The Schmidt reaction is a useful tool for the synthesis of nitrogenous organic compounds. Numerous variations of this process exist, the oldest being the combination of a carbonyl compound and a hydrazoic acid precursor to afford an amide or lactam. Mechanistically, this process has been understood to involve the intermediacy of a nitrilium ion intermediate since first proposed by P. A. S. Smith in 1948, which traditionally has been reacted with water to form an amide (usually the desired pathway) or, in specialized cases, a tetrazole that incorporates parts of two molecules of hydrazoic acid into the final product. In this presentation, the effect of solvent medium on this process will be discussed. For example, we have determined that the use of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) shifts the product distribution in classical Schmidt reactions to favor tetrazole formation. In addition, carrying out the reaction in the presence of an electron-rich aromatic group (again in HFIP) leads to an “interrupted Schmidt reaction” in which the Smith nitrilium ion reacts to form a carbon–carbon bond in the final product. <br/>

HFIP and the development of an interrupted Schmidt reaction

2019 Spring National Meeting

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