Hydrogen sodium cyanoborohydride

A variation of the classical reductive amination procedure uses sodium cyanoboro hydride (NaBH3CN) instead of hydrogen as the reducing agent and is better suited to amine syntheses m which only a few grams of material are needed All that is required IS to add sodium cyanoborohydride to an alcohol solution of the carbonyl compound and an amine... 

Isoquinoline can be reduced quantitatively over platinum in acidic media to a mixture of i j -decahydroisoquinoline [2744-08-3] and /n j -decahydroisoquinoline [2744-09-4] (32). Hydrogenation with platinum oxide in strong acid, but under mild conditions, selectively reduces the benzene ring and leads to a 90% yield of 5,6,7,8-tetrahydroisoquinoline [36556-06-6] (32,33). Sodium hydride, in dipolar aprotic solvents like hexamethylphosphoric triamide, reduces isoquinoline in quantitative yield to the sodium adduct [81045-34-3] (25) (152). The adduct reacts with acid chlorides or anhydrides to give N-acyl derivatives which are converted to 4-substituted 1,2-dihydroisoquinolines. Sodium borohydride and carboxylic acids combine to provide a one-step reduction—alkylation (35). Sodium cyanoborohydride reduces isoquinoline under similar conditions without N-alkylation to give... 

In a fume hood, dissolve 125 mg of sodium cyanoborohydride in 1ml water (makes a 2M solution). Caution Highly toxic compound handle with care. This solution may be allowed to sit for 30 minutes to eliminate most of the hydrogen-bubble evolution that could affect the vesicle suspension. 

Reduction of the Oximino Fragment in Substituted 5,6-Dihydro-4H-Oxazines Catalytic hydrogenation of substituted dihydro-477-oxazines (552), as well as their reduction with sodium cyanoborohydride (553), were studied in sufficient detail and were used in several total syntheses. However, the use of silylation of six-membered cyclic nitronates enables the synthesis of previously unknown dihydrooxazines containing functionalized substituents at the C-3 and C-4 atoms from easily available precursors. 

Hydrogen will not reduce ketones or imines using CATHy or related catalysts. Inorganic hydrogen donors that have been used include dithionite and di-hydrogenphosphite salts, metal hydrides such as sodium borohydride, and sodium cyanoborohydride. Recently, amines have been shown to function as hydrogen donors with some catalysts. The enzymic cofactor NADH can be used stoichiometrically, and the potential exists to use this catalytically [56]. 

A major achievement in augmenting the chemical potential of antibodies has been in the area of redox processes. Many examples now exist of stereoselective reductions, particularly recruiting sodium cyanoborohydride (Appendix Section 22). A growing number of oxidation reactions can now be catalysed by abzymes, with augmentation from oxidants such as hydrogen peroxide and sodium periodate (Appendix Section 21). 

Tetra-n-butylammonium cyanoborohydride has been prepared by metathesis from the quaternary ammonium hydrogen sulphate and sodium cyanoborohydride. Other tetraalkylammonium cyanoborohydrides have also been synthesized [10]. 

Replacement of hydrogen by alkyl groups gives compounds like lithium triethylborohydride (Super-Hydride ) [100], lithium tris sec-butyl)borohydride [101] (L-Selectride ) and potassium tris sec-butyl)borohydride (K-Selectride ) [702], Replacement by a cyano group yields sodium cyanoborohydride [103], a compound stable even at low pH (down to 3), and tetrabutylammonium cyanoborohydride [93],... 

The double bond in indole and its homologs and derivatives is reduced easily and selectively by catalytic hydrogenation over platinum oxide in ethanol and fluoroboric acid [456], by sodium borohydride [457], by sodium cyanoborohydride [457], by borane [458,459], by sodium in ammonia [460], by lithium [461] and by zinc [462]. Reduction with sodium borohydride in acetic acid can result in alkylation on nitrogen giving JV-ethylindoline [457]. 

