BHC Ibuprofen process

The Boots Hoechst Celanese (BHC) ibuprofen process involves palladium-catalyzed carbonylation of a benzylic alcohol (IBPE). More recently, we performed this reaction in an aqueous biphasic system using Pd/tppts as the catalyst (Figure 9.6 tppts = triphenylphosphinetrisulfonate). This process has the advantage of easy removal of the catalyst, resulting in less contamination of the product. 

The novel BHC ibuprofen process with its three catalytic steps and 80% atom utilization (99% with recycle) replaces a process with six stoichiometric steps at < 40% atom utilization. 

The BHC ibuprofen process is an innovative, efficient technology that revolutionized bulk pharmaceutical manufacturing. The new technology with its three catalytic steps achieves approximately 80% atom utilization, which is increased to almost 99% if recovery of the by-product acetic acid is included. It replaces a pro-... 

The BHC ibuprofen process is an innovative, efficient technology that has revolutionized bulk pharmaceutical manufacture. The process provides an elegant solution to a prevalent problem encountered in bulk pharmaceutical synthesis It avoids the large quantities of solvents and waste (especially aqueous salt waste... 

In the BHC (Boots-Hoechst Celanese) process about 3500 tons of ibuprofen per annum are produced by Pd/PPh3-catalysed carbonylation of IBPE (Figure 9) in the presence of HC1, in organic media.446 447,459 461 However, a shortcoming of this process is the cumbersome separation of the Pd/PPh3 catalyst from the... 

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. 

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

It is instructive to compare the atom economies of the two pathways. Atom economy is a measure of the efficiency of a chemical process, defined in percentage terms as x (formula wt. of atoms utilized)/(formula wt. of all reactants). For the old six-step ibuprofen synthesis the atom economy was only 40% (with MeC02H, EtOH, NaCl, Et0C02H, 2H2O and NH3 as waste). This is dramatically improved to 77% for the new three-step route with only MeC02H as a by-product from the first step. Recovery and use of this increases the atom economy to 99%. Additionally, the catalytic amounts of HF and Pd complex used in the BHC process are recovered and reused, whereas stoichiometric quantities of AICI3 hydrate were produced as waste by the old route. 

In the 1990s the Hoechst Celanese Corporation (together with the Boots company they formed the BHC process to prepare and market ibuprofen, 1.16) developed a new three-stage process (Scheme 1.9), with an atom economy of 77.4%. 

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%. 

Ibuprofen, an analgesic (marketed under the brand names Advil and Matrix ), was traditionally synthesized in six stoichiometric steps involving an atom-efficiency of less than 40%. A new catalytic process designed for the synthesis of Ibuprofen by BHC (BHC, 1997) involves three steps, with an atom-efficiency of 80%. Though the usage of HF, a toxic substance, is a drawback of the process, the recovery of HF is effected with 99.9% efficiency. This is a fine example of an eco-efficient process being commercialized. 

The BHC Company is a joint venture of the Hoechst Celanese Corporation and the Boots Company. BASF purchased the Boots Company and Celanese sold its interest in the BHC Company to BASF. Celanese operates the new ibuprofen manufacturing facility in Bishop, Texas, for BASF. Ibuprofen manufactured via the BHC process is marketed under the brand names Advil and Motrin. The industrial-scale facility created in Bishop, Texas, in 1992 is the world s largest ibuprofen manufacturing plant, is operated by the Celanese Corporation for BASF, and currently produces approximately 20-25 % (more than 7 million pounds) of the world s yearly supply of ibuprofen. 

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