Stannous chloride nitriles

From nitriles by treatment with anhydrous Stannous chloride dissolved in ether saturated with hydrogen chloride the resulting crystaUine aldimine stannichloride, [(RCH=NHj)2] SnCl, or (RCH=NH,HCl)2SnCl4, is hydrolysed by warm water, and the aldehyde is isolated by distillation with steam or by extraction with a solvent (Stephen reaction), for example, for R = CH3(CH2)4, i.e., n-amyl ... 

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). 

Aniline 77 was converted into its diazonium salt with nitrous acid and this was followed by reduction with stannous chloride to afford the corresponding arylhydrazine 78. Condensation of 78 with 3-cyanopropanal dimethylacetal 79 gave the arylhydrazone 80. Treatment of 80 with PPE resulted in cyclization to indole 81. The nitrile group was then reduced to the primary amine by catalytic hydrogenation. Reaction of the amine with excess formalin and sodium borohydride resulted in Imitrex (82). 

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... 

Nitriles are reduced to corresponding imine with stannous chloride in the presence of hydrochloric acid, which on hydrolysis give corresponding aldehyde. 

Stannous chloride is used most frequently for the reduction of nitro compounds [177, 178, 179] and of quinones [180, 181], It is also suitable for conversion of imidoyl chlorides [182] and of nitriles [183] to aldehydes, for transformations of diazonium salts to hydrazines [184], for reduction of oximes [f[Pg.30]

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]. 

In nitriles containing a nitro group the latter is reduced preferentially by iron and by stannous chloride. 2-Chloro-6-nitrobenzonitrile was reduced to 2-chloro-6-aminobenzonitrile with iron in methanol and hydrochloric acid in 89% yield [7769], and o-nitrobenzonitrile to o-aminobenzonitrile with stannous chloride and hydrochloric acid in 80% yield [779]. 

Selective reduction of the nitrile group in 87% yield without the reduction of the carbonyl was achieved by stannous chloride [1153]. Oximes of keto nitriles are reduced preferentially at the oximino group by catalytic hydrogenation in acetic anhydride over 5% platinum on carbon (yield 85%)... 

Nitriles also can be reduced to imines with stannous chloride in ethyl acetate containing hydrogen chloride [26]. The imines are isolated as the stannous chloride salt. 

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 ... 

Nitriles may be converted to their imino chloride salts by the action of dry hydrogen chloride in ether. These intermediates ate reduced by anhydrous stannous chloride to stannic aldimonium chlorides, which on hydrolysis yield aldehydes. Chloroform may be added to facilitate the solution of the nitrile. The quality of the stannous chloride catalyst is important the preparation of an active and dependable form has been described. The yields are usually high for many aromatic nitriles, as in the preparation of /3-naphthaldehyde (95%). The reaction has also been employed in the heterocyclic series, as in the synthesis of 4-methyl-thiazole-5-aldehyde (40%). The reduction of the cyano group in the... 

Reaction of nitriles with dry hydrogen chloride in anhydrous ether or in an ether-chloroform mixture affords imidoyl chlprides which are reduced by stannous chloride to products that afford aldehydes on hydrolysis. The method seems to be generally applicable only to aromatic and heterocyclic aldehydes the activity of the stannous chloride used for the reduction seems to be the most important factor in the reaction.580 2-Naphthaldehyde has been synthesized580 in 95% yield by this method, and 4-methyl-5-thiazolecarbaldehyde in 40% yield.581... 

A similar conversion of nitriles into aldehydes has been reported by Henle.582 He used sodamide in place of stannous chloride and added phenylhydrazine to the mixture this led to phenylhydrazones that were cleaved to the aldehydes in the usual way. 

This intermediate is reduced by stannous chloride to give 545 and SnCl2 is converted to tin tetrachloride (SnClq). Subsequent treatment with aqueous HCl converts imine 545 to the aldehyde (546) via hydrolysis, in 73% overall yield. Stannous bromide (SnBr2) often gives better yields of aldehyde than stannous chloride. Most aromatic nitriles give good yields of the aromatic aldehyde. ... 

Without reference to Pschorr and Hoppe, Steven in 1925, in the context of a new aldehyde synthesis, prepared indole in 55% yield from o-nitrophenylacetonitrile using anhydrous stannous chloride and gaseous hydrogen chloride (Scheme 2, equation 1) [2]. The reduction of the nitrile proceeds to form initially the aldimine stannic chloride complex ([RCH=NH HClJ SnCl ), which can be isolated. 

Reaction sequence employed to convert nitriles to aldehydes. Treatment of the nitrile with a mixture of stannous chloride and hydrochloric acid yields the imine salt complex which is subsequently hydrolyzed to the aldehyde. Practically applied only to aromatic aldehydes ... 

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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