Sodium borohydride Acids

Deamination studies have aided attempts to locate the positions of the O-sulfate groups in heparin. From the results of deamination and periodate-oxidation studies, it was concluded239 that half of the uronic acid residues are sulfated at C-2, and sequential periodate oxidation, reduction with sodium borohydride, acid treatment, and deamination gave 2,5-anhydro-D-mannose 6-sulfate.240,241 Sulfated O-(hexosyluronic acid)-2,5-anhydro-D-mannose and sulfated uronic acids were subsequently isolated, and the isolation (in 65% yield) of the disulfated 0-(idosyluronic acid)-2,5-anhydro-D-mannose (137) from heparin, together with the 13C n.m.r. spectra of 137 and heparin, suggested243 that at least two thirds of the heparin structure consists of the repeating unit 138. 

Hydride generation (HG) is one of the most frequently used methods for the determination of arsenic at trace concentrations. The advantage of this method is that the hydride (arsine) generation is easily connected to various detection systems and improves the detection limits of almost all methods 100-fold. Hydride generation is based on the production of volatile arsines either by zinc/ hydrochloric acid or sodium borohydride/acid mixtures. The volatile arsines are transported by an inert gas to the detection system. When the pH of the hydride generation reaction is carefully controlled, differentiation between As(ni) and... 

The silylenol ether formed from (47) and trimethylchlorosilane was cyclized in situ, and the reaction mixture was worked up under acidic conditions to give the ketone (558). This was subjected to reduction with sodium borohydride, acid-catalyzed elimination of water, and oxidation with dichlorodicyanobenzoquinone (DDQ) to give the bicyclic ester (560). Introduction of a methoxy substituent into the retinoid structure (560) was likewise effected via the ketone (558). When this ketone was ketalized with methyl o-formate, methanol was eliminated and the product was oxidized, its six-membered ring system undergoing aromatization to form a substituted phenyl group. 

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. ... 

Sodium borohydride is not nearly as potent a hydride donor as lithium aluminum hydride and does not reduce carboxylic acids... 

The enzyme is a single enantiomer of a chiral molecule and binds the coenzyme and substrate m such a way that hydride is transferred exclusively to the face of the carbonyl group that leads to (5) (+) lactic acid Reduction of pyruvic acid m the absence of an enzyme however say with sodium borohydride also gives lactic acid but as a racemic mixture containing equal quantities of the R and S enantiomers... 

The structure of the bicychc monoterpene borneol is shown in Figure 26 7 Isoborneol a stereoisomer of borneol can be prepared in the labora tory by a two step sequence In the first step borneol is oxidized to camphor by treatment with chromic acid In the second step camphor is reduced with sodium borohydride to a mixture of 85% isoborneol and 15% borneol On the basis of these transformations deduce structural formulas for isoborneol and camphor... 

The elements listed in the table of Figure 15.2 are of importance as environmental contaminants, and their analysis in soils, water, seawater, foodstuffs and for forensic purposes is performed routinely. For these reasons, methods have been sought to analyze samples of these elements quickly and easily without significant prepreparation. One way to unlock these elements from their compounds or salts, in which form they are usually found, is to reduce them to their volatile hydrides through the use of acid and sodium tetrahydroborate (sodium borohydride), as shown in Equation 15.1 for sodium arsenite. 

Fluoroalkjiations are frequentiy performed indirectly using tandem reactions. Arenes react with sodium borohydride in trifluoroacetic acid to afford otherwise difficult to obtain l,l,l-trifluoro-2,2-diarylethanes. Presumably sodium borohydride reacts initially with the trifluoroacetic acid to produce the trifluoroacetaldehyde or its equivalent, which rapidly undergoes Friedel-Crafts-type condensation to give an intermediate carbinol. The carbinol further alkylates ben2ene under the reaction conditions giving the observed product. The reaction with stericaHy crowded arenes such as mesitylene and durene... 

Lynestrenol is the des-3-oxo derivative of norethindrone (28). It has been prepared through a similar synthetic pathway as aHylestrenol (37) (52), ie, addition of potassium acetyUde, rather than aHyl magnesium bromide, affords lynestrenol (73). Lynestrenol is also available from norethindrone (28). Reduction of the 3-keto group is accompHshed by treating norethindrone (28) with sodium borohydride in the presence of trifluoro- or trichloroacetic acid... 

Sodium borohydride and potassium borohydride [13762-51 -1] are unique among the complex hydrides because they are stable in alkaline solution. Decomposition by hydrolysis is slow in water, but is accelerated by increasing acidity or temperature. 

Other Borohydrides. Potassium borohydride was formerly used in color reversal development of photographic film and was preferred over sodium borohydride because of its much lower hygroscopicity. Because other borohydrides are made from sodium borohydride, they are correspondingly more expensive. Generally their reducing properties are not sufficiently different to warrant the added cost. Zinc borohydride [17611-70-0] Zn(BH 2> however, has found many appHcations in stereoselective reductions. It is less basic than NaBH, but is not commercially available owing to poor thermal stabihty. It is usually prepared on site in an ether solvent. Zinc borohydride was initially appHed to stereoselective ketone reductions, especially in prostaglandin syntheses (36), and later to aldehydes, acid haHdes, and esters (37). 

