Cyanoborohydride, sodium

Alkyl groups are not the only substituents that can be attached to boron in order to generate new borohydride derivatives. Reaction of NaBH4 with HCN gives sodium cyanoborohydride (NaBH3CN), for example, a remarkably stable reagent that does not decompose in acid solution (the pH should be less acidic than pH 3). It is soluble in THF, MeOH, H2O, HMPA, DMF and sulfolane and is unreactive, making it very 

Ketones and aldehydes are reduced in acidic media, but not at neutral pH. Sodium cyanoborohydride is stable at pH 3-4 and in this acid medium, a carbonyl is converted to the protonated form (C=OH+) which is susceptible to reduction. At pH 3-A, ketones and aldehydes are rapidly reduced,as illustrated by the reduction of the aldehyde unit in 163 to give 164 in 89% yield (at pH 4 in this case), in Varela s asymmetric synthesis of 4-hydroxypipecolic acid. Note that neither the lactone moiety or the benzyl carbamate were reduced under these conditions. 

The ability to reduce compounds under acidic conditions is ideal for the reduction of enamines. Protonation of nitrogen gives an iminium salt in acidic media that is then reduced with cyanoborohydride to an amine.Imines can be reduced in acidic media in the presence of many other functional groups, as shown by Cook s reduction of imine 165 to give 166 in 79% yield in a synthesis of substituted tetrahydro-P-carbolines. 2 This reagent is excellent for the reduction of iminium salts at neutral pH as well,l 3 and it is also useful for the reductive alkylation of amines. Dimethylamino derivatives such as 168 can be prepared from the amine (167 in this case) by treatment with formaldehyde and cyanoborohydride, even in the presence 

InChl = l/CH3BN.Na/c2-l-3 /h2H3 /q-l +l InChIKey = CVDUGUOQTVTBJH-UHFFFAOYAX 

Physical Data white, hygroscopic solid, mp 240-242 °C (dec). Solubility sol most polar solvents (e.g. MeOH, EtOH, H2O, carboxylic acids) and polar aprotic solvents (e.g. HMPA, DMSO, DMF, sulfolane, THE, digl3une) insol nonpolar solvents (e.g. ether, CH2CI2, benzene, hexane). 

Form Supplied in widely available the corresponding deuter-ated (or tritiated) reagent is available via acid-catalyzed exchange with D2O (or X20).  

Functional Group Reductions General. The chemoselecti-vity available with NaBHsCN is remarkably dependent on solvent and pH. Under neutral or slightly acidic conditions (pH 5), only iminium ions are reduced in protic and ether (e.g. THF) solvents. Most other functional groups including aldehydes, ketones, esters, lactones, amides, nitro groups, halides, and epoxides are inert under these conditions. 

Reductive Aminations. The relative inertness of aldehydes and ketones toward NaBHsCN at pH 5 allows reductive aminations with amine and amine derivatives (usually in MeOH) via in situ generation of iminium ions which are then reduced to 

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The catalyst needed is called sodium cyanoborohydride (NaBHaCN). It is not very common but there are few places that still sell it. It is very prone to take up water out of the air so the chemist makes sure that she doesn t leave it sitting out ail night. The method is simplicity itself. 

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... 

Sodium Cyanoborohydride. NaBH CN is a hygroscopic white soHd that is remarkably stable, both thermally and hydrolytically. It is... 

Sodium cyanoborohydride is remarkably chemoselective. Reduction of aldehydes and ketones are, unlike those with NaBH pH-dependent, and practical reduction rates are achieved at pH 3 to 4. At pH 5—7, imines (>C=N—) are reduced more rapidly than carbonyls. This reactivity permits reductive amination of aldehydes and ketones under very mild conditions (42). 

In addition, sodium cyanoborohydride reduces a wide variety of substrates (43) (see Table 6). 

Sodium cyanoborohydride has become important in biochemical appHcations that require hydrolytic stabiHty of the reducing agent and chemoselectivity, in sensitive molecules. It is also a preferred reagent for oxime reductions. 

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... 

