Sodium cyanoborohydride preparation

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]. 

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... 

An interesting procedure has been proposed for the synthesis of amylose-b-PS block copolymers through the combination of anionic and enzymatic polymerization [131]. PS end-functionalized with primary amine or dimethylsilyl, -SiMe2H groups were prepared by anionic polymerization techniques, as shown in Scheme 56. The PS chains represented by the curved lines in Scheme 56 were further functionalized with maltoheptaose oligomer either through reductive amination (Scheme 57) or hydrosilyla-tion reactions (Scheme 58). In the first case sodium cyanoborohydride was used to couple the saccharide moiety with the PS primary amine group. 

Add 10 pi of 5 M sodium cyanoborohydride in 1N NaOH (Aldrich) per ml of the macromolecule solution volume prepared in (1). Caution Highly toxic compound. Use a fume hood and be careful to avoid skin contact with this reagent. 

In a fume hood, add 10 pi of 5M sodium cyanoborohydride (Sigma) per ml of reaction solution. Caution Cyanoborohydride is extremely toxic. All operations should be done with care in a fume hood. Also, avoid any contact with the reagent, as the 5 M solution is prepared in 1N NaOH. 

In a fume hood, add 10 pi of 5M sodium cyanoborohydride (Sigma) per ml of reaction solution. Caution Cyanoborohydride is extremely toxic. All operations should be done with care in a fume hood. Also, avoid any contact with the reagent, as the 5M solution is prepared in IN NaOH. The addition of a reductant is necessary for stabilization of the Schiff bases formed between an amine-containing protein and the aldehydes on the antibody. For coupling to a hydrazide-activated protein, however, most protocols do not include a reduction step. Even so, hydrazone linkages may be further stabilized by cyanoborohydride reduction. The addition of a reductant during hydrazide/aldehyde reactions also increases the efficiency and yield of the reaction. 

Takano s group reported the first enantioselective total synthesis of (—)-anti-rhine as well (146). Chiral product 235 was prepared via a number of stereoselective reactions. Reductive condensation of 235 with tryptamine, using sodium cyanoborohydride at pH 6, supplied lactam 236, which was reduced by di-isobutylalminum hydride to hemiacetal 237. The latter could be cyclized to (-)-antirhine by simple acid treatment (146). 

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]. 

This lengthy procedure requiring protection and deprotection of the hydroxy group can be circumvented by preparing the 3-hydroxy derivatives in 60-65% yield by the straightforward reduction of the corresponding 3-oxo derivatives with sodium cyanoborohydride (Scheme 9) [15,16]. 

A valuable application of sodium cyanoborohydride is in the synthesis of amines by reductive amination. What combination of carbonyl and amine components would you choose to prepare the following amines by this route Explain your choices. 

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). 

Stractures of 3-alkyl-5-methylindolizidines, found in thief ants, Solenopsis species (Table II), arrived at by gas chromatographic and mass spectral analysis were confirmed by coinjection and direct comparison with the synthetic sample. Indolizidine 15a from S. conjurata exhibits characteristic peaks at miz 152 (M — CHj) and 138 (M — C2H5, a base peak) as well as a parent peak at m/z 167 in the mass spectram. It corresponds to an isomer of 3-ethyl-5-methylindolizidine (15) which was prepared as a mixture of four stereoisomers by reductive amination of triketone 391 with ammonium acetate-sodium cyanoborohydride and sodium borohydride (Scheme 47). 

In the reductive animation method, it is important to use reagents and reactants of high purity. The carbohydrate sample should not contain carbohydrate contaminants, as, if they were present, an adsorbent containing more than one type of ligand would be obtained. The sodium cyanoborohydride should be of high purity, because reduction of the Schiff base may not occur with impure preparations. Special procedures have been developed for purifying sodium cyanoborohydride, and these should be employed.25... 

Dialkylpyrrolidines. These compounds can be prepared by reductive amination of 1,4-diketones with sodium cyanoborohydride and ammonium acetate (4, 448-449). 1-Pyrrolines are usually formed also, but they can be reduced to pyrrolidines by NaBH4 in a second step.1... 

Indolines are produced in good yield from 1-benzenesulfonylindoles by reduction with sodium cyanoborohydride in TFA at 0°C (Equation 5) (89TL6833). If acyl groups are present at C-2 or C-3 in the substrate, they are reduced to alkyl groups. Indole is also reduced to 2,3-dihydroindole by sodium cyanoborohydride and acetic acid or triethylamineborane and hydrochloric acid. An alternative method for preparing indolines involves treatment of indoles with formic acid (or a mixture of formic acid and ammonium formate) and a palladium catalyst (82S785). Reduction of the heterocyclic ring under acidic conditions probably involves initial 3-protonation followed by reaction with hydride ion. 

These preparations that illustrate the use of sodium cyanoborohydride in hexamethylphosphoramide as an effective, selective, and convenient procedure for the reduction of alkyl halides and tosylates is essentially the same as previously described.8 The very mild reducing ability of sodium cyanoborohydride makes the method particularly valuable when other functional groups are present in the molecule... 

A large family of other N-substituted homologues of 2,4-DMA were similarly prepared from the above ketone and sodium cyanoborohydride. Methyl-amine, ethylamine, propylamine, isopropylamine and hexylamine gave the corre-... 

SYNTHESIS A stirred solution of 9.0 g 1 -(3,4-methylenedioxypheny l)-2-butanone (see the recipe for J for its preparation) in 150 mL MeOH was treated with 9.0 g ethylamine hydrochloride, 4.0 g anhydrous NaOAc, and 3.0 g sodium cyano-borohydride. The pH was maintained between 6 and 7 by the periodic addition of HC1. After the base formation had stabilized, there was added an additional 9.0 g ethylamine hydrochloride, 9.0 g NaOAc and 2.0 g sodium cyanoborohydride. With continuous stirring, there was HC1 added over the course of 1 h until the final pH was approximately 2. The reaction mixture was poured into 700 mL dilute NaOH, and extracted with 3x75 mL CH2C1,. These extracts were pooled, and back-extracted with dilute H2S04. This was washed with 2x50 mL CH,CI2, then made basic with dilute NaOH and extracted with 2x75 mL CH2Clr Removal of the solvent... 

The diethyl compound without the iodine is 2,5-dimethoxy-N,N-diethylamphetamine, which was prepared by the reductive alkylation of DMA with acetaldehyde and sodium cyanoborohydride. This product, DEDMA, was a clear white oil, bp 82-92 °C at 0.15 mm/Hg which did not form a crystalline hydrochloride. An interesting measure of just how different these N,N-dialkylated homologues can be from the psychedelic primary amines, pharmacologically, can be seen in the published report that the beta-hydroxy derivative of DEDMA is an antitussive, with a potency the same as codeine. 

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