Reduction reaction nitriles

The Stephen s method allows the reduction of nitriles by stannous chloride in acid medium. If the amine chlorhydrate initially formed is hydrolyzed, the corresponding aldehyde is obtained (37, 91). Harington and Moggridge (37) have reduced 4-methyl-5-cyanothiazole by this method (Scheme 23). However, Robba and Le Guen (91) did not obtain the expected products with 4.5-dicyanothiazole and 2-methyl-4,5-dicyanothiazole. These compounds have been reduced with diisobutyl-aluminium hydride with very low yields (3 to 6%) (Scheme 24). In other conditions the reaction gives a thiazole nitrile aldehyde with the same yield as that of the dialdehyde. 

Method 5. Nitrile reduction reaction of a nitrile with hydrogen over a hydrogenation catalyst. 

Nitriles. The electrolytic reduction of nitriles requires a high negative potential, but can lead to amines in good yields under the right conditions. This reaction occurs in acidic media according to the following equation (62). 

One development involves the use of vitamin B 2 to cataly2e chemical, in addition to biochemical processes. Vitamin B 2 derivatives and B 2 model compounds (41,42) cataly2e the electrochemical reduction of alkyl haUdes and formation of C—C bonds (43,44), as well as the 2inc—acetic acid-promoted reduction of nitriles (45), alpha, beta-unsaturated nitriles (46), alpha, beta-unsaturated carbonyl derivatives and esters (47,48), and olefins (49). It is assumed that these reactions proceed through intermediates containing a Co—C bond which is then reductively cleaved. 

Nickel in the presence of ammonia is often used for reduction of nitriles to primary amines. The reaction is done at elevated temperatures and pressures ( 100 C, 1000 psig) unless massive amounts of nickel are used. Cobalt is used similarly but mainly under even more vigorous conditions. Nitriles containing a benzylamine can be reduced over Raney nickel to an amine without hydrogenolysis of the benzyl group (7). A solution of butoxycarbonyl)-3-aminopropyl]-N-<3-cyanopropyl)benzylamine (13.6 g) in 100 ml of ethanol containing 4 g. NaOH was reduced over 3.0 g Raney nickel at 40 psig for 28 h. The yield of A/ -benzyl-Air -(f-butoxycarbonyl)s >ermidine was 95% (7). 

Woodward s strychnine synthesis commences with a Fischer indole synthesis using phenylhydrazine (24) and acetoveratrone (25) as starting materials (see Scheme 2). In the presence of polyphosphor-ic acid, intermediates 24 and 25 combine to afford 2-veratrylindole (23) through the reaction processes illustrated in Scheme 2. With its a position suitably masked, 2-veratrylindole (23) reacts smoothly at the ft position with the Schiff base derived from the action of dimethylamine on formaldehyde to give intermediate 22 in 92% yield. TV-Methylation of the dimethylamino substituent in 22 with methyl iodide, followed by exposure of the resultant quaternary ammonium iodide to sodium cyanide in DMF, provides nitrile 26 in an overall yield of 97%. Condensation of 2-veratryl-tryptamine (20), the product of a lithium aluminum hydride reduction of nitrile 26, with ethyl glyoxylate (21) furnishes Schiff base 19 in a yield of 92%. 

White-rot fungus has been used as a biocatalyst for reduction and alkylation. The reaction of aromatic -keto nitriles with the white-rot fungus Curvularia lunata CECT 2130 in the presence of alcohols afforded alkylation-reduction reaction [291]. Alcohols such as ethanol, propanol, butanol, and isobutanol could be used (Figure 8.39d). 

In contrast to the related organoboranes, which are mostly used in the addition to non-polar carbon-carbon multiple bonds, aluminum hydrides have found their widest use in organic synthesis in the addition reaction to polar carbon-carbon and carbon-heteroatom multiple bonds including carbonyl, nitrile and imino groups as well as their a,(J-unsaturated analogs. Although these reduction reactions are also sometimes referred as hydroalumination reactions in the Hterature, they are outside the scope of this review. 

