Alkylation by Mannich bases

A number of very successful preparative methods involve removal of an amino group and depend on treatment of a Mannich base or its hydrochloride or methiodide with a compound containing an acidic CH group. Relatively few examples can be given here, but others can be found in the excellent review by Hellmann and Opitz.697c 

When 3-(dimethylamino)propiophenone hydrochloride is boiled for 0.5 hour with aqueous potassium cyanide solution, 4-oxo-4-phenylbutyronitrile is formed in 67% yield, dimethylamine being split off 806 

Analogously TV -methylgraminium iodide and potassium cyanide yield 3-indole-acetic acid in 76% yield by way of the nitrile.807,808 This nitrile can also be obtained, in 33-44% yield, from indole and (diethylamino)acetonitrile 809 

Heating 3-(dimethylamino)propiophenone with a ketone at 160° for 20 minutes affords a 1,5-diketone, as in the following example (95% yield) 810 

When gramine reacts with diethyl nitromalonate, the primary product obtained is diethyl -(3-indolylmethyl)-a-nitromalonate (96.5%), which is converted into tryptophan by partial hydrolysis and decarboxylation, followed by reduction and further hydrolysis.812 

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