SODIUM BORO HYDRIDE

Semicarbazones are used as protecting groups as a consequence of their stability to reducing agents such as potassium borohydride, sodium boro-hydride and lithium borohydride. Semicarbazones are cleaved by strong acids and by heating in acetic anhydride-pyridine. " ... 

Both the 4- (38) and 6-(31) nitrimines are reduced with sodium boro-hydride to the corresponding y5-nitramine derivatives, e.g., (41)], which are methylated with methyl iodide and potassium carbonate. The A -methyl derivative is reduced in modest yield to the 5a-fluoride (43) with lithium aluminum hydride. 

A 500-ml three-necked flask is fitted with a condenser, a pressure-equalizing dropping funnel, a magnetic stirrer, and a thermometer. The flask is charged with a mixture of 33.6 g (0.48 mole) of 2-methyl-2-butene and 180 ml of a 1 M solution of sodium boro-hydride in diglyme. The flask is cooled in an ice bath and stirring begun. Boron trifluoride etherate (0.24 mole) is added dropwise to the mixture and the solution is stirred at 0° for 2 hours. 

Dihydrostreptomycin sulfate may be prepared from streptomycin sulfate by catalytic hydrogenation (Merck, Pfizer, Cyanamid), electrolytic reduction (Schenley, Olin Mathieson), or by sodium boro hydride reduction (Bristol), or by isolation from a fermentation process (Takeda). 

The synthesis of key intermediate 12, in optically active form, commences with the resolution of racemic trans-2,3-epoxybutyric acid (27), a substance readily obtained by epoxidation of crotonic acid (26) (see Scheme 5). Treatment of racemic 27 with enantio-merically pure (S)-(-)-1 -a-napthylethylamine affords a 1 1 mixture of diastereomeric ammonium salts which can be resolved by recrystallization from absolute ethanol. Acidification of the resolved diastereomeric ammonium salts with methanesulfonic acid and extraction furnishes both epoxy acid enantiomers in eantiomerically pure form. Because the optical rotation and absolute configuration of one of the antipodes was known, the identity of enantiomerically pure epoxy acid, (+)-27, with the absolute configuration required for a synthesis of erythronolide B, could be confirmed. Sequential treatment of (+)-27 with ethyl chloroformate, excess sodium boro-hydride, and 2-methoxypropene with a trace of phosphorous oxychloride affords protected intermediate 28 in an overall yield of 76%. The action of ethyl chloroformate on carboxylic acid (+)-27 affords a mixed carbonic anhydride which is subsequently reduced by sodium borohydride to a primary alcohol. Protection of the primary hydroxyl group in the form of a mixed ketal is achieved easily with 2-methoxypropene and a catalytic amount of phosphorous oxychloride. 

Another photochemical method was reported by Kessar et al. (157). l-o-Toluyl-3,4-dihydroisoquinoline 299a, derived from dihydroberberine metho salt (298a), was irradiated and then reduced with sodium boro-hydride to provide the ring D-inverted 11,12-oxygenated protoberberine 482 (Scheme 100). 

Aldehydes attached to the tricyclic ring system can be readily reduced on standard treatment with sodium boro-hydride as illustrated in (Equation 18) for the conversion of aldehyde 88 to alcohol 89 <1997JME2196>. 

The key intermediate 124 was prepared starting with tryptophyl bromide alkylation of 3-acetylpyridine, to give 128 in 95% yield (Fig. 37) [87]. Reduction of 128 with sodium dithionite under buffered (sodium bicarbonate) conditions lead to dihydropyridine 129, which could be cyclized to 130 upon treatment with methanolic HC1. Alternatively, 128 could be converted directly to 130 by sodium dithionite if the sodium bicarbonate was omitted. Oxidation with palladium on carbon produced pyridinium salt 131, which could then be reduced to 124 (as a mixture of isomers) upon reaction with sodium boro-hydride. Alternatively, direct reduction of 128 with sodium borohydride gave a mixture of compounds, from which cyclized derivative 132 could be isolated in 30% yield after column chromatography [88]. Reduction of 132 with lithium tri-f-butoxyaluminum hydride then gave 124 (once again as a mixture of isomers) in 90% yield. 

