Sodium borohydride acetals

Reduction. Quinoline may be reduced rather selectively, depending on the reaction conditions. Raney nickel at 70—100°C and 6—7 MPa (60—70 atm) results in a 70% yield of 1,2,3,4-tetrahydroquinoline (32). Temperatures of 210—270°C produce only a slightly lower yield of decahydroquinoline [2051-28-7]. Catalytic reduction with platinum oxide in strongly acidic solution at ambient temperature and moderate pressure also gives a 70% yield of 5,6,7,8-tetrahydroquinoline [10500-57-9] (33). Further reduction of this material with sodium—ethanol produces 90% of /ra/ j -decahydroquinoline [767-92-0] (34). Reductions of the quinoline heterocycHc ring accompanied by alkylation have been reported (35). Yields vary widely sodium borohydride—acetic acid gives 17% of l,2,3,4-tetrahydro-l-(trifluoromethyl)quinoline [57928-03-7] and 79% of 1,2,3,4-tetrahydro-l-isopropylquinoline [21863-25-2]. This latter compound is obtained in the presence of acetone the use of cyanoborohydride reduces the pyridine ring without alkylation. 

Sodium borohydride Acetic anhydride Methyl bromide... 

Naphtho[2,l-c]-l,2,5-oxatellurazolium chlorides were converted to 2-methyl-naphtho[l,2-c]-l,3-tellurazoles upon treatment with sodium borohydride, acetic anhydride, concentrated hydrochloric acid, and finally concentrated ammonia1,2 (p.777). 

Sodium borohydride-acetic acid treatment of 5- and 6-substituted quinoxalines yields 1,2,3,4-tetrahydroquinoxalines. Alternatively, reduction is effected with hydrogen and a platinum catalyst.The acetic acid-borohydride technique gives excellent yields of 5- and 6-amino-... 

The same type of seven-membered d ring occurs in cadambine (74) " and 3a-dihydrocadambine (75a) (which was shown to be identical with the glycosidic alkaloid reported from Nauclea diderrichii) from Anthocephalus cadamba and in nauclechine. " The relationship between cadambine and dihydrocadambine was established (Scheme 8) by the sodium borohydride-acetic acid reduction of the tetra-acetate of the former to a mixture of 3a-dihydro-cadambine (75a) tetra-acetate corresponding to the natural isomer, and its 3 -epimer (major product). The C-3 carbinolamine ether system in cadambine was diagnosed by the u.v. spectral shift observed in acidic solution. Reversible, acid-catalysed cleavage of the N—C—O system led to the well-known, characteristic chromophore (76). 

Treating a benzene suspension of sodium borohydride (4 equiv.) With glacial acetic acid (3.25 equiv.) And refluxing the mixture for 15 min under nitrogen, after the initial rapid gas evolution subsided (ca. 3 mol of Hz liberated) [No Smoking ], gave a clear solution of NaBH(OAc)3. ... 

Unusual reducing properties can be obtained with borohydride derivatives formed in situ. A variety of reductions have been reported, including hydrogenolysis of carbonyls and alkylation of amines with sodium borohydride in carboxyHc acids such as acetic and trifluoroacetic (38), in which the acyloxyborohydride is the reducing agent. 

With mercuric acetate (Hg(OOCCH2)2), olefins and / fZ-butyl hydroperoxide form organomercury-containing peroxides (66,100). The organomercury compound can be treated with bromine or a mild reducing agent, such as sodium borohydride, to remove the mercury. 

A solution of 1 g of the dione in 200 ml of methanol at 0° is treated with 75 mg of sodium borohydride and the mixture is kept for 2 hr. After addition of 0.1 ml of acetic acid the mixture is concentrated to ca. 20 ml. Dilution with water gives 0.9 g of crystals which are chromatographed on 20 g of unwashed alumina. Elution with benzene-ether (40 60) yields 0.73 g of the methyl-hydroxytestosterone, mp 245-249°, which after crystallization from acetone has mp 255-256° [a] 111° (CHCI3). 

