Sodium borohydride, reaction with ketones

Sodium borohydride, reaction with ketones and aldehydes,... 

In Chapter 19 (Section 19.2), lithium aluminum hydride and sodium borohydride reacted with ketones or aldehydes via acyl addition to reduce the carbonyl to the corresponding alcohol. This reaction is complicated by the presence of a conjugating n-bond. When cyclohexenone reacts with LiAlH4, the product is a mixture of cyclohexenol (66) and cyclohexanol (67). Cyclohexenol results from 1,2 addition of the hydride, but 67 results from 1,4 addition and 1,2 addition. 

Two years later, the same group reported a formal synthesis of ellipticine (228) using 6-benzyl-6H-pyrido[4,3-f>]carbazole-5,ll-quinone (6-benzylellipticine quinone) (1241) as intermediate (716). The optimized conditions, reaction of 1.2 equivalents of 3-bromo-4-lithiopyridine (1238) with M-benzylindole-2,3-dicarboxylic anhydride (852) at —96°C, led regioselectively to the 2-acylindole-3-carboxylic acid 1233 in 42% yield. Compound 1233 was converted to the corresponding amide 1239 by treatment with oxalyl chloride, followed by diethylamine. The ketone 1239 was reduced to the corresponding alcohol 1240 by reaction with sodium borohydride. Reaction of the alcohol 1240 with f-butyllithium led to the desired 6-benzylellipticine quinone (1241), along with a debrominated alcohol 1242, in 40% and 19% yield, respectively. 6-Benzylellipticine quinone (1241) was transformed to 6-benzylellipticine (1243) in 38% yield by treatment with methyllithium, then hydroiodic acid, followed... 

Sodium borohydride is one of the weakest hydride donors available. The feet that it can be used in water is evidence of this as more powerful hydride donors such as lithium aluminium hydride, LiAlI-fe, react violently with water. Sodium borohydride reacts with both aldehydes and ketones, though the reaction with ketones is slower for example, benzaldehyde is reduced about 400 times faster than acetophenone in isopropanol. 

The first traceless linker was developed by Kamogawa and coworkers in 1983 [82]. Starting from a polymer-bound sulfonylhydrazine, sulfonylhydrazone resin 88 was formed by reaction with ketones or aldehydes. The cleavage step was conducted either by reduction with sodium borohydride or lithium aluminium hydride to yield alkanes 89 or by treatment with base to give the corresponding alkenes 90 in a Bamford-Stevens reaction (Scheme 16.20). This work was a pioneering approach in the field of traceless tinkers. 

Diselenanes (27) are available through the reactions of 1,3-propanediselenols with aldehydes and ketones in the presence of a Lewis acid such as zinc(II) chloride (Equation (3)) <85T4793, 93TL8517>. The diselenols are normally synthesized from the corresponding diselenocyanates by reduction with, for example, sodium borohydride, or with sodium in liquid ammonia <71BSB639>. 

Chitosan is a multi-nucleophilic polymer due to the presence of the NH2 and OH functional groups. The initial sites where substitution occurs are the more nucleophilic amino groups. However, the experimental conditions and protection of the NH2 groups reduces the intermolecular hydrogen bonding and creates space for water molecules to fill in and solvate the hydrophilic groups of the polymer backbone (Sashiwa and Shigemasa 1999). A -alkylated derivatives can be obtained by the treatment of chitosan with aldehydes or ketones via formation of Schiff base intermediates, aldimines (from reactions with aldehydes), or ketimines (from reactions with ketones) followed by reduction of the imine with sodium borohydride. 

Using a condensed reaction form, treatment of 2-butanone with NaBI leads to 2-butanol, and the first step delivers the hydrogen marked in blue in the illustration, whereas aqueous ammonium chloride (a weakly acidic solution) is the second step that delivers the hydrogen marked in red. Sodium borohydride reduces both ketones and aldehydes. Indeed, the reduction of an aldehyde with NaBH4 is somewhat easier than the similar reduction of a ketone. Aldehydes are easier to reduce than ketones because the carbonyl unit is less stericaUy hindered. 

After the reaction between sodium borohydride and the ketone is complete, the reaction mixture is treated with water and acid to produce the desired secondary alcohol. Explain this reaction by indicating the source of the hydrogen atom that ends up on the oxygen atom. 

A solution of 1 g of the ethyleneketal of the trione in 40 ml of methanol is treated with 0.2 g of sodium borohydride and the mixture is stirred at 20° for 2 hr. Slow drop wise addition of water precipitates the reaction product as crystals. These are filtered, washed with water and dried, to give 1.02 g of hydroxy ketone, which after crystallization from methylene dichloride-hexane has mp 182-184° (reported 184-186°) -23° (CHCI3). 

Ketones undergo a reduction when treated with sodium borohydride, NaBH What is the structure of the compound produced by reaction of 2-butanone with NaBH4 if it has an IR absorption at 3400 cm-1 and M+ = 74 in the mass spectrum ... 

Sodium hydrogen telluride, (NaTeH), prepared in situ from the reaction of tellurium powder with an aqueous ethanol solution of sodium borohydride, is an effective reducing reagent for many functionalities, such as azide, sulfoxide, disulfide, activated C=C bonds, nitroxide, and so forth. Water is a convenient solvent for these transformations.28 A variety of functional groups including aldehydes, ketones, olefins, nitroxides, and azides are also reduced by sodium hypophosphite buffer solution.29... 

In the general context of donor/acceptor formulation, the carbonyl derivatives (especially ketones) are utilized as electron acceptors in a wide variety of reactions such as additions with Grignard reagents, alkyl metals, enolates (aldol condensation), hydroxide (Cannizzaro reaction), alkoxides (Meerwein-Pondorff-Verley reduction), thiolates, phenolates, etc. reduction to alcohols with lithium aluminum hydride, sodium borohydride, trialkyltin hydrides, etc. and cyloadditions with electron-rich olefins (Paterno-Buchi reaction), acetylenes, and dienes.46... 

Ketone 166, the key intermediate of deplancheine was obtained in 63% overall yield by the reaction of harmalane (150) with l-bromo-2,3-epoxypropane, followed by sodium borohydride reduction and Moffat oxidation (116). Methods for the elaboration of the exocyclic, -configurated double bond are reviewed (117). 

The synthetic sequence, which shows only the succesful solutions adopted in every step, is outlined in Scheme 13.1.11. Reaction of l Chloroadamantan-4-one (39) [15] with sodium-potassium alloy in ether gave a mixture of ketonic and hydroxylated material which upon oxidation with Jones reagent gave 7-methylenebicyclo[3.3.1]nonan-2-one (40) in 75% yield. Reduction of 40 with sodium borohydride gave the alcohol 41 which could be also obtained in better yields from l-chloroadamantan-4-one with a large excess of sodium-potassium... 

The authors then go on to measure the kinetics in the presence of two oxazabor-ole catalysts, (92a) and (92b).The rate-determining step is the reaction of the ketone with an oxazaborole-borane complex, with the direct reduction competing with the catalytic cycle (as mentioned above). The oxazaborole reaction, like the direct reduction, is significantly accelerated by the presence of sodium borohydride. 

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