Extractive alkylation with pentafluorobenzyl bromide

To be able to determine theophylline in the ng range, Arbin and Edlund improved their method by derivatizing theophylline and the internal standard theobromine using penta-fluorobenzyl bromide, in connection with an electron capture detector. To 100 ul samples of plasma containing 50-1000 ng theophylline, 100 yl of a solution of the internal standard were added. The extraction was performed by column extraction (cellulose) using dichloro-methane as solvent. After back extraction into an alkaline aqueous phase (NaOH), theophylline and theobromine were alkylated with pentafluorobenzyl bromide by an extractive alkylation technique. The derivatives were extracted with cyclohexane and, after concentration to 3 ml, 2 yl were injected for the gas chromatographic assay. Standard deviation of the method was 2.5 % at a concentration level of 200 ng per sample, and 8 % at 20 ng per sample. The sample amounts were 100 yl plasma and 250 mg rat brain tissue, and the sensitivity limit... 

Huhtikangas et al. used also glass capillary columns for quantitative determination of morphine in plasma levels. A relative simple method was developed based on extractive alkylation of morphine with pentafluorobenzyl bromide. A glass capillary, 18 m by o.35 mm I.D. coat ed with 0V-225, and nalorphine as internal standard were used. The detection limit with FID... 

The thyrostatics can be alkylated to obtain better GC behavior. After extraction, an alkylation with methyl iodide can be made [71]. Alternatively, an extractive alkylation can be performed [68]. Recendy, an acylation with pentafluorobenzyl bromide has been successfully applied [72]. After a TLC separation, the thyrostatics can be isolated from the two dimensional TLC plate and sUylated with MSTFA, as was described by Batjoens et al. [73], yielding additional qualitative information. 

Extractive alkylation has a reaction scheme identical with that for the previous procedure. The substrate with a carboxyl group reacts in an aqueous solution with a quaternary base and is extracted in the form of an ion pair into a polar solvent of low solvation capacity (dichloromethane) that contains alkyl halide. Low solvation of the anion of the acid and high solvation of the reaction product lead to increased reactivity of the anion and to a rapid reaction with the alkylation agent in the organic phase. Methyl iodide [27] is used to prepare methyl esters and pentafluorobenzyl bromide [28] is used for the preparation of esters providing a high ECD response. 

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