Stephen reduction nitriles

There are two principal methods for the reduction of nitriles to aldehydes. In one of these, known as the Stephen reduction, the nitrile is treated with HCl to form... 

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]. 

The Stephen reduction has been applied to a variety of nitriles, but is genuinely useful only for aromatic substrates. Table 11 gives a number of representative examples, and more are available elsewhere. The failure with o-toluonitrile is untypical, and was attributed to steric hindrance. A variant employing tin(II) bromide was successful in synthesizing cinnamaldehyde and its vinylog (45) in 65% and 50% yields, respectively. ... 

Table 11 Yields of Aldehydes Prepared by the Stephen Reduction of Aromatic Nitriles ...

Iminium salt 47 is reduced with anhydrous SnCl2 to RCH=NH, which precipitates as a complex with SnCl4 and is then hydrolyzed (16-2) to the aldehyde. The Stephen reduction is most successful when R is aromatic, but it can be done for aliphatic R up to about six carbons.It is also possible to prepare 47 in a different way, by treating ArCONHPh with PCI5, which can then be converted to the aldehyde. This is known as the Sonn-Muller method. Aqueous formic acid in the presence of Pt02, followed by treatment with aqueous acid, converts aryl nitriles to aryl aldehydes. ... 

In the laboratory of N. Suzuki, the synthesis of several heterocyclic condensed 1,8-naphthyridine derivatives with potential antimicrobial activity was executed. The preparation of pyrazolo[3,4-b][1,8]naphthyridines required 7-chloro-6-formyl-3-ethyl ester as the precursor that was obtained by the Stephen reduction of the corresponding aromatic nitrile. The solution of the aromatic nitrile in chloroform was added to the solution of SnC /dry HCI gas in ether. After two days of stirring, the aldimine hexachlorostannane product was treated with warm water to obtain the desired aromatic aldehyde in modest yield. Heating of the aldehyde with methyl hydrazine afforded the pyrazole derivative. 

L.-M. Yang and co-workers designed and synthesized a new series of frans-stilbene benzenesulfonamide derivatives as potential antitumor agents.A common precursor diethylphosphonate was prepared from commercially available sulfanilamide in six steps. The aromatic nitrile-to-aldehyde reduction was affected by the modified Stephen reduction using Raney nickel alloy in aqueous formic acid. The corresponding aldehyde was obtained in high yield. 

Stephen reduction The reduction of a nitrile to an aldehyde using HC1, followed by anhydrous SnCl2, which produces the intermediate imine, which is then hydrolysed. 

Stephen reduction of an aromatic nitrile to the aldehyde.1 A 2-1. two-necked, round-bottomed flask fitted with a mechanical stirrer and a reflux condenser is charged with 40 g. of p-cyanobenzenesulfonamide, 600 ml. of 75% (v/v) formic acid, and 40 g. of... 

A nitrile is reduced to an aldehyde by treatment with tin chloride and HCl, in what is known as a Stephen reduction. 

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. 

As mentioned previously, aldehydes can be prepared by Stephen s method of reduction of nitriles by stannous chloride (37, 91). Polaro-graphic reduction of thiazolecarboxylic acids and their derivatives gives lower yields of aldehydes (58). Ozonolysis of styrylthiazoles, for example, 2-styryl-4-methylthiazole, followed by catalytic reduction gives aldehyde with 47% yield of crude product (30). 

The reduction of the nitrile groups and subsequent Stephen reaction followed by... 

Most of the methods for preparation of /3-naphthaldehyde have been given previously.2 A recent procedure describes the preparation of /3-naphthaldehyde from 2-bromomethylnaphthalene and hexamethylenetetramine in boiling acetic acid.3 The method of reduction of nitriles by stannous chloride was discovered by Stephen.4... 

STEPHEN ALDEHYDE SYNTHESIS. Preparation of aldehydes from nitriles by reduction with stannous chloride in ether saturated with hydrochloric acid. The intermediate aldimine salts have to be hydrolyzed. The best results are obtained in the aromatic series. 

Reaction XCIV. Conversion of Nitriles to Aldehydes by the Action of Hydrochloric Acid and Stannous Chloride followed by Hydrolysis of the Aldime-Stannichloride so formed (Stephen). (J. C. S., 127,1874.)—When a nitrile is added to anhydrous stannous chloride (p. 507) in dry ether saturated with hydrogen chloride, a white crystalline aldime-stanni-chloride separates, owing to the reduction of the imino-chloride first formed ... 

The reduction of a nitrile is achieved with anhydrous tin(n) chloride dissolved in ether or ethyl acetate saturated with dry hydrogen chloride (the Stephen reaction). The resulting aldimine hydrochloride (probably in the form of a complex with tin(iv) chloride) is then hydrolysed with warm water. 

The synthesis of aldehydes by the Sommclet reaction, the Rosenmund reduction and the Stephens reaction all involve the conversion of a group already present in the molecule. The Rosenmund reduction (Scheme 6.7) is the catalytic hydrogenation of a benzoyl chloride in the presence of a catalyst poison, quinoline/sulfur, which prevents over-reduction to the alcohol. In the Stephens reaction (Scheme 6.7), a nitrile group is reduced by tin(II) chloride and hydrochloric acid to an imine salt, which is then hydrolysed. 

Stephen aldehyde synthesis Reduction of nitriles with SnCl2/HCI to give the corresponding aldehydes. 430... 

Several reduction methods are available to convert nitriles (Stephen reaction) or acyl chlorides (Rosenmund reduction) or amides to aldehydes. The use of lithium aluminum hydride at low temperatures or lithium triethoxyaluminum hydride appears to be a more effective means of reduction than the stannous chloride-HCl used in the Stephen method or palladium and hydrogen used in the Rosenmund reduction. 

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