Borohydride sodium

Ethanolic solutions of sodium borohydride reduce aldehydes and ketones in the presence of epoxides, esters, lactones, acids, nitriles, and nitro groups. 1 419 xhe reaction is very selective for reactive functional groups such as acid chlorides, aldehydes or ketones, and the yields are commonly 80%. The reduction of simple aldehydes or ketones that are part of more complex structures is perhaps the most prevalent use of sodium borohydride. The reduction of the ketone moiety in 91 to give the secondary alcohol in 92 (88% yield)l 0is a typical application involving sensitive functionality. Sodium borohydride often gives the 1,2- 

In section 4.2.C.ii, LiAlH4 was used to reduce ozonides to the alcohol (sec. 4.2.C.ii). Sodium borohydride can be used in an identical manner,127 as seen in the ozonolysis of 95, where borohydride reduction gave 96 without reduction of the sensitive trimethylsilyl ester. 128 Subsequent hydrolysis gave lactone 97, a key intermediate in Heathcock s synthesis of vernolepin.128 

One of the more important uses of sodium borohydride is the reduction of enamines, imines, and iminium salts, particularly useful in alkaloid and amino acid syntheses. Imine 98 was reduced to amine derivative 99 in 

74% yield in the Takano et al. enantiocontrolled synthesis of ( 5J-2-aminoadipic acid.1 9 in a similar manner, Werner used sodium borohydride to selectively reduce enamine 100 at the 1,2-position, giving 101 in a synthesis of Opioid antagonists. 30 Pyridinium salts can also be reduced, and this is illustrated by the conversion of 102 to 103 as part of Julia s synthesis of lysergic acid.l l in this reaction, initial reduction of the iminium salt generated a dienamine and 1,2-reduction gave the final product, 103. 

A good deal of interest has recently been shown in the nse of sodium tetrahydridoborate, or sodium borohydride as it is usually called, as a chemical hydrogen carrier. This reacts with water to form hydrogen according to the reaction 

If mixed with a snitable catalyst, NaBH4 can be used in solid form, and water is added to make hydrogen. The disadvantage of this method is that the material to be transported is a flammable solid, which spontaneously gives off H2 gas if it comes into contact with water. This is obviously a safety hazard. It is possible to purchase sodium borohydride mixed with 1% cobalt chloride for this purpose. However, this is not the most practical way to use the compound. 

The maximnm practical solution strength used is about 30%. Higher concentrations are possible, bnt take too long to prepare, and are subject to loss of solid at lower temperatures. The solution is made alkaline by the addition of about 3% sodium hydroxide - otherwise the hydrogen evolntion occurs spontaneously. The 30% solution is quite thick, and so weaker solutions are sometimes used, even though their effectiveness as a hydrogen carrier is worse. 

Such solutions are stable for long periods, though hydrogen evolution does occur slowly. The half-life of such solutions has empirically been shown to follow the equation 

In this equation the half-life fi/2 is in minutes, and the temperature T is in Kelvin. A solution of the type described has a half-life of about two years at 20°C. So it is best if the solutions are used fairly promptly after being made up, but rapid loss of hydrogen is not a problem. One litre of a 30% solution will give 67 g of hydrogen, which equates to about 800 ML. This is a very good volumetric storage efficiency. 

Form Supplied in colorless solid in powder or pellets supported on silica gel or on basic alumina 0.5 M solution in diglyme 2.0 M solution in trigl)me 12 wt % solution in 14 M aqueous NaOH. Typical impurities are sodium methoxide and sodium hydroxide. 

Analysis of Reagent Purity can be assessed by hydrogen evolution.  

The isolation of products is usually accomplished by diluting the reaction mixture with water, making it slightly acidic to destroy any excess hydride, and then extracting the organic product from the aqueous solution containing boric acid and its salts. 

Luca Banfi, Enrica Narisano Renata Riva University, di Genova, Italy 

Trialkyl borohydrides such as Lithium Tri-s-butylborohydride and Potassium Tri-s-butylborohydride are superior reagents for the chemoselective 1,4-reduction of enones. On the other hand, 1,2-reduction can be obtained by using NaBHj in the mixed solvent MeOH-THF (1 9), or with NaBHj in combination with CeCH or other lanthanide salts.  

