Primary alkyl halides synthesis from acid chlorides

A simple example of using combinatorial chemistry to prepare a library of small molecules is the synthesis of secondary amides (9.46) from primary amines (9.44) and acid chlorides (9.45) (Scheme 9.4). Amides of type 9.46 have two points of variation the R-group of the amine and the R -group from the acid chloride. A third point of variation may be introduced by V- a I k y I ation with an alkyl halide (9.47) to form a tertiary amide (9.48). With just 15 building blocks—five amines, five acid chlorides, and five alkyl halides—125 (53) different tertiary amides may be prepared. 

The reaction of a -halocarboxylic acids with sodium nitrite has been used to synthesize ni-tromethane, nitroethane and nitropropane, although the reaction fails for higher nitroalkanes. " A number of other reactions have been reported which use nitrite anion as a nucleophile, including (1) reaction of alkyl halides with potassium nitrite in the presence of 18-crown-6, (2) reaction of alkyl halides with nitrite anion bound to amberlite resins, (3) synthesis of 2-nitroethanol from the acid-catalyzed ring opening of ethylene oxide with sodium nitrite, and (4) reaction of primary alkyl chlorides with sodium nitrite in the presence of sodium iodide. ... 

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