Optimization of the Mizoroki-Heck reaction using Design of Experiment (DoE)

Organic Process Research and Development

Volumn 10, Issue 1, 2006, Pages 64-69

  Aggarwal, Varinder K ^a   Staubitz, Anne C ^a   Owen, Martin ^b  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 33344460691     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op058013q     Document Type: Article

References (19)

1. Amorese, A.; Arcadi, A.; Bernocchi, E.; Cacchi, S.; Cerrini, S.; Fedeli, W.; Ortar, G. Tetrahedron 1989, 45, 813.
2. For an introduction into DoE, see for factorial designs: (a) Box, G. E. P.; Hunter, W. G.; Hunter, J. S. Statistics for Experiments - An Introduction to Design, Data Analysis, and Model Building; Wiley: New York, 1978.
3. For response surface models, see: (b) Box, G. E. P.; Draper, N. R. Empirical Model-Building and Response Surfaces; Wiley: New York, 1987.
4. Solvent, type of catalyst, and base might also have an effect. There are methods such as principle component analysis (PCA) to convert categorical variables into numerical variables, and had the current study not been successful, these would have been studied.
5. Initially, we suspected that the catalyst stability would be reduced at higher temperatures. However, we were proven wrong, as the results of the factorial and later of the RSM study clearly showed.
6. The rationale behind the values chosen in the paper is not clear since they vary with different bases.
7. As the number of variables under consideration increase, the possible permutations of high and low settings increase rapidly.
8. The calculations and randomisations for this optimisation were done using a commercially available computer program: DesignExpert, version 6.0.10; StatEase, Inc.: 2021 East Hennepin Ave., Suite 480, Minneapolis, MN 55413, USA, 2003.
9. A half normal plot is a tool to visualize whether a factor or factor interaction has a significant effect. The red line is used to denote the factors that do not lead to a significant effect and follow the normal distribution. The further a factor falls to the right away from the line, the more pronounced the effect.
10. Reactions were run for 4 and 9 h and showed no further conversion at the first time point. Product decomposition was not evident.
11. As all reactions had to be done in the parallel reactor, this meant that to achieve this dilution the complete scale (and thus the volumes) had to be divided by two. However, to give some comparability to the factorial design, the tables will show the values in a molar volume scale (mL/mmol 18). For simplicity, this will be hinted at in the Supporting Information.
12. (a) Reetz, M. T.; Westermann, E. Angew. Chem., Int. Engl. Ed. 2000, 39, 165.
13. (b) Reetz, M. T.; Lohmer, G. Chem. Commun. 1996, 1912.
14. (a) de Vries, A. H. M.; Mulders, J. M. C. A.; Mommers, J. H. M.; Henderickx, H. J. W.; de Vries, J. G. Org. Lett. 2003, 5, 3285.
15. (b) Reetz, M. T.; de Vries, J. G. Chem. Commun. 2004, 1559.
16. For a discussion of Jefferey's conditions, see: (a) Jeffery, T.; David, M. Tetrahedron Lett. 1998, 39, 5751.
17. (b) Jefferey, T. Tetrahedron 1996, 52, 10113.
18. First characterization (microanalysis, mp): (a) Kohler, E. P.; Larsen, R. G. J. Am. Chem. Soc. 1935, 57, 1448.
19. For NMR, mass, IR, see: (b) Kurosawa, K.; Tsujita, T. Bull. Chem. Soc. Jpn. 1981, 54, 2391.