Aluminum nitrogen hydrides

Nitrogen azoles are less easily reduced benzimidazole with lithium aluminum hydride gives dihydrobenzimidazole (52CB390). 

Anhydrous ether was distilled from lithium aluminum hydride under dry nitrogen imnedlately before use. 

The determination of position of protonation by reaction with diazomethane was performed as follows The enamine was treated at —70° with ethereal hydrogen chloride and the suspension of precipitated salt was treated with diazomethane and allowed to warm slowly to —40°, at which temperature nitrogen was liberated. The reaction with lithium aluminum hydride (LAH) was carried out similarly except that an ether solution of LAH was added in place of diazomethane. The results from reaction of diazomethane and LAH 16) are summarized in Table 1. 

The reduction of iminium salts can be achieved by a variety of methods. Some of the methods have been studied primarily on quaternary salts of aromatic bases, but the results can be extrapolated to simple iminium salts in most cases. The reagents available for reduction of iminium salts are sodium amalgam (52), sodium hydrosulfite (5i), potassium borohydride (54,55), sodium borohydride (56,57), lithium aluminum hydride (5 ), formic acid (59-63), H, and platinum oxide (47). The scope and mechanism of reduction of nitrogen heterocycles with complex metal hydrides has been recently reviewed (5,64), and will be presented here only briefly. 

Preparation of 11 -Hydroxy-6a-Methylprogesterone A mixture of 2.68 g of 11-keto-6(3-methylprogesterone 3,20-bis-(ethylene ketal), 161 ml of tetrahydrofuran (previously distilled from lithium aluminum hydride), 1.34 g of lithium aluminum hydride and 14.5 ml of absolute ether was stirred and refluxed under nitrogen for 1.5 hours, then 27 ml of water was added cautiously, to decompose excess hydride. The resulting mixture was filtered and the filter cake was washed with 135 ml of ether. The combined filtrate and wash was shaken with 135 ml of water and separated. The aqueous layer was washed with four 55-ml portions of ether, then the organic layer and the washes were combined, washed once with water, and evaporated to dryness under diminished pressure leaving a tan residue. 

The same auxiliary at nitrogen is used in the diastereoselective reduction of a series of bicyclic imides with sodium bis(2-methoxyethoxy)aluminum hydride or sodium diethylalu-minum hydride at — 78 "C, proceeding in 85-97% yield45 with d.r. values >75 25. 

A 300 ml three-neck flask equipped with condenser, stirrer, dropping funnel, dry nitrogen inlet tube, and containing 5.5 g (0.145 mol) lithium aluminum hydride LAH suspension in 100 ml anhydrous diethyl ether, was placed in an ice bath. Over a period of 25 min 30 ml (0.123 mol) 1 was added dropwise into the stirred suspension. The mixture was stirred for an additional hour at 0 °C, then poured over a mixture of 50 ml ether, 100 g crushed ice, and 50 ml ice water with stirring. When necessary more crushed ice was added to cool the mixture. The layers were separated, and the organic layer was concentrated first by distillation over calcium hydride, then by vacuum distillation over calcium hydride. The yield of 4 was 22.5 g (86%). Bp. 78-9 °C, 0.4 mm. The product was stored in a freezer. The structure of 4 was confirmed by its H NMR spectrum as shown in Fig. 4. 

Perfluorosuccinamide-Lithium Aluminum Hydride (Danger of Explosion). In an attempt to reduce perfluorosuccinamide to the corresponding diamine, it was added to an ether soln of lithium aluminum hydride in a nitrogen atm. Hydrolysis was then attempted, but as a second drop of w was added, a violent expln and ether fire resulted. It was shown that the diamide and the lithium aluminum hydride reacted to give an unstable complex which detonated at room temp Ref T.S. Reid G.H. Smith, C EN 29,3042 (1951) CA 46, 3279 (1952)... 

The required working time is 3 to 4 hours. All equipment is thoroughly dried prior to use and is flushed with an inert gas (argon or nitrogen). Commercial sodium hydroborate is used without purification. The dimethyl ether of diethylene glycol (diglyme) is refluxed over calcium hydride for 8 hours and subsequently distilled over lithium tetrahydroaluminate (lithium aluminum hydride). Commercial tri-n-butylamine is refluxed with acetic anhydride and distilled at atmospheric pressure. 

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