Lithium aluminum hydride imines

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 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. 

Typical imine reactivity is also displayed in 1//-1,2-diazepines which react with phthaloyl acetyl chloride in the presence of triethylamine to give a / -lactam fused system (76H(5)47l). 1H-2,3-Dihydro-l,2-benzodiazepines, obtained by the lithium aluminum hydride... 

Lithium aluminum hydride in tetrahydrofuran has been found to reduce aromatic nitriles to give an amine and to give an imine which is formed from the addition of the amine to the nonisolatable imine intermediate followed by an elimination of ammonia [24] (Eq. 14). This is simpler than catalytic hydrogenation of nitriles [25], which gives poor yields of imines. 

Sodium borohydride is an effective reductant for the imine bond of dihydro-1,3-oxazines affording tetrahydro derivatives, but predictably where lactam or sultam functions form part of the heterocycle, treatment with lithium aluminum hydride is necessary. Dihydro-1,3-benzothiazinones for instance are reduced by this reagent to the corresponding dihydroben-zothiazines (Scheme 29) <77ACH(92)317). 

Nitriles can be reduced to amines by lithium aluminum hydride. An imine salt is an intermediate product if the reaction is carried out under the proper conditions, this salt is the major product and provides an aldehyde on hydrolysis (see Section 16-4C) ... 

Excellent procedures are available for the preparation of primary, secondary, and tertiary amines by the reduction of a variety of nitrogen compounds. Primary amines can be obtained by hydrogenation or by lithium aluminum hydride reduction of nitro compounds, azides, oximes, imines, nitriles, or unsubstituted amides [all possible with H2 over a metal catalyst (Pt or Ni) or with LiAlH4] ... 

A new solid-phase technique used a relatively nontoxic cleaving agent for peptide aldehydes, which would prevent lithium aluminum hydride reduction byproduct contamination 51 A support-bound threonine or serine was treated with the substrate aldehyde to give an imine intermediate that immediately cyclized to give the stable oxazolidine linker, which was stable to Fmoc conditions including treatment with TFA. The peptide was cleaved under mild aqueous conditions at 60 °C 51 ... 

Camphorsultam. A dry, 2-L, three-necked, round-bottomed flask is equipped with a 1.5-in egg-shaped Teflon stirring bar, a 250-mL addition funnel, and a 300-mL Soxhlet extraction apparatus equipped with a mineral oil bubbler connected to an inert gas source. The flask is charged with 600 mL of dry tetrahydrofuran (THF) (Note 1) and 6.2 g (0.16 mol) of lithium aluminum hydride (Note 2). Into the 50-mL Soxhlet extraction thimble is placed 35.0 g (0.16 mol) of (-)-(camphorsulfonyl)imine (Note 3) and the reaction mixture is stirred and heated at reflux. After all of the (camphorsulfonyl)imine has been siphoned into the reaction flask (3-4 hr), the mixture is allowed to cool to room temperature. The unreacted lithium aluminum hydride is cautiously hydrolyzed by dropwise addition of 200 mL of 1 N hydrochloric acid via the addition funnel (Note 4). After the hydrolysis is complete the contents of the flask are transferred to a 1-L separatory funnel, the lower, silver-colored aqueous layer is separated, and the upper layer placed in a 1-L Erlenmeyer flask. The aqueous phase... 

Camphorsultam was first prepared by the catalytic hydrogenation of (-)-(camphorsulfonyl)imine over Raney nickel.2 Lithium aluminum hydride reduction was used by Oppolzer and co-workers in their synthesis of the sultam.3-4 However, because of the low solubility of the sultam in tetrahydrofuran, a large amount of solvent was required.4 In the procedure described here the amount of solvent is significantly reduced by using a Soxhlet extractor to convey the imine slowly into the reducing medium.5... 

Reduction of SMA imines with sodium borohydride or lithium aluminum hydride allows the synthesis of the corresponding secondary amine in good yields.95,238... 

Imines are formed by condensation of aldehydes or ketones with primary amines, but they form with more difficulty than enamines.84,85 A special case of enamine preparation was described with 20-oxo-steroids.86 Treatment of these ketones with a primary amine gives a 20-ketimine, which is acetylated with acetic anhydride, with migration of the double bond and formation of 20-(A-acetylalkylamino)-J17(20)-pregnene (14) reduction of 14 with lithium aluminum hydride affords the enamine. 

Reactions of Nitriles Nitriles undergo acidic or basic hydrolysis to amides, which may be further hydrolyzed to carboxylic acids. Reduction of a nitrile by lithium aluminum hydride gives a primary amine, and the reaction with a Grignard reagent gives an imine that hydrolyzes to a ketone. 

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