Hydrogenation alkyl azides

Formation and Reduction of Azides Azide ion ( N3) is an excellent nucleophile that displaces leaving groups from unhindered primary and secondary alkyl halides and tosylates. The products are alkyl azides (RN3), which have no tendency to react further. Azides are easily reduced to primary amines, either by LiAlH4 or by catalytic hydrogenation. Alkyl azides can be explosive, so they are reduced without purification. 

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... 

A better method for preparing primary amines is to use the azide synthesis, in which azjde ion, N3, is used for SN2 reaction with a primary or secondary alkyl halide to give an alkyl azide, RN3. Because alkyl azides are not nucleophilic, overalkylation can t occur. Subsequent reduction of the alkyl azide, either by catalytic hydrogenation over a palladium catalyst or by reaction with LiAlK4. then leads to the desired primary amine. Although the method works well, low-molecular-weight alkyl azides are explosive and must be handled carefully. 

Tertiary alkyl chlorides, which cannot be aminated directly, react with trimethylsilyl azide under tin(IV) chloride catalysis to yield the corresponding alkyl azides. The crude products are directly converted into Z-alkylarnine hydrochlorides by consecutive treatment with triethyl phosphite and gaseous hydrogen chloride (equation 14)44. 

The photochemistry of ferf-butylazide in a nitrogen matrix at 12 K was followed by IR spectroscopy. Only one product, trimethyhmine, was observed. Thus, the removal of alpha hydrogen from the alkyl azide does not suppress 1,2-migration reactions. 

The alkyl azide produced can be reduced to the primary amine by a number of methods such as catalytic hydrogenation (Chapter 24) or LiAlH4 (Chapter 12). This method has a similar philosophy to the reductive amination discussed in Chapter 14. 

Gurtius and co-workers studied the acid-catalysed decomposition of alkyl azides such as benzyl azide. This was decomposed in either warm 1 1 (v/v) sulphuric acid-water or with concentrated hydrochloric acid to give a mixture of products corresponding to hydrogen migration [benzaldiinine (1)], phenyl migration [formaldehyde anil (2)], the azide reduction product [benzylamine (3)], and the solvolysis product [benzyl alcohol (4)]. The first two were obtained as the... 

In agreement with equation (109), recent work has shown that the thermolysis (150°) under nitrogen of mesitylene-2-sulphonyl azide (251) in n-dodecane gave rise to dodecyl azides (2 3%) This was thought to occur by the triplet nitrene (253) abstracting a hydrogen from the solvent to produce C12H25 which could then attack azide (251) to produce an alkyl azide and 254 °. The same products... 

Reports of reactions characteristic of nitrenes (aromatic substitution, intramolecular C—H insertion and hydrogen abstraction) obtained by photolysis of various alkyl azides proved to be... 

In agreement with the latter results, it was found that photolysis of tertiary alkyl azides in cyclohexane gave, in addition to small amounts of hydrocarbons (C—N fission, ca. 1%) products corresponding only to rearrangementNo intramolecular cyclization, solvent insertion or hydrogen abstraction products were detected (<0-2%). 

Photolysis of the aryl-alkyl azide CH CPhaNa showed that the migratory aptitudes of the methyl and phenyl groups were almost identical and this and the formation of triphenylmethyl amine from irradiation of triphenylmethyl azide in the presence of efficient hydrogen donors were taken to confirm the existence of discrete nitrene intermediates. Although the occurrence of a triplet-sensitized decomposition from alkyl azides and triphenylmethyl azides (the... 

Azide anion, which is more nucleophilic than amines, reacts with alkyl halides and activated alcohols giving the corresponding alkyl azides. Phase-transfer conditions can also be utilized. For details, readers are referred to a comprehensive review. Alkyl azides thus formed can be readily transformed into primary amines by a variety of reagents or reaction systems which involve catalytic hydrogenation, LiAlH4, NaBH4 under phase-transfer conditions, NaBH /THF/MeOH, PhsP ... 

Barton and Morgan described another synthesis of conessine 140, 141) based upon photolytic cyelization of alkyl azides to pyrrolidines. They explained this reaction by the assumption that alkyl azide gives an activated nitrene which may react in different ways—one of the possibilities being, if necessary steric requirements are satisfied, 1,5-hydrogen abstraction followed by cyelization to pyrrolidine. They applied this principle to 3(8,20a-diazidopregn-5-ene, prepared from the... 

A working hypothesis for this inactivation mechanism has been proposed (63) and is presented in Scheme 11 (compounds 16-20). Consistent with the mechanisms of substrate and inhibitor utilization by RDPR, the initial step is proposed to be abstraction of the 3 -hydrogen by the tyrosyl radical X to generate a 3 -nucleotide radical, 16. There are no known good chemical precedents for decomposition of )3-azidoalkyl radicals such as 16. The best analogy is an inter-molecular reaction of 1-hydroxy-1-methylene radical with primary alkyl azides... 

Recently, Kim has reported a modified Hofmann-Loffler-Freytag reaction under reducing conditions [70], Treatment of alkyl azides with Bu3SnH afforded N-tributylstannyl radicals. These radicals proved to be more reactive than ordinary aminyl radicals towards hydrogen atom abstraction presumably because of their higher nucleophilicity. Two examples are shown in Scheme 14. In the first one (Eq. 

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