Lithium aluminum hydride, reducing esters

Reactions of Esters Esters are much more stable than acid chlorides and anhydrides. For example, most esters do not react with water under neutral conditions. They hydrolyze under acidic or basic conditions, however, and an amine can displace the alkoxyl group to form an amide. Lithium aluminum hydride reduces esters to primary alcohols, and Grignard and organolithium reagents add twice to give alcohols (after hydrolysis). 

Lithium aluminum hydride reduces esters as well as other carbonyl groups. 

Section 19.13 Lithium aluminum hydride reduces esters to alcohols. Two alcohols are formed the acyl group is reduced to the primary alcohol. 

Grignard reagents add twice to give tertiary alcohols (or secondary alcohols, from formates). Lithium aluminum hydride reduces esters all the way to alcohols, whereas bis(2-methylpropyl)aluminum (diisobutylaluminum) hydride allows the process to be stopped at the aldehyde stage. With LDA, it is possible to form ester enolates, which can be alkylated by electrophiles. 

Esters are also reduced by sodium aluminum hydride (yields 95-97%) [<9<9] and by lithium trimethoxyaluminum hydride (2 mol per mol of the ester) [94] but not by lithium tris tert-butoxy)aluminum hydride [96], Another complex hydride, sodium bis(2-methoxyethoxy)aluminum hydride, reduces esters in benzene or toluene solutions (1.1 -1.2 mol per ester group) at 80° in 15-90 minutes in 66-98% yields [969], Magnesium aluminum hydride (in the form of its tetrakistetrahydrofuranate) reduced methyl benzoate to benzyl alcohol in 58% yield on refluxing for 2 hours in tetrahydrofuran [59]. 

Lithium aluminum hydride reduces acids, acid chlorides, anhydrides, and esters to primary alcohols. (The reduction of acids was covered in Section 20-13.) Acid chlorides are more reactive than the other acid derivatives. Either lithium aluminum hydride or sodium borohydride converts acid chlorides to primary alcohols. 

Lithium aluminum hydride reduces an ester to form two alcohols. 

The UV, NMR, and mass spectra of adifoline and its derivatives revealed a phenolic carboxy-j8-carboline unit identical with that of cordifoline (q.v.) treatment of trimethyladifoline with lithium aluminum hydride reduced both esters and changed the UV spectrum to one identical with that of... 

Aldehydes react rapidly with lithium aluminum hydride to give primary alcohols (Section 15.2). The aldehyde produced during the reduction of the ester reacts with a second equivalent of hydride, to give the primary alcohol. One mole of lithium aluminum hydride reduces two moles of ester to alcohol. 

Sodium borohydride is a less powerful reducing agent than lithium aluminum hydride. Lithium aluminum hydride reduces acids, esters, aldehydes, and ketones, but sodium borohydride reduces only aldehydes and ketones ... 

Lithium aluminum hydride reduces an ester to two alcohols the alcohol derived from the acyl group is primary and is usually the objective of the reduction. 

Many carbonyl compounds, including aldehydes and ketones, acids, esters, acid halides, and amides, can be reduced with lithium aluminum hydride. For example, hthium aluminum hydride reduces esters to primary alcohols. 

We recall that LLAIH4 reduces esters of carboxylic acids, yielding primary alcohols (Section 15.9). An aldehyde occurs as an intermediate in the reaction, but cannot be isolated because lithium aluminum hydride reduces it more readily than the ester. Sodium borohydride does not reduce esters. 

Lithium aluminum hydride is the reagent of choice for reducing esters to alcohols O... 

Section 20 9 Esters react with Gngnard reagents and are reduced by lithium aluminum hydride (Table 20 4)... 

Lithium borohydride is a more powerful reducing agent than sodium borohydride, but not as powerful as lithium aluminum hydride (Table 6). In contrast to sodium borohydride, the lithium salt, ia general, reduces esters to the corresponding primary alcohol ia refluxing ethers. An equimolar mixture of sodium or potassium borohydride and a lithium haUde can also be used for this purpose (21,22). 

In general, if the desired carbon—phosphoms skeleton is available in an oxidi2ed form, reduction with lithium aluminum hydride is a powerful technique for the production of primary and secondary phosphines. The method is appHcable to halophosphines, phosphonic and phosphinic acids as well as thein esters, and acid chlorides. Tertiary and secondary phosphine oxides can be reduced to the phosphines. 

Generally, the carboxyl group is not readily reduced. Lithium aluminum hydride is one of the few reagents that can reduce these organic acids to alcohols. The scheme involves the formation of an alkoxide, which is hydroly2ed to the alcohol. Commercially, the alternative to direct reduction involves esterification of the acid followed by the reduction of the ester. 

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). 

NaBH4, H0(CH2)20H, 40°, 18 h, 87% yield. Lithium aluminum hydride can be used to effect efficient ester cleavage if no other functional group is present that can be attacked by this strong reducing agent. ... 

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... 

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