1. An environmentally bening technology: selective liquid-phase catalytic hydrogenation Antal Tungler Department of Chemical Technology BUTE 2004

2. E fa c tor Comparison of atom utilisation Topics of the presentation : Types of selectivity Methods of improving selectivity Asymmetric catalysis New substrates and modifiers in enantioselective hydrogenations Diastereoselective hydrogenations Perspectives of the preparation of optically active compounds with hydrogenation Results from our laboratory are highlighted! PhNO 2 + 3H 2 = PhNH 2 + 2H 2 O A U = 93/129 = 72 % PhNO 2 + 2Fe +H 2 O = PhNH 2 + Fe 2 O 3 A U = 93/253 = 36,8 % PhCOCH 3 + H 2  PhCH(OH)CH 3 A U = 120/120 = 100 %  4 PhCOCH 3 + NaBH 4 + 4 H 2 O  4 PhCH(OH)CH 3 + NaB(OH) 4 A U = 122/147,5 = 82,7 %  Reduction Catalytic Stoichiometric

5. Stereoselectivity thymol

6. Enantioselectivity β -ketoester hydrogenation with tartaric acid modified Raney-nickel catalyst Hydrogenation of the C=C bond of isophorone with Pd in the presence of (S)-proline Tungler and his co-workers, 1989 Best ee > 60%

8. Comparison of homogeneous and heterogeneous catalysts Comparison of homogeneous and heterogeneous asymmetric catalysts Uniform active sites: zeolites, better characterisation Improve separation: two-phase systems, heterogenisation, encapsulation, increase productivity What to do? Difficult preparation, poorly defined, transport limitations Sensitivity, small stability and activity, difficult separation Disadvantages Activity, separation, stability, recovery Selectivity, scope, variability, well defined Advantages Heterogeneous Homogeneous Characteristics Uniform active sites: zeolite support, better characterisation Improve separation: two-phase systems, heterogenisation, encapsulation, increase productivity What to do? Poorly defined, usually small ee, only on low temperature, up till now only metal catalysts Sensitivity, small activity, difficult separation, complicated ligand synthesis Disadvantages Activity, separation Selectivity, broad scope, variability, high ee Advantages

9. How can be infuenced selectivity? Change the solvent Replace the catalyst

10. Modification of the catalyst with alloying of the active metal The preparation of aromatic aldehydes with the hydrogenation of the corresponding acid chlorides with SELCAT RA Pd-Cu/C catalyst

12. Influencing the selectivity with the mode of preparation, metal deposition aliphatic tetralol aromatic tetralol 80% regioselectivity with the SELCAT Q catalyst

13. Extend the scope : new substrates in Pt/cinchona mediated reactions 96.5

14. Hydrogenation of isophorone in the presence of ( S )-proline as a chiral auxiliary A. Tungler, M. Kajtár, T. Máthé, G. Tóth, E. Fogassy, J. Petró: Catalysis Today, 5, 159-171, (1989). A. Tungler, T. Máthé, J. Petró, T. Tarnai: J. of Molecular Catal. 61 , 259-267, (1990).

15. Search for new catalysts, modifiers and substrates

16. Diastereoselective hydrogenations

17. Perspectives of different hydrogenation methods for the preparation of optically active compounds hopeful no limited promising good Industrial application broad narrow increasing increasing broad Scope acceptable poor good good excellent Chemical yield poor  excellent good good  excellent good  excellent good  excellent Optical purity Schiff’s bases Picolinic acid amide Pd/C Isophorone Pd-(S)-proline Ethyl pyruvate Pt/cinchonidine Dehydroamino acid DIPAMP/PTA Al 2 O 3 Metolachlor/ Josiphos Examples Diastereo- selective hydrogenation Use of chiral auxiliaries in the reaction mixture Chiral modification of heterogeneous catalysts Anchored homogeneous catalysis Homogeneous transition metal complex catalysis Methods