Lithium aluminum hydride, reducing nitriles

The intermediate in the reaction is an imine, which is rapidly reduced to the amine. However, lithium aluminum hydride reduces nitriles to primary amines. 

Since sodium borohydride usually does not reduce the nitrile function it may be used for selective reductions of conjugated double bonds in oc,/l-un-saturated nitriles in fair to good yields [7069,1070]. In addition some special reagents were found effective for reducing carbon-carbon double bonds preferentially copper hydride prepared from cuprous bromide and sodium bis(2-methoxyethoxy)aluminum hydride [7766], magnesium in methanol [7767], zinc and zinc chloride in ethanol or isopropyl alcohol [7765], and triethylam-monium formate in dimethyl formamide [317]. Lithium aluminum hydride reduced 1-cyanocyclohexene at —15° to cyclohexanecarboxaldehyde and under normal conditions to aminomethylcyclohexane, both in 60% yields [777]. 

Lithium aluminum hydride reduces amides and nitriles to amines, providing some of the best synthetic routes to amines (Sections 19-19 and 19-20B). Primary amides and nitriles are reduced to primary amines. Secondary amides are reduced to secondary amines, and tertiary amides are reduced to tertiary amines. 

Substituents such as alkene units, alkyne units, and carbonyls can be reduced by catalytic hydrogenation. Lithium aluminum hydride reduces many heteroatom substituents, including nitrile and acid derivatives. 

Substituents such as alkene units, alkyne units, and carbonyls can be reduced by catalytic hydrogenation. Lithium aluminum hydride reduces many heteroatom substituents, including nitrile and acid derivatives 56, 57, 104, 105, 106, 107, 108, 109. Polycyclic aromatic compounds such as naphthalene, anthracene, and phenanthrene give electrophilic aromatic substitution reactions. The major product is determined by the number of resonance-stabilized intermediates for attack at a given carbon and the number of fully aromatic rings (intact rings) in the resonance structures 59, 60, 61, 62, 63, 64, 65, 85, 104, 106, 107, 108,109,110,113,114,118. 

Lithium aluminum hydride reduces the cyano group of a nitrile to a primary amino... 

AletalHydrides. Metal hydrides can sometimes be used to prepare amines by reduction of various functional groups, but they are seldom the preferred method. Most metal hydrides do not reduce nitro compounds at all (64), although aUphatic nitro compounds can be reduced to amines with lithium aluminum hydride. When aromatic amines are reduced with this reagent, a2o compounds are produced. Nitriles, on the other hand, can be reduced to amines with lithium aluminum hydride or sodium borohydride under certain conditions. Other functional groups which can be reduced to amines using metal hydrides include amides, oximes, isocyanates, isothiocyanates, and a2ides (64). 

Lithium aluminum hydride (LiAlH4) is the most powerful of the hydride reagents. It reduces acid chlorides, esters, lactones, acids, anhydrides, aldehydes, ketones and epoxides to alcohols amides, nitriles, imines and oximes to amines primary and secondary alkyl halides and toluenesulfonates to... 

Reduction of nitriles (Section 22.9) Nitriles are reduced to primary amines by lithium aluminum hydride or by catalytic hydrogenation. 

Aromatic nitriles were converted to aldehydes in 50-95% yields on treatment with 1.3-1.7mol of sodium triethoxy aluminum hydride in tetrahydrofuran at 20-65° for 0.5-3.5 hours [1149. More universal reducing agents are lithium trialkoxyaluminum hydrides, which are applicable also to aliphatic nitriles. They are generated in situ from lithium aluminum hydride and an excess of ethyl acetate or butanol, respectively, are used in equimolar quantities in ethereal solutions at —10 to 12°, and produce aldehydes in isolated ytelds ranging from 55% to 84% [1150]. Reduction of nitriles was also accomplished with diisobutylalane but in a very low yield [7/5/]. 

Nitriles of keto acids are reduced with lithium aluminum hydride at both functions. Benzoyl cyanide afforded 2-amino-1-phenylethanol in 86% yield... 

The benzodioxan ring also serves as the aromatic moiety for one of the ubiquitous analogues of the spirone anxiolytic agents discussed in Chapter 9. In the absence of a specific reference, the requisite intermediate (62-1) could be obtained by reducing the cyano group in nitrile (60-1) with lithium aluminum hydride. Alkylation with the spirone side chain chloride (62-2) would then afford binospirone (62-3). 

Lithium aluminum hydride in tetrahydrofuran has been found to reduce aromatic nitriles to give an amine and to give an imine which is formed from the addition of the amine to the nonisolatable imine intermediate followed by an elimination of ammonia [24] (Eq. 14). This is simpler than catalytic hydrogenation of nitriles [25], which gives poor yields of imines. 

Metal hydrides, such as lithium aluminum hydride, also can be used to reduce derivatives of carboxylic acids (such as amides and nitriles see Table 16-6) to aldehydes. An example follows ... 

Nitriles can be reduced to amines by lithium aluminum hydride. An imine salt is an intermediate product if the reaction is carried out under the proper conditions, this salt is the major product and provides an aldehyde on hydrolysis (see Section 16-4C) ... 

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. 

This preparation illustrates the alkylation of malononitrile under acid-catalyzed conditions, and the use of diborane for the reduction of a dinitrile to a diamine. The procedure for the preparation of tert-butylmalononitrile has been outlined briefly by Boldt and co-workers.2 The generation of diborane in situ and the general method for nitrile reduction is that described by Brown and co-workers.3 Attempts to reduce the dinitrile to the diamine by other methods including catalytic hydrogenation (5% rhodium on alumina, 5 atm.), lithium aluminum hydride, and lithium aluminum hydride-aluminum chloride were singularly unsuccessful. 

The first step incorporates generation of a tnllalc leaving group in 35, which is then replaced by a cyanide ion to give 36. Lithium aluminum hydride and sulfuric acid react lo lorm aluminum hydride, capable of selectively reducing the nitrile lo primary amine 9... 

Alkylation of iV-methylbenzylamine with 4-bromobutanenitrile has been achieved in 92% yield in the presence of potassium carbonate as a weak base to neutralize the hydrogen bromide produced. The nitrile may be reduced with lithium aluminum hydride, as shown in the equation, or by catalytic hydrogenation. Catalytic hydrogenation over platinum gave the desired diamine, isolated as its hydrochloride salt, in 90% yield. 

Nitriles can be reduced by lithium aluminum hydride (LiAIH,) to primary amines. 

By contrast, addition of hydrogen cyanide to J -pyrrolines yields stable nitriles, which are reduced by lithium aluminum hydride to diamines and can be saponified to acids318 (Scheme 14). 

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. 

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