Consequently, by choosing proper conditions, especially the ratios of the carbonyl compound to the amino compound, very good yields of the desired amines can be obtained [322, 953]. In catalytic hydrogenations alkylation of amines was also achieved by alcohols under the conditions when they may be dehydrogenated to the carbonyl compounds [803]. The reaction of aldehydes and ketones with ammonia and amines in the presence of hydrogen is carried out on catalysts platinum oxide [957], nickel [803, 958] or Raney nickel [956, 959,960]. Yields range from low (23-35%) to very high (93%). An alternative route is the use of complex borohydrides sodium borohydride [954], lithium cyanoborohydride [955] and sodium cyanoborohydride [103] in aqueous-alcoholic solutions of pH 5-8. 

Catalytic hydrogenation of the unstable pyrroles (281a-c), which are prepared by heating the 1,4-diketones (280a-c) with an excess of ammonium carbonate at 120°C, gives 2,5-dialkylpyrrolidines (lOa-c) (cis trans = 85 15, 85% conversion) (Scheme 25) 133). Reductive amination of 1,4-diketones (282b,f,h,i) with ammonium acetate and sodium cyanoborohydride produces 2,5-dialkylpyr-rolidines (10b,f,h,i) identical to natural products in 50-90% yields. Each pyrrolidine is an approximately 1 1 mixture of cis and trans isomers (Scheme 26) 25,138). 

Tertiary amines are made from iminium salts by catalytic hydrogenation or by LiAlH4 reduction. The iminium salts are usually unstable, and so are reduced as they are formed by a reducing agent already in the reaction mixture. A mild reducing agent, e.g. sodium cyanoborohydride (NaBHsCN), can also be used. 

Hydrogen chloride in diethyl ether at room temperature was added to a mixture of 7 [34] (1.00 g, 2.16 mmol) and sodium cyanoborohydride (1.70 g, 27.0 mmol) in tetrahydrofuran (30 mL, distilled from LiAlH ) containing 3-A molecular sieves, until the evolution of gas biased. Use of TLC [silica gel, light petroleum (bp 40-60°)/ethyl acetate 5 1] after 5 min, PrHcated complete reaction. The mixture was diluted with CHjClj (50 mL) and water, [filtered, and the solution was extracted with water and then with saturated aqueous... 

To a solution of the disaccharide 28 (500 mg, 0.55 mmol) and sodium cyanoborohydride (230 mg, 3.70 mmol) in tetrahydrofnran (25 mL) was added powdered 4-A MS (1 g). The solution was stirred for 20 min at 0°C, then a solution of hydrogen chloride saturated in ether (2 mL) was added dropwise. Stirling was continued for 3 h at 0°C, and the course of the reaction was monitored by TLC. The suspension was filtered through Celite, and the filtrate was processed as usnal. Purification by flash chromatography on silica gel with hexane-EtOAc (3 1) afforded the desired product 29 (300 mg, 60%). 

Esters of racemic pyrazolidine-3-carboxylic acid (5-azaproline, 16) are obtained by a two-step reaction via addition of diazomethane to acrylic acid esters to form the corresponding dihydropyrazoline derivatives, which are converted into the desired pyrazolidine-3-carb-oxylic acid derivative by hydrogenation over palladium on charcoal,11621 or by reduction with sodium cyanoborohydride,[164l or with zinc in acetic acid. Details are given in Table 6J1651... 

Add sodium cyanoborohydride (Aldrich) to a concentration of 20 mg/ml. Caution Highly toxic Use a fume hood and avoid inhalation of dust or vapors. Seal the reaction vessel with parafilm. Do not use a rigid sealing cap, since cyanoborohydride will liberate hydrogen gas bubbles over time and may rupture the vessel. 

The 6 -0-benzyl-methylthioglycoside (107) was prepared [119] by opening the 4, 6 -Obenzylidene derivative with the sodium cyanoborohydride — hydrogen chlo-... 

In a further synthesis of (345) by Rana and Matta [234], the disaccharide (353), prepared by the action of sodium cyanoborohydride — hydrogen chloride [120, 121] on the benzylidene derivative (352), was condensed with the fucosyl bromide (322) to give the trisaccharide (354) in 82 % yield. 

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