Introduction

1. Renelle Gagnon Organic Chemistry SYNTHESIS OF IBUPROFEN Introduction Green Chemistry Ibuprofen is a popular over-the-counter drug that has pain relief and anti-inflammatory properties. It was originally developed in the 1960’s by the Boots Company of England. The Boots synthesis of Ibuprofen involved a six-step process that generated millions of pounds of unwanted waste. This became known as the Brown process due to reactants of the process not being incorporated into the product because of poor atom utilization. The solution to this problem was developed by the BHC Company in 1991. The implemented the green synthesis of Ibuprofen, which only required three steps. This process also incorporated most of the reactants into the final product, reducing or eliminating most of the waste by-products. The switch from the Boots process to the BHC process has resulted in a more efficient creation of Ibuprofen. Green chemistry is the change of chemical reactions and products that reduce hazardous waste for a healthier environment. There are twelve principles that have been adapted for chemical companies to follow when developing products. These are: Waste prevention Atom utilization Less hazardous chemical syntheses Safer chemical products Safer solvents and reaction conditions Energy efficiency Renewable feedstock No chemical derivatives Catalysts, rather than stoichiometric reagents Degradable products after use Minimize production of by-products Accident prevention with safer chemistry The green synthesis of ibuprofen utilizes at least five of these principles. The replacement of the six stoichiometric steps with the three catalytic steps relates to principles two, three and nine. The use of anhydrous hydrogen fluoride as a catalyst and a solvent covers principles nine and five. All together, the whole process of the synthesis of Ibuprofen also utilizes principle one, waste prevention. Conclusion Ibuprofen is the leading active ingredient in brand name drugs such as Motrin and Advil. When first developed by the Boots Company, the process generated millions of pounds of waste that was costly to dispose and posed hazardous risks to the environment. The greening of Ibuprofen production by the BHC Company has significantly reduced this waste and the hazards making it environmentally friendly. This innovation earned the Presidential Green Chemistry Award in 1997. Boots Method (Brown) BHC Method (Green) The making of Ibuprofen begins with the compound Isobutyl benzene. Step1: a Friedel-Crafts acylation that uses the catalyst aluminum-chloride that generates aluminum trichloride hydrate as waste by-product. Step 2: a Darzens reaction with ethyl-chloroacetate that results in an epoxy ester compound. Step 3: involves decarboxylation and hydrolyzation forming an aldehyde. Step 4: a reaction with hydroxylamine giving an oxime. Step 5: the oxime is converted to a nitrile. Step 6: hydrolyzation of the nitrile resulting in the final product 2,4-isobutylphenyl-propanoic acid. This process has a 40% atom economy which translates into 60% waste products. This means that if 30 million pounds of Ibuprofen is produced each year, then more than 35 million pounds of waste is generated. The green synthesis of Ibuprofen also begins with the compound isobutyl benzene. Step 1: a Friedel-Crafts acylation using hydrogen fluoride as the catalyst that can be recovered and reused. Step 2: involves hydrogenation with Raney nickel, which is recovered and reused, to produce an alcohol. Step 3: the alcohol undergoes carbonylation with the catalyst, palladium, also recovered and reused, to produce Ibuprofen or 2,4-isobutyl- phenylpropanoicacid. This process has a 99% atom economy, includes the recovered acetic acid that was generated in Step 1. This means that only 1% is waste by-products which Translated to less than 500,000 pounds of waste for the production of 30 million pounds of Ibuprofen. References BHC Company Ibuprofen Process. Green Chemistry Resource Exchange retrieved October 12, 2010 from www.greenchemex.org. Cann, M.C. & Connelly, M.E.(2000). Real World Cases in Green Chemistry, American Chemical Society: Washington, DC. Twelve Principles of Green Chemistry retrieved October 18, 2010 from www.epa.gov. What is green chemistry retrieved October 30, 2010 from www.dtsc.ca.gov/pollutionprevention/ All images reproduced from public domain of Wikipedia.