Lithium amide azide

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. 

Under special conditions (addition of lithium amide, phase-transfer catalysis), compounds with apparently unactivated methylene groups (e.g., 5-methoxy-l-tetra-lone, Lombardo and Mander, 1980) or even with a methyl group at an arylcarbonyl group (Sugihara et al., 1987) undergo diazo transfer with arenesulfonyl azides. This is also the case for esters of 4-arylbut-3-enoic acid and related compounds (Davies et al., 1989, and references therein). 

Finally, small quantities of lithium azide have been obtained from lithium amide and nitrous oxide [85] details are given below under sodium azide (Wislicenus method). The formation of some lithium azide was detected when lithium metal and ammonium azide were reacted in liquid ammonia, but the reaction has not been used for preparation purposes [86]. 

Carhon nucleophiles of pXa 10-20 have heen most studied and often work hest with these substrates (eq 1), hut enamines, cyclopentadiene anions, enolates (eq 2), organotin, -thaUium, -zinc, -aluminum, -lithium, and -zirconiums, as weU as Grignards (eq 3) and horates, also add to r-allylpaUadium complexes. Heteroatom nucleophiles also add successfully these include amines (eq 4), amides, azides, magnesium amides, sulfonamides, alcohols, acids (eq 5), nitrites, sulhnic acids, thiols, phosphines, and phosphites. Limited use of transition metal nucleophiles is also known. ... 

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... 

A number of compounds of the types RSbY2 and R2SbY, where Y is an anionic group other than halogen, have been prepared by the reaction of dihalo- or halostibines with lithium, sodium, or ammonium alkoxides (118,119), amides (120), azides (121), carboxylates (122), dithiocarbamates (123), mercaptides (124,125), or phenoxides (118). Dihalo- and halostibines can also be converted to compounds in which an antimony is linked to a main group (126) or transition metal (127). 

The only example of nitrogen-nitrogen bond cleavage promoted by lithium and a catalytic amount of DTBB (10%) in THF at room temperature was performed with alkyl and aryl azides 87. After hydrolysis, the corresponding primary amides 88 were isolated (Scheme 37). ... 

An improved route to milnacipran (2) and derivatives is described in Scheme 14.5. In this approach, lactone 20 was opened with lithium diethylamide to provide amide alcohol 25, which was readily transformed into azide 26. Hydrogenation on palladium-carbon directly led to the desired target in 86% yield over the three steps. 

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] ... 

Applying Danheiser s method (96JOC134), phenyldiazenyl ketone 67 reacts with lithium bis(trimethylsilyl)amide in absolute tetrahydrofuran followed by 2,2,2-trifluoroethyl triflate forming a mixture of C- and O-triflate intermediates 68 and 69, respectively. Upon treatment with mesyl azide, the mixture of 68 and 69 provides the desired l-diazo-4-methyl-4-[(E)-phenyldiazenyl]pentan-2-one (58) as yellow crystals in very good yield (87%) (Scheme 16). 

Sodium borohydride is a mild and selective reducing reagent. In ethanol solution it reduces aldehydes and ketones rapidly at 25°C, esters very slowly, and is inert toward functional groups that are readily reduced by lithium aluminum hydride carboxylic acids, epoxides, lactones, nitro groups, nitriles, azides, amides, and acid chlorides. 

Lithium aminoborohydrides are obtained by the reaction of -BuLi with amine-boranes [FF2, FH5, NT2]. They can be generated in situ as THF solutions or as solids when formed in diethylether or hexane (n-BuLi must then be used in sub-stoichiometric amounts). They are stable under dry air and are slowly decomposed by water [NT2] or methanol so that workup of the reactions mixtures can be carried out with 3M HCl. They reduce alkyl halides (Section 2.1), epoxides (Section 2.3), aldehydes, and ketones (Section 3.2.1) (in the latter case with an interesting stereoselectivity [HFl]), and esters to primary alcohols (Section 3.2.5). a,(3-Unsaturated aldehydes, ketones, and esters are reduced to allyl alcohols (Section 3.2.9) [FF2, FS2]. Depending on the bulkiness of the amines associated with the reagent and to the substrate, tertiary amides give amines or alcohols (Section 3.2.8) [FFl, FF2]. Amines are also formed from imines (Section 3.3.1) [FB1 ] and from azides (Section 5.2) [AFl]. However, carboxylic acids remain untouched. 

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