Borohydrides aldehydes

The alkali metal tetrahydridoborates are salts those of sodium and potassium are stable in aqueous solution, but yield hydrogen in the presence of a catalyst. They are excellent reducing agents, reducing for example ion(III) to iron(II). and silver ions to the metal their reducing power is used in organic chemistry, for example to reduce aldehydes to alcohols. They can undergo metathetic reactions to produce other borohydrides, for example... 

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 ... 

For most laboratory scale reductions of aldehydes and ketones catalytic hydro genation has been replaced by methods based on metal hydride reducing agents The two most common reagents are sodium borohydride and lithium aluminum hydride...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

Common catalyst compositions contain oxides or ionic forms of platinum, nickel, copper, cobalt, or palladium which are often present as mixtures of more than one metal. Metal hydrides, such as lithium aluminum hydride [16853-85-3] or sodium borohydride [16940-66-2] can also be used to reduce aldehydes. Depending on additional functionahties that may be present in the aldehyde molecule, specialized reducing reagents such as trimethoxyalurninum hydride or alkylboranes (less reactive and more selective) may be used. Other less industrially significant reduction procedures such as the Clemmensen reduction or the modified Wolff-Kishner reduction exist as well. 

In pharmaceutical appHcations, the selectivity of sodium borohydride is ideally suited for conversion of high value iatermediates, such as steroids (qv), ia multistep syntheses. It is used ia the manufacture of a broad spectmm of products such as analgesics, antiarthritics, antibiotics (qv), prostaglandins (qv), and central nervous system suppressants. Typical examples of commercial aldehyde reductions are found ia the manufacture of vitamin A (29) (see Vitamins) and dihydrostreptomycia (30). An acyl azide is reduced ia the synthesis of the antibiotic chloramphenicol (31) and a carbon—carbon double bond is reduced ia an iatermediate ia the manufacture of the analgesic Talwia (32). 

Other Borohydrides. Potassium borohydride was formerly used in color reversal development of photographic film and was preferred over sodium borohydride because of its much lower hygroscopicity. Because other borohydrides are made from sodium borohydride, they are correspondingly more expensive. Generally their reducing properties are not sufficiently different to warrant the added cost. Zinc borohydride [17611-70-0] Zn(BH 2> however, has found many appHcations in stereoselective reductions. It is less basic than NaBH, but is not commercially available owing to poor thermal stabihty. It is usually prepared on site in an ether solvent. Zinc borohydride was initially appHed to stereoselective ketone reductions, especially in prostaglandin syntheses (36), and later to aldehydes, acid haHdes, and esters (37). 

Higher nitroalkanes are prepared from lower primary nitroalkanes by a one-pot synthesis (69). Successive condensations with aldehydes and acylating agents are followed by reduction with sodium borohydride. Overall conversions in the 75—80% range are reported. 

Pyridoxal Derivatives. Various aldehydes of pyridoxal (Table 3) react with hemoglobin at sites that can be somewhat controlled by the state of oxygenation (36,59). It is thereby possible to achieve derivatives having a wide range of functional properties. The reaction, shown for PLP in Figure 3, involves first the formation of a Schiff s base between the amino groups of hemoglobin and the aldehyde(s) of the pyridoxal compound, followed by reduction of the Schiff s base with sodium borohydride, to yield a covalendy-linked pyridoxyl derivative in the form of a secondary amine. 

Greater selectivity in purification can often be achieved by making use of differences in chemical properties between the substance to be purified and the contaminants. Unwanted metal ions may be removed by precipitation in the presence of a collector (see p. 54). Sodium borohydride and other metal hydrides transform organic peroxides and carbonyl-containing impurities such as aldehydes and ketones in alcohols and ethers. Many classes of organic chemicals can be purified by conversion into suitable derivatives, followed by regeneration. This chapter describes relevant procedures. 

Potassium borohydride is similar in properties and reactions to sodium borohydride, and can similarly be used as a reducing agent for removing aldehydes, ketones and organic peroxides. It is non-hygroscopic and can be used in water, ethanol, methanol or water-alcohol mixtures, provided some alkali is added to minimise decomposition, but it is somewhat less soluble than sodium borohydride in most solvents. For example, the solubility of potassium borohydride in water at 25° is 19g per lOOmL of water (as compared to sodium borohydride, 55g). 

Table 8.3. Rates of Reduction of Aldehydes and Ketones by Sodium Borohydride...

FIGURE 15.2 Mechanism of sodium borohydride reduction of an aldehyde or ketone. 

Reduction to alcohols (Section 15.2) Aldehydes 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. 

Condensation between aldehyde 40 and amine 29 followed by sodium borohydride reduction of the resultant imine and cyclisation yielded isoquinoline 41 in good yield. Cyclisation occurred exclusively at the more electron-rich aromatic group. 

Conjugate addition of methyl magnesium iodide in the presence of cuprous chloride to the enone (91) leads to the la-methyl product mesterolone (92) Although this is the thermodynamically unfavored axially disposed product, no possibility for isomerization exists in this case, since the ketone is once removed from this center. In an interesting synthesis of an oxa steroid, the enone (91) is first oxidized with lead tetraacetate the carbon at the 2 position is lost, affording the acid aldehyde. Reduction of this intermediate, also shown in the lactol form, with sodium borohydride affords the steroid lactone oxandrolone... 

The key intermediate 21 is in principle accessible in any of several ways. Thus reaction of thiophenecarbox-aldehyde with amninoacetal would lead to the Schiff base 20 treatment with acid would result in formation of the fused thiophene-pyridine ring (21). Alkylation of that intermediate with benzyl chloride gives the corresponding ternary imini urn salt 23. Treatment with sodium borohydride leads to reduction of the quinolinium ring and thus formation of ticlopidine (24). ... 

---