Lithium amides metallating agent

An isolated acetoxyl function would be expected to be converted into the alkoxide of the corresponding steroidal alcohol in the course of a metal-ammonia reduction. Curiously, this conversion is not complete, even in the presence of excess metal. When a completely deacetylated product is desired, the crude reduction product is commonly hydrolyzed with alkali. This incomplete reduction of an acetoxyl function does not appear to interfere with a desired reduction elsewhere in a molecule, but the amount of metal to be consumed by the ester must be known in order to calculate the quantity of reducing agent to be used. In several cases, an isolated acetoxyl group appears to consume approximately 2 g-atoms of lithium, even though a portion of the acetate remains unreduced. Presumably, the unchanged acetate escapes reduction because of precipitation of the steroid from solution or because of conversion of the acetate function to its lithium enolate by lithium amide. 

Thioamides (86) are readily reduced to amines (93) (Scheme 50). The reduction generally occurs more easily than with amides and can be achieved with a variety of reducing agents, e.g. metal-acid, sodium amalgam, lithium aluminium hydride or Raney nickel. 

In case of the direct reaction of the natural oil or lower alkyl ester of natural fatty acid and the amine the reaction method for producing the amide derivatives is as follows That is, about 1 mol of the said oils and 1 to 100 equivalent mols of the said amines are mixed in the absence or presence of solvents such alcohols as methanol, ethanol or the like, such aromatic hydrocarbons as benzene, toluene, xylene or the like, such halogenoalkanes as methylene chloride, chloroform, carbon tetrachloride or the like, and such alkenes or alkanes as petroleum ether, benzene, gasoline, ligroin or cyclohexane, such ethers as tetrahyrofuran, dioxane and the like, or a mixture thereof, and the mixture is subjected to the reaction in the absence or presence of catalyst amount or equimolar amount to the amine of an auxiliary agent of condensation, such as alkoholate of alkali metal, i.e. lithium, methylate, lithium ethylate, sodium methylate, sodium ethylate, potassium-t-butylate and the like, or acidic auxiliary agents, i.e. p-toluenesulfonic acid and the like, thereby to yield the amide derivatives. In this reaction, a formal alcohol may be removed from the reaction system. 

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