Sodium aluminum hydride nitriles

Aldehydes. The reduction of carboxylic acid derivatives such as esters and nitriles is stopped at the aldehyde stage with the modified sodium aluminum hydride. The reagent is prepared from NaAlH2Et2 and piperidine in THF-toluene at 0°C. Interestingly, acid chlorides can be converted to aldehydes by treatment with piperidine and then with NaAlH2Et2- ... 

AletalHydrides. Metal hydrides can sometimes be used to prepare amines by reduction of various functional groups, but they are seldom the preferred method. Most metal hydrides do not reduce nitro compounds at all (64), although aUphatic nitro compounds can be reduced to amines with lithium aluminum hydride. When aromatic amines are reduced with this reagent, a2o compounds are produced. Nitriles, on the other hand, can be reduced to amines with lithium aluminum hydride or sodium borohydride under certain conditions. Other functional groups which can be reduced to amines using metal hydrides include amides, oximes, isocyanates, isothiocyanates, and a2ides (64). 

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%. 

Intramolecular nitrile oxide—olefin cycloaddition of oxazolidine and thiazoli-dine oximes 407 (R = H, Me R1 =H, Me X = 0, S n = 1,2) proceed stereose-lectively, yielding tricyclic fused pyrrolidines and piperidines. Thus, 407 (n =2 R = H R1 =Me X=S) has been oxidized to the nitrile oxides with sodium hypochlorite, in the presence of triethylamine in methylene chloride, to give the isoxazolothiazolopyridine 408 in 68% yield. Reduction of 408 with lithium aluminum hydride affords mercaptomethylmethylpiperidine 409 in 24% yield (448). 

A different approach involving cyanohydrin formation from the 3-keto sugar was also explored in the D-Fru series (Scheme 17). A mixture of epimeric cyanohydrins was quantitatively formed by reaction with sodium cyanide in methanol, albeit without stereoselectivity. Chromatographic separation of (R)- and (A)-isomers was straightforward and the former epimer was selected to exemplify the two-step transformation into an OZT. Reduction of this nitrile by lithium aluminum hydride led to the corresponding aminoalcohol, which was further condensed with thiophosgene to afford the (3i )-spiro-OZT in ca. 30% overall yield. Despite its shorter pathway, the cyanohydrin route to the OZT was not exploited further, mainly because of the disappointing yields in the last two steps. 

If the reduction has been carried out in ether, the ether layer is separated after the acidification with dilute hydrochloric or sulfuric acid. Sometimes, especially when not very pure lithium aluminum hydride has been used, a gray voluminous emulsion is formed between the organic and aqueous layers. Suction filtration of this emulsion over a fairly large Buchner funnel is often helpful. In other instances, especially in the reductions of amides and nitriles when amines are the products, decomposition with alkalis is in order. With certain amounts of sodium hydroxide of proper concentration a granular by-product - sodium aluminate - may be separated without problems [121],... 

Aromatic nitriles were converted to aldehydes in 50-95% yields on treatment with 1.3-1.7mol of sodium triethoxy aluminum hydride in tetrahydrofuran at 20-65° for 0.5-3.5 hours [1149. More universal reducing agents are lithium trialkoxyaluminum hydrides, which are applicable also to aliphatic nitriles. They are generated in situ from lithium aluminum hydride and an excess of ethyl acetate or butanol, respectively, are used in equimolar quantities in ethereal solutions at —10 to 12°, and produce aldehydes in isolated ytelds ranging from 55% to 84% [1150]. Reduction of nitriles was also accomplished with diisobutylalane but in a very low yield [7/5/]. 

Since sodium borohydride usually does not reduce the nitrile function it may be used for selective reductions of conjugated double bonds in oc,/l-un-saturated nitriles in fair to good yields [7069,1070]. In addition some special reagents were found effective for reducing carbon-carbon double bonds preferentially copper hydride prepared from cuprous bromide and sodium bis(2-methoxyethoxy)aluminum hydride [7766], magnesium in methanol [7767], zinc and zinc chloride in ethanol or isopropyl alcohol [7765], and triethylam-monium formate in dimethyl formamide [317]. Lithium aluminum hydride reduced 1-cyanocyclohexene at —15° to cyclohexanecarboxaldehyde and under normal conditions to aminomethylcyclohexane, both in 60% yields [777]. 

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. 

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. 

Wear nitrile rubber gloves, laboratory coat, and eye protection. Work in the fume hood. Cover the hydride with a 1 1 1 mixture by weight of sodium or calcium carbonate, clay cat litter (bentonite), and sand. Mix carefully. Place material in a large container behind a safety shield in the hood. Slowly add dry butyl alcohol (31 mL per gram of aluminum hydride). After reaction ceases, slowly and cautiously add water (three times the volume of alcohol added). Neutralize with 6 M hydrochloric acid (prepared by adding concentrated acid to an equal volume of cold water), and let stand until solids settle. Decant the liquid into drain and discard the solid residue as normal refuse.7,8... 

The new metallic hydrides are excellent reducing agents for carbonyl compounds. These hydrides now include lithium aluminum hydride, lithium borohydride, and sodium borohydride. The last reagent may be used in either aqueous or methanolic solutions. It does not reduce esters, acids, or nitriles and, for this reason, is superior for certain selective reductions. Other groups which are unaffected by this reagent include a,/S-double bonds and hydroxyl, methoxyl, nitro, and dimethylamino groups. ... 

Reduction may also be brought about by sodium and alcohol, although extensive cleavage, of the cyanide group may occur, viz., RCN— RH + NaCN. Lithium aluminum hydride has been successfully employed for the reduction of aliphatic and aromatic nitriles as well as several cyanides in the thiophene series. ... 

Sodium borohydride is a mild and selective reducing reagent. In ethanol solution it reduces aldehydes and ketones rapidly at 25°C, esters very slowly, and is inert toward functional groups that are readily reduced by lithium aluminum hydride carboxylic acids, epoxides, lactones, nitro groups, nitriles, azides, amides, and acid chlorides. 

Prepared by the reaction of aluminum ethoxide with sodium hydride, it is a colorless, microcrystalline powder stable for several weeks in the absence of air and is used in ether or THF. A somewhat milder reducing agent than lithium aluminum hydride, it is recommended particularly for the reduction of aromatic nitriles to aldehydes C H,C N — C H.,CHO (95%). 

The paper reports preparation of two new copper hydride complexes. The lithium complex (1) is prepared from CuBr and 2 equiv. of lithium trimethoxy-aluminum hydride (cf. 5, 168) the sodium complex (2) is prepared from CuBr and 1 equiv. of sodium bis(2-methoxyethoxy)aluminum hydride. Both complexes are useful for selective reduction of the double bond of conjugated cnones 1 is more efficient for reduction of cyclohexenones and 2 is more efficient for reduction of acyclic enones. Aldehydes, ketones, and halides are also reduced nitrile and ester units are inert. The effective stoichiometry of both reagents is consistent with the structures LiCuHj and NaCuHs, but complex 1 is clearly different from a reagent assigned the structure LiCuHa by Ashby et al. ... 

---