Nitriles hydride reduction

Aldehydes have also been obtained by lithium trialkoxyaluminum hydride reduction of 5-nitriles or 5-acid chlorides, and, as the thio-semicarbazones, by the McFadyen-Stevens reaction in surprisingly good yields (50-60%) considering the severity of the reaction conditions. ... 

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%. 

Although the hydride reduction of nitriles frequently requires the use of vigorous conditions (LiAlH4, B2H6), aryl nitriles and benzyl nitriles are reduced to the... 

Nitriles on reduction with lithium aluminium hydride (LIAIH ) or catalytic hydrogenation produce primary amines. This reaction is used for ascent of amine series, i.e., for preparation of amines containing one carbon atom more than the starting amine. 

The stoichiometry of lithium aluminum hydride reductions with other compounds such as nitriles, epoxides, sulfur- and nitrogen-containing com-... 

The complex hydride reductions of nitriles to aldehydes compare favorably with the classical Stephen reduction which consists of treatment of a nitrile with anhydrous stannous chloride and gaseous hydrogen chloride in ether or diethylene glycol and applies to both aliphatic and aromatic nitriles [183,285, 1152]. An advantage of the Stephen method is its applicability to polyfunctional compounds containing reducible groups such as carbonyl that is reduced by hydrides but not by stannous chloride [1153]. 

Thus, for example, guanidine analogues guanoxyf n (79) and guanochlor (82) also possess antihypertensive activity. Guanoxyfen is synthesized by base-catalyzed condensation of phenol with chloroaceto-nitrile, followed by hydride reduction to amine 78. 

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. 

Similarly, lipase-catalyzed kinetic resolution has also been applied to intermediate nitrile alcohol 46 (Scheme 14.14). Best results were obtained by using immobilized Pseudomonas cepacia (PS-D) in diisopropyl ether, leading to excellent yield and enantiomeric excess of the desired (5)-alcohol 46a, along with (/J)-nitrile ester 47. Reduction of 46a with borane-dimethylsulhde complex, followed by conversion to the corresponding carbamate and subsequent lithium aluminum hydride reduction gave rise to the desired (S)-aminoalcohol intermediate 36, a known precursor of duloxetine (3). 

Precursors of type E (erythro fragment) (Scheme 6.69) were obtained by cycloaddition of a nitrile oxide dipole to a-alkoxyalkenes. This strategy was used in the syntheses of dl- and D-hvidosamine (298) (Scheme 6.73). Fithium aluminum hydride reduction of the erythro adduct 130 produced aminoalcohols 135 in a 78 22 ratio (2,4-erythro/threo) in high yield. The mixture was subjected to HCl hydrolysis to give the hexosamine hydrochlorides 136, which after several steps, produced D-hvidosamine 137 possessing the D-ribo configuration (298). 

Amides, azides and nitriles are reduced to amines by catalytic hydrogenation (H2/Pd—C or H2/Pt—C) as well as metal hydride reduction (LiAlH4). They are less reactive towards the metal hydride reduction, and cannot be reduced by NaBITj. Unlike the LiAlIU reduction of all other carboxylic acid derivatives, which affords 1° alcohols, the LiAlIU reduction of amides, azides and nitriles yields amines. Acid is not used in the work-up step, since amines are basic. Thus, hydrolytic work-up is employed to afford amines. When the nitrile group is reduced, an NH2 and an extra CH2 are introduced into the molecule. 

In order to avoid the rather vigorous conditions of nitrile hydrolysis a sequence involving hydride reduction of the nitrile71 was investigated. 

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] ... 

Base-Catalyzed Hydrolysis of a Nitrile 1014 Hydride Reduction of an Ester 1015 Reduction of an Amide to an Amine 1016 Reaction of an Ester with Two Moles of a Grignard Reagent 1018... 

Beckmann rearrangement of a 17-oxime has also been used to furnish A13<18)-13,17-seco-5a-androstene-17-nitrile (249), which on methylation with methyl-lithium gave the ketone (256 R = H) and thence by hydride reduction the alcohol (257 R1 = H, R2 = OH, R3 = Me).115 Conversion of this alcohol into its tosylate and further hydride reduction furnished the exocyclic olefin A13(18)-13,17-seco-D-homoandrostene (257 R1 = R2 = H, R3 = Me). Reaction of the nitrile (249) with trideuteriomethyl-lithium gave the ketone (256 R = D) and conversion into the hydrocarbon as outlined above gave the olefin (257 R1 = R2 = H, R3 = CD3). Reduction of the ketone (256 R = H) with lithium aluminium deuteride furnished the alcohol (257 R1 = D, R2 = OH, R3 = Me) which could in turn be converted into... 

Complex hydride reductions of Nj, N O, [CN] and nitriles in reactions containing complex mixtures of metal-ion species produce N—H bonded products " by reactions that may relate to those of the biological nitrogenases". Complete reaction stoichiometries are not well established. These reactions are not competitive with other methods for NH or amine synthesis. Nitrogen reacts in H O with a mixture of NaBH, S-donor ligands (e.g., NH CjM SH) and Mo and Fe salts to form NHj and NjH in low yield . In similar systems, nitriles and isonitriles are reduced to NHj and amines in low yield . 

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