1. Alexander Stadler and C. Oliver Kappe* First Symposium of the European Society For Combinatorial Sciences, Eurocombi-1, July 1-5, 2001, Budapest, Hungary Institute of Chemistry, Organic and Bioorganic Chemistry, Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria email: alexander.stadler@uni-graz.at Introduction: (A) Isourea-Method (B) Anhydride-Method (1:2) DCM / DMF 0°C, 30 min Ph O O Ph O + NCN Ph O HO O O Ph P P OH DMAP (cat.) NMP, 200°C 99 % 500 W, 10 min DCM / DMF 9:1 DMAP (cat.) + NCN N H NO O Ph Ph HO O O O Ph P P OH N H ON O Ph 58 % thermodynamically more stable http://www.milestonesci.com „open vessel“ system T (°C)Time(PhCO) 2 OConversion 10 min 50 80 120 150 200 3 eq 5 eq 27 % 39 % 48 % 53 % 74 % 99 % open vessel T (°C)TimeConversion 15 min 68 (50W) 89 (100W) 132 (200W) 153 (400W) 48 % 73 % 53 % 50 % sealed vessel NMP, 700 W, 5-10 min Cs 2 CO 3 (2.0 eq) O O Ar P (Merrifield) P Cl Ar-CO 2 H (1.5 eq)   Esterification of Polymer-Supported Alcohol Acknowledgement: This work was supported by the Austrian Science Fund (FWF, Project P-11994-CHE)   Microwave Equipment   Acid Attachment to Merrifield Resin (NMP, 200°C) P TFA/DCM = 1:1 500 W, 30 min > 99 % 120°C, 7 bar O O O Ph P h O H (Merrifield) Our experiments have shown that efficient attachment of carboxylic acids to chloromethylated polystyrene support is achieved by microwave flash heating in N-methylpyrrolidone (NMP) within 5-10 min. Employing microwave irradiation, acidolysis of the Merrifield linker can furthermore be carried out quantitatively using a conventional TFA/DCM mixture under elevated pressure. Stadler A., Kappe C.O., Eur. J. Org. Chem., 2001, 919-925 The Effect Of Microwave Irradiation Towards Carbodiimide-Mediated Esterifications On Solid Phase One of the most common solid-phase reactions in combinatorial synthesis involves the coupling of an acid (i.e. an amino acid) to polystyrene solid supports (i.e. Wang or Merrifield resin). A number of publications have reported the coupling of carboxylic acids to Merrifield resin via the cesium salt method and the esterification of Wang resin using carbodiimide either via the isourea method or the symmetrical anhydride method. Since the reaction times using conventional conditions have been reported to be rather long (16-48 h) we have investigated the effects of microwave irradiation towards both of these reactions using benzoic acid derivatives. Milestone MLS 1600 Multimode Batch Reactor Based on earlier results, esterification of Wang resin should also be achieved more rapidly by microwave irradiation, following the standard protocols. However, during the isourea-method, rearrangement of the thermolabile intermediate into the thermodynamically stable N-acylurea is observed. On the other hand significant rate enhancements were observed for the coupling of benzoic anhydride derivatives to polystyrene-supported alcohol using microwave flash heating in NMP. Reaction times were reduced from 2-3 days to 10 min by microwave dielectric heating. Stadler A., Kappe C.O., Tetrahedron, 2001, 3915-3920 Institut für Chemie Graz Microwave & Combichem shielded thermocouple