A solution of 0.25 g sodium borohydride in 140 ml of ethanol is added to a stirred solution of 0.56 g of calcium chloride in 60 ml of ethanol at —25°. The vigorously stirred mixture is treated dropwise at —25° over 5 min with 4.87 g of 1 la-hydroxy-5/S-pregnane-3,20-dione in 100 ml of ethanol. After a further 3 hr at —20°, 10 ml of 40% aqueous acetic acid is added and the mixture is evaporated to dryness under vacuum. The residue is dissolved in 150 ml of ether and the ethereal solution is washed with 30 ml of 2 A hydrochloric acid and twice with 30 ml of water and dried over Na2S04. Removal of the solvent gives 4.6 g of crystals, which are recrystallized from 20 ml of ether to yield 2.9 g (60%) of the dihydroxy ketone, mp 182-184° [aj 110° (ethanol). 

Enamines of A" -3-ketones (45) are stable to lithium aluminum hydride, but lithium borohydride reduces the 3,4-double bond of the enamine system." In the presence of acetic acid the enamine (45) is reduced by sodium borohydride to the A -3-amine (47) via the iminium cation (46). ... 

The properties of chlorine azide resemble those of bromine azide. Pon-sold has taken advantage of the stronger carbon-chlorine bond, i.e., the resistance to elimination, in the chloro azide adducts and thus synthesized several steroidal aziridines. 5a-Chloro-6 -azidocholestan-3 -ol (101) can be converted into 5, 6 -iminocholestan-3l -ol (102) in almost quantitative yield with lithium aluminum hydride. It is noteworthy that this aziridine cannot be synthesized by the more general mesyloxyazide route. Addition of chlorine azide to testosterone followed by acetylation gives both a cis- and a trans-2iddMct from which 4/S-chloro-17/S-hydroxy-5a-azidoandrostan-3-one acetate (104) is obtained by fractional crystallization. In this case, sodium borohydride is used for the stereoselective reduction of the 3-ketone... 

Olefins are also the products of hydroboratlon of enamines, followed by treatment of the organoborane products with hot acid (543,544). The reduction of enamines with sodium borohydride and acetic acid (545) and the selective reduction of dienamines with sodium borohydride to give homo-allylic tertiary amines (138-140,225,546,547), has been applied to the synthesis of conessine (548) and other aminosteroid analogs (545,549-552). Further examples of the reduction of imonium salts by sodium borohydride can be found in the reduction of Bischler-Napieralski products, and other cyclic imonium salts (102). 

The residual gum was dissolved in 360 ml of ethanol and cooled to 15°C in an ice/water bath, 8 g of sodium borohydride was then added in portions over 30 minutes while maintaining the temperature at 15°-20°C. After a further 30 minutes at 20°C the solution was stirred at room temperature for 2 hours. The solution was again cooled In ice and 250 ml of 2 N sulfuric acid were slowly added, then the solution was evaporated In vacuo until the ethanol had been removed. The clear aqueous solution was then treated with 250 ml of 10% sodium carbonate solution and the oil which precipitated was extracted into ethyl acetate. The ethyl acetate layer was washed with sodium carbonatesolution, then with water, and was dried over anhydrous sodium sulfate and evaporated in vacuo, to a small volume. Petroleum ether (BP 40°- 0°C) was added, and after standing overnight a white solid was obtained. This was filtered off to give 23 g of the product, MP 110°-114°C. 

D) Preparation of 2-(1-Hydroxyethyi)-3-Methyi-5-(2-Oxo-2,5-Dihydro-4-Furyi)Benzo[b] Furan (3574 CB) 13,2 grams of compound 3556 CB of which the preparation is described in (C) are treated successively with 66 ml of methylene chloride, 27 ml of methanol and, with stirring, 1.6 grams of sodium borohydride added in stages. The reaciton takes 1 hour. The mixture is poured into water acidified with a sufficient amount of acetic acid, the solvents are stripped under vacuum, the crystalline product removed, washed with water, and recrystallized from ethyl acetate. Yield 90%. MP <=158°C. 

