Selective conversion of aldehydes to functional esters utilizing the Tishchenko reaction

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Report / Technical University of Helsinki, Department of Chemical Technology, Laboratory for Organic Chemistry, 1/2002
Different modifications of the Tishchenko reaction were studied in order to develop new catalysts and technology to produce 1,3-diol monoester derivatives. Related monoesters are the most common coalescing agents in paint industry with over 100 kilo tonnes total global annual production. The products can also be utilized as solvents and lubricants. During this project a selective process for the preparation of 1,3-diol monoesters with aldol-Tishchenko type mixed Tishchenko reaction via 1,3-dioxan-4-ols was developed and optimized to give a selective and economical method that can be scaled up to industrial scale. The 1,3-dioxan-4-ol type intermediates were initially prepared by dimerization of the isolated β-hydroxy aldehyde and another monofunctional aldehyde. New information concerning the formation, isolation and stability of 1,3-dioxan-4-ol type structures was also obtained. Due to the instability of 1,3-dioxan-4-ol like intermediates the method is temperature sensitive and should be conducted at relatively low temperatures. The catalyst studies in the esterification of 1,3-dioxan-4-ols indicated that the basic nature of the catalyst is essential for the initiation of the reaction. Also sufficient Lewis acidity is required due to the coordination of the counter cation to the oxygens of dioxanol and the formation of the transition state. New 1,3-diol based catalysts were found to give esterification rates of 1,3-dioxan-4-ols faster than previously used metal hydroxides. High yields were obtained without observable product hydrolysis. Another process developed was the homo aldol-Tishchenko reaction of monofunctional enolizable aldehydes to 1,3-diol monoesters under water free reaction conditions. The use of 1,3-diol based monoalcoholate catalysts and one of the formed side products as the solvent provides an advantageous and economical process as the costs due to the formation of wastes are minimized. This work focused on the production of the most important paint industry coalescing agents (2,2-dimethyl-3-hydroxyl-1-isopropyl-propyl)-2-methylpropionate and (3-hydroxy-2,2,4-trimethylpentyl)-2-methylpropionate with the highest yields reported ever. Finally, a new pathway to synthesize a Taxol™ A-ring building block was investigated. In the final step of the synthesis different forms of formaldehyde were utilized successfully as the electrophiles in the Shapiro reaction. The synthesis developed gives the Taxol™ A-ring in good stepwise yields and is clearly superior to the previously described pathways.
Tishchenko reaction, esterification, aldehyde dioxanol, monoester, alkoxide, Taxol A-ring
  • Törmäkangas, O. P.; Koskinen, A. M. P., The Tishchenko Reaction and Its Modifications in Organic Synthesis, Recent Res. Devel. Organic Chem 2001, 5, 225-255. [article1.pdf] © 2001 Transworld Research Network. By permission.
  • Törmäkangas, O. P.; Saarenketo, P.; Koskinen, A. M. P., Selective Mixed Tishchenko Reaction via Substituted 1,3-Dioxan-4-ols, Org. Proc. Res. & Dev. 2002, 6, 125-131. [article2.pdf] © 2002 American Chemical Society. By permission.
  • Törmäkangas, O. P.; Koskinen, A. M. P., Monoalcoholates of 1,3-Diols as Effective Catalysts in the Tishchenko Esterification of 1,3-dioxan-4-ols, Tetrahedron Lett. 2001, 42, 2743-2746. [article3.pdf] © 2001 Elsevier Science. By permission.
  • Törmäkangas, O. P.; Koskinen, A. M. P., Fast Aldol-Tishchenko Reaction Utilizing 1,3-Diol Monoalcoholates as the Catalysts, Org. Proc. Res. & Dev. 2001, 5, 421-425. [article4.pdf] © 2001 American Chemical Society. By permission.
  • Törmäkangas, O. P.; Toivola, R. J.; Karvinen, E. K.; Koskinen, A. M. P., A Short and Convenient Way to Produce the Taxol™ A-Ring Utilizing the Shapiro Reaction, Tetrahedron 2002, 58, 2175-2181. [article5.pdf] © 2002 Elsevier Science. By permission.
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