A convenient method to affect the oxidation p- to nitrogen in piperidines is based on the anodic oxidation of N-carboalkoxy piperidines (Scheme 35). The electrochemical oxidation of piperidine (152) in the presence of acetic acid and potassium acetate, for example, afforded a mixture of isomeric 2-hydroxy-3-acetoxypiperidines (153) in a combined yield of 93%, following an aqueous workup [61]. Reduction with sodium boro-hydride severed the C-OH bond. Treatment with acid and then base completed a synthesis of pseudoconhydrine (154). 

To circumvent this problem, several methods have been developed (157). Probably, the most prominent method is treatment with sodium boro-hydride (0.1% in PBS, 30 minutes prior to staining). NaBILi is known to neutralize Schiff s bases through reduction of amine-aldehyde compounds into nonfluorescent salts. 

Photolytic. PCB-1254 in a 90% acetonitrile/water solution containing 0.2-0.3 M sodium boro-hydride and irradiated with UV light (X = 254 nm) reacted to yield dechlorinated biphenyls. After 16 h, no chlorinated biphenyls were detected. Without sodium borohydride, only 25% of PCB-1254 were destroyed after 16 h (Epling et al, 1988). In a similar experiment, PCB-1254 (1,000 mg/L) in an alkaline 2-propanol solution was exposed to UV light (X = 254 nm). After 30 min, all of the PCB-1254 isomers were converted to biphenyl. When the radiation source was sunlight, only 25% was degraded after a 20-h exposure. But when the sensitizer phenothiazine (5 mM) was added to the solution, photodechlorination of PCB-1254 was complete after 1 h at 350 nm. In addition, when PCB-1254 contaminated soil was heated at about 80 °C in the presence of di-ferf-butyl peroxide, complete dechlorination to biphenyl was observed (Hawari et al., 1992). 

A coupling of vindoline (3) with catharanthine A-oxide (45), mediated by trifluoroacetic anhydride, and subsequent reduction with sodium boro-hydride delivered anhydrovinblastine (42) in up to 40% yield, accompanied by minor amounts of the undesired C-16 (R) isomer 24 as well as some 17-deacetylanhydrovinblastine (46) (Scheme 13) (38-41). The struc-... 

In a 100-ml. round-bottomed flask equipped with a reflux condenser are placed 1.00 g. (0.0035 mole) of 5a-androstan-17jS-ol-3-one (Note 1), 0.90 g. (0.0048 mole) of tosylhydrazide (Note 2), and 70 ml. of methanol (Note 3). The mixture is heated under gentle reflux for 3 hours then cooled to room temperature. To the solution is added 2.5 g. (0.075 mole) of sodium boro hydride in small portions during one hour (Note 4) and the resulting mixture is heated under reflux for an additional 8 hours. The reaction mixture is cooled to room temperature and the solvent is removed under reduced pressure. The residue is dissolved in ether, transferred to a separatory funnel, and... 

Marchand and co-workers have provided synthetic routes to both 8,8,11,11 -tetranitro- (72) and4,4,8,8,11,11-hexanitro- (80) pentacyclo[5.4.0.0 .0 °.0 ]undecanes. Initial attempts to synthesize target (72) from the dioxime (63) failed when it was found that sodium boro-hydride reduction of the gm-bromonitro intermediate (64) gave the aza-heterocycle (65) as the major product. Consequently, an indirect route was explored where one of the two ketone groups of (62) is protected as an acetal (66) while the other ketone group is converted to a... 

Fig. 2 Apparatus for hydrogenation with hydrogen generated from sodium boro-hydride.

Complex hydrides can be used for the selective reduction of the carbonyl group although some of them, especially lithium aluminum hydride, may reduce the a, -conjugated double bond as well. Crotonaldehyde was converted to crotyl alcohol by reduction with lithium aluminum hydride [55], magnesium aluminum hydride [577], lithium borohydride [750], sodium boro-hydride [751], sodium trimethoxyborohydride [99], diphenylstarmane [114] and 9-borabicyclo[3,3,l]nonane [764]. A dependable way to convert a, -un-saturated aldehydes to unsaturated alcohols is the Meerwein-Ponndorf reduction [765]. 

