Ibuprofen chemistry

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. 

Similar chemistry been used by Faigl and Schlosser in an elegant and simple synthesis of ibuprofen 632 using only superbase chemistry (Scheme 245). Starting with para-xylene 630, two successive metallations and alkylations give 631, which is once more metallated at the less hindered benzylic site and carbonated to give ibuprofen 632. 

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. 

Zwiener C., S. Seeger, T. Glauner, and F.H. Frimmel (2002). Metabolites of the biodegradation of pharmaceutical residues of ibuprofen in biofilm reactors and batch experiments. Analytical and Bioanalytical Chemistry 372 569-575. 

In 1992 BHC (Boots Hoechst-Celanese) Company commercialized a new synthetic process to manufacture ibuprofen in BHC s 3500 metric-ton-per-year facility in Bishop/TX, USA, which was cited as an industry model of environmental excellence in chemical processing technology. For its innovation, BHC was the recipient of the 1997 Alternative Synthetic Pathways Award of the Presidential Green Chemistry Challenge. 

Figure 12.20 A designer C H oxidation catalyst the positions the reactive CH-bond over the catalyst active site using molecular recognition. The ibuprofen substrate is oxidised to the 2-(4-Isobutyryl-phenyl) -propionic acid product in > 98 % selectivity (reproduced by permission of The Royal Society of Chemistry).

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. 

Green chemistry reduces toxicity, minimizes waste, saves energy, and cuts down on the depletion of natural resources. It allows for advances in chemistry to occur in a much more environmentally benign way. In the future, when green chemistry is practiced by all chemists and all chemical-related companies, the term green chemistry will ideally disappear as all chemistry becomes green, see also Ibuprofen Industrial Chemistry, Organic Solution Chemistry. 

There are basically two processes for the production of ibuprofen (see Fig. 2.31). Both involve a Friedel-Crafts acylation as the first step. In the classical route, developed by Boots, the p-isobutylacetophenone is subsequently converted to ibuprofen in five steps involving conventional organic chemistry. In the catalytic route, more recently developed by Hoechst, the p-isobutylacetophenone is converted in two steps. 

Reactions are at the heart of organic chemistry. An understanding of chemical processes has made possible the conversion of natural substances into new compounds with different, and sometimes superior, properties. Aspirin, ibuprofen, nylon, and polyethylene are all products of chemical reactions between substances derived from petroleum. 

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... 

An interesting example is ibuprofen and naxoprofen chemistry. The 20 years of naxoprofen technology have been reviewed recently [71], and the electrochemical route has also been described [72], Ibuprofen electrochemistry has been described by SNPE [73]. 

Levin, C.S., Kundu, J., Janesko, B.G., Scuseria, G.E., Raphael, R.M., and Halas, N.(. (2008) Interactions of ibuprofen with hybrid lipid bilayers probed by complementary surface-enhanced vibrational spectroscopies. Journal of Physical Chemistry B, 112, 14168-14175. 

After giving written informed consent, subjects provided a blood sample for a complete metabolic panel (blood chemistry and hematology), which the PI reviewed before the start of the study. On the test day, each subject s medical history was taken, and a brief medical exam was performed. Subjects were thrai randomized to one of three test groups to receive either a single dose of ibuprofen 400 mg a single dose of hops resin 450 mg or four doses of hops powder 300 mg, one dose every 2 horns for 6 horns (Table 4.2). 

The formation of C-C bonds is of key importance in organic synthesis. An important catalytic process for generating C-C bonds is provided by carbonylation. Most carbonylation reactions have a good atom economy, because most reagent atoms are transferred to the product. Therefore, there are some applications of carbonylation processes in fine chemistry, too. For example, the analgesic ibuprofen is produced by Hoechst-Celanese by carbonylation of a substituted alcohol with 100% atom efficiency according to Eq. (8-20) [7] ... 

The conventional process for the manufacture of ibuprofen consists of a six-step synthesis involving the use of stoichiometric reagents and large volumes of toxic solvents. A new catalytic route, which exploits carbonylation chemistry in one of the steps, is compared with the conventional route in Figure 8.10. The carbonylation step is critical and has many advantages. Further, this new catalytic route gives almost 99% atom utilization efficiency. 

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. 

RSC Ibuprofen - A Case Study in Green Chemistry in http //www.rsc.org/ Education/Teachers/Resources/green/ibuprofen/ibuprofen.pdf. 

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