Strong Hydrogen Bond Donating Solvents Accelerate the Passerini Three-Component Reaction

The Journal of Organic Chemistry, vol. 90, pp. 5000–5007

Abstract

We report enhanced reaction rates of the Passerini reaction (P-3CR) using 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a cosolvent. Although alcoholic solvents typically increase the energy barrier of the rate-determining step for the P-3CR, we observed significant rate enhancements even when employing strong hydrogen bond donating (HBD) alcohols as cosolvents. This rate enhancement was observed for most aprotic organic solvents, with the exception of strong hydrogen bond accepting (HBA) solvents such as DMF. Experimental kinetic studies and DFT calculations provided a mechanistic rationale for our observations. An investigation of the substrate scope showed that this rate enhancement generally resulted in a (slight) increase of the overall yield in the P-3CR.

Authors 9

1. Claudio Ferdeghini

   Maastricht University

   Affiliation as printed

   Biobased Organic Chemistry, Aachen-Maastricht Institute for Biobased Materials (AMIBM), Maastricht University, Urmonderbaan 22, Geleen 6167RD, The Netherlands

2. Minghui Wu

   Maastricht University

   Affiliation as printed

   Biobased Organic Chemistry, Aachen-Maastricht Institute for Biobased Materials (AMIBM), Maastricht University, Urmonderbaan 22, Geleen 6167RD, The Netherlands

3. Prabhat Ranjan

   Maastricht University

   Affiliation as printed

   Biobased Organic Chemistry, Aachen-Maastricht Institute for Biobased Materials (AMIBM), Maastricht University, Urmonderbaan 22, Geleen 6167RD, The Netherlands

4. Martien A. Würdemann

   Maastricht University

   Affiliation as printed

   Biobased Organic Chemistry, Aachen-Maastricht Institute for Biobased Materials (AMIBM), Maastricht University, Urmonderbaan 22, Geleen 6167RD, The Netherlands

5. Jan F. Pyschik Aachen Process Systems Engineering (AVT.SVT)

   RWTH Aachen University

   Affiliation as printed

   Process Systems Engineering, RWTH Aachen University, Schinkelstrasse 8, Aachen 52062, Germany

6. Alexander Mitsos Aachen Process Systems Engineering (AVT.SVT)

   RWTH Aachen University

   Affiliation as printed

   Process Systems Engineering, RWTH Aachen University, Schinkelstrasse 8, Aachen 52062, Germany

7. Eelco Ruijter

   Vrije Universiteit Amsterdam

   Affiliation as printed

   Department of Chemistry & Pharmaceutical Sciences and Amsterdam Institute for Molecular & Life Science (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, Amsterdam 1081 HZ, The Netherlands

8. Romano V. A. Orrù

   Maastricht University

   Affiliation as printed

   Biobased Organic Chemistry, Aachen-Maastricht Institute for Biobased Materials (AMIBM), Maastricht University, Urmonderbaan 22, Geleen 6167RD, The Netherlands

9. Jordy M. Saya corresponding

   Maastricht University

   Affiliation as printed

   Biobased Organic Chemistry, Aachen-Maastricht Institute for Biobased Materials (AMIBM), Maastricht University, Urmonderbaan 22, Geleen 6167RD, The Netherlands