Lithium aluminum hydride azides reduction

Reduction of an azide a nitrile or a nitro compound furnishes a primary amine A method that provides access to primary secondary or tertiary amines is reduction of the carbonyl group of an amide by lithium aluminum hydride... 

Iodine azide, on the other hand, forms pure adducts with A -, A - and A -steroids by a mechanism analogous to that proposed for iodine isocyanate additions. Reduction of such adducts can lead to aziridines. However, most reducing agents effect elimination of the elements of iodine azide from the /mwj -diaxial adducts of the A - and A -olefins rather than reduction of the azide function to the iodo amine. Thus, this sequence appears to be of little value for the synthesis of A-, B- or C-ring aziridines. It is worthy to note that based on experience with nonsteroidal systems the application of electrophilic reducing agents such as diborane or lithium aluminum hydride-aluminum chloride may yet prove effective for the desired reduction. Lithium aluminum hydride accomplishes aziridine formation from the A -adducts, Le., 16 -azido-17a-iodoandrostanes (97) in a one-step reaction. The scope of this addition has been considerably enhanced by the recent... 

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. 

Butyl alcohol in synthesis of phenyl 1-butyl ether, 46, 89 1-Butyl azidoacetate, 46, 47 hydrogenation of, 46, 47 1-Butyl chloroacetate, reaction with sodium azide, 46, 47 lre l-4-i-BUTYLCYCLOHEXANOL, 47,16 4-(-Butylcyclohexanonc, reduction with lithium aluminum hydride and aluminum chloride, 47, 17 1-Butyl hypochlorite, reaction with cy-clohexylamine, 46,17 l-Butylthiourea, 46, 72... 

The importance of reactions with complex, metal hydrides in carbohydrate chemistry is well documented by a vast number of publications that deal mainly with reduction of carbonyl groups, N- and O-acyl functions, lactones, azides, and epoxides, as well as with reactions of sulfonic esters. With rare exceptions, lithium aluminum hydride and lithium, sodium, or potassium borohydride are the... 

Excellent procedures are available for the preparation of primary, secondary, and tertiary amines by the reduction of a variety of nitrogen compounds. Primary amines can be obtained by hydrogenation or by lithium aluminum hydride reduction of nitro compounds, azides, oximes, imines, nitriles, or unsubstituted amides [all possible with H2 over a metal catalyst (Pt or Ni) or with LiAlH4] ... 

Lithium aluminum hydride is a convenient reagent for reduction of nitro compounds, nitriles, amides, azides, and oximes to primary amines. Catalytic hydrogenation works also. Aromatic nitro compounds are reduced best by reaction of a metal and aqueous acid or with ammonium or sodium polysulfides (see Section 23-12B). Reduction of /V-substituted amides leads to secondary amines. 

Formation and Reduction of Nitriles Like the azide ion, cyanide ion (- C=N ) is a good Sn2 nucleophile it displaces leaving groups from unhindered primary and secondary alkyl halides and tosylates. The product is a nitrile (R—C=N), which has no tendency to react further. Nitriles are reduced to primary amines by lithium aluminum hydride or by catalytic hydrogenation. 

LVI) was proved 54) by Esohweiler-Clarke methylation to methyl-holaphylline and was further confirmed by a synthesis from pregnenolone (LIX) via 3 8-tosyloxy-20-oximinopregn-5-ene (LX) which on treatment with sodium azide in methanol yielded a mixture of 3 3-azido-20-oximino-pregn-5-ene (LXI) and the 3a,6a-cyclo-6 -azido isomer. Selective reduction with lithium aluminum hydride followed by acid hydrolysis yielded holaphyllamine along w ith its 3,5-cyclo isomer which could be separated by chromatography (55). 

Dihydroxylation of the stilbene double bond in the trans isomers of Combretastatin A-1 and A-4 produced diols which by treatment with boron trifluoride in ethyl ether [44] or with trifluoroacetic acid [17] resulted in pinacolic rearrangement to produce an aldehyde. The aldehyde was converted in a variety of derivatives, as illustrated in the Scheme 20, via the following reaction sequence reduction with sodium borohydride to primary alcohol which was derivatized to the corresponding mesylate or tosylate, substitution with sodium azide and final reduction to amine with lithium aluminum hydride. Alternatively the aldehyde was converted to oxime which was catalitically hydrogenated to amine [17]. 

Thus, addition of iodine monochloride and sodium azide to 1 -methylcyclobutene in acetonitrile gave rra i-l-azido-2-iodo-l-methylcyclobutane (1) in 70% yield. Lithium aluminum hydride reduction of this trans-0L,p- odiethyl ether at 20 °C gave, instead of the expected l-methyl-5-azabicyclo[2.1.0]pentane, the product of ring contraction, i.e. 1-aminoethylcyclo-propane (3). Formation of an intermediate 2-iodocyclobutylamine, which then underwent C4 -> C3 ring contraction, analogously to the 2-halocyclobutanols (Section 4.1.2.2.1) appeared likely to explain this result. 

The addition of iodine azide to l,2-dimethylcyclobutene gave the normal adduct, i.e. trans-i-azido-2-iodo-l, 2-dimethylcyclobutene (4) in 65% yield, only when equimolar amounts of iodine monochloride and sodium azide in acetonitrile were employed and the reaction worked up within 90 minutes. Lithium aluminum hydride reduction gave l-(l-aminoethyl)- -methyl-cyclopropane (6) in 63% yield. 

Reduction of aikyi azides (Section 22.10) Alkyl azides, prepared by nucleophilic substitution by azide ion in primary or secondary alkyl halides, are reduced to primary alkylamines by lithium aluminum hydride or by catalytic hydrogenation. 

Aziridines2 )3-Iodoazides, available by the addition of iodine azide to olefins, undergo reduction of the azide function followed by base-catalyzed ring closure to aziridines. The most satisfactory reagent for this purpose is lithium aluminum hydride, which can accomplish both reaction steps since it is a Lewis acid as well as a reducing agent. Competing side reactions are elimination of the elements... 

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