Polymer bound borohydrides

In a recent study, the group of Moser has described the use of a polymer-bound borohydride in reductive aminations of tetrameric isoquinolines (Scheme 7.101) [122]. These tetrameric isoquinolines, which represented lead compounds in a search for antibacterial distamicyn A analogues, were prepared from the appropriate... 

Polymer-bound borohydride reagents were first reported in 1961 by two independent groups (1,2). More recently other authors have reported on polymer-bound borohydride attached to ion-exchange resins... 

We have investigated the solvolytic stability and reactivity of polymer-bound borohydrides and have evaluated these materials in several applications such as solvent purification, arsine generation, and metal reduction. These polymer-bound borohydrides offer several advantages over sodium or tetraethylammonium borohydride. The primary advantages are the convenience of use and the minimal introduction of ionic species or organic by-products into the treated bulk media. With the polymer-bound borohydrides, the cation is bonded covalently to the insoluble resin while the borohydride anion or its oxidation product (borate) is retained by ionic bonding. Typically, boron at levels of less than 5 ppm is the only impurity introduced into the treated medium. 

Figure 1. Preparation, use, and regeneration of polymer-bound borohydride...

This procedure assures quantitative conversion to the resin-boro-hydride form, obtained as a purified dry resin. Quantities of polymer-bound borohydride of up to 500 g have been prepared successfully by this procedure. 

B. Conversion of Resin Chloride to Polymer-Bound Borohydride. The resin was converted to the borohydride form by washing twice with aqueous IN NaBH4 solution stabilized with a small amount of sodium hydroxide (< 1.0 wt % ). (Each wash used twice the theoretical quantity of NaBH4 based on the total resin capacity of the column.) During use in chemical reductions, polymer-bound borohydride is oxidized to the borate form. Exhausted resin may be regenerated directly from the borate to the borohydride form by washing with the NaBH4 solution as described previously. 

C. Postpurification of Polymer-Bound Borohydride. The polymer-bound borohydride is washed with either deionized water or ethanol, depending on the media of intended use. Washing with anhydrous ethanol was used when essentially water-free resin was desired. Washing volumes were approximately two to three times the resin volume. In the case of Resin A-26 or IRA-400, washing was continued until a colorless effluent was obtained, signifying essentially complete removal of impurities present in the commercial resin. The polymer-bound borohydride may be used directly at this point for the purification of organic chemicals by column treatment. 

D. Drying of Polymer-Bound Borohydride and Analysis for Hydride Content. Residual solvents were removed from the polymer-bound borohydride for hydride content analysis. For this purpose, a sample (2-3g) of the polymer-bound borohydride was transferred to a suitable vessel and dried in a vacuum desiccator under a pressure of about 20 torr at ambient temperature. Percent hydride of the dry polymer-bound borohydride was determined by measuring the volume of hydrogen evolved on hydrolysis of the borohydride with acid. 

Purification of 9 5% Ethanol with Polymer-Bound Borohydride. A 90-cm3 bed (height = 17.8 cm area = 5.1 cm2) was charged with A-26 resin, borohydride form. A solution of 95% ethanol spiked with crotonaldehyde (initial aldehyde level = 82 ppm as CO, mol wt 28) was pumped continuously through the bed in an upflow manner. Aliquot samples were removed at various times and analyzed for aldehyde (ASTM Method E411-70). Contact time was calculated by dividing the empty bed volume by the flow rate. Several runs were made at various face velocities (i.e., flow rate/cross-sectional area) to determine the effect of face velocity on the aldehyde reduction/contact time relationship. 

Aldehyde Reduction. The results of 2-ethylhexanal reduction in 95% ethanol, 2-ethylhexanol, and hexane with the various types of polymer-bound borohydrides, sodium borohydride, and tetraethylammonium borohydride are shown in Table I. 

In nonpolar solvents such as hexane, the macroreticular styrene-DVB (A-26) polymer-bound borohydride was substantially more effective in aldehyde reduction than the other reducing agents. 

In 95% ethanol, sodium borohydride and the acrylate-DVB-based polymer-bound borohydrides (XE-279 and IRA-458) were not as reactive as tetraethylammonium borohydride or the styrene-DVB-based polymeric borohydrides (A-26 and IRA-400). In the 2-ethylhexanol and hexane evaluation, the macroreticular styrene-DVB polymer-bound borohydride (A-26) was, in general, more reactive than the other resins or sodium or tetraethylammonium borohydrides. 

Solvolytic Stability. Solvolytic stability of all four polymer-bound borohydrides was investigated in 100% ethanol as a function of temperature and in water as a function of pH. Comparative studies for sodium borohydride and tetraethylammonium borohydride were conducted. Solvolytic decomposition of the borohydride group results in the generation of hydrogen gas. Stability measurements were obtained by observing volume of hydrogen gas evolved as a function of time. Percent loss of hydride as a function of time was calculated from resin weight and initial hydride content. 

Figure 2. Stability of polymer-bound borohydride in 100% ethanol at 40°C percentage loss hydride vs.

Based on the stability and aldehyde and hydroperoxide reduction studies, the macroreticular borohydride-form styrene-DVB resin (A-26) appears to be the most reactive reducing agent of those investigated. This polymer-bound borohydride reagent was thus selected for investigation of several application areas of interest. 

In addition to offering convenient and effective removal of boro-hydride-reducible impurities, this system offers several unique advantages over sodium borohydride. First, the polymer-bound borohydride is remarkably stable in alcohols (with the exception of methanol). Second, since the hydride capacity is on the order of 12 meq of hydride per gram of dry resin, a small amount of polymer-bound borohydride will remove trace carbonyl impurities from a substantial volume of alcohol. Third and most importantly, no new contaminants such as Na+ or B02" are added to the alcohol since the borate ion remains bonded to the resin. 

Presently we are evaluating further the use of these polymer-bound borohydrides for purification of beverage ethanol as a supplement to existing purification methods. 

Generation of Volatile Hydrides (11). The use of commercial sodium borohydride as a reducing agent for the generation of volatile arsine (AsH3) in trace arsenic analysis is often complicated by trace (ppb) arsenic impurities in the borohydride. The following procedure using polymer-bound borohydride has eliminated these problems ... 

Reduction of Metal Ions. In terms of metal reduction, these polymer-bound borohydrides react analogously to sodium borohydride. Several examples of this reduction are shown in Table III. In most cases, the reduced metal was attached quite strongly to the resin beads. 

Based on the results of these studies we feel that polymer-bound borohydrides offer several advantages in the treatment of systems where introduction of ionic species is undesirable. These borohydrides are... 

We are continuing more detailed studies on the use of polymer-bound borohydrides for solvent and ethanol purification. 

In a more recent study, polymer-bound borohydride was used for reductive ami-nation of tetrameric isoquinolines [116]. These tetrameric isoquinolines, serving as lead compounds in research to find antibacterial distamicyn A analogues, have been prepared from the corresponding isoquinoline, imidazole, and pyrrole building blocks by standard amide bond formation reactions. The final derivatization by reductive amination was efficiently accelerated by microwave irradiation in the presence of Merrifield resin-supported cyanoborohydride (Scheme 16.76). 

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