Lithium aluminum hydride, acids Aldehydes

REDUCTION WITH LITHIUM ALUMINUM HYDRIDE Acidic Quenching. Reduction of Aldehydes and Ketones [ 5]... 

An alternative but equally cumbersome synthesis utilizes the more accessible bis(2-carboxyphenyl)disulfide, easily prepared from anthranilic acid. Byconversion to the corresponding anilide, then by successive reduction with zinc dust and acetic acid (yielding 2-mercaptobenzoyl anilide) and lithium aluminum hydride, the aldehyde (6) is obtained in fair overall yield.Although... 

On the basis of what we have already learned about the reactions of lithium aluminum hydride with aldehydes and ketones (Chapter 18) and the mechanisms presented so far in this chapter, we can readily predict the product that results when hydride reacts with a carboxylic acid derivative. Consider, for example, the reaction of ethyl benzoate with lithium aluminum hydride. As with all of the reactions in this chapter, this reaction begins with attack of the nucleophile, hydride ion, at the carbon of the carbonyl group, displacing the pi electrons onto the oxygen (see Figure 19.7). Next, these electrons help displace ethoxide from the tetrahedral intermediate. The product of this step is an aldehyde. But recall from Chapter 18 that aldehydes also react with lithium aluminum hydride. Therefore, the product, after workup with acid, is a primary alcohol. 

Lithium aluminum hydride (LiAlH4) is the most powerful of the hydride reagents. It reduces acid chlorides, esters, lactones, acids, anhydrides, aldehydes, ketones and epoxides to alcohols amides, nitriles, imines and oximes to amines primary and secondary alkyl halides and toluenesulfonates to... 

A rather special procedure for the preparation of 21-hydroxy-20-ketopreg-nanes starts with the 17a-ethoxyethynyl-17 -hydroxy steroids described earlier. Free radical addition of ethanethiol to the triple bond, followed by acid-catalyzed hydrolysis and dehydration gives the 20-thioenol ether 21-aldehyde. This can be reduced with lithium aluminum hydride to the C-21 alcohol and then hydrolyzed to the C-20 ketone in the presence of mercuric chloride. The overall yield, without isolation of intermediates, is in the order of 50% ... 

Anet et al. ( 04) obtained in 1947 the alkaloids hygrine (191) and kusk-hygrine (192) in a very good yield by treatment of y-methylaminobutyralde-hyde with acetoacetic or acetonedicarboxylic acids at pH 7. The same reaction was later accomplished by Galinovsky et al. (305-307), who prepared the starting aldehyde by partial reduction of 1-methyl-2-pyrroli-done with lithium aluminum hydride. He used acetonedicarboxylic acid for the synthesis of both alkaloids and showed that a mixture of both alkaloids is formed, the composition of which depends on the ratio of components. 

The Rosenmund reduction is usually applied for the conversion of a carboxylic acid into the corresponding aldehyde via the acyl chloride. Alternatively a carboxylic acid may be reduced with lithium aluminum hydride to the alcohol, which in turn may then be oxidized to the aldehyde. Both routes require the preparation of an intermediate product and each route may have its advantages over the other, depending on substrate structure. 

Lithium aluminum hydride, reaction with aldehydes, 610 reaction with carboxylic acids. 611-612... 

The lithium cnolate generated by deprotonation of 2-/m-butyl-6-methyl-l,3-dioxan-4-onc, readily available from polyhydroxybutyric acid (PHB), predominantly affords the diastereo-mers 7 when reacted with aldehydes. The diastereomeric ratios of aldol adducts 7/8, produced by reactions with aliphatic aldehydes, range from 87.5 12.5 to >99 1. Pure diastereoiners7are obtained by recrystallization in 25-74% yield116-118. Only marginal diastereoselectivities with respect to the carbinol center are obtained with aromatic aldehydes111-119. Benzoylation of the dioxanones 7, followed by reduction with lithium aluminum hydride, affords enan-tiomerically and diastereomerically pure triols 9 in >85% yield 11. ... 

Prepare 3,5-dimethoxy benzyl alcohol by reducing the acid with lithium aluminum hydride as described elsewhere here, by hydrogenating the aldehyde (2-3 atmospheres H2, room temperature,Pt02 in ethanol - or by the NaBH4 method), in five steps as described in J ACS 70,666(1948), or prepare (II) directly by the doborane procedure. 

Ortho esters were reduced to acetals. Refluxing with 0.25mol of lithium aluminum hydride in ether-benzene solution for 4 hours transformed 3-methyl-mercaptopropanoic acid trimethyl orthoester to 3-methylmercaptopropion-aldehyde dimethylacetal in 97% yield [1098]. 

Thioamides were converted to aldehydes by cautious desulfurization with Raney nickel [1137, 1138] or by treatment with iron and acetic acid [172]. More intensive desulfurization with Raney nickel [1139], electroreduction [172], and reduction with lithium aluminum hydride [1138], with sodium borohydride [1140] or with sodium cyanoborohydride [1140] gave amines in good to excellent yields. 

The hydrazide of 2,2-diphenyl-3-hydroxypropanoic acid was reduced with lithium aluminum hydride in 7V-ethylmorpholine at 100° to 3-amino-2,2-di-phenylpropanol in 72.5% yield [1145], Much more useful is reduction of N-arenesulfonylhydrazides of acids to aldehydes McFadyen-Stevens reduction) [284, 285] based on an alkali-catalyzed thermal decomposition according to Scheme 174. 

The reduction of carboxylic acids or esters requires very powerful reducing agents such as lithium aluminum hydride (LiAlH,) or sodium (Na) metal. Aldehydes and ketones are easier to reduce, so they can use sodium borohy-dride (NaBH,j). Examples of these reductions are shown in Figure 3-13. 

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. ... 

Aldehydes and ketones have also been prepared by nucleophilic cleavage of resin-bound O-alkyl hydroxamic acids (Weinreb amides [744]) with lithium aluminum hydride [745] or Grignard reagents (Entries 1 and 2, Table 3.41). Similarly, support-bound thiol esters can be cleaved with Grignard reagents to yield ketones [272], or with reducing agents to yield aldehydes (Entry 3, Table 3.41). Polystyrene-bound sele-nol esters (RCO-Se-Pol) react with alkynyl cuprates to yield alkynyl ketones [746]. 

Sodium borohydride is a milder reducing agent than lithium aluminum hydride and will reduce aldehydes and ketones, but not acids or esters. It... 

Metal hydrides, such as lithium aluminum hydride, also can be used to reduce derivatives of carboxylic acids (such as amides and nitriles see Table 16-6) to aldehydes. An example follows ... 

Reduction then proceeds by successive transfers of hydride ion, H e, from aluminum to carbon. The first such transfer reduces the acid salt to the oxidation level of the aldehyde reduction does not stop at this point, however, but continues rapidly to the alcohol. Insufficient information is available to permit very specific structures to be written for the intermediates in the lithium aluminum hydride reduction of carboxylic acids. However, the product is a complex aluminum alkoxide, from which the alcohol is freed by hydrolysis ... 

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