introduction to green chemistry, atom economy, and the synthesis of ibuprofen. 

The BHC synthesis of ibuprofen has a high atom economy. Does this fact make the process green ... 

In 1992, BASF opened a 35 000 tons per year ibuprofen production plant in Bishop, Texas. This plant was the result of the elegant green chemistry route developed by the BHC consortium. The clean synthesis of ibuprofen is an excellent example of how combining catalysis and green chemistry can yield both commercial success and environmental benefits. Ibuprofen is a nonsteroidal, anti-inflammatory painkiller. It is a popular over-the-counter drug against headache, toothache, and muscular pains. You may know it better as Advil , Motrin , or Nurofen. 

The most frequently discussed green chemistry topic was catalysts, followed by the synthesis of ibuprofen, ionic liquids, supercritical solvents, atom economy, pesticides, polymers, renewable feedstocks, and the principles of green chemistry. Other green chemistry topics that were found included... 

In 1997, the Presidential Green Chemistry Challenge Greener Synthetic PathwaysAward was given to BHC Company (now BASF) for a novel method of ibuprofen synthesis.The new process consists of three catalytic steps, with the only byproduct being acetic acid, and has overall atom efficiency of about 80%. Since the acetic acid byproduct does not end up in the waste but is recovered, the process can be considered virtually 99% atom efficient. The older process, replaced by the award-winning one, consisted of six stoichiometric steps with an overall atom efficiency of less than 40%. 

The industrial synthesis of ibuprofen is a well-known case study for green chemistry . [190] The original Boots route, starting from benzene, comprised seven steps, p-lsobutylacetophenone is accessible by alkylation of benzene with isobutene, followed by a Friedel-Crafts acylation with acetic chloride. Homologation to the corresponding aryl-propionaldehyde is achieved by a Darzens reaction. Transformations via the oxime and nitrile, and hydrolysis of the latter, finally give ibuprofen. 

On page 299, A Word About... Green Chemistry and Ibuprofen A Case Study showed how efficiently ibuprofen can be prepared on a large scale. Another nonsteroidal, anti-inflammatory drug (NSAID) is acetaminophen. Suggest a short synthesis of acetaminophen from p-hydroxyaniline. 

To illustrate the benefits of atom economy, consider the synthesis of ibuprofen, mentioned earlier, which won the Presidential Green Chemistry Challenge Award in 1997. In the former process, developed in the 1960s, only 40% of the reactant atoms were incorporated into the desired ibuprofen product the remaining 60% of the reactant atoms found their way into unwanted by-products or wastes that required disposal. The new method requires fewer reaction steps and recovers 77% of the reactant atoms in the desired product. This "green" process eliminates millions of pounds of waste chemical by-products every year, and it reduces by millions of pounds the amount of reactants needed to prepare this widely used analgesic. 

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. 

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