Mixed hydrides

A second example exploits the fact that the mixed hydride reagent is capable of hydrogenolysis of certain carbon-oxygen bonds. Thus, treatment of cyclohexanone ketal (Chapter 7, Section IX) with lithium aluminum hydride-aluminum chloride results in the rupture of a C-O bond to give the oxyethanol derivative. 

In a 500-ml three-necked flask, equipped with a mechanical stirrer, a dropping funnel, and a reflux condenser (drying tube), is placed 6.7 g (0.05 mole) of anhydrous aluminum chloride. The flask is cooled in an ice bath, 50 ml of dry ether is slowly added from the dropping funnel, and the mixture is stirred briefly. Powdered lithium aluminum hydride (0.6 g) is placed in a 100-ml flask fitted with a condenser, and 20 ml of dry ether is added slowly from the top of the condenser while the flask is cooled in an ice bath. The mixture is refluxed for 30 minutes then cooled, and the resulting slurry is transferred to the dropping funnel on the 500-ml flask. The slurry is added to the stirred ethereal solution of aluminum chloride over 10 minutes, and the reaction mixture is stirred for an additional 30 minutes without cooling to complete the formation of the mixed hydride . 

The dropping funnel is charged with a solution of 7.7 g (0.05 mole) of 4-/-butylcyclo-hexanone (Chapter 1, Section 1) in 50 ml of dry ether. The solution is slowly added to the mixed hydride solution at a rate so as to maintain a gentle reflux. The reaction mixture is then refluxed for an additional 2 hours. Excess hydride is consumed by the addition of 1 ml of dry t-butyl alcohol, and the mixture is refluxed for 30 minutes more. 4-/-Butylcyclohexanone (0.3 g) in 5 ml of dry ether is added to the reaction mixture, and refluxing is continued for 4 hours. The cooled (ice bath) reaction mixture is decomposed by the addition of 10 ml of water followed by 25 ml of 10% aqueous sulfuric acid. The ether layer is separated, and the aqueous layer is extracted with 20 ml of ether. The combined ether extracts are washed with water and dried over anhydrous magnesium sulfate. After filtration, the ether is removed (rotary evaporator), and the residue... 

The continuance of gentle refluxing as the last portion of the ketone is added assures that there is an excess of mixed hydride present. 

The procedure employs a readily available starting material and produces the pure trans isomer in high yield. The method described is an improvement on that used by Eliel and Rerick2 in that it is not necessary to use a clear solution of lithium aluminum hydride in ether for the preparation of the mixed hydride. It is not necessary to know the precise amount of lithium aluminum hydride used so long as a slight excess is present. The excess hydride is destroyed by adding /-butanol the excess /-butanol has no effect on the subsequent equilibration and purification. The equilibration of the 4 / butylcyclohexanol is effected by adding a small amount of 4-/-butylcyclohexanone. 

M. N. Rerick, The Chemistry of the Mixed Hydrides, Reduction Techniques, S. 1, Marcel Dekker Inc., New York 1968. 

Of several mixed hydrides, the magnesium-nickel hydrides were the most hazardous in terms of dust explosions. 

The mixed hydride chlorodiphenylstannane also forms by an exchange reaction with diphenyltin chloride and, in turn, converts rapidly to the dimer ... 

Williams [1] has given an excellent review on Early Carboranes and Their Structural Legacy and he defines carboranes as follows Carboranes are mixed hydrides of carbon and boron in which atoms of both elements feature in the electron-deficient polyhedral molecular skeleton . According to the electron counting rules [2] for closo- (2n + 2 SE), nido- (2n + 4 SE) and arachno-clusters (2n + 6 SE SE = skeletal electrons, n = number of framework atoms) and the An + 2 n electron Hiickel rule, small compounds with skeletal carbon and boron atoms may have an electron count for carboranes and for aromatics (see Chapters 1.1.2 and 1.1.3). 

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). 

The first, direct application of mixed hydrides in the carbohydrate series was described by Bhattacharjee and Gorin.214 Using a 1 1 ratio of lithium aluminum hydride to aluminum chloride, and a one-molar equivalent of this reagent, they obtained, after 40 hours, a 64% yield of... 

It may be noted that most of the reactions conducted with mixed hydrides employed diethyl ether as the solvent. Some other solvents may be not suitable for reductive cleavages, as they can themselves be hydrogenolyzed by the reducing agent. For instance, oxolane is cleaved both by lithium aluminum hydride-aluminum chloride (Ref. 256), and by tri-tert-butoxyaluminohydride in the presence of triethylborane (Ref. 257). 

The main methods of reducing ketones to alcohols are (a) use of complex metal hydrides (b) use of alkali metals in alcohols or liquid ammonia or amines 221 (c) catalytic hydrogenation 14,217 (d) Meerwein-Ponndorf reduction.169,249 The reduction of organic compounds by complex metal hydrides, first reported in 1947,174 is a widely used technique. This chapter reviews first the main metal hydride reagents, their reactivities towards various functional groups and the conditions under which they are used to reduce ketones. The reduction of ketones by hydrides is then discussed under the headings of mechanism and stereochemistry, reduction of unsaturated ketones, and stereochemistry and selectivity of reduction of steroidal ketones. Finally reductions with the mixed hydride reagent of lithium aluminum hydride and aluminum chloride, with diborane and with iridium complexes, are briefly described. 

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