Reductive hydrolysis86 of organic nitriles is known to lead to the corresponding aldehydes. Application of Backeberg and Staskun s87 modification of this reaction to reduction of nitrile 82 was reported... 

As we shall see later, other reactions of nitriles extend the usefulness of this reaction. Thus, reduction of nitriles gives amines (see Section 7.6.1), whereas hydrolysis generates a carboxylic acid (see Box 7.9). 

A number of organic species, including amides, oximes, and nitriles, undergo reductive amination, a variety of reduction reactions that produce cimines. In general, these processes involve imines, R=N-R, or related species. Reduction processes include hydrogenation using Raney nickel as the catalyst (for nitriles), the reaction with sodium/EtOH (for oximes), and the use of lithium aluminum hydride, LiAlH (for amides or nitriles). Figure 13-16 illustrates the preparation of amphetamine by reductive amination. 

Reduction of nitrile with a less powerful reducing reagent, e.g. DIBAH, produces aldehyde. The reaction is carried out at low temperatures (—78 °C) in toluene. 

Reduction of carboxylic acids 9-42 Reduction of carboxylic esters 9-43 Reduction of carboxylic esters with titanocene dichloride 9-44 Reduction of anhydrides 9-45 Reduction of acyl halides 9-53 Reduction of nitriles 9-57 Reduction of hydroperoxides 9-60 Reduction of peroxides 9-69 Reaction between aldehydes and base (Cannizzaro)... 

The reduction is usually effected catalytically in ethanol solution using hydrogen under pressure in the presence of Raney nickel. As in the reduction of nitriles (Section 5.16.1, p. 771), which also involves the intermediate imine, ammonia or the amines should be present in considerable excess to minimise the occurrence of undesirable side reactions leading to the formation of secondary and tertiary amines. These arise from the further reaction of the carbonyl compound with the initially formed amine product. Selected experimental conditions for these reductive alkylation procedures have been well reviewed.210 Sodium borohydride has also been used as an in situ reducing agent and is particularly effective with mixtures of primary amines and aliphatic aldehydes and ketones.211... 

The two reducing agents considered so far in this section—LiAlH4 and DIBAL—also are the reagents of choice for the reduction of nitriles (Figure 17.64). The mechanistic details of these reactions can be gathered from the figure, and the result can be summarized as follows. 

Another method that can be used to prepare primary amines is the reduction of nitriles with lithium aluminum hydride. The mechanism for this reaction involves sequential addition of two hydride nucleophiles to the electrophilic carbon of the cyano group. The addition of water in the workup step supplies the two protons on the nitrogen in the product. An example follows ... 

The electron adduct of benzonitrile has also been found to be converted into a cyclohexadienyl-type radical (Chutny and Swallow, 1970). Aliphatic nitriles, on the other hand, protonate rapidly on the CN carbon following reduction [reaction (82)] (Neta and Fessenden, 1970b). 

Just as amines are easily obtained by reduction of nitriles with sodium amalgam or sodium and alcohol, so this reaction can be carried out electrolytically (p. 121). 

Aluminum hydrides can reduce nitriles to the corresponding aldehydes. Diisobutylaluminum hydride, abbreviated (i-Bu AlH or DIBAL-H, is commonly used for the reduction of nitriles. The initial reaction forms an aluminum complex that hydrolyzes in the aqueous workup. 

Reduction of nitriles by organomagnesium compounds has not often been reported, though it may well occur, by mechanisms analogous to those for reduction of carbonyl compounds see p. 112. A few cases are also known in which the cyano group is displaced see Section 8.3.2). These initial reactions may then be followed by others, involving an excess of either the organomagnesium compound or of the nitrile [E], These further reactions are of limited usefulness in synthesis, but the more important ones are summarized in Scheme 5.3. 

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