Nitriles, catalytic hydrogenation reagents

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. 

A few 6- and 8-cyanopurines have been prepared and undergo characteristic nitrile addition reactions rather readily. Thus, alkaline hydrolysis produces carboxamides, then carboxylic acids, alcoholysis leads to imidates, ammonolysis to amidines, hydrazinolysis to amidhydrazines, hydroxylamine to amidoximes, and hydrogen sulfide to thioamides. Acid hydrolysis tends to give the decarboxylated acid derivative. Reduction either by sodium-ethanol or, preferably, by catalytic hydrogenation affords aminoalkylpurines and addition of Grignard reagents produces, in the first place, acylpurines. As with aldehydes, most of the compounds examined have been relatively non-polar derivatives. Table 28 lists some reactions and relevant literature. 

Selective reduction of the olefin unit of the a,p-unsaturated nitrile is accomplished essentially with two systems one by catalytic hydrogenation using Pd/C, the other using magnesium in MeOH, a reagent combination known for its ability to reduce a,P-unsaturated nitriles. 

Hydrogenation of nitro compounds is rather straightforward, and palladium, platinum, and nickel catalysts have been used. Palladium is the most common catalyst for both aromatic and aliphatic nitro compounds. The poor results obtained for reduction of aromatic nitriles with hydride reagents (sec. 4.2.C.iii) make catalytic hydrogenation the preferred method. Reduction of 407 involved conversion of the aromatic nitrile moiety to the benzylamine derivative when palladium and a trace of platinum oxide was used. Hydrogenation using platinum oxide converts aromatic nitro compounds to aniline derivatives, even in the presence of other reducible groups. OS... 

As the Heck reaction protocol is quite robust to the presence of various electrophihc and nucleophilic functional groups and reagents, its combination with other reaction types is highly appealing. The one-pot performance of a Heck reaction and a catalytic hydrogenation is definitely one of the most useful approaches to P-aryl-substituted esters and nitriles (Section 8.8). 

In previous sections, hydride reagents such as NaBH4 or LiAlH4 reduce ketones or aldehydes and most acid derivatives to the corresponding alcohol. LiAlH4 reduces amides to amines and also reduces nitriles to amines. Catalytic hydrogenation reduces alkenes and alkynes, as well as ketones, aldehydes, acid chlorides, and nitriles. Acid chlorides may be reduced to aldehydes, and nitriles are also reduced to amines by catalytic hydrogenation. 

Many other functional groups are also reactive under conditions of catalytic hydrogenation. The reduction of nitro compounds to amines, for example, usually proceeds very rapidly. Ketones, aldehydes, and esters can all be reduced to alcohols, but in most cases these reactions are slower than alkene reductions. For most synthetic applications, the hydride transfer reagents to be discussed in Section 5.2 are used for reduction of carbonyl groups. Amides and nitriles can be reduced to amines. Hydrogenation of amides requires extreme conditions and is seldom used in synthesis, but reduction of nitriles is quite useful. Scheme 5.3 gives a summary of the approximate conditions for catalytic reduction of some common functional groups. 

Nitriles can be reduced to amines by either catalytic hydrogenation or lithium aluminum hydride. However, the modified hydride reagent lithium triethoxyaluminum hydride adds to the bond only once to give an imine anion derivative. 

The nitrile is then hydrogenated to a primary amine from which amine derivatives can be made by utilization of a variety of reagents [6, 7]. The example in eqns 6.1.1-6.1.3 shows the conversion of fatty acid to dialkyl secondary amine via catalytic deammoniafication (for this and all subsequent structures n = 80-20 unless otherwise noted) ... 

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