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. 

The chain-growth catalyst is prepared by dissolving two moles of nickel chloride per mole of bidentate ligand (BDL) (diphenylphosphinobenzoic acid in 1,4-butanediol). The mixture is pressurized with ethylene to 8.8 MPa (87 atm) at 40°C. Boron hydride, probably in the form of sodium borohydride, is added at a molar ratio of two borohydrides per one atom of nickel. The nickel concentration is 0.001—0.005%. The 1,4-butanediol is used to solvent-extract the nickel catalyst after the reaction. 

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. 

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 the absence of organic matter, silver nitrate is not photosensitive. It is easily reduced to silver metal by glucose, tartaric acid, formaldehyde, hydrazine, and sodium borohydride. 

A McMurry coupling of (176, X = O Y = /5H) provides ( )-9,ll-dehydroesterone methyl ether [1670-49-1] (177) in 56% yield. 9,11-Dehydroestrone methyl ether (177) can be converted to estrone methyl ether by stereoselective reduction of the C —double bond with triethyi silane in triduoroacetic acid. In turn, estrone methyl ether can be converted to estradiol methyl ether by sodium borohydride reduction of the C17 ketone (199,200). 

Xyhtol also is obtained by sodium borohydride reduction of D-xylonic acid y-lactone (32) and from glucose by a series of transformations through diacetone glucose (46). 

Uses. The dominant use of sulfur dioxide is as a captive intermediate for production of sulfuric acid. There is also substantial captive production in the pulp and paper industry for sulfite pulping, and it is used as an intermediate for on-site production of bleaches, eg, chlorine dioxide or sodium hydrosulfite (see Bleaching agents). There is a substantial merchant market for sulfur dioxide in the paper and pulp industry. Sulfur dioxide is used for the production of chlorine dioxide at the paper (qv) mill site by reduction of sodium chlorate in sulfuric acid solution and also for production of sodium dithionite by the reaction of sodium borohydride with sulfur dioxide (315). This last appHcation was growing rapidly in North America as of the late 1990s. 

Industrial Synthetic Improvements. One significant modification of the Stembach process is the result of work by Sumitomo chemists in 1975, in which the optical resolution—reduction sequence is replaced with a more efficient asymmetric conversion of the meso-cyc. 02Lcid (13) to the optically pure i7-lactone (17) (Fig. 3) (25). The cycloacid is reacted with the optically active dihydroxyamine [2964-48-9] (23) to quantitatively yield the chiral imide [85317-83-5] (24). Diastereoselective reduction of the pro-R-carbonyl using sodium borohydride affords the optically pure hydroxyamide [85317-84-6] (25) after recrystaUization. Acid hydrolysis of the amide then yields the desired i7-lactone (17). A similar approach uses chiral alcohols to form diastereomic half-esters stereoselectivity. These are reduced and direedy converted to i7-lactone (26). In both approaches, the desired diastereomeric half-amide or half-ester is formed in excess, thus avoiding the cosdy resolution step required in the Stembach synthesis. 

Another viable method for the synthesis of L-foUc acid (1) starts from 6-formylpterin (23). The diester of L-glutamic acid (24) is condensed with 6-formylpterin (23). Reduction of the Schiff base with sodium borohydride is followed by hydrolysis to yield L-foUc acid (37). 

The reducing agents generally used in bleaching include sulfur dioxide, sulfurous acid, bisulfites, sulfites, hydrosulfites (dithionites), sodium sulfoxylate formaldehyde, and sodium borohydride. These materials are used mainly in pulp and textile bleaching (see Sulfur compounds Boron compounds). 

Methyl borate is beheved to be the boric acid ester produced in the largest quantity, approximately 8600 metric tons per year (28). Most methyl borate is produced by Morton International and used captively to manufacture sodium borohydride [16940-66-2]. Methyl borate production was studied in detail during the 1950s and 1960s when this compound was proposed as a key intermediate for production of high energy fuels. Methyl borate is sold as either the pure compound or as the methanol azeotrope that consists of approximately a 1 1 molar ratio of methanol to methyl borate. 

Recent papers by a manufacturer of sodium borohydride, NaBH (145,146), have demonstrated that excellent removal of metals and color of acid, direct, and reactive dyes for textiles and paper can be achieved with bisulfite-catalyzed borohydride reduction in combination with polymer flocculation. 

Carbonyl-containing and unsaturated materials are removed by treatment with sodium borohydride (227,228) and boric acid (229). Other methods used to remove carbonyl impurities include treatment with hydroxyl amine hydrochloride, potassium permanganate, or A/-hydroxyben2enesulfonamide (229). 

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