Using one- and two-dimensional NMR techniques to characterize reaction products bound to Chiron SynPhase crowns

Solid-phase MAS techniques have proved to be very useful in characterizing compounds bound to resin; however, little has been reported on using NMR to characterize compounds attached to Chiron SynPhase crowns. We have used proton, carbon, and COSY spectra obtained with a Varian Nano.nmr probe to characterize products from a published reaction sequence attached to MD (methacrylic acid/dimethylacrylamide copolymer) crowns. We have also performed solvent surveys to determine the best solvents for acquiring spectra of materials bound to both MD and PS (polystyrene) crowns.     

High-throughput manual parallel synthesis using SynPhase crowns and lanterns

The high-throughput manual solid-phase parallel synthesis of libraries comprising thousands of discrete samples using pellicular supports (i.e. SynPhase crowns and lanterns) and a suite of novel tools and techniques is described. Key aspects of this approach include the combination of a split-split-split synthesis strategy with spatial encoding to differentiate thousands of crowns, the rapid washing and filtration of up to 48 reaction vessels in parallel, the application of an inexpensive and environmentally friendly technique to remove trifluoroacetic acid from sixteen 96-well plates in parallel, and a high-throughput method for removing cleaved crowns from reusable pin racks. Tens of thousands of discrete samples have been produced in-house using this conceptually and operationally straightforward strategy.     

An efficient one-pot synthesis of 3-aryl-5-methylisoxazoles from aryl aldehydes

An efficient protocol for the one-pot preparation of alkyl 3-aryl-5-methylisoxazole-4-carboxylates from aryl aldehydes is described. This method is readily amenable to the large scale preparation of isoxazoles as well as the parallel synthesis of isoxazole libraries.     

2,5-Dimethylfuran (DMFu): An Internal Standard for the "Traceless" Quantitation of Unknown Samples via (1)H NMR

The use of 2,5-dimethylfuran (DMFu) as an internal standard for the quantitation of unknown samples by (1)H NMR is described. DMFu was selected based upon its low chemical reactivity, good solubility in standard NMR solvents, appropriate volatility (bp 92 degrees C), and the chemical shifts of its two singlets (5.80 and 2.20 ppm). In particular, the widely separated singlets of DMFu offer two advantages over more traditional "single peak" internal standards (e.g., hexamethyldisiloxane): (1) they reduce the possibility for overlap between analyte and internal standard signals; and (2) they enable the chemist to assess the accuracy of integration (and ergo, the quantitation) by calculating the ratio of the two singlets and comparing the observed ratio to the theoretical value. Our experiments have shown that the precision of the ratio of DMFu singlets strongly correlates to the precision of sample quantitation, an observation which greatly simplifies the assessment of the quality of the quantitation. Utilizing this technique, we have developed straightforward conditions for (1)H NMR experiments which consistently provide quantitative results with less than 5.0% error.