Reduction by lithium aluminum hydride

Lithium aluminum hydride powder is best dissolved in ether by stirring the mixture in a flask fitted with a reflux condenser connected to a soda-lime tube. According to the nature of the material, stirring must be continued under gentle reflux for from several hours to two days. Technical products leave a grey, insoluble residue, wherefore it is advisable to start with an excess of 5-10% of hydride. It is advantageous to carry out the reduction in the same vessel. 

To obtain a solution for storage, the liquid is decanted through a syphon by means of a nitrogen pressure alternatively, it may be filtered under nitrogen. The filter residue and all the remaining LiAlH4 are destroyed by covering with dioxan and addition of moist dioxan or methanol when all the active hydride has been destroyed for certain, the apparatus is cleaned with dilute acid. 

In many cases it is unnecessary to wait for complete dissolution of the LiAlH4 the suspension can be used directly for the reduction. 

The most convenient method of preparing a solution of LiAlH4 is to use the commercially available ampoules into which calculated amounts of the two components LiH and AlBr3 have been sealed. The ampoules are opened 

337 (a) V. M. Micovic and M. Lj. Mihailovic, Lithium Aluminium Hydride in Organic Chemistry, Izdavacko Preduzece, Belgrade, 1955 W. G. Brown, Org. Reactions, 6, 469 (1951) U. Solms, Chimia, 5, 25 (1951). 

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Diclofenac Diclofenac, 2-[(2,6-dichlorophenyl)-amino]-phenylacetic acid (3.2.42), is synthesized from 2-chIorobenzoic acid and 2,6-dichloroaniline. The reaction of these in the presence of sodium hydroxide and copper gives iV-(2,6-dichlorophenyl)anthranyIic acid (3.2.38), the carboxylic group of which undergoes reduction by lithium aluminum hydride. The resulting 2-[(2,6-dicholorphenyl)-amino]-benzyl alcohol (3.2.39) undergoes further chlorination by thionyl chloride into 2-[(2,6-dichlorophenyl)-amino]-ben-zylchloride (3.2.40) and further, upon reaction with sodium cyanide converts into... 

The complexation, proposed by R. K. Brown and coworkers (Refs. 199-207), of either one of the ring-oxygen atoms by aluminum chloride is reproduced here as a simplification. It seems evident that the intimate mechanism does not imply (i) attack by aluminum chloride, and then (ii) reduction by lithium aluminum hydride actually, the mixed hydride is the reactive species (Ref. 210), and its identity depends on the ratio between the Lewis acid and the hydride (see, for instance, Refs. 211 and 212, and references cited therein, for a discussion of the nature of mixed hydrides). 

In the similar structure of l.l,1,2,4,4,4-heptafluoro-3-phenylbut-2-ene, the reduction with sodium borohydride takes place readily under mild conditions and both products of vinylic and allylic Sn2 displacement are obtained the relative amounts of the products can be controlled by adding triphenylphosphane to the mixture80 (Table 2). The nonfluorinated chain in Hpenta-fluorophenyl)-2-phenylethane (12) selectively activates the para C-F bond to reduction by lithium aluminum hydride, giving the monoreduced product 13 in high yield.81... 

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

The method described is more convenient than earlier methods of preparing 2-cyclohexyloxyethanol. It may be adapted to the preparation of other /3-hydroxyethyl and 7-hydro xypropyl ethers5 and the corresponding thio ethers.6 Although ketals are resistant to reduction by lithium aluminum hydride alone, the presence of a Lewis acid facilitates C—O cleavage, presumably via an oxocarbonium ion,10 as the procedure demonstrates. 

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. ... 

The cleavage of the 1,2,4-triazolidine-3,5-diones prepared with 3//-l,2,4-triazole-3,5(4//)-diones requires prolonged treatment with potassium hydroxide in refluxing water-ethylene glycol35 or reduction by lithium aluminum hydride in refluxing tetrahydrofuran36. The 1,2,4-triazolidine-3,5-dione derived from 4-(4-nitrophenyl)-3//-l,2,4-triazole-3,5(4/f)-diones should be more easily hydrolyzed 31. The hydrazinolysis of the 1,2,4-triazolidine-3,5-diones should also be a useful and mild procedure38. 

