Optimizing selective partial hydrogenations of 4-nitroacetophenone via parallel reaction screening

Organic Process Research and Development

Volumn 5, Issue 3, 2001, Pages 328-330

  Hawkins, Joel M ^a   Makowski, Teresa W ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0035533038     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op010016p     Document Type: Article

References (17)

1. Rylander, P. N. Hydrogenation Methods; Academic Press: New York, 1985.
2. Augustine, R. L. Heterogeneous Catalysis for the Synthetic Chemist; Marcel Dekker: New York, 1995.
3. Argonaut Technologies, San Carlos, California (www.argotech.com).
4. For other commercially available parallel pressure reactors with varying configurations and specifications, see products from: Hazard Evaluation Laboratories, Hertfordshire, England, and Chemspeed, Augst, Switzerland.
5. For other approaches to catalyst screening, see: Simons, K. E. Top. Catal. 2000, 13, 201. Simms, C.; Singh, J. Org. Process Res. Dev. 2000, 4, 554. Blackmond, D. G.; Rosner, T.: Pfaltz, A. Org. Process Res. Dev. 1999, 3, 275. Petra, D. G. I.; Reek, J. N. H.; Kamer. P. C. J.; Schoemaker, H. E.; van Leeuwen, P. W. N. M. Chem. Commun. (Cambridge) 2000, 8, 683.
6. For other approaches to catalyst screening, see: Simons, K. E. Top. Catal. 2000, 13, 201. Simms, C.; Singh, J. Org. Process Res. Dev. 2000, 4, 554. Blackmond, D. G.; Rosner, T.: Pfaltz, A. Org. Process Res. Dev. 1999, 3, 275. Petra, D. G. I.; Reek, J. N. H.; Kamer. P. C. J.; Schoemaker, H. E.; van Leeuwen, P. W. N. M. Chem. Commun. (Cambridge) 2000, 8, 683.
7. For other approaches to catalyst screening, see: Simons, K. E. Top. Catal. 2000, 13, 201. Simms, C.; Singh, J. Org. Process Res. Dev. 2000, 4, 554. Blackmond, D. G.; Rosner, T.: Pfaltz, A. Org. Process Res. Dev. 1999, 3, 275. Petra, D. G. I.; Reek, J. N. H.; Kamer. P. C. J.; Schoemaker, H. E.; van Leeuwen, P. W. N. M. Chem. Commun. (Cambridge) 2000, 8, 683.
8. For other approaches to catalyst screening, see: Simons, K. E. Top. Catal. 2000, 13, 201. Simms, C.; Singh, J. Org. Process Res. Dev. 2000, 4, 554. Blackmond, D. G.; Rosner, T.: Pfaltz, A. Org. Process Res. Dev. 1999, 3, 275. Petra, D. G. I.; Reek, J. N. H.; Kamer. P. C. J.; Schoemaker, H. E.; van Leeuwen, P. W. N. M. Chem. Commun. (Cambridge) 2000, 8, 683.
9. We did not attempt to selectively partially hydrogenate the nitro group or to hydrogenate the ketone in the presence of the nitro group. The latter reaction is known for 4-nitroacetophenone with homogeneous catalysts, e.g., Penicaud, V.; Maillet, C.; Janvier, P.; Pipelier, M.; Bujoli, B. Eur. J. Org. Chem. 1999, 7, 1745 and (enantioselectively) Ohkuma, T.; Koizumi, M.; Doucet, H.; Pham, T.; Kozawa, M.; Murata, K.; Katayama, E.; Yokozawa, T.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1998, 120, 13529.
10. We did not attempt to selectively partially hydrogenate the nitro group or to hydrogenate the ketone in the presence of the nitro group. The latter reaction is known for 4-nitroacetophenone with homogeneous catalysts, e.g., Penicaud, V.; Maillet, C.; Janvier, P.; Pipelier, M.; Bujoli, B. Eur. J. Org. Chem. 1999, 7, 1745 and (enantioselectively) Ohkuma, T.; Koizumi, M.; Doucet, H.; Pham, T.; Kozawa, M.; Murata, K.; Katayama, E.; Yokozawa, T.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1998, 120, 13529.
11. In situ yields were determined at the end of the reactions by HPLC using an external standard as described in the Experimental Section.
12. Havilcek, L. L.; Crain, R. D. Practical Statistics for the Physical Sciences; American Chemical Society: Washington, DC, 1988; Chapter 13.
13. Unreacted 4-nitroacetopherione was also measured by HPLC but is not listed in Figure 1 for clarity. The mass balance for 4-nitroacetophenone + 1 + 2 + 3 averaged 96%.
14. The HPLC selectivity data from the full factorial screen with midpoints can be further analyzed using Design of Experiment software. In this particular case, the predicted optimum conditions were very close to the listed conditions.
15. Eight curves are generated at a time when using each of the reaction vessels on the Endeavor. Selected curves are shown in Figures 2 and 3 with the vertical axis converted from mmol to equiv of hydrogen for clarity.
16. These hydrogenation screens were preformed using the anchor-shaped stirrers originally supplied by Argonaut. We now generally use the oarshaped stirrers currently supplied by Argonaut.
17. Satterfield, C. N. Heterogeneous Catalysis in Industrial Practice. 2nd ed.; McGraw-Hill: New York, 1991; Chapter 3.