Aluminum Hydride LiAlH

The conversion of carboxylic acid derivatives (halides, esters and lactones, tertiary amides and lactams, nitriles) into aldehydes can be achieved with bulky aluminum hydrides (e.g. DIBAL = diisobutylaluminum hydride, lithium trialkoxyalanates). Simple addition of three equivalents of an alcohol to LiAlH, in THF solution produces those deactivated and selective reagents, e.g. lithium triisopropoxyalanate, LiAlH(OPr )j (J. Malek, 1972). 

Although a few simple hydrides were known before the twentieth century, the field of hydride chemistry did not become active until around the time of World War II. Commerce in hydrides began in 1937 when Metal Hydrides Inc. used calcium hydride [7789-78-8J, CaH2, to produce transition-metal powders. After World War II, lithium aluminum hydride [16853-85-3] LiAlH, and sodium borohydride [16940-66-2] NaBH, gained rapid acceptance in organic synthesis. Commercial appHcations of hydrides have continued to grow, such that hydrides have become important industrial chemicals manufactured and used on a large scale. 

Dimethoxyamphetamine. A solution of the above nitropropene (17.0 g) in 500 ml of dry ether is added slowly to a stirred solution of lithium aluminum hydride (LiAlH or LAH) 12 g suspended in 150 ml of dry ether. After completing the addition, the mixture is refluxed for 20 hours, then cooled. The excess LAH is decomposed by careful addition of water. The resulting suspension is filtered and the solid removed is washed with ether. The combined ether solutions are dried with MgS04, and then saturated with dry hydrogen chloride. This precipitates the title compound which is filtered and recrystallized from ethanol. Yield 13 g, mp 111.5-112.5°. 

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. 

The azide ion is a better nucleophile than amines, but it has to be reduced to the cimine cifter nucleophilic substitution. Lithium aluminum hydride (LiAlH ) in ether followed by treatment with water reduces the azide ion to the amine. Figures 13-11 and 13-12 illustrate two examples of this reaction. 

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. 

Lithium aluminum hydride, LiAlH, in anhydrous ether can also be used. 

Lithium aluminum hydride is not safe for drying methyl ethers (Ref 86). Tetrahydrofuran can cause fire when used as a solvent for LiAlH. 

The distillation of ethers from lithium aluminum hydride occasionally leads to an explosion. The exact cause is not known, but C02 may be involved. The danger can be minimized by predrying the ether with calcium hydride and then using a minimum amount of LiAlH for final distillation. Also, the distillation should be performed behind a blast shield, and the still pot should never be allowed to go dry. Frequently, a safe but powerful desiccant, such as benzophenone ketyl or sodium-potassium alloy, may be used in place of LiAIH4. 

In these formulas, the R or R group may be either an aliphatic or aromatic group. In a ketone, the R and R groups may represent the same group or different groups. These types of compounds are best reduced by complex metal hydrides, such as lithium aluminum hydride (LiAlH) or sodium borohydride (NaBU). 

Lithium. Lithium aluminum hydride, LiAlH, is the only lithium compound of interest for Li analysis in IH work. Little work has been reported, except for standard ionization interferences (3) corrected by addition of 1000 ppm Cs to the final solution. 

Reduction to Aldehydes Reduction of carboxylic acids to aldehydes is difficult because aldehydes are more reactive than carboxylic acids toward most reducing agents. Almost any reagent that reduces acids to aldehydes also reduces aldehydes to primary alcohols. In Section 18-10, we saw that lithium tri-ferf-butoxyaluminum hydride, LiAlH(0-f-Bu)3 is a weaker reducing agent than lithium aluminum hydride. It reduces acid chlorides to aldehydes because acid chlorides are strongly activated toward nucleophilic addition of a hydride ion. Under these conditions, the aldehyde reduces more slowly and can be isolated. Therefore, reduction of an acid to an aldehyde is a two-step process Convert the acid to the acid chloride, then reduce using lithium tri-ferf-butoxyaluminum hydride. 

Direct methods for large-scale synthesis stemmed from studies by K. Ziegler that showed that aluminum hydride or LiAlH reacts with olefins to give alkyls or alkyl anions—a reaction specific for B and A1 hydrides ... 

Reduction of [V(bipy)3]l2 with the metals Mg or Zn yields the complex [V(bipy)3], which will undergo ftulher reduction by lithium aluminum hydride to Li[V(bipy)3] 4THF, which formally contains V". Similarly, reduction of [V(phen)3] with dUithium naphthalenide or dihthium benzophenone in THF yields [V(phen)3]l2. Further reduction with dilithium benzophenone gives the V complex Li[V(phen)3] 3.5THF. The terpyridyl complex [V(terpy)2] can be obtained as black crystals by reduction of DMF solutions of [V(terpy)2]l2 with Mg or LiAlH. Such low oxidation state complexes are highly air sensitive and decompose if heated to 100 - 200 °C in a vacuum. In these systems, the ligands may have an anion radical character. ... 

Lithium aluminum hydride, LiAlH, is another reducing agent often used for reduction of ketones and aldehydes. A grayish powder soluble in ether and tetrahydrofuran, LiAlH4 is much more reactive than NaBH4 but also more dangerous. It reacts violently with water and decomposes explosively when heated above 120°C. 

The aldehyde intermediate can be isolated if 1 equivalent of diisobutyl aluminum hydride (DIBAH) is used as the reducing agent instead of LiAlH The reaction has to be carried out at -78 C to avoid further reduction i. the alcohol. 

Lithium aluminum hydride. 14,190-Reductive esterification. A carl LiAlH reduction and then quenched w-Cleavage of TBS ethers. L sual... 

H. C. Brown and co-workers found that lithium aluminum hydride in ether solution reacts with 4 moles of methanol, ethanol, or isopropanol but with only 3 moles of t-butanol. Dropwise addition of 1 mole of /-butanol at room temperature to a stirred solution of 0.31 mole of LiAlH, in ether produces a white precipitate of lithium tri-/-butoxyaluminum hydride in essentially quantitative yield. The new reagent proved to be a milder reducing agent than LiAlH4, since it reduces aldehydes, ketones, and acid chlorides in diethyl ether or diglyme at 0° but fails to react with esters and nitriles. 

With few exceptions, organometalUcs add only once to nitriles (Section 8.6.4). Only if there is a very strong Lewis acid present to activate the anionic intermediate of the first nucleophilic attack will a second addition take place. An example of this second addition is the reduction of nitriles with LiAlH4, which proceeds all the way to the amine (Section 8.6.3). The AIH3 formed from the initial reduction acts as a Lewis acid to catalyze the second addition. This second addition can be prevented by using one equivalent of a less reactive aluminum hydride like LiAlH(OEt)3 or diisobutylaluminum hydride, [(CH3)2CHCH2l2AlH. The reactions in the acidic water workup are the reverse of imine formation (Section 10.5.2). 

Reduction of a variety of compounds that contain the carbonyl group provides s)mthetic methods to produce primary and secondary alcohols. A common, very powerful reducing agent is lithium aluminum hydride, LiAlH other reducing agents include sodium in alcohol and sodium borohydride, NaBH. ... 

The reactivity of aluminum hydrides toward organomercurials decreases" LiAlH > HjAl NMej. The reaction of AI hydrides with alkenylmercurials gives alkenyl aluminums " ... 

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