A new fluorous 2-chloropyridinium hexafluorophosphate was prepared as a modified Mukaiyama condensation reagent, and it was applied in amide formation reactions. Good to excellent purities of amides were obtained after fluorous solid-phase extraction of reaction mixtures without additional chromatography.
Chlorella pyrenoidosa (Chick) was grown heterotrophically in batch culture on defined medium with glucose. Morphometric analysis of cells in the exponential growth phase showed that starch accounted for 57% of the volume of the chloroplast and 36% of the total cell volume. During the stationary growth phase, the amount of starch accounted for only 36% of the chloroplast volume and 13% of the total cell volume. This represented a 36% decrease in the amount of starch/cell between the exponential and stationary phase. Determination of starch as grams/cell using quantitative techniques on cell extracts showed a comparable decrease in the amount of starch during this same transition. Based on these results, morphometric techniques provided an accurate assay of starch and have the added advantage of visualization of cellular structures not available when quantitative techniques are used.
Chlorella pyrenoidosa (Chick) was grown heterotrophically in batch culture on defined medium with glucose. Morphometric analysis of cells in the exponential growth phase showed that starch accounted for 57% of the volume of the chloroplast and 36% of the total cell volume. During the stationary growth phase, the amount of starch accounted for only 36% of the chloroplast volume and 13% of the total cell volume. This represented a 36% decrease in the amount of starch/cell between the exponential and stationary phase. Determination of starch as grams/cell using quantitative techniques on cell extracts showed a comparable decrease in the amount of starch during this same transition. Based on these results, morphometric techniques provided an accurate assay of starch and have the added advantage of visualization of cellular structures not available when quantitative techniques are used.
A new fluorous 2-chloropyridinium hexafluorophosphate was prepared as a modified Mukaiyama condensation reagent, and it was applied in amide formation reactions. Good to excellent purities of amides were obtained after fluorous solid-phase extraction of reaction mixtures without additional chromatography.
Keywords fluorous reagent; amide coupling; fluorous solid-phase extractionAmide formation is one of the most common transformations in organic synthesis. As a part of our ongoing effort on the development of new fluorous reagents for high-speed organic synthesis, 1 we recently initiated a project to develop chromatography-free, solution-phase amide formation protocols. Reactions involving fluorous reagents are usually conducted in common organic solvents, and the byproducts from fluorous reagents are removed by fluorous solid-phase extraction (F-SPE). 2 Reactions with fluorous reagents have advantages of homogeneous reaction environment, while reactions with polymer-bound reagents are conducted under heterogeneous conditions where mode of agitation, quality of resin, and degree of swelling often affect the outcome of reactions. 3Since the Mukaiyama condensation reagent (N-methyl-2-chloropyridinium iodide) was first introduced in 1975 for esterification of carboxylic acids, 4 various N-alkyl-2-halopyridinium salts have been used for coupling and dehydrating reactions. 5 Here we report the synthesis of a new N-alkyl-2-chloropyridinium hexafluorophosphate containing a C 9 F 19 fluorous tag, and its application as separation friendly Mukaiyama condensation reagent for amide formation reactions. 6Fluorous tagged 2-chloropyridinium hexafluorophosphate 3 was prepared from the corresponding benzyl alcohol 1 7 in 4 steps (Scheme 1). Pyridinium salt 3 is stable white powder that can be stored under air with no significant indication of decomposition over a year.Because pyridinium salt 3 directly reacts with primary and secondary amines rapidly, we decided to activate carboxylic acid first by adding N,N-diisopropylethylamine (DIEA) to a mixture of carboxylic acid and pyridinium salt 3, and then to add an amine to form the corresponding amide (Scheme 2). LC-MS analysis of a mixture of N-methylindole-3-carboxylic acid 4, pyridinium salt 3, and DIEA showed three major peaks; two of which were assigned as carboxylic anhydride 5 and pyridone 6. The unidentified peak was presumably from acyloxypyridinium intermediate 7 since the peak disappeared immediately after the In contrast, formation of the carboxylic anhydride 5 was completely suppressed in the presence of 1-hydroxybenzotriazole (HOBt). As shown in Scheme 3, DIEA was added to a mixture of carboxylic acid 4, pyridinium salt 3, and HOBt. LC-MS analysis of the mixture indicated that the corresponding OBt ester 9 formed within a few minutes after the addition of DIEA. Dibenzylamine was then added to form amide 8. 9 To isolate amide 8, MP-Trisamine and MPCarbonate were used to scavenge the remaining OBt ester 9 and HOBt, and then F-SPE was conducted to remove fluorous...
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