Reduction of unsaturated ketones to unsaturated alcohols is best carried out Nit v complex hydrides. a,/3-Unsaturated ketones may suifer reduction even at the conjugated double bond [764, 879]. Usually only the carbonyl group is reduced, especially if the inverse technique is applied. Such reductions are accomplished in high yields with lithium aluminum hydride [879, 880, 881, 882], with lithium trimethoxyaluminum hydride [764], with alane [879], with diisobutylalane [883], with lithium butylborohydride [884], with sodium boro-hydride [75/], with sodium cyanoborohydride [780, 885] with 9-borabicyclo [3.3.1]nonane (9-BBN) [764] and with isopropyl alcohol and aluminum isopro-... 

High yields of amines have also been obtained by reduction of amides with an excess of magnesium aluminum hydride (yield 100%) [577], with lithium trimethoxyaluminohydride at 25° (yield 83%) [94] with sodium bis(2-methoxy-ethoxy)aluminum hydride at 80° (yield 84.5%) [544], with alane in tetra-hydrofuran at 0-25° (isolated yields 46-93%) [994, 1117], with sodium boro-hydride and triethoxyoxonium fluoroborates at room temperature (yields 81-94%) [1121], with sodium borohydride in the presence of acetic or trifluoroacetic acid on refluxing (yields 20-92.5%) [1118], with borane in tetrahydrofuran on refluxing (isolated yields 79-84%) [1119], with borane-dimethyl sulflde complex (5 mol) in tetrahydrofuran on refluxing (isolated yields 37-89%) [1064], and by electrolysis in dilute sulfuric acid at 5° using a lead cathode (yields 63-76%) [1120]. 

Dialkyl-1,2,4-oxadiazoles are reduced with diborane in tetrahydrofuran or sodium boro-hydride in ethanol to 4,5-dihydro-1,2,4-oxadiazoles <73BSF2996,78JHC1373>. 

Selenium is converted to its volatile hydride by reaction with sodium boro-hydride, and the cold hydride vapor is introduced to flame AA for analysis. Alternatively, selenium is digested with nitric acid and 30% H2O2, diluted and analyzed by furnace-AA spectrophotometer. The metal also may be analyzed by ICP-AES or ICP/MS. The wavelengths most suitable for its measurements are 196.0 nm for flame- or furnace-AA and 196.03 nm for ICP-AES. Selenium also may be measured by neutron activation analysis and x-ray fluorescence. 

Reduction of the 1,2,4-thiadiazine 1,1-dioxides 32 with sodium boro hydride in isopropanol gives the dihydro derivatives 33 (Equation 2) <1998JME2946>. 

Figure 3.4 The synthesis of ibuprofen is initiated by a Friedel-Crafts acylation of an aUcyl-substituted benzene ring. The resulting ketone is then reduced to an alcohol with sodium boro-hydride. The alcohol functionality then undergoes a functional group interchange by conversion to a bromide. In turn, this permits the introduction of an additional carbon atom in the form of a nitrile introduced via an 8, 2 nucleophilic displacement. This is then hydrolyzed to give the target molecule.

Cyclization of the acid chloride by means of aluminum chloride gives tetralone (19-2). This is then converted to its A -methylimine (19-3) by means of methylamine and titanium tetrachloride. That intermediate is next reduced with sodium boro-hydride to give a mixture of cis and trans aminotetralins (19-4). The tmns isomer tametraline (19-5) is separated by fractional crystallization of the hydrochloride salt [20]. Detailed pharmacological investigations showed that this compound owes its antidepressant action to the inhibition of reuptake of dopamine and norepinephrine from the synaptic cleft. 

Crotchet, R. A. Blanton, C. D. TV-Monoalkylation of Primary Aromatic and Heteroaromatic Amines with Trialkyl Orthocarboxylates and Sodium Boro-hydride, Synthesis 1974, 55. 

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