Sodium borohydride handling

Sodium borohydride reacts with boron halides to form diborane [19287-45-7] 2 6 more conveniendy handled as the monomer... 

Literally dozens of reagents are used in the laboratory to reduce aldehydes and ketones, depending on the circumstances, but sodium borohydride, NaBH4, is usually chosen because of its safety and ease of handling. Sodium borohydride... 

Braman et al. [713] suggested the use of sodium borohydride (NaBH4) as a reducing agent to replace the metallic zinc used in the classical Marsh test, which is awkward to handle and often contains large blanks of the elements of interest. Sodium borohydride is now used almost exclusively in the various modifications of the hydride method. 

A boron analog - sodium borohydride - was prepared by reaction of sodium hydride with trimethyl borate [84 or with sodium fluoroborate and hydrogen [55], and gives, on treatment with boron trifluoride or aluminum chloride, borane (diborane) [86. Borane is a strong Lewis acid and forms complexes with many Lewis bases. Some of them, such as complexes with dimethyl sulfide, trimethyl amine and others, are sufficiently stable to have been made commercially available. Some others should be handled with precautions. A spontaneous explosion of a molar solution of borane in tetrahydrofuran stored at less than 15° out of direct sunlight has been reported [87]. 

Caution. Hydrogen tetrachloroaurate(III) hydrate is corrosive plastic or Teflon implements should be used to handle this material. Gas evolution can be violent on addition of sodium borohydride, and the contents of the flask may... 

Solid sodium borohydride does not ignite upon contact with moisture and is not shock sensitive. These characteristics allow it to be handled safely in air. Because it does liberate hydrogen upon contact with water it should be handled with care. 

Lithium borohydride is intermediate in activity as a reducing agent between lithium aluminium hydride and sodium borohydride. In addition to the reduction of aldehydes and ketones it will readily reduce esters to alcohols. It can be prepared in situ by the addition of an equivalent quantity of lithium chloride to a 1m solution of sodium borohydride in diglyme. Lithium borohydride should be handled with as much caution as lithium aluminum hydride. It may react rapidly and violently with water contact with skin and clothing should be avoided. 

Compared with boranes, borohydrides are inexpensive and easy to handle. As early as 1978 Colonna and Fornasier reported that aryl alkyl ketones such as acetophenone can be reduced asymmetrically by sodium borohydride by use of an aqueous-organic two-phase system and chiral phase transfer catalysts [20], In this study, the best enantiomeric excess (32%) was achieved when pivalophenone (11) was reduced in the presence of 5 mol% benzylquininium chloride (12) (Scheme 11.4) [20]. Other chiral phase-transfer catalysts, for example ephedrinium salts, proved less effective. 

Three years after Narasaka and Pai s disclosure, Prasad et al. developed a modified procedure to improve syn -diastereoselecti vi ty in the reduction of certain (3-hydroxy ketones6 (Scheme 4.Id). When methoxydiethylborane, in lieu of tributylborane, reacts with p-hydroxy ketones at —70 C in anhydrous methanol, the complex 5BEt2 is formed. Subsequent treatment of the complex with sodium borohydride and quenching the reaction mixture with acetic acid affords yyn-diols in excellent levels of diastereoselectivity regardless of the structure of p-hydroxy ketones. Another practical advantage of Prasad et al. s modification may be an enhanced safety feature, as methoxydiethylborane is generally less hazardous to handle than triethylborane.6... 

Like alkene double bonds, carbonyl double bonds can be reduced by catalytic hydrogenation. Catalytic hydrogenation is slower with carbonyl groups than with olefinic double bonds, however. Before sodium borohydride was available, catalytic hydrogenation was often used to reduce aldehydes and ketones, but any olefinic double bonds were reduced as well. In the laboratory, we prefer sodium borohydride over catalytic reduction because it reduces ketones and aldehydes faster than olefins, and no gas-handling equipment is required. Catalytic hydrogenation is still widely used in industry, however, because H2 is much cheaper than NaBH4, and pressure equipment is more readily available there. 

We don t need to spend much time on this—sodium borohydride does it very well, and is a lot easier to handle than lithium aluminium hydride. It is also more selective it will reduce this nitroketone, for example, where LiAlH4 would reduce the nitro group as well. 

L1AIH4 is often the best reagent, and gives alcohols by the mechanism we discussed in Chapter 12. As a milder alternative (L1AIH4 has caused countless fires through careless handling), lithium borohydride in alcoholic solution will reduce esters—in fact, it has useful selectivity for esters over acids or amides that LiAlH4 does not have. Sodium borohydride reduces most esters only rather slowly. 

Hazards Wear gloves when handling sodium borohydride, which can cause skin burns. 

Ozonides are rarely isolated [75, 76, 77, 78, 79], These substances tend to decompose, sometimes violently, on heating and must, therefore, be handled with utmost safety precautions (safety goggles or face shield, protective shield, and work in the hood). In most instances, ozonides are worked up in the same solutions in which they have been prepared. Depending on the desired final products, ozonide cleavage is done by reductive or oxidative methods. Reductions of ozonides to aldehydes are performed by catalytic hydrogenation over palladium on carbon or other supports [80, 81, 82, S3], platinum oxide [84], or Raney nickel [S5] and often by reduction with zinc in acetic acid [72, 81, 86, 87], Other reducing agents are tri-phenylphosphine [SS], trimethyl phosphite [89], dimethyl sulfide (DMS) [90, 91, 92], and sodium iodide [93], Lithium aluminum hydride [94, 95] and sodium borohydride [95, 96] convert ozonides into alcohols. 

In 1978, Colonna and coworkers first demonstrated that in the presence of cinchona-derived PTCs, alkyl aryl ketones can be reduced asymmetrically with the inexpensive and easily handled sodium borohydride under aqueous-organic biphasic conditions. However, the enantiomeric excess of the corresponding alcohols was very disappointing. The best ee obtained in their study was 32% when pivalophenone was reduced in the presence of 5 mol% of benzylquininium chloride 1 (Scheme 5.28) [34]. Variants of this procedure were tried later by several research groups, but in all cases the enantioselectivities were too low for synthetic applications [35]. 

Although the catalytic asymmetric borane reductions mentioned above are a powerful tool to obtain highly enantio-enriched alcohols, these require the use of a rather expensive and potentially dangerous borane complex. Sodium borohydride and its solution are safe to handle and inexpensive compared to borane complexes. Thus sodium borohydride is one of the most common industrial reducing agents. However its use in catalytic enantioselective reductions has been limited. One of the most simple asymmetric catalysts is an enantiopure quaternary armnonium salt that acts as phase-transfer catalyst. For instance, in the presence of the chiral salt 81 (Fig. 9), sodium borohydride reduction of acetophenone gave the secondary alcohol in 39% ee [124]. The polymer-supported chiral phase-transfer catalyst 82 (Fig. 10) was developed for the same reduction to give the alcohol in 56% ee [125]. 

The hydrogen can be generated either by adding acid to Zn metal or the newer method of using a sodium borohydride solution. The borohydride is preferred because it is easier to handle, and the reaction appears to go better. 

Sodium borohydride reduction of autofluorescence (Beisker et al 1987 Clancy and Cauller, 1998). Note that sodium borohydride is a highly reactive and potentially explosive compound, handle with care maintain a dry environment, and avoid contact with water. 

---