The reduction of 3,5-diphenylisoxazoline with sodium cyanoborohydride produced a mixture of isomeric 3,5-diphenylisoxazolidines. The H and NMR spectra were utilized to distinguish the isomers SOLAIOI). Sodium borohydride reductions likewise reduce isoxazolines to isoxazolidines (equation 56) (80JA4265). 

The first total synthesis of 87 was published in 1990 (90TL1523). 5-Hydroxyindole (88) was mesylated and then reduced with sodium cyanoborohydride to give an indoline which was brominated to afford the bromoindoline 89 in good yield (Scheme 33). Cross-coupling with ortho-formyl boronic acid under Suzuki conditions, followed by air oxidation of the resulting cyclized product, followed by reduction of the lactam formed with excess Red-Al gave the target compound 87. 

To a solution of 5 g of sisomicin in 250 ml of water add 1 N sulfuric acid until the pH of the solution is adjusted to about 5. To the solution of sisomicin sulfuric acid addition salt thereby formed, add 2 ml of acetaldehyde, stir for 10 minutes, then add 0.B5 g of sodium cyanoborohydride. Continue stirring at room temperature for 15 minutes, then concentrate solution In vacuo to a volume of about 100 ml, treat the solution with a basic ion exchange resin [e.g., Amberlite IRA401S (OH )], then lyophilize to a residue comprising 1-N-ethyl-sisomicin. 

Manx- different reducing agents are effective, but the most common choice in the laboratory is sodium cyanoborohydride, NaBH3CN. Sodium cyanoboro-hydride is similar in reactivity to sodium borohydride (NaBH4) but is more stable in weak acid solution. 

Sodium cyanoborohydride. reductive ami nation with, 931 Sodium cyclamate, LP50 of, 26 Sodium hydride, reaction with alcohols, 605... 

Reductive aziridine ring-opening with sodium cyanoborohydride has been described [74, 91]. In the presence of a catalytic amount of TsOH, compound 111 (Scheme 3.37) gave 112 in 68% yield on treatment with sodium cyanoborohydride [74, 91]. 

Reductive amination of AT-succinyl chitosan and lactose using sodium cyanoborohydride in a phosphate buffer (pH 6.0) for 6 days was suitable for the preparation of lactosaminated M-succinyl chitosan (Fig. 3). Over 10% of dose/g-tissue was distributed to the prostate and lymph nodes at 48 h postadministration in both chitosan and lactosaminated N-succinyl chitosan. The labeled lactosaminated M-succinyl chitosan was easily distributed into not only the liver but also prostate, intestine, preputial gland and lymph nodes [153]. 

CNNa 143-33-9) see Alclofenac Alpidem Amphetaminil Atorvastatin calcium Azatadine Calcium pantothenate Carnitine Clopidogrel hydrogensulfate Clortermine Dexrazoxane Diclofenac Diloxanide Edetic acid Epinastine hydrochloride Ethosuximide Ethotoin Fenoprofen Ibuprofen Irbesartan Ketoprofen Lonazolac Mephenytoin Mepindolol Montelukast sodium Nabilone Oxymetazoline Paramethadione Pentorex Saquinavir Suprofen Thiamphenicol Tolmetin Trimazosin Zolpidem sodium cyanoborohydride... 

N,N-Dibenzyl (z -amino a-chloroketimines 202 can be prepared from the corresponding ketones, which in turn are available by the addition of chloromethyllithium to esters of natural cz-amino acids. Reduction of 202 with sodium cyanoborohydride directly afforded a-aminoalkyl-substituted aziridines 203 with high syn diastereoselectivity, which was only moderately affected by the size of the substituent [96] (Scheme 30). A complemen-... 

Rather than preforming the a-amino ketimines to be reduced, it is often advantageous to form in situ the more reactive iminium ions from a-aminoketones and primary amines or ammonium salts in the presence of the reducing agent, e.g., sodium cyanoborohydride. Use of this procedure (reductive amination) with the enantiopure a-aminoketone 214 and benzylamine allowed the preparation of the syn diamines 215 with high yields and (almost) complete diastereoselectivities [100] (Scheme 32). Then, the primary diamines 216 were obtained by routine N-debenzylation. Similarly, the diamine 217 was prepared using ammonium acetate. In... 

Scheme 32 Reductive amination of chiral a-aminoketones with sodium cyanoborohydride...

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