The usual range of carboxylic acid derivatives can be prepared and interconverted. Both carboxylic acid and ester functions are capable of reduction by lithium aluminum hydride to alcohols, or by controlled potential reduction to aldehydes. Attempts to form the anhydride from imidazole-4,5-dicarboxylic acid by heating with acetic anhydride failed. Instead, compound (199) is formed. This product forms the monoester (200) when heated with methanol and the hydrazide (201) when treated similarly with hydrazine (Scheme 107) (75S162). The corresponding l-methyl-4,5-dicarboxylic acid loses the 4-carboxyl group when heated with acetic anhydride, but in boiling aniline it is transformed into the 1-methyl-4-carboxanilide (79H(12)186). 

Mesylates are less reactive toward solvolysis than the corresponding tosylates. Mesylates are better suited to reduction by lithium aluminum hydride than tosylates (1, 58) because the mesylate fragment is reduced to methyl mercaptan, which is easily removed. 

Hydrogenolysis of polyfluoro and perfluoro aromatics by lithium aluminum hydride has already been shown in equations (24) and (25). Additional examples are replacement of fluorine by hydrogen in pentafluorobenzene, where the predominant product is 1,2,4,5-tetrafluorobenzene (20), resulting from the reduction by lithium aluminum hydride para to the hydrogen (equation 38), and replacement of fluorine in the -position in 1,2,3,4-tetrafluoronaphthalene (equation 39). ... 

A simple route to the berberine ring system has been described recently by Dyke and Brown (118, 119). Treatment of the isoquinolinium salt LXXXII (R = H) with aqueous base, and without isolation of the intermediates LXXXIII (R = H) and LXXXIV (R = H), gave on treatment with hydrochloric acid 2,3-dimethoxyberbine (LXXXI) and the lactam LXXXV (R = H). Evidence for the structure of the lactam was obtained from its reduction by lithium aluminum hydride to LXXXI and by its dehydrogenation to the isocarbostyril LXXXVI, which had been prepared by an independent route from LXXXI via LXXXVII, according to the scheme shown in Chart IV. The isolation of the lactam LXXXV from the reaction is interesting and illustrates an unusual acid-catalyzed cyclization of the intermediate isocarbostyril LXXXIII (R = H). By employing the simple modification of reducing this intermediate to LXXXIV (R = H) before cyclization, a 50% yield of 2,3-dimethoxyberbine was realized. 

Reduction of quinolizinium salts by metal hydrides goes through the 4//-quinolizine (114). With the parent compound, reduction by lithium aluminum hydride was thought to give the 2-pyridylbutadiene (115a) while... 

Reductions by Lithium Aluminum Hydride Weldon G. Brown... 

The location of the hydroxyl group was deduced mainly from the mass spectrum, which showed a base peak at M+—17, m/e 281. Because no M+ —18 peak was observed, it was thought the hydroxy group must be located at a position which not only allows reduction by lithium aluminum hydride but has no neighboring carbons bearing hydrogen. The only position which satisfies these requirements is position 21. Fendlispermine therefore has the structure 83. 

Isotactic polycarbosilane was synthesized for the first time by polyaddition via the hydrosilylation reaction. The starting optically active aHylsUane was synthesized from methylphenyldi[(—)-bomyloxy]silane, another optically pure starting material, and allyllithium, followed by the reduction by lithium aluminum hydride to give a colorless oil. = — 16.0(c 0.50, pentane). The reaction scheme of the synthesis... 

Reduction by Lithium Aluminum Hydride (Section 13.5) Lithium aluminum hydride reduces a carboxyl group to a primary alcohol ... 

Reduction by lithium aluminum hydride gives an amine ... 

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