Reducing agents lithium aluminum hydride

Lithium aluminum hydride reduction (Sec tion 15 3) Carboxylic acids are reduced to primary alcohols by the powerful reducing agent lithium aluminum hydride... 

Reduction of carboxylic acids are the most difficult, but they can be accomplished with the powerful reducing agent lithium aluminum hydride (LiAlH4, abbreviated LAH). 

The neutralization values were influenced by reduction with strong reducing agents, lithium aluminum hydride, sodium borohydride, and amalgamated zinc plus hydrochloric acid (35, 46). For the most part, the consumption of NajCOj and of NaOEt decreased in equivalent amounts. This is further confirmation of the assumption that lactones of the fluorescein type or of the lactol type are present. The reaction with sodium ethoxide was shown to be no true neutralization, that is, exchange of H+for Na+, at all, but an addition reaction w ith the formation of the sodium salt of a semi-acetal or ketal ... 

The reactions of complex metal hydrides occur by an attack of the nucleophilic hydride ion on an electrophilic center.1 Aromatic nitrogen heterocycles in which the nitrogen has contributed only one electron to the -system (1) are electrophilic as compared with benzene, and have been shown to undergo reduction by the active reducing agent, lithium aluminum hydride. The nitrogen heterocycles in which the heteroatom has contributed two electrons to the 77-system (2) are electron-rich as compared with benzene and usually do not undergo reaction by reduction with complex metal hydrides.2 A combination of these two structural features, as in oxazoles (3), usually induces sufficient electrophilicity to allow attack by the hydride ion and reduction. 

Cyclopropanecarboxylic acids have been transformed to the corresponding primary alcohols using several reducing agents. Lithium aluminum hydride in diethyl ether or tetrahydrofu-ran has been most frequently... 

Dialkyl- and diarylfuroxans and benzofuroxans are reduced by sodium borohydride to the dioximes,422 while acylfuroxans can be converted into the corresponding furoxan alcohols.80,422 The more vigorous reducing agent lithium aluminum hydride cleaves the ring C—C bond, giving amines (Eq. 7)182 283 423 424 this reaction is considered again in Section V,E. 

From among the common chemical reducing agents lithium aluminum hydride and similar compounds, and alkali metals in liquid ammonia, are the most usually used for saturation of acetylenic bonds. 

The carboxyl group is one of the organic functional groups that is most resistant to reduction. It is not affected by catalytic reduction (H2/M) under conditions that easily reduce aldehydes and ketones to alcohols and that reduce alkenes to alkanes. The most common reagent for the reduction of a carboxylic acid to a primary alcohol is the very powerful reducing agent lithium aluminum hydride (Section 12.10). 

A wide variety of chiral modifications of the commonly employed reducing agent lithium aluminum hydride have been examined [23, 111, 112). Noyori described one of the most effective reagents namely BINAL-H (176), produced upon treating LiAlH4 with BINOL (Equation 17) [122, 123]. BINAL-H has been shown to be particularly useful in the enantioselective reduction of aromatic and unsaturated ketones [111]. For example, reduction of 175 with (S)-BINAL-H furnishes 177 in 92% yield and with >99% ee [122]. 

A slightly more complex Scheme is required for preparation of an antihistaminic agent bearing a secondary amine, e. g., tofenacin (32). In the synthesis of tofenacin, alkylation of the benzhydrol (29) with ethyl bromoacetate affords the alkoxy ester (30) saponification followed by conversion to the methylamide gives (31), which is reduced with lithium aluminum hydride to complete the synthesis of 32. 10... 

Oral progestational activity is retained when the ketone at the 3 position is reduced to an alcohol. Treatment of ethindrone (13-6) with the bulky reducing agent lithium aluminum-tri-ferf-butoxy hydride leads to attack from the more open a face and the formation of the 3 3 hydroxy derivative (14-1). Acylation under forcing conditions affords the 3,17-diacetate derivative, ethynodiol diacetate (14-2) [17]. 

The oxidation of azo compounds with hydrogen peroxide in an acetic acid medium or with peracetic acid has been carried out by many investigators. For example, in a study of the 4,4 -dialkoxyazoxybenzenes, which are of interest in the field of liquid crystals, the corresponding alkoxynitrobenzenes were reduced with lithium aluminum hydride to the corresponding azo stage and, after decomposition of the reducing agent and removal of the solvent, the product residue was taken up in acetic acid and oxidized at 65°C for 36 hr with... 

C (R = OH, Ri = H) by hydriodic acid. Benzylation of this product and conversion to the acid chloride provided an acylating agent for CII, which was prepared from 0-benzyl isovanillin (Cl). The amide (CIII R, R2 = CH2C6H5, Ri = 0) was reduced by lithium aluminum hydride and palladium-on-charcoal to the desired phenol (CIII R, Ri, R2 = H), the structure of which was verified by conversion to belladine (CIII R, R2 = CH3 Ri = H) by diazomethane. Manganese dioxide, lead dioxide, silver oxide, and potassium ferricyanide were effective in the oxidation of cm (R,Ri,R2 = H)to( + )-narwedine. A maximum yield of 1.4% was obtained. Polymerization products predominated in all cases 103). 

It is used as a powerful reducing agent in organic synthesis. Except for olefinic double bonds, almost all organic functional groups are reduced by lithium aluminum hydride (Sullivan and Wade 1980). It is used extensively in pharmaceutical synthesis and in catalytic hydrogenation. 

The milder reducing agent lithium aluminum tri(rcrt-butoxy) hydride reduces acid chlorides to yield aldehydes without further reduction to an alcohol. 

For most laboratory scale reductions of aldehydes and ketones catalytic hydro genation has been replaced by methods based on metal hydride reducing agents The two most common reagents are sodium borohydride and lithium aluminum hydride... 

Carboxylic acids are exceedingly difficult to reduce Acetic acid for example is often used as a solvent in catalytic hydrogenations because it is inert under the reaction con ditions A very powerful reducing agent is required to convert a carboxylic acid to a pri mary alcohol Lithium aluminum hydride is that reducing agent... 

Reduction to alcohols (Section 15 2) Aide hydes are reduced to primary alcohols and ketones are reduced to secondary alcohols by a variety of reducing agents Catalytic hydrogenation over a metal catalyst and reduction with sodium borohydride or lithium aluminum hydride are general methods... 

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). 

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