Determination of the absolute amount of resin bound hydroxyl or carboxyl groups for the optimization of solid phase combinatorial and parallel organic synthesis

We have developed quantitative methods for the rapid determination of the absolute amount of hydroxyl or carboxyl groups directly on resin support. These methods are based on specific reactions between reagent 9-anthroylnitrile or 1-pyrenyldiazomethane (PDAM) and resin-bound hydroxyl or carboxyl groups. After the reaction, the remaining reagent molecules in the supernatant are quantitatively determined by UV-visible spectroscopy. The quantitation can be accomplished by analyzing 2-10 mg of resin sample in 30-60 min. The lowest amount of hydroxyl groups quantitatively analyzed in this work was 0.05 mmol/g of resin. For an array of reference samples, our results agree with the results obtained by the tedious derivatization method. Our methods have also been applied to the analysis of a series of solid-phase organic synthesis samples with various loading levels. The PDAM method is highly specific for carboxylic acid groups and the 9-anthroylnitrile method is also free from interference from most organic functional groups. The later method can also be used for nonhindered primary amine groups directly on resin. Both methods can also be used as a quick qualitative "color" test to identify whether hydroxyl or carboxyl groups are present on the resin.