Novel methods for the quantification of toxic, residual phase transfer catalyst in fluorine-18 labeled radiotracers.

INTRODUCTION: Fluorine-18 labeled radiopharmaceuticals undergo quality control testing for residual phase-transfer-catalyst content. The almost universally used quality-control test is a silica plate spot-test comparison of the radiopharmaceutical beside a 50-ppm standard. Once developed by staining, the radiopharmaceutical spot must be of equal or less intensity to pass the test. There is currently a need for a quantitative, inexpensive, and less subjective quality control method that allows the automatic incorporation of the acquired measurement directly into electronic batch reports. RESULTS: In the developed method, a resazurin test solution is mixed with an aliquot of the radiopharmaceutical analyte along with dichloromethane (DCM). The mixture is vortexed. The potassium resazurin-phase transfer catalyst complex solubilizes into the DCM imparting a blue color. The organic layer is then removed for analysis. Three measurement methods were utilized: visual colorimetry against pre-prepared standards, spectrophotometric measurement of transmittance, and electrical conductance. A simple prototype spectrophotometer and an electrical test cell were constructed to acquire data. Sodium Resazurin dye was found to be a suitable test chromophore for residual phase transfer catalyst analysis of aqueous solutions. Quantitative spectrophotometric measurements are possible in the 0-100-ppm range (18-crown-6) and 0-150-ppm range (Kryptofix® or tetrabutylammonium). Electrical resistance measurements of the phase transfer-catalyst resazurin complex in DCM are also a viable method, allowing quantitative phase transfer catalyst measurements in the 0-100-ppm range. CONCLUSION: The methodologies developed are more quantitative alternatives to the current spot-test method. The spectrophotometric method was determined to be the most accurate method.

Synthesis of PEG-supported organotrifluoroborates and their applications in palladium-catalyzed homo-coupling reactions.

A general synthetic route to water-soluble PEG-supported organotrifluoroborates has been developed. In the presence of air and catalytic amounts of Pd(OAc)2, the PEG-supported organotrifluoroborates undergo homo-coupling reactions smoothly at room temperature. No additional oxidizing agent, base, or phosphine ligands are required.

Chemoselective bromodeboronation of organotrifluoroborates using tetrabutylammonium tribromide: application in (Z)-dibromoalkene syntheses.

Tetrabutylammonium tribromide (TBATB) has been found to be a unique bromodeboronation reagent for organotrifluoroborates. When compared to previously reported bromodeboronation methods, the mild and metal-free reaction conditions tolerate a wider range of functional groups. High regio- and chemoselectivity are observed in the presence of both unsaturated carbon-carbon bonds and aldehyde functional groups. An efficient synthetic route to (Z)-dibromoalkenes from terminal alkynes has been developed using the TBATB-mediated bromodeboronation as a key step.