This group of reagents is commercially available in large quantities some of its members - notably lithium aluminium hydride (LiAlH4), calcium hydride (CaH2), sodium borohydride (NaBH4) and potassium boro-hydride (KBH4) - have found widespread use in the purification of chemicals. 

This powerful drying agent is suitable for use with hydrogen, argon, helium, nitrogen, hydrocarbons, chlorinated hydrocarbons, esters and higher alcohols. 

White to pale gray hygroscopic crystals dihydrate melts 36-370C. 2 

Soluble in water (55% at 25°C) decomposes in water with evolution of hydrogen decomposes rapidly in boiling water.1 2 

Interaction with anhydrous acids (fluorophosphoric, phosphoric, or sulfuric) is 

Alkali. Alkaline solution may spontaneously heat and decompose while liberating hydrogen.4 

Aluminum Chloride. Violent explosion resulted from mixing a 4% solution of NaBH4 in diglyme with a 27% solution of A1C13 also in diglyme.5,6 

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The tetrahydridoborate ion, as "sodium borohydride" NaBH is soluble in water and is similarly an excellent reducing agent in this solvent. (Lithium tetrahydridoaluminate cannot be used in water, with which it reacts violently to give hydrogen.)... 

Potassium and sodium borohydride show greater selectivity in action than lithium aluminium hydride thus ketones or aldehydes may be reduced to alcohols whilst the cyano, nitro, amido and carbalkoxy groups remain unaffected. Furthermore, the reagent may be used in aqueous or aqueous-alcoholic solution. One simple application of its use will be described, viz., the reduction of m-nitrobenzaldehyde to m-nitrobenzyl alcohol ... 

The synthetic equivalents of the synthon H" are the hydride donors sodium borohydride NaBH4, and lithium aluminium hydride LiAIHi. How might you make TM 21 using this disconnection ... 

Treating a benzene suspension of sodium borohydride (4 equiv.) With glacial acetic acid (3.25 equiv.) And refluxing the mixture for 15 min under nitrogen, after the initial rapid gas evolution subsided (ca. 3 mol of Hz liberated) [No Smoking ], gave a clear solution of NaBH(OAc)3. ... 

Synthesis of Alkviamines. General Procedures. Method (A). The synthesis of p-phenethylamine is representative. A flame dried, nitrogen-flushed, 100 ml flask, equipped with a septum inlet, magnetic stirring bar and reflux condenser ivas cooled to 0°C. Sodium borohydride (9.5 mmol, 0.36 g) was placed in the flask followed by sequential addition of THF (13-15 ml) and BF3-Et20 (12 mmol, 1.5 ml) at 0°C. After the addition, the ice bath was removed and the contents were stirred at room temperature for 15 min. The solution... 

In this preparation, phenyi-2-nitropropene is reduced to phenyl-2-nitropropane with sodium borohydride in methanol, followed by hydrolysis of the nitro group with hydrogen peroxide and potassium carbonate, a variety of the Nef reaction. The preparation is a one-pot synthesis, without isolation of the intermediate. 

Direct Borohydride Reduction of Alcohols to Alkanes with Phosphonium Anhydride Activation N-Proovlbenzene. To a solution of 5.56 g (20 mmol) of triphenylphosphine oxide in 30mL of dry methylene chloride at CfC was added dropwise a solution of 1.57 mL (10 mmol) of triflic anhydride in 30mL of dry methylene chloride. After 15 min when the precipitate appeared, a solution of 1.36g (10 mmol) of 3-phenyl-1-propanol in 10 mL of dry methylene chloride was added and the precipitate vanished in 5 min. An amount of 1.5g (40 mmol) of sodium borohydride was added as a solid all at once and the slurry was stirred at room temperature for... 

The above product (24 g, 0.067 mol) was dissolved in 90 10 dioxane-water (300 ml) and sodium borohydride (92.5 g, 0.067 mol) was added. The mixture was refluxed for 4h. The cooled solution was poured into 0.1 N HCl (1.11). A solid precipitated and was collected by filtration, dried and recrystallized from ether hexane to give 6,7-dibromo-4-methoxyindole (18.5 g, 90%). 

The conditions required for the sodium borohydride reduction of 2-amino-5-acylthiazoles are stronger than those used for the reduction of 2-acylamino-5-acylthiazole (476). 