In the laboratory, alkenes are often hydrated by the oxymercuration procedure. When an alkene is treated with mercury(II) acetate Hg(02CCH3)2, usually abbreviated Hg(OAc)2l in aqueous tetrahydrofuran (THF) solvent, electrophilic addition of Hg2+ to the double bond rapidly occurs. The intermediate orgnnomercury compound is then treated with sodium borohydride, NaBH4, and an alcohol is produced. For example ... 

On heating with sodium borohydride in glacial acetic acid. 5//-dibenz[/t,/ azepine (5) undergoes sequential acylation and reduction to yield 5-ethyl-5/7-dibcnz[A,/ ]azepine (8, R = Et).192 Similarly, reduction in trifluoroacetic acid produces the trifluoroethyl derivative 8 (R = CF3CH2 61% mp 69-70 C).193... 

The reaction of butyllithium with 1-naphthaldehyde cyclohexylimine in the presence of (/C )-l,2-diphenylethane-1,2-diol dimethyl ether in toluene at —78 °C, followed by treatment with acetate buffer, gave 2-butyl-1,2-dihydronaphthalene-l-carbaldehyde, which was then reduced with sodium borohydride in methanol to afford (1 R,2.S)-2-butyl-1 -hydroxymcthyl-1,2-dihydronaphthalene in 80% overall yield with 91 % ee83. Similarly, the enantioselective conjugate addition of organolithium reagents to several a,/J-unsaturated aldimines took place in the presence of C2-symmetric chiral diethers, such as (/, / )-1,2-butanediol dimethyl ether and (/, / )- ,2-diphenylethane-1,2-diol dimethyl ether. 

Reduction and preparation of derivatives Concentrate the aqueous mixture to 0.5 ml. Add 20 mg of sodium borohydride dissolved in 0.5 ml of ion exchange water. Let this solution stand at room temperature for 1 hour. Destroy the excess sodium borohydride by adding acetic acid until gas evolution stops. Evaporate the solution to dryness. Add 5 ml of methanol and evaporate again to dryness. 

Preparation of the acetate derivative Concentrate the aqueous mixture of saccharides to approximately 0.5 ml in a 20-50 ml container. Reduce the saccharides by adding 20 mg of sodium borohydride that has been dissolved carefully into 0.5 ml of water and let the reducing mixture stand at room temperature for at least 1 hour. Destroy the excess sodium borohydride by adding acetic acid until the gas evolution stops. Evaporate the solution to dryness with clean nitrogen. Add 10 ml of methanol and evaporate the solution to dryness. Acetylate with 0.5 ml (three parts acetic anhydride and two parts pyridine) overnight. Evaporate to a syrupy residue and add 1 ml of water. Evaporate again to dryness to remove the excess acetic anhydride. Dissolve the residue in 250 /d methylene chloride. 

Polymerization of 6,8-dioxabicyclo[3.2.1]octane, 2, has been most extensively studied among bicyclic acetals. This monomer is readily prepared from 3,4-dihydro-2H-pyran-2-carbaldehyde 1 by reduction with sodium borohydride followed by add-... 

Although catalytic hydrogenation is the method most often used, double bonds can be reduced by other reagents, as well. Among these are sodium in ethanol, sodium and rerr-butyl alcohol in HMPA, lithium and aliphatic amines (see also 15-14), " zinc and acids, sodium hypophosphate and Pd-C, (EtO)3SiH—Pd(OAc)2, trifluoroacetic acid and triethylsilane (EtsSiH), and hydroxylamine and ethyl acetate.However, metallic hydrides, such as lithium aluminum hydride and sodium borohydride, do not in general reduce carbon-carbon double bonds, although this can be done in special cases where the double bond is polar, as in 1,1-diarylethenes and in enamines. " °... 

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