Amides by lithium aluminum hydride

Reduction of an azide a nitrile or a nitro compound furnishes a primary amine A method that provides access to primary secondary or tertiary amines is reduction of the carbonyl group of an amide by lithium aluminum hydride... 

A thio-substituted, quaternary ammonium salt can be synthesized by the Michael addition of an alkyl thiol to acrylamide in the presence of benzyl trimethyl ammonium hydroxide as a catalyst [793-795]. The reaction leads to the crystallization of the adducts in essentially quantitative yield. Reduction of the amides by lithium aluminum hydride in tetrahydrofuran solution produces the desired amines, which are converted to desired halide by reaction of the methyl iodide with the amines. The inhibitor is useful in controlling corrosion such as that caused by CO2 and H2S. 

Reduction of amides by lithium aluminum hydride can be used to prepare 1°, 2°, or 3° amines, depending on the degree of substitution of the amide ... 

Reduction of an Amide by Lithium Aluminum Hydride (Section I8.10B)... 

In most other reactions the azolecarboxylic acids and their derivatives behave as expected (cf. Scheme 52) (37CB2309), although some acid chlorides can be obtained only as hydrochlorides. Thus imidazolecarboxylic acids show the normal reactions they can be converted into hydrazides, acid halides, amides and esters, and reduced by lithium aluminum hydride to alcohols (70AHC(12)103). Again, thiazole- and isothiazole-carboxylic acid derivatives show the normal range of reactions. 

Properly substituted isoxazolecarboxylic acids can be converted into esters, acid halides, amides and hydrazides, and reduced by lithium aluminum hydride to alcohols. For example, 3-methoxyisoxazole-5-carboxylic acid (212) reacted with thionyl chloride in DMF to give the acid chloride (213) (74ACS(B)636). Ethyl 3-ethyl-5-methylisoxazole-4-carboxylate (214) was reduced with LAH to give 3-ethyl-4-hydroxymethyl-5-methylisoxazole (215) (7308(53)70). 

The ultrasonic preparation of thioamides from amides and phosphorus pentasulfide by Raucher(51) and of dichlorocarbene from chloroform and potassium hydroxide by Regen(52) are some of the more recent examples of nonmetallie applications. We were surprised to find that ultrasound greatly accelerates the reduction of haloaroma-tics by lithium aluminum hydride, permitting the reaction to be... 

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]. 

A carboxylic acid group may be introduced into the 2-position of dibenzofuran by Friedel-Crafts reaction with 2,2-dichloro-l,3-benzodioxole (catechol dichloromethylene ether) and hydrolysis of the resultant ester. Similarly, reaction with methylphenylcarbamoyl chloride produces the 2-(N-methyl-yV-phenylcarboxamide) or the 2,8-disubstituted derivative under more stringent conditions. Controlled reduction of these amides with lithium aluminum hydride supplies the corresponding aldehydes. ... 

Carbamates can be reduced by lithium aluminum hydride (Entry 3, Table 3.22 [179]) or by Red-Al (Entry 5, Table 10.11). Illustrative examples of the reduction of amides and carbamates on solid phase are listed in Table 10.11. 

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] ... 

Secondary and tertiary amines, particularly those with different R groups, are prepared easily by lithium aluminum hydride reduction of substituted amides (Section 18-7C). 

Enantiomerically pure a-amino aldehydes containing nonpolar side chains such as Boc-Ala-H, Boc-Leu-H, and Boc-Phe-H are synthesized by lithium aluminum hydride reduction of the corresponding Weinreb amides, Boc-Ala-N(Me)OMe, Boc-Leu-N(Me)OMe, and Boc-Phe-N(Me)OMe, respectively (Table 4). The lithium aluminum hydride does not affect the Boc group due to the low temperature and short 15-minute reaction time. Successful synthesis of side-chain Bzl-protected Boc-Thr(Bzl)-H gives a 95% yield of crude product, however, reduction of N-protected aspartyl and glutamyl aldehydes from their corresponding A-methoxy-A-methylamides leads to overreduction and unreacted hydroxamateJ1920 ... 

Table 4 Synthesis of a-Amino Aldehydes by Lithium Aluminum Hydride Reduction of Weinreb Amides 20-32 ...

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... 

Oxidation of methyl 3,4-isopropylidene-2-desoxy-a-D-galactoside with potassium permanganate in the presence of potassium hydroxide afforded methyl 3,4-isopropylidene-2-desoxy-a-D-galacturonoside (LXXXIV) as its potassium salt. This could readily be converted into methyl 2-desoxy-a-D-galacturonoside (LXXXV) and both LXXXIV and LXXXV afforded crystalline esters and amides.230 The uronic acid derivative could be reduced by lithium aluminum hydride in ethereal solution to give methyl 3,4-isopropylidene-2-desoxy-a-D-galactoside.230 Although 2-des-... 

Like other carboxylic acid derivatives, amides can be reduced by lithium aluminum hydride. The product of this reduction is an amine. 

Amides yield primary amines on reduction by lithium aluminum hydride, while N-substituted and N, N-disubstituted amides produce secondary and tertiary amines, respectively. 

Mechanism of the reduction of an amide to an amine by lithium aluminum hydride. 

Carboxytellurophenes were esterified, reduced by lithium aluminum hydride, converted to amides, and decarboxylated. Esters of carboxytellurophenes were saponified. Esterification of carboxytellurophenes with diazomethanc produced methoxy-carbonyltellurophenes2... 

Reactions of Nitriles Nitriles undergo acidic or basic hydrolysis to amides, which may be further hydrolyzed to carboxylic acids. Reduction of a nitrile by lithium aluminum hydride gives a primary amine, and the reaction with a Grignard reagent gives an imine that hydrolyzes to a ketone. 

The carboxylic acids of the 1,2,4-triazole series are readily decarboxylated on heating, but otherwise stable. Esters, amides and hydrazides react normally. Reduction of esters by lithium aluminum hydride affords triazolylmethanols. 

Aminocyclopropanes were easily acylated by acid chlorides, isocyanates or isothiocyanates (e.g. Refs 3, 24, 27, 36, 71, 80, 82, 125, 178, 179, 184, 224). Polyureas, polyurethanes or polyamides have been prepared from 1,2-diaminocyclopropane Reduction of the carbonyl group in 423 by lithium aluminum hydride worked quite well for tertiary amides 5,473.495. longer reaction times effected a ring-opening in the case of a secondary amide (423, R = H) (LiAlH4 reduction of secondary... 

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. 

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