The only reduction investigated more recently on thiazole derivatives concerns the action of sodium borohydride upon thiazolium salts chosen as model molecules for thiamine (478-480). 

The alkaline conditions of the reduction with aqueous sodium borohydride leads to competitive reactions of the OH nucleophile, but the product usually obtained from a thiazolium salt (195) is the corresponding thiazolidine (196). 

The salt sodium borohydride NaBH4 has an ionic bond between ] and the anion BH4 What are the H—B—H angles in the borohydride anion J... 

For most laboratory scale reductions of aldehydes and ketones catalytic hydro genation has been replaced by methods based on metal hydride reducing agents The two most common reagents are sodium borohydride and lithium aluminum hydride... 

Sodium borohydride (NaBH4) Lithium aluminum hydnde (L1AIH4)... 

Sodium borohydride is especially easy to use needing only to be added to an aque ous or alcoholic solution of an aldehyde or a ketone... 

Sodium borohydride and lithium aluminum hydride react with carbonyl compounds in much the same way that Grignard reagents do except that they function as hydride donors rather than as carbanion sources Figure 15 2 outlines the general mechanism for the sodium borohydride reduction of an aldehyde or ketone (R2C=0) Two points are especially important about this process... 

The mechanism of lithium aluminum hydride reduction of aldehydes and ketones IS analogous to that of sodium borohydride except that the reduction and hydrolysis... 

Neither sodium borohydride nor lithium aluminum hydride reduces isolated carbon-carbon double bonds This makes possible the selective reduction of a carbonyl group m a molecule that contains both carbon-carbon and carbon-oxygen double bonds... 

Sodium borohydride is not nearly as potent a hydride donor as lithium aluminum hydride and does not reduce carboxylic acids... 

Sodium borohydride reduces esters but the reaction is too slow to be useful Hydrogenation of esters requires a special catalyst and extremely high pressures and tern peratures it is used m industrial settings but rarely m the laboratory... 

Reduction to alcohols (Section 15 2) Aide hydes are reduced to primary alcohols and ketones are reduced to secondary alcohols by a variety of reducing agents Catalytic hydrogenation over a metal catalyst and reduction with sodium borohydride or lithium aluminum hydride are general methods... 

Nucleophilic addition to carbonyl groups sometimes leads to a mixture of stereoisomeric products The direction of attack is often controlled by stenc factors with the nude ophile approaching the carbonyl group at its less hindered face Sodium borohydride reduction of 7 7 dimethylbicyclo[2 2 IJheptan 2 one illustrates this point... 

The enzyme is a single enantiomer of a chiral molecule and binds the coenzyme and substrate m such a way that hydride is transferred exclusively to the face of the carbonyl group that leads to (5) (+) lactic acid Reduction of pyruvic acid m the absence of an enzyme however say with sodium borohydride also gives lactic acid but as a racemic mixture containing equal quantities of the R and S enantiomers... 

Sodium borohydride has also been used to reduce aryl diazonium salts m reductive deam mation reactions... 

Does sodium borohydride reduction of o ribose yield an opti... 

The structure of the bicychc monoterpene borneol is shown in Figure 26 7 Isoborneol a stereoisomer of borneol can be prepared in the labora tory by a two step sequence In the first step borneol is oxidized to camphor by treatment with chromic acid In the second step camphor is reduced with sodium borohydride to a mixture of 85% isoborneol and 15% borneol On the basis of these transformations deduce structural formulas for isoborneol and camphor... 

The elements listed in the table of Figure 15.2 are of importance as environmental contaminants, and their analysis in soils, water, seawater, foodstuffs and for forensic purposes is performed routinely. For these reasons, methods have been sought to analyze samples of these elements quickly and easily without significant prepreparation. One way to unlock these elements from their compounds or salts, in which form they are usually found, is to reduce them to their volatile hydrides through the use of acid and sodium tetrahydroborate (sodium borohydride), as shown in Equation 15.1 for sodium arsenite. 

Some elements (S, Se, Te, P, As, Sb, Bi, Ge, Sn, Pb) are conveniently converted into their volatile hydrides before passed into the plasma. The formation of the hydrides by use of sodium tetrahydroborate (sodium borohydride) can be batchwise or continuous. 

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