Sodium aluminum hydride amides

The challenge of this reaction is to reduce the Weinreb amide to the aldehyde while simultaneously reducing the methyl ester to the primary allylic alcohol. Different reagents were tested, but only an excess of sodium aluminum hydride delivered the desired product 13. The substrate was either inert or degraded if LiAlH4 or DIBAL were used. NaBH4 in methanol selectively reduced only the amide, but to form the primary alcohol. Because of its instability, hydroxyaldehyde 13 was not purified but directly subjected to the next reaction. 

Silver trifluoroacetate, 327, 328 Silyl ethers, 477-478 Simmons-Smith reagent, 436-437 (3-Sinensal, 283 Sirenin, 424 Sodium, 246, 268, 437 Sodium acetate, 578 Sodium aluminum chloride, 438 Sodium aluminum diethyl dihydride, 438 Sodium aluminum hydride, 316 Sodium amalgam, 41,438-439 Sodium amide, 231, 305,403,439 Sodium amide-Sodium f-butoxide, 439-440 Sodium-Ammonia, 26, 32,134, 260,438 Sodium azide, 9, 77, 210, 323, 440-441 Sodium benzoxide, 111 Sodium bis-(2-methoxyethoxy)aluminum hydride, 164, 293, 360,441-442 Sodium bistrimethylsilylamide, 442-443,... 

Sodium acetate, 433,1024-1627,1132 Sodium acetylide, 573, 1627 Sodium aluminum chloride, 709,1627-1629 Sodium aluminum hydride, 1036 Sodium amalgam, 1630-1633 40% Sodium amalgam (liquid), 1633-1634 Sodium amide, 185,250,357,392,698,1634-1041, 1217... 

One of the ways to dispose of chemicals that are reactive with water is hydrolysis, that is, the reaction with water under controlled conditions. Inorganic chemicals that can be treated by hydrolysis include metals that react with water metal carbides, hydrides, amides, alkoxides, and halides and nonmetal oxyhalides and sulfides. An example of a waste chemical treated by hydrolysis is the reaction with water of sodium aluminum hydride (used as a reducing agent in organic chemical reactions) ... 

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). 

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],... 

Reduction of amides to aldehydes was accomplished mainly by complex hydrides. Not every amide is suitable for reduction to aldehyde. Good yields were obtained only with some tertiary amides and lithium aluminum hydride, lithium triethoxyaluminohydride or sodium bis 2-methoxyethoxy)aluminum hydride. The nature of the substituents on nitrogen plays a key role. Amides derived from aromatic amines such as JV-methylaniline [1103] and especially pyrrole, indole and carbazole were found most suitable for the preparation of aldehydes. By adding 0.25 mol of lithium aluminum hydride in ether to 1 mol of the amide in ethereal solution cooled to —10° to —15°, 37-60% yields of benzaldehyde were obtained from the benzoyl derivatives of the above heterocycles [1104] and 68% yield from N-methylbenzanilide [1103]. Similarly 4,4,4-trifluorobutanol was prepared in 83% yield by reduction of N-(4,4,4-trifluorobutanoyl)carbazole in ether at —10° [1105]. 

V-Acylsaccharins prepared by treatment of the sodium salt of saccharin with acyl chlorides were reduced by 0.5 molar amounts of sodium bis(2-methoxyethoxy)aluminum hydride in benzene at 0-5° to give 63-80% yields of aliphatic, aromatic and unsaturated aldehydes [1108 Fair yields (45-58%) of some aliphatic aldehydes were obtained by electrolytic reduction of tertiary and even secondary amides in undivided cells fitted with platinum electrodes and filled with solutions of lithium chloride in methylamine. However, many secondary and especially primary amides gave 51-97% yields of alcohols under the same conditions [130]. 

High yields of amines have also been obtained by reduction of amides with an excess of magnesium aluminum hydride (yield 100%) [577], with lithium trimethoxyaluminohydride at 25° (yield 83%) [94] with sodium bis(2-methoxy-ethoxy)aluminum hydride at 80° (yield 84.5%) [544], with alane in tetra-hydrofuran at 0-25° (isolated yields 46-93%) [994, 1117], with sodium boro-hydride and triethoxyoxonium fluoroborates at room temperature (yields 81-94%) [1121], with sodium borohydride in the presence of acetic or trifluoroacetic acid on refluxing (yields 20-92.5%) [1118], with borane in tetrahydrofuran on refluxing (isolated yields 79-84%) [1119], with borane-dimethyl sulflde complex (5 mol) in tetrahydrofuran on refluxing (isolated yields 37-89%) [1064], and by electrolysis in dilute sulfuric acid at 5° using a lead cathode (yields 63-76%) [1120]. 

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. 

A different approach to enantiotopic group differentiation in bicyclic anhydrides consists of their two-step conversion, first with (/ )-2-amino-2-phcnylethanol to chiral imides 3, then by diastereoselective reduction with sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) to the corresponding chiral hydroxy lactames 4, which may be converted to the corresponding lactones 5 via reduction with sodium borohydride and cyclization of the hydroxyalkyl amides 101 The overall yield is good and the enantioselectivity ranges from moderate to good. Absolute configurations of the lactones are based on chemical correlation. 

An efficient synthesis of ( )-quebrachamine is based on the construction of a suitable precursor via ring cleavage of an a-diketone monothioketal (810) (80JCS(P1)457). This monothioketal, available from 4-ethoxycarbonylcyclohexanone ethylene ketal, was fragmented to the dithianyl half ester (811) with sodium hydride in the presence of water. Reaction of (811) with tryptamine and DCC provided an amide which was converted to the stereoisomeric lactams (812) on hydrolysis of the dithiane function. Reduction of either the a- or /3-ethyl isomer with lithium aluminum hydride followed by conversion of the derived amino alcohol to its mesylate produced the amorphous quaternary salt (813). On reduction with sodium in liquid ammonia, the isomeric salts provided ( )-quebrachamine (814 Scheme 190). 

The reduction of dihydro-1,4-thiazines to tetrahydro forms is achieved by the action of a variety of reagents including formic acid, hydrogen sulfide, sodium borohydride and lithium aluminum hydride. The last is particularly useful for the reduction of carbonyl derivatives, although in the case of the amide (105) only partial reduction is effected, leading in due course to the thiazine (106), the hydroxyethyl side chain of which then cyclizes to position 5 of the ring to yield the bicyclic product (107 Scheme 45) (66CPB742). 

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. 

Horner-Emmons reaction of N-terminal blocked aldehyde 1 with sulfonylphosphonates in the presence of sodium hydride gives the amino acid vinyl sulfone 2, which is deprotected with acid and converted into its chloride or tosylate salt 3 and coupled by the mixed anhydride method with an N-terminal protected peptide or amino acid to give the desired peptide vinyl sulfones 4 (Scheme 2). 4 5 N-Terminal protected aldehydes 1 are obtained from reduction of Boc amino acid V-methoxy-A-methylamides (Weinreb amides, see Section 15.1.1) by lithium aluminum hydride. 9 The V-methoxy-V-methylamide derivatives are prepared by reaction of Boc amino acids with N,O-dimethylhydroxylamine hydrochloride in... 

Reduction of amides is an important preparative method for the synthesis of primary amines. Reducing agents used for this purpose include lithium aluminum hydride, sodium borohydride, triphenyl-phosphine (Staudinger reduction), and thiols. In the present case it is important to consider the compatibility of the reduction system with the carboxylic and methanesulfonic acid functions. Platinum and palladium arc often used for catalytic reduction. 

In contrast to lithium aluminum hydride, sodium borohydride does not reduce amides. Another possible reagent would be DIB AH. However, in the present case four equivalents of borane-dimethyl sulfide complex was used as a 2M solution in THE The amine was obtained in 94% yield after workup with ethanol. 

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