I&EC 68 |
| Bisphosphonates have found significant use in pharmaceutical industry as well in ion sequestering and detergent applications. Blockbuster osteoporosis drug, sodium alendronate, is currently commercialized by several pharmaceutical companies. Cabot is interested in making aniline derivatized bisphosphonates for its applications. For carbon black and color pigments, surface modification with various bisphosphonates has lead to new generation pigment based inks with significantly better optical density, color saturation and other properties. Herein we present scale-up process study of one particular molecule, EDP, 2-(4-aminophenyl)-ethylidene-1,1-diphosphonic acid, mono sodium salt. Previous literature procedure (Benedicts et al, US patent 4830847) for the preparation of EDP has been found not suitable for large-scale production. We have come up with more improved and reliable synthesis. The synthesis of EDP involves several steps starting from tetraalkylmethylenediphosphonate (MDP). Coupling MDP with 4-nitrobenzaldehyde in the presence of TiCl4 at low temperature afforded vinyldiphosphonate, which is first reduced and then hydrogenated to an aniline phosphonate ester derivative, which is hydrolysis to afford the final product. Alternatively, the vinyldiphosphonate can be hydrolyzed and then hydrogenated to give EDP. The optimized conditions for the coupling reaction and the pros and cons of two follow-up processes are discussed. |
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IEC Poster Session
8:00 PM-10:00 PM, Tuesday, August 21, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Industrial & Engineering Chemistry |