Azides sodium borohydride

In pharmaceutical appHcations, the selectivity of sodium borohydride is ideally suited for conversion of high value iatermediates, such as steroids (qv), ia multistep syntheses. It is used ia the manufacture of a broad spectmm of products such as analgesics, antiarthritics, antibiotics (qv), prostaglandins (qv), and central nervous system suppressants. Typical examples of commercial aldehyde reductions are found ia the manufacture of vitamin A (29) (see Vitamins) and dihydrostreptomycia (30). An acyl azide is reduced ia the synthesis of the antibiotic chloramphenicol (31) and a carbon—carbon double bond is reduced ia an iatermediate ia the manufacture of the analgesic Talwia (32). 

Sodium alkoxide Sodium azide Sodium borohydride Tetrabromoethane Tetrachloroethane... 

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... 

The azidohydrins obtained by azide ion opening of epoxides, except for those possessing a tertiary hydroxy group, can be readily converted to azido mesylates on treatment with pyridine/methanesulfonyl chloride. Reduction and subsequent aziridine formation results upon reaction with hydrazine/ Raney nickel, lithium aluminum hydride, or sodium borohydride/cobalt(II)... 

The azido mesylate may also be reduced with lithium aluminum hydride in the same manner as previously described for iodo azide reductions. The sodium borohydride/cobalt(II)tris(a,a -dipyridyl)bromide reagent may be used, but it does not seem to offer any advantages over the more facile lithium aluminum hydride or hydrazine/Raney nickel procedures. 

Bromo-6,7,8,9-tetrahydro-l//-3-benzazepin-2-amine(6) with thiocyanate ion undergoes substitution of bromide to give the thiocyanatotetrahydro-l//-3-benzazepine 7.105 Attempts to replace bromide by azide ion failed, as did diazotization of the amine group with sodium nitrite in 6 M sulfuric acid. Oddly, treatment of the aminobromo compound with sodium borohydride in methanol results not in reduction, but in methoxy-debromination to give the 2-methoxy derivative which, on the basis of HNMR spectral data, is best represented as the 2-imino tautomer 8. 

Sodium hydrogen telluride, (NaTeH), prepared in situ from the reaction of tellurium powder with an aqueous ethanol solution of sodium borohydride, is an effective reducing reagent for many functionalities, such as azide, sulfoxide, disulfide, activated C=C bonds, nitroxide, and so forth. Water is a convenient solvent for these transformations.28 A variety of functional groups including aldehydes, ketones, olefins, nitroxides, and azides are also reduced by sodium hypophosphite buffer solution.29... 

Sodium, with l-bromo-3-chloro-cyclobutane to give bicyclo [l.l.O]butane, 51, 55 Sodium amalgam, 50, 50, 51 Sodium amide, with 2,4-pentane-dione and diphenyliodonium chloride to give l-phenyl-2, 4-pentanedione, 51, 128 Sodium azide, 50, 107 with mixed carboxylic-carbonic anhydrides, 51, 49 Sodium borohydride, reduction of erythro-3-methanesulfony-loxy-2-butyl cyclobutanecar-boxylate, 51, 12 reduction of 2-(1-phenylcyclo-pentyl)-4,4,6-trimethyl-5,6-dihydro-1,3(4H)-oxazine to 2-(1-phenylcyclopentyl)-4,4, 6-trimethyltetrahydro-l,3-oxazine, 51, 25 Sodium cyanoborohydride, used... 

The pyrrolidine derivative 314, a skeletal analog of the antitumor antibiotic anisomycin, was synthesized from the acetal derivative 16b. The 5-OH group of 16b was tosylated and then substituted with sodium azide. Reduction (sodium borohydride) of the lactone group afforded an open-chain derivative, which was selectively protected to give 313. Hydrogenation of the azide function, followed by p-toluenesulfonylation, led to 314 by an intramolecular nucleophilic displacement (284). 

Y. Ali and A. C. Richardson, The reduction of azides with sodium borohydride. A convenient synthesis of methyl 2-acetamido-2-deoxy4,6-0-benzylidene-a-D-allopyranoside, Carbohydr. Res., 5 (1967) 441 448. 

Michael addition of sodium borohydride or piperidine across 3-methyleneazetidin-2-one (60) affords the adducts (61) (85T375). 4-(Iodomethyl)azetidin-2-one undergoes nucleophilic substitution by sodium azide in DMF to give the azido compound (88JOC4006). 

About a half-dozen cases are recorded on the formation of A3-triazolines the sodium borohydride reduction of triazolium compounds5 and the vinyl azide additions to triazolinediones6 appear most promising for extended application. Only three synthetic approaches exist for the A4-compounds, of which the route employed by Mohr and Hertel2-2a has greater general applicability. 

A one-pot PTC reaction procedure for the overall conversion of an alkyl halide into a primary amine via an azide is particularly illustrative.204 Thus the reduction of the azide is effected by the addition of sodium borohydride to a reaction mixture arising from the PTC displacement reaction of an alkyl halide with sodium azide (the preparation of 1-octylamine, Expt 5.193). The reaction appears to be applicable to primary and secondary alkyl halides, alkyl methane-sulphonates and benzylic halides. 

THIOL ESTERS Chlorodiphenylphosphine. Diphenylphosphinyl azide. Polyphosphate ester. Sodium borohydride. 2,4,6-Trichlorobenzyl chloride. Triphenylphosphine-Diisopropyl azodicarboxylate-Thiolacetic acid. 

Reduction of an azide functionality at C-3 of azetidin-2-one 355 followed by acylation afforded 3-amidoazetidin-2-one 356 (Scheme 50). O-Debenzylation, followed by treatment with the Jones reagent, afforded a m-3,4-disubsti-tuted azetidin-2-one 357, which is a precursor of the antibiotic loracarbef <2001TL4519>. The reduction of an ethoxycarbonyl group and an acetoxy group at C-3 to a hydroxyl group has been accomplished by sodium borohydride (Equation 134) <2001T10155>. 

Vinyl azides have been prepared by treating epoxides (78) with azide ion to give azido alcohols (79) which are then dehydrated to the vinyl azide.30 This method also complements the iodine azide method since the epoxide route usually gives the isomeric vinyl azide. -Hydroxy azides (81) can also be prepared by the sodium borohydride reduction of a-azidoketones (80). 

A valuable route to benzofurazans is provided by deoxygenation of the corresponding benzofuroxan. This may be accomplished either directly using trialkyl phosphites, tributyl-or triphe nyl-phosphine, or indirectly via the quinone dioxime using, for example, methanol and potassium hydroxide, hydroxylamine and alkali, sodium azide in DMSO or ethylene glycol, sodium borohydride, and occasionally thermolysis alone. More detailed discussion of these reactions is included in Section 4.22